bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals
Authors: Park Jiyoung , Choe Sung Sik , Choi A Hyun , Kim Kang Ho , Yoon Myeong Jin , Suganami Takayoshi , Ogawa Yoshihiro , Kim Jae Bum
Published: October 2006

In adipocytes, oxidative stress and chronic inflammation are closely associated with metabolic disorders, including insulin resistance, obesity, cardiovascular disease, and type 2 diabetes. However, the molecular mechanisms underlying these metabolic disorders have not been thoroughly elucidated. In this report, we demonstrate that overexpression of glucose-6-phosphate dehydrogenase (G6PD) in adipocytes stimulates oxidative stress and inflammatory responses, thus affecting the neighboring macrophages. Adipogenic G6PD overexpression promotes the expression of pro-oxidative enzymes, including inducible nitric oxide synthase and NADPH oxidase, and the activation of nuclear factor-κB (NF-κB) signaling, which eventually leads to the dysregulation of adipocytokines and inflammatory signals. Furthermore, secretory factors from G6PD-overexpressing adipocytes stimulate macrophages to express more proinflammatory cytokines and to be recruited to the adipocytes; this would cause chronic inflammatory conditions in the adipose tissue of obesity. These effects of G6PD overexpression in adipocytes were abolished by pretreatment with NF-κB inhibitors or antioxidant drugs. Thus, we propose that a high level of G6PD in adipocytes may mediate the onset of metabolic disorders in obesity by increasing the oxidative stress and inflammatory signals.
PDH-E1α Dephosphorylation and Activation in Human Skeletal Muscle During Exercise
Authors: Pilegaard Henriette , Birk Jesper B. , Sacchetti Massimo , Mourtzakis Marina , Hardie D. Graham , Stewart Greg , Neufer P. Darrell , Saltin Bengt , van Hall Gerrit , Wojtaszewski Jorgen F.P.
Published: October 2006

To investigate pyruvate dehydrogenase (PDH)-E1α subunit phosphorylation and whether free fatty acids (FFAs) regulate PDH activity, seven subjects completed two trials: saline (control) and intralipid/heparin (intralipid). Each infusion trial consisted of a 4-h rest followed by a 3-h two-legged knee extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1α site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion. Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1α phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1α phosphorylation, but exercise overrules this effect of FFA on PDH-E1α phosphorylation leading to even greater dephosphorylation during exercise with intralipid infusion than with saline.
The HADHSC Gene Encoding Short-Chain l-3-Hydroxyacyl-CoA Dehydrogenase (SCHAD) and Type 2 Diabetes Susceptibility
Authors: van Hove Els C. , Hansen Torben , Dekker Jacqueline M. , Reiling Erwin , Nijpels Giel , Jørgensen Torben , Borch-Johnsen Knut , Hamid Yasmin H. , Heine Robert J. , Pedersen Oluf , Maassen J. Antonie , 't Hart Leen M.
Published: October 2006

The short-chain l-3-hydroxyacyl-CoA dehydrogenase (SCHAD) protein is involved in the penultimate step of mitochondrial fatty acid oxidation. Previously, it has been shown that mutations in the corresponding gene (HADHSC) are associated with hyperinsulinism in infancy. The presumed function of the SCHAD enzyme in glucose-stimulated insulin secretion led us to the hypothesis that common variants in HADHSC on chromosome 4q22-26 might be associated with development of type 2 diabetes. In this study, we have performed a large-scale association study in four different cohorts from the Netherlands and Denmark (n = 7,365). Direct sequencing of HADHSC cDNA and databank analysis identified four tagging single nucleotide polymorphisms (SNPs) including one missense variant (P86L). Neither the SNPs nor haplotypes investigated were associated with the disease, enzyme function, or any relevant quantitative measure (all P > 0.1). The present study provides no evidence that the specific HADHSC variants or haplotypes examined do influence susceptibility to develop type 2 diabetes. We conclude that it is unlikely that variation in HADHSC plays a major role in the pathogenesis of type 2 diabetes in the examined cohorts.
Ghrelin Attenuates the Inhibitory Effects of Glucagon-Like Peptide-1 and Peptide YY(3-36) on Food Intake and Gastric Emptying in Rats
Authors: Chelikani Prasanth K. , Haver Alvin C. , Reidelberger Roger D.
Published: October 2006

Ghrelin stimulates, while glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) [PYY(3-36)] inhibit, food intake and gastric emptying in rats. We determined the dose-dependent effects of a 3-h intravenous infusion of ghrelin at dark onset on food intake in freely feeding rats, and on the inhibitory effects of intravenous infusion of GLP-1 and PYY(3-36) on food intake and gastric emptying. Ghrelin (150 pmol · kg−1 · min−1) stimulated food intake by 28% during the infusion period primarily by increasing meal frequency; doses of 15 and 50 pmol · kg−1 · min−1 had no effect. GLP-1 (15 pmol · kg−1 · min−1) inhibited food intake by 35–54%; coinfusion of ghrelin at 50 and 150 pmol · kg−1 · min−1 attenuated this effect by 60 and 64%, respectively. PYY(3-36) (15 pmol · kg−1 · min−1) inhibited food intake by 32%; ghrelin at 15 and 50 pmol · kg−1 · min−1 attenuated this effect by 54 and 74%, respectively. A 20-min intravenous infusion of ghrelin (15–150 pmol · kg−1 · min−1) attenuated GLP-1–and PYY(3-36)-induced inhibition of gastric emptying of saline by 6–29%. Thus, intravenous infusion of ghrelin during the early dark period stimulates food intake in freely feeding rats by increasing meal frequency, and similar doses of ghrelin attenuate gastric emptying and feeding responses to GLP-1 and PYY(3-36). These results suggest that ghrelin may stimulate food intake in part by attenuating the inhibitory effects of GLP-1 and PYY(3-36) on gastric emptying and food intake.
Prevalence and Determinants of Insulin Resistance Among U.S. Adolescents
Authors: Lee Joyce M. , Okumura Megumi J. , Davis Matthew M. , Herman William H. , Gurney James G.
Published: October 2006

OBJECTIVE—We sought to examine the distribution of insulin and homeostasis model assessment of insulin resistance (HOMA-IR) and associations of HOMA-IR with sex, race/ethnicity, age, and weight status, as measured by BMI, among U.S. adolescents.

RESEARCH DESIGN AND METHODS—Of 4,902 adolescents aged 12–19 years who participated in the National Health and Nutrition Examination Survey 1999–2002, analysis was performed for a nationally representative subsample of 1,802 adolescents without diabetes who had fasting laboratory measurements. The main outcome measure was HOMA-IR, calculated from fasting insulin and glucose and log transformed for multiple linear regression analyses.

RESULTS—In adjusted regression models that included age and weight status, girls had higher HOMA-IR than boys and Mexican-American children had higher HOMA-IR levels than white children. There were no significant differences in adjusted HOMA-IR between black and white children. Obese children (BMI ≥95th percentile) had significantly higher levels of HOMA-IR compared with children of normal weight (BMI <85th percentile) in adjusted comparisons (mean HOMA-IR 4.93 [95% CI 4.56–5.35] vs. 2.30 [2.21–2.39], respectively). Weight status was by far the most important determinant of insulin resistance, accounting for 29.1% of the variance in HOMA-IR. The prevalence of insulin resistance in obese adolescents was 52.1% (95% CI 44.5–59.8).

CONCLUSIONS—Obesity in U.S. adolescents represents the most important risk factor for insulin resistance, independent of sex, age, or race/ethnicity. The prevalence of insulin resistance in obese children foreshadows a worrisome trend for the burden of type 2 diabetes in the U.S.
Quality of Diabetes Care in the Middle- and High-Income Group Populace
Authors: Nagpal Jitender , Bhartia Abhishek
Published: October 2006

OBJECTIVE—We sought to evaluate the quality of care in known diabetic patients from the middle- and high-income group populace of Delhi.

RESEARCH DESIGN AND METHODS—A cross-sectional survey was conducted using a probability proportionate to size (systematic), two-stage cluster design. Thirty areas were selected for a house-to-house survey to recruit a minimum of 25 subjects (known diabetes ≥1 year; aged 35–65 years) per area. Data were collected by interview, by blood sampling, and from medical records.

RESULTS—A total of 819 subjects (of 1,153 eligible) were enrolled from 20,666 houses. In total, 13.0% (95% CI 9.6–17.3) of the patients had an HbA1c (A1C) estimation and 16.2% (13.5–19.4) had a dilated eye examination in the last year, 32.1% (27.5–36.6) had serum cholesterol estimation in the last year, and 17.5% (14.2–21.5) were taking aspirin. An estimated 42.0% (37.7–46.2) had an A1C value >8%, 40.6% (36.5–44.7) had an LDL cholesterol level >130 mg/dl, and 63.2% (59.6–66.6) had blood pressure levels >140/90 mmHg.

CONCLUSIONS—A wide gap exists between practice recommendations and delivery of diabetes care in Delhi.
Clinical Benefit of a Gluten-Free Diet in Type 1 Diabetic Children With Screening-Detected Celiac Disease
Authors: Hansen Dorte , Brock-Jacobsen Bendt , Lund Elisabeth , Bjørn Christina , Hansen Lars P. , Nielsen Christian , Fenger Claus , Lillevang Søren T. , Husby Steffen
Published: October 2006

OBJECTIVE—This study was performed to 1) determine the prevalence of celiac disease in Danish children with type 1 diabetes and 2) estimate the clinical effects of a gluten-free diet (GFD) in patients with diabetes and celiac disease.

RESEARCH DESIGN AND METHODS—In a region comprising 24% of the Danish population, all patients <16 years old with type 1 diabetes were identified and 269 (89%) were included in the study. The diagnosis of celiac disease was suspected in patients with endomysium and tissue transglutaminase antibodies in serum and confirmed by intestinal biopsy. Patients with celiac disease were followed for 2 years while consuming a GFD.

RESULTS—In 28 of 33 patients with celiac antibodies, an intestinal biopsy showed villous atrophy. In 5 patients, celiac disease had been diagnosed previously, giving an overall prevalence of 12.3% (95% CI 8.6–16.9). Patients with celiac disease had a lower SD score (SDS) for height (P < 0.001) and weight (P = 0.002) than patients without celiac disease and were significantly younger at diabetes onset (P = 0.041). A GFD was obtained in 31 of 33 patients. After 2 years of follow-up, there was an increase in weight SDS (P = 0.006) and in children <14 years old an increase in height SDS (P = 0.036). An increase in hemoglobin (P = 0.002) and serum ferritin (P = 0.020) was found, whereas HbA1c remained unchanged (P = 0.311) during follow-up.

CONCLUSIONS—This population-based study showed the highest reported prevalence of celiac disease in type 1 diabetes in Europe. Patients with celiac disease showed clinical improvements with a GFD. We recommend screening for celiac disease in all children with type 1 diabetes.
Evaluation of a New Measure of Blood Glucose Variability in Diabetes
Authors: Kovatchev Boris P. , Otto Erik , Cox Daniel , Gonder-Frederick Linda , Clarke William
Published: October 2006

OBJECTIVE—Recent studies show the importance of controlling blood glucose variability in relationship to both reducing hypoglycemia and attenuating the risk for cardiovascular and behavioral complications due to hyperglycemia. It is therefore important to design variability measures that are equally predictive of low and high blood glucose excursions.

RESEARCH DESIGN AND METHODS—We introduce the average daily risk range (ADRR), a variability measure computed from routine self-monitored blood glucose (SMBG) data. The ADRR was constructed using a development dataset for 39 and 31 adults with type 1 and type 2 diabetes, respectively. The formula was then fixed, and the ADRR was compared against other variability measures using an independent validation dataset containing ∼4 months of SMBG for 254 and 81 adults with type 1 and type 2 diabetes.

RESULTS—From the 1st month of validation SMBG data, we computed the ADRR, blood glucose SD and coefficient of variation, daily blood glucose range and interquartile range, mean amplitude of glycemic excursion, M-value, and lability index. Then all measures were tested as predictors of low blood glucose (<2.2 mmol/l; <3.9 mmol/l) and high (>10 mmol/l; >22.2 mmol/l) events in the subsequent 3 months. The ADRR was the best predictor of both hypoglycemia and hyperglycemia, with a 6-fold increase in the likelihood of hypoglycemia and 3.5-fold increase in the likelihood of hyperglycemia across its risk categories.

CONCLUSIONS—In a large SMBG database, the ADRR showed strong association with subsequent out-of-control glucose readings. Compared with other variability measures, the ADRR demonstrated a superior balance of sensitivity to predicting both hypoglycemia and hyperglycemia. This prediction was independent from type of diabetes.
Residence time distribution study for the catalytic packing MULTIPAK®
Authors: Górak A. , Jaroszyński M. , Kołodziej A.
Published: October 2006

Residence time distribution (RTD) experiments were carried out using the catalytic packing MULTIPAK® in a 250 mm inner diameter column. The axial dispersion coefficients and dynamic liquid hold-up were derived from the RTD curves. Both hold-up and axial Péclet number were correlated in terms of gas and liquid Reynolds numbers. Free-draining experiments were performed to determine the dynamic and static liquid hold-ups.

The measured axial dispersion coefficients were higher than those presented in other studies. The dynamic hold-up derived from RTD agreed with total hold-up from free-draining experiments. The static hold-up was found very high, even higher than the dynamic one, due to the liquid accumulated inside the catalyst bed. Possibly, the liquid considered “static” from the viewpoint of the free-draining experiments becomes “dynamic” during the normal column operation.
Prediction of gaseous emissions from industrial stacks using an artificial intelligence method
Authors: Anghel C. , Ozunu A.
Published: October 2006

A novel technique based on artificial intelligence methods able to predict pollutant emission concentrations from industrial stacks is presented. This procedure combines regression and classification problems into a unified technique, named minimax decision procedure. The core of this procedure is based on the minimax probability machine regression model. Using experimental databases, the trend of pollutant emissions and the level of pollution for one industrial thermal power station stack were presented. Based on this unified technique, numerical experiments provided the estimates of concentrations of CO, NOx, NO, and SO2 confirming the predictive power of this procedure.
HIV‐related stigma in England: experiences of gay men and heterosexual African migrants living with HIV
Authors: Dodds Catherine
Published: October 2006

Focus group research was undertaken in three English cities among Gay and Bisexual men (British and non‐British), heterosexual African women and heterosexual African men, all with diagnosed HIV. It was found that prevalent social discourses of homophobia, racism and xenophobia underpin individuals' experiences of HIV‐related stigma. Members of marginalized communities themselves employ HIV‐related stigma as a governance mechanism to exclude positive people from tightly woven networks of support. Copyright © 2006 John Wiley & Sons, Ltd.
Church leaders confront HIV/AIDS and stigma: a case study from Tanzania
Authors: Hartwig Kari A. , Kissioki Seelah , Hartwig Charlotte D.
Published: October 2006

HIV/AIDS stigma continues to be a major obstacle to prevention and care interventions in Sub‐Saharan Africa. Faith‐based organizations (FBOs) have been shown to both foster HIV stigma as well as mitigate it. The present case study with 15 male and female Tanzanian church leaders emerged from a participatory evaluation workshop to assess their HIV health promoting activities following a series of HIV/AIDS and reproductive health training sessions. The workshop allowed participants to define root social causes of HIV underlying stigma and revealed the lack of a language to talk about stigma. Many participants in the discussions and focus groups had moved from positions of silence and condemnation to one of teaching about HIV/AIDS. Only 10 of the participants actively did some form of HIV education; they told how their own actions influenced their church membership's attitude towards HIV. However, others faced opposition from senior pastors. The case study suggests that narratives about HIV work within the church community create opportunities for reflection and compassion. We need further research on the role of different types of religious leaders in their institutions and the opportunities for diffusion and structural change. Copyright © 2006 John Wiley & Sons, Ltd.
From the physical self to the social body: expressions and effects of HIV‐related stigma in South Africa
Authors: Mills Elizabeth Anne
Published: October 2006

This paper discusses some of the forms and consequences of HIV‐related stigma in a community living in KTC, an informal settlement in South Africa, drawing on ethnographic research findings. The first section presents a dynamic form of stigma sign language that is used to label the HIV‐positive ‘other’ in this community. The second section highlights some of the pernicious consequences of HIV‐related stigma, including fear of disclosure and downward social mobility, and the way in which these prompt some HIV‐positive people to avoid local clinics and treatment altogether, and drive others to mask or hide the fact that they are receiving medical treatment, such as antiretroviral drugs. Copyright © 2006 John Wiley & Sons, Ltd.
The Biochemistry of Drug Metabolism – An Introduction
Authors: Testa Bernard , Krämer Stefanie D.
Published: October 2006

This paper reviews the general principles and concepts underlying Drug and Xenobiotic Metabolism. Its five Chapters deal with:1.1.Drugs and Xenobiotics,1.2.What are Drug Disposition and Metabolism?,1.3.Where does Drug Metabolism Occur?,1.4.Consequences of Drug Metabolism ‐‐ An Overview, and1.5.Drug Metabolism and Drug Discovery. This review is the first of seven Parts which will be published at intervals. The subsequent Parts will cover:2.Redox Reactions and Their Enzymes,3.Reactions of Hydrolysis and Their Enzymes,4.Conjugation Reactions and Their Enzymes,5.Metabolism and Bioactivity,6.Inter‐Individual Factors Affecting Drug Metabolism, and7.Intra‐Individual Factors Affecting Drug Metabolism.
Synthesis of 4/5‐Deoxy‐4/5‐nucleobase Derivatives of 3‐O‐Methyl‐D‐chiro‐inositol as Potential Antiviral Agents
Authors: Zhan Tian‐Rong , Ma Yu‐Dao , Fan Pei‐Hong , Ji Mei , Lou Hong‐Xiang
Published: October 2006

Using D‐pinitol (= 3‐O‐methyl‐D‐chiro‐inositol) as starting material, a concise synthesis of 4/5‐deoxy‐4/5‐nucleobase derivatives 11–19 has been achieved. The key intermediate 9 was obtained in good yield via an epoxidation from mono‐methanesulfonate of D‐pinitol. The process of opening of the epoxide ring in 9 by nucleobases appeared to be regioselective in presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). All the synthesized carbocyclic nucleosides were assayed against several viruses and tumors such as HIV‐1, HSV‐1, and HSV‐2, and lung and bladder cancer. However, only compounds 14b, 14a, 16a, 16b, and 19 showed mild inhibitory effect against human lung cancer cell lines (PG) with IC50 values ranging from 50 to 100 μM, and the other compounds did not exhibit any significant antiviral activity or cytotoxicity even at concentrations up to 200 μM.
Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols
Authors: Purser Sophie , Odell Barbara , Claridge Timothy D. W. , Moore Peter R. , Gouverneur Véronique
Published: October 2006

An asymmetric synthesis of enantioenriched, highly functionalized fluorinated carbocycles has been developed based on an enantioselective Sharpless dihydroxylation of cyclohexadienylsilanes, combined with a diastereoselective electrophilic fluorodesilylation. Several parameters define the level of diastereocontrol for the fluorination step. These include the relative stereochemistry of the starting endocyclic allylsilanes and the structural features of the reactants. As expected for an SE2′ mechanism, the fluorodesilylation occurred with clean transposition of the double bond, with the attack of the electrophilic fluorinating agent taking place preferentially anti to the silyl group. For the fluorination step, the best selectivities were observed for the monocyclic anti,syn benzyl‐protected precursors and for the syn,syn starting allylsilane. Full NMR spectroscopic analysis of the fluorinated monocyclic compounds, which possess an endocyclic double bond flanked by two electronegative groups (the methoxy group and the fluorine substituent) revealed that a subtle combination of steric (1,3‐axial/pseudoaxial interaction) and stereoelectronic effects (π–σ* interaction) favours the preferential conformers featuring the methoxy group in a pseudoaxial position.
Photosynthetic Reaction Center Mimicry of a “Special Pair” Dimer Linked to Electron Acceptors by a Supramolecular Approach: Self‐Assembled Cofacial Zinc Porphyrin Dimer Complexed with Fullerene(s)
Authors: D'Souza Francis , Chitta Raghu , Gadde Suresh , Rogers Lisa M. , Karr Paul A. , Zandler Melvin E. , Sandanayaka Atula S. D. , Araki Yasuyaki , Ito Osamu
Published: October 2006

Biomimetic bacterial photosynthetic reaction center complexes have been constructed using well‐defined self‐assembled supramolecular approaches. The “special pair” donor, a cofacial porphyrin dimer, was formed via potassium ion induced dimerization of meso‐(benzo‐[15]crown‐5)porphyrinatozinc. The dimer was subsequently self‐assembled with functionalized fullerenes via axial coordination and crown ether–alkyl ammonium cation complexation to form the donor–acceptor pairs, mimicking the noncovalently bound entities of the photosynthetic reaction center. The adopted self‐assembly methodology yielded supramolecular complexes of higher stability, with defined geometry and orientation. Efficient forward electron transfer from the singlet excited zinc porphyrin dimer to the fullerene entity and relatively slow reverse electron transfer, important steps in the photosynthetic light energy conversion have been achieved in these novel biomimetic model systems.
Total Synthesis of Peridinin and Related C37‐Norcarotenoid Butenolides
Authors: Vaz Belén , Domínguez Marta , Alvarez Rosana , de Lera Angel R.
Published: October 2006

As an extension of our synthesis of symmetrical carotenoids, the preparation of the highly functionalized C37‐norcarotenoid butenolide peridinin (1), its 6′‐epi‐ and 11′Z stereoisomers has been completed. Featuring a central dihalogenated C8 linchpin unit 6, two synthetic routes, differing in the ordering of the last three steps were explored by using the C3,C3′‐bisdehydroxylated target as the model system. The first route uses the combination of a modified Z‐selective Julia reaction and two sequential Stille couplings, the last one producing the isomerisation of the polyene Z double bond. The second route inverts these steps and makes the isolation of the 11′Z stereoisomers as major products possible. An efficient Z to E isomerisation of the final carotenoid skeleton simply uses the Stille reaction conditions at ambient temperature. As the reaction of bromoallene 12 with alkenylstannane 11 occurs with inversion of configuration, 6′‐epi‐peridinin could also be prepared by route A. The advantages and limitations of the sequential Stille cross‐coupling approach to carotenoids are highlighted.
Inorganic–Organic Hybrid Structures: Open‐Framework Iron Phosphite–Oxalates of Varying Dimensionality
Authors: Mandal Sukhendu , Natarajan Srinivasan
Published: October 2006

Inorganic–organic hybrid structures belonging to the family of iron phosphite–oxalates have been prepared by employing hydrothermal methods. Their structures, determined by single‐crystal X‐ray diffraction, show a hierarchy within the family. While compounds I and II are low dimensional, III–VI have three‐dimensional structures. Compound I has edge‐shared ladders of iron phosphite with oxalate units hanging from the iron centers. Compound II has a layer structure with a honeycomb‐like arrangement. The three‐dimensional hybrid structures have the oxalate units connected in both in‐plane and out‐of‐plane modes. A newly identified secondary building unit (SBU‐7) and the oxalate units satisfying the valence and coordination requirements in the structure of V are novel and noteworthy structural features. Magnetic studies show that the dominant interactions between the iron centers are antiferromagnetic. Similar to other known hybrid structures, the phosphite–oxalate structures appear to show wide compositional and structural diversity.
Numerical simulation of natural and mixed convection flows by Galerkin‐characteristic method
Authors: El‐Amrani Mofdi , Seaïd Mohammed
Published: October 2006

A numerical investigation is performed to study the solution of natural and mixed convection flows by Galerkin‐characteristic method. The method is based on combining the modified method of characteristics with a Galerkin finite element discretization in primitive variables. It can be interpreted as a fractional step technique where convective part and Stokes/Boussinesq part are treated separately. The main feature of the proposed method is that, due to the Lagrangian treatment of convection, the Courant–Friedrichs–Lewy (CFL) restriction is relaxed and the time truncation errors are reduced in the Stokes/Boussinesq part. Numerical simulations are carried out for a natural convection in squared cavity and for a mixed convection flow past a circular cylinder. The computed results are compared with those obtained using other Eulerian‐based Galerkin finite element solvers, which are used for solving many convective flow models. The Galerkin‐characteristic method has been found to be feasible and satisfactory. Copyright © 2006 John Wiley & Sons, Ltd.
Direct sensitivity analysis for smooth unsteady compressible flows using complex differentiation
Authors: Lu Shang‐Yi , Sagaut Pierre
Published: October 2006

A method for the direct computation of the instantaneous sensitivities of unsteady compressible flows is proposed. It is based on the complex differentiation of the full compressible Navier–Stokes equations and does not require the storage of the unsteady flow solution to be differentiated. The method does not rely on any assumption on the basic Navier–Stokes solver, and can therefore be implemented in a straightforward way. The method is assessed on several cases, including a two‐dimensional subsonic mixing layer. It is observed that the sensitivity patterns can be interpreted thanks to Kovasznay's decomposition for perturbations in a compressible flow. Copyright © 2006 John Wiley & Sons, Ltd.
Photophysical Investigations on Photoinitiators with Covalently Linked Thioxanthone Sensitizer Moieties
Authors: Dietliker Kurt , Broillet Stephanie , Hellrung Bruno , Rzadek Piotr , Rist Guenther , Wirz Jakob , Neshchadin Dmytro , Gescheidt Georg
Published: October 2006

The photophysical properties of three photoinitiators with a covalently linked thioxanthone sensitizer unit absorbing up to 410 nm were investigated by laser‐flash photolysis and CIDNP spectroscopy. These complementary techniques revealed two competing reaction pathways of the molecular dyads 1–3: i) triplet‐energy transfer from the sensitizer to the morpholine moiety followed by α‐cleavage to yield a radical pair, which initiates radical polymerization, and ii) bimolecular electron transfer from the morpholine to the thioxanthone subunit followed by proton transfer. The relative efficiency of these routes is determined by the triplet energy of the photoinitiator moiety relative to that of the sensitizer.
Rearrangements in Model Peptide‐Type Radicals via Intramolecular Hydrogen‐Atom Transfer
Authors: Moran Damian , Jacob Rebecca , Wood Geoffrey P. F. , Coote Michelle L. , Davies Michael J. , O'Hair Richard A. J. , Easton Christopher J. , Radom Leo
Published: October 2006

Intramolecular H‐atom transfer in model peptide‐type radicals was investigated with high‐level quantum‐chemistry calculations. Examination of 1,2‐, 1,3‐, 1,5‐, and 1,6[C ↔ N]‐H shifts, 1,4‐ and 1,7[C ↔ C]‐H shifts, and 1,4[N ↔ N]‐H shifts (Scheme 1), was carried out with a number of theoretical methods. In the first place, the performance of UB3‐LYP (with the 6‐31G(d), 6‐31G(2df,p), and 6‐311+G(d,p) basis sets) and UMP2 (with the 6‐31G(d) basis set) was assessed for the determination of radical geometries. We found that there is only a small basis‐set dependence for the UB3‐LYP structures, and geometries optimized with UB3‐LYP/6‐31G(d) are generally sufficient for use in conjunction with high‐level composite methods in the determination of improved H‐transfer thermochemistry. Methods assessed in this regard include the high‐level composite methods, G3(MP2)‐RAD, CBS‐QB3, and G3//B3‐LYP, as well as the density‐functional methods B3‐LYP, MPWB1K, and BMK in association with the 6‐31+G(d,p) and 6‐311++G(3df,3pd) basis sets. The high‐level methods give results that are close to one another, while the recently developed functionals MPWB1K and BMK provide cost‐effective alternatives. For the systems considered, the transformation of an N‐centered radical to a C‐centered radical is always exothermic (by 25 kJ ⋅ mol−1 or more), and this can lead to quite modest barrier heights of less than 60 kJ ⋅ mol−1 (specifically for 1,5[C ↔ N]‐H and 1,6[C ↔ N]‐H shifts). H‐Migration barriers appear to decrease as the ring size in the transition structure (TS) increases, with a lowering of the barrier being found, for example when moving from a rearrangement proceeding via a four‐membered‐ring TS (e.g., the 1,3[C ↔ N]‐H shift, CH3C(O)NH. → .CH2C(O)NH2) to a rearrangement proceeding via a six‐membered‐ring TS (e.g., the 1,5[C ↔ N]‐H shift, .NHCH2C(O)NHCH3 → NH2CH2C(O)NHCH2.).
Titanocene‐Mediated Homolytic Opening of Epoxysilanes
Authors: Puljic Nicolas , Albert Matthias , Dhimane Anne‐Lise , Fensterbank Louis , Lacôte Emmanuel , Malacria Max
Published: October 2006

The titanocene(III) chloride mediated opening of silyloxiranes has been examined. Electron transfer from the metal leads to α‐silyl radicals with total regiocontrol. The radicals could be trapped by various olefins, and the corresponding adducts were obtained in good yields (Table). Further substitution of the oxirane by alkyl groups proved detrimental to the reactions, but ring opening remained essentially regioselective.
The Tris(trimethylsilyl)silane/Thiol Reducing System: A Tool for Measuring Rate Constants for Reactions of Carbon‐Centered Radicals with Thiols
Authors: Chatgilialoglu Chryssostomos
Published: October 2006

An extension of the well‐known ‘free‐radical‐clock’ methodology is described that allows one to determine the rate constants of carbon‐centered radicals with a variety of thiols by using the tris(trimethylsilyl)silane/thiol couple as a reducing system. A total of 20 rate constants for the hydrogen abstraction from a variety of alkyl‐, silyl‐, and aryl‐substituted thiols by the primary‐alkyl radical 2 in toluene at 80° were determined with the aid of the 5‐exo‐trig cyclization as a timing device. Further, seven rate constants for the hydrogen abstraction from a variety of alkyl‐ and silyl‐substituted thiols by the acyl radical 9 in benzene at 80° were measured using the decarbonylation process as a timing device. The rate constants varied over two orders of magnitude from 106 to 108 M−1 s−1. Substituent effects were rationalized. The radical‐trapping abilities of these reducing systems and those of other common hydrogen donors were compared.
Trifluoromethyl‐Radical‐Mediated Carbonylation of Alkanes Leading to Ethynyl Ketones
Authors: Uenoyama Yoshitaka , Fukuyama Takahide , Morimoto Keisuke , Nobuta Osamu , Nagai Hidefumi , Ryu Ilhyong
Published: October 2006

The carbonylation of alkanes 1 under radical‐reaction conditions was examined by using ethynyl triflone A as the unimolecular chain‐transfer (UMCT) reagent. Good to moderate yields of ethynyl ketones 2 were prepared by means of this three‐component coupling reaction. Higher CO pressures as well as lower concentrations of triflone A improved the efficiency of the reaction over the direct addition, the latter leading to alkylated ethynes 3. In contrast to the reaction with A, the reaction of cyclohexane (1a) with allyl triflone B (= ethyl 2‐methylene‐3‐[(trifluoromethyl)sulfonyl]propanoate) in the presence of CO gave a mixture of carbonylation products, including 8a formed from two molecules each of cyclohexane, CO, and allyl triflone B.
Suppression of ovarian cancer by muscle‐mediated expression of soluble VEGFR‐1/Flt‐1 using adeno‐associated virus serotype 1‐derived vector
Authors: Takei Yuji , Mizukami Hiroaki , Saga Yasushi , Yoshimura Ichiro , Hasumi Yoko , Takayama Takeshi , Kohno Takahiro , Matsushita Takashi , Okada Takashi , Kume Akihiro , Suzuki Mitsuaki , Ozawa Keiya
Published: October 2006

Vascular endothelial growth factor (VEGF) is known to play a major role in angiogenesis in a variety of tumors. A soluble form of Flt‐1 (sFlt‐1), a VEGF receptor, is potentially useful as an antagonist of VEGF, and accumulating evidences suggest the applicability of sFlt‐1 in tumor suppression by means of anti‐angiogenesis. We previously demonstrated the efficacy of sflt‐1 gene expression in situ to suppress tumor growth and ascites in ovarian cancer. Here, we demonstrate the therapeutic applicability of muscle‐mediated expression of sFlt‐1 in tumor‐bearing mice. Initially, tumor suppressive action was confirmed by inoculating sFlt‐1‐expressing ovarian cancer (SHIN‐3) cells into mice, both subcutaneously and intraperitoneally. To validate the therapeutic efficacy in a more clinically relevant model, adeno‐associated virus vectors encoding sflt‐1 were introduced into mouse skeletal muscles and were subsequently inoculated with tumor cells. As a result, high serum sFlt‐1 levels were constantly observed, and the growth of both subcutaneously‐ and intraperitoneally‐inoculated tumors was significantly suppressed. No delay in wound healing or adverse events of neuromuscular damage were noted, body weight did not change, and laboratory data, such as those representing liver and renal functions, were not affected. These results indicate that sFlt‐1 suppresses growth and peritoneal dissemination of ovarian cancer by the inhibition of angiogenesis, and thus suggest the usefulness of gene therapy for ovarian cancer. © 2006 Wiley‐Liss, Inc.
Life‐style and environmental factors in the development of nasal NK/T‐cell lymphoma: A case–control study in East Asia
Authors: Xu Jing‐Xian , Hoshida Yoshihiko , Yang Woo‐Ick , Inohara Hidenori , Kubo Takeshi , Kim Gwi‐Eon , Yoon Joo‐Heon , Kojya Shizuo , Bandoh Nobuyuki , Harabuchi Yasuaki , Tsutsumi Kouichiro , Koizuka Izumi , Jia Xin‐Shan , Kirihata Mitsunori , Tsukuma Hideaki , Aozasa Katsuyuki
Published: October 2006

Cases of nasal NK/T‐cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life‐style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000–2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74–9.87) for farmers, 2.81 (CI, 1.49–5.29) for producers of crops, 4.01 (CI, 1.99–8.09) for pesticide users, 11.65 (CI, 1.17–115.82) for residents near garbage burning plants, 2.95 (CI, 1.25–6.95) for former drinkers, and 0.49 (CI, 0.23–1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28–8.54), 1.18 (95% CI, 0.11–12.13) and 2.20 (95% CI, 0.88–5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life‐style and environmental factors might be risk factors for NKTCL. © 2006 Wiley‐Liss, Inc.
Overexpression of regucalcin suppresses cell response for tumor necrosis factor‐α or transforming growth factor‐β1 in cloned normal rat kidney proximal tubular epithelial NRK52E cells
Authors: Nakagawa Taeko , Yamaguchi Masayoshi
Published: October 2006

The regulatory role of regucalcin on cell responses for tumor necrosis factor‐α (TNF‐α) or transforming growth factor‐β1 (TGF‐β1) was investigated using the cloned normal rat kidney proximal tubular epithelial NRK52E cells overexpressing regucalcin. NRK52E cells (wild type) and stable regucalcin (RC)/pCXN2‐transfected cells (transfectant) were cultured for 72 h in a medium containing 5% bovine serum (BS) to obtain subconfluent monolayers. After culture, cells were further cultured for 24–72 h in medium without BS containing either vehicle, TNF‐α (0.1 or 1.0 ng/ml of medium), or TGF‐β1 (1.0 or 5.0 ng/ml). Culture with TNF‐α or TGF‐β1 caused a significant decrease in the number of wild‐type cells. This decrease was significantly prevented in transfectants overexpressing regucalcin. Agarose gel electrophoresis showed the presence of low‐molecular‐weight deoxyribonucleic acid (DNA) fragments of adherent wild‐type cells cultured with TNF‐α (1.0 ng/ml) or TGF‐β1 (5.0 ng/ml). This DNA fragmentation was significantly suppressed in transfectants. TNF‐α‐ or TGF‐β1‐induced cell death was significantly prevented in culture with caspase‐3 inhibitor (10−8 M). Nitric oxide (NO) synthase activity in wild‐type cells was significantly increased by addition of calcium chloride (10 µM) and calmodulin (5 µg/ml) into the enzyme reaction mixture. This increase was significantly suppressed in transfectants. Culture with TNF‐α caused a significant increase in NO synthase activity in wild‐type cells. The effect of TNF‐α was not seen in transfectants. Culture with TGF‐β1 did not cause a significant increase in NO synthase activity in wild‐type cells and transfectants. Culture with TNF‐α or TGF‐β1 caused a remarkable increase in α‐smooth muscle actin in wild‐type cells. This increase was significantly prevented in transfectants. The expression of Smad 2 or NF‐κB mRNAs was significantly increased in transfectants as compared with that of wild‐type cells. Smad 3 or glyceroaldehyde‐3‐phosphate dehydrogenase (G3PDH) mRNA expression was not significantly changed in transfectants. NF‐κB mRNA expression in wild‐type cells was significantly increased with culture of TNF‐α. Smad 2 mRNA expression was significantly enhanced in wild‐type cells cultured with TGF‐β1. These effects of TNF‐α or TGF‐β1 were not significantly enhanced in transfectants. This study demonstrates that overexpression of regucalcin has suppressive effects on cell responses which are mediated through intracellular signaling pathways of TNF‐α or TGF‐β1 in kidney NRK52E cells. J. Cell. Biochem. 100: 1178–1190, 2007. © 2006 Wiley‐Liss, Inc.
A role for PLCγ2 in platelet activation by homocysteine
Authors: Leoncini Giuliana , Bruzzese Debora , Signorello Maria Grazia
Published: October 2006

The aim of this study was to examine the homocysteine effect on phospholipase Cγ2 (PLCγ2) activation and to investigate the signaling pathway involved. We found that homocysteine stimulated the tyrosine phosphorylation and activation of platelet PLCγ2. The tyrosine kinases p60src and p72syk appeared to be involved upstream. Reactive oxygen species were increased in homocysteine treated platelets. Likely oxidative stress could prime the non receptor‐mediated tyrosine kinase p60src, inducing phosphorylation and activation of p72syk. The antioxidant N‐acetyl‐L‐cysteine prevented the activation of these kinases. The phosphorylation and activation of PLCγ2 were greatly reduced by the inhibition of p72syk through piceatannol. Moreover indomethacin diminished the homocysteine effect on p60src, p72syk and PLCγ2, suggesting that thromboxane A2 could be involved. In addition the treatment of platelets with homocysteine caused intracellular calcium rise and protein kinase C activation. Finally homocysteine induced platelet aggregation, that was partially reduced by indomethacin and by N‐acetyl‐L‐cysteine of 35% or 50% respectively, while the PLCγ2 specific inhibitor U73122 diminished platelet response to homocysteine of 70%. Altogether the data indicate that PLCγ2 plays an important role in platelet activation by homocysteine and that the stimulation of this pathway requires signals through oxygen free radicals and thromboxane A2. J. Cell. Biochem. 100: 1255–1265, 2007. © 2006 Wiley‐Liss, Inc.
Gastric neuroendocrine carcinoma: Clinicopathologic review and immunohistochemical study of E‐cadherin and Ki‐67 as prognostic markers
Authors: Boo Yoon‐Jung , Park Sung‐Soo , Kim Jong‐Han , Mok Young‐Jae , Kim Seong‐Joo , Kim Chong‐Suk
Published: October 2006

Background and Objectives

Gastric neuroendocrine carcinoma (NEC) is an uncommon cancer of the stomach. The classification of NEC and its clinical behavior remains controversial, and prognostic markers and their therapeutic guidelines have not been clearly defined. The aim of this study was to evaluate the clinicopathologic characteristics of these tumors and analyze the expression of E‐cadherin and Ki‐67 as prognostic markers in gastric NECs.

Methods

We retrospectively reviewed 17 cases of gastric NECs. Tumor pathology was reviewed and the tumors were categorized as well‐differentiated NEC (n = 5) and poorly differentiated NEC (n = 12) according to the WHO classification. With the aim of evaluating the expression of E‐cadherin and Ki‐67 and their prognostic role in gastric NEC, immunohistochemical analysis of the tumors was performed.

Results

The median survival of patients was 20.0 months (95% confidence interval (CI), 13.2–28.8). There was a statistically significant difference in overall survival between well and poorly differentiated NECs (P = 0.021). However, there was no significant difference in overall survival between patients with poorly differentiated small cell and large cell NEC (P = 0.796). Loss of E‐cadherin was correlated with lymph node metastasis (P= 0.044). A high Ki‐67 proliferation index (PI) (>60%) was correlated with tumor recurrence (P = 0.013) and histologic differentiation (P= 0.028).

Conclusions

Loss of E‐cadherin may predict lymph node metastasis in gastric NECs. A high Ki‐67 PI (>60%) could be used as a prognostic marker to predict aggressive gastric NECs in addition to standard pathologic classification. J. Surg. Oncol. 2007;95:110–117. © 2007 Wiley‐Liss, Inc.
Speciation of arsenic by ion chromatography inductively coupled plasma mass spectrometry using ammonium eluents
Authors: Chen ZuLiang , Akter Kazi Farzana , Rahman Mohammad Mahmudur , Naidu Ravendra
Published: October 2006

A method based on ion chromatography (IC) and inductively coupled plasma MS (ICP‐MS) was developed for the speciation of arsenic in water and soil extracts. An anion‐exchange column (G3154A/101) was used to separate As(III), As(V), dimethylarsinic acid (DMA), and monomethylarsonic acid (MMA) with excellent resolution. Various ammonium salts, including NH4H2PO4, (NH4)2HPO4, (NH4)2CO3, and NH4HCO3, were examined as eluents to reduce matrix interference from chloride and to solve clogging problems. The best arsenic speciation was obtained within 9 min with excellent resolution and without interference from high chloride concentrations using an eluent containing 7.5 mM (NH4)2HPO4 at pH 7.9. The detection limits for the target arsenic species ranged from 0.1 to 0.4 μg/L with direct injection of sample without matrix elimination. The proposed method was effectively demonstrated by determining arsenic species in contaminated waters and soils of Bangladesh.
The pediatric preclinical testing program: Description of models and early testing results
Authors: Houghton Peter J. , Morton Christopher L. , Tucker Chandra , Payne Debbie , Favours Edward , Cole Claire , Gorlick Richard , Kolb E. Anders , Zhang Wendong , Lock Richard , Carol Hernan , Tajbakhsh Mimi , Reynolds C. Patrick , Maris John M. , Courtright Joshua , Keir Stephen T. , Friedman Henry S. , Stopford Charles , Zeidner Joseph , Wu Jianrong , Liu Tiebin , Billups Catherine A. , Khan Javed , Ansher Sherry , Zhang Jian , Smith Malcolm A.
Published: October 2006

Background

The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide.

Procedures

Solid tumors were grown subcutaneously in immune‐deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45‐positive cells were enumerated weekly.

Results

Vincristine‐induced objective responses in 6 of 24 (25%) and cyclophosphamide‐induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated.

Conclusions

We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad‐spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity. Pediatr Blood Cancer 2007;49:928–940. Published 2006 Wiley‐Liss, Inc.
Chinese herbal medicines used in pregnancy: a population‐based survey in Taiwan
Authors: Chuang Chao‐Hua , Hsieh Wu‐Shiun , Guo Yueliang Leon , Tsai Yih‐Jian , Chang Pei‐Jen , Lin Shio‐Jean , Chen Pau‐Chung
Published: October 2006

Purpose

To explore the use (prevalence and related factors) of Chinese herbal medicines used by pregnant women.

Methods

We used multistage stratified systematic sampling to recruit 2048 postpartum women from the Taiwan national birth register between November and December 2003. Subjects underwent a home interview 6 months after their deliveries. A structured questionnaire was successfully applied to 87% of the sampled population.

Results

At least one Chinese herbal medicine was used during pregnancy by 24.1% of the interviewed subjects. Pregnant women with threatened abortion appeared to use more Chinese herbal medicines than other pregnant women.

Conclusion

Chinese herbal medicines are frequently used by pregnant women in Taiwan and are very frequently used by those with a threatened abortion. Copyright © 2006 John Wiley & Sons, Ltd.