tbuckley/cabot-search huggingface dataset:
Health Status of Vietnam Veterans
Authors: Eugenia E. Calle
Journal: JAMA (1988)

The Vietnam Experience Study was a multidimensional assessment of the health of Vietnam veterans. From a random sample of enlisted men who entered the US Army from 1965 through 1971, 7924 Vietnam and 7364 non-Vietnam veterans participated in a telephone interview; a random subsample of 2490 Vietnam and 1972 non-Vietnam veterans also underwent a comprehensive medical examination. During the telephone interview, Vietnam veterans reported more adverse reproductive and child health outcomes than did non-Vietnam veterans. However, children of Vietnam veterans were not more likely to have birth defects recorded on hospital birth records than were children of non-Vietnam veterans. The rates of total, major, minor, and suspected defects were similar among children of Vietnam and non-Vietnam veterans (odds ratios, 1.0, 1.1, 1.0, and 0.9, respectively). These results are consistent with the findings of three epidemiologic studies conducted since 1981 on the relationship of Vietnam service and birth defects in children of male veterans.  ( JAMA 1988;259:2715-2719)
Functional Effects of Protein Kinase C Activation on the Human Cardiac Na sup + Channel
Authors: Katherine T. Murray, NingNing Hu, J. Richard Daw, Hyeon-Gyu Shin, Marshall T. Watson, Amy B. Mashburn, Alfred L. George
Journal: Circulation Research (1997)

The cardiac Na sup + current plays an important role in determining normal and abnormal impulse propagation in the heart. We have investigated the effects of protein kinase C (PKC) activation on the recombinant human cardiac Na sup + channel (hH1) following heterologous expression in Xenopus laevis oocytes. Phorbol 12-myristate 13-acetate (PMA), which directly activates PKC, reduced current amplitude at all test potentials (43 +/- 12% at -10 mV). In contrast to the rat brain IIA (rBIIA) channel, there was no apparent change in either macroscopic Na sup + current decay or the voltage dependence of channel gating. Further experiments indicate that the effects of PMA were mediated by PKC activation: (1) an inactive stereoisomer, 4 alpha-PMA, had no effect; (2) preincubation with the protein kinase inhibitor chelerythrine prevented the PMA effects; and (3) a hydrolyzable diacylglycerol analogue, 1-oleoyl-2-acetyl-glycerol, also reduced current (22 +/- 5%). In addition, when the alpha 1B -adrenergic receptor was coexpressed with hH1, the alpha-receptor agonist methoxamine reduced hH1 current (45 +/- 10%), an effect that could be eliminated by chelerythrine preincubation. When a conserved consensus PKC site (serine 1503) in the III-IV interdomain linker thought to be responsible for the PKC effects on rBIIA was mutated, PMA still reduced Na sup + current, but the magnitude of the effect was smaller compared with that for the wild-type channel. Similar findings were obtained with alpha 1 -receptor stimulation following receptor coexpression with the mutant channel. We conclude that activation of PKC modulates the human cardiac Na sup + channel by at least two mechanisms, one similar to that seen with rat brain channels, involving a conserved putative PKC site, and a second more specific to the cardiac isoform.
A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes
Authors: Terje Sagvolden, Espen Borgå Johansen, Heidi Aase, Vivienne Ann Russell
Journal: Behavioral and Brain Sciences (2005)

Attention-deficit/hyperactivity disorder (ADHD) is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Inattentiveness, overactivity, and impulsiveness are presently regarded as the main clinical symptoms. The dynamic developmental behavioral theory is based on the hypothesis that altered dopaminergic function plays a pivotal role by failing to modulate nondopaminergic (primarily glutamate and GABA) signal transmission appropriately. A hypofunctioning mesolimbic dopamine branch produces altered reinforcement of behavior and deficient extinction of previously reinforced behavior. This gives rise to delay aversion, development of hyperactivity in novel situations, impulsiveness, deficient sustained attention, increased behavioral variability, and failure to "inhibit" responses ("disinhibition").A hypofunctioning mesocortical dopamine branch will cause attention response deficiencies (deficient orienting responses, impaired saccadic eye movements, and poorer attention responses toward a target) and poor behavioral planning (poor executive functions). A hypofunctioning nigrostriatal dopamine branch will cause impaired modulation of motor functions and deficient nondeclarative habit learning and memory. These impairments will give rise to apparent developmental delay, clumsiness, neurological "soft signs," and a "failure to inhibit" responses when quick reactions are required.A hypofunctioning mesocortical dopamine branch will cause attention response deficiencies (deficient orienting responses, impaired saccadic eye movements, and poorer attention responses toward a target) and poor behavioral planning (poor executive functions). A hypofunctioning nigrostriatal dopamine branch will cause impaired modulation of motor functions and deficient nondeclarative habit learning and memory. These impairments will give rise to apparent developmental delay, clumsiness, neurological "soft signs," and a "failure to inhibit" responses when quick reactions are required.
Prediction and Classification of Human G-protein Coupled Receptors Based on Support Vector Machines
Authors: Yun-Fei Wang, Huan Chen, Yan-Hong Zhou
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract A computational system for the prediction and classification of human G-protein coupled receptors (GPCRs) has been developed based on the support vector machine (SVM) method and protein sequence information. The feature vectors used to develop the SVM prediction models consist of statistically significant features selected from single amino acid, dipeptide, and tripeptide compositions of protein sequences. Furthermore, the length distribution difference between GPCRs and non-GPCRs has also been exploited to improve the prediction performance. The testing results with annotated human protein sequences demonstrate that this system can get good performance for both prediction and classification of human GPCRs.
Normalization of boutique two-color microarrays with a high proportion of differentially expressed probes.
Authors: Alicia Oshlack, Dianne Emslie, Lynn M Corcoran, Gordon K Smyth
Journal: Genome biology (2007)

Abstract Normalization is critical for removing systematic variation from microarray data. For two-color microarray platforms, intensity-dependent lowess normalization is commonly used to correct relative gene expression values for biases. Here we outline a normalization method for use when the assumptions of lowess normalization fail. Specifically, this can occur when specialized boutique arrays are constructed that contain a subset of genes selected to test particular biological functions.
Predictive and Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Non–Small-Cell Lung Cancer Patients Treated With Gefitinib
Authors: Sae-Won Han, Tae-You Kim, Pil Gyu Hwang, Soohyun Jeong, Jeongmi Kim, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Dong-Wan Kim, Doo Hyun Chung, Seock-Ah Im, Young Tae Kim, Jong Seok Lee, Dae Seog Heo, Yung-Jue Bang, Noe Kyeong Kim
Journal: Journal of Clinical Oncology (2005)

This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non-small-cell lung cancer (NSCLC) patients treated with gefitinib.For 90 consecutive NSCLC patients who had received gefitinib, EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 21, and 23 in the EGFR tyrosine kinase domain. Expressions of phosphorylated (p) -Akt and p-Erk were determined via immunohistochemistry. Response rate, time to progression (TTP), and overall survival were compared between each group according to EGFR mutation, as well as p-Akt and p-Erk expression.Seventeen patients (18.9%; 95% CI, 10.8 to 27.0) harbored EGFR mutations. These mutations include deletions in exon 19 in seven patients, L858R in six patients, G719A in three patients, and a novel A859T in one patient. Response rate in patients with EGFR mutation was 64.7% (11 of 17 patients; 95% CI, 42.0 to 87.4), in contrast to 13.7% (10 of 73 patients; 95% CI, 5.8 to 21.6) in patients without mutation (P < .001). Moreover, these 17 patients with EGFR mutation had significantly prolonged TTP (21.7 v 1.8 months; P < .001) and overall survival (30.5 v 6.6 months; P < .001) compared with the remaining 73 patients without mutation. Although no significant correlation was detected between EGFR mutation and expressions of p-Akt or p-Erk, p-Akt overexpression was associated with prolonged TTP in patients with EGFR mutation.Our data further support the importance of EGFR mutation with regard to gefitinib sensitivity. In addition to its predictive role, EGFR mutation confers significant survival benefits on NSCLC patients treated with gefitinib.
A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice
Authors: Ying Tian, Ying Liu, Tao Wang, Ning Zhou, Jun Kong, Li Chen, Melinda Snitow, Michael Morley, Deqiang Li, Nataliya Petrenko, Su Zhou, Minmin Lu, Erhe Gao, Walter J. Koch, Kathleen M. Stewart, Edward E. Morrisey
Journal: Science Translational Medicine (2015)

A microRNA-based therapeutic approach could be used to promote cardiac regeneration through the transient activation of cardiomyocyte proliferation.
Hypercapnic Acidosis Activates K <sub>ATP</sub> Channels in Vascular Smooth Muscles
Authors: Xueren Wang, Jianping Wu, Li Li, Fuxue Chen, Runping Wang, Chun Jiang
Journal: Circulation Research (2003)

ATP-sensitive K + channels (K ATP ) couple intermediary metabolism to cellular activity, and may play a role in the autoregulation of vascular tones. Such a regulation requires cellular mechanisms for sensing O 2 , CO 2 , and pH. Our recent studies have shown that the pancreatic K ATP isoform (Kir6.2/SUR1) is regulated by CO 2 /pH. To identify the vascular K ATP isoform(s) and elucidate its response to hypercapnic acidosis, we performed these studies on vascular smooth myocytes (VSMs). Whole-cell and single-channel currents were studied on VSMs acutely dissociated from mesenteric arteries and HEK293 cells expressing Kir6.1/SUR2B. Hypercapnic acidosis activated an inward rectifier current that was K + -selective and sensitive to levcromakalim and glibenclamide with unitary conductance of ≈35pS. The maximal activation occurred at pH 6.5 to 6.8, and the current was inhibited at pH 6.2 to 5.9. The cloned Kir6.1/SUR2B channel responded to hypercapnia and intracellular acidification in an almost identical pattern to the VSM current. In situ hybridization histochemistry revealed expression of Kir6.1/SUR2B mRNAs in mesenteric arteries. Hypercapnia produced vasodilation of the isolated and perfused mesenteric arteries. Pharmacological interference of the K ATP channels greatly eliminated the hypercapnic vasodilation. These results thus indicate that the Kir6.1/SUR2B channel is a critical player in the regulation of vascular tones during hypercapnic acidosis.
Expansion of the Homeostasis Model Assessment of β-Cell Function and Insulin Resistance to Enable Clinical Trial Outcome Modeling Through the Interactive Adjustment of Physiology and Treatment Effects: iHOMA2
Authors: Nathan R. Hill, Jonathan C. Levy, David R. Matthews
Journal: Diabetes Care (2013)

OBJECTIVE To describe and make available an interactive, 24-variable homeostasis model assessment (iHOMA2) that extends the HOMA2 model, enabling the modeling of physiology and treatment effects, to present equations of the HOMA2 and iHOMA2 models, and to exemplify iHOMA2 in two widely differing scenarios: changes in insulin sensitivity with thiazolidinediones and changes in renal threshold with sodium glucose transporter 2 (SGLT2) inhibition. RESEARCH DESIGN AND METHODS iHOMA2 enables a user of the available software to examine and modify the mathematical functions describing the organs and tissues involved in the glucose and hormonal compartments. We exemplify this with SGLT2 inhibition modeling (by changing the renal threshold parameters) using published data of renal effect, showing that the modeled effect is concordant with the effects on fasting glucose from independent data. RESULTS iHOMA2 modeling of thiazolidinediones effect suggested that changes in insulin sensitivity in the fasting state are predominantly hepatic. SGLT2 inhibition modeled by iHOMA2 resulted in a decrease in mean glucose of 1.1 mmol/L. Observed data showed a decrease in glucose of 0.9 mmol/L. There was no significant difference between the model and the independent data. Manipulation of iHOMA2's renal excretion threshold variable suggested that a decrease of 17% was required to obtain a 0.9 mmol/L decrease in mean glucose. CONCLUSIONS iHOMA2 is an extended mathematical model for the assessment of insulin resistance and β-cell function. The model can be used to evaluate therapeutic agents and predict effects on fasting glucose and insulin and on β-cell function and insulin sensitivity.
Allergic disease and sensitization in Steiner school children
Authors: Helen Flöistrup, Jackie Swartz, Anna Bergström, Johan S. Alm, Annika Scheynius, Marianne van Hage, Marco Waser, Charlotte Braun-Fahrländer, Dieneke Schram-Bijkerk, Machteld Huber, Anne Zutavern, Erika von Mutius, Ellen Üblagger, Josef Riedler, Karin B. Michaels, Göran Pershagen
Journal: Journal of Allergy and Clinical Immunology (2005)
Proteinuria in Diabetes
Authors: Janaka Karalliedde, Giancarlo Viberti
Journal: Journal of the American Society of Nephrology (2010)

The development of albuminuria in diabetics is closely associated with an enhanced risk of renal and cardiovascular disease. However, the role of albuminuria in the pathogenesis of these clinical conditions remains controversial. Whether albuminuria is simply a biomarker or qualifies as a surrogate endpoint for cardiorenal disease has wide-ranging implications from the monitoring and treatment of patients to the design of clinical trials and drug development. We critically review available data to determine whether the association between albuminuria and cardiorenal disease is causative. Current evidence suggests the significance of albuminuria depends on its severity (degree or level) and on the specific clinical outcome under consideration. For diabetic kidney disease, there is convincing epidemiologic and experimental evidence to assign clinical albuminuria status as a surrogate endpoint, but for lower levels of albuminuria (microalbuminuria and normoalbuminuria), the evidence is inconclusive or not available. Albuminuria of any degree is unlikely to be causally related to diabetic cardiovascular disease, but its onset might be useful to identify those subjects at cardiovascular risk and to detect and treat other modifiable risk factors.
Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: A randomized, controlled trial
Authors: Emanuel K. Manesis, Gregory Giannoulis, Pavlos Zoumboulis, Irini Vafiadou, Stephanos J. Hadziyannis
Journal: Hepatology (1995)

We tested the hypothesis that a combination of sex hormone suppression and inhibition of their target receptors might improve survival for patients with hepatocellular carcinoma (HCC). Eighty-five consequent, previously untreated HCC patients with inoperable disease, were randomized to receive the luteinizing hormone-releasing hormone (LR-RH)-analogue triptorelin and the antiestrogen tamoxifen (33 patients) or triptorelin plus the antiandrogen flutamide (23 patients), or only placebo (29 patients) in a double blind fashion. All groups were comparable as to age, sex, tumor extension, underlying cirrhosis and biochemical parameters. The tamoxifen (TMX) group had a significantly longer survival (282 days) compared with flutamide (112 days) and with placebo (127 days) groups (P = .0238, log rank test). The upper quartile of patients in the TMX group lived 384 days or longer, and most of them (57.1%) were women (P < .0005), in contrast to the upper quartile of the placebo (170 days, 16.7% women) and the flutamide group (134 days, 33.3% women). The calculated tumor volume doubling time (TVDT) was significantly higher in the TMX group (296 days) than in the other two groups (99 and 101 days for placebo and flutamide groups, respectively, P = .023). In a Cox proportional hazards model, the TMX treatment, along with the baseline Okuda's HCC stage, the hepatitis B surface antigen, the portal vein diameter, the carcino embryonic antigen (CEA) and a self-assessment score of quality of life, were covariates predicting survival. Although the degree of serum sex hormone suppression was not a significant predictor of survival, the interaction of female sex and TMX treatment, it was (P = .0052).(ABSTRACT TRUNCATED AT 250 WORDS)
A Cohort Study of Stomach Cancer Risk in Men After Gastric Surgery for Benign Disease
Authors: S. G. Fisher, F. Davis, R. Nelson, L. Weber, J. Goldberg, W. Haenszel
Journal: JNCI Journal of the National Cancer Institute (1993)

For the past 40 years, investigators have suggested that there exists an increased risk of stomach cancer following gastric surgery for benign disease. Recent cohort studies have consistently identified an increased risk of stomach cancer beginning 20 years or more following gastric surgery. Validation of this association and elucidation of risk factors related to gastric cancer have been complicated by variability in study designs.This cohort study was designed to investigate the risk of stomach cancer following gastric surgery and to identify patient and treatment characteristics that may alter this risk.Medical admission records of 17077 male military veterans hospitalized during 1970-1971 in U.S. Department of Veterans Affairs (VA) hospitals were examined. From this initial cohort, 1094 patients who died within the 1st year following gastric surgery were excluded. Data analysis was performed on the final cohort consisting of 15,983 patients divided into the following two groups: 1) an exposed group (gastric surgery group) that included 7609 patients receiving gastric surgery for a documented benign disorder and 2) an unexposed group (comparison group) that included 8374 male patients randomly selected from all other hospitalized male patients in the patient database. The comparison group was matched to the gastric surgery group by age (within 10 years), race, hospital, and year of admission. Mortality follow-up utilized the following three sources to identify vital status: 1) the VA Patient Treatment File (1970-1988), 2) the VA Beneficiary Identification Record Linkage System (1970-1989), and 3) the National Death Index (1979-1988). Death certificates were obtained for 99% of the deceased patients. Analyses included estimations of risk using standardized rate ratios (SRRs) and proportional hazards techniques.A statistically significant increase in risk of stomach cancer was demonstrated among males during the 20 years following gastric surgery (SRR = 1.9; 95% confidence interval [CI] = 1.3-2.4; P = .0001). The risk of developing gastric cancer was greatest during the 2nd to 5th postoperative years (SRR = 2.8; 95% CI = 1.6-4.5; P < .01) and during years 11-15 (SRR = 2.5; 95% CI = 1.2-4.8; P < .01). Also, the risk of developing gastric cancer was greatest among those treated by gastrectomy for any type of ulcer (SRR = 2.6; 95% CI = 1.2-4.9; P < .01) and those having any type of gastric surgery when the primary diagnosis was gastric ulcer (SRR = 2.9, 95% CI = 1.4-5.3; P < .01).This study confirms that men undergoing gastrectomy for benign disease and men receiving any gastric surgery for gastric ulcer are at increased risk for developing gastric cancer. Unlike earlier studies, we find that the increased risk is not delayed for 20 years.
Peyer patches are not required for acute graft-versus-host disease after myeloablative conditioning and murine allogeneic bone marrow transplantation
Authors: Lisbeth A. Welniak, Dmitry V. Kuprash, Alexei V. Tumanov, Angela Panoskaltsis-Mortari, Bruce R. Blazar, Kai Sun, Sergei A. Nedospasov, William J. Murphy
Journal: Blood (2005)
The Putative Tumor Suppressor Cdx2 Is Overexpressed by Human Colorectal Adenocarcinomas
Authors: Matthew E. Witek, Karl Nielsen, Rhonda Walters, Terry Hyslop, Juan Palazzo, Stephanie Schulz, Scott A. Waldman
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The current paradigm suggests that the homeodomain transcription factor Cdx2, which directs the development and maintenance of the intestinal epithelium, is a tumor suppressor in the colon and rectum. Although a cardinal property of tumor suppressors is their inactivation during carcinogenesis, the expression of Cdx2 in colorectal tumors has not been compared with that in normal mucosa. Here, Cdx2 expression and function was quantified in tumors and matched normal mucosa from patients with colorectal cancer. Experimental Design: Cdx2 expression was quantified by reverse transcription-PCR, immunoblot analysis, and immunohistochemistry. Transcriptional activity was explored by quantifying expression of an endogenous downstream target of Cdx2, guanylyl cyclase C (GCC), in tissues by quantitative reverse transcription-PCR and expression of exogenous Cdx2-specific luciferase promoter constructs in epithelial cells isolated from tumors and normal mucosa. Results: Most (&amp;gt;80%) colorectal tumors overexpressed Cdx2 mRNA and protein compared with normal mucosa, with median fold increases of 3.6 and 1.4, respectively (P &amp;lt; 0.002). Concomitantly, immunohistochemistry revealed elevated levels of Cdx2 in nuclei of tumor cells compared with normal epithelial cells. Further, tumors exhibited increased expression of GCC compared with normal mucosa. Moreover, cells isolated from tumors overexpressed a Cdx2-specific luciferase promoter construct compared with normal mucosal cells. Conclusion: These observations show, for the first time, the structural and functional overexpression of Cdx2 by human colorectal tumors compared with matched normal mucosa. They suggest that loss of Cdx2 expression or transcriptional activity is an infrequent event during tumorigenesis, which does not contribute to molecular mechanisms underlying initiation and progression of most colorectal tumors.
Increased Matrix Metalloproteinase-9 Predicts Poor Wound Healing in Diabetic Foot Ulcers
Authors: Yu Liu, Danqing Min, Thyra Bolton, Vanessa Nubé, Stephen M. Twigg, Dennis K. Yue, Susan V. McLennan
Journal: Diabetes Care (2008)

We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-beta1 (TGF-beta1) with wound healing rate.The ulcers were cleansed to remove exudates, and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1, and TGF-beta1.At presentation, MMP-9 and the MMP-9-to-TIMP-1 ratio correlated inversely with the wound healing rate at 28 days (P < 0.001). MMP-9 and the MMP-9-to-TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 who did not. The pro-MMP-9 concentration was predictive of healing within 12 weeks. Addition of cutoffs for TIMP-1 (>480 pg/ml) and TGF-beta (>115 pg/ml) further improved its predictive power (area under the curve 0.94).These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1, and TGF-beta in wound fluid may help to identify ulcers at risk of poor healing.