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A simple tracer-based method for calculating the rate of appearance of endogenous substances in the non-steady state, free from the inconsistencies of Steele's equation, is still lacking. This paper presents a method based on a two-compartment model by which the rate of appearance can be calculated with only a modest increase in complexity over Steele's approach. An equation is developed where the rate of appearance is expressed as a sum of three terms: a steady-state term, a term for the first compartment, and a term for the second compartment. The formula employs three parameters and makes the relationship between rate of appearance and specific activity changes explicit. An equation is also provided for estimating the error of the method in each individual run. The algorithm can be implemented with a spreadsheet on a personal computer. Simulated and experimental data obtained by the hyperinsulinemic euglycemic glucose clamp technique were used as a test. The accuracy with which the time course of glucose production could be reconstructed was clearly better than that using Steele's equation. Marked negative values for endogenous glucose output were calculated with Steele's equation but not with the new method. The characteristics of generality, simplicity, and accuracy and the availability of an error estimate make this new method suitable for routine application to non-steady-state tracer analysis. | [
"Algorithms",
"Animals"
] |
Interleukin (IL)-5 induces CD38-activated splenic B cells to differentiate into immunoglobulin M-secreting cells and undergo micro to gamma 1 class switch recombination (CSR) at the DNA level, resulting in immunoglobulin G1 (IgG1) production. Interestingly, IL-4, a well-known IgG1-inducing factor does not induce immunoglobulin production or micro to gamma 1 CSR in CD38-activated B cells. In the present study, we implemented complementary DNA microarrays to investigate the contribution of IL-5-induced gene expression in CD38-stimulated B cells to immunoglobulin-secreting cell differentiation and micro to gamma 1 CSR. IL-5 and IL-4 stimulation of CD38-activated B cells induced the expression of 418 and 289 genes, respectively, that consisted of several clusters. Surprisingly, IL-5-inducible 78 genes were redundantly regulated by IL-4. IL-5 and IL-4 also suppressed the gene expression of 319 and 325 genes, respectively, 97 of which were overlapped. Genes critically regulated by IL-5 include immunoglobulin-related genes such as J chain and immunoglobulinkappa, and genes involved in B-cell maturation such as BCL6, activation-induced cytidine deaminase (Aid) and B lymphocyte-induced maturation protein-1 (Blimp-1) and tend to be induced slowly after IL-5 stimulation. Intriguingly, among genes, the retroviral induction of Blimp-1 and Aid in CD38-activated B cells could induce IL-4-dependent maturation to Syndecan-1+ antibody-secreting cells and micro to gamma 1 CSR, respectively, in CD38-activated B cells. Taken together, preferential Aid and Blimp-1 expression plays a critical role in IL-5-induced immunoglobulin-secreting cell differentiation and micro to gamma 1 CSR in CD38-activated B cells. | [
"ADP-ribosyl Cyclase 1",
"Animals"
] |
This study evaluated the utility of the psychosocial vulnerability model for understanding the hostility-coronary heart disease (CHD) relationship among college students at risk for CHD. Interrelationships of cognitive, affective, and behavioral hostility with structural and functional social support were examined. College undergraduates with a parental history of CHD (n = 121) and a control group of 125 students with no CHD family history completed measures of hostility and social support. Among women, a significant negative correlation was found between affective-experiential hostility and functional support. Among men, a significant negative correlation was observed between cognitive-experiential hostility and structural support. Path analyses revealed a significant positive effect of expressive hostility on functional support for CHD-negative men and CHD-positive women. CHD family history was not associated with hostility or family environment. CHD-positive participants reported less support satisfaction than did CHD-negative participants. Thus, results indicated qualified support for the psychosocial vulnerability model of the hostility-CHD relationship. | [
"Adult",
"Affect"
] |
Properties of retinoic acid receptors and glucocorticoid receptors of rat liver were influenced by retinol status in a nonsimilar manner. The binding of the retinoic acid receptors which was lowered in vitamin A--deficient animals relative to controls was restored by a single dose (100 micrograms) of retinoic acid; in vitamin A--overloaded animals (40-fold the control intake) the binding was greater than in controls. The binding of the glucocorticoid receptor was higher in vitamin A--deficient rats than in controls and restored by retinoic acid supplementation, but did not differ from controls in the vitamin A--overloaded rats. The cellular actions of glucocorticoid hormone and retinoic acid were investigated by assaying the activity of some related enzymes. The activity of tyrosine aminotransferase reflected glucocorticoid receptor binding in vitamin A--deficient and vitamin A--restored rats. The decreased tyrosine amino transferase activity observed in vitamin A--overloaded rats could be related to the inhibition of expression of tyrosine amino transferase gene by retinoic acid. Alcohol dehydrogenase activity was unaffected or only slightly affected by vitamin A status. The known existence of glucocorticoid hormone- and retinoic acid--sensitive elements in the alcohol dehydrogenase gene could explain such observations. Furthermore, the changes in the binding of retinoic acid receptors and glucocorticoid receptors were often in opposite directions. These results provide new evidence for the mechanisms by which the amount of dietary vitamin A modulates hormonal status. | [
"Administration, Oral",
"Alcohol Dehydrogenase"
] |
We have previously shown that a 13-residue basic peptide, derived from the presequence of a mitochondrial precursor, blocked the cationic channel of the outer mitochondrial membrane. The properties of the blockade suggested that the peptide could go through the pore in the presence of a sufficient driving force. In an attempt to evaluate more precisely the relevance of such an interpretation, we have examined the effect on the same channel of basic peptides from 16 to 34 residues, most of which are parts of or derive from mitochondrial presequences. Two peptides were found to induce a reversible voltage-dependent blockade, the properties of which were the same as those of the blockade induced by the 13-residue peptide. The others had a similar effect, but triggered in addition a modification of the voltage gating that persisted after washing the peptide out. The modification was in turn abolished by trypsin added to the side of the channel previously exposed to the peptide. The protease acted on the bound peptide and not on the channel itself. The irreversible modification of the voltage gating, the mechanism of which remains obscure, was not specific for mitochondrial-addressing sequences. | [
"Adrenal Cortex",
"Amino Acid Sequence"
] |
BACKGROUND: Asymptomatic erosive esophagitis (AEE) is considered an erosive esophagitis without the typical reflux symptoms, but the clinical course and significance of AEE is still unclear.AIM: We investigated the prevalence and predisposing factors of AEE, and tried to determine its clinical features and significance.METHODS: Subjects, who had at least two health inspections (upper endoscopy, self-reporting questionnaire, and serum Helicobacter pylori IgG antibody test) at our center, were enrolled. The questionnaire included typical reflux symptoms, previous medical history, underlying disease, smoking, alcohol intake, and medication history. Based on the results of follow-up study, the changes in endoscopic findings and reflux symptoms were also investigated.RESULTS: Of the 2961 patients visiting our clinic, 568 (19.2 %) were diagnosed with AEE. Age over 50 years, male sex, a body mass index over 25, current smoking, heavy drinking, negativity for H. pylori infection, and hiatal hernia were independent predisposing factors for AEE (p = 0.020, p < 0.001, p < 0.001, p = 0.013, p = 0.003, p < 0.001, p = 0.038, respectively). Within the follow-up period (mean 25 ± 9.5 months), reflux symptoms developed in 30 subjects (7.9 %), and current smoking was the only risk factor for the development of AEE symptoms (p = 0.015). On the follow-up endoscopy, erosive esophagitis disappeared in nearly half of the subjects with AEE (174, 45.6 %).CONCLUSIONS: AEE is common, but many cases of AEE may be spontaneously cured without treatment. Although symptom development is rare, quitting smoking may be helpful as a prevention strategy.CLINICAL TRIAL REGISTRATION NUMBER: KCT0001716. | [
"Adult",
"Aged"
] |
In 1975, Heinrich, F?rster and Oschartz developed the radioresistometry as a method of intraoperative assessment of the peripheral resistance. In this report the authors describe a full-electronic apparatus of their own construction making possible to introduce the above mentioned method into the routine clinical programme of surgical treatment of chronic occlusions of peripheral arteries. A combined use of the intraoperative angiography with measurement of peripheral resistance permits a more exact indication for vascular reconstruction and an early detection of technical failures. | [
"Angiography",
"Humans"
] |
An account is given of what is being done in the GDR in the context of social gynaecology, with reference being made to the subject proper as well as to its position in society and the tasks relating to it. Prepartal attention is described as an example. An appraisal of various concepts of social gynaecology has shown that these have always depended on the social conditions under which they have come into being. Their potentials and outcome are in conformity with those conditions, as well. Attempts have been made to define social gynaecology by the ways it is practised in certain "charitable" institutions or with closer reference to certain groups of people. However, such attempts have proved to be unacceptable to practitioners in the GDR where social gynaecology is considered a discipline of research and education to provide a profound scientific basis for action in reality. It is a social component of public health and an integral element of gynaecology and obstetrics. | [
"Female",
"Germany, East"
] |
The Eurasian badger (Meles meles) is implicated in the transmission of bovine tuberculosis (TB) to cattle in the UK and Republic of Ireland. Badger culling has been employed for the control of TB in cattle in both countries, with varying results. Social perturbation of badger populations following culling has been proposed as an explanation for the failure of culling to consistently demonstrate significant reductions in cattle TB. Field studies indicate that culling badgers may result in increased immigration into culled areas, disruption of territoriality, increased ranging and mixing between social groups. Our analysis shows that some measures of sociality may remain significantly disrupted for up to 8 years after culling. This may have epidemiological consequences because previous research has shown that even in a relatively undisturbed badger population, movements between groups are associated with increases in the incidence of Mycobacterium bovis infection. This is consistent with the results from a large-scale field trial, which demonstrated decreased benefits of culling at the edges of culled areas, and an increase in herd breakdown rates in neighbouring cattle. | [
"Animals",
"Cattle"
] |
OBJECTIVE: To determine the plasma concentrations of lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in a homogeneous group of septic patients and to evaluate the effect of antibiotic treatment, imipenem or ceftazidime, on the release of lipopolysaccharide and cytokines.DESIGN: Prospective, randomized study.SETTING: Sixteen-bed multidisciplinary intensive care unit.PATIENTS: Twenty-four septic patients with documented Gram-negative nosocomial pneumonia. Controls were 20 patients admitted without sepsis and 20 healthy volunteers.INTERVENTIONS: Septic patients were randomized between imipenem and ceftazidime. Blood samples were collected before (0 hrs) and after (4 and 12 hrs) antibiotic treatment. Concentrations of lipopolysaccharide were measured by using the limulus assay, and cytokine concentrations were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed by Kruskal-Wallis test, Mann-Whitney U test, and Student's t-test.MEASUREMENTS AND MAIN RESULTS: The mean age was 48.5 +/- 19.5. The mean Acute Physiology and Chronic Health Evaluation II score was 18.4 +/- 4.5. Overall mortality rate was 45.4%. All septic patients showed significant higher concentrations of lipopolysaccharide (p <.001), tumor necrosis factor-alpha (p <.04), and interleukin-6 (p <.001) than the controls, but interleukin-1 beta was never detected. We did not find statistically significant changes in lipopolysaccharide or cytokine plasma concentrations over time within any of the two arms of the study (ceftazidime vs. imipenem). There were no statistically significant differences in lipopolysaccharide and interleukin-6 plasma concentrations between the two antibiotic treatments. Although tumor necrosis factor-alpha plasma concentrations were significantly higher in the group treated with ceftazidime compared with the group treated with imipenem at the baseline and 4 hrs later, these differences were not statistically significant after 12 hrs of initiation of both treatments.CONCLUSIONS: Patients with Gram-negative nosocomial pneumonia have high plasma concentrations of lipopolysaccharide, interleukin-6, and tumor necrosis factor-alpha, but the antibiotic therapy evaluated did not significantly modify these concentrations. | [
"Anti-Bacterial Agents",
"Ceftazidime"
] |
OBJECTIVE: To report on unexpected findings in 4 patients with chronic paraplegia who underwent the laparoscopic implantation of neuroprosthesis procedure in the pelvic lumbosacral nerves.DESIGN: Observational case series.SETTING: Tertiary referral unit specialized in advanced gynecological surgery and neuropelveology.PARTICIPANTS: Three patients with incomplete American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade B (n=2) and AIS grade C (n=1) spinal cord injury (SCI) and 1 patient with flaccid complete chronic SCI (AIS grade A) (n=1).INTERVENTION: Functional electrical stimulation (FES)-assisted locomotor training and continuous low-frequency pelvic-lumbosacral neuromodulation.MAIN OUTCOME MEASURES: Change in ASIA Lower Extremity Motor Scores, ASIA sensory scores for light touch and pinprick sensation, and Walking Index for Spinal Cord Injury scores.RESULTS: All 4 patients developed progressive recovery of some sensory and voluntary motor functions below the lesions. Three are currently capable of voluntary weight-bearing standing and walking a few meters with a walker without FES. The first patient with the longest follow-up is even capable of electrically assisted standing/walking with 2 crutches without braces or assistance for a distance of about 900 meters, and of weight-bearing standing and walking for 30 meters with a walker without stimulation.CONCLUSIONS: We report unexpected sensory and locomotor recovery in 4 people with paraplegia with SCI. Our findings suggest that FES-assisted locomotor training with continuous low-frequency pelvic nerve stimulation in patients with SCI may induce changes that affect the central pattern generator and allow supra- and infraspinal inputs to engage residual spinal pathways. | [
"Adult",
"Crutches"
] |
Few tools for risk assessment of coronary heart disease (CHD) have yet been made available in Japan. This study aims to examine the validity of the updated Framingham risk score as applied to a Japanese male population. Using the annual health examination database of a Japanese company, we followed-up 5,611 male subjects, aged 30 to 59 years, who had initially recorded neither history of cardiovascular disease nor electrocardiographical ischemic changes, in order to observe the occurrence of CHD over a period of 5 to 7 years. The total score calculated by the Framingham risk score sheet (the Framingham point score) was used as an indicator of CHD risk for the subject individually. The mean of the Framingham point score for 80 CHD cases was significantly higher than that for 5,531 non-CHD cases. The incidence of CHD gradually increased with the Framingham point score. In the receiver operating characteristic analysis, the area under the curve reached 0.71. At 6 points, the curve came closest to the upper left-hand corner, with a specificity of 0.74 and sensitivity of 0.59. On the other hand, multivariable-adjusted relative risks associated with old age, high blood pressure, low HDL cholesterol and smoking in the Japanese male population were different from those in the Framingham population. Despite the low incidence of CHD, the updated Framingham risk score could provide a reasonable rank ordering of CHD risk and could identify Japanese men (and possible other individuals) at high risk for CHD with considerable accuracy. However, further study of Japanese populations may be required to reappraise several coefficients of risk factor in the risk scoring model. | [
"Adult",
"Asian Continental Ancestry Group"
] |
Dose-dependent kinetics of intravenous bolus-dose mezlocillin, a newly developed ureidopenicillin, have been reported by several investigators. In eight healthy subjects we examined renal, biliary, and total clearance at different steady-state levels. After infusion of doses of 22.4 +/- 1.5, 11.4 +/- 0.7, and 5.6 +/- 0.4 mg/min mean plasma steady-state levels of 88.4 +/- 15.9, 40.3 +/- 7.5, and 18.4 +/- 4.6 micrograms/ml were achieved. Metabolic clearance was estimated as the difference between total clearance and the sum of renal and biliary clearance, assuming that no other route of excretion plays an important role in the elimination of the drug. Total clearance varied between 355.7 +/- 59.3 and 286.5 +/- 54.6 ml/min when doses of 5.6 +/- 0.4 and 22.4 +/- 1.5 mg/min were given. Since neither renal clearance (137.6 +/- 32.6 ml/min) nor biliary clearance (98.6 +/- 42.5 ml/min) was shown to be dose dependent, nonlinear mezlocillin kinetics must be due to dose dependent metabolic clearance (108.4 +/- 26.2 versus 60.2 +/- 32.3 ml/min at 5.6 +/- 0.4 and 22.4 +/- 1.5 mg/min). The apparent Km was 27.5 micrograms/ml and apparent Vmax 4.3 mg/min. The apparent Km is so low that after therapeutic doses of mezlocillin the kinetics are nonlinear for several hours. | [
"Adult",
"Bile"
] |
After few seconds, a figure steadily presented in peripheral vision becomes perceptually filled-in by its background, as if it "disappeared". We report that directing attention to the color, shape, or location of a figure increased the probability of perceiving filling-in compared to unattended figures, without modifying the time required for filling-in. This effect could be augmented by boosting attention. Furthermore, the frequency distribution of filling-in response times for attended figures could be predicted by multiplying the frequencies of response times for unattended figures with a constant. We propose that, after failure of figure-ground segregation, the neural interpolation processes that produce perceptual filling-in are enhanced in attended figure regions. As filling-in processes are involved in surface perception, the present study demonstrates that even very early visual processes are subject to modulation by cognitive factors. | [
"Adult",
"Attention"
] |
Vertebrate endogenous lectins have been implicated in cellular interactions that contribute to embryonic development. We have isolated a cloned segment of the gene for chick 14K type beta-galactoside-binding lectin from a genomic DNA library. Analysis of the structure of the cloned gene as well as the results of genomic Southern blot hybridization revealed that the gene is unique and that the mRNA for the lectin is encoded by four exons separated by three introns. The whole sequence spans 3.1 kilobases in the gene. The first exon encodes only two amino acid residues of the N-terminus of the mature protein and the other three exons encode, respectively, one of the three repeating sequences found in this lectin. These facts strongly support the idea that gene duplications have occurred during the evolution of this lectin. The previous study (Y. Ohyama et al. (1986) Biochem. Biophys. Res. Commun. 134, 51-56) suggested that this lectin is not synthesized as a precursor molecule with a cleavable signal sequence at its amino terminus, although it is known to be secreted into the extracellular matrix. Sequence determination of the upstream region of the mRNA indicated that the ATG located just before the codon for the N-terminal amino acid of the mature protein is the actual translation initiator. Thus it was proved that this lectin is synthesized without an N-terminal cleavable signal sequence, as suggested before. | [
"Animals",
"Base Sequence"
] |
Fibroblast growth factor-8b (FGF8b) exerts nonredundant autocrine/paracrine functions in steroid hormone-regulated tumors. Previous observations had shown that the soluble pattern recognition receptor long pentraxin-3 (PTX3) is a natural selective antagonist for a restricted number of FGF family members, inhibiting FGF2 but not FGF1 and FGF4 activity. Here, we assessed the capacity of PTX3 to antagonize FGF8b and to inhibit the vascularization and growth of steroid hormone-regulated tumors. Surface plasmon resonance analysis shows that PTX3 binds FGF8b with high affinity (K(d) = 30-90 nmol/L). As a consequence, PTX3 prevents the binding of FGF8b to its receptors, inhibits FGF8b-driven ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells, and suppresses FGF8b-induced neovascularization in vivo. Also, PTX3 inhibits dihydrotestosterone (DHT)- and FGF8b-driven proliferation of androgen-regulated Shionogi 115 (S115) mouse breast tumor cells. Furthermore, DHT-treated, PTX3 overexpressing hPTX3_S115 cell transfectants show a reduced proliferation rate in vitro and a limited angiogenic activity in the chick embryo chorioallantoic membrane and murine s.c. Matrigel plug assays. Accordingly, hPTX3_S115 cells show a dramatic decrease of their tumorigenic activity when grafted in immunodeficient male mice. These results identify PTX3 as a novel FGF8b antagonist endowed with antiangiogenic and antineoplastic activity with possible implications for the therapy of hormonal tumors. | [
"Androgens",
"Angiogenesis Inhibitors"
] |
Large colonic polyps have large vessels, which often cause post-polypectomy hemorrhage. Some of the stalks of large pedunculated polyps are formed by the weight of the polyps and disappear after polypectomy. There are some reports suggesting that pre-ligation with Endoloop(R) may minimize the risk of post-polypectomy hemorrhage. However, the current density increases more at the site of pre-ligation as compared with that at the site of polypectomy, because polypectomy is carried out with gradual snaring. This implies that burn injury may also occur at the site of pre-ligation, causing the loss of pre-ligation and, consequently, post-polypectomy hemorrhage. Ligation of stalks after polypectomy is very difficult. The Endoloop(R) rolls back when it is tightened, because of the lack of torsional stiffness. We have developed a simple and improved post-polypectomy ligation technique using the Anchor clip. Before polypectomy, an Endoclip(R) is placed partially at the base of the pedunculated polyp. When the stalk is tightened completely with the Endoclip(R) before polypectomy, burn injury occurs around the Endoclip(R) . The Anchor clip at the base of the pedunculated polyp holds the stalk after polypectomy and the constricted part formed by the Anchor clip prevents the rolling up of the Endoloop(R) and helps in easy ligation of the stalk. We have used the Anchor clip for 50 patients. Application of the Endoloop(R) after polypectomy was impossible in two patients. The remaining 48 patients underwent Endoloop(R) -assisted polypectomy with the Anchor clip, and in none of the cases did bleeding occur after polypectomy. | [
"Colonic Polyps",
"Gastrointestinal Hemorrhage"
] |
OBJECTIVE: We aimed to investigate whether the number of pregnancies during childbearing age was associated with diabetes in postmenopausal women with no history of gestational diabetes.METHODS: Our data source was the continuous National Health and Nutrition Examination Survey 1999 to 2014. We selected 9,138 postmenopausal women over 40 years old who did not have a history of gestational diabetes during pregnancy. Logistic regression analyses were applied for the association of the number of pregnancies with diabetes.RESULTS: We found women with ?4 pregnancies had significantly greater fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), 2-hour plasma glucose, and the Homeostatic Model Assessment of Insulin Resistance than those with two to three pregnancies (all P < 0.01). These women also had a significantly higher prevalence of diabetes (28.4% vs 20.7%; P < 0.001). Using the two to three pregnancies group as the reference, we observed a positive association of log-FPG and log-HbA1c with 4 or more pregnancies after adjustment for sociodemographic, lifestyle, and reproductive factors, and body mass index (both P < 0.05). Compared to women with two to three pregnancies, the odds ratios for diabetes were 1.31 (95% confidence interval [CI] 1.01-1.71) for women who never got pregnant and 1.28 (95% CI 1.10-1.48) for those with at least 4 pregnancies after multivariate adjustment.CONCLUSIONS: At least 4 pregnancies through childbearing age may be a potential risk factor for diabetes in postmenopausal women without a history of gestational diabetes. | [
"Adult",
"Blood Glucose"
] |
BACKGROUND: Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a dual antagonist of both histamine and platelet-activating factor.OBJECTIVE: To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU.METHODS: A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge.RESULTS: After rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold (P < .001) and reduced scores for cold provocation-induced wheal reactions (P = .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment.CONCLUSION: Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms. | [
"Adult",
"Cold Temperature"
] |
Methysergide depresses the contractile effects of 5-hydroxytryptamine (5-HT) in bovine large coronary arteries devoid of endothelium. The IC50 of methysergide for depression of the response to 5-HT was (-log mol/l) 9.8. A low sensitivity contractile effect of 5-HT was not influenced by 1-1,000 nmol/l methysergide. The maximum force of this residual response is approximately 1/3 of the maximum force elicited by 5-HT in the absence of methysergide. Ketanserin restored the 5-HT-induced contraction depressed by methysergide. In the presence of 0.1 mumol/l ketanserin, methysergide caused depression of the 5-HT-induced effects with an IC50 (-log mol/l) of 6.5 without affecting the residual response. We propose that methysergide depresses 5-HT-induced contractions by acting on an allosteric site. The effect of binding of methysergide to the allosteric site would lead to a conformational change of the 5-HT2-receptor, thereby only allowing the production of a residual 5-HT-induced contraction. Ketanserin competes with high affinity not only with 5-HT for the 5-HT2-receptor but also with methysergide for the allosteric site, thus shifting the receptor back into its original conformation. The affinity estimate of ketanserin for the allosteric site yielded a KB (-log mol/l) of 10.3. Ketanserin (1-1,000 nmol/l) antagonized the contractile effects of 5-HT with a potency expected from its affinity for 5-HT2-receptors (-log KB, mol/l 9.4). However, micromolar concentrations of ketanserin antagonized the effects of 5-HT less than expected from its affinity for 5-HT2-receptors.(ABSTRACT TRUNCATED AT 250 WORDS) | [
"Allosteric Regulation",
"Animals"
] |
In our institution, systematic renal graft biopsies are performed 1 year after transplantation before deciding to switch to alternate-day steroid therapy, which has been shown to be beneficial for statural growth. We analyzed the results of systematic graft biopsies in 145 children with a creatinine clearance > or =45 ml/min per 1.73 m2. Biopsies were classified according to Banff diagnostic categories. Normal parenchyma was observed in 19 cases (13%), non-specific lesions in 42 cases (29%), chronic allograft nephropathy grade 1-3 in 68 cases (49%), and acute rejection in 8 cases (5%). Clinicopathological correlations indicated that patients with chronic allograft nephropathy had received kidneys from older donors, with longer cold ischemia time and with a higher incidence of delayed graft function. There was a strong correlation between the donor age and the presence of vascular lesions. There was also a good correlation between the severity of histological lesions and the occurrence of acute rejection episodes during the 1st year after transplantation. Renal function remained stable for up to 10 years in patients with normal parenchyma or non-specific lesions, while serum creatinine levels increased after the 2nd year in patients with chronic allograft nephropathy. | [
"Acute Disease",
"Adolescent"
] |
AIM: Optimal dose and schedule of paclitaxel in combined drug-irradiation treatment could not be determined for most of tumors yet. The aim of this study was to compare in vitro cytotoxicity and radiosensitizing abilities as a function of single paclitaxel (Taxol) exposure in tumor and fibroblastic cells using different drug incubation irradiation intervals.MATERIAL AND METHOD: A lung-carcinoma (SK-LU-1), glioblastoma (U-138 MG) and rodent fibroblast cell line (HyB14FAF28) were used. The clonogenic assay was applied for survival investigation. alpha beta-values were calculated using the linear-quadratic model (log S = -alpha D - beta D2). Cytotoxicity of Taxol was examined at 0 to 50 microM. Combined Taxol-radiotherapy exposure was accomplished with 10 microM Taxol plus 10 Gy irradiation (RT) following after a 1-hour and 9-hour interval. For controls cells were exposed to Cremophor EL/ethanol (CEL/eth) and a phosphate buffered saline (PBS).RESULTS: Single Taxol exposure (10 microM) resulted in 0.54/0.50/0.84 (3-hours incubation) and 0.094/0.48/0.82 (15-hours incubation) survival of SK-LU-1, U-138 MG and HyB14FAF28 cells, respectively. Taxol concentrations from 2 to 50 microM only had cytotoxic effect in tumor cells. Single dose RT (10 Gy) led to cell survival of 0.0006/0.006/0.03. The diluent CEL/eth also showed cytotoxic activity. Taxol plus RT led to cell survival of 0.00025/0.0014/0.042 (1 hour) and 0.0004/0.0019/0.04 (9 hours) without significant difference between chosen time intervals. alpha beta-values showed great variation lacking evidence for definite radiosensitization. alpha increase after Taxol and alpha decrease after CEL/eth exposure were detected.CONCLUSIONS: The data presented demonstrate a potential beneficial effect, described as co-operation, by combining Taxol and RT in human tumor cells and rodent fibroblasts. High intrinsic alpha components of the tumor cells as well as CEL/eth's antagonizing actions could be likely to disturb and influence paclitaxel's abilities leading to radiosensitization. | [
"Adenocarcinoma",
"Animals"
] |
Since the advent of laparoscopic surgery, the number of suits against surgeons has risen. One of the most frequent complaints is the lack of sufficient information. Physicians in France have a formal obligation to provide information in the contractual legal context established since 1936. This notion has been confirmed in several court cases. The requirement for patient informed consent has been confirmed by several decisions of the Appeals Court and is stated in the code of deontology. The value of classical oral information has been recently questioned in certain court cases. We analyse the current legal situation in France and try to define the content of information required in the case of laparoscopic surgery in addition to the way this information is provided and the means of obtaining informed consent. The information provided must be personalised. The patient must informed that laparoscopy remains a surgical operation. It is licit to warn the patient of predictable risks according to statistical probabilities, of the team's experience and of the patients own status including past history and psychological factors. A written statement may be prepared but must remain a document complementary to personalised oral information. The surgeon must obtain and assure good patient comprehension. The surgical community should publish risk rates in order for surgeons to have reliable references which can be used to define the notion of exceptional risk. | [
"Cognition",
"Forecasting"
] |
The design, synthesis, and spectral properties of four pyrene labeled oligonucleotide probes with G-quadruplex structure (Tel22-Tpy, Tel22-Upy, Tel22-6Upy, Tel22-18Upy) based on the 22-mer human telomeric sequence (Tel22) have been reported. Pyrene labels in the form of ethynylpyrenyldeoxyuridine have been inserted efficiently into oligodeoxynucleotides probes using phosphoramidite chemistry. The probes exhibited abilities to fold into G-quadruplex structures and to bind metal cations (Na+ and K+). Folding properties of probes and their spectral behavior were examined by recording the UV-vis, fluorescence, and CD spectra as well as by analyzing melting profiles. Fluorescence characteristics and G-quadruplex folding of probes were also studied at the interface of cationic dioctadecyldimethylammonium bromide (DODAB) monolayer. Investigations included film balance measurements (ð-A isotherms) and fluorescence spectra recording using a fiber optic accessory interfaced with a spectrofluorimeter. | [
"Deoxyuridine",
"Fluorescent Dyes"
] |
BACKGROUND: A growing body of literature has been produced on the potential role of statins in reducing perioperative cardiac events in patients undergoing non-cardiac surgery. However, evidence remains inconsistent, and little is known about the patterns of perioperative statin use in routine care.OBJECTIVES: The objective of this study was to examine patterns of perioperative statin initiation among adults undergoing non-cardiac elective surgery in the USA.METHODS: Using data from a large US healthcare insurer, we identified patients aged ?18 years who underwent moderate-risk to high-risk non-cardiac elective surgery between 2003 and 2012 and initiated statins within 30 days before surgery. We evaluated temporal trends of statin initiation and patient characteristics. In a matched analysis, we assessed the effect of temporal proximity to surgery on the likelihood of statin initiation.RESULTS: Of 460,154 patients undergoing surgery, 5628 (12 per 1000 patients) initiated a statin within 30 days before surgery. Statin initiation increased from 8 per 1000 patients in 2003 to 15 in 2012 (p = 0.0022). The increase was more pronounced among patients undergoing vascular surgery (149 initiators per 1000 patients by the end of 2012) and with Revised Cardiac Risk Index (RCRI) score ?2 (72 per 1000 patients). Proximity to surgery, in particular vascular surgery, was predictive of statin initiation.CONCLUSIONS: Despite the lack of robust evidence, perioperative statin initiation progressively increased from 2003 to 2012, particularly among patients undergoing major vascular surgery and with higher RCRI score. These trends were largely attributable to the initiation of statins in anticipation of non-cardiac surgery rather than routine dyslipidemia treatment. | [
"Adolescent",
"Adult"
] |
We describe the developmental validation study performed on the PowerPlex(®) ESX 16 (European Standard Extended 16) and the PowerPlex(®) ESX 17 Systems, part of a suite of four new DNA profiling kits developed by Promega in response to the ENFSI and EDNAP groups' call for new STR multiplexes for Europe. The PowerPlex(®) ESX 16 System combines the 11 loci compatible with the UK National DNA Database, contained within the AmpFlSTR(®) SGM Plus(®) PCR Amplification Kit, with five additional loci: D2S441, D10S1248, D22S1045, D1S1656 and D12S391. The multiplex was designed to incorporate these five new loci as mini- and midi-STRs while maintaining the loci found in the AmpFlSTR(®) SGM Plus(®) kit as standard size. The PowerPlex(®) ESX 17 System amplifies the same loci as the PowerPlex(®) ESX 16 System, but with the addition of a primer pair for the SE33 locus. Tests were designed to address the developmental validation guidelines issued by the Scientific Working Group on DNA Analysis Methods (SWGDAM), and those of the DNA Advisory Board (DAB). Samples processed include DNA mixtures, PCR reactions spiked with inhibitors, a sensitivity series, and 306 United Kingdom donor samples to determine concordance with data generated with the AmpFlSTR(®) SGM Plus(®) kit. Allele frequencies from 242 white Caucasian samples collected in the United Kingdom are also presented. The PowerPlex(®) ESX 16 and ESX 17 Systems are robust and sensitive tools, suitable for the analysis of forensic DNA samples. Full profiles were routinely observed with 62.5 pg of a fully heterozygous single source DNA template. In mixture analysis, a range of 52-95% of unique minor contributor alleles was observed at 19:1 mixture ratios where only 25 pg of the minor component was present. Improved sensitivity combined with the robustness afforded by smaller amplicons has substantially improved the quantity of information obtained from degraded samples, and the improved chemistry confers exceptional tolerance to high levels of laboratory prepared inhibitors. | [
"DNA",
"Gene Frequency"
] |
Following secondary in vitro sensitization with AKR/Gross virus-induced tumors, AKR.H-2b:Fv-1b mice develop cytotoxic T lymphocytes (CTL) specific for AKR/Gross viral antigens. It has recently been determined that the responder status of AKR.H-2b:Fv-1b to AKR/Gross virus declines with age. The nonresponsiveness observed in AKR.H-2b:Fv-1b is similar to that observed in AKR.H-2b mice which (regardless of age) does not develop anti-AKR/Gross virus CTL. It was of interest to determine the ability of these congenic mouse strains to respond to other murine leukemia viruses (MuLV). This was accomplished by immunizing AKR.H-2b and young or moderately aged AKR.H-2b:Fv-1b with Friend-Moloney-Rauscher (FMR) virus-induced tumors, and assessing the ability of anti-FMR CTL to develop following secondary in vitro stimulation. It was observed that both AKR.H-2b and AKR.H-2b:Fv-1b developed specific anti-FMR virus CTL. Similarly, following tumor challenge AKR.H-2b mice were unable to prevent the outgrowth of a syngeneic AKR/Gross virus-induced tumor, but were able to reject a syngeneic FMR virus-induced tumor. | [
"AKR murine leukemia virus",
"Age Factors"
] |
Circulating levels of four specific placental proteins, human chorionic gonadotrophin (hCG), Schwangerschafts protein 1 (SP1), placental protein 5 (PP5) and pregnancy-associated plasma protein A (PAPP-A), were measured in 31 patients with hydatidiform mole before treatment. Seven patients subsequently developed clinical choriocarcinoma and three of them had pulmonary metastases. The estimations of hCG, PP5 and PAPP-A levels were found to be of no value in the prediction of malignant sequelae. Levels of SP1 greater than or equal to 16.5 i.u./l were associated with a higher incidence of subsequent malignant disease (P less than 0.05), the risk being at least nine times greater in these patients. The predictive value of high levels of SP1 was 35%, the specificity 45.8% and sensitivity 100%. | [
"Adult",
"Choriocarcinoma"
] |
UNLABELLED: This study examined the effects of glovebox gloves for 11 females on maximum grip and key pinch strength and on contact forces generated from simulated tasks of a roller, a pair of tweezers and a crescent wrench. The independent variables were gloves fabricated of butyl, CSM/hypalon and neoprene materials; two glove thicknesses; and layers of gloves worn including single, double and triple gloving. CSM/hypalon and butyl gloves produced greater grip strength than the neoprene gloves. CSM/hypalon gloves also lowered contact forces for roller and wrench tasks. Single gloving and thin gloves improved hand strength performances. However, triple layers lowered contact forces for all tasks. Based on the evaluating results, selection and design recommendations of gloves for three hand tools were provided to minimise the effects on hand strength and optimise protection of the palmar hand in glovebox environments.PRACTITIONER SUMMARY: To improve safety and health in the glovebox environments where gloves usage is a necessity, this study provides recommendations for selection and design of glovebox gloves for three hand tools including a roller, a pair of tweezers and a crescent wrench based on the results discovered in the experiments. | [
"Adult",
"Biomechanical Phenomena"
] |
Perovskoate, an isorinic acid derivative (1) and perovskoside, the catechol derivative (2) have been isolated from the ethyl acetate soluble fraction of the whole plant of Perovskia atriplicifolia and assigned the structure 3(7-hydroxyphenyl)-2-hydroxy propanoic acid; (R)-form, 2-O-(6',7'-dihydroxy-E-cinnamoyl) (1) and 2-methoxy-4-(undecyl-4'-O-beta-D-glucopyranosyl) phenol (2). In addition, caffeic acid (3) and ferulic acid (4) have been reported for the first time from this species. The structures of these compounds were assigned on the basis of 1D and 2D NMR techniques. The compound 1 showed significant inhibitory activity against lipoxygenase and weak to moderate activity against cholinesterases. | [
"Caffeic Acids",
"Catechols"
] |
BACKGROUND: The economic evaluation of treatments usually requires access to individual patient data, which is difficult to obtain. Moreover, in osteoarthritis, health utility scores are unavailable and can be assessed only using a validated equation model based on various clinical data. We aimed to develop and validate a methodology to simulate individual health utility scores from aggregated clinical data available in published studies to calculate the cost-effectiveness of different glucosamine preparations (i.e., crystalline glucosamine sulfate, glucosamine sulfate, and glucosamine hydrochloride) used for osteoarthritis.METHODS: We developed a method to simulate individual utility values and validated the model by comparing the results obtained with the simulation and the results of one trial where the utility scores are available. Then, we simulated the utility scores of 10 published trials that used different glucosamine preparations. The utility estimates were used to calculate the quality-adjusted life year (QALY) using the area-under-the-curve method. Costs were for the glucosamine product only. The incremental cost/effectiveness ratio (ICER) was then calculated.RESULTS: The values of utility scores calculated from data sources and those simulated with the model were similar. From 10 studies where utility was simulated, four used crystalline glucosamine sulfate, and six used other formulations. The ICER revealed that compared to placebo, crystalline glucosamine sulfate only was cost-effective at all time points and up to 3 years with a median ICER of 5347.2 €/QALY at month 3, 4807.2 €/QALY at month 6 and 11535.5 €/QALY at year 3. The use of other formulations was not cost-effective.CONCLUSION: Using a new model to simulate individual health utility scores of patients included in ten published trials, ICER analysis showed that the use of crystalline glucosamine sulfate is cost-effective, while other formulations were not. The results confirm the importance of the formulation of glucosamine products. | [
"Adult",
"Cost-Benefit Analysis"
] |
BACKGROUND AND PURPOSE: While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients.METHODS: Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24).RESULTS: The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7).CONCLUSIONS: The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment. | [
"Adult",
"Atrophy"
] |
We present the LiSEQ (Listeria SEQuencing) project, funded by the European Food Safety Agency (EFSA) to compare Listeria monocytogenes isolates collected in the European Union from ready-to-eat foods, compartments along the food chain (e.g. food-producing animals, food-processing environments) and humans. In this article, we report the molecular characterization of a selection of this data set employing whole-genome sequencing analysis. We present an overview of the strain diversity observed in different sampled sources, and characterize the isolates based on their virulence and resistance profile. We integrate into our analysis the global L. monocytogenes genome collection described by Moura and colleagues in 2016 to assess the representativeness of the LiSEQ collection in the context of known L. monocytogenes strain diversity. | [
"Animals",
"Cross-Sectional Studies"
] |
BACKGROUND: Exercise-induced ST-segment elevation is a relatively uncommon problem and occurs more frequently in patients who have had a myocardial infarction. Data is limited on the characteristics of Taiwanese patients without prior myocardial infarction who develop exercise-induced ST-segment elevation.METHODS AND RESULTS: Exercise-induced ST-segment elevation developed in 9 of 6,147 consecutive patients without myocardial infarction who underwent treadmill exercise testing at out institution over a 4-year period. The clinical and angiographic characteristics of these patients were studied. Angiographically normal coronary arteries with coronary vasospasm were found in 5 patients, hemodynamically significant coronary stenosis was found in 3 patients, and coexisting spasm in angiographically normal coronary arteries combined with hemodynamically significant coronary stenosis in the different vessel was found in 1 patient. During a median follow-up of 71 months, 2 patients with coronary vasospasm developed recurrent angina after self-discontinuation of calcium antagonists and 2 patients (1 with coronary vasospasm and 1 with hemodynamically significant coronary stenosis) died of cardiac causes before arrival at the emergency department.CONCLUSION: Coronary vasospasm was a more common underlying pathology of exercise-induced ST-segment elevation in this Taiwanese cohort. Coronary angiography +/- intracoronary ergonovine provocation testing is necessary in these patients to identify the underlying pathology and appropriate treatment. | [
"Acute Disease",
"Adult"
] |
ST8SIA2 and NCAM1 are functionally related genes forming polysialic acid (PSA) - neural cell adhesion molecule (NCAM) complex in suprachiasmatic nucleus (SCN), the regulating site of circadian biological rhythm. In this study, the relationship of ST8SIA2 and NCAM1 with circadian and seasonal rhythms of human behavior was explored. Subjects were 261 healthy Korean adults who were free of any history of clinically significant psychiatric symptoms. The phenotypes were circadian preference and seasonal change of mood and behavior (seasonality) measured by the Composite Scale of Morningness and the Seasonal Pattern Assessment Questionnaire, respectively. Thirty-four single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and 15 SNPs of NCAM1 were analyzed. A nominally significant association with seasonality and circadian preference was observed in 21 variants of both genes. After corrections for multiple testing, associations of 8 SNPs of ST8SIA2 and 2 SNPs of NCAM1 with seasonality remained significant. Some of these SNPs were also associated with psychiatric disorders in previous studies. This study demonstrated a meaningful and/or suggestive evidence of association between behavioral phenotypes reflecting human biological rhythm and two interplaying genes involved in the plasticity of SCN's neuronal network. | [
"Adult",
"Affect"
] |
Malaria parasites demonstrably increase the permeability of the membrane of the erythrocyte in which they develop and propagate. New permeability pathways (NPPs) generated by parasite activity and identified in the erythrocyte membrane are held responsible for these changes. Here, we present a novel analysis of hemolysis curves of infected cells in iso-osmotic solutions of solutes that penetrate selectively into infected cells, as a function of parasite development. The analysis yields three parameters: the t(1/2) of lysis (reciprocally related to permeability), the maximal lysis, and a parameter that expresses the variation of the cell population. Different developmental stages of the parasite were obtained either by sampling synchronized cultures with time or by the fractionation of asynchronous cultures on a Percoll-sorbitol density gradient. While the results confirm previous reports on the stage-dependent evolution of NPPs, they also reveal that the evolution of NPPs is not synchronous: NPPs evolve differentially throughout the ring stage and only at the mid-trophozoite stage they are fully deployed in the majority of the infected cells, but not in all. This leads to desynchronization in the culture and to less than the maximal possible rate of multiplication. | [
"Animals",
"Cell Membrane Permeability"
] |
Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient's condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824-0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4?CTP<0.8 intermediate; 0.8?CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition. | [
"Blotting, Western",
"Enzyme-Linked Immunosorbent Assay"
] |
The presence and distribution of human atrial natriuretic polypeptide (ANP) were investigated immunohistochemically in the ventricles of hearts of 14 cases with endocardial fibroelastosis and 15 cases with noncardiac disease in children. Paraffin sections of autopsied hearts with endocardial fibroelastosis were stained with polyclonal antibodies against human alpha-ANP. Immunoreactive myocytes were clearly demonstrated in the ventricles of 10 hearts with endocardial fibroelastosis. The distribution of ANP-positive cells was most frequent in the inner one-third of the left ventricle. No ANP immunoreactivity was detected in any heart in cases with noncardiac disease. The left ventricular volume index of hearts with ANP-positive cells was larger than that with ANP-negative cells. The mean diameter of ANP-positive myocytes was greater than that of ANP-negative myocytes. These results suggest that ANP expression in ventricular myocytes is related to severe dilatation of the ventricular cavity and to development of myocardial hypertrophy in endocardial fibroelastosis. | [
"Atrial Natriuretic Factor",
"Child"
] |
Cyanobacteria developed efficient carbon concentrating mechanisms which significantly improve the photosynthetic performance and survival of cells under limiting CO(2) conditions. Dynamic changes of the Synechocystis proteome to CO(2) limitation were investigated using shotgun LC-MS/MS approach with isobaric tag for relative and absolute quantification (iTRAQ) technique. Synechocystis cells grown at high (3%) CO(2) were shifted to air-level CO(2) followed by protein extraction after 6, 24, and 72 h. About 19% of the cyanobacterial proteome was identified and the expression changes were quantified for 17% of theoretical ORFs. For 76 proteins, up- or down-regulation was found to be significant (more than 1.5 or less than 0.7). Major changes were observed in proteins participating in inorganic carbon uptake, CO(2) fixation, nitrogen transport and assimilation, as well as in the protection of the photosynthetic machinery from excess of light. Further, a number of hypothetical proteins with unknown functions were discovered. In general, the cells appear to acclimate to low CO(2) without a significant stress since the stress-related molecular chaperones were down-regulated and only a minor decline was detected for proteins of phycobilisomes, photosynthetic complexes, and translation machinery. The results of iTRAQ experiment were validated by the Western blot analysis for selected proteins. | [
"Bacterial Proteins",
"Carbon"
] |
A patient presenting with a pacemaker lead infection and tricuspid regurgitation underwent a minimally invasive video-assisted tricuspid valve replacement. The valve was approached through a right anterior mini thoracotomy. Under thoracoscopic vision and peripheral cardiopulmonary bypass, a catheter was placed on the ascending aorta for antegrade cardioplegia delivery. A transthoracic aortic cross-clamp was introduced through the third right intercostal space. Tricuspid valve replacement added to the pacemaker leads ablation was exclusively performed under thoracoscopic vision, providing an excellent video-image in this reduced operative field. After 22 months of follow up, the patient is asymptomatic, the echocardiography showing a normally functioning valve. | [
"Cardiopulmonary Bypass",
"Echocardiography, Transesophageal"
] |
IMPORTANCE: Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies.OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013.EVIDENCE REVIEW: The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs.FINDINGS: In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries.CONCLUSIONS AND RELEVANCE: Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation. | [
"Adolescent",
"Adult"
] |
Two 9-cis-epoxycarotenoid dioxygenase (NCED) cDNAs have been cloned from a petal library of Gentiana lutea. Both cDNAs carry a putative transit sequence for chloroplast import and differ mainly in their length and the 5'-flanking regions. GlNCED1 was evolutionary closely related to Arabidopsis thaliana NCED6 whereas GlNCED2 showed highest homology to tomato NCED1 and A. thaliana NCED3. The amounts of GlNCED2 transcript were below Northern detection in G. lutea. In contrast, GlNCED1 was specifically expressed at higher levels in developing flowers when petals start appearing. By genetic engineering of tobacco with coding regions of either gene under a constitutive promoter, their function was further analyzed. Although mRNA of both genes was detectable in the corresponding transgenic plants, a physiological effect was only found for GlNCED1 but not for GlNCED2. In germination experiments of GlNCED1 transgenic lines, delayed radicle formation and cotyledon appearance were observed. However, the transformants exhibited no improved tolerance against desiccation stress. In contrast to other plants with over-expressed NCEDs, prolonged delay of seed germination is the only abscisic-acid-related phenotypic effect in the GlNCED1 transgenic lines. | [
"Adaptation, Physiological",
"Dioxygenases"
] |
Olives (Olea europaea L.) are classic ingredients in the Mediterranean diet with well-known health benefits, but their lipid composition has not been fully addressed. In this work, we characterised triacylglycerol (TAG) and polar lipid profiles of the olive pulp while using a complementary methodological approach that was based on solid-phase extraction to recover the neutral lipid (NL) and the polar lipid-rich fractions. The TAG profile was analysed in the NL-fraction by C30 reversed-phase liquid chromatography (LC) and the polar lipid profile by normal-phase hydrophilic interaction liquid chromatography (HILIC), with both being coupled to electrospray ionization-mass spectrometry (ESI-MS) and ESI-MS/MS. This approach identified 71 TAG ions that were attributed to more than 350 molecular species, with fatty acyl chain lengths from C11:0 to C26:0, including different polyunsaturated acyl chains. The polar lipids included 107 molecular species that belonged to 11 lipid classes that comprised phospholipids, glyceroglycolipids, glycosphingolipids, and betaine lipids. In addition to polyunsaturated fatty acids, some of the phospholipids, glycolipids, and glycosphingolipids that were identified in the olive pulp have been described as biologically active molecules. Lipidomic phenotyping of the olive pulp has led to the discovery of compounds that will allow for a better assessment of its nutritional value and new applications of bioactive lipid components in this functional food. | [
"Chromatography, Liquid",
"Chromatography, Reverse-Phase"
] |
Dejour's radiographic criteria are commonly used to diagnose and assess femoral trochlear dysplasia in case of patello-femoral instability. The aim of this study was to establish the intra- and interobserver reliability of these radiographic criteria. Sixty-eight lateral knee radiographs were examined independently by 7 observers (2 juniors, 5 seniors) to assess interobserver agreement, and the 2 juniors repeated the observations to test intraobserver agreement. These 68 true lateral views were harvested from clinical records of 64 patients who underwent a trochleoplasty because of patellofemoral instability. To evaluate the agreement on analytic data (morphologic type of trochlea) we used the kappa statistical method, and to evaluate the agreement on numerical data (depth and prominence of the trochlear groove) we used interclass correlation analysis. The "crossing sign" (between the trochlear groove and the anterior aspect of both condyles) was reliable since the probability of rating as normal a pathologic trochlea was only 3.1% (0 to 8.8%). In classifying trochlear morphology interobserver agreement was slight (kappa = 0.17) and intraobserver agreement was fair (kappa = 0.3). On the other hand, the measurements of the depth and prominence of the trochlear groove were more reliable since the interclass coefficients between observers were 0.62 and 0.38 respectively. The most frequent interobserver error was related to misdiagnosis of type II. To clarify Dejour's criteria we propose a diagnosis of type II only when 5 mm or more are measured between the intersections with the medial and lateral femoral condyles. We recommend the use of the prominence of the trochlear groove to evaluate the grade of bony trochlear dysplasia. | [
"Adult",
"Female"
] |
Outcomes for follicular lymphoma (FL) have greatly improved, but most patients will ultimately relapse. High total metabolic tumor volume (TMTV), computed from baseline 18F-fluorodeoxyglucose-positron emission tomography (PET), is associated with shorter progression-free survival (PFS), but circulating tumor cells (CTCs) and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at diagnosis and to determine their prognostic values. We retrospectively analyzed 133 patients (with previously untreated FL and a baseline PET) from 2 cohorts with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral blood (PB) sample (n = 68). Quantification of circulating bcl2-JH+ cells and cfDNA was performed by droplet digital polymerase chain reaction. A significant correlation was found between TMTV and both CTCs (P < .0001) and cfDNA (P < .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with TMTV > 510 cm3 (P = .0004), CTCs >0.0018 PB cells (P = .03), or cfDNA >2550 equivalent-genome/mL (P = .04). In comparison with TMTV alone, no additional prognostic information was obtained by measuring CTCs. In contrast, Cox multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome. PFS was shorter for patients with high cfDNA and TMTV, suggesting that these parameters provide relevant information for tumor-tailored therapy. | [
"Adult",
"Aged"
] |
BACKGROUND: Pancreatic fistula is a major cause of morbidity and mortality after pancreatoduodenectomy. To prevent this complication, many technical procedures have been described.AIM: To present a novel technique based on slight modifications of the original Heidelberg technique, as new pancreatojejunostomy technique for reconstruction of pancreatic stump after pancreatoduodenectomy and present initial results.METHOD: The technique was used for patients with soft or hard pancreas and with duct size smaller or larger than 3 mm. The stitches are performed with 5-0 double needle prolene at the 2 o'clock, 4 o'clock, 6 o'clock, 8 o'clock, 10 o'clock, and 12 o'clock, positions, full thickness of the parenchyma. A running suture is performed with 4-0 single needle prolene on the posterior and anterior aspect the pancreatic parenchyma with the jejunal seromuscular layer. A plastic stent, 20 cm long, is inserted into the pancreatic duct and extended into the jejunal lumen. Two previously placed hemostatic sutures on the superior and inferior edges of the remnant pancreatic stump are passed in the jejunal seromuscular layer and tied.RESULTS: Seventeen patients underwent pancreatojejunostomy after pancreatoduodenectomy for different causes. None developed grade B or C pancreatic fistula. Biochemical leak according to the new definition (International Study Group on Pancreatic Surgery) was observed in four patients (23.5%). No mortality was observed.CONCLUSION: Early results of this technique confirm that it is simple, reliable, easy to perform, and easy to learn. This technique is useful to reduce the incidence of pancreatic fistula after pancreatoduodenectomy. | [
"Adult",
"Aged"
] |
A series of bimetallic catalysts containing nickel supported over MgO-ZrO2 were tested for activity in the dry reforming of carbon dioxide. A nickel-cobalt bimetallic catalyst gave the best performance in terms of conversion and coke resistance from a range of Ni-X bimetallic catalysts, X=Ca, K, Ba, La, and Ce. The nitrogen-adsorption and hydrogen-chemisorption studies showed the Ni-Co bimetallic supported catalyst to have good surface area with high metal dispersion. This contributed to the high catalytic activity, in terms of conversion activity and stability of the catalyst, at an equimolar methane/carbon dioxide feed ratio. The kinetics of methane dry reforming are studied in a fixed-bed reactor over an Ni-Co bimetallic catalyst in the temperature range 700-800 °C by varying the partial pressures of CH4 and CO2. The experimental data were analyzed based on the proposed reaction mechanism using the Langmuir-Hinshelwood kinetic model. The activation energies for methane and carbon dioxide consumption were estimated at 52.9 and 48.1 kJ mol(-1), respectively. The lower value of CO2 activation energy compared to the activation energy of CH4 indicated a higher reaction rate of CO2, which owes to the strong basicity of nanocrystalline support, MgO-ZrO2. | [
"Carbon Dioxide",
"Catalysis"
] |
This meeting report summarizes the proceedings of the fifth Genomic Standards Consortium (GSC) workshop held December 12-14, 2007, at the European Bioinformatics Institute (EBI), Cambridge, UK. This fifth workshop served as a milestone event in the evolution of the GSC (launched in September 2005); the key outcome of the workshop was the finalization of a stable version of the MIGS specification (v2.0) for publication. This accomplishment enables, and also in some cases necessitates, downstream activities, which are described in the multiauthor, consensus-driven articles in this special issue of OMICS produced as a direct result of the workshop. This report briefly summarizes the workshop and overviews the special issue. In particular, it aims to explain how the various GSC-led projects are working together to help this community achieve its stated mission of further standardizing the descriptions of genomes and metagenomes and implementing improved mechanisms of data exchange and integration to enable more accurate comparative analyses. Further information about the GSC and its range of activities can be found at http://gensc.org. | [
"Education",
"Genomics"
] |
OBJECTIVES: There is significant evidence that articaine and lidocaine buccal injections alone are sufficient for painless extraction of maxillary teeth. The aim of this study was to evaluate the extraction of permanent maxillary teeth and to compare pain control between articaine and lidocaine without palatal injection.MATERIALS AND METHODS: Group A received buccal and palatal injections of 2% lidocaine with 0.015 mg/ml epinephrine. Group B received only buccal local anesthetic injection of 2% lidocaine with 0.015 mg/ml epinephrine. Group C received only buccal injection of 4% articaine with 0.012 mg/ml epinephrine. The patients' perception of pain was assessed using visual analogue scale and verbal response scale after the injection and the extraction.RESULTS: Statistical analysis showed that the difference in pain perception of local anesthetic injection was statistically significant between groups A and B and between groups A and C (p < 0.05).CONCLUSION: The extraction of permanent maxillary teeth is possible without palatal injections and there is no difference between articaine and lidocaine.CLINICAL RELEVANCE: Local anesthetic agents are the most frequently administered drugs in dentistry and represent the primary method of pain control for patients undergoing intraoral procedures. | [
"Anesthesia, Dental",
"Anesthetics, Local"
] |
BACKGROUND: Oral clonidine is used as premedication in children. The bioavailability of clonidine given orally in adults is 75-100% but is unknown in children.METHODS: Children (3-10 years) undergoing adenotonsillectomy were administered oral clonidine 4 mcg·kg(-1) mixed with apple fruit drink as premedication. Intravenous plasma was assayed for clonidine concentration at 5, 15, 30, 45 min and 1, 2, 4, 6, 12, 18 h after administration. Clonidine plasma concentrations were determined by liquid chromatography-mass spectroscopy, and pharmacokinetic parameters were calculated using nonlinear effects mixed-effects models. Current data were pooled with published time-concentration profiles from children (n = 49) administered intravenous clonidine to determine oral bioavailability.RESULTS: There were eight children studied (age 3-10 years, weight 10.5-36 kg). A two-compartment model with first-order absorption and elimination was used to describe time-concentration profiles. Population parameter estimates (CV%; 95% CI), standardized to a 70-kg person, were absorption half-life (Tabs), 0.45 (85.1; 0.221-0.884) h, absorption lag time (Tlag), 0.148 (91.2; 0.002-0.316) h, Clearance (CL) 17.9 (30.3; 16-20.3) l·h(-1) per 70 kg, between compartment clearance (Q) 121 (44.3; 80.1-165) l·h(-1) per 70 kg, central volume (V1) 81.2 (71.5; 60.7-105) l·70 kg(-1), peripheral volume of distribution (V2) 113 (33.9; 91-131) l·70 kg(-1). The oral bioavailability was 55.4% (CV 6.4%; 95% CI 0.469, 0.654).CONCLUSIONS: Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration (T(max) 1.04 h, C(max) 0.77 mcg·l(-1)). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults. | [
"Administration, Oral",
"Adrenergic alpha-Agonists"
] |
PURPOSE: Malposition of dental elements can be easily corrected when the patient is young; however, the opposite is true for adults. Middle-age patients normally request a rapid solution, but they usually also have associated pathologic features, such as advanced periodontal disease, dental migration, and ankylosis. Shortening the orthodontic treatment time is possible but not easy to achieve. We applied piezosurgical bone cuts to 10 patients affected by different dental malformations to determine the effects of a shorter treatment time.MATERIALS AND METHODS: A total of 10 patients (8 women and 2 men) were treated using the monocortical tooth dislocation and ligament distraction technique. We included 5 patients with dental ankylosis (group A, with a range of 4 to 5 mm of dental intrusion into the bone), who presented with at least 4 elements included in the mandible, and 5 preoperative patients affected by maxillary hypoplasia and transverse maxillary diameter reduction (group B, with a range of 6 to 8 mm measured at the first molar palatal cusp).RESULTS: Dental repositioning was achieved within 18 to 25 days for the dental intrusion group (group A) and within 68 to 150 days for the preoperative group (group B). The average period was 20 days for group A and 100 days for both dental arches in group B. The decrease in orthodontic treatment time was 70% for the ankylotic teeth and 65% for the preoperative group. We observed no periodontal or gingival damage, although all 10 patients experienced moderate edema and pain.CONCLUSIONS: This method of shortening the orthodontic treatment time is simple, and performing osteotomic lines laterally and apically to the tooth radix on the bone has proved useful in reducing the treatment time. In addition, the technique is very easy to use and has a low incidence of side effects. | [
"Adolescent",
"Alveolar Process"
] |
PURPOSE: To explore faculty perspectives on which characteristics of high-performing clerkship students are most important when determining an honors or top grade designation for clinical performance.METHOD: In 2016-2017, the authors surveyed faculty (teaching ward attendings) for internal medicine clerkships and 1 pediatrics clerkship in inpatient settings at 5 U.S. academic medical centers. Survey items were framed around competencies, 24 student characteristics, and attitudes toward evaluation. Factor analysis examined constructs defining high-performing students.RESULTS: Of 516 faculty invited, 319 (62%) responded. The top 5 characteristics as rated by respondents were taking ownership, clinical reasoning, curiosity, dependability, and high ethical standards (in descending order). Twenty-one characteristics fit into 3 factors (Cronbach alpha, 0.81-0.87). Clinical reasoning did not fit into a factor. Factor 1 was the most important (mean rating, 8.7/10 [95% confidence interval (CI), 8.6-8.8]). It included professionalism components (ownership, curiosity, dependability, high ethical standards), presentation and interviewing skills, seeking feedback, and documentation. Factor 2 (mean, 7.9 [95% CI, 7.7-8.0]) included aspects of teamwork and communication, such as positive attitude and comments from others. Factor 3 (mean, 7.6 [95% CI, 7.4-7.7]) addressed systems-based thinking, including patient safety and care transitions.CONCLUSIONS: Professionalism components, clinical reasoning, and curiosity were among the most important characteristics distinguishing high-performing clerkship students. These may represent behaviors that are highly valued, observable, and relevant to training stage. Improved definition of the characteristics associated with clinical honors would assist students, faculty, and residency program directors when interpreting clinical performance within core clerkships. | [
"Academic Medical Centers",
"Awards and Prizes"
] |
1. We report a controlled retrospective cohort study of respiratory adverse reactions to ACE inhibitors. Bronchospasm and cough occurred at a higher rate in patients treated with ACE inhibitors, no links with sex, past history of bronchospasm, drug type or dose were found. 2. Cohorts of 1013 patients on angiotensin converting enzyme (ACE) inhibitors and 1017 patients on lipid lowering drugs (LLDs) were compared for the occurrence of new bronchospasm, relapse of previous bronchospasm, increase of current bronchospasm, and cough. 3. The prevalence of bronchospasm was 5.5% for patients on ACE inhibitors and 2.3% for patients on LLDs, P < 0.001. The relative risk of a bronchospasm adverse reaction for a patient on an ACE inhibitor compared with a patient on a LLD was 2.39, 95% confidence interval 1.47 to 3.90. 4. No ACE inhibitor specificity, or significant sex differences were found in the prevalence of bronchospasm or cough after correcting for bias implicit in the original cohorts. The bronchospastic reactions were not dose dependent. 5. The prevalence of a past history of bronchospasm in patients reporting ACE inhibitor-induced bronchospasm (16%) was not significantly different from the prevalence in patients on ACE inhibitors without an adverse reaction (13%), P = 0.447. 6. The prevalence of ACE inhibitor cohort cough was 12.3% and 2.7% in the patients on LLDs, P < 0.0001. Cough did not occur more commonly in patients on ACE inhibitors who had experienced any bronchospasm (28%) than in patients on LLDs with bronchospasm (27%). | [
"Aged",
"Bronchial Spasm"
] |
BACKGROUND: One of the approaches for conducting genomics research in organisms without extant microarray platforms is to profile their expression patterns by using Cross-Species Hybridization (CSH). Several different studies using spotted microarray and CSH produced contradicting conclusions in the ability of CSH to reflect biological processes described by species-specific hybridization (SSH).RESULTS: We used a tomato-spotted cDNA microarray to examine the ability of CSH to reflect SSH data. Potato RNA was hybridized to spotted cDNA tomato and potato microarrays to generate CSH and SSH data, respectively. Difficulties arose in obtaining transcriptomic data from CSH that reflected those obtained from SSH. Nevertheless, once the data was filtered for those corresponding to matching probe sets, by restricting proper cutoffs of probe homology, the CSH transcriptome data showed improved reflection of those of the SSH.CONCLUSIONS: This study evaluated the relative performance of CSH compared to SSH, and proposes methods to ensure that CSH closely reflects the biological process analyzed by SSH. | [
"Cluster Analysis",
"Gene Expression Profiling"
] |
We studied the effects of fatty acid oxidation on insulin secretion of db/db mice and underlying molecular mechanisms of these effects. At 2-3 months of age, db/db mice were markedly obese, hyperglycemic, and hyperinsulinemic. Serum free fatty acid (FFA) levels were increased in 2-month-old (1.5 +/- 0.1 vs. 1.1 +/- 0.1 mmol/l, P < 0.05) and 3-month-old (1.9 +/- 0.1 vs. 1.2 +/- 0.1 mmol/l, P < 0.01) mice compared with the age and sex-matched db/+ mice serving as controls. Glucose-induced insulin release from db/db islets was markedly decreased compared with that from db/+ islets and was specifically ameliorated (by 54% in 2-month-old and 38% in 3-month-old mice) by exposure to a carnitine palmitoyltransferase I inhibitor, etomoxir (1 micromol/l). Etomoxir failed to affect the insulin response to alpha-ketoisocaproate. The effect of etomoxir on glucose-induced insulin release was lost after culturing db/db islets in RPMI medium containing 22 mmol/l glucose but no fatty acid. Culture of db/+ islets with 0.125 mmol/l palmitate led to a decrease in glucose-induced insulin secretion, which was partially reversible by etomoxir. Both islet glucose oxidation and the ratio of glucose oxidation to utilization were decreased in db/db islets. Etomoxir significantly enhanced glucose oxidation by 60% and also the ratio of oxidation to glucose utilization (from 27 +/- 2.5 to 37 +/-3.0%, P < 0.05). Pyruvate dehydrogenase (PDH) activity was decreased in islets of db/db mice (75 +/-4.2 vs. 91 +/- 2.9 nU/ng DNA, P < 0.01), whereas PDH kinase activity was increased (rate of PDH inactivation -0.25 +/- 0.02 vs. - 0.11 +/- 0.02/min, P < 0.0 1). These abnormalities were partly but not wholly reversed by a 2-h preexposure to etomoxir. In conclusion, elevated FFA levels in the db/db mouse diminish glucose-induced insulin secretion by a glucose-fatty acid cycle in which fatty acid oxidation inhibits glucose oxidation by decreasing PDH activity and increasing PDH kinase activities. | [
"Aging",
"Animals"
] |
Modified nucleosides in the anticodon domain of Escherichia coli tRNA(Lys) are necessary for high-affinity codon recognition and reading frame maintenance. Human tRNA(Lys,3) is the specific primer for HIV-1 reverse transcriptase and also requires nucleoside modification for proper function. We now present NMR solution structures for the fully modified 17-nucleotide E. coli tRNA(Lys) anticodon stem-loop domain (ASL). NMR data were also collected for several partially modified ASLs, revealing the contributions each modified nucleoside (mnm(5)s(2)U34, t(6)A37, and psi39) makes in transforming the disordered, unmodified tRNA ASL into the highly ordered native structure. The solution structure of the native ASL domain provides insight into longstanding questions regarding both wobble position modification and the nearly ubiquitous t(6)A37 found in tRNAs with an adjacent U at position 36. Native tRNA(Lys) has a U-turn structure similar to the yeast tRNA(Phe) crystal structure, unlike previously proposed "unconventional" anticodon structures characterized by stable interactions between mnm(5)s(2)U-34 and t(6)A-37. | [
"Anticodon",
"Circular Dichroism"
] |
N-Me-anthranylaldoximes possess a hydrogen-bonded pseudocyclic A' ring in place of the typical phenolic A-ring that is characteristic of most estrogen receptor (ER) ligands. We have investigated the role played by substituents introduced into either one or both of the peripheral 3- and 4-phenyl rings in modulating ER binding affinity. An efficient synthetic strategy was employed for the preparation of differentially substituted 3- and 4-aryl derivatives that involved exploiting the different reactivity of bromo- versus chloro-aryl groups in palladium-catalyzed cross-couplings. The binding data showed that ERalpha affinity could be improved by a single p-OH group in the 4-phenyl ring, whereas the same substitution on the 3-phenyl ring caused a dramatic reduction of ERbeta affinity. The most ERalpha-selective compound was the one with two p-OH groups on both phenyl substituents. To rationalize these results, ligand docking followed by molecular mechanics Poisson-Boltzmann/surface area (MM-PBSA) studies were carried out. These analyses suggested a molecular basis for the interaction of these compounds with the ERs and enabled the development of models able to predict the mode of ligand binding. | [
"Benzene Derivatives",
"Binding Sites"
] |
Depending on the pH of the growth medium, the yeast Yarrowia lipolytica secretes an acidic protease or an alkaline protease, the synthesis of which is also controlled by carbon, nitrogen, and sulfur availability, as well as by the presence of extracellular proteins. Previous results have indicated that the alkaline protease response to pH was dependent on YlRim101p, YlRim8p/YlPalF, and YlRim21p/YlPalH, three components of a conserved pH signaling pathway initially described in Aspergillus nidulans. To identify other partners of this response pathway, as well as pH-independent regulators of proteases, we searched for mutants that affect the expression of either or both acidic and alkaline proteases, using a YlmTn1-transposed genomic library. Four mutations affected only alkaline protease expression and identified the homolog of Saccharomyces cerevisiae SIN3. Eighty-nine mutations affected the expression of both proteases and identified 10 genes. Five of them define a conserved Rim pathway, which acts, as in other ascomycetes, by activating alkaline genes and repressing acidic genes at alkaline pH. Our results further suggest that in Y. lipolytica this pathway is active at acidic pH and is required for the expression of the acidic AXP1 gene. The five other genes are homologous to S. cerevisiae OPT1, SSY5, VPS28, NUP85, and MED4. YlOPT1 and YlSSY5 are not involved in pH sensing but define at least a second protease regulatory pathway. | [
"Amino Acid Sequence",
"Aspartic Acid Endopeptidases"
] |
We evaluated the diagnostic value of pulse oximetry during sleep in pediatric obstructive sleep apnea syndrome (OSAS) caused by adenoid-tonsil hypertrophy. Subjects were 22 healthy children free of symptoms such as snoring, sleep apnea and oral breathing and 163 children suspected of OSAS with snoring or sleep apnea. Subjects were measured for percutaneous oxygen saturation (SpO2) during sleep. Of those with suspected OSAS, 69 underwent adenotonsillectomy and were measured for SpO2, both pre- and postoperatively, then pre- and postoperative measurements were compared. After measurement, we analyzed three parameters: lowest saturation (LSpO2), the desaturation index, and total desaturation duration under 95% (TDD95). Few abnormal findings were seen in healthy children. We calculated the mean and standard deviation (SD) of each parameter and set borderlines of mean-2SD for LSpO2 and mean + 2SD for ODI and TDD95. With these borderlines, 105 children for LSpO2, 75 for ODI and 76 for TDD 95 were judged to be normal among the 163 with suspected OSAS. Histograms showed that the mode of each parameter was situated near the borderline. Comparison between pre- and postoperative measurements showed that the effect of the surgery strongly correlated with preoperative measurement in patients undergoing surgery. Assuming that a patient with postoperative improvement is positive, we calculated sensitivity and specificity for each borderline measurement. We found that if success is 100%, the borderline should be 87% for LSpO2, 3.5 for ODI, and 30.0 for TDD95. If success exceeds 90%, the borderline should be 90% for LSpO2, 2.0 for ODI, and 7.0 for TDD95. We therefore conclude that measurement of SpO2 during sleep is useful in screening for pediatric OSAS. | [
"Adenoidectomy",
"Child"
] |
High-resolution melting analysis (HRMA) was compared with denaturing high-performance liquid chromatography (dHPLC) for mutation scanning of common mutations in the cystic fibrosis transmembrane conductance regulator gene. We amplified (polymerase chain reaction under conditions optimized for melting analysis or dHPLC) 26 previously genotyped samples with mutations in exons 3, 4, 7, 9, 10, 11, 13, 17b, and 21, including 20 different genotypes. Heterozygous mutations were detected by a change in shape of the melting curve or dHPLC tracing. All 20 samples with heterozygous mutations studied by both techniques were identified correctly by melting (100% sensitivity), and 19 were identified by dHPLC (95% sensitivity). The specificity of both methods also was good, although the dHPLC traces of exon 7 consistently revealed 2 peaks for wild-type samples, risking false-positive interpretation. Homozygous mutations could not be detected using curve shape by either method. However, when the absolute temperatures of HRMA were considered, G542X but not F508del homozygotes could be distinguished from wild type. HRMA easily detected heterozygotes in all single nucleotide polymorphism (SNP) classes (including A/T SNPs) and 1- or 2-base-pair deletions. HRMA had better sensitivity and specificity than dHPLC with the added advantage that some homozygous sequence alterations could be identified. HRMA has great potential for rapid, closed-tube mutation scanning. | [
"Chromatography, High Pressure Liquid",
"Cystic Fibrosis Transmembrane Conductance Regulator"
] |
We present the case of a 23-year-old man with a combined scaphoid fracture and comminuted trapezium fracture, treated surgically with percutaneous fixation of the scaphoid fracture and concomitant Arthrex Mini TightRope(®) stabilisation of base of thumb metacarpal to base of index finger metacarpal. The patient made a good functional recovery, returning to usual activities within six weeks. We suggest that this technique could be used to treat complex trapezium fractures that cannot be reconstructed with surgery. | [
"Accidents, Traffic",
"Bone Screws"
] |
DNA unzipping is a powerful tool to study protein-DNA interactions at the single-molecule level. In this chapter, we provide a detailed and practical guide to performing this technique with an optical trap, using nucleosome studies as an example. We detail protocols for preparing an unzipping template, constructing and calibrating the instrument, and acquiring, processing, and analyzing unzipping data. We also summarize major results from utilization of this technique for the studies of nucleosome structure, dynamics, positioning, and remodeling. | [
"Base Sequence",
"Chromatin Assembly and Disassembly"
] |
The interaction between renin, nitric oxide (NO), and its second messenger cGMP is controversial. cAMP is the stimulatory second messenger for renin but is degraded by phosphodiesterases (PDEs). We previously reported that increasing endogenous cGMP in rats by inhibiting its breakdown by PDE-5 stimulated renin secretion rate (RSR). This could be reversed by selective inhibition of neuronal nitric oxide synthase (nNOS). PDE-3 metabolizes cAMP, but this can be inhibited by cGMP, suggesting that renal cGMP could stimulate RSR by diminishing PDE-3 degradation of cAMP. Rats were anesthetized with Inactin before determination of blood pressure (BP), renal blood flow (RBF), and sampling of renal venous and arterial blood to determine RSR. In 13 rats, basal BP was 104 +/- 2 mmHg, RBF was 6.1 ml x min(-1) x g kidney wt(-1) and RSR was 2.9 +/- 1.4 ng ANG I x h(-1) x min(-1). Inhibiting PDE-5 with 20 mg/kg body wt i.p. Zaprinast did not change hemodynamic parameters but increased RSR fivefold to 12.2 +/- 4.9 ng ANG I x h(-1) x min(-1) (P < 0.05). Renal venous cAMP was increased by Zaprinast from 93.8 +/- 27.9 to 149.2 +/- 36.0 pM x min(-1) x g kidney wt(-1) (P < 0.05). When another 10 rats were treated with the PDE-3 inhibitor Milrinone (0.4 microg/min over 30 min, which did not affect hemodynamics), RSR was elevated to 10.4 +/- 4.4 ng ANG I x h(-1) x min(-1). Milrinone also increased renal venous cAMP from 212 +/- 29 to 304 +/- 29 pM x min(-1) x g kidney wt(-1) (P < 0.025). Administration of Zaprinast to rats pretreated with Milrinone (n = 10) did not further increase in RSR (7.5 +/- 3.3 ng ANG I x h(-1) x min(-1)). These results are consistent with endogenous renal cGMP inhibiting PDE-3, which diminishes renal metabolism of cAMP. The resulting increase in cAMP serves as an endogenous stimulus for renin secretion. This suggests a pathway by which NO can indirectly stimulate RSR through its second messenger cGMP. | [
"3',5'-Cyclic-AMP Phosphodiesterases",
"3',5'-Cyclic-GMP Phosphodiesterases"
] |
OBJECTIVES: Despite the central importance of pulmonary exacerbations (PExs) as an outcome measure in cystic fibrosis clinical trials, no standardized definition of PEx exists. We conducted a prospective, multicenter study to establish a standardized PEx definition and score for use in clinical trials, based on clinical status rather than on treatment decisions.STUDY DESIGN: Subjects were 246 patients enrolled in the placebo arm of a randomized, controlled trial of tobramycin for inhalation. Physician-investigators completed PEx questionnaires on all subjects at scheduled intervals during the 6-month study, indicating new or worsening symptoms, physical examination findings, and impression of PEx status (presence or absence and severity). Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx.RESULTS: We developed 2 PEx scores that use easily ascertained symptoms and chest examination findings; one also includes change in forced expiratory volume in 1 second over the preceding month. Both scores were sensitive and specific for predicting the presence of a PEx (sensitivity, 86%; specificity, 86%). The scores were validated in subjects in the intervention arm of the trial.CONCLUSION: We hope that the proposed PEx score might serve as a standardized outcome measure for future clinical trials in cystic fibrosis, allowing meaningful comparisons of study results. | [
"Administration, Inhalation",
"Adult"
] |
Ten screw-shaped commercially pure titanium implants were inserted in 10 rabbit tibia. The implants with surrounding bone were harvested after 12 weeks. The samples were processed to be cut and ground. Histomorphometrical analyses of the bone-to-metal contact and the bone area around the entire implants were performed on transvertically cut sections at intervals, starting with 100 microns thick sections; then the same sections were further ground down to 50, 30 and 10 microns. The thicker the section the more bone-to-metal contacts were demonstrated. A statistically significant difference was obtained when comparing the 100-30, 100-10, 50-30 and the 50-10 microns thick sections. Comparing the area measurements of 100-10, 50-30, 50-10 and 30-10 microns revealed a statistically significant difference. Bone-to-metal contact measurements on ground sections that are too thick (over 30 microns) may result in overestimations of the 'true' bony contacts. | [
"Animals",
"Bone and Bones"
] |
RATIONALE: The long-term respiratory sequelae of infants born extremely preterm (EP) and now graduating from neonatal intensive care remains uncertain.OBJECTIVES: To assess the degree of respiratory morbidity and functional impairment at 11 years in children born EP (i.e., at or less than 25 completed weeks of gestation) in relation to neonatal determinants and current clinical status.METHODS: Pre- and postbronchodilator spirometry were undertaken at school in children born EP and classroom control subjects. Physical examination and respiratory health questionnaires were completed. Multivariable regression was used to estimate the predictive power of potential determinants of lung function.MEASUREMENTS AND MAIN RESULTS: Spirometry was obtained in 182 of 219 children born EP (129 with prior bronchopulmonary dysplasia [BPD]) and 161 of 169 classmates, matched for age, sex, and ethnic group. Children born EP had significantly more chest deformities and respiratory symptoms than classmates, with twice as many (25 vs. 13%; P < 0.01) having a current diagnosis of asthma. Baseline spirometry was significantly reduced (P < 0.001) and bronchodilator responsiveness was increased in those born EP, the changes being most marked in those with prior BPD. EP birth, BPD, current symptoms, and treatment with beta-agonists are each associated independently with lung function z-scores (adjusted for age, sex, and height) at 11 years. Fifty-six percent of children born EP had abnormal baseline spirometry and 27% had a positive bronchodilator response, but less than half of those with impaired lung function were receiving any medication.CONCLUSIONS: After extremely preterm birth, impaired lung function and increased respiratory morbidity persist into middle childhood, especially among those with BPD. Many of these children may not be receiving appropriate treatment. | [
"Asthma",
"Bronchial Hyperreactivity"
] |
Endothelial cells respond to fluid flow by elongating in the direction of flow. Cytoskeletal changes and activation of signalling molecules have been extensively studied in this response, including: activation of receptors by mechano-transduction, actin filament alignment in the direction of flow, changes to cell-substratum adhesions, actin-driven lamellipodium extension, and localised activation of Rho GTPases. To study this process we model the force over a single cell and couple this to a model of the Rho GTPases, Rac and Rho, via a Kelvin-body model of mechano-transduction. It is demonstrated that a mechano-transducer can respond to the normal component of the force is likely to be a necessary component of the signalling network in order to establish polarity. Furthermore, the rate-limiting step of Rac1 activation is predicted to be conversion of Rac-GDP to Rac-GTP, rather than activation of upstream components. Modelling illustrates that the aligned endothelial cell morphology could attenuate the signalling network. | [
"Actin Cytoskeleton",
"Animals"
] |
Previous studies have demonstrated the presence of multiple strains of Marek's disease virus simultaneously circulating within poultry flocks, leading to the assumption that individual birds are repeatedly exposed to a variety of virus strains in their lifetime. Virus competition within individual birds may be an important factor that influences the outcome of co-infection under field conditions, including the potential outcome of emergence or evolution of more virulent strains. A series of experiments was designed to evaluate virus competition within chickens following simultaneous challenge with two virulent serotype 1 Marek's disease virus strains, using either pathogenically similar (rMd5 and rMd5/pp38CVI) or dissimilar (JM/102W and rMd5/pp38CVI) virus pairs. Bursa of Fabricius, feather follicle epithelium, spleen, and tumour samples were collected at multiple time points to determine the frequency and distribution of each virus present using pyrosequencing, immunohistochemistry and virus isolation. In the similar pair, rMd5 appeared to have a competitive advantage over rMd5/pp38CVI, which in turn had a competitive advantage over the less virulent JM/102W in the dissimilar virus pair. Dominance of one strain over the other was not absolute for either virus pair, as the subordinate virus was rarely eliminated. Interestingly, competition between two viruses with either pair rarely ended in a draw. Further work is needed to identify factors that influence virus-specific dominance to better understand what characteristics favour emergence of one strain in chicken populations at the expense of other strains. | [
"Animals",
"Antibodies, Monoclonal"
] |
Telomeres prevent chromosome ends from being repaired as double-strand breaks (DSBs). Telomere identity in Drosophila is determined epigenetically with no sequence either necessary or sufficient. To better understand this sequence-independent capping mechanism, we isolated proteins that interact with the HP1/ORC-associated protein (HOAP) capping protein, and identified HipHop as a subunit of the complex. Loss of one protein destabilizes the other and renders telomeres susceptible to fusion. Both HipHop and HOAP are enriched at telomeres, where they also interact with the conserved HP1 protein. We developed a model telomere lacking repetitive sequences to study the distribution of HipHop, HOAP and HP1 using chromatin immunoprecipitation (ChIP). We discovered that they occupy a broad region >10 kb from the chromosome end and their binding is independent of the underlying DNA sequence. HipHop and HOAP are both rapidly evolving proteins yet their telomeric deposition is under the control of the conserved ATM and Mre11-Rad50-Nbs (MRN) proteins that modulate DNA structures at telomeres and at DSBs. Our characterization of HipHop and HOAP reveals functional analogies between the Drosophila proteins and subunits of the yeast and mammalian capping complexes, implicating conservation in epigenetic capping mechanisms. | [
"Animals",
"Binding Sites"
] |
The partition coefficient of solutes into the polyamide active layer of reverse osmosis (RO) membranes is one of the three membrane properties (together with solute diffusion coefficient and active layer thickness) that determine solute permeation. However, no well-established method exists to measure solute partition coefficients into polyamide active layers. Further, the few studies that measured partition coefficients for inorganic salts report values significantly higher than one (?3-8), which is contrary to expectations from Donnan theory and the observed high rejection of salts. As such, we developed a benchtop method to determine solute partition coefficients into the polyamide active layers of RO membranes. The method uses a quartz crystal microbalance (QCM) to measure the change in the mass of the active layer caused by the uptake of the partitioned solutes. The method was evaluated using several inorganic salts (alkali metal salts of chloride) and a weak acid of common concern in water desalination (boric acid). All partition coefficients were found to be lower than 1, in general agreement with expectations from Donnan theory. Results reported in this study advance the fundamental understanding of contaminant transport through RO membranes, and can be used in future studies to decouple the contributions of contaminant partitioning and diffusion to contaminant permeation. | [
"Boric Acids",
"Membranes, Artificial"
] |
Microaerobic (oxygen-limited) conditions are critical for inducing many important microbial processes in industrial or environmental applications. At very low oxygen concentrations, however, the process performance often suffers from technical limitations. Available dissolved oxygen measurement techniques are not sensitive enough and thus control techniques, that can reliable handle these conditions, are lacking. Recently, we proposed a microaerobic process control strategy, which overcomes these restrictions and allows to assess different degrees of oxygen limitation in bioreactor batch cultivations. Here, we focus on the design of a control strategy for the automation of oxygen-limited continuous cultures using the microaerobic formation of photosynthetic membranes (PM) in Rhodospirillum rubrum as model phenomenon. We draw upon R. rubrum since the considered phenomenon depends on the optimal availability of mixed-carbon sources, hence on boundary conditions which make the process performance challenging. Empirically assessing these specific microaerobic conditions is scarcely practicable as such a process reacts highly sensitive to changes in the substrate composition and the oxygen availability in the culture broth. Therefore, we propose a model-based process control strategy which allows to stabilize steady-states of cultures grown under these conditions. As designing the appropriate strategy requires a detailed knowledge of the system behavior, we begin by deriving and validating an unstructured process model. This model is used to optimize the experimental conditions, and identify properties of the system which are critical for process performance. The derived model facilitates the good process performance via the proposed optimal control strategy. In summary the presented model-based control strategy allows to access and maintain microaerobic steady-states of interest and to precisely and efficiently transfer the culture from one stable microaerobic steady-state into another. Therefore, the presented approach is a valuable tool to study regulatory mechanisms of microaerobic phenomena in response to oxygen limitation alone. Biotechnol. Bioeng. 2014;111: 734-747. © 2013 Wiley Periodicals, Inc. | [
"Aerobiosis",
"Bioreactors"
] |
Most reported carbazolyl G-quadruplex DNA (G4-DNA) ligands possess a rigid structure rather than a flexible one. The conformationally flexible ligands are paid much less attention. In this study, we report a novel class of non-rigid methylene-bridged biscarbazolyl ligand and their G4-DNA binding properties. Moreover, the antitumor activities of all these oligomers have been evaluated. The results show that this family of oligomers could be facilely synthesized via solely one step. Among them, compound 2, the bis-carbazole derivative, displays the best antitumor activity and IC50 values against HT-29, HepG2, A375 and MCF-7 cells are 0.69, 5.09, 3.15 and 3.8 ì mol/L, respectively. Although conformationally flexible, 2 is still capable of binding to as well as stabilizing G4-DNA via ð-ð stacking interaction. Moreover, 2 selectively binds to G4-DNA over duplex DNA. The current study enriches the category of carbazolyl G4-DNA ligands and paves the way for the search of more efficient G4-DNA ligands and antitumor leads. | [
"Antineoplastic Agents",
"Apoptosis"
] |
The menisci are first seen as triangular aggregations of cells in the 20-day rabbit fetus. At 25-days, a matrix that contains types I, III and V collagens has formed. These collagens are also found in the 1-week neonatal meniscus, but by 3 weeks, type II collagen is present in some regions. By 12 to 14 weeks, typically cartilaginous areas with large cells in lacunae are found and by 2 years, these occupy the central regions of the inner two-thirds of the meniscus. The surface layers of the meniscus contain predominantly type I collagen. From 12 to 14 weeks onwards, there is little overlap between the regions with types I or II collagens, that is, these are discrete regions of type I-containing fibrocartilage and type II-containing cartilage. Types III and V collagens are found throughout the menisci, particularly in the pericellular regions. All the cells in the fetal and early neonatal menisci express the mRNA for type I collagen. At 3 weeks postnatal, cells that express type I collagen mRNA are found throughout the meniscus, but type II collagen mRNA is expressed only in the regions of developing cartilage. At 12- to 14-weeks, only type II collagen mRNA is expressed, except at the periphery next to the ligament where a few cells still express type I collagen mRNA. Rabbit menisci, therefore, undergo profound changes in their content and arrangement of collagens during postnatal development. | [
"Aging",
"Animals"
] |
PURPOSE: To assess the performance, in the presence of scanner instabilities, of three dynamic correction methods which integrate ?B0 mapping into the chemical exchange saturation transfer (CEST) measurement and three established static ?B0 -correction approaches.METHODS: A homogeneous phantom and five healthy volunteers were scanned with a CEST sequence at 7 T. The in vivo measurements were performed twice: first with unaltered system frequency and again applying frequency shifts during the CEST acquisition. In all cases, retrospective voxel-wise ?B0 -correction was performed using one intrinsic and two extrinsic [prescans with dual-echo gradient-echo and water saturation shift referencing (WASSR)] static approaches. These were compared with two intrinsic [using phase data directly generated by single-echo or double-echo GRE (gradient-echo) CEST readout (CEST-GRE-2TE)] and one extrinsic [phase from interleaved dual-echo EPI (echo planar imaging) navigator (NAV-EPI-2TE)] dynamic ?B0 -correction approaches [allowing correction of each Z-spectral point before magnetization transfer ratio asymmetry (MTRasym ) analysis].RESULTS: All three dynamic methods successfully mapped the induced drift. The intrinsic approaches were affected by the CEST labeling near water (?ù < |0.3| ppm). The MTRasym contrast was distorted by the frequency drift in the brain by up to 0.21%/Hz when static ?B0 -corrections were applied, whereas the dynamic ?B0 corrections reduced this to <0.01%/Hz without the need of external scans. The CEST-GRE-2TE and NAV-EPI-2TE resulted in highly consistent MTRasym values with/without drift for all subjects.CONCLUSION: Reliable correction of scanner instabilities is essential to establish clinical CEST MRI. The three dynamic approaches presented improved the ?B0 -correction performance significantly in the presence of frequency drift compared to established static methods. Among them, the self-corrected CEST-GRE-2TE was the most accurate and straightforward to implement. | [
"Adult",
"Brain"
] |
Ethyl alcohol is a toxin that, when consumed at high levels, produces organ damage and death. One way to prevent or ameliorate this damage in humans is to reduce the exposure of organs to alcohol by reducing alcohol ingestion. Both the propensity to consume large volumes of alcohol and the susceptibility of human organs to alcohol-induced damage exhibit a strong genetic influence. We have developed an integrative genetic/genomic approach to identify transcriptional networks that predispose complex traits, including propensity for alcohol consumption and propensity for alcohol-induced organ damage. In our approach, the phenotype is assessed in a panel of recombinant inbred (RI) rat strains, and quantitative trait locus (QTL) analysis is performed. Transcriptome data from tissues/organs of na?ve RI rat strains are used to identify transcriptional networks using Weighted Gene Coexpression Network Analysis (WGCNA). Correlation of the first principal component of transcriptional coexpression modules with the phenotype across the rat strains, and overlap of QTLs for the phenotype and the QTLs for the coexpression modules (module eigengene QTL) provide the criteria for identification of the functionally related groups of genes that contribute to the phenotype (candidate modules). While we previously identified a brain transcriptional module whose QTL overlapped with a QTL for levels of alcohol consumption in HXB/BXH RI rat strains and 12 selected rat lines, this module did not account for all of the genetic variation in alcohol consumption. Our search for QTL overlap and correlation of coexpression modules with phenotype can, however, be applied to any organ in which the transcriptome has been measured, and this represents a holistic approach in the search for genetic contributors to complex traits. Previous work has implicated liver/brain interactions, particularly involving inflammatory/immune processes, as influencing alcohol consumption levels. We have now analyzed the liver transcriptome of the HXB/BXH RI rat panel in relation to the behavioral trait of alcohol consumption. We used RNA-Seq and microarray data to construct liver transcriptional networks, and identified a liver candidate transcriptional coexpression module that explained 24% of the genetic variance in voluntary alcohol consumption. The transcripts in this module focus attention on liver secretory products that influence inflammatory and immune signaling pathways. We propose that these liver secretory products can interact with brain mechanisms that affect alcohol consumption, and targeting these pathways provides a potential approach to reducing high levels of alcohol intake and also protecting the integrity of the liver and other organs. | [
"Alcohol Drinking",
"Animals"
] |
Nucleosides cross the human erythrocyte membrane by a facilitated-diffusion process which is selectively inhibited by nanomolar concentrations of nitrobenzylthioinosine (NBMPR). The chemical asymmetry of the transporter was investigated by studying the effects of p-chloromercuriphenyl sulphonate (PCMBS) on uridine transport and high-affinity NBMPR binding in inside-out and right-side-out membrane vesicles, unsealed erythrocyte ghosts and intact cells. PCMBS was an effective inhibitor of the transporter (50% inhibition at 30 microM), but only when the organomercurial had access to the cytoplasmic membrane surface. PCMBS inhibition of NBMPR binding to ghosts was reversed by incubation with dithiothreitol. Both uridine and NBMPR were able to protect the transporter against PCMBS inhibition. | [
"4-Chloromercuribenzenesulfonate",
"Biological Transport, Active"
] |
Lupus-like syndrome is characterized by multiple organ injuries including lungs and kidneys. Endotoxin induces a transiently intent systemic inflammatory response and indirectly transient acute lung injury in normal condition. However, whether endotoxin may trigger the persistent development of lung injury in chronic, inflammatory lupus-like syndrome compared with normal condition remains unclear. We examined the pulmonary vascular permeability and production of proinflammatory cytokines, such as TNF-alpha, IL-6, IL-10 and IFN-gamma, which play prominent roles in the pathogenesis of lupus-like tissue injury, 6 h and 72 h after i.p. lipopolysaccharide (LPS; endotoxin) injection in pristane-primed chronic inflammation ICR mice characterized by a lupus-like syndrome. These results demonstrated that levels of serum IL-6, IL-10 and IFN-gamma and bronchoalveolar lavage (BAL) IL-6 and IFN-gamma were remarkably increased 6 h in LPS-exposed pristane-primed mice compared with pristane-primed controls, while pulmonary vascular permeability and levels of serum and BAL TNF-alpha were not. And levels of BAL TNF-alpha, IL-6 and IL-10 were significantly enhanced 72 h in LPS-exposed pristane-primed mice compared with pristane-primed controls. Also, LPS significantly induced the increased in vitro production of TNF-alpha, IL-6 and IL-10 by lung cells obtained from LPS-exposed pristane-primed mice compared with LPS-exposed normal mice. Our findings indicate that LPS may trigger persistent progression of lung injury through late overproduction of BAL TNF-alpha, IL-6, and IL-10 in lupus-like chronic inflammation syndrome compared with normal condition. | [
"Animals",
"Bronchoalveolar Lavage Fluid"
] |
Leukaemic blast cells from 20 patients with acute leukaemia were examined for their capacity to mediate cytotoxicity against ox red blood cells in the presence of phorbol myristate acetate (PMA), a system widely employed as an in vitro model of tissue damage by metabolically activated mature phagocytes. Blasts from certain patients with myelomonocytic and monocytic leukaemia behaved like efficient killer cells. Conversely, leukaemic myeloblasts and promyelocytes as well as leukaemic lymphoblasts were ineffective. Blast cells capable of inducing the target cell lysis were also capable of mounting an oxidative respiratory burst upon challenge with PMA, as detected by the superoxide anion release. N-ethyl-maleimide, superoxide dismutase and catalase completely inhibited the cytotoxicity by monocytoid blast cells, suggesting the involvement of oxygen reactive products in the lethal hit itself. The cytolytic potential of blasts committed to monocytic differentiation might be an additional factor contributing to the tissue damage in a subpopulation of leukaemic patients. | [
"Adult",
"Cytotoxicity Tests, Immunologic"
] |
In 1865, Spanish Jesuits founded the Manila Observatory, the earliest of the Far East centres devoted to typhoon and earthquake studies. Also on Philippine soil and under the direction of the Jesuits, in 1884 the Madrid government inaugurated the first Meteorological Service in the Spanish Kingdom, and most probably in the Far East. Nevertheless, these achievements not only went practically unnoticed in the historiography of science, but neither does the process of geophysical dissemination that unfolded fit in with the two types of transmitter of knowledge identified by historians in the missionary diffusion of the exact sciences in colonial contexts. Rather than regarding science as merely a stimulus to their functionary and missionary tasks, Spanish Jesuits used their overseas posting to produce and publish original research--feature that would place them within the typology of the 'seeker' rather than the 'functionary' (in stark contrast to what the standard typology sustains). This paper also analyses examples of synergies between science, education and trade, which denotes, inter alia, the existence of a broad and solid educational structure in the Manila Mission that sustained the strength of research enterprise. | [
"Colonialism",
"Commerce"
] |
OBJECTIVE: Scorpion venom, considered as a treasure trove of various bioactive molecules, is a new approach to induce cancer cell death via apoptosis pathways. In the present study, we evaluated for first time the anti-proliferative efficacy of Hemiscorpius lepturus scorpion venom and its pathway on a colon carcinoma cell.MATERIALS AND METHODS: The CT26 and VERO cell lines were treated with various concentrations of the venom. The IC50 values were estimated by MTT assay test, and the apoptosis was evaluated by flow cytometry. Moreover, RT-PCR analysis was used to investigate the levels of Bax, Bcl2, Trp53, and Casp3 mRNA expression. The mice xenograft model was established to evaluate the therapy efficiency of venom. Some valuable exponential growth parameters were evaluated in treated mice.RESULT: The scorpion venom inhibited the growth of CT26 cells with an IC50 value about 120 ìg/ml. However, VERO cells increased to 896 ìg/ml under the same condition. A remarkable apoptotic cells in CT26 cells were revealed by flow cytometry assay. A significant over-expression was observed in Bax, Casp3, and Trp53 and downregulated in Bcl2 mRNA level in tumor tissue after treatment with scorpion venom (p < 0.05). All changes of valuable exponential growth parameters showed a shrinking tumor size.CONCLUSION: Our findings indicated that Hemiscorpius lepturus venom has a special anti-proliferative effect on CT26 cells via Trp53/Bcl2/Casp3 pathway. Considering its powerful cytotoxic vigor against a colon cancer cell (CT26) and low toxicity to non-tumorigenic cell (VERO), we propose that this venom probably has a specific effect on other colon cancer cells and may turn out to be a novel therapeutic strategy in treating colon cancer. | [
"Animals",
"Apoptosis"
] |
On the basis of nucleotide sequences of the coding region and their predicted amino acid sequences, 58 glycoprotein hormone subunit genes were compared, aligned and used to construct phylogenetic trees for this family. The analysis included 17 alpha-subunits, eight TSH beta-, six FSH beta-, 17 LH beta/CG beta-, four fish gonadotropin (GTH)-I beta-, five fish GTH-II beta- and one additional fish GTH beta-subunit. The reliability of the phylogenetic trees was probed with the bootstrapping test. Our results indicated that: both the alpha- and beta-subunits of the family diverged from a common ancestral gene about 927 million years ago, the initial precursor of the beta-subunit duplicated to give rise to the LH beta and a second hormone, the latter then duplicating to FSH beta and TSH beta, so that FSH beta is related more to TSH beta than to LH beta; and bony fish GTH-I beta is highly related to mammalian FSH beta, whereas the bony fish GTH-II beta is more related to mammalian LH beta. For scientific consistency and convenience, we propose that the following nomenclature be adopted, all fish gonadotropins of type I be classified as FSH and all type II be classified as LH hormones. In addition, on the basis of results from this and other studies, we propose an evolutionary history for this glycoprotein hormone family. Reconstruction of the evolutionary history of this family would not only provide clues to understanding thyrotropin and gonadotropin functions, but would also allow further revision of the present nomenclature of the gonadotropins in fish. | [
"Amino Acid Sequence",
"Animals"
] |
BACKGROUND AND OBJECTIVE: To assess the role of ultrasound biomicroscopy in the surgical management of eyes with stage 5 retinopathy of prematurity.PATIENTS AND METHODS: Ultrasound biomicroscopy was performed preoperatively in 18 eyes with stage 5 retinopathy of prematurity to view the access to the anterior surgical space.RESULTS: Of the 15 (83.3%) eyes with anterior open funnel on B-scan ultrasonography, only 8 (53.3%) eyes had open access to the anterior surgical space and were scheduled for lensectomy.CONCLUSION: Ultrasound biomicroscopy is an effective tool for assessing anterior surgical space and helps surgical decision making in vitreoretinal surgery in eyes with stage 5 retinopathy of prematurity. | [
"Female",
"Follow-Up Studies"
] |
OBJECTIVES: Currently, there are no cardiovascular (CV) preprocedure screening parameters for patients undergoing in-office laryngeal procedures (IOLP). Studies have shown significant changes in CV measures for IOLP. The aim was to develop and evaluate a pre-IOLP CV screening protocol.METHODS: Review of IOLP literature and consultation with an anesthesiologist and cardiologist led to the development of CV parameters and questions related to four metabolic equivalents (METS) of work as a patient-screening tool before IOLP. A separate cohort was screened with only a modified CV protocol. All patients were screened for heart rate (HR) and blood pressure (BP) elevation prior to the procedure. Need for further CV evaluation was characterized as systolic blood pressure BP >160, diastolic BP >100, and/or HR >110 beats/minute. Patients whose BP/HR exceeded these values were referred to their primary care physician (PCP) before re-screening. If parameters were exceeded again at the second screen, then the procedure was done under monitored anesthesia care.RESULTS: The first study phase included 56 patients. The fail rate was 40% largely related to four METS of work. The second study phase included 440 patients. The screen fail rate was 15 patients of 572 (2.6%). Of these, 12 patients of 132 (9.1%) failed the initial screen and were sent to their PCP for further evaluation, and five of 440 (1.4%) patients failed on the day of the procedure. Overall, five of 440 (1.5%) patients would qualify to have their site of service changed for their laryngology procedure from an unmonitored to a monitored setting due to the prescreening criteria.CONCLUSION: Few patients needed further workup based upon the in-office CV parameters set in this study. Patients with CV risk factors were identified by the screening protocol. Having established hemodynamic parameters in place may improve the safety of IOLP with a very low physician burden.LEVEL OF EVIDENCE: 2b Laryngoscope, 127:1845-1849, 2017. | [
"Adult",
"Aged"
] |
The HIV/AIDS epidemic along Honduras' north coast has intensified in recent years and become particularly severe in Gar?funa communities. Based on a qualitative study in the community of Las Espinas and comparison with results from an earlier knowledge, attitudes, beliefs and practices survey, this article explores Gar?funa ideas about the disease, focusing on issues of risk perception and stigma. Using correspondence analysis with data from systematic elicitation techniques we abstract the local schema of HIV/AIDS, showing how accurate knowledge of transmission co-occurs with cultural judgments about safe partners, increasing chances for infection. Despite broad familiarity with the disease in the community it remains highly stigmatized, suggesting continuing problems in coming to terms with the epidemic as treatment becomes more widely available in Honduras. Questions of power, sexuality and affective expectations about partners complicate the situation for women hoping to prevent infection. Given the broader risk environment characterized by labor migration and transnational movement, vital interventions and educational efforts in Gar?funa communities will need to be complemented with prevention efforts in contexts where men make a living. | [
"Adolescent",
"Adult"
] |
BACKGROUND: The use of complementary and alternative medicines (CAM) and CAM practitioners is common, most frequently for the management of musculoskeletal conditions. Knowledge is limited about the use of CAM practitioners by older people, and specifically those with other long term or chronic conditions.METHODS: In 2011 we conducted an Australia wide survey targeting older adults aged over 50 years (n = 2540). Participants were asked to identify their chronic conditions, and from which health professionals they had 'received advice or treatment from in the last 3 months', including 'complementary health practitioners, e.g. naturopath'. Descriptive analyses were undertaken using SPSS and STATA software.RESULTS: Overall, 8.8% of respondents reported seeing a CAM practitioner in the past three months, 12.1% of women and 3.9% of men; the vast majority also consulting medical practitioners in the same period. Respondents were more likely to report consulting a CAM practitioner if they had musculoskeletal conditions (osteoporosis, arthritis), pain, or depression/anxiety. Respondents with diabetes, hypertension and asthma were least likely to report consulting a CAM practitioner. Those over 80 reported lower use of CAM practitioners than younger respondents. CAM practitioner use in a general older population was not associated with the number of chronic conditions reported, or with the socio-economic level of residence of the respondent.CONCLUSION: Substantial numbers of older Australians with chronic conditions seek advice from CAM practitioners, particularly those with pain related conditions, but less often with conditions where there are clear treatment guidelines using conventional medicine, such as with diabetes, hypertension and asthma. Given the policy emphasis on better coordination of care for people with chronic conditions, these findings point to the importance of communication and integration of health services and suggest that the concept of the 'treating team' needs a broad interpretation. | [
"Aged",
"Aged, 80 and over"
] |
To assess the possible role of amine neurotransmitters in human epilepsy, we measured metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylethylene glycol [MHPG]) in the lumbar cerebrospinal fluid (CSF) of patients with partial complex seizures and in neurologic controls. Untreated epileptic patients had lower concentrations of 5-HIAA and HVA in the lumbar CSF than the controls, but the differences were not statistically significant. Among epileptic patients receiving effective antiepileptic drug treatment, the HVA concentration was within the control range. Mean MHPG concentrations were similar in patients and controls. From the epileptic patients whose CSF was obtained at pneumoencephalography we obtained a second sample of CSF that was originally in the basal cisterns. No significant differences between treated and untreated patients were found for any of the three metabolites. The concentrations of HVA and 5-HIAA were higher in cisternal than in lumbar CSF, but there was no such gradient for MHPG. | [
"Adolescent",
"Adult"
] |
BACKGROUND: The aim of this study was to assess the long-term risk of death or acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) compared with that in patients without DM after coronary artery bypass grafting (CABG).METHODS: National registers were used to record death or AMI occurring in 6727 patients who had CABG during 1980 to 1995. Diabetes mellitus in 856 patients (13%) was classified as type 1 (6%) or type 2 treated with insulin (29%), oral drugs (46%), or diet (19%).RESULTS: The risk of death < or = 30 days of the operation was increased in patients with insulin-treated type 2 DM (odds ratio [OR] 4.6, 95% CI 2.5-8.4) and in those on oral antidiabetic drugs (OR 2.0, 95% CI 1.0-3.8), but not in diet-treated diabetic patients, compared with that in patients without diabetes. At 10 years, the relative risk of death or having an AMI was 1.8 (95% CI 1.5-2.2) in insulin-treated patients and 1.4 (95% CI 1.2-1.7) in patients on oral drugs. No increased risk of late death or AMI was observed in diet-treated patients with diabetes compared with patients without diabetes. Survival at 10 years without an AMI was 40% in insulin-treated type 2 diabetic patients, 48% if on oral drugs, and 59% if diet managed, compared with 66% in nondiabetic patients.CONCLUSION: Type 2 DM requiring insulin treatment or oral antidiabetic drugs is associated with an increased early and long-term risk of death or AMI after CABG, whereas diet-treated patients have a risk similar to that in patients without diabetes. | [
"Adult",
"Aged"
] |
Metabolic cooperation between cells from three human hepatoma cell lines was studied by the clonogenic method and by autoradiography. It was found that human HGPRT+/HGPRT- SK-HEP-1 cells only, showed a metabolic cooperation capacity that was inhibited by tumour promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and phenobarbital, and was not inhibited by the non-promoter 4-O-methyl TPA, provided suitable experimental conditions (short exposure times) were used. This biological system might be the basis of a new in vitro short-term screening test for potential tumour-promoting chemicals. | [
"Carcinogens",
"Carcinoma, Hepatocellular"
] |
Renal calculous disease is an infrequent but not insignificant occurrence during pregnancy. In 50 to 80% of the cases conservative management is appropriate and the stone will pass spontaneously. Should intervention be required, recent advances in stone management and techniques for urinary tract drainage may be successfully applied to the obstetric population. Concerns regarding surgical and anesthetic risks, and the potential hazards of radiation exposure during pregnancy favor a minimally invasive approach with definitive treatment late in pregnancy or post partum. We review our experience during a 5-year period in managing 29 patients with urinary calculous disease during pregnancy. Based on our experience and review of the literature an algorithm for treatment of urolithiasis during pregnancy is proposed. | [
"Adolescent",
"Adult"
] |
A protocol was developed for the detection of fatty acid oxidation disorders (FOD) in cases of sudden unexpected death in infancy (SUDI). Tandem mass spectrometry blood acylcarnitine analysis of Guthrie card blood spots was performed. In the first 5 years, 1.2% of Oregon's 247 SUDI cases were identified with FOD, 2 with medium-chain acyl-CoA dehydrogenase deficiency, and one with very long-chain acyl-CoA dehydrogenase deficiency. | [
"Acyl-CoA Dehydrogenase, Long-Chain",
"Fatty Acids"
] |
We investigated whether in utero exposure to the Gram(-) bacteriotoxin lipopolysaccharide (LPS) induces dopamine (DA) neuron loss in rats. The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) kills DA neurons and is elevated in the brains of patients with Parkinson's disease (PD). LPS is a potent inducer of TNF-alpha, and both are increased in the chorioamniotic environment of women who have bacterial vaginosis (BV) during pregnancy, suggesting that BV might interfere with the normal development of fetal DA neurons. Gravid female rats were injected intraperitoneally with either LPS or normal saline at embryonic day 10.5 and their pups were killed at postnatal day 21. The brains of the pups were assessed for DA and TNF-alpha levels and DA cell counts in the mesencephalon using tyrosine hydroxylase immunoreactive (THir) cells as a DA neuron marker. Prenatal LPS exposure significantly reduced striatal DA (29%) and increased DA activity (72%) as well as TNF-alpha (101%). Stereological cell counts in the mesencephalon were also significantly reduced (27%) by prenatal LPS exposure. Prenatal exposure to LPS, as might occur in humans with BV, produces a significant loss of THir cells in rats that is still present 33 days following a single injection of LPS. Since this cell loss is well past the normal phase of DA neuron apoptosis that occurs in early postnatal life, rats so exposed may have a permanent loss of DA neurons, suggesting that prenatal infections may represent risk factors for PD. | [
"Animals",
"Animals, Newborn"
] |
This paper presents an electronic registry system for the purposes of the eENERCA for rare congenital conditions that require lifelong follow up and treatment. The main objective of the eENERCA project focusses on the prevention of major rare anaemias (RAs) by facilitating the access, at a European level, to the best genetic counselling, diagnosis and clinical management of the patients with RA independently of their country of origin. This can be achieved by promoting an extension of the full Electronic Health Record system and specifically the electronic registries for RAs, across Europe for the purposes stated hence promoting service development for the benefit of patients. The proposed eRegistry will serve as an epidemiological tool to improve the management of patient services and ultimately improve patient care. | [
"Anemia",
"Congenital Abnormalities"
] |
OBJECTIVE: To investigate the effects of different concentrations of lipopolysaccharide (LPS), tumor necrosis factor á (TNFá), interleukin-6 (IL-6), dexamethasone (Dex), and insulin on the mRNA and protein expressions of GPR54 in the MCF7 cell line in vitro.METHODS: MCF7 breasr cancer cells were cultured and treated with different concentrations of LPS (10 and 20 µg/ml), TNFá (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L). Those treated with culture fluid only served as controls. The mRNA and protein expressions of GPR54 were measured by real-time PCR and Western blot, respectively, after 6, 24, 48, and 72 hours of treatment.RESULTS: Compared with the blank con- trol, LPS (10 and 20 µg/ml), TNFá (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L) significantly increased the expressions of GPR54 mRNA (P < 0.05) and protein (P < 0.05).CONCLUSION: LPS, TNFá, IL-6, Dex, and insulin evidently increase the expression of GPR54 in the MCF7 cell line, indicating their influence on the function of gonads by regulating the GPR54 level. | [
"Blotting, Western",
"Dexamethasone"
] |
RNA molecules play many pivotal roles in a cell that are still not fully understood. Any detailed understanding of RNA function requires knowledge of its three-dimensional structure, yet experimental RNA structure resolution remains demanding. Recent advances in sequencing provide unprecedented amounts of sequence data that can be statistically analyzed by methods such as direct coupling analysis (DCA) to determine spatial proximity or contacts of specific nucleic acid pairs, which improve the quality of structure prediction. To quantify this structure prediction improvement, we here present a well curated data set of about 70 RNA structures of high resolution and compare different nucleotide-nucleotide contact prediction methods available in the literature. We observe only minor differences between the performances of the different methods. Moreover, we discuss how robust these predictions are for different contact definitions and how strongly they depend on procedures used to curate and align the families of homologous RNA sequences. | [
"Data Analysis",
"Datasets as Topic"
] |
It is well established that schizophrenia is associated with difficulties in recognizing facial emotional expressions, but few studies have reported the presence of this deficit among their unaffected relatives. This study attempts to add new evidence of familial association on an emotional expression processing test. The study evaluated the performance of 93 paranoid schizophrenia patients, 110 first-degree relatives of probands from multiplex schizophrenia families, and 109 nonpsychiatric controls on a facial emotional recognition test using a computer morphing technique to present the dynamic expressions. The task entailed the recognition of a set of facial expressions depicting the six basic emotions presented in 21 successive frames of increasing intensity. The findings indicated that schizophrenia patients were consistently impaired for the recognition of the six basic facial expressions. In contrast, their unaffected relatives showed a selective impairment for the recognition of disgust and fearful expressions. Familial association of selective facial emotional expressions processing deficit may further implicate promising new endophenotypes that can advance the understanding of affective deficits in schizophrenia. | [
"Adult",
"Analysis of Variance"
] |
Differentiation of male germ cells requires a continuous cross-talk with their somatic support, the Sertoli cell. An in vitro model of Sertoli cells was recently provided by established cell lines which maintain Sertoli-specific characteristics, among which is a regulated phagocytic capacity. In vivo, Sertoli cells take up the residual cytoplasm expelled from the maturing sperm, a process restricted to a limited period of germinal maturation, and they also eliminate abnormally differentiated germ cells in case of hormonal deficiency. Cells of the Sertoli line efficiently take up latex beads, as well as dead cells in the cultures. A semiquantitative assay of phagocytosis was developed, based on the uptake of fluorescent latex beads. 15P-1 cultures were found to contain a minor fraction of active phagocytes. After addition of a defined fraction of germ cells, however, all the cells internalized beads as efficiently as macrophages. The inducing cell was identified as the pachytene spermatocyte, a cell type which, in vivo, is associated with Sertoli cells when they express their phagocytic potential. These inducing meiotic cells were not internalized themselves. Rather, they interacted with Sertoli cells via a surface signal that was resistant to formaldehyde fixation. The whole induction process does not involve changes in Sertoli gene expression, since it occurs even in the presence of high doses of cycloheximide. After the required initial contact, further maintenance of the activity was dependent on factor(s) secreted in the medium of the activated culture. Phagocytosis was, on the other hand, abrogated in the presence of factor(s) secreted by a distinct fraction of germ cells, enriched in the late stages (second division) of meiosis. | [
"Animals",
"Cell Communication"
] |
Vacuolar system-associated protein-60 (VASAP-60) constitutes the bovine ortholog of the human "protein kinase C substrate 80K-H" (PRKCSH or 80K-H). We characterized the bovine VASAP-60/PRKCSH gene structure and promoter, identified cis-acting elements controlling VASAP-60 expression, searched for mRNA splice variants, and analyzed mRNA expression in ovarian follicles. Expression of VASAP-60 mRNA showed a 2.4-fold increase (P<0.0001) in granulosa cells of dominant follicles compared to small follicles (2-4 mm) or ovulatory follicles, and no mRNA splice variant was identified. The bovine VASAP-60 gene encompasses 12.5 kb and is composed of 18 exons and 17 introns. Primer extension analysis revealed a single transcription initiation site, and the promoter lacks a TATA box. Promoter activity assays were performed with a series of deletion constructs in different bovine cell lines (endometrial epithelial glandular, kidney epithelial and aortic endothelial) to identify cis-acting elements. The -53/+16 bp fragment (+1 = transcription start site) conferred minimal promoter activity whereas activator and repressor elements were located in the -200/-53 bp and -653/-200 bp fragments, respectively. Analysis of cis-acting elements in the -200/-53 bp activation domain revealed by gel shift assays and chromatin immunoprecipitation assay that transcription factor YY1 binds to VASAP-60 promoter. This study is the first to report that VASAP-60 is up-regulated in granulosa cells of dominant follicles, to document the primary structure of the bovine VASAP-60 gene and promoter, and to demonstrate that YY1 binds to the VASAP-60 proximal promoter and may act as a positive transcriptional regulator. | [
"Alternative Splicing",
"Amino Acid Sequence"
] |
The Clinical and Translational Science Awards (CTSA) program is one of the most important initiatives in translational medical funding. The quantitative evaluation of the efficiency and performance of the CTSA program has a significant referential meaning for the decision making of global translational medical funding. Using science mapping and scientometric analytic tools, this study quantitatively analyzed the scientific articles funded by the CTSA program. The results of the study showed that the quantitative productivities of the CTSA program had a stable increase since 2008. In addition, the emerging trends of the research funded by the CTSA program covered clinical and basic medical research fields. The academic benefits from the CTSA program were assisting its members to build a robust academic home for the Clinical and Translational Science and to attract other financial support. This study provided a quantitative evaluation of the CTSA program based on science mapping and scientometric analysis. Further research is required to compare and optimize other quantitative methods and to integrate various research results. | [
"Awards and Prizes",
"Bibliometrics"
] |
The influence of neurotrophins on GABAergic properties of developing striatal neurons was investigated both in vivo and in vitro. Brain-derived neurotrophic factor (BDNF) specifically elevated cellular GABA content in striatal culture without altering neuronal survival. Neurotrophin-5 produced a similar effect on GABA, but nerve growth factor and neurotrophin-3 had no effect. An increase in GABA content in the striatum was also observed following BDNF injections into the cerebroventricle of neonatal rats. The increase of GABA levels in culture mainly resulted from an increase in holoenzyme activity of the GABA synthetic enzyme glutamic acid decarboxylase (GAD) and elevation of GABA uptake activity. In BDNF-treated striatal cultures, the newly differentiated neurons extended elaborate neurites and exhibited strong GAD immunoreactivity. These alterations were presumably caused by the upregulation of mRNA encoding GAD67 and the neuronal GABA transporter GAT-1. BDNF treatment also promoted other phenotypic differentiation of striatal neurons: BDNF increased the frequency of parvalbumin-immunoreactive neurons and calbindin-immunoreactive neurons and neuropeptide content for neuropeptide Y and somatostatin. These observations suggest that neurotrophins may contribute to phenotypic differentiation of GABAergic neurons in the developing striatum. | [
"Animals",
"Animals, Newborn"
] |
PURPOSE: Balanced steady-state free precession (bSSFP) sequences can provide superior signal-to-noise ratio efficiency for hyperpolarized (HP) carbon-13 (13 C) magnetic resonance imaging by efficiently utilizing the nonrecoverable magnetization, but managing their spectral response is challenging in the context of metabolic imaging. A new spectrally selective bSSFP sequence was developed for fast imaging of multiple HP 13 C metabolites with high spatiotemporal resolution.THEORY AND METHODS: This novel approach for bSSFP spectral selectivity incorporates optimized short-duration spectrally selective radiofrequency pulses within a bSSFP pulse train and a carefully chosen repetition time to avoid banding artifacts.RESULTS: The sequence enabled subsecond 3D dynamic spectrally selective imaging of 13 C metabolites of copolarized [1-13 C]pyruvate and [13 C]urea at 2-mm isotropic resolution, with excellent spectral selectivity (?100:1). The sequence was successfully tested in phantom studies and in vivo studies with normal mice.CONCLUSION: This sequence is expected to benefit applications requiring dynamic volumetric imaging of metabolically active 13 C compounds at high spatiotemporal resolution, including preclinical studies at high field and, potentially, clinical studies. Magn Reson Med 78:963-975, 2017. © 2016 International Society for Magnetic Resonance in Medicine. | [
"Animals",
"Artifacts"
] |
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