tbuckley/cabot-search huggingface dataset:
Probiotic carbohydrates reduce intestinal permeability and inflammation in metabolic diseases
Authors: M. Z. Strowski, B. Wiedenmann
Journal: Gut (2009)

The epidemic of obesity and type 2 diabetes mellitus is dramatically increasing. Environmental factors, such as sedentary life-style, hypercaloric, fat-rich diet and genetic susceptibility are considered major determinants of type 2 diabetes mellitus. Obesity and peripheral insulin resistance are hallmarks and major risk factors for development of type 2 diabetes mellitus. Cardiovascular complications (eg, atherosclerosis, coronary heart disease) of both metabolic disorders are associated with chronic subclinical inflammation.1 2 The low degree of inflammation in obesity and type 2 diabetes mellitus results from increased expression and production of cytokines and acute phase reactants such as C-reactive proteins, interleukins (ILs), tumour necrosis factor (TNF)α, or lipopolysaccharides (LPS).1 2 Inflammatory cytokines induce peripheral insulin resistance by impairing the insulin receptor (IR)-dependent signalling.1 2 For instance, experimental application of TNFα leads to the phosphorylation of the serine residues of the insulin receptor substrate-1 (IRS-1) with the consecutive inhibition of insulin-stimulated tyrosine autophosphorylation of the IR. The consequence of the impaired IR signalling is a blunted glucose uptake by peripheral tissues. The resulting chronic hyperglycaemia causes deleterious effects on pancreatic beta-cell function and morphology. Inflammatory cytokines reduce insulin secretion, induce apoptosis of pancreatic beta-cells in type 2 diabetes mellitus.3 Administration of anti-inflammatory agents (eg, high doses of aspirin) or experimental deletion of receptors for inflammatory cytokines results in increased insulin sensitivity and improved pancreatic beta-cell function, which is paralleled by a reduction of hyperglycaemia and loss of body weight.4 5 Despite numerous studies describing the activation …
The Esterase and PHD Domains in CR1-Like Non-LTR Retrotransposons
Authors: Vladimir V. Kapitonov, Jerzy Jurka
Journal: Molecular Biology and Evolution (2003)

Most active non-LTR (long terminal repeat) retrotransposons carry two open reading frames (ORFs) encoding ORF1p and ORF2p proteins. The ORF2p proteins are relatively well studied and are known to contain endonuclease/reverse transcriptase domains. At the same time, the biological function of ORF1p proteins remains poorly understood, except in that they nonspecifically bind single-stranded mRNA/DNA molecules. CR1-like elements form the most widely distributed clade/superfamily of non-LTR retrotransposons. We found that ORF1p proteins encoded by diverse CR1-like elements contain conserved esterase domain (ES) or plant homeodomain (PHD). This indicates that CR1-like ORF1p proteins are either lipolytic enzymes or are involved in protein-protein interactions related to chromatin remodeling. Sequence conservation of ES suggests that interaction with cellular membranes is an important phase in life circles of CR1-like elements. Presumably such interaction helps in penetrating host cells. As a consequence, the presence of multiple young CR1 families characterized by ∼10% intrafamily and 40% interfamily identities may be explained by a relatively frequent horizontal transfer of these CR1-like elements. Unexpectedly, ES links together non-LTR retrotransposons and single-stranded RNA viruses like influenza C and coronaviruses, which are known to depend on their own ES.
Stages of Change for Healthy Eating in Diabetes
Authors: Michael Vallis, Laurie Ruggiero, Geoffrey Greene, Helen Jones, Bernard Zinman, Susan Rossi, Lynn Edwards, Joseph S. Rossi, James O. Prochaska
Journal: Diabetes Care (2003)

OBJECTIVES—To identify diabetes-related characteristics of individuals at different stages of readiness to change to healthy, low-fat eating. RESEARCH DESIGN AND METHODS—Stage-based differences in demographic, eating-related, health care utilization, and psychosocial factors were examined in a sample of 768 overweight (BMI &amp;gt;27 kg/m2) individuals with diabetes enrolled in a randomized behavioral intervention trial. RESULTS—Stage-based differences occurred for type 1 diabetic participants on percent of calories from fat and number of daily vegetable servings. For type 2 diabetic participants, sex, disease-specific quality of life, percent calories from fat, and number of daily vegetables servings differed across stages. Those in action stages were more likely to be female and have a better quality of life and healthier eating habits. Type 2 diabetic insulin-requiring participants in action stages were more likely to be married. Social support was highest for those in the contemplation stage and lowest for those in the action stage. Type 2 diabetic participants on pills in the action stages were older, had a lower BMI, ate more fruit, were nonsmokers, recently attended diabetes education, had a better quality of life and social support, and had less stress. One anomalous finding for type 2 diabetic participants was that precontemplators scored similarly to those in action stages. CONCLUSIONS—These data validate the Transtheoretical Model, where those in the action stages displayed healthier eating. They also indicate that demographic and psychosocial factors may mediate readiness to change diet. Precontemplators were a heterogeneous group and may need individually tailored interventions.
Local adenosine infusion and myocardial oxygen supply and consumption in reperfused canine myocardium
Authors: T. Gerlock, D. Bentsen, H. R Weiss
Journal: Cardiovascular Research (1991)

Journal Article Local adenosine infusion and myocardial oxygen supply and consumption in reperfused canine myocardium Get access Teresa Gerlock, Teresa Gerlock Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, University of Medicine and Dentistry, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854-5635, USA Correspondence to: Dr Weiss Search for other works by this author on: Oxford Academic PubMed Google Scholar Danielle Bentsen, Danielle Bentsen Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, University of Medicine and Dentistry, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854-5635, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Harvey R Weiss Harvey R Weiss Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, University of Medicine and Dentistry, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854-5635, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 8, August 1991, Pages 630–636, https://doi.org/10.1093/cvr/25.8.630 Published: 01 August 1991 Article history Received: 23 July 1990 Accepted: 08 April 1991 Published: 01 August 1991
Similar Outcomes Between African American and Non–African American Patients With Extensive-Stage Small-Cell Lung Carcinoma: Report From the Cancer and Leukemia Group B
Authors: A. William Blackstock, James E. Herndon, Electra D. Paskett, Antonius A. Miller, Christopher Lathan, Harvey B. Niell, Mark A. Socinski, Everett E. Vokes, Mark R. Green
Journal: Journal of Clinical Oncology (2005)

Among patients with small-cell lung carcinoma, African Americans have lower survival rates than non-African Americans. We investigated whether the disparity in survival would persist when patients were treated with similar therapies (ie, phase II/III Cancer and Leukemia Group B [CALGB] trials).We assessed 995 patients (928 non-African American and 67 African American) receiving chemotherapy in CALGB studies for extensive-stage small-cell lung cancer (ES-SCLC). Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. The Cox proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two sided.The unadjusted survival distribution of African American patients was not significantly different from that of non-African American patients; median survival was 11.5 months (95% CI, 9.4 to 13.4 months) for African American patients versus 9.9 months (95% CI, 9.6 to 10.3 months) for non-African American patients. Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the outcome for African American patients. Survival was similar even though African American patients were more likely to have a poorer performance status, present with significant weight loss, and be Medicaid recipients (20% v 6%), which is an indicator of lower socioeconomic status.African American patients tended to present with prognostic features associated with a worse survival. However, when offered equivalent therapy, the outcome for African American patients was the same as that observed for non-African American patients.
Mechanism and Management of AKT Inhibitor-Induced Hyperglycemia
Authors: Ming-Chih Crouthamel, Jason A. Kahana, Susan Korenchuk, Shu-Yun Zhang, Gobalakrishnan Sundaresan, Derek J. Eberwein, Kathleen K. Brown, Rakesh Kumar
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Insulin-like growth factor-I receptor and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways are among the most active areas of drug discovery in cancer research. However, due to their integral roles in insulin signaling, inhibitors targeting these pathways often lead to hyperglycemia and hyperinsulinemia. We investigated the mechanism of hyperglycemia induced by GSK690693, a pan-AKT kinase inhibitor in clinical development, as well as methods to ameliorate these side effects. Experimental Design: The effect of GSK690693 on blood glucose, insulin, and glucagon levels was characterized in mice. We then evaluated the effects of commonly prescribed antidiabetic agents on GSK690693-induced hyperglycemia. The mechanism of blood glucose increase was evaluated using fasting and tracer uptake studies and by measuring liver glycogen levels. Finally, approaches to manage AKT inhibitor-induced hyperglycemia were designed using fasting and low carbohydrate diet. Results: We report that treatment with antidiabetic agents does not significantly affect GSK690693-induced hyperglycemia in rodents. However, administration of GSK690693 in mice significantly reduces liver glycogen (∼90%), suggesting that GSK690693 may inhibit glycogen synthesis and/or activate glycogenolysis. Consistent with this observation, fasting before drug administration reduces baseline liver glycogen levels and attenuates hyperglycemia. Further, GSK690693 also inhibits peripheral glucose uptake and introduction of a low-carbohydrate (7%) or 0% carbohydrate diet after GSK690693 administration effectively reduces diet-induced hyperglycemia in mice. Conclusions: The mechanism of GSK690693-induced hyperglycemia is related to peripheral insulin resistance, increased gluconeogenesis, and/or hepatic glycogenolysis. A combination of fasting and low carbohydrate diet can reduce the magnitude of hyperglycemia induced by an AKT inhibitor.
Specific Mutations in ABCA1 Have Discrete Effects on ABCA1 Function and Lipid Phenotypes Both In Vivo and In Vitro
Authors: Roshni R. Singaraja, Henk Visscher, Erick R. James, Angeliki Chroni, Jonathan M. Coutinho, Liam R. Brunham, Martin H. Kang, Vassilis I. Zannis, Giovanna Chimini, Michael R. Hayden
Journal: Circulation Research (2006)

Mutations in ATP-binding cassette transporter A1 ( ABCA1 ) cause Tangier disease and familial hypoalphalipoproteinemia, resulting in low to absent plasma high-density lipoprotein cholesterol levels. However, wide variations in clinical lipid phenotypes are observed in patients with mutations in ABCA1 . We hypothesized that the various lipid phenotypes would be the direct result of discrete and differing effects of the mutations on ABCA1 function. To determine whether there is a correlation between the mutations and the resulting phenotypes, we generated in vitro 15 missense mutations that have been described in patients with Tangier disease and familial hypoalphalipoproteinemia. Using localization of ABCA1, its ability to induce cell surface binding of apolipoprotein A-I, and its ability to elicit efflux of cholesterol and phospholipids to apolipoprotein A-I we determined that the phenotypes of patients correlate with the severity and nature of defects in ABCA1 function.
Altered gut transcriptome in spondyloarthropathy
Authors: D Laukens
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn’s disease. Inflammation is manifested clinically in Crohn’s disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn’s disease. <b>Aims:</b> To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn’s disease and to examine global gene expression in non-inflamed colon biopsy specimens and screen patients for differentially expressed genes. <b>Methods:</b> Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn’s disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn’s disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass-based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn’s disease and 10 controls. <b>Results:</b> 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn’s disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn’s disease. <b>Conclusion:</b> The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn’s disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn’s disease in patients with SpA can be considered.
Effects of Nurse-Managed Protocols in the Outpatient Management of Adults With Chronic Conditions
Authors: Ryan J. Shaw, Jennifer R. McDuffie, Cristina C. Hendrix, Alison Edie, Linda Lindsey-Davis, Avishek Nagi, Andrzej S. Kosinski, John W. Williams
Journal: Annals of Internal Medicine (2014)

Background: Changes in federal health policy are providing more access to medical care for persons with chronic disease. Providing quality care may require a team approach, which the American College of Physicians calls the "medical home." One new model may involve nurse-managed protocols. Purpose: To determine whether nurse-managed protocols are effective for outpatient management of adults with diabetes, hypertension, and hyperlipidemia. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and CINAHL from January 1980 through January 2014. Study Selection: Two reviewers used eligibility criteria to assess all titles, abstracts, and full texts and resolved disagreements by discussion or by consulting a third reviewer. Data Extraction: One reviewer did data abstractions and quality assessments, which were confirmed by a second reviewer. Data Synthesis: From 2954 studies, 18 were included. All studies used a registered nurse or equivalent who titrated medications by following a protocol. In a meta-analysis, hemoglobin A1c level decreased by 0.4% (95% CI, 0.1% to 0.7%) (n = 8); systolic and diastolic blood pressure decreased by 3.68 mm Hg (CI, 1.05 to 6.31 mm Hg) and 1.56 mm Hg (CI, 0.36 to 2.76 mm Hg), respectively (n = 12); total cholesterol level decreased by 0.24 mmol/L (9.37 mg/dL) (CI, 0.54-mmol/L decrease to 0.05-mmol/L increase [20.77-mg/dL decrease to 2.02-mg/dL increase]) (n = 9); and low-density-lipoprotein cholesterol level decreased by 0.31 mmol/L (12.07 mg/dL) (CI, 0.73-mmol/L decrease to 0.11-mmol/L increase [28.27-mg/dL decrease to 4.13-mg/dL increase]) (n = 6). Limitation: Studies had limited descriptions of the interventions and protocols used. Conclusion: A team approach that uses nurse-managed protocols may have positive effects on the outpatient management of adults with chronic conditions, such as diabetes, hypertension, and hyperlipidemia. Primary Funding Source: U.S. Department of Veterans Affairs.
Altered Expression of Disintegrin Metalloproteinases and Their Inhibitor in Human Dilated Cardiomyopathy
Authors: Paul W.M. Fedak, Christine S. Moravec, Patrick M. McCarthy, Svetlana M. Altamentova, Amy P. Wong, Marko Skrtic, Subodh Verma, Richard D. Weisel, Ren-Ke Li
Journal: Circulation (2006)

Background— Disintegrin metalloproteinases (ADAMs) may contribute to structural cardiac remodeling by altering cell-surface matrix receptors (integrins) and activating potent biomolecules. We compared expression of ADAMs, their endogenous inhibitor tissue inhibitor of metalloproteinases (TIMP)-3, and integrins in human heart tissue with varied patterns of structural remodeling. Methods and Results— Myocardium was obtained from patients with dilated cardiomyopathy (n=20), hypertrophic obstructive cardiomyopathy (n=5), and nonfailing donor hearts (n=7). Paired samples (n=10) were obtained before left ventricular assist device insertion and at transplantation. The expressions of ADAM10, ADAM12, ADAM15, and ADAM17, TIMP-3, and integrin receptors β1D and β3 were determined by quantitative immunoblotting. Integrin shedding was assessed by the ratio of integrin cleavage products to intact protein abundance. Confocal microscopy was performed. Dilated cardiomyopathy was characterized by increased ADAM10 and ADAM15 expression and reduced TIMP-3 expression. The integrin β1D cleavage ratio was elevated, indicating receptor shedding. ADAM10 and ADAM15 expressions correlated with the cleavage ratio. ADAM10 colocalized with integrin β1D by confocal microscopy. ADAM10 expression correlated with clinical indices of chamber dilatation and systolic dysfunction. Hemodynamic unloading reduced ADAM10 and ADAM12 expressions and increased integrin β1D expression. ADAM12 and integrin β1D expressions were increased in HOCM. ADAM17 was increased in both dilated cardiomyopathy and hypertrophic obstructive cardiomyopathy. Conclusions— Disintegrin metalloproteinases are differentially expressed in human myocardium, reflecting the underlying pattern of structural remodeling. ADAM10 and ADAM15 may contribute to cardiac dilatation by reducing cell-matrix interactions via integrin shedding. Targeting disintegrin metalloproteinases, perhaps by restoring deficient TIMP-3 levels with gene or cell-based therapies, may prevent progressive chamber dilatation in human dilated cardiomyopathy.
PUBLIC REPORTING OF PROVIDER PERFORMANCE: Can Its Impact Be Made Greater?
Authors: David L. Robinowitz, R. Adams Dudley
Journal: Annual Review of Public Health (2005)

Public reporting of provider performance is becoming increasingly commonplace. In this chapter, we first review studies of prior public reports (or report cards) that show real but small impact on provider attempts to improve quality, on consumers' impressions of providers, and even on consumer selection of providers. Among other factors, two potential explanations for the low level of impact are that, in most early reports, the large majority of providers have been labeled "average" and consumers may have had difficulty understanding the statistical assessments. In response, some current report card producers are using or considering a variety of methods to increase the number of distinctions among providers and the ease of comprehension of the labels used. Therefore, we also consider the advantages and disadvantages of several novel approaches to analyzing and reporting provider performance.
Mitochondrial Cytochrome B Gene Mutation Promotes Tumor Growth in Bladder Cancer
Authors: Santanu Dasgupta, Mohammad Obaidul Hoque, Sunil Upadhyay, David Sidransky
Journal: Cancer Research (2008)

Abstract Mitochondria-encoded Cytochrome B (CYTB) gene mutations were reported in different cancers, but the effect of these mutations on cellular metabolism and growth is unknown. In a murine xenograft and human model of bladder cancer, we show the functional effect of overexpression of a 21-bp deletion mutation (mt) of CYTB. Overexpression of mtCYTB generated increased reactive oxygen species (ROS) accompanied by increased oxygen consumption and lactate production. MtCYTB overexpression induced significant tumor growth in vitro and in vivo by triggering rapid cell cycle progression through up-regulation of the nuclear factor-κB2 signaling pathway. Tumor-generated ROS induced in vitro lysis of normal splenocytes. Thus, we present physiologic and functional evidence for the role of a bonafide mitochondrial gene mutation in cancer. [Cancer Res 2008;68(3):700–06]
Long-term clinical follow-up after operation for lung carcinoma
Authors: R. A. Smith
Journal: Thorax (1970)

From 1951 to July 1969, 964 lung resections for primary lung carcinoma have personally been carried out. All except eight patients, whose follow-up has been continued by colleagues elsewhere, have been examined at intervals in the outpatient department and chest radiographs have been taken. No patient has been lost from follow-up. The results of this follow-up are presented. The quality of the patient9s life after operation, the cause of death, the results, and the relationship of survival to extent of operation are discussed. Details of 151 patients surviving more than five years, and of 49 surviving more than 10 years, are given. Information on the aspects under consideration is believed to be as complete as possible. The cause of death is doubtful in only two patients.
Electrocardiographic QT Interval Prolongation and Risk of Primary Cardiac Arrest in Diabetic Patients
Authors: Eric A. Whitsel, Edward J. Boyko, Pentti M. Rautaharju, Trivellore E. Raghunathan, Danyu Lin, Rachel M. Pearce, Sheila A. Weinmann, David S. Siscovick
Journal: Diabetes Care (2005)

Sudden cardiac death, also known as primary cardiac arrest (PCA), is a major cause of mortality among diabetic patients and typically occurs in the setting of coronary heart disease. Because it can occur as the first clinical manifestation of coronary heart disease, identifying diabetic patients at risk of PCA remains challenging. Interrelated sequelae of diabetes, including QT prolongation and autonomic failure (1, 2), have been repeatedly implicated in the pathophysiology of PCA (3–6). However, it remains unknown whether the QT interval on a 12-lead electrocardiogram (ECG) has potential utility in risk stratification of diabetic patients without prior physician-diagnosed heart disease for PCA (7–12).

We therefore conducted a case-control study of PCA in a large prepaid health plan, Group Health Cooperative of Puget Sound. We included patients age 18–79 years who were enrolled for ≥1 year or had four or more clinic visits in the prior year, had physician-diagnosed diabetes noted in their ambulatory care medical record or were treated with oral hypoglycemics or insulin, and had an ECG recorded before their index date (see below). We excluded enrollees with prior physician-diagnosed heart disease (Table 1).

Patients were diabetic enrollees who experienced out-of-hospital PCA (a sudden, pulseless condition without a known noncardiac cause) between …