bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression, processing and transcriptional regulation of granulysin in short-term activated human lymphocytes
Authors: Latinovic-Golic Sonja , Walch Michael , Sundstrom Hanna , Dumrese Claudia , Groscurth Peter , Ziegler Urs 
Published: June 2007

AbstractBackgroundGranulysin, a cytotoxic protein expressed in human natural killer cells and activated T lymphocytes, exhibits cytolytic activity against a variety of intracellular microbes. Expression and transcription have been partially characterised in vitro and four transcripts (NKG5, 519, 520, and 522) were identified. However, only a single protein product of 15 kDa was found, which is subsequently processed to an active 9 kDa protein.ResultsIn this study we investigated generation of granulysin in lymphokine activated killer (LAK) cells and antigen (Listeria) specific T-cells. Semiquantitative RT-PCR revealed NKG5 to be the most prominent transcript. It was found to be up-regulated in a time-dependent manner in LAK cells and antigen specific T-cells and their subsets. Two isoforms of 519 mRNA were up-regulated under IL-2 and antigen stimulation. Moreover, two novel transcripts, without any known function, comprising solely parts of the 5 prime region of the primary transcript, were detected. A significant increase of granulysin expressing LAK cells as well as antigen specific T-cells was shown by fluorescence microscopy. On the subset level, increase in CD4+granulysin expressing cells was found only under antigen stimulation.Immunoblotting showed the 15 kDa form of granulysin to be present in the first week of stimulation either with IL-2 or with bacterial antigen. Substantial processing to the 9 kDa form was detected during the first week in LAK cells and in the second week in antigen specific T-cells.ConclusionThis first comprehensive study of granulysin gene regulation in primary cultured human lymphocytes shows that the regulation of granulysin synthesis in response to IL-2 or bacterial antigen stimulation occurs at several levels: RNA expression, extensive alternative splicing and posttranslational processing.
Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure
Authors: Hao Ying , Sood Sumita , Triadafilopoulos George , Kim Jong Hyeok , Wang Zheng , Sahbaie Peyman , Omary M Bishr , Lowe Anson W 
Published: June 2007

Abstract

Background
Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation.

Methods
Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment.

Results
The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure.

Conclusion
Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.
Acute drug induced hepatitis secondary to a weight loss product purchased over the internet
Authors: Joshi Deepak , Cross Tim JS , Wong Voi Shim 
Published: June 2007

Abstract

Background
Many people now seek alternative methods of weight loss. The internet provides a readily available source of weight reduction products, the ingredients of which are often unclear. The authors describe a case of acute hepatitis in a 20 year old woman caused by such a product purchased over the internet.

Case Presentation
A 20-year old woman presented with a two day history of abdominal pain, vomiting and jaundice. There were no identifiable risk factors for chronic liver disease. Liver function tests demonstrated an acute hepatitis (aminoaspartate transaminase 1230 IU/L). A chronic liver disease screen was negative. The patient had started a weight loss product (Pro-Lean), purchased over the internet two weeks prior to presentation. The patient was treated conservatively, and improved. The sequence of events suggests an acute hepatitis caused by an herbal weight loss product.

Conclusion
This case report highlights the dangers of weight loss products available to the public over the internet, and the importance of asking specifically about alternative medicines in patients who present with an acute hepatitis.
Cardioprotective and Anti-Inflammatory Effects of Interleukin Converting Enzyme Inhibition in Experimental Diabetic Cardiomyopathy
Authors: Westermann Dirk , Van Linthout Sophie , Dhayat Sameer , Dhayat Nasser , Escher Felicitas , Bücker-Gärtner Carola , Spillmann Frank , Noutsias Michel , Riad Alexander , Schultheiss Heinz-Peter , Tschöpe Carsten 
Published: June 2007

OBJECTIVE—We investigated the effect of pharmacological inhibition of the interleukin converting enzyme (ICE) on cardiac inflammation, apoptosis, fibrosis, and left ventricular function in an animal model of diabetes.RESEARCH DESIGN AND METHODS—Diabetes was induced in 24 Sprague-Dawley rats by injection of streptozotozin (STZ) (70 mg/kg). Diabetic animals were treated with the interleukin converting enzyme (ICE) inhibitor (ICEI) (n = 12) or with a placebo (n = 12). Nondiabetic rats served as controls (n = 12). Left ventricular function was documented 6 weeks after induction of diabetes. Cardiac tissue was analyzed for the expression of cytokines, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, leukocyte and macrophage integrins, and collagen. Phosphorylation of Akt was analyzed by Western blot and apoptosis by Blc-2 and Bax measurements.RESULTS—Left ventricular function was significantly impaired in diabetic animals. This was accompanied by a significant increase of cytokines, cell adhesion molecules, leukocytes and macrophages, and collagen content. In addition, the phosphorylation state of Akt was reduced. These changes were significantly attenuated in the diabetic group treated with ICEI.CONCLUSIONS—Cardiac dysfunction is associated with cardiac inflammation in experimental diabetic cardiomyopathy. Both of these—cardiac dysfunction and inflammation—are attenuated after treatment with ICEI. These data suggest that anticytokine-based therapies might be beneficial in diabetic cardiomyopathy.
Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes
Authors: Li Zhen-guo , Zhang Weixian , Sima Anders A.F. 
Published: June 2007

OBJECTIVE—To examine whether changes characteristic of Alzheimer's disease occur in two rat models with spontaneous onset of type 1 and type 2 diabetes.
RESEARCH DESIGN AND METHODS—The frontal cortices of 8-month-diabetic rats were examined with respect to neuronal densities, neurite degeneration, expression, and/or immunolocalization of amyloid precursor protein (APP), β-secretase, β-amyloid, COOH-terminal fragment (CTF), insulin receptor, IGF-1 receptor, glycogen synthase kinase 3-β (GSK-3β), protein kinase B (Akt), phosphorylated τ (phospho-τ), synaptophysin, and phosphorylated neurofilaments (SMI-31).
RESULTS—Neuronal loss occurred in both models, significantly more so in type 2 diabetic BBZDR/Wor rats compared with type 1 diabetic BB/Wor rats and was associated with a ninefold increase of dystrophic neurites. APP, β-secretase, β-amyloid, and CTF were significantly increased in type 2 diabetic rats, as was phospho-τ. The insulin receptor expression was decreased in type 1 diabetes, whereas IGF-1 receptor was decreased in both models, as were Akt and GSK-3β expression.
CONCLUSIONS—The data show that β-amyloid and phospho-τ accumulation occur in experimental diabetes and that this is associated with neurite degeneration and neuronal loss. The changes were more severe in the type 2 diabetic model and appear to be associated with insulin resistance and possibly hypercholesterolemia. The two models will provide useful tools to unravel further mechanistic associations between diabetes and Alzheimer's disease.
Changing Patterns of Type 2 Diabetes Incidence Among Pima Indians
Authors: Pavkov Meda E. , Hanson Robert L. , Knowler William C. , Bennett Peter H. , Krakoff Jonathan , Nelson Robert G. 
Published: June 2007

OBJECTIVE— The rising prevalence of obesity and high prevalence of diabetes among Pima Indians suggest that the incidence of diabetes has risen over time. We examined trends in the incidence rate of type 2 diabetes among Pima Indians between 1965 and 2003.
RESEARCH DESIGN AND METHODS— Incidence rates were computed independently in three 13-year time periods in Pima Indians aged ≥5 years. Diabetes was defined by the presence of at least one of two criteria: 1) 2-h plasma glucose concentration ≥200 mg/dl (11.1 mmol/l) or 2) hypoglycemic treatment.
RESULTS— Among 8,236 subjects without diabetes at baseline, 1,005 incident cases occurred during follow-up. Age- and sex-adjusted incidence rates of diabetes were 25.3 cases/1,000 patient-years (95% CI 22.5–28.0) in 1965–1977, 22.9 cases/1,000 patient years (20.0–25.8) in 1978–1990, and 23.5 cases/1,000 patient years (20.5–26.5) in 1991–2003 (P = 0.3). The incidence rate in subjects aged 5–14 years was 5.7 (1.9–17.4) times as high in the last as in the first period, but the rate declined in those aged 25–34 years (incidence rate ratio 0.6 [0.4–0.8]). Sex-adjusted prevalence increased significantly over time only in those aged 5–24 years (Ptrend &lt; 0.0001).
CONCLUSIONS— The overall incidence of diabetes among Pima Indians remained stable over the past four decades, with a significant rise occurring only in the youth.
Circulating Retinol-Binding Protein-4, Insulin Sensitivity, Insulin Secretion, and Insulin Disposition Index in Obese and Nonobese Subjects
Authors: Broch Montserrat , Vendrell Joan , Ricart Wifredo , Richart Cristóbal , Fernández-Real José-Manuel 
Published: June 2007

OBJECTIVE—Recent investigations disclosed an upregulation of retinol-binding protein-4 (RBP4) in the adipose tissue of several insulin-resistant mouse models and increased serum RBP4 concentration in subjects with obesity and type 2 diabetes in association with insulin resistance. There is some experimental evidence that RBP4 also could been linked to insulin secretion.
RESEARCH DESIGN AND METHODS—We aimed to evaluate insulin secretion, insulin sensitivity, insulin disposition index (minimal model analysis), and circulating RBP4 (enzyme-linked immunosorbent assay) in nondiabetic men with a wide range of obesity (n = 107).
RESULTS—Serum RBP4 concentration was nonsignificantly different among lean, overweight, and obese subjects. Circulating RBP4 was not associated with age, BMI, waist-to-hip ratio, or metabolic parameters, including insulin sensitivity (r = −0.03, P = 0.6). On the contrary, circulating RBP4 was negatively associated with insulin secretion, especially in obese subjects (r = −0.48, P = 0.007), in whom RBP4 also was linked to insulin disposition index (r = −0.44, P = 0.01). On multiple regression analyses to predict insulin secretion (acute insulin response [AIRg]), insulin sensitivity was the only factor that contributed to 17% of AIRg variance in nonobese subjects. In obese subjects, however, RBP4 emerged as an independent factor that contributed independently to AIRg variance (23%).
CONCLUSIONS—Our results suggest that oversecretion of RBP4 may negatively affect β-cell function directly or by preventing the binding of transthyretin to its receptor. These mechanisms could be behind the association between increased circulating RBP4 and type 2 diabetes. RBP4 could be one signal from insulin-resistant tissues that impacts on β-cell secretion.
Outpatient Assessment of Karlsburg Diabetes Management System–Based Decision Support
Authors: Augstein Petra , Vogt Lutz , Kohnert Klaus-Dieter , Freyse Ernst-Joachim , Heinke Peter , Salzsieder Eckhard 
Published: June 2007

OBJECTIVE— We sought to assess the benefit of the Karlsburg Diabetes Management System (KADIS) in conjunction with the continuous glucose monitoring system (CGMS) in an outpatient setting.
RESEARCH DESIGN AND METHODS— A multicentric trial was performed in insulin-treated outpatients (n = 49), aged 21–70 years, with a mean diabetes duration of 14.2 years. Subjects were recruited from five outpatient centers and randomized for CGMS- or CGMS/KADIS-based decision support and followed up for 3 months. After two CGMS monitorings, the outcome parameters A1C (%), mean sensor glucose of the CGMS profile (MSG) (mmol/l), and duration of hyperglycemia (h/day) were evaluated.
RESULTS— In contrast with the CGMS group (0.27 ± 0.67%), mean change in A1C decreased in the CGMS/KADIS group during the follow-up (−0.34 ± 0.49%; P &lt; 0.01). MSG levels were not affected in the CGMS group (7.75 ± 1.33 vs. 8.45 ± 2.46 mmol/l) but declined in the CGMS/KADIS group (8.43 ± 1.33 vs. 7.59 ± 1.47 mmol/l; P &lt; 0.05). Net KADIS effect (−0.60 [95% CI −0.96 to − 0.25%]; P &lt; 0.01) was associated with reduced duration of hyperglycemia (4.6 vs. 1.0 h/day; P &lt; 0.01) without increasing hypoglycemia. Multiple regression revealed that the A1C outcome was dependent on KADIS-based decision support. Age, sex, physician's specialty, diabetes type, and BMI had no measurable effect.
CONCLUSIONS— If physicians were supported by CGMS/KADIS in therapeutic decisions, they achieved better glycemic control for their patients compared with support by CGMS alone. KADIS is a suitable decision support tool for physicians in outpatient diabetes care and has the potential to improve evidence-based management of diabetes.
Ferritin and Transferrin Are Associated With Metabolic Syndrome Abnormalities and Their Change Over Time in a General Population
Authors: Vari Istvan S. , Balkau Beverley , Kettaneh Adrian , André Philippe , Tichet Jean , Fumeron Frédéric , Caces Emile , Marre Michel , Grandchamp Bernard , Ducimetière Pierre ,   for the DESIR Study Group
Published: June 2007

OBJECTIVE—The aim of this work was to study cross-sectional and longitudinal relations between iron stocks (ferritin) and the iron transport protein (transferrin) with the metabolic syndrome and its abnormalities.
RESEARCH DESIGN AND METHODS—A total of 469 men and 278 premenopausal and 197 postmenopausal women from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, aged 30–65 years, were followed over 6 years.
RESULTS—Higher concentrations of both ferritin and transferrin were associated with the International Diabetes Federation (IDF) and the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III original and revised definitions of the metabolic syndrome at baseline: for the IDF definition of the metabolic syndrome, the standardized, age-adjusted odds ratios (95% CI) for log(ferritin) were 1.49 (1.14–1.94) for men, 2.10 (1.27–3.48) for premenopausal women, and 1.80 (1.21–2.68) for postmenopausal women; for transferrin they were, respectively, 1.94 (1.53–2.47), 2.22 (1.32–3.75), and 2.14 (1.47–3.10). After 6 years of follow-up, the change in the presence of the metabolic syndrome was associated with higher baseline values in all three groups: log(ferritin), 1.46 (1.13–1.89), 1.28 (0.85–1.94), and 1.62 (1.10–2.38); and transferrin, 1.41 (1.10–1.81), 1.63 (1.05–2.52), and 1.51 (1.02–2.22). Among syndrome components, hypertriglyceridemia at 6 years was the component most strongly associated with baseline ferritin and transferrin. The odds of an incident IDF-defined metabolic syndrome after 6 years was more than fourfold higher when ferritin and transferrin values were both above the group-specific top tertile, in comparison with participants with both parameters below these thresholds.
CONCLUSIONS—This is the first prospective study associating ferritin and transferrin with the metabolic syndrome and its components. When both markers of the iron metabolism are elevated, the incidence of the metabolic syndrome is increased in men and both pre- and postmenopausal women.
Clustering of Multiple Healthy Lifestyle Habits and Health-Related Quality of Life Among U.S. Adults With Diabetes
Authors: Li Chaoyang , Ford Earl S. , Mokdad Ali H. , Jiles Ruth , Giles Wayne H. 
Published: June 2007

OBJECTIVE— We sought to examine the association between clustering of multiple healthy lifestyle habits (HLHs) and health-related quality of life (HRQOL) among adults with diabetes.
RESEARCH DESIGN AND METHODS— We analyzed the representative sample of the civilian, noninstitutionalized U.S. population aged ≥18 years with diabetes using data from the 2005 Behavioral Risk Factor Surveillance System (n = 16,428). Four HRQOL measures were general health rating, physically unhealthy days, mentally unhealthy days, and impaired activity days. Three HLHs included not smoking, engaging in adequate leisure time physical activity, and consuming five or more servings of fruits and vegetables per day.
RESULTS— The proportion of having 0, 1, 2, and 3 HLHs was 10.5, 44.7, 32.9, and 11.9%, respectively. The age-adjusted prevalence rates of poor or fair health, ≥14 physically unhealthy days, ≥14 mentally unhealthy days, and ≥14 impaired activity days were 43.07, 27.61, 17.22, and 18.87%, respectively. After adjustment for potential confounders and comparison with none of the three HLHs, people with all three HLHs were less likely to report poor or fair health (adjusted odds ratio 0.49 [95% CI 0.33–0.71]), ≥14 physically unhealthy days (0.56 [0.39–0.80]), ≥14 mentally unhealthy days (0.35 [0.23–0.55]), or ≥14 impaired activity days (0.35 [0.23–0.56]).
CONCLUSIONS— Accumulation of multiple HLHs was significantly associated with better HRQOL among people with diabetes.
Diabetic Retinopathy and the Risk of Coronary Heart Disease
Authors: Cheung Ning , Wang Jie Jin , Klein Ronald , Couper David J. , Sharrett A. Richey , Wong Tien Y. 
Published: June 2007

OBJECTIVE— We sought to examine the relation of diabetic retinopathy to incident coronary heart disease (CHD).RESEARCH DESIGN AND METHODS— A population-based, prospective cohort study consisting of 1,524 middle-aged individuals with type 2 diabetes without prevalent CHD and stroke at baseline was conducted. Diabetic retinopathy signs were graded from retinal photographs according to the Early Treatment for Diabetic Retinopathy Study severity scale. Incident CHD events (myocardial infarction, fatal CHD, or coronary revascularization) were identified and validated following standardized protocols.RESULTS— In our study, 214 (14.7%) participants had diabetic retinopathy. Over an average follow-up of 7.8 years, there were 209 (13.7%) incident CHD events. After controlling for age, sex, race, study center, fasting glucose, A1C, duration of diabetes, blood pressure, antihypertensive treatment, cigarette smoking, BMI, and lipid profile, the presence of diabetic retinopathy was associated with a twofold higher risk of incident CHD events (hazard rate ratio [HR] 2.07 [95% CI 1.38–3.11]) and a threefold higher risk of fatal CHD (3.35 [1.40–8.01]). Further adjustments for inflammatory markers, carotid artery intima-media thickness, or nephropathy had minimal impact on the association. The increased risk of CHD was significant in both men (1.89 [1.08–3.31]) and women (2.16 [1.16–4.02]) with diabetic retinopathy.CONCLUSIONS— In individuals with type 2 diabetes, the presence of retinopathy signifies an increased CHD risk, independent of known risk factors. Our data support the role of microvascular disease in the pathogenesis of CHD in diabetes.
Risk Factors for Mortality Among Patients With Diabetes
Authors: McEwen Laura N. , Kim Catherine , Karter Andrew J. , Haan Mary N. , Ghosh Debashis , Lantz Paula M. , Mangione Carol M. , Thompson Theodore J. , Herman William H. 
Published: June 2007

OBJECTIVE— We sought to examine demographic, socioeconomic, and biological predictors of all-cause, cardiovascular, and noncardiovascular mortality in patients with diabetes.
RESEARCH DESIGN AND METHODS— Survey, medical record, and administrative data were obtained from 8,733 participants in the Translating Research Into Action for Diabetes Study, a multicenter, prospective, observational study of diabetes care in managed care. Data on deaths (n = 791) and cause of death were obtained from the National Death Index after 4 years. Predictors examined included age, sex, race, education, income, duration, and treatment of diabetes, BMI, smoking, microvascular and macrovascular complications, and comorbidities.
RESULTS— Predictors of adjusted all-cause mortality included older age (hazard ratio [HR] 1.04 [95% CI 1.03–1.05]), male sex (1.57 [1.35–1.83]), lower income (&lt;$15,000 vs. &gt;$75,000, HR 1.82 [1.30–2.54]; $15,000–$40,000 vs. &gt;$75,000, HR 1.58 [1.15–2.17]), longer duration of diabetes (≥9 years vs. &lt;9 years, HR 1.20 [1.02–1.41]), lower BMI (&lt;26 vs. 26–30 kg/m2, HR 1.43 [1.13–1.69]), smoking (1.44 [1.20–1.74]), nephropathy (1.46 [1.23–2.73]), macrovascular disease (1.46 [1.23–1.74]), and greater Charlson index (≥2–3 vs. &lt;1, HR 2.01 [1.04–3.90]; ≥3 vs. &lt;1, HR 4.38 [2.26–8.47]). The predictors of cardiovascular and noncardiovascular mortality were different. Macrovascular disease predicted cardiovascular but not noncardiovascular mortality.
CONCLUSIONS— Among people with diabetes and access to medical care, older age, male sex, smoking, and renal disease are important predictors of mortality. Even within an insured population, socioeconomic circumstance is an important independent predictor of health.
Pharmacological Management of Gestational Diabetes
Authors: Coustan Donald R. 
Published: June 2007

OBJECTIVE—To provide a review of the background literature regarding the pharmacological management of gestational diabetes.
RESEARCH DESIGN AND METHODS—This is a literature review.
RESULTS—Information is available regarding the use of some, but not all, oral antidiabetes agents in pregnancy.
CONCLUSIONS—Available evidence supports the use of glyburide during pregnancy. Evidence is inadequate to support or refute the use of metformin, an agent that has been shown to cross the placenta and thus could be helpful or harmful to the developing fetus.