tbuckley/cabot-search huggingface dataset:
Abstract 15220: Myocardial Biomarker Testing With Troponin I: Are We Ordering Too Many Studies?
Authors: Tami L Bair, Heidi T May, Jeffrey L Anderson, Brian Whisenant, Donald L Lappe, Viet Le, Joseph B Muhlestein
Journal: Circulation (2013)

Background:  Myocardial biomarker testing with some form of troponin assay has become standard of care for diagnosing acute myocardial infarction (AMI) among patients presenting with symptoms consistent with acute coronary syndrome. However, in order to “not miss anyone,” troponin assays may be ordered on patients presenting with non-cardiac diagnoses, but the frequency, justification and outcome of this practice are unknown.   Methods:  During the year 2007, in a large multi-hospital integrated health system, all patients with a troponin-I (trpI) measurement obtained were studied. Baseline clinical characteristics, primary and secondary admit and discharge diagnoses, as well as maximum trpI were collected and analyzed. A trpI level >0.4 was considered consistent with AMI. Independent predictors of a positive trpI were determined by logistic regression analysis.   Results:  At least one trpI test was obtained in a total of 22,410 unique encounters in 18,730 unique patients (age=67±16 years, males=52%, diabetes=38%; history of AMI, coronary artery disease without prior AMI (CAD), heart failure (HF), atrial fibrillation (AF), stroke or renal failure history = 19.8%, 33.6%, 39.5%, 28.9%, 5.7% and 24.1% respectively). Of these, the admit diagnosis was CAD-related in 1,896 (8.5%), other cardiac-related in 6,883 (30.7%) and non-cardiac related in 13,631 (60.8%) patients. Of the patients with a non-cardiac related admit diagnosis, trpI level was >0.4 in 1,238 (9.1%) of cases. Of these, a primary or secondary discharge diagnosis of AMI was given in only 375 (30.3%) of cases. Independent predictors of trpI>0.4 in patients with a non-cardiac admit diagnosis included only a prior history of AMI (OR=6.80, p   Conclusions:  In a large integrated health system, nearly two thirds of troponin assays are ordered on patients without a cardiac-related admit diagnosis, who had a positive trpI rate of
Phase III Study of Bolus Versus Infusion Fluorouracil With or Without Cisplatin in Advanced Colorectal Cancer
Authors: R. M. Hansen, L. Ryan, T. Anderson, B. Krzywda, E. Quebbeman, A. Benson, D. G. Haller, D. C. Tormey
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:Phase II studies of fluorouracil (5-FU) administered by protracted intravenous infusion have suggested an improved response rate and decreased toxicity profile when compared with 5-FU given by bolus injection in patients with metastatic colorectal cancer. Additional studies have suggested further enhancement of infusion 5-FU activity when it is combined with low-dose weekly cisplatin administration.
Improved insulin-sensitivity in mice heterozygous for PPAR-γ deficiency
Authors: Philip D.G. Miles, Yaacov Barak, Weiman He, Ronald M. Evans, Jerrold M. Olefsky
Journal: Journal of Clinical Investigation (2000)

The thiazolidinedione class of insulin-sensitizing, antidiabetic drugs interacts with peroxisome proliferator–activated receptor γ (PPAR-γ). To gain insight into the role of this nuclear receptor in insulin resistance and diabetes, we conducted metabolic studies in the PPAR-γ gene knockout mouse model. Because homozygous PPAR-γ–null mice die in development, we studied glucose metabolism in mice heterozygous for the mutation (PPAR-γ+/– mice). We identified no statistically significant differences in body weight, basal glucose, insulin, or FFA levels between the wild-type (WT) and PPAR-γ+/– groups. Nor was there a difference in glucose excursion between the groups of mice during oral glucose tolerance test, but insulin concentrations of the WT group were greater than those of the PPAR-γ+/– group, and insulin-induced increase in glucose disposal rate was significantly increased in PPAR-γ+/– mice. Likewise, the insulin-induced suppression of hepatic glucose production was significantly greater in the PPAR-γ+/– mice than in the WT mice. Taken together, these results indicate that — counterintuitively — although pharmacological activation of PPAR-γ improves insulin sensitivity, a similar effect is obtained by genetically reducing the expression levels of the receptor.
A VISIT TO THE ARGENTINE
Authors: JOSEPH WORTIS
Journal: American Journal of Psychiatry (1961)

Argentina has its fair share of talented and public spirited psychiatrists, but their professional development and usefulness are hampered by inadequate support and facilities. The opinion was frequently expressed, even by Government officials, that general planning for medical services on a national level is long overdue, and will have to be initiated. Even the 1200 pesos per year per capita that are now being spent by the public could yield far better health services, including psychiatric services, if expended in some planned and rational way. Until that is done, there seems to be little prospect of providing adequate psychiatric care to meet the needs of the Argentine population. Meanwhile it is to be hoped that some of the most urgent and immediate needs will be satisfied. A question I often asked was how we in the U. S. A. could be helpful. Many younger physicians expressed the wish to spend a period of training in the U. S. A., but it is my impression that in the past many or most of the American-trained physicians have returned to give their major interest to private practice and have neglected hospital work. "How else could we earn a livehood?" they ask. It seems to me American training resources could be used much more effectively if our responsible agencies negotiated with Argentine agencies to exchange personnel, or perhaps teams of personnel, with some assurance that these would help satisfy some of the broader psychiatric needs of that country. Now especially, when there is emerging in the Argentine a new interest in the development of psychiatric services in general hospitals, perhaps ways could be found to train some of their younger men to prepare for full time career positions in general hospitals, in research or in psychiatric public health work. I think brief sojourns of visiting teams from our country would not only be well received and would help to train many young psychiatrists, but would provide useful opportunities for some of our psychiatrists to get the stimulus of new contacts, problems and ideas, and to cultivate an interest in the growing psychiatric work of our South American neighbors. Joint conferences or group training seminars could also provide very fruitful results at relatively little cost. I am sure that programs of this type would help to revive those good neighborly feelings which have not flourished in recent years.
The generation of antibody diversity
Authors: David R. Rose
Journal: American Journal of Hematology (1982)

Abstract By their nature, antibody molecules exhibit a wide range of binding specificities. The antigen‐binding properties of the antibody reside entirely in the amino‐terminal portion of the molecule, termed the variable domain. Structurally, the combining site specificity is determined by the amino‐acid residues within 6 short lengths, 3 each in the heavy and light chains, of unusually variable sequence. The hypervariability of 2 of these lengths arises from the somatic recombination of short gene segments into a single stretch of mRNA which encodes the entire variable region of 1 polypeptide chain. For example, a V gene segment that codes for most of the variable portion of a light chain, can combine with one of a number of much shorter J gene segments to create the complete variable region gene. In heavy chain genes, a third element, the D gene segment, increases the potential for diversity even further. A mechanism has been proposed by which variability occurs at the point where 2 gene segments join. Thus, a large part of the generation of antibody diversity occurs in the somatic recombination of small genetic elements.
Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis
Authors: Johann Morelle, Amadou Sow, Nicolas Hautem, Caroline Bouzin, Ralph Crott, Olivier Devuyst, Eric Goffin
Journal: Journal of the American Society of Nephrology (2015)

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.
Characterization of the Mouse Aortic Carboxypeptidase-Like Protein Promoter Reveals Activity in Differentiated and Dedifferentiated Vascular Smooth Muscle Cells
Authors: Matthew D. Layne, Shaw-Fang Yet, Koji Maemura, Chung-Ming Hsieh, Xiaoli Liu, Bonna Ith, Mu-En Lee, Mark A. Perrella
Journal: Circulation Research (2002)

The dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) contribute to the formation of vascular lesions. In this study, the regulation of aortic carboxypeptidase-like protein (ACLP) expression in VSMCs was investigated. After mouse carotid injury, the expression of ACLP increases in the dedifferentiated VSMCs of the neointima in a pattern that differs from that of smooth muscle α-actin. To better understand the regulation of ACLP in VSMCs, we characterized the 21-exon mouse ACLP gene and 5′-flanking region and examined its promoter activity. In transient transfection assays, 2.5 kb of the ACLP 5′-flanking sequence directed high levels of luciferase reporter activity in primary cultured rat aortic smooth muscle cells, and this activity was not dependent on serum response factor. We identified a positive element between base pairs −156 and −122 by analysis of 5′ deletion and mutant constructs. By use of electrophoretic mobility shift assays with rat aortic smooth muscle cell nuclear extracts, Sp1 and Sp3 transcription factors bound to this region, and transfection assays in D.Mel.2 cells revealed that both Sp1 and Sp3 transactivated the ACLP promoter. Transgenic mice harboring the −2.5-kb ACLP promoter upstream from a nuclear-targeted LacZ gene were generated, and expression was detected in the VSMCs of large blood vessels, arterioles, and veins. Interestingly, ACLP promoter–LacZ reporter activity increased within the neointimal VSMCs of injured carotid vessels, consistent with the expression of the endogenous ACLP protein. The ACLP promoter may provide a novel tool to target gene expression to dedifferentiated VSMCs.
Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses
Authors: Jooyeon Woo, Seok-Kyu Kwon, Seungwon Choi, Seho Kim, Jae-Ran Lee, Anthone W Dunah, Morgan Sheng, Eunjoon Kim
Journal: Nature Neuroscience (2009)
Homing commitment of lymphocytes activated in the human gastric and intestinal mucosa
Authors: M Quiding-Jarbrink
Journal: Gut (2001)

<h3>BACKGROUND</h3> Gastric infection with the human pathogen <i>Helicobacter pylori</i> results in a large accumulation of IgA and IgM secreting cells in the gastric mucosa. The molecular mechanisms resulting in B cell migration to the gastric mucosa in <i>H pylori</i> infection are however not known. <h3>AIMS</h3> To examine expression of the mucosal homing receptor integrin α4β7 and the homing receptor for secondary lymphoid tissues, l-selectin, on lymphocytes activated by gastric, intestinal, or systemic antigens. Furthermore, to examine gastric expression of the mucosal addressin cellular adhesion molecule 1 (MAdCAM-1), the endothelial counter-receptor to integrin α4β7. <h3>SUBJECTS AND METHODS</h3> H pylori infected individuals were immunised by either gastric (n=8) or intestinal (n=8) delivery of an inactivated cholera vaccine. The resulting circulating vaccine specific B cells were sorted according to α4β7 and l-selectin expression and assayed for production of IgA and IgG using an enzyme linked immunospot assay. In addition, circulating CD4+ T cells from seven <i>H pylori</i> infected individuals were fractionated according to α4β7 and l-selectin expression. The resulting T cell fractions were then assayed for specific proliferation against<i>H pylori</i> or the systemic antigen tetanus toxoid. Finally, gastric expression of MAdCAM-1 was determined by immunohistochemistry in <i>H pylori</i> infected (n=16) and uninfected (n=8) individuals. <h3>RESULTS</h3> Virtually all B cells induced by both gastric and intestinal antigen delivery expressed α4β7 whereas less then half coexpressedl-selectin. Furthermore, <i>H pylori</i> reactive T cells were mainly found in the α4β7+l-selectin+ T cell fraction whereas tetanus specific T cells were largely α4β7−l-selectin+. MAdCAM-1 was present in similar amounts in gastric mucosa from<i>H pylori</i> infected and uninfected individuals. <h3>CONCLUSIONS</h3> B cells and T cells activated by antigens delivered to the gastric mucosa express the mucosal homing receptor integrin α4β7, as do cells activated in the intestine. Together with the observation that gastric endothelial cells express MAdCAM-1, this may partly explain the homing of lymphocytes activated in the stomach or in the small intestine to the gastric mucosa.
Effect of Mechanical Ventilator Weaning Protocols on Respiratory Outcomes in Infants and Children&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Adrienne G. Randolph
Journal: JAMA (2002)

Ventilator management protocols shorten the time required to wean adult patients from mechanical ventilation. The efficacy of such weaning protocols among children has not been studied.To evaluate whether weaning protocols are superior to standard care (no defined protocol) for infants and children with acute illnesses requiring mechanical ventilator support and whether a volume support weaning protocol using continuous automated adjustment of pressure support by the ventilator (ie, VSV) is superior to manual adjustment of pressure support by clinicians (ie, PSV).Randomized controlled trial conducted in the pediatric intensive care units of 10 children's hospitals across North America from November 1999 through April 2001.One hundred eighty-two spontaneously breathing children (<18 years old) who had been receiving ventilator support for more than 24 hours and who failed a test for extubation readiness on minimal pressure support.Patients were randomized to a PSV protocol (n = 62), VSV protocol (n = 60), or no protocol (n = 60).Duration of weaning time (from randomization to successful extubation); extubation failure (any invasive or noninvasive ventilator support within 48 hours of extubation).Extubation failure rates were not significantly different for PSV (15%), VSV (24%), and no protocol (17%) (P =.44). Among weaning successes, median duration of weaning was not significantly different for PSV (1.6 days), VSV (1.8 days), and no protocol (2.0 days) (P =.75). Male children more frequently failed extubation (odds ratio, 7.86; 95% confidence interval, 2.36-26.2; P<.001). Increased sedative use in the first 24 hours of weaning predicted extubation failure (P =.04) and, among extubation successes, duration of weaning (P<.001).In contrast with adult patients, the majority of children are weaned from mechanical ventilator support in 2 days or less. Weaning protocols did not significantly shorten this brief duration of weaning.
Neanderthal Origin of the Haplotypes Carrying the Functional Variant Val92Met in the MC1R in Modern Humans
Authors: Qiliang Ding, Ya Hu, Shuhua Xu, Chuan-Chao Wang, Hui Li, Ruyue Zhang, Shi Yan, Jiucun Wang, Li Jin
Journal: Molecular Biology and Evolution (2014)

Skin color is one of the most visible and important phenotypes of modern humans. Melanocyte-stimulating hormone and its receptor played an important role in regulating skin color. In this article, we present evidence of Neanderthal introgression encompassing the melanocyte-stimulating hormone receptor gene MC1R. The haplotypes from Neanderthal introgression diverged with the Altai Neanderthal 103.3 ka, which postdates the anatomically modern human-Neanderthal divergence. We further discovered that all of the putative Neanderthal introgressive haplotypes carry the Val92Met variant, a loss-of-function variant in MC1R that is associated with multiple dermatological traits including skin color and photoaging. Frequency of this Neanderthal introgression is low in Europeans (∼5%), moderate in continental East Asians (∼30%), and high in Taiwanese aborigines (60-70%). As the putative Neanderthal introgressive haplotypes carry a loss-of-function variant that could alter the function of MC1R and is associated with multiple traits related to skin color, we speculate that the Neanderthal introgression may have played an important role in the local adaptation of Eurasians to sunlight intensity.
Panic and Phobic Anxiety: Defining Phenotypes for Genetic Studies
Authors: J W Smoller, M T Tsuang
Journal: American Journal of Psychiatry (1998)

Objective: With recent advances in molecular genetics, the rate-limiting step in identifying susceptibility genes for psychiatric disorders has become phenotype definition. The success of psychiatric genetics may require the development of a "genetic nosology" that can classify individuals in terms of the heritable aspects of psychopathology. The authors" aim is to begin to apply this analysis to the anxiety disorders, focusing on panic and phobic disorders. Method: Two parallel traditions of defining anxiety phenotypes are reviewed: the first, more closely identified with clinical psychiatry, has identified categorical diagnoses (e.g., panic disorder and social phobia). The other, more closely identified with psychological studies of personality development, has examined dimensional traits (e.g., neuroticism) and anxious temperament (e.g., behavioral inhibition). Results: The authors suggest that a genetic nosology of panic and phobic disorders may incorporate features of both traditions and discuss strategies for optimizing genetic approaches to anxiety including 1) studying phenotypic extremes, 2) identifying biological trait markers, and 3) using animal models to identify candidate loci. Conclusions: An important dividend from the effort to define the boundaries of heritable phenotypes for genetic studies of anxiety may be a refinement of the nosology of anxiety disorders. Am J Psychiatry 1998; 155: 1152-1162
Microorganisms isolated in COPD patients hospitalised for acute exacerbations and their clinical correlations
Authors: Tacettin Örnek, Fatma Erboy, Figen Atalay, Remzi Altin, Meltem Tor
Journal: European Respiratory Journal (2012)

Microorganisms isolated in hospitalised patients with COPD increase morbidity and mortality. We analysed the microorganisms isolated in blood, sputum, tracheal aspirate and/or bronchial lavage cultures of COPD patients hospitalised for acute exacerbations.135 COPD patients were included in the study. Mean age of patients was 69.4±11.6 year and 74.1% of the patients was male. The length of hospital stay was 13.9±8.3 day and 57.0%(n=77) of the patients were followed up in intensive care unit (ICU). Mortality rate was 28.1%. In 51.1%(n=69) at least one culture was positive. Cultures of blood, sputum, tracheal aspirate and bronchial lavage were positive in 34.3%, 48.8%, 71.2% and 6.7% respectively. Acinetobacter was the most isolated microorganism.  The most common microorganism in the ward, and ICU patients were Pseudomonas(8.6%) and Acinetobacter(32.5%) respectively. Mean age was 72.2±9.4 vs 66.4±12.9(p=0.004), mortality rate was 47.8% vs 7.6%(p
Effects of endothelin in radiocontrast-induced nephropathy in rats are mediated through endothelin-A receptors.
Authors: J E Bird, M R Giancarli, J R Megill, S K Durham
Journal: Journal of the American Society of Nephrology (1996)

A role for endothelin in the pathogenesis of radiocontrast-induced nephropathy has been suggested by several studies, but the specific contributions of endothelin-A and endothelin-B receptors to the changes in renal function induced by endothelin in this form of renal failure have not been defined. This study examined the effects of the nonselective endothelin receptor antagonist SB-209,670, and the less potent, but selective, endothelin-A receptor antagonist BMS-182,874 in radiocontrast-induced nephropathy in rats. The doses used in this study were chosen from pressor testing data. BMS-182,874 (100 mumol/kg, iv) and SB-209,670 (30 mumol/kg, iv) maximally inhibited the endothelin-1-induced pressor response in rats. BMS-182,874 had no effect on the endothelin-B-mediated depressor response, whereas SB-209,670 abolished it. These results suggest that this is an endothelin-A selective dose of BMS-182,874, and an endothelin-A/B inhibitory dose of SB-209,670. Radiocontrast-induced nephropathy was produced in anesthetized rats (N = 6/group) by intravenous injection of indomethacin (5.0 mg/kg), the nitric oxide synthesis inhibitor N-nitro-L-arginine methyl ester (10.0 mg/kg), vehicle or antagonist, and the radiocontrast agent lopamidol (2,9 g iodine/kg). GFR was partially protected (P < 0.05) by BMS-182,874 (-43 +/- 3.0% change from baseline) compared with vehicle (-65 +/- 6.0%). The decrease in GFR in SB-209,670-treated rats that received lopamidol was intermediate between the other two groups. The fall in RPF induced by lopamidol was unchanged by either antagonist. The marked diuresis in lopamidol treated rats (630 +/- 125.1%) was reduced (P < 0.01) by BMS-182,874 (176 +/- 77.1%) or SB-209,670 (173 +/- 60.1%). Kidneys were collected for histopathologic evaluation approximately 1 h after lopamidol administration, and the percentage of medullary tubular ascending limbs (mTAL) with morphologic features of necrosis were enumerated by semiquantitative analysis. The percentage of mTAL necrosis was significantly decreased in the BMS-182,874- or SB-209,670-treated rats (P < 0.01) compared with vehicle plus lopamidol-treated animals. In summary, endothelin-A receptor blockade with a highly selective, well-characterized endothelin-A receptor antagonist partly protected GFR, and reduced the marked diuresis and mTAL necrosis in radiocontrast-induced nephropathy in rats. Administration of a nonselective endothelin receptor antagonist provided essentially equivalent ameliorative effects in this model, suggesting that blockade of endothelin-B receptors did not yield any additional protection. These results are consistent with the hypothesis that endothelin-A receptors mediate endothelin-induced changes in renal function and structure in this acute model of radiocontrast-induced nephropathy.