tbuckley/cabot-search huggingface dataset:
Occupational asthma due to glutaraldehyde and formaldehyde in endoscopy and x ray departments.
Authors: P F Gannon, P Bright, M Campbell, S P O'Hickey, P S Burge
Journal: Thorax (1995)

BACKGROUND--Glutaraldehyde is the best disinfectant for fibreoptic endoscopes. It is also used in the processing of x ray films. A number of studies have reported eye, nose, and respiratory symptoms in exposed workers. Three individual case reports of occupational asthma in endoscopy workers and a radiographer have also been published. We describe a further seven cases of occupational asthma due to glutaraldehyde in endoscopy and x ray departments, together with exposure levels measured during the challenge tests and in 19 endoscopy and x ray departments in the region. METHODS--Eight workers were referred for investigation of suspected occupational asthma following direct or indirect exposure to glutaraldehyde at work. They were investigated by serial measurements of peak expiratory flow (PEF) and specific bronchial provocation tests. Glutaraldehyde levels were measured using personal and static short and longer term air samples during the challenge tests and in 13 endoscopy units and six x ray darkrooms in the region where concern about glutaraldehyde exposure had been expressed. Three of the workers investigated with occupational asthma came from departments where glutaraldehyde air measurements had been made; the others came from other hospitals or departments. RESULTS--The diagnosis of occupational asthma was confirmed in seven workers, all of whom had PEF records suggestive of occupational asthma and positive specific bronchial challenge tests to glutaraldehyde. Bronchial provocation testing was negative in one worker who was no longer exposed and who had a less clearcut history of occupational asthma. Three workers also had a positive specific bronchial challenge to formaldehyde. The mean level of glutaraldehyde in air during the challenge tests was 0.068 mg/m3, about one tenth of the short term occupational exposure standard of 0.7 mg/m3. The levels obtained in the challenge chamber were similar to those measured in 13 endoscopy suites and six x ray darkrooms where median short term levels were 0.16 mg/m3 during decantation in endoscopy suites and &lt; 0.009 mg/m3 in darkrooms. CONCLUSIONS--Glutaraldehyde can cause occupational asthma. The exposure levels measured in the workplace suggest that sensitisation may occur at levels below the current occupational exposure standard.
Mutations in the promoter region of the gene for gp91-phox in X-linked chronic granulomatous disease with decreased expression of cytochrome b558.
Authors: P E Newburger, D G Skalnik, P J Hopkins, E A Eklund, J T Curnutte
Journal: Journal of Clinical Investigation (1994)

We examined the molecular defect in two kindreds with "variant" X-linked chronic granulomatous disease (CGD). Western blots of neutrophil extracts showed decreased immunoreactive cytochrome b558 components gp91-phox and p22-phox. Analysis of mRNA demonstrated reduced gp91-phox transcripts, with relative preservation of an alternative mRNA species created by transcription initiation in the third exon of the gene. Single strand conformation polymorphism analysis of the 5' flanking region of the patients' gp91-phox genes revealed an electrophoretic abnormality not detected in 40 other gp91-phox genes. Genomic sequencing demonstrated a single base change associated with CGD in each kindred: in one, adenine to cytosine at base pair-57 and in the other, thymidine to cytosine at -55. These mutations are located between the "CCAAT" and "TATA" box consensus sequences involved in eukaryotic gene transcription. Gel shift assays revealed two specific DNA-protein complexes formed between phagocyte nuclear extracts and an oligonucleotide probe representing bases -31 to -68 of the gp91-phox promoter region; the faster-migrating complex could not be formed with oligonucleotides containing either of the promoter mutations. Thus, these promoter region mutations appear to be causally related to the loss of association of a DNA-binding protein and lead to diminished gp91-phox expression, abnormal transcription initiation, and the development of CGD.
Receptor binding of angiotensin II and antagonists. Correlation with aldosterone production by isolated canine adrenal glomerulosa cells.
Authors: J Douglas, S Saltman, P Fredlund, T Kondo, K J Catt
Journal: Circulation Research (1976)

The binding properties of the angiotensin II receptors of the adrenal cortex have been studied in isolated cells prepared by collagenase dispersion of the zona glomerulosa of the canine adrenal gland. Such cell preparations are responsive to physiological concentrations of angiotensin II, and permit correlation of binding of angiotensin II and its analogues with aldosterone production in vitro. Uptake of 125I-angiotensin II (5 X 10(-11) M) by glomerulosa cells at 37 degrees C reached a steady state at 45 minutes, with a subsequent plateau for at least 60 minutes. Angiotensin II binding was also dependent upon the hormone and cell concentrations employed during uptake studies. Bound angiotensin II was rapidly dissociated from canine adrenal cells after addition of the unlabeled octapeptide. High affinity sites with equilibrium association constant (Ka) of 3.3 X 10(9) M-1 comprised 25-33% of the receptor population and the remainder of the sites were of lower affinity, 2.5 X 10(8)M-1. Binding of angiotensin II analogues and antagonists was found to be consistent with their biological activities. The analogue most extensively evaluated was [Sar-1]angiotensin II, which exhibited enhanced binding activity when compared to angiotensin II, and had a higher equilibrium association constant by kinetic analysis and direct binding studies. Direct binding of labeled angiotensin II to the adrenal glomerulosa receptor has been correlated with a progressive response in aldosterone production. The steroidogenic response to angiotensin II was maximal when 25% of the receptor population was occupied; this fraction corresponds to the proportion of high affinity receptor sites measured by binding analysis. In addition, inhibition of angiotensin II binding to receptor sites by the competitive antagonist [Sar-1, Ala-8]angiotensin II has been correlated with inhibition of aldosterone production. These findings serve to demonstrate the biological significance of the angiotensin II binding sites of the adrenal cortex, and confirm their role as receptors which mediate the steroidogenic responses to angiotensin II.
Clinically silent myocardial scars are common in middle aged and older people, study finds
Authors: M. McCarthy
Journal: BMJ (2015)

Nearly 8% of middle aged and older people in the United States have myocardial scars suggestive of myocardial infarction, almost 80% of which have not been detected by electrocardiography or clinical evaluation, a study published in JAMA has found.1

The researchers wrote, “The clinical significance of unrecognized myocardial scar remains to be defined, although prior myocardial scar has been noted pathologically in more than 70% of patients with sudden cardiac death but without prior known coronary artery disease.”

The …
THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION
Authors: Patricia Byfield, Eli Sercarz
Journal: The Journal of Experimental Medicine (1969)

Short-term IgM memory is established within 1 day after primary injection. This 1 day priming is independent of cell division as it can take place in the pressence of methotrexate or hydroxyurea. The primary response involves a similar 1 day nonproliferative phase. On the contrary, cells responding to a second injection of antigen after short priming intervals begin to proliferate within hours. This implies a qualitative difference between the antigen-sensitive cells in primed and normal animals. After 1 day, further proliferative expansion of memory can occur, which is probably antigen dependent. The response to several dose regimens indicates that repeated antigenic contact is needed to maintain the IgM response.
Somatostatin in gastroenterology
Authors: A Shulkes, J S Wilson
Journal: BMJ (1994)

Somatostatin in gastroenterologyFor unresectable hormone secreting neuroendocrine tumours, secretory diarrhoeas, and bleeding varices Somatostatin was isolated from ovine hypothalamus in 1973, and eight years later a long acting analogue, octreotide, was synthesised.More than 1000 clinical applications have since been suggested for these paninhibitory peptides, particularly in gastroenterology.The enormous clinical potential in the gastrointestinal tract for a universal inhibitor and the remarkable non-toxicity of the agents fuelled this enthusiasm.Although a lack of randomised controlled trials with sufficient numbers of subjects hampered clinical progress, the recent publication of several large, well controlled trials has helped to delineate a role for somatostatin and its analogues in gastroenterology.In clinical practice octreotide is preferable to the native compound because of its longer half life, which permits intermittent subcutaneous administration.Recently an orally active somatostatin analogue has been described.' Octreotide is useful in the management of unresectable hormone secreting neuroendocrine tumours, particularly carcinoids and vipomas.2It inhibits both the secretion and the effect of the active agent.For example, in vipomas charac- terised by profuse secretory diarrhoea, octreotide reduces the
Enhanced Store Overload–Induced Ca <sup>2+</sup> Release and Channel Sensitivity to Luminal Ca <sup>2+</sup> Activation Are Common Defects of RyR2 Mutations Linked to Ventricular Tachycardia and Sudden Death
Authors: Dawei Jiang, Ruiwu Wang, Bailong Xiao, Huihui Kong, Donald J. Hunt, Philip Choi, Lin Zhang, S. R. Wayne Chen
Journal: Circulation Research (2005)

Ventricular tachycardia (VT) is the leading cause of sudden death, and the cardiac ryanodine receptor (RyR2) is emerging as an important focus in its pathogenesis. RyR2 mutations have been linked to VT and sudden death, but their precise impacts on channel function remain largely undefined and controversial. We have previously shown that several disease-linked RyR2 mutations in the C-terminal region enhance the sensitivity of the channel to activation by luminal Ca2+. Cells expressing these RyR2 mutants display an increased propensity for spontaneous Ca2+ release under conditions of store Ca2+ overload, a process we referred to as store overload-induced Ca2+ release (SOICR). To determine whether common defects exist in disease-linked RyR2 mutations, we characterized 6 more RyR2 mutations from different regions of the channel. Stable inducible HEK293 cell lines expressing Q4201R and I4867M from the C-terminal region, S2246L and R2474S from the central region, and R176Q(T2504M) and L433P from the N-terminal region were generated. All of these cell lines display an enhanced propensity for SOICR. HL-1 cardiac cells transfected with disease-linked RyR2 mutations also exhibit increased SOICR activity. Single channel analyses reveal that disease-linked RyR2 mutations primarily increase the channel sensitivity to luminal, but not to cytosolic, Ca2+ activation. Moreover, the Ca2+ dependence of [3H]ryanodine binding to RyR2 wild type and mutants is similar. In contrast to previous reports, we found no evidence that disease-linked RyR2 mutations alter the FKBP12.6-RyR2 interaction. Our data indicate that enhanced SOICR activity and luminal Ca2+ activation represent common defects of RyR2 mutations associated with VT and sudden death. A mechanistic model for CPVT/ARVD2 is proposed.
Infectional factors influences on cytomorphological picture of bronchial biopsies at COPD exacerbation
Authors: Ekaterina Bukreeva, Gulnara Seitova, Raisa Pleshko
Journal: European Respiratory Journal (2011)

Purpose:  To match and analyze bronchial biopsies in dependence on infectional factor at COPD exacerbation.   Material:  46 COPD patients were examined, infectional nature of exacerbation was confirmed at 30 patients. In common group patients intraepithelial lymphocytes count in brush-biopsy was 29.5±3.4/mm 2 , intraepithelial eosinophiles–2.3±0.7/mm 2 , intraepithelial neutrophiles–0.0/mm 2 , stromal neutrophiles 5.4±1.4/mm 2 , stromal eosinophiles 9.6±2.6/mm 2 , squamous cell methaplasia expressiveness–0.5±0.3/point, reserved cell hyperplasia 0.6±0.2/point, goblet cell hyperplasia–0.3±0.1/point.  Endobronchail biopsies and morphometrical estimation of biopsy were made.  Intraepithelial lymphocytes count–28.2±4.6/mm 2  and 31.2±5.3/ mm 2 , intraepithelial eosinophiles count–2.4±0.7/mm 2  and 2.2±0.6/mm 2 , stromal neutrophiles count–5.2±0.8/mm 2  and 5.6±0.9/mm 2  were the same in dependent on exacerbation etiology and the same expressiveness of goblet cell hyperplasia.  At noninfectional COPD exacerbation stromal eosinophiles cell count was 12.3±1.5/mm 2  vs 7.6±1.5/mm 2  (p
Hepatitis B Virus Infection: The Impact of Molecular Biology
Authors: Sheila Sherlock, Howard C. THomas
Journal: Hepatology (1983)

Assays for the detection of nucleic acid in serum are likely to be better systems for determining infectivity than indirect ones dependent on detection of virus-encoded proteins such as HBeAg. The hybridization assays are particularly useful in monitoring spontaneous or treatment-related conversion from the "replicative" to "nonreplicative" phase of HBV infection. The simplified technology described in the papers reported in this issue of Hepatology (9, 14) and their future adaptation to nonisotopic systems will rapidly bring these techniques into everyday clinical practice.
Formylpeptide Receptor FPR and the Rapid Growth of Malignant Human Gliomas
Authors: Ye Zhou, Xiuwu Bian, Yingying Le, Wanghua Gong, Jinyue Hu, Xia Zhang, Lihua Wang, Pablo Iribarren, Rosalba Salcedo, O. M. Zack Howard, William Farrar, Ji Ming Wang
Journal: JNCI Journal of the National Cancer Institute (2005)

The formylpeptide receptor (FPR) is a G-protein-coupled receptor (GPCR) that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF). We previously showed that selected human glioma cell lines also express functional FPR. We therefore investigated the relationship between FPR expression and the biologic behavior of glioma cells.Expression and function of FPR in the human glioblastoma cell line U-87 were examined by reverse transcription-polymerase chain reaction (RT-PCR) and chemotaxis assays, respectively. FPR protein expression was detected in specimens from 33 human primary gliomas by immunohistochemistry. FPR short interfering (si) RNA was used to block FPR expression in U-87 cells. Cell proliferation was assessed by measuring DNA synthesis. Xenograft tumor formation and growth were measured in nude mice. Endogenous FPR agonist activity released by necrotic tumor cells was assessed by measuring FPR activation in an FPR-transfected basophil leukemia cell line and live U-87 cells. Vascular endothelial growth factor (VEGF) mRNA was assessed by RT-PCR, and VEGF protein was assessed by enzyme-linked immunosorbent assay. All statistical tests were two-sided.FPR was selectively expressed by the highly malignant human glioblastoma cell line U-87 and most primary grade IV glioblastomas multiforme and grade III anaplastic astrocytomas. U-87 cells responded to the FPR agonist fMLF by chemotaxis (i.e., increased motility), increased cell proliferation, and increased production of VEGF protein. FPR siRNA substantially reduced the tumorigenicity of U-87 cells in nude mice (38 days after implantation, mean tumor volume from wild-type U-87 cells = 842 mm3, 95% confidence interval [CI] = 721 to 963 mm3; and from FPR-siRNA transfected U-87 cells = 225 mm3, 95% CI = 194 to 256 mm3; P = .001). Necrotic glioblastoma cells released a factor(s) that activated FPR in live U-87 cells.FPR is expressed by highly malignant human glioma cells and appears to mediate motility, growth, and angiogenesis of human glioblastoma by interacting with host-derived agonists. Thus, FPR may represent a molecular target for the development of novel antiglioma therapeutics.
Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2
Authors: Michael J. Orlich, Pramil N Singh, Joan Sabaté, Karen Jaceldo-Siegl, Jing Fan, Synnove Knutsen, W. Lawrence Beeson, Gary E. Fraser
Journal: JAMA Internal Medicine (2013)

IMPORTANCE Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established.OBJECTIVE To evaluate the association between vegetarian dietary patterns and mortality.DESIGN Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders.SETTING Adventist Health Study 2 (AHS-2), a large North American cohort.PARTICIPANTS A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions.EXPOSURES Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. MAIN OUTCOME AND MEASUREThe relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index.RESULTS There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years.The mortality rate was 6.05 (95% CI, 5.82-6.29)deaths per 1000 person-years.The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97).The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94);and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13)compared with nonvegetarians.Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality.Associations in men were larger and more often significant than were those in women. CONCLUSIONS AND RELEVANCEVegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality.Results appeared to be more robust in males.These favorable associations should be considered carefully by those offering dietary guidance.
Drug Interactions: The Importance of Looking Inside Cancer Cells
Authors: Jeffrey W. Clark
Journal: Cancer Discovery (2012)

Abstract nab-Paclitaxel increased intratumoral gemcitabine levels by reactive oxygen species–mediated degradation of cytidine deaminase, the rate-limiting enzyme in gemcitabine inactivation. This not only has implications for how this drug combination mediates anticancer effects but also demonstrates the importance of evaluating mechanisms of drug activity within malignant cells. Cancer Discovery; 2(3); 208–10. ©2012 AACR. Commentary on Frese et al., p. 260.
In vitro comparative activity of meropenem with 15 other antimicrobial agents against 1798 Pseudomonas aeruginosa isolates in a French multicenter study
Authors: M.O. Husson, H. Richet, A. Aubert, C. Cattoen, A. Chardon, V. Jarlier, D. Izard, E. Lecaillon, M. Melon, A. Morel, M.H. Nicolas
Journal: Clinical Microbiology and Infection (1999)
Long Noncoding RNA GAPLINC Regulates CD44-Dependent Cell Invasiveness and Associates with Poor Prognosis of Gastric Cancer
Authors: Ye Hu, Jilin Wang, Jin Qian, Xuan Kong, Jieting Tang, Yingchao Wang, Haoyan Chen, Jie Hong, Weiping Zou, Yingxuan Chen, Jie Xu, Jing-Yuan Fang
Journal: Cancer Research (2014)

It is increasingly evident that long noncoding RNAs (lncRNA) have causative roles in carcinogenesis. In this study, we report findings implicating a novel lncRNA in gastric cancer, termed GAPLINC (gastric adenocarcinoma predictive long intergenic noncoding RNA), based on the use of global microarray and in situ hybridization (ISH) analyses to identify aberrantly expressed lncRNA in human gastric cancer specimens. GAPLINC is a 924-bp-long lncRNA that is highly expressed in gastric cancer tissues. GAPLINC suppression and with gene expression profiling in gastric cancer cells revealed alterations in cell migration pathways, with CD44 expression the most highly correlated. Manipulating GAPLINC expression altered CD44 mRNA abundance and the effects of GAPLINC on cell migration and proliferation were neutralized by suppressing CD44 expression. Mechanistic investigations revealed that GAPLINC regulates CD44 as a molecular decoy for miR211-3p, a microRNA that targets both CD44 and GAPLINC. Tissue ISH analysis suggested that GAPLINC overexpression defines a subgroup of patients with gastric cancer with very poor survival. Taken together, our results identify a noncoding regulatory pathway for the CD44 oncogene, shedding new light on the basis for gastric cancer cell invasiveness.
THE MECHANISM OF THE INSULIN EFFECT ON ABNORMAL BEHAVIOR
Authors: BERNARD F. RIESS, LOUIS BERMAN
Journal: American Journal of Psychiatry (1944)

1. The effect of insulin injections, sufficient in strength to cause convulsive seizures and/or lethargy, has been systematically studied in relation to various aspects of the learning process. 2. For maze learning the following statements have been experimentally verified and established: (a) Insulin has a greater disintegrative effect on the learning of a habit which has been less well fixed than on a habit of greater fixation. (b) Insulin has a greater disintegrative effect on the learning of a longer and more difficult maze than on a shorter and easier maze, when both are learned to the same norm. (c) Insulin has a disintegrating effect on the initial acquisition of a maze habit when compared to the acquisition of the same habit under normal conditions. (d) The effects described in the above statement are definitely the result of insulin injection. Comparison of the use of insulin and saline solution proves insulin to have a disintegrative effect which is lacking in the saline situation. Our work has demonstrated that the insulin effect may be used as a means of testing the relative age and stability of different habits and habit systems. Its employment may be regarded as a kind of "chemical surgery." We are continuing with the work and expect ultimately to apply it to the experimental neurosis which may be produced in the rat, and also to compare it with similar work carried out on human beings. The consistency of the results clearly substantiates our concept as to how the insulin effect operates to bring about a remission in schizophrenia and other psychotic and psychoneurotic conditions. We do not claim that it is the whole explanation of a lasting cure or complete recovery; as other factors, such as the response of the entire endocrine system, particularly the pituitary and adrenal glands, may also be involved in the final return to the normal. However, our work appears to explain the mechanism by which the immediate remission of the abnormal behavior is brought about.