Miracle-dz/UniFAR-FTUs huggingface dataset:
lnterleukin-10 Inducing Activity of LK423, a Phthalimido-desmuramyldipeptide Compound

Summary A new phthalimido compound, N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-glutamic acid (CAS 142489-47-2, LK423), was examined along with other N-acyl-desmuramyldipeptide compounds for possible immunomodulating activities in cyclophosphamide (Cy)-treated mice. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot assays demonstrated that multiple subcutaneous injections of LK423 (1 to 50 µg/day for 4 days) into these mice resulted in upregulating interleukin-10 (IL-10) gene expression in the spleen. In contrast to IL-10, expression of interferon-y (IFN-y) gene was reduced by treating with this compound. The culture supernatantof spleen cells obtained from the mice that had received LK423 injections was found to contain a larger amount of IL-10 protein than in the culture supernatant of the spleen obtained from the mice that received no LK423 injections when tested by enzyme-linked immunosorbent assay (ELISA). Conversely to IL-10, the concentration of IFN-γ was lower in the culture supernatant from the LK423-treated group than that in the control group. In contrast to this compound, other N-acyl-desmuramyldipeptide derivatives carrying a L-alanyl-D-isoglutamine moiety, and other immunological stimulants showed an activity to augment production of IFN-γ and reduce the gene expression of IL-10. The immunological activities of this new phthalimido desmuramyldipeptide compound, LK423, are discussed from the point of view of its therapeutic application.
Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG

In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite‐based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members.
Effect of alcohol on vagal regulation of cardiovascular function: contributions of the polyvagal theory to the psychophysiology of alcohol.

Research was conducted to evaluate the influence of acute alcohol consumption on vagal regulation of heart rate. Nine men with histories of polydrug use participated in this residential study. On 5 separate days, they drank liquids consisting of cold water (on 2 days), a moderate dose of alcohol (0.64 g/kg), a high dose of alcohol (1.12 g/kg), and a placebo. Continuous recordings of heart period were quantified to produce 3 measures of heart rate variability, reflecting the amplitude of 3 neurophysiologically mediated rhythms. Heart period, respiratory rhythm (i.e., respiratory sinus arrhythmia [RSA]), and the 0.064-0.10-Hz vasomotor rhythm were significantly lower during the high alcohol dose condition, relative to the placebo and water conditions. Because the neural regulation of the heart by the vagus contributes to these variables, these findings suggest that alcohol reduces cardiac vagal tone. In support of this explanation, alcohol also decreased the coupling between changes in heart period and changes in RSA. This study demonstrated that alcohol produces a dysregulated state in which heart rate is relatively uncoupled from vagal activity.
A New On-Chip CMOS Active Balun Integrated With LNA

The design and simulation of an innovative monolithic active balun integrated with low noise amplifier, is described in this paper. The fully integrated circuit was implemented in a 0.35 mum AMS CMOS standard technology. The simulations, optimized to noise performance, minimum differential phase and magnitude error, were performed with BSIM3 model Circuit simulations present 20.6dB differential power gain at 2.4 GHz, a phase and a transducer gain magnitude errors less than 0.2deg and 0.04 dB, respectively, in a 1GHz span around 2.4 GHz, a 3.7dB noise figure, a 2 dBm output-referred ldB compression point, 50 Omega input and output match, while drawing 11mA from a 3V power supply.
Antihypertensive therapy causes erectile dysfunction

Purpose of review Erectile dysfunction is a common sexual disorder affecting 40% of men in the United States. However, the pathophysiologic mechanism involved in the causation of erectile dysfunction is multifactorial and not well delineated. Recent findings Several recent studies disclose that erectile dysfunction is the result of multiple interrelated comorbid conditions that include hypertension, coronary artery disease (CAD), heart failure, and diabetes mellitus among them. In addition to comorbid conditions, certain cardiovascular and antihypertensive drugs are also involved in the development of erectile dysfunction, with the most prominent being the thiazide type diuretics, the aldosterone receptor blockers, and the &bgr;-adrenergic receptor blockers. Also, knowledge by the patient of the drug and its action on erectile dysfunction may increase the incidence of erectile dysfunction (Hawthorn effect). Before treatment is initiated, patients should be screened for the presence of erectile dysfunction, because this condition is associated with hypertension, CAD, heart failure, diabetes mellitus, and their treatment and an appropriate treatment regimen should be selected. If that fails, the addition of phosphodiesterase 5 inhibitors to the treatment regimen is recommended. The only exception is a patient with CAD treated with organic nitrates, in which the coadministration of phosphodiesterase 5 inhibitors is strictly prohibited. Summary Knowledge of the various comorbid conditions and their treatment associated with the development of erectile dysfunction will help the caring physician to treat his patients appropriately and safely. All these aspects will be discussed in this review.
Prevention of nutritionally induced diabetes by rosiglitazone in the gerbil Psammomys obesus

Psammomys obesus is a desert gerbil developing hyperglycaemia, hyperinsulinaemia and insulin resistance when placed for 2 weeks on a high‐energy (HE) diet. The mechanism underlying the antidiabetic effect of rosiglitazone (RG) treatment (20 mg/kg per day for 2 weeks) was studied.
Interaction between endometrial epithelial cells and blood leucocytes promotes cytokine release and epithelial barrier function in response to Chlamydia trachomatis lipopolysaccharide stimulation

Chlamydia trachomatis infection is currently the most common cause of infection‐related sterility in women. However, it remains largely unknown how uterine epithelial cells interact with recruited leucocytes in response to C. trachomatis infection in the female genital tract. To study the defence mechanism of the endometrium against C. trachomatis infection, we established an in vitro co‐culture of EEC (endometrial epithelial cells) and PBL (peripheral blood leucocytes) isolated from mice and investigated the immune response of these cells upon C. trachomatis LPS (lipopolysaccharide) challenge using a cytokine antibody array and RT‐PCR (reverse transcription‐PCR). Our results showed that upon C. trachomatis LPS stimulation, proinflammatory cytokines/chemokines, such as TNF‐α, IL‐1β, MIPs (macrophage inflammatory proteins), IL‐12p40p70, KC, GCSFs (granulocyte colony stimulating factors), IL‐6 and TIMPs (tissue inhibition metalloproteinases) are up‐regulated and/or released from EEC–PBL co‐culture. Further, the TER (transepithelial resistance), measured by the Isc (short‐circuit current) technique was significantly increased in EEC/PBL co‐cultured cells and also when stimulated with C. trachomatis LPS compared with EEC alone. These changes appear to be mediated by the change in cytokine‐induced expression of tight junction‐related protein ZO‐1. The present results demonstrated that the epithelial–immune cross‐talk could promote the release of proinflammatory cytokines and enhance the barrier function of the endometrium against C. trachomatis infection in the female reproductive tract.
An experimentally induced duplication of retinotopic mapping within the hamster primary visual cortex

Primary cortical areas normally have a single mapping of the receptor array arising from a ‘point‐to‐point’ projection from the thalamus. We show that, for the visual cortex, this simple mapping rule breaks down when retinal input to the thalamus is altered. We utilize the monocular enucleation paradigm, which alters subcortical mappings ipsilateral to the remaining eye. We show that this manipulation produces an altered visuotopic map in area 17 with two separated, mirror‐imaged representations of the central visual field. Furthermore, thalamic point‐to‐point connectivity is dramatically changed. There are now two overlapping geniculocortical projections: the predominant projection maps with apparently normal topography, and a second projection maps with the opposite polarity. The plane of symmetry of the duplicated anatomical projection coincides precisely with the functional map reversal and, notably, geniculocortical magnification factors are identical in the two projections. We suggest that the duplicated, abnormal geniculocortical projection is retinotopically matched to the normal projection. We speculate that aberrant geniculocortical terminals are stabilized because they have coherent activity patterns with topographically normal terminals.
Retinal vessel diameters and risk of hypertension: the Multiethnic Study of Atherosclerosis

Objective To describe the prospective relationship of retinal vessel diameters with risk of hypertension in a multiethnic population-based cohort. Methods The Multi-Ethnic Study of Atherosclerosis is a population-based study of subclinical cardiovascular disease among white, African–American, Hispanic, and Chinese American adults aged 45–84 years. Retinal vessel diameters were measured using a standardized imaging software at the second examination (considered baseline in this analysis) and summarized as the central retinal artery/vein equivalent. Presence of retinopathy and retinal focal arteriolar narrowing and arteriovenous nicking was assessed by trained graders. Incidence of hypertension was defined among participants at risk as systolic blood pressure at least 140 mmHg, diastolic blood pressure at least 90 mmHg, or use of an antihypertensive medication. Results Of the initial 6237 participants at baseline, 2583 were at risk of hypertension. After 3.2 ± 0.5 years of follow-up, 448 (17.3%) participants developed hypertension. After adjusting for age, sex, race/ethnicity, the average of mean arterial blood pressure in the first and second examination, and other vascular risk factors, persons with narrower retinal arteriolar diameter and wider venular diameter at baseline were more likely to develop hypertension [odds ratio per SD decrease in central retinal artery equivalent 1.20, 95% confidence intervals 1.02, 1.42; and odds ratio per SD increase in central retinal vein equivalent 1.18, 95% confidence interval 1.02, 1.37]. Persons with focal arteriolar narrowing were also more likely to develop hypertension (odds ratio 1.80, 95% confidence interval 1.09, 2.97). Conclusion Findings from this multiethnic population confirm that narrower retinal arteriolar diameter and wider venular diameter are associated with the development of hypertension independent of traditional risk factors.
A prospective evaluation of fibrosis progression in patients with recurrent hepatitis C virus following liver transplantation

Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal. A subset of these patients develop advanced fibrosis and cirrhosis and it is believed that this leads to increased posttransplantation mortality. The specific aims of this study were to determine the incidence of advanced fibrosis and those factors associated with this process, and to evaluate causes for mortality in patients with recurrent HCV. A total of 227 patients who underwent LT with chronic HCV were monitored prospectively. The mean age of this group at LT was 49.5 yr; 76% were male and 85% were Caucasian. Fibrosis progression was monitored by protocol liver biopsy, initially performed 6 months after LT and then at 6‐ to 24‐month intervals. Advanced fibrosis, defined as the bridging fibrosis or cirrhosis, developed in 1%, 11%, 25%, and 41% of patients after 1, 3, 5, and 6‐10 yr, respectively. Acute cellular rejection hepatic steatosis, a persistent elevation in serum alanine aminotransferase and donor‐race were associated with the development of advanced fibrosis. In contrast, the development of advanced fibrosis was not affected by the use of interferon prior to undergoing LT, cytomegalovirus disease, or donor age. A total of 60 patients (26%) died over 15 yr of follow‐up. Although graft failure accounted for 45% of deaths in patients with advanced fibrosis, this represented only 8% of all deaths in patients with recurrent HCV. Sepsis was the most common cause of death and this was observed with similar frequency in patients who developed advanced fibrosis (45%) and in those with less advanced fibrosis (47%). In conclusion, approximately 41% of patients with recurrent HCV developed advanced fibrosis 6‐10 yr after LT. However, complications associated with sepsis, not recurrent cirrhosis, was the most common cause of death in patients with recurrent HCV and this was similar in patients with or without advanced fibrosis. Liver Transpl 13:975–983, 2007. © 2007 AASLD.
Gene Expression Profiling of p53+/‐ Knockout and Wild‐type Mice Following Diethylstilbestrol Administration

Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/‐ knockout mice and wild‐type mice on the kidney and uterus of female mice. p53+/‐ knockout mice and wild‐type mice were treated with DES (500 μmole kg‐1) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES‐treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl‐2, bcl‐w, bcl‐x, caspase‐3, caspase‐7, caspase‐8, c‐myc, E124, GADD45, mdm2, NKκb1, p53, p21, Rb and trail were up‐regulated and six genes; caspase‐1, caspase‐2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild‐type mice compared to p53+/‐ knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl‐x, mdm2, p53 and p21 gene expression in wild‐type mice compared to p53+/‐ knockout mice. In comparing p53 and p21 gene expression in wild‐type mice and p53+/‐ knockout mice, there was an 4.4‐fold vs. 1.8‐fold; 8‐fold vs. 5.2‐fold for kidney and16‐fold vs. 5.5‐fold; 2.1‐fold vs. 8.3‐fold for uterus samples increase in induction (respectively). RT‐PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/‐ knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model. IUBMB Life, 56: 409‐416, 2004
Why Has the Antidepressant–Placebo Difference in Antidepressant Clinical Trials Diminished over the Past Three Decades?

The increasing rate of failure of antidepressant clinical trials has led to the assertion that antidepressants do not have meaningful clinical benefits. Our hypothesis was that the decrease in antidepressant–placebo differences in antidepressant clinical trials over the past three decades could be explained by changes in research design features rather than a lack of potency of the antidepressants being tested. We collected data from 130 double blind placebo controlled antidepressant clinical trials conducted between 1981 and 2008 that included 35,122 depressed patients with 23,157 patients assigned to antidepressants and 11,965 assigned to placebo. We conducted a hierarchical regression analysis of change in HAM‐D scores in antidepressant and placebo groups separately with year of publication, and research design features as independent variables. We found that antidepressant–placebo differences in antidepressant clinical trials have declined markedly over the past three decades. Decline in change scores in the antidepressant group was related to mean total baseline HAM‐D scores in the trial, the version of HAM‐D used, and duration of trial. Similarly, decline in change scores in the placebo group was related to mean total baseline HAM‐D scores, duration of trial, and year of publication. Overall, we found that antidepressant–placebo differences were statistically significantly higher in trials that used HAM‐D 21 rather than HAM‐D 17 and in trials that lasted 6 weeks or less. These data suggest that, apart from the efficacy of the antidepressant being tested, factors such as baseline HAM‐D scores, version of HAM‐D used and duration of trial have a significant impact on outcome. As such a clinician's assessment of the usefulness of antidepressants should not be based solely on the results of such clinical trials. In the meantime there is a need for continuing research to improve the methodology of antidepressant clinical trials. These data suggest that many aspects of the design of antidepressant trials have a significant impact on outcome. Further, these data suggest that the results of more recent placebo controlled trials do not adequately inform clinicians about the potential utility of antidepressants.
PHARMACOKINETICS AND PHARMACODYNAMICS OF 2,4‐DIAMINOPYRIDINE IN THE CAT

Summary— The pharmacokinetics, antagonistic effects, and cardiovascular effects of 2,4‐diaminopyridine (2,4‐DAP) were studied in 7 anaesthetized cats. Cats received a pancuronium infusion at a constant rate to cause a 90% block of contraction of the anterior tibialis muscle, stimulated through the sciatic nerve. After steady state was reached, 2,4‐DAP (750 μg/kg IV) was administered. Plasma, urine, and bile were collected over 8 h and analyzed by means of an HPLC assay. Plasma concentrations decreased biexponen‐tially with half‐lives of 9.0± 5.7 min and 140 ± 36 min, respectively. The volume of the central compartment was 0.85 ± 0.27 L/kg, and the volume of distribution in the steady state was 3.1 ± 1.1 L/kg. Total plasma clearance was 18 ±5 ml/kg/min. Ninety percent of the administered dose was recovered in the urine and 0.1 percent in the bile in 8 h. The antagonism of the pancuronium‐induced steady‐state block was 98%±5%, with onset and duration of 3.5±2 min and 165±40 min, respectively.
The Effects of a Learning-Goal Orientation Training on Self-Regulation: A Field Experiment Among Unemployed Job Seekers

Finding reemployment after job loss is a complex and difficult task that requires extensive motivation and self-regulation. This study aimed to examine whether improving unemployed job seekers’ cognitive self-regulation can increase reemployment probabilities. Based on the goal orientation literature, we developed a learning-goal orientation (LGO) training, which focused on goal setting aimed at improving rather than demonstrating competences and creating a climate of development and improvement. We predicted that the LGO training would influence peoples’ goal orientation towards job seeking, which in turn would relate to learning from failure, strategy awareness, and self-efficacy, leading to job-search intentions, resulting in increased reemployment status. Using a 2-group quasi-experimental design with 223 unemployed job seekers, we found support for these predictions, except for self-efficacy. The results suggest that an LGO training is a promising tool to improve self-regulation in and effectiveness of job search.
Identification of Conserved Residues Required for the Binding of a Tetratricopeptide Repeat Domain to Heat Shock Protein 90*

The sequential binding of heat shock protein 90 (hsp90) to a series of tetratricopeptide repeat (TPR) proteins is critical to its function as a molecular chaperone. We have used site-directed mutagenesis to clarify the structural basis for the binding of hsp90 to the TPR domain of phosphoprotein phosphatase 5 (PP5). This TPR domain was chosen for study because its three-dimensional structure is known. We examined co-immunoprecipitation of hsp90 with wild type and mutant TPR constructs from transfected cells. Only mutations located on one face of the TPR domain affected hsp90 binding. This allowed the identification of a binding groove. Three basic residues that are highly conserved in hsp90-binding TPR proteins extend prominently into this groove. Lys-97 and Arg-101 were absolutely required for hsp90 binding, while mutation of Arg-74 diminished, but did not abrogate, hsp90 binding. Mutation of Lys-32, another conserved basic residue in the binding groove, also blocked hsp90 binding. The TPR domain of PP5 bound specifically to a 12-kDa C-terminal fragment of hsp90. This binding was reduced by mutation of acidic residues in the hsp90 fragment. These data suggest conservation, among hsp90-binding TPR proteins, of a binding groove containing basic residues that interact with acidic residues near the C terminus of hsp90.
Hepatitis of viral origin in Leporidae: introduction and aetiological hypotheses.

In less than ten years, two very serious viral hepatic diseases have spread through Leporidae populations (rabbits and hares) in numerous countries. In May 1989, the Office International des Epizooties designated this new disease of rabbits "viral haemorrhagic disease" and entered it as a List B disease in the International Animal Health Code. Clinically, the disease is very similar to the European brown hare syndrome. However, numerous uncertainties prevail today on the true nature of the viruses of the two species. Although they are related, the viruses appear to be different and cross infection between species has given contradictory results. Hepatitis of Leporidae have probably existed in Europe for several years, although their viral aetiology has been demonstrated only recently. The acute form has occurred in hares in Northern Europe since approximately 1980, while the inapparent (or ignored) form has been present in rabbits in Czechoslovakia since 1975. These diseases of Leporidae are true viral hepatitis which, in their fulminating forms, bear a remarkable resemblance to human viral hepatitis (B and non-A non-B) with regard to clinical symptoms, pathological lesions and mode of transmission. The dominant faecal-oral transmission observed for types A and E hepatitis would explain the particular susceptibility of family-kept rabbits, as they are fed potentially contaminated fodder. As the clinically similar fulminating hepatitis in human beings is caused by a diversity of viruses (both RNA and DNA), the disease in Leporidae might also be caused by different viruses. (ABSTRACT TRUNCATED AT 250 WORDS)