bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUMO4 M55V Variant Is Associated With Diabetic Nephropathy in Type 2 Diabetes
Authors: Lin Hsing-Yi , Wang Chiao-Ling , Hsiao Pi-Jung , Lu Yung-Chuan , Chen Su-Yu , Lin Kun-Der , Hsin Shih-Chie , Hsieh Ming-Chia , Shin Shyi-Jang 
Published: March 2007

OBJECTIVE—SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-κB (NF-κB) activity. Because NF-κB is known to mediate the development of diabetic nephropathy, we examined the association between the SUMO4 M55V variant and the severity of diabetic nephropathy.
RESEARCH DESIGN AND METHODS—We recruited a total of 430 patients with type 2 diabetes. The M55V (rs237025, 163A→G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay.
RESULTS—The frequencies of SUMO4 AA, GA, and GG were 52.6, 40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1% in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric group. We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups. The mean urine albumin–to–creatinine ratio (42.3 ± 108.82 mg/mmol) in the GG group was significantly higher than in the AA (14.9 ± 51.49 mg/mmol) and GA (17.0 ± 43.74 mg/mmol) groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy.
CONCLUSIONS—This study indicates that the SUMO4 gene M55V variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes.
Glimepiride Versus Metformin as Monotherapy in Pediatric Patients With Type 2 Diabetes
Authors: Gottschalk Michael , Danne Thomas , Vlajnic Aleksandra , Cara José F. 
Published: March 2007

OBJECTIVE—To compare the efficacy and safety of glimepiride versus metformin in pediatric subjects with type 2 diabetes inadequately controlled with diet and exercise alone or oral monotherapy.
RESEARCH DESIGN AND METHODS—This 26-week, single-blind, active-controlled, multinational study randomized 285 subjects to receive glimepiride (1–8 mg once daily) or metformin (500–1000 mg twice daily) for 24 weeks. The primary end point was mean change in A1C from baseline to week 24. Safety was assessed by incidence of hypoglycemia and other adverse events.
RESULTS—Significant reductions from baseline A1C were seen in both the glimepiride (−0.54%, P = 0.001) and metformin (−0.71%, P = 0.0002) groups. A total of 42.4% (56 of 132) and 48.1% (63 of 131) of subjects in the glimepiride and metformin groups, respectively, in the intent-to-treat population achieved A1C &lt;7.0% at week 24. No significant differences were observed between groups in reductions in A1C and self-monitored blood glucose levels, changes in serum lipid concentrations, or hypoglycemia incidence. Significant differences were observed in mean changes from baseline in BMI between groups (0.26 kg/m2 for glimepiride and −0.33 kg/m2 for metformin; P = 0.003). The adjusted mean body weight increase was 1.97 kg for glimepiride and 0.55 kg for metformin (P = 0.005). A hypoglycemic episode with blood glucose &lt;50 mg/dl (&lt;2.8 mmol/l) was experienced by 4.9 and 4.2% of glimepiride- and metformin-treated subjects, respectively. A single severe hypoglycemic event occurred in each group.
CONCLUSIONS—Glimepiride reduced A1C similarly to metformin with greater weight gain, and there was comparable safety over 24 weeks in the treatment of pediatric subjects with type 2 diabetes.
Effects of Vildagliptin on Glucose Control Over 24 Weeks in Patients With Type 2 Diabetes Inadequately Controlled With Metformin
Authors: Bosi Emanuele , Camisasca Riccardo Paolo , Collober Carole , Rochotte Erika , Garber Alan J. 
Published: March 2007

OBJECTIVE—We sought to evaluate the efficacy and safety of vildagliptin, a new dipeptidyl peptidase-4 inhibitor, added to metformin during 24 weeks of treatment in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—This was a double-blind, randomized, multicenter, parallel group study of a 24-week treatment with 50 mg vildagliptin daily (n = 177), 100 mg vildagliptin daily (n = 185), or placebo (n = 182) in patients continuing a stable metformin dose regimen (≥1,500 mg/day) but achieving inadequate glycemic control (A1C 7.5–11%).
RESULTS—The between-treatment difference (vildagliptin − placebo) in adjusted mean change (AMΔ) ± SE in A1C from baseline to end point was −0.7 ± 0.1% (P &lt; 0.001) and −1.1 ± 0.1% (P &lt; 0.001) in patients receiving 50 or 100 mg vildagliptin daily, respectively. The between-treatment difference in the AMΔ fasting plasma glucose (FPG) was −0.8 ± 0.3 mmol/l (P = 0.003) and −1.7 ± 0.3 mmol/l (P &lt; 0.001) in patients receiving 50 or 100 mg vildagliptin daily, respectively. Adverse events (AEs) were reported by 63.3, 65.0, and 63.5% of patients receiving 50 mg vildagliptin daily, 100 mg vildagliptin daily, or placebo, respectively. Gastrointestinal AEs were reported by 9.6 (P = 0.022 vs. placebo), 14.8, and 18.2% of patients receiving 50 mg vildagliptin daily, 100 mg vildagliptin daily, or placebo, respectively. One patient in each treatment group experienced one mild hypoglycemic event.
CONCLUSIONS—Vildagliptin is well tolerated and produces clinically meaningful, dose-related decreases in A1C and FPG as add-on therapy in patients with type 2 diabetes inadequately controlled by metformin.
Overexpression of GLUT5 in Diabetic Muscle Is Reversed by Pioglitazone
Authors: Stuart Charles A. , Howell Mary E.A. , Yin Deling 
Published: March 2007

OBJECTIVE—This study was undertaken to quantify the expression of muscle GLUT in type 2 diabetes and to determine if treatment with an insulin-enhancing thiazolidenedione drug, pioglitazone, would alter its expression.
RESEARCH DESIGN AND METHODS—Twelve patients with type 2 diabetes were randomly assigned to treatment with either pioglitazone or placebo in a double-blinded 8-week protocol. Protein and mRNA for GLUT4 and GLUT5 were quantified in muscle homogenates from biopsies of vastus lateralis before and after treatment. The five additional GLUT family isoforms expressed in muscle had mRNA quantified in these samples.
RESULTS—Baseline and posttreatment repeat measurements of GLUT4 protein were not different from control measurements. Compared with normal subjects, GLUT5 protein increased 2.5-fold, and GLUT5 mRNA was 82% higher in the pretreatment samples from the diabetic subjects. Concentrations of mRNA for the six other GLUTs (GLUT1, GLUT3, GLUT4, GLUT8, GLUT11, and GLUT12) were not different from control subjects before or after treatment. The proportion of type I (red) fibers (46%) in diabetic muscle was not affected by pioglitazone treatment. Pioglitazone treatment decreased muscle GLUT5 mRNA and protein by 52 and 40%, respectively, whereas placebo did not alter GLUT5 expression. Both red and white fibers had higher GLUT5 expression in the baseline diabetic muscle samples, and a pioglitazone-related decrease in GLUT5 protein also occurred in both.
CONCLUSIONS—GLUT5 was dramatically increased in diabetic muscle, and pioglitazone treatment reversed this overexpression. The role of this fructose transporter expression in the insulin-enhancing effect of pioglitazone in muscle is unclear.
Serum Interleukin-6 Correlates With Endothelial Dysfunction in Healthy Men Independently of Insulin Sensitivity
Authors: Esteve Eduardo , Castro Antoni , López-Bermejo Abel , Vendrell Joan , Ricart Wifredo , Fernández-Real Jose-Manuel 
Published: March 2007

OBJECTIVE—Interleukin (IL)-6 is a proinflammatory cytokine that is implicated in the pathogenesis of atherosclerosis and insulin resistance. Both endothelial dysfunction and insulin resistance are among the earliest abnormalities that can be detected in people at risk for cardiovascular events. We aimed to evaluate whether increased serum IL-6 concentrations associated with endothelial dysfunction are independent of insulin sensitivity in apparently healthy men.
RESEARCH DESIGN AND METHODS—Association studies were performed in well-characterized nondiabetic Caucasian men (n = 99) recruited for energy balance studies. Insulin sensitivity (minimal model) and brachial vascular reactivity (high-resolution external ultrasound) were assessed. Circulating IL-6 concentrations were measured by enzyme-linked immunosorbent assay.
RESULTS—Serum IL-6 was an independent contributor to the variance of endothelium-dependent vasodilatation after adjusting for age, BMI, smoking status, LDL cholesterol, systolic blood pressure, diastolic blood pressure, and insulin sensitivity (P = 0.001). In fact, circulating IL-6 was negatively associated with endothelium-dependent vasodilatation (r = −0.247, P = 0.014) and insulin sensitivity (r = −0.262, P = 0.011) and correlated positively with age (r = 0.241, P = 0.016), BMI (r = 0.240, P = 0.017), systolic blood pressure (r = 0.299, P = 0.003), diastolic blood pressure (r = 0.295, P = 0.003), and triglycerides (r = 0.212, P = 0.035). No significant associations were observed between endothelium-independent vasodilatation and serum IL-6 concentrations.
CONCLUSIONS—Circulating IL-6 is linked to endothelial dysfunction independently of insulin sensitivity in apparently healthy men.
Gestational Diabetes Mellitus: Clinical Predictors and Long-Term Risk of Developing Type 2 Diabetes
Authors: Lee Anna J. , Hiscock Richard J. , Wein Peter , Walker Susan P. , Permezel Michael 
Published: March 2007

OBJECTIVE—We sought to determine the long-term risk of type 2 diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM) and assess what maternal antepartum, postpartum, and neonatal factors are predictive of later development of type 2 diabetes.
RESEARCH DESIGN AND METHODS—This was a retrospective cohort study using survival analysis on 5,470 GDM patients and 783 control subjects who presented for postnatal follow-up at the Mercy Hospital for Women between 1971 and 2003.
RESULTS—Risk of developing diabetes increased with time of follow-up for both groups and was 9.6 times greater for patients with GDM. The cumulative risk of developing type 2 diabetes for the GDM patients was 25.8% at 15 years postdiagnosis. Predictive factors for the development of type 2 diabetes were use of insulin (hazard ratio 3.5), Asian origin compared with Caucasian (2.1), and 1-h blood glucose (1.3 for every 1 mmol increase above 10.1 mmol). BMI was associated with an increased risk of developing type 2 diabetes but did not meet the assumption of proportional hazards required for valid inference when using Cox proportional hazards.
CONCLUSIONS—While specific predictive factors for the later development of type 2 diabetes can be identified in the index pregnancy, women with a history of GDM, as a group, are worthy of long-term follow-up to ameliorate their excess cardiovascular risk.
The Impact of Maternal Glycemia and Obesity on Early Postnatal Growth in a Nondiabetic Caucasian Population
Authors: Knight Bridget , Shields Beverley M. , Hill Anita , Powell Roy J. , Wright David , Hattersley Andrew T. 
Published: March 2007

OBJECTIVE—Offspring of mothers with diabetes have increased birth weight and higher rates of obesity in early childhood. The relative role of maternal glycemia and maternal obesity is uncertain. We therefore studied the impact of maternal glycemia and maternal obesity on offspring birth measures and early postnatal growth in nondiabetic pregnancies.RESEARCH DESIGN AND METHODS—We studied 547 full-term singleton babies of nondiabetic parents. Data available included parental height and weight; maternal prepregnant weight; maternal fasting plasma glucose (FPG) at 28 weeks of gestation; and offspring weight and length at birth, 12 weeks of age, and 1 and 2 years of age. Relationships between parental and offspring measures were estimated using Pearson correlations.RESULTS—Maternal FPG was correlated with offspring birth weight (r = 0.25, P &lt; 0.001), length (r = 0.17, P &lt; 0.001), and BMI (r = 0.2, P &lt; 0.001) but was not correlated with offspring growth at 12 weeks. Maternal prepregnancy BMI was significantly correlated with offspring weight (r = 0.26, P &lt; 0.001), length (r = 0.12, P = 0.01), and BMI at birth (r = 0.26, P &lt; 0.001) and remained correlated with offspring weight (r = 0.13–0.14, P = 0.007–0.002) and BMI (r = 0.14–0.19, P = 0.002 to &lt;0.001) during the first 2 years. Paternal BMI was correlated with offspring weight from 12 weeks onwards (r = 0.11–0.22, P = 0.017 to &lt;0.001), length (r = 0.10–0.12, P = 0.01–0.05), and BMI from 1 year onwards (r = 0.16–0.25, P = &lt;0.001).CONCLUSIONS—In a nondiabetic cohort, the effect of maternal glycemia on birth weight is transitory, while the impact on growth of maternal BMI continues into early childhood. The independent association of paternal BMI with offspring postnatal growth suggests that the impact of parental BMI could be explained by genetic factors, shared environment, or both.
Intensive Insulin Therapy in Critical Care
Authors: Wilson Mark , Weinreb Jane , Hoo Guy W. Soo 
Published: March 2007

OBJECTIVE—To review performance characteristics of 12 insulin infusion protocols.
RESEARCH DESIGN AND METHODS—We systematically identify and compare 12 protocols and then apply the protocols to generate insulin recommendations in the management of a patient with hyperglycemia. The main focus involves a comparison of insulin doses and patterns of insulin administration.
RESULTS—There is great variability in protocols. Areas of variation include differences in initiation and titration of insulin, use of bolus dosing, requirements for calculation in adjustment of the insulin infusion, and method of insulin protocol adjustments. Insulin recommendations for a sample patient are calculated to highlight differences between protocols, including the patterns and ranges of insulin dose recommended (range 27–115 units [mean ± SD 66.7 ± 27.9]), amount recommended for glucose readings &gt;200 mg/dl, and adjustments nearing target glucose.
CONCLUSIONS—The lack of consensus in the delivery of intravenous insulin infusions is reflected in the wide variability of practice noted in this survey. This mandates close attention to the choice of a protocol. One protocol may not suffice for all patients.
The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults
Authors: Pittas Anastassios G. , Harris Susan S. , Stark Paul C. , Dawson-Hughes Bess 
Published: March 2007

OBJECTIVE—We sought to compare the effects of combined calcium and vitamin D supplementation versus placebo on blood glucose and markers of inflammation in nondiabetic adults aged ≥65 years.RESEARCH DESIGN AND METHODS—A total of 314 Caucasian adults without diabetes received either 500 mg calcium citrate and 700 IU vitamin D3 or placebos daily for 3 years in a double-blind, randomized, controlled trial designed for bone-related outcomes. In a post hoc analysis, fasting plasma glucose (FPG), insulin sensitivity (estimated by homeostasis model assessment of insulin resistance [HOMA-IR]), plasma C-reactive protein, and interleukin-6, were measured at baseline and 3 years.RESULTS—The effects of combined calcium–vitamin D supplementation on 3-year change in FPG depended on baseline FPG (P = 0.02 for interaction). Therefore, we conducted analyses separately in participants with normal fasting glucose (NFG) (FPG &lt;5.6 mmol/l, n = 222) and impaired fasting glucose (IFG) (FPG 5.6–6.9 mmol/l, n = 92) at baseline. Among participants with IFG at baseline, those who took combined calcium–vitamin D supplements had a lower rise in FPG at 3 years compared with those on placebo (0.02 mmol/l [0.4 mg/dl] vs. 0.34 mmol/l [6.1 mg/dl], respectively, P = 0.042) and a lower increase in HOMA-IR (0.05 vs. 0.91, P = 0.031). In the NFG subgroup, there was no difference in the change in FPG or HOMA-IR between the two treatment arms. There were no differences in C-reactive protein or interleukin-6 between the two treatment arms in either subgroup.CONCLUSIONS—In healthy, older adults with IFG, supplementation with calcium and vitamin D may attenuate increases in glycemia and insulin resistance that occur over time. However, our findings should be considered hypothesis generating and need to be confirmed in randomized trials specifically designed for the outcomes of interest.
Effects of Treatment Targets on Subsequent Cardiovascular Events in Chinese Patients With Type 2 Diabetes
Authors: Kong Alice P.S. , Yang Xilin , Ko Gary T.C. , So Wing-Yee , Chan Wing-Bun , Ma Ronald C.W. , Ng Vanessa W.S. , Chow Chun-Chung , Cockram Clive S. , Tong Peter C.Y. , Wong Vivian , Chan Juliana C.N. 
Published: March 2007

OBJECTIVE—International guidelines recommend optimal control of risk factors in diabetes to prevent cardiovascular events. We examined risk associations between achieving treatment targets for glycemia, blood pressure and lipid control, and other risk factors on subsequent cardiovascular events in Chinese patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—Between 1995 and 2005, 6,386 Chinese type 2 diabetic patients without a history of coronary heart disease (CHD) or stroke were recruited. They were classified according to the number of treatment targets attained at baseline, and their cardiovascular outcomes were compared. Treatment targets were defined as A1C &lt;7.0%, blood pressure &lt;130/80 mmHg, and LDL cholesterol &lt;2.6 mmol/l.
RESULTS—After a median follow-up of 5.7 years, cumulative incidence of CHD or stroke (n = 749) increased with decreasing numbers of treatment targets attained at baseline. Attainment of two or more targets at baseline was associated with reduced risk of CHD compared with those with no target achieved (hazard ratio 0.69 [95% CI 0.50–0.94], P = 0.020). However, the association lost its significance after adjustment for urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and hemoglobin.
CONCLUSIONS—Reaching more treatment targets was associated with reduced risk of new onset of CHD in Chinese patients with type 2 diabetes.
Characterization of Dopamine Receptors
Authors: Levant Beth 
Published: March 2007

AbstractDopamine receptors are the principal targets of drugs used for the treatment of neuropsychiatric disorders such as schizophrenia and Parkinson's disease. This unit details protocols for radioligand binding assays for various subtypes of dopamine receptor. The scope is limited primarily to the most widely used, well established protocols for binding assays, which employ commercially available tritiated ligands. Protocols are given for radioligand binding assays for D1‐like and D2‐like receptors. A protocol for the putatively selective labeling of D3 sites is also presented. The basic protocols are used to assay dopamine receptors in membrane homogenates, and support protocols describe the preparation of these homogenates from organs and from cultured cells. The calculation of the radioligand's molar concentration is also included.
Palladium‐Catalyzed Cross‐Coupling Reactions in C6 Modifications of Purine Nucleosides
Authors: Hocek Michal , Šilhár Peter 
Published: March 2007

AbstractThis unit describes the cross‐coupling methodology for introduction of diverse C‐substituents to position 6 of purine nucleosides. Protected 6‐chloropurine nucleosides undergo Pd‐catalyzed cross‐coupling reactions with trialkylaluminium, alkylzinc halides, aryl(tributyl)stannanes, and arylboronic acids to give the corresponding 6‐substituted intermediates, which can be deprotected by treatment with NaOMe. (Acetyloxy)methylzinc iodide is used for introduction of the hydroxymethyl group, which can further be transformed to fluoromethyl and difluoromethyl groups. Most of the title 6‐substituted purine ribonucleosides possess cytostatic and/or anti‐HCV activity.
Differentiation of Mouse Embryonic Stem Cells and of Human Adult Stem Cells into Adipocytes
Authors: Wdziekonski Brigitte , Villageois Phi , Dani Christian 
Published: March 2007

AbstractThe authors describe protocols for culture conditions in which mouse ES cells can be maintained in an undifferentiated state or committed to undergo adipocyte differentiation at a high rate and in a highly reproducible fashion. There is also a protocol for maintaining and differentiating human adult stem cells, isolated form adipose tissue and from bone marrow, into adipocytes. These culture systems provide a powerful means for studying the first step of adipose cell development and a means to investigate effects of drugs on the biology of adipocytes. There are also protocols for detection of adipocytes and analysis of their gene expression.
The UCSC Genome Browser
Authors: Karolchik Donna , Hinrichs Angie S. , Kent W. James 
Published: March 2007

AbstractThe University of California Santa Cruz (UCSC) Genome Browser (genome.ucsc.edu) is a popular Web‐based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation “tracks”. The annotations—generated by the UCSC Genome Bioinformatics Group and external collaborators—display gene predictions, mRNA and expressed sequence tag alignments, simple nucleotide polymorphisms, expression and regulatory data, and pairwise and multiple‐species comparative genomics data. All information relevant to a region is presented in one window, facilitating biological analysis and interpretation. The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web‐based application, the UCSC Table Browser. Users can upload personal data as custom annotation tracks in both browsers for research or educational use. This unit describes how to use the Genome Browser and Table Browser for genome analysis, download the underlying database tables, and create and display custom annotation tracks.
Using the Generic Genome Browser (GBrowse)
Authors: Donlin Maureen J. 
Published: March 2007

AbstractA genome browser is software that allows users to visualize DNA, protein, or other sequence features within the context of a reference sequence, such as a chromosome or contig. The Generic Genome Browser (GBrowse) is an open‐source browser developed as part of the Generic Model Organism Database project (Stein et al., 2002). GBrowse can be configured to display genomic sequence features for any organism and is the browser used for the model organisms Drosophila melanogaster (Grumbling and Strelets, 2006) and Caenorhabditis elegans (Schwarz et al., 2006), among others. The software package can be downloaded from the web and run on a Windows, Mac OS X, or Unix‐type system. Version 1.64, as described in this protocol, was released in November 2005, but the software is under active development and new versions are released about every six months.
Cover Picture: Length‐Dependent Uptake of DNA‐Wrapped Single‐Walled Carbon Nanotubes (Adv. Mater. 7/2007)
Authors: Becker M. L. , Fagan J. A. , Gallant N. D. , Bauer B. J. , Bajpai V. , Hobbie E. K. , Lacerda S. H. , Migler K. B. , Jakupciak J. P. 
Published: March 2007

AbstractWell‐defined length fractions of DNA‐wrapped single‐walled carbon nanotubes (SWNTs) of below 200 nm are taken up preferentially by IMR‐90 human lung fibroblasts, while longer DNA wrapped SWNTs are excluded from the cell interior (inset), report Matt Becker and coworkers on p. 939. The cover image construct includes overlaid images of the labeled cell membrane, the nuclei (blue), and the fluorescently labeled DNA wrapped SWNTs (red) that have gained access to the cell interior.