bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells
Authors: Caballero Sergio , Sengupta Nilanjana , Afzal Aqeela , Chang Kyung-Hee , Li Calzi Sergio , Guberski Dennis L. , Kern Timothy S. , Grant Maria B.
Published: March 2007

Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34+ cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34+ cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34+ cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells’ natural robust reparative function.
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.
Genome-Wide Linkage Analyses to Identify Loci for Diabetic Retinopathy
Authors: Looker Helen C. , Nelson Robert G. , Chew Emily , Klein Ronald , Klein Barbara E.K. , Knowler William C. , Hanson Robert L.
Published: March 2007

Hyperglycemia and long duration of diabetes are widely recognized risk factors for diabetic retinopathy, but inherited susceptibility may also play a role because retinopathy aggregates in families. A genome-wide linkage analysis was conducted in 211 sibships in which ≥2 siblings had diabetes and retinal photographs were available from a longitudinal study. These sibships were a subset of 322 sibships who had participated in a previous linkage study of diabetes and related traits; they comprised 607 diabetic individuals in 725 sibpairs. Retinal photographs were graded for presence and severity of diabetic retinopathy according to a modification of the Airlie House classification system. The grade for the worse eye was adjusted for age, sex, and diabetes duration and analyzed as a quantitative trait. Heritability of diabetic retinopathy in this group was 18% (95% CI 2–36). A genome-wide linkage analysis using variance components modeling found evidence of linkage on chromosome 1p. Using single-point analysis, the peak logarithm of odds (LOD) was 3.1 for marker D1S3669 (34.2 cM), whereas with multipoint analysis the peak LOD was 2.58 at 35 cM. No other areas of suggestive linkage were found. We propose that an area on chromosome 1 may harbor a gene or genes conferring susceptibility to diabetic retinopathy.
Uncoupling Protein-2 Controls Adiponectin Gene Expression in Adipose Tissue Through the Modulation of Reactive Oxygen Species Production
Authors: Chevillotte Emmanuel , Giralt Marta , Miroux Bruno , Ricquier Daniel , Villarroya Francesc
Published: March 2007

Uncoupling protein-2 (UCP2) is a mitochondrial membrane transporter expressed in white adipose tissue. We observed that circulating adiponectin levels and adiponectin gene expression in adipose tissue are reduced in UCP2-null mice. We studied whether mitochondrial activity and its control by UCP2 may regulate adiponectin gene expression. In 3T3-L1 cells, increasing UCP2 mitochondrial levels by adenoviral-mediated gene transfer induced adiponectin gene expression, whereas oligomycin and antimycin A, inhibitors of ATP synthesis and mitochondrial respiration, led to a downregulation. Reactive oxygen species (ROS) scavengers alleviated the repression of adiponectin gene expression caused by oligomycin or antimycin A. The action of ROS involves the transcription factor CHOP-10, the abundance of which was reduced in response to UCP2 and was induced by oligomycin. CHOP-10 inhibited adiponectin gene expression by interfering with the −117/−73 CCAAT/enhancer binding protein–binding region in the adiponectin gene promoter. Moreover, CHOP-10 levels were increased in adipose tissue from UCP2-null mice. Results indicate that the modulation of ROS levels by mitochondrial activity, and specifically as a consequence of the action of UCP2, controls adiponectin gene expression. This provides a physiological mechanism by which the adipose tissue energetic status may determine the extent of adiponectin release and influence systemic insulin sensitivity.
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 <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 <50 mg/dl (<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 < 0.001) and −1.1 ± 0.1% (P < 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 < 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 < 0.001), length (r = 0.17, P < 0.001), and BMI (r = 0.2, P < 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 < 0.001), length (r = 0.12, P = 0.01), and BMI at birth (r = 0.26, P < 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 <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 <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 = <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 >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 <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 <7.0%, blood pressure <130/80 mmHg, and LDL cholesterol <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.
Interaction of a focused laser beam and a coaxial powder jet in laser surface processing
Authors: Diniz Neto O. O. , Alcalde A. M. , Vilar R.
Published: March 2007

Laser cladding, laser alloying, and laser free-form manufacturing are promising techniques where a laser beam is frequently used in conjunction with a coaxial powder jet for surface treating or rapid manufacturing. In the present work, a computational model was developed and used to simulate several experimental setups in order to optimize the processing conditions. More specifically, the model was used to calculate the distribution of particles temperature and the transmitted laser beam power as a function of the position of the origin of the powder jet in relation to the converging lens that focuses the laser beam. Two cases were analyzed, the first assuming that the powder density varies with the inverse of the square of the distance, and the second one considering a Gaussian powder density distribution. The intensity distribution in the laser beam was assumed to be Gaussian. In the present work, it was shown that when the characteristic parameters of the laser beam and of the powder jet are kept constant, the distance between the lens and the powder origin determines the particles temperature distribution and the laser beam attenuation and it is an important aspect in the optimization of energy transfer in the process.
Laser micro adjustment—from new basic process knowledge to the application
Authors: Schmidt Michael , Dirscherl Manfred , Rank Matthias , Zimmermann Maik
Published: March 2007

Laser micro bending and its controlled variant, laser micro adjustment, have been known for many years. Different theories on the working principle, mainly differing in interaction time and energy flux density, have been evolved and experimentally proven. The temperature gradient mechanism and the buckling mechanism are the most established laser adjustment techniques. However, as interaction times are getting shorter with the development of new laser sources, additional phenomena are being detected and new interaction principles have to be investigated. In this paper the use of the thermal upsetting mechanism for adjusting fiber optical components will be demonstrated. An actuator for micro positioning of optical fibers relative to collimating optics is designed using numerical simulations and experimental results. The benefit of laser adjustable actuators in building an automated, modular production line will then be presented by introducing a system developed for the assembly of fiber optical components. As heat impact and thermally induced damaged are becoming a serious issue for laser adjustment in micro technology, new nonthermal adjustment mechanisms using ultrashort laser pulses are experimentally demonstrated and their interaction principles derived. Thus this contribution will both give the latest scientific information on the latest theories concerning novel laser forming mechanisms and focus on examples for the migration of well established process variants into industrial use.
Intrabeam viewing of extended-source lasers with telescopes
Authors: Marshall Wesley J. , Brumage E. Christopher , Sliney David H.
Published: March 2007

Magnifying optics can increase the hazards for intrabeam viewing of lasers. Although it is rather straightforward to evaluate these increased hazards for point-source lasers at distance, limited information is available for determining the hazards from viewing extended-source lasers from within the beam when magnifying optics are used. Since intrabeam viewing of nearly all lasers results in an extremely small retinal image, commonly known as a “point source,” extended-source maximum permissible exposures (MPEs) are seldom applicable; however, a substantial correction factor is allowed for extended-source lasers in the determination of the MPE. In those rare cases where an extended-source laser is viewed by an optical aid, it is important to avoid applying an incorrect and sometimes very large extended-source correction factor. Extended-source lasers were constructed and then measured to determine if standard hazard classification techniques, mainly developed for point-source lasers, would adequately assess the true optical viewing hazards from viewing extended-source lasers with telescopes. It was found that current techniques are adequate since telescopes would normally be expected to be used at tens or hundreds of meters from the laser source, although purposeful exposure at close distance would require specialized hazard evaluation techniques.
Characterization of Dopamine Receptors
Authors: Levant Beth
Published: March 2007

Dopamine 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

This 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

The 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

The 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.
Installing and Configuring CMap
Authors: Faga Ben
Published: March 2007

CMap is a Web‐based tool for viewing comparisons between biological maps of different types. It allows for correspondences to be displayed between maps as disparate as genetic and physical maps. The protocols in this unit comprise a guide to installing, configuring, and importing data into CMap.
Using the Generic Genome Browser (GBrowse)
Authors: Donlin Maureen J.
Published: March 2007

A 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

Well‐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.
Cryptic duplication of 12q24.33 → qter in a child with Angelman syndrome—simultaneous occurrence of two unrelated cytogenetic events
Authors: Sathanoori M. , Hu J. , Murthy V. , Byrnes A. , Vockley J. , Safier R. , Bedoyan J. , Jalal S.M. , Huber H. , Surti U.
Published: March 2007

Simultaneous occurrence of two unrelated cytogenetic events is rare. We present a case of Angelman Syndrome (AS) deletion and 12q duplication in a child with a history of developmental delay, microcephaly, cerebral palsy, and seizures. Traditional cytogenetic studies showed a normal 46,XY karyotype. Fluorescence in situ hybridization (FISH) using probe D15S10 (AS region/15q11.2) revealed a deletion. In addition, we serendipitously detected 12q24.3 duplication by FISH with 12q subtelomere probe. He inherited this duplication from the mother who presented with a balanced translocation karyotype 46,XX,add(12)(q24.3).ish t(12;13)(q24.3;p11.2)(12qtel‐;12qtel+,D13Z1/D21Z1+,RB1+). Array comparative genomic hybridization (array‐CGH) revealed a duplication of three bacterial artificial chromosome (BAC) clones (RP11‐46H11, RP11‐386I8, and RP11‐309H3) covering about 423 Kb of DNA sequence. The published 12q terminal duplication cases had a detectable segment by classical banded cytogenetics techniques. To our knowledge, this is the smallest 12q cryptic rearrangement characterized by array‐CGH and confirmed by BAC‐clone FISH analysis. Based on these findings, we attempted to separate the clinical features associated with AS deletion and those features that are probably due to partial 12q duplication. We then reviewed the genes mapped in the duplicated region using the human genome database to understand the clinical significance. A subsequent pregnancy in the mother revealed an apparently balanced t(12;13) karyotype. We compare our case with the published cases, and discuss the implications of our findings and its relevance in addressing genetic counseling issues. © 2007 Wiley‐Liss, Inc.
Cationic cyclization of purified natural rubber in latex form with a trimethylsilyl triflate as a novel catalyst
Authors: Riyajan Sa‐ad , Liaw Der‐Jang , Tanaka Yasuyuki , Sakdapipanich Jitladda Tangpakdee
Published: March 2007

Cyclization of deproteinized natural rubber (DPNR) or purified natural rubber latex was effectively performed in latex phase by using trimethylsilyl‐trifluoromethane sulfonate or trimethylsilyl triflate (TMSOTF) as a novel catalyst, which is still not reported in the case of natural rubber latex. Various cyclization conditions affecting the degree of cyclization were studied, such as dry rubber contents, temperature, TMSOTF concentrations, and time. The cyclized products were characterized by FTIR, Raman, 1H‐, and 13C‐NMR spectroscopies, as well as DSC and TGA. The degree of cyclization was estimated by 1H‐NMR spectrum. It was found that the degree of cyclization in NR was a function of cyclization conditions. The thermal stability of cyclized DPNR increased with the degree of cyclization. Solubility of the obtained rubber was good in chloroform, toluene, cyclohexanone, and cyclohexane, and bad in tetrahydrofuran. The average number molecular weight of cyclized DPNR with 76% degree of cyclization was about 4.2 × 104 g/mol. On the basis of FTIR, Raman, 1H‐, and 13C‐NMR, the CC of cyclized DPNR dramatically decreased after prolonged reaction time. In addition, the topology of cyclization DPNR particles was rough on its rubber particle as analyzed by TEM. The mechanism for this reaction will also be discussed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007.
Peel and shear strength of pressure‐sensitive adhesives prepared from epoxidized natural rubber
Authors: Poh B. T. , Kwo H. K.
Published: March 2007

Peel and shear strength of two grades of epoxidized natural rubber (ENR 25 and ENR 50)‐based pressure‐sensitive adhesive was studied. Coumarone‐indene resin was used as the tackifier, whereas toluene was chosen as the solvent throughout the experiment. The tackifier loading was varied from 0 to 80 parts per hundred parts of rubber (phr). A SHEEN hand coater was used to coat the adhesive on substrate to give a coating thickness of 30, 60, 90, and 120 μm. Peel strength and shear strength of the adhesive were determined by using a Lloyd adhesion tester and Texture analyzer, respectively. Results show that maximum peel strength occurs at 40 phr of coumarone‐indene resin for both ENRs studied an observation, which is attributed to the maximum wettability of the substrate. However, the shear strength shows a gradual decrease with increasing tackifier loading because of the decrease in cohesive strength of adhesive. ENR 25 consistently indicates higher peel strength and shear strength than ENR 50. Generally, peel and shear strength increases with coating thickness. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007.
Sol‐gel‐derived alumina/polyvinylpyrrolidone hybrid nanocomposite film on metal for corrosion resistance
Authors: Jing Chengbin , Hou Jinxia
Published: March 2007

With the addition of polyvinylpyrrolidone (PVP), alumina sol with an aluminum sec‐butoxide/water molar ratio of 1 : 45 was synthesized. The surface tension of this alumina sol was found to be lower by 35% than the sol without PVP. Alumina/PVP hybrid film with a critical thickness up to 2 μm was fabricated by dip‐coating method. The heat treatment between 200 and 300°C could produce a film with perfect hybrid nanocomposite structures. Alumina particles with a size of about 20 nm were uniformly distributed in this material. The hardness of the film samples increased with the increment of heat treatment temperature, and hardness values higher than the original metal were detected after heat treated above 400°C. The film‐coated metals that were heat treated below 150°C or above 400°C exhibited relatively weak adhesion, but strong adhesion was obtained when heat treated between 200 and 300°C for 30 min. The corrosion rate of the film‐coated metal that was heat treated between 200°C and 300°C for 30 min was lower by 95% than the uncoated metal. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007.
Geophysical exploration in the Church of Protaton at Karyes of Mount Athos (Holy Mountain) in northern Greece
Authors: Tsokas G. N. , Stampolidis A. , Mertzanidis I. , Tsourlos P. , Hamza R. , Chrisafis C. , Ambonis D. , Tavlakis I.
Published: March 2007

The area around the Church of Protaton at Karyes on Mount Athos (Holy Mountain) in northern Greece, was explored by means of resistance mapping and electrical tomography. Ruins of foundation walls were detected and mapped around the Church, and additionally geological information was retrieved by the tomography. The floor of the Church was investigated with ground‐penetrating radar transects wherever was possible. The presence of reflection patterns, which appeared aligned in parallel transects, led to the conclusion that they were caused by structures concealed beneath the floor of the Church. The survey, which took place in and around an existing monument, required different geophysical methods, used in a synergetic manner. Copyright © 2007 John Wiley & Sons, Ltd.
A new murine model to define the critical pathologic and therapeutic mediators of polymyositis
Authors: Sugihara Takahiko , Sekine Chiyoko , Nakae Takashi , Kohyama Kuniko , Harigai Masayoshi , Iwakura Yoichiro , Matsumoto Yoh , Miyasaka Nobuyuki , Kohsaka Hitoshi
Published: March 2007

Objective

To establish a new murine model of polymyositis (PM) for the understanding of its pathologic mechanisms and the development of new treatment strategies.

Methods

C protein–induced myositis (CIM) was induced by a single immunization of recombinant human skeletal C protein in C57BL/6 mice, as well as in CD4‐depleted, CD8‐depleted, and mutant mice as controls. Some mice were treated with high‐dose intravenous immunoglobulin (IVIG) after disease induction. Muscle tissues were examined histologically.

Results

In mice with CIM, inflammation was confined to the skeletal muscles. Histologic examination revealed a common pathologic feature of CIM and PM, involving abundant infiltration of CD8 and perforin‐expressing cells in the endomysial site of the injured muscle. Suppression of myositis was achieved by depletion of both CD4 and CD8 T cells. Despite the development of serum anti–C protein antibodies in wild‐type mice, severe myositis was induced in mice deficient in B cells. Induction of myositis was suppressed in interleukin‐1α/β (IL‐1α/β)–null mutant mice, but not in tumor necrosis factor α (TNFα)–null mutant mice. Use of IVIG, a treatment with proven efficacy in PM, suppressed CIM in the subgroup of treated mice.

Conclusion

CIM mimics PM pathologically and clinically. Infiltration of CD8 T cells is the most likely mechanism of muscle injury, and IL‐1, but not B cells or TNFα, is crucial in the development of CIM. IVIG has therapeutic effects in CIM, suggesting that the effects of IVIG are not mediated by suppression of antibody‐mediated tissue injury. This murine model provides a useful tool for understanding the pathologic mechanisms of PM and for developing new treatment strategies.
Therapy of patients with rheumatoid arthritis: Outcome of infliximab failures switched to etanercept
Authors: Buch Maya H. , Bingham Sarah J. , Bejarano Victoria , Bryer Domini , White Jo , Emery Paul , Reece Richard , Quinn Mark
Published: March 2007

Objective

The role of alternative tumor necrosis factor (TNF) antagonist therapies in the context of failure of initial TNF antagonist therapy in patients with rheumatoid arthritis (RA) has yet to be clearly defined. The goal of this study was to determine the efficacy of etanercept in patients who failed to respond to infliximab.

Methods

Ninety‐five patients with RA who failed to respond to infliximab and methotrexate were treated with etanercept (with continuation of concomitant methotrexate). Thirty‐four patients never achieved a response to infliximab (primary nonresponse), 38 had an initial response to infliximab but relapsed (secondary nonresponse), and 23 demonstrated toxicity. Disease Activity Score in 28 joints (DAS28), European League Against Rheumatism (EULAR) response, and American College of Rheumatology (ACR) response were determined after 12 weeks of etanercept.

Results

After 12 weeks of etanercept, 38% of patients achieved an ACR 20% response (ACR20) on etanercept. Of these, 24% and 15% achieved ACR50 and ACR70 responses, respectively. In the primary infliximab nonresponse group, 42%, 30%, and 15% achieved ACR20, ACR50, and ACR70 responses, respectively; the percentages for the secondary nonresponse group were 34%, 21%, and 14%, respectively. Significant DAS28 reductions were observed in the entire cohort and nonresponse subtype groups. Sixty‐one percent of the cohort achieved either a moderate or good EULAR score (67% of primary and 56% of secondary infliximab failures). No toxicity was observed in patients who stopped infliximab due to intolerance; 19 of 23 continued etanercept after week 12.

Conclusion

This study confirms that etanercept is effective in patients who fail to respond to infliximab and suggests a higher response in patients who have never had a response to infliximab.
Full‐limb and knee radiography assessments of varus‐valgus alignment and their relationship to osteoarthritis disease features by magnetic resonance imaging
Authors: Issa Sakeba N. , Dunlop Dorothy , Chang Alison , Song Jing , Prasad Pottumarthi V. , Guermazi Ali , Peterfy Charles , Cahue September , Marshall Meredith , Kapoor Dipali , Hayes Karen , Sharma Leena
Published: March 2007

Objective

To examine the correlation between hip‐knee‐ankle and femur‐tibia radiograph angles, calculate the offset of the femur‐tibia angle with respect to the hip‐knee‐ankle angle, calculate the sensitivity and specificity and area under the receiver operating characteristic (ROC) curve of the femur‐tibia angle, and examine the relationship of malalignment by each approach with osteoarthritis (OA) tissue pathology in the mechanically stressed compartment using magnetic resonance imaging (MRI).

Methods

Individuals with knee OA underwent full‐limb and knee radiographs and knee MRI. Linear regression was used to determine if the 2 angles differed systematically and to identify the cutoff. Alignment means for MRI grades were compared using Dunnett's t‐test.

Results

In the 146 participants (109 women, mean age 70 years, body mass index 30.6 kg/m2), femur‐tibia and hip‐knee‐ankle angles correlated (r = 0.86; 95% confidence interval [95% CI] 0.81, 0.90). On average, the femur‐tibia angle was 3.4° more valgus (3.0° in women and 4.7° in men); after correction, its sensitivity and specificity (to predict the hip‐knee‐ankle angle) were 0.84 and 0.84 for identifying varus and 0.98 and 0.73 for valgus, respectively. The area under the ROC curve (95% CI) was 0.91 (0.86, 0.96) for varus and 0.94 (0.89, 0.99) for valgus. Varus severity worsened comparably with each alignment measure as medial lesion score on MRI worsened. Laterally, as lesion score worsened, comparably worse valgus was seen with either assessment approach.

Conclusion

In knee OA, the knee radiograph femur‐tibia and full‐limb radiograph hip‐knee‐ankle angles were correlated. The femur‐tibia angle, corrected for mean offset, was sensitive, specific, and had excellent discriminative ability for identifying varus and valgus alignment evidenced by area under the ROC curve. The relationship between alignment and specific OA MRI features was comparable with the 2 approaches. Use of the femur‐tibia angle, corrected for offset, should be considered in research and clinical settings.