tbuckley/cabot-search huggingface dataset:
<i>Jumonji Domain Containing 1A</i> Is a Novel Prognostic Marker for Colorectal Cancer: <i>In vivo</i> Identification from Hypoxic Tumor Cells
Authors: Mamoru Uemura, Hirofumi Yamamoto, Ichiro Takemasa, Koshi Mimori, Hideyuki Hemmi, Tsunekazu Mizushima, Masataka Ikeda, Mitsugu Sekimoto, Nariaki Matsuura, Yuichiro Doki, Masaki Mori
Journal: Clinical Cancer Research (2010)

Abstract Purpose: This study aimed to identify novel hypoxia-inducible and prognostic markers in vivo from hypoxic tumor cells. Experimental Design: Using carbonic anhydrase 9 and CD34 as a guide for hypoxic tumor cells, laser capture microdissection was used to isolate colorectal cancer (CRC) liver metastases. The samples were analyzed by microarray analysis, in parallel with five CRC cell lines cultured under hypoxic conditions. To evaluate the prognostic impact of the expression of certain genes, samples from a total of 356 CRC patients were analyzed by microarray or quantitative reverse transcription-PCR. In vitro mechanistic studies and in vivo therapeutic experiments were also done about a histone H3 Lys9 demethylase, Jumonji domain containing 1A (JMJD1A). Results: Several candidate genes were identified by microarray analysis of liver metastases and culturing of CRC cells under hypoxic conditions. Among them, we found that JMJD1A was a novel independent prognostic factor for CRC (P = 0.013). In vitro assays revealed that loss of JMJD1A by small interfering RNA treatment was associated with a reduction of proliferative activity and decrease in invasion of CRC cell lines. Furthermore, treatment with an adenovirus system for antisense JMJD1A construct displayed prominent therapeutic effects when injected into established tumor xenografts of the CRC cell lines HCT116 and DLD1. Conclusions: JMJD1A is a useful biomarker for hypoxic tumor cells and a prognostic marker that could be a promising therapeutic target against CRC. Clin Cancer Res; 16(18); 4636–46. ©2010 AACR.
Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity
Authors: Ricardo V. Cohen, Jose C. Pinheiro, Carlos A. Schiavon, João E. Salles, Bernardo L. Wajchenberg, David E. Cummings
Journal: Diabetes Care (2012)

Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class I obesity.Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication).Participants had severe, longstanding diabetes, with disease duration 12.5 ± 7.4 years and HbA(1c) 9.7 ± 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 ± 1.5 to 5.9 ± 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved β-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke.This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).
Enzyme-linked Immunospot and Tuberculin Skin Testing to Detect Latent Tuberculosis Infection
Authors: Homayoun Shams, Stephen E. Weis, Peter Klucar, Ajit Lalvani, Patrick K. Moonan, Janice M. Pogoda, Katie Ewer, Peter F. Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin skin test. The enzyme-linked immunospot assay (ELISPOT) is a new blood test to diagnose LTBI.To compare the ELISPOT and the tuberculin skin test for detecting LTBI in contacts of patients with tuberculosis.Prospective study of 413 contacts of patients with tuberculosis.Because there is no gold standard for LTBI, the sensitivity and specificity of the ELISPOT and tuberculin skin test cannot be directly measured. For each contact, we therefore estimated the likelihood of having LTBI by calculating a contact score that quantified exposure to and infectiousness of the index case. We analyzed the relationship of contact score to ELISPOT and tuberculin skin test results. The likelihood of a positive ELISPOT (p = 0.0005) and a tuberculin skin test (p = 0.01) increased significantly with rising contact scores. The contact score was more strongly related to the ELISPOT than to the tuberculin skin test results, although this difference was not statistically significant. Among U.S.-born persons and those who were not vaccinated with bacille Calmette-Guérin, approximately 30% had positive ELISPOT or tuberculin skin test results. Foreign-born, bacille Calmette-Guérin-vaccinated persons were significantly more likely to have a positive tuberculin skin test than a positive ELISPOT result (p < 0.0001).Compared with the tuberculin skin test, the ELISPOT appears to be at least as sensitive for diagnosis of LTBI in contacts of patients with tuberculosis.
Effects of acetylcholine on the ventricular specialized conducting system of neonatal and adult dogs.
Authors: P Danilo, M R Rosen, A J Hordof
Journal: Circulation Research (1978)

We determined the effects of acetylcholine on automaticity of isolated cardiac Purkinje fibers from neonatal and adult dogs and on the idioventricular rhythm of adult dogs with complete atrioventricular block. Isolated Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. For both age groups, spontaneous rate was decreased by acetylcholine, an effect which was reduced by atropine. The magnitude of the effect is equal in both neonatal and adult dogs. The negative chronotropic effect of acetylcholine was not prevented by phentolamine, indicating that an alpha-adrenergic mechanism was not involved. The idioventricular rate of conscious dogs with formalin-induced heart block was decreased by administration of acetylcholine. The effect was augmented by propranolol and attenuated by atropine. Thus, for both the in vitro and in situ ventricular specialized conducting system, acetylcholine decreases automaticity presumably through combination with a muscarinic receptor.
The Fitness, Obesity, and Health Equation
Authors: Steven N. Blair, Tim S. Church
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Central Neural Integration for the Control of Autonomic Responses Associated with Emotion
Authors: Orville A. Smith, June L. DeVito
Journal: Annual Review of Neuroscience (1984)

The continual search for the neural substrates underlying integrated behavior has been aided dramatically by the development of tracer techniques based on axoplasmic transport, cytochemistry , and metabolic markers. Over the past ten years the major use of these approaches has been to revamp our ideas of how the nervous system is interconnected and, to the delight of publishers, to revise the textbooks in the field. The race to establish what is connected to what has peaked and there are now more attempts to use the knowledge and techniques to study the neural basis of integrated functions. Recent particularly fine examples are those of Swanson and colleagues (Swanson & Mogenson 1981, Swanson & Sawchenko 1983). In this regard there are few areas of research that need elucidation regarding the underlying neural basis more than that of emotion and its relation to the activity of the autonomic nervous system. For several reasons this area has been particularly refractory to experimental analysis. The first problem lies in the specification of what is meant by emotion and how to measure it. Psychologists have criticized the concept to the point where many refuse even to use the term; it is clearly a situation that calls for the use of a stringent operational definition,
Considering Usual Medical Care in Clinical Trial Design
Authors: Liza Dawson, Deborah A. Zarin, Ezekiel J. Emanuel, Lawrence M. Friedman, Bimal Chaudhari, Steven N. Goodman
Journal: PLoS Medicine (2009)

N Challenges often arise when researchers propose clinical trials incorporating usual care comparison groups.N Disagreements may arise about current levels of evidence supporting usual care or failures to use best known methods in clinical practice; about the need for customized care, or about the difficulty in choosing best treatments when available interventions have trade-offs.N Clinical trial designs incorporating usual care arms must be based on scientific validity, consideration of risks and benefits to patients, relevance to the clinical care community, and feasibility.
Alteration of the adrenal antioxidant defense system during aging in rats.
Authors: S Azhar, L Cao, E Reaven
Journal: Journal of Clinical Investigation (1995)

The goal of this study was to determine to what extent aging affects the antioxidant defense system of the rat adrenal and to evaluate the impact of any change in this system on the recognized age-related decline in steroidogenic capacity of adrenocortical cells. The studies were conducted on young (2-5 mo) and aging (12-27 mo) Sprague-Dawley rats and involved procedures measuring steroidogenesis; oxidative damage to tissue; non enzymatic antioxidants such as vitamin C, E, and glutathione; and tissue antioxidant enzyme (Mn and CuZn superoxide dismutases, catalase, and glutathione peroxidase) activity and expression (mRNA, protein mass, and location). Some measurements were made also on rats maintained on vitamin E-deficient diets. The data show that adrenals from young animals are especially well protected against oxidative events; i.e., these adrenals show the least endogenous lipid peroxidation and the highest level of resistance to prooxidant-induced damage (of various tissues measured) and show exceedingly high levels of tissue antioxidants. Aging, on the other hand, results in oxidative changes in adrenal tissue that are generally linked in time to a reduction in efficiency of the normally protective antioxidant defense system and to the decline in corticosterone production. We speculate that these events are causally related, i.e., that the age-related reduction in oxidative mechanisms in adrenal tissues leads to oxidative damage of membrane or cytosolic factors important to cholesterol transport, and, as a consequence of this damage, cholesterol cannot reach appropriate mitochondrial cholesterol side chain cleavage sites, and corticosterone production fails.
Association between Development of the Coronary Collateral Arteries and Epicardial Adipose Tissue Thickness
Authors: Bilal Geyik, Flora Özkalaycı, Özcan Özdemir, Çağdaş Kaynak, Mustafa Yılmaztepe, Selçuk Öztürk, Gökay Taylan, Aykut Yılmaz, Yücel Kaçmaz, Ali Manav, Uğur Özkan, İbrahim Özyamaç, Yüksel Aksoy
Journal: Journal of the American College of Cardiology (2013)
Matrix Metalloproteinase-7 and Premalignant Host Responses in <i>Helicobacter pylori</i>–Infected Mice
Authors: Seth R. Ogden, Jennifer M. Noto, Shannon S. Allen, Dilan A. Patel, Judith Romero-Gallo, M. Kay Washington, Barbara Fingleton, Dawn A. Israel, Nuruddeen D. Lewis, Keith T. Wilson, Rupesh Chaturvedi, Zhiguo Zhao, Yu Shyr, Richard M. Peek
Journal: Cancer Research (2010)

Abstract Helicobacter pylori–induced gastritis is the strongest singular risk factor for gastric adenocarcinoma. Matrix metalloproteinase-7 (MMP-7) is a proteolytic enzyme that can modify the intestinal microbial replicative niche as well as affect tumorigenesis, and H. pylori stimulates expression of MMP-7 in gastric epithelial cells in vitro. Utilizing a transgenic murine model of H. pylori–mediated injury, our experiments now show that gastric inflammation is increased within the context of MMP-7 deficiency, which involves both Th1- and Th17-mediated pathways. Enhanced gastritis in H. pylori–infected mmp-7−/− mice is strongly linked to accelerated epithelial cellular turnover. However, more severe inflammation and heightened proliferation and apoptosis are not dependent on MMP-7–mediated bacterial eradication. Collectively, these studies indicate that H. pylori–mediated induction of MMP-7 may serve to protect the gastric mucosa from pathophysiologic processes that promote carcinogenesis. Cancer Res; 70(1); 30–5
Lineage-Specific Variation in Intensity of Natural Selection in Mammals
Authors: M. Toll-Riera, S. Laurie, M. M. Alba
Journal: Molecular Biology and Evolution (2010)

The molecular clock hypothesis states that protein-coding genes evolve at an approximately constant rate. However, this is only expected to be true as long as the function and the tertiary structure of the molecule remain unaltered. An important implication of this statement is that significant deviations in the rate of evolution of a gene with respect to the species clock are likely to reflect functional and/or structural alterations. Here, we present a method to identify such deviations and apply it to a data set of 2,929 high-quality coding sequence alignments corresponding to one-to-one orthologous genes from six mammalian species—human, macaque, mouse, rat, cow, and dog. Deviated branches are defined as those that present significant alterations in both the rate of nonsynonymous substitutions (dN) and the selective pressure (dN/dS). Strikingly, we find that as many as 24.5% of the genes show branch-specific deviations in dN and dN/dS, though this is a relatively well-conserved set of genes. Around half of these genes show branch-specific acceleration of evolutionary rates. Positive selection (PS) tests based on divergence data only identify 17.7% of the accelerated branches. Failure to identify PS in accelerated branches with an excess of radical amino acid replacements suggests that these tests are conservative. Interestingly, genes with accelerated branches are significantly enriched in neural proteins, indicating that this type of protein might play a more important role than previously thought in species diversification, although they are generally not detected by PS tests. We discuss in detail several examples of genes that show lineage-specific evolutionary rate acceleration and are involved in synaptic transmission, chemosensory perception, and ubiquitination.
EFFECT OF VASODILATOR THERAPY ON VALVULOARTERIAL IMPEDANCE AND DIASTOLIC FUNCTION IN LOW FLOW, LOW GRADIENT AORTIC STENOSIS WITH PRESERVED EJECTION FRACTION
Authors: Mackram Eleid, Barry Borlaug, Paul Sorajja, Vuyisile Nkomo, Sorin Pislaru, Youssef Maalouf, Philippe Pibarot, Rick Nishimura
Journal: Journal of the American College of Cardiology (2014)
A STUDY OF CULTURES FROM SPUTUM AND BLOOD IN LOBAR PNEUMONIA
Authors: T. W. Hastings, Emil Boehm
Journal: The Journal of Experimental Medicine (1913)

In the thirty-two unselected cases studied, cultures were taken from both the blood and the sputum, and in five of these more than one blood culture was taken. In one case the culture was taken from the blood only, and in this instance the pneumococcus was found. This case will be considered only with reference to the incidence of the pneumococci in blood cultures in lobar pneumonia. The results in the thirty-two cases in which cultures were made both from the blood and the sputum are as follows: 1. In eleven cases the blood and sputum cultures were positive. (a) In nine cases the pneumococcus was isolated, and five of these patients died. (b) In two cases, instead of the pneumococcus, Streptococcus hemolysans (longus) was found. One of these patients died. 2. In twenty-one cases the blood cultures were negative, and in eighteen of these the sputum cultures were positive and in three negative. In these three the only result recorded was the absence of the pneumococcus. (a) In nine cases the pneumococcus was isolated. Two of these patients died. (b) In twelve cases no pneumococcus was found. Two of these patients died. Of the patients in which no pneumococcus was found, in two cases Bacillus coli was isolated; in one case Micrococcus catarrhalis; in one case a staphylococcus (type not stated); in two cases staphylococcus and streptococcus; in one case Bacillus influenzae, in one case Bacillus fluorescens non-liquefaciens; in one case an unidentified Gram positive chromogenic organism, probably saprophytic; and in three cases there are no recorded results except that the pneumococcus was absent. In the total of thirty-three blood cultures, the pneumococcus was found in ten cases (30.3 per cent.), and six of the patients died. During the years 1910 to 1912 sputum cultures were taken from forty-four cases of pneumonia, of which twenty-four showed pneumococci (54 per cent.), and twenty showed no pneumococci (45 per cent.).
Fetal Programming of Type 2 Diabetes
Authors: Chittaranjan S. Yajnik, Koumudi Godbole, Suhas R. Otiv, Himangi G. Lubree
Journal: Diabetes Care (2007)

Hales and Barker (1) caused a paradigm shift in our thinking about diabetes prevention when they demonstrated that low birth weight (due to growth retardation) predicted type 2 diabetes (the “thrifty phenotype” or “fetal origins” hypothesis). On the other hand, larger babies of diabetic mothers are also at higher risk of diabetes, apart from their genetic susceptibility (“fuel mediated teratogenesis”) (2,3). A concept evolved that the intrauterine experiences mold the fetal systems (“programming”) and influence future health (4). If the postnatal experiences are at variance with the intrauterine ones, the programmed fetus is susceptible to disease (5). For example, low birth weight babies who put on excess weight in later life are at a higher risk of type 2 diabetes than those who continue to be low weight (6). In the programming hypothesis, the focus is on the role of intrauterine environment and on gene-environment interaction rather than the differences in gene structure, which are the basis of conventional genetics. Genes are clearly important, and their role in intrauterine development and risk of diabetes was highlighted by Hattersley and Tooke (the “fetal insulin hypothesis”) (7). The most exciting thought in fetal programming is that intrauterine environment may modify gene expression permanently. A heritable change in gene expression without a change in DNA sequence is called “epigenetic” (8), a term first used by Waddington in developmental biology. Epigenetic changes alter gene function and can be silencing …
CHF1/Hey2 Plays a Pivotal Role in Left Ventricular Maturation Through Suppression of Ectopic Atrial Gene Expression
Authors: Nobutaka Koibuchi, Michael T. Chin
Journal: Circulation Research (2007)

We previously reported that mice lacking the hairy-related basic helix-loop-helix (bHLH) transcription factor CHF1/Hey2 develop a thin-walled left ventricle. To explore the basis for this phenotype, we examined regional gene expression patterns in the developing myocardium. We found that atrial natriuretic factor (ANF), which is normally expressed in the atria and trabeculae and is restricted from the developing compact myocardium beginning at embryonic day 13.5, is persistently expressed in the left ventricular compact myocardium of the knockout animals. We also examined the expression pattern of the T-box transcription factor Tbx5, a known regulator of ANF, and an additional Tbx5-dependent gene, connexin 40 (Cx40), both of which share a similar expression pattern to ANF during development. Tbx5 and Cx40 were similarly expressed ectopically in the compact myocardium of the CHF1/Hey2 knockout mouse. The atrial contractile genes mlc1a and mlc2a were also expressed ectopically in the left ventricular compact myocardium, providing evidence for a general dysregulation of atrial gene expression. Crossing of a myocardial-specific CHF1/Hey2 transgenic mouse with the knockouts led to rescue of the thin-walled myocardial phenotype and restoration of the normal patterns of gene expression. Myocardial cell proliferation, which has been shown previously to be suppressed by Tbx5, was also decreased in the knockout mice and rescued by the transgene. Our findings suggest that CHF1/Hey2 suppresses atrial identity in the left ventricular compact myocardium, facilitates myocardial proliferation by suppressing Tbx5, and thereby promotes proper ventricular myocardial maturation.
Inactivation of <i>von Hippel-Lindau</i> Gene Induces Constitutive Phosphorylation of MET Protein in Clear Cell Renal Carcinoma
Authors: Noboru Nakaigawa, Masahiro Yao, Masaya Baba, Shingo Kato, Takeshi Kishida, Keiko Hattori, Yoji Nagashima, Yoshinobu Kubota
Journal: Cancer Research (2006)

Abstract It is well known that inactivation of von Hippel-Lindau (VHL) gene predisposes for human clear cell renal carcinoma (CCRC). However, details about critical roles of VHL inactivation during tumorigenesis are still unknown. MET protein is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), which regulates cell growth, cell morphology, and cell motility. We showed that MET protein overexpressed in CCRC cells was phosphorylated without HGF/SF. This constitutive phosphorylation of MET protein in CCRC cells was inhibited by the rescue of exogenous wild-type VHL gene without a decrease in expression level of MET protein. Interestingly, wild-type VHL gene suppressed the phosphorylation of MET protein only under high cell density conditions. Additionally, MET protein activated by the inactivation of VHL gene modified cell adherence, including N-cadherin and β-catenin. When activation of MET protein in CCRC cells was inhibited by the MET inhibitor K252a, the growth of CCRC cells in vitro and the tumorigenesis induced by CCRC cells in nude mice were suppressed. From these results, we concluded that inactivation of VHL gene induced constitutive phosphorylation of MET protein and modified intercellular adherence structure to trigger the cell growth released from contact inhibition, finally resulting in tumorigenesis. This is one of the mechanisms of CCRC oncogenesis, and MET protein has potential as a molecular target for novel CCRC therapies. (Cancer Res 2006; 66(7): 3699-705)