bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific
Authors: Chamson-Reig Astrid , Thyssen Sandra M , Arany Edith , Hill David J
Published: October 2006

Restriction of dietary protein during gestation and lactation in the rat results in a reduction in β cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1–2)), the second week only (LP (2)), or the third week (LP (3)). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 μm2) and medium (between 5000 and 10 000 μm2) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of β cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in mid-gestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both β cell development and insulin gene transcription, was decreased in female offspring following LP (1–2) and LP (3), but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of β cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of β cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.
Plasma hormone levels in the green turtles Chelonia mydas during peak period of nesting at Ras Al-Hadd-Oman
Authors: Al-Habsi A A , AlKindi A Y A , Mahmoud I Y , Owens D W , Khan T , al-Abri Aisha
Published: October 2006

Circulating estradiol (E2), progesterone (Pro), testosterone, and corticosterone (B) levels were monitored in the green turtles Chelonia mydas during different nesting phases. Successful nesting includes emergence from sea, chamber and nest excavation, oviposition, burying the nest, and returning to sea. Unsuccessful nesting includes chamber and nest excavations but without oviposition. Blood samples were taken from the cervical sinus and collected within 5-min of capture to minimize stress. The samples were collected between 2000 and 0100 h during the peak season (May–October). High-performance liquid chromatography using a u.v. detection system coupled with tandem quadrupole mass spectrometry was used to measure B. Plasma B levels were significantly higher in successful and unsuccessful phases over emergence and excavation phases. However, B levels in successful versus unsuccessful or emergence versus excavation phases were not significantly different. Plasma steroid levels were measured by the Coat-A-Count RIA technique. Pro levels were significantly higher (P<0.005) in successful over unsuccessful turtles and also successful turtles over turtles in the other phases (P<0.01). The Pro levels immediately after nesting were found to be higher than that reported previously. Plasma testosterone values were higher in successful turtles but not significantly different from the turtles in other phases. Estrogen levels were undetected in all phases. Overall, the hormone values during different phases of nesting may play a major role in formulating the nesting behavior and physiology of the nesting activities in the green turtle.
Immunocytochemical identification of low-affinity NTS2 neurotensin receptors in parietal cells of human gastric mucosa
Authors: Schulz Stefan , Röcken Christoph , Ebert Matthias P A , Schulz Solveig
Published: October 2006

The biological effects of neurotensin (NT) are mediated by two distinct G protein-coupled receptors, NTS1 and NTS2. Although it is well established that neurotensin inhibits gastric acid secretion in man, the plasma membrane receptor mediating these effects has not been visualized yet. We developed and characterized a novel antipeptide antibody to the carboxy-terminal region of the human NTS2 receptor. The cellular and subcellular distribution of NTS2 receptors was evaluated in various human gastrointestinal tissues. Specificity of the antiserum was demonstrated by (1) detection of a broadband migrating at Mr 90 000–100 000 in Western blots of membranes from NTS2-expressing tissues; (2) cell-surface staining of NTS2-transfected cells; (3) translocation of NTS2 receptor immunostaining after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with its immunizing peptide. In the gastrointestinal tract, NTS2 receptor immunoreactivity was highly abundant in parietal cells of the gastric mucosa, in neuroendocrine cells of the stomach small and large intestine, and in cells of the exocrine pancreas. NTS2 receptors were clearly located in the plasma membrane and uniformly present on nearly all target cells. The presence of NTS2 receptors was rarely detected in human tumors. This is the first localization of NTS2 receptors in human formalin-fixed, paraffin-embedded tissues at the cellular level. The abundant expression of low-affinity NTS2 receptors on the plasma membrane of human parietal cells provides a morphological substrate for the direct inhibition of gastric acid secretion observed after i.v. administration of neurotensin.
cAMP response element-binding (CREB) signalling and ovarian surface epithelial cell survival
Authors: Gubbay O , Rae M T , McNeilly A S , Donadeu F X , Zeleznik A J , Hillier S G
Published: October 2006

cAMP response-element binding (CREB) transcription factors transduce cell survival responses to peptide hormones and growth factors in normal tissues and mutant CREB proteins are implicated in tumorigenesis. Ovarian cancer most frequently arises from the ovarian surface epithelium (OSE), possibly due to repeat inflammation-associated injury-repair episodes that promote neoplasia. We asked if post-receptor signalling involving the CREB family of proteins plays a role in OSE cell survival. In an ovine ovulation model, abundant expression of phospho-CREB/activating transcription factor (ATF) protein was detected immunohistochemically, strongly localised to OSE cells in the proximity of pre-ovulatory follicles. Treatment of primary sheep OSE cell cultures with LH stimulated cAMP accumulation and reduced apoptosis (caspase 3/7 activity) in response to serum withdrawal. When OSE cells were infected with an adenovirus containing a CRE-luciferase construct, exposure to LH and FSH induced CRE-directed transcription. Finally, when a non-phosphorylatable mutant of CREB (Ad CREBS133A) was adenovirally expressed, apoptosis measured by activation of caspases was increased several fold relative to that caused by transfection with wild-type CREB (Ad CREBWT) or lacZ (Ad lacZ). To test the potential clinical relevance of these findings, we expressed mutant CREB protein in normal human OSE cells from four women and a series of cell lines derived from human ovarian cancers. Infection with Ad CREBS133A markedly increased apoptosis in normal human OSE but had no detectable effect on apoptosis in any of the cancer cell lines. We conclude that CREB/ATF signalling is important for the maintenance of OSE cell survival in vitro and is altered in human cell lines derived from ovarian cancers.
Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: detection of a non-endothelial function of VEGF in pituitary tumours
Authors: Onofri Chiara , Theodoropoulou Marily , Losa Marco , Uhl Eberhard , Lange Manfred , Arzt Eduardo , Stalla Günter K , Renner Ulrich
Published: October 2006

As for any solid tumour, pituitary adenoma expansion is dependent on neovascularization through angiogenesis. In this process, vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) may play an outstanding role. The intention of this work was to study the expression/localization and possible function of VEGF receptors in pituitary adenomas. VEGF receptor mRNA and protein expression was studied by in situ hybridization, immunohistochemistry and RT-PCR in 6 normal human pituitaries, 39 human pituitary adenomas and 4 rodent pituitary adenoma cell lines. VEGFR-1 expressing somatotroph MtT-S cells were used as a model to study the role of VEGF on cell proliferation and to elucidate the underlying mechanism of action. In normal pituitaries, VEGFR-1 was detected in endocrine cells, whereas VEGFR-2 and NRP-1 were exclusively expressed in endothelial cells. In pituitary tumours, a heterogeneous VEGFR expression pattern was observed by IHC. VEGFR-1, VEGFR-2 and NRP-1 were detected in 24, 18 and 17 adenomas respectively. In the adenomas, VEGFR-1 was expressed in epithelial tumour cells and VEGFR-2/NRP-1 in vessel endothelial cells. Functional studies in VEGFR-1-positive MtT-S cells showed that the ligands of VEGFR-1 significantly stimulated cell proliferation. This effect was mediated through the phosphatidylinositol-3-kinase-signalling pathway and involves induction of cyclin D1 and Bcl-2. Based on our results, we speculate that the ligands of VEGF receptors, such as VEGF-A and placenta growth factor, not only play a role in angiogenesis in pituitary adenomas, but also affect the growth of pituitary tumour cells through VEGFR-1.
Saturated, but Not Unsaturated, Fatty Acids Induce Apoptosis of Human Coronary Artery Endothelial Cells via Nuclear Factor-κB Activation
Authors: Staiger Katrin , Staiger Harald , Weigert Cora , Haas Carina , Häring Hans-Ulrich , Kellerer Monika
Published: October 2006

High nonesterified fatty acid (NEFA) concentrations, as observed in the metabolic syndrome, trigger apoptosis of human umbilical vein endothelial cells. Since endothelial apoptosis may contribute to atherothrombosis, we studied the apoptotic susceptibility of human coronary artery endothelial cells (HCAECs) toward selected NEFAs and the underlying mechanisms. HCAECs were treated with single or combined NEFAs. Apoptosis was quantified by flow cytometry, nuclear factor κB (NFκB) activation by electrophoretic mobility shift assay, and secreted cytokines by enzyme-linked immunosorbent assay. Treatment of HCAECs with saturated NEFAs (palmitate and stearate) increased apoptosis up to fivefold (P < 0.05; n = 4). Unsaturated NEFAs (palmitoleate, oleate, and linoleate) did not promote apoptosis but prevented stearate-induced apoptosis (P < 0.05; n = 4). Saturated NEFA-induced apoptosis neither depended on ceramide formation nor on oxidative NEFA catabolism. However, NEFA activation via acyl-CoA formation was essential. Stearate activated NFκB and linoleate impaired stearate-induced NFκB activation. Pharmacological inhibition of NFκB and inhibitor of κB kinase (IKK) also blocked stearate-induced apoptosis. Finally, the saturated NEFA effect on NFκB was not attributable to NEFA-induced cytokine production. In conclusion, NEFAs display differential effects on HCAEC survival; saturated NEFAs (palmitate and stearate) are proapoptotic, and unsaturated NEFAs (palmitoleate, oleate, and linoleate) are antilipoapoptotic. Mechanistically, promotion of HCAEC apoptosis by saturated NEFA requires acyl-CoA formation, IKK, and NFκB activation.
Defective Metabolism of Oxidized Phospholipid by HDL From People With Type 2 Diabetes
Authors: Mastorikou Maria , Mackness Mike , Mackness Bharti
Published: October 2006

HDL protects against atherosclerosis development. Defective functioning of HDL in type 2 diabetes may be one cause of increased cardiovascular disease associated with type 2 diabetes. HDL modulates LDL oxidation through the action of paraoxonase-1 (PON1), which is one of the major mechanisms by which HDL is antiatherogenic. We have compared the ability of HDL from people with type 2 diabetes (n = 36) with no coronary heart disease (CHD) to metabolize oxidized palmitoyl arachidonyl phosphatidylcholine (ox-PAPC), a major product of LDL oxidation and a PON1 substrate, with that of HDL isolated from healthy control subjects (n = 19) and people with CHD but no diabetes (n = 37). HDL from people with type 2 diabetes metabolized 11% less ox-PAPC, and HDL from people with CHD metabolized 6% less, compared with HDL from control subjects (both P < 0.01). The ability of HDL from control and type 2 diabetic subjects containing the PON1-192RR alloform to metabolize ox-PAPC was significantly reduced compared with PON1-192QQ or QR genotypes (P < 0.05). The defective ability of HDL to metabolize ox-PAPC was reflected in a significant increase in circulating plasma oxidized LDL concentration in the two patient groups (37 ± 5, 53 ± 7, and 65 ± 7 mmol/l for control, CHD, and type 2 diabetic subjects, respectively; P < 0.001), with PON1-192RR genotype carriers having the highest concentrations. In the control group, there was a significant negative correlation between serum PON1 activity and oxidized LDL concentration (r = 0.856, P < 0.001); however, this correlation was not evident in the patient groups. HDL from type 2 diabetic subjects without CHD had a decreased ability to metabolize oxidized phospholipids, which could lead to increased susceptibility to develop cardiovascular disease.
Islet Microvasculature in Islet Hyperplasia and Failure in a Model of Type 2 Diabetes
Authors: Li Xianquan , Zhang Lanjing , Meshinchi Sasha , Dias-Leme Claudia , Raffin Diane , Johnson Jeffery D. , Treutelaar Mary K. , Burant Charles F.
Published: October 2006

Gene expression profiling of islets from pre-diabetic male Zucker diabetic fatty (ZDF) rats showed increased expression of hypoxia-related genes, prompting investigation of the vascular integrity of the islets. The islet microvasculature was increased approximately twofold in young male ZDF rats by both morphometric analysis and quantifying mRNA levels of endothelial markers. ZDF rats at 12 weeks of age showed a significant reduction in the number of endothelial cells, which was prevented by pretreatment with pioglitazone. Light and electron microscopy of normoglycemic 7-week-old ZDF rats showed thickened endothelial cells with loss of endothelial fenestrations. By 12 weeks of age, there was disruption of the endothelium and intra-islet hemorrhage. Islets from 7- and 12-week-old ZDF rats showed an approximate three- and twofold increase in vascular endothelial growth factor (VEGF)-A mRNA and VEGF protein secretion, respectively, compared with lean controls. Thrombospondin-1 mRNA increased in 7- and 12-week-old rats by 2- and 10-fold, respectively, and was reduced by 50% in 12-week-old rats pretreated with pioglitazone. Islets from young male control rats induced migration of endothelial cells in a collagen matrix only after pretreatment with matrix metalloproteinase (MMP)-9. Islets from 7-week-old ZDF rats showed a fivefold increase in migration score compared with wild-type controls, even without MMP-9 treatment. Islets from 15-week-old ZDF rats did not induce migration; rather, they caused a significant rounding up of the duct-derived cells, suggesting a toxic effect. These data suggest that in the ZDF rat model of type 2 diabetes, an inability of the islet to maintain vascular integrity may contribute to β-cell failure.
Multi-Objective Design Problem of Tire Wear and Visualization of Its Pareto Solutions
Authors: Koishi M. , Shida Z.
Published: October 2006

Since tires carry out many functions and many of them have tradeoffs, it is important to find the combination of design variables that satisfy well-balanced performance in conceptual design stage. To find a good design of tires is to solve the multi-objective design problems, i.e., inverse problems. However, due to the lack of suitable solution techniques, such problems are converted into a single-objective optimization problem before being solved. Therefore, it is difficult to find the Pareto solutions of multi-objective design problems of tires. Recently, multi-objective evolutionary algorithms have become popular in many fields to find the Pareto solutions. In this paper, we propose a design procedure to solve multi-objective design problems as the comprehensive solver of inverse problems. At first, a multi-objective genetic algorithm (MOGA) is employed to find the Pareto solutions of tire performance, which are in multi-dimensional space of objective functions. Response surface method is also used to evaluate objective functions in the optimization process and can reduce CPU time dramatically. In addition, a self-organizing map (SOM) proposed by Kohonen is used to map Pareto solutions from high-dimensional objective space onto two-dimensional space. Using SOM, design engineers see easily the Pareto solutions of tire performance and can find suitable design plans. The SOM can be considered as an inverse function that defines the relation between Pareto solutions and design variables. To demonstrate the procedure, tire tread design is conducted. The objective of design is to improve uneven wear and wear life for both the front tire and the rear tire of a passenger car. Wear performance is evaluated by finite element analysis (FEA). Response surface is obtained by the design of experiments and FEA. Using both MOGA and SOM, we obtain a map of Pareto solutions. We can find suitable design plans that satisfy well-balanced performance on the map called “multi-performance map.” It helps tire design engineers to make their decision in conceptual design stage.
Influence of biomass on hydrodynamics of an internal loop airlift reactor
Authors: Juraščík M. , Hucík M. , Sikula I. , Annus J. , Markoš J.
Published: October 2006

The effect of the biomass presence on the overall circulation velocity, the linear velocities both in the riser and the downcomer and the overall gas hold-up was studied in a three-phase internal loop airlift reactor (ILALR). The measured data were compared with those obtained using a two-phase system (air—water). All experiments were carried out in a 40 dm3 ILALR at six different biomass concentrations (ranging from 0 g dm−3 to 7.5 g dm−3), at a temperature of 30°C, under atmospheric pressure. Air and water were used as the gas and liquid model media, respectively. Pellets of Aspergillus niger produced during the fermentation of glucose to gluconic acid in the ILALR were considered solid phase. In addition, liquid velocities were measured during the fermentation of glucose to gluconic acid using Aspergillus niger. All measurements were performed in a bubble circulation regime. At given experimental conditions the effect of the biomass on the circulation velocities in the ILALR was negligible. However, increasing of the biomass concentration led to lower values of the total gas hold-up.
Selection of carrier for immobilization of fructosyltransferase from Aureobasidium pullulans
Authors: Platková Z. , Polakovič M. , Štefuca V. , Vandáková M. , Antošová M.
Published: October 2006

The study deals with the development of an immobilized biocatalyst for the production of fructooligosaccharides. Several commercial anion-exchange resins and polymethacrylate carriers were tested for the immobilization either by the direct attachment of fructosyltransferase or by the attachment accompanied by simultaneous glutaraldehyde crosslinking in the pH range from 5.7 to 7.1. On the basis of the efficiency of immobilization and the storage stability, Amberlite IRA 900 and Dowex Marathon MSA were selected as the best carriers for fructosyltransferase immobilization by direct attachment at pH 5.7.
Homozygosity of the interleukin‐10 receptor 1 G330R allele is associated with schizophrenia
Authors: Schosser Alexandra , Aschauer Harald N. , Wildenauer Dieter B. , Schwab Sibylle G. , Albus Margot , Maier Wolfgang , Schloegelhofer Monika , Leisch Friedrich , Hornik Kurt , Murray Sarah S. , Gasche Christoph
Published: October 2006

Infections of unknown origin and an altered immune response have been hypothesized to play a role in the pathogenesis of schizophrenia. We have previously identified two single nucleotide polymorphisms (SNPs) of the IL‐10 receptor 1 (IL‐10R1) causing a substitution of glycine 330 to arginine (G330R) and of serine 138 to glycine (S138G). A possible association between these IL‐10R1 variants and schizophrenia has been investigated in the present study. DNA of 101 unrelated Austrian patients with a DSM‐III‐R (Diagnostic and Statistical Manual of Mental Disorders) consensus diagnosis of schizophrenia (n = 70) or schizoaffective disorder (n = 31) and DNA of 121 German schizophrenic patients (DSM‐III‐R) was analyzed for the presence of S138G and G330R by allele‐specific multiplex PCRs. Data from patients were compared with 250 unrelated, psychiatric healthy controls. No difference in allele frequency was detected between patients and controls (G330R: 34.0% vs. 30.0%, P = 0.208; S138G: 19.7% vs. 16.6%, P = 0.235; by Fisher's exact test). However, there was a significant difference in genotype distribution (wt/wt, wt/mut, mut/mut) for G330R between patients (46.8%, 38.3%, 14.9%) and controls (47.6%, 44.8%, 7.6%; Fisher's test P = 0.032). No such difference was seen for S138G. Our results suggest that homozygosity of the IL‐10R1 G330R allele is associated with schizophrenia and may contribute to the expression of disease phenotype in susceptible individuals. © 2006 Wiley‐Liss, Inc.
Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia
Authors: Del Zompo Maria , De Luca Vincenzo , Severino Giovanni , Ni Xingqun , Mulas Stefania , Congiu Donatella , Piccardi Maria Paola , Kennedy James L.
Published: October 2006

Based on the dopaminergic hypothesis, the dopamine D1 receptor gene (DRD1) is considered to be a good candidate gene involved in the susceptibility of bipolar disorder (BP). Genetic association between three DRD1 single nucleotide polymorphisms (SNPs) (−800T/C, −48A/G, and 1403T/C) and bipolar type I (BP I) disorder was performed in a case‐control sample of Sardinian origin (170 BP I and 209 controls) and in an enlarged sample (229 families) of BP I trios from Toronto. The haplotype analyses generated significant global chi‐square in both samples (P‐value 0.024 in Toronto and 0.00042 in Sardinian). The main representative haplotypes in both samples were the −800T/−48A/1403C and the −800C/−48G/1403T. Considering each group individually, the −800C/−48G/1403T was transmitted more frequently from parents to BP I probands in Toronto sample (nominally P‐value = 0.047) and was more frequent in cases than in control subjects in Sardinian sample although showing no significant evidence of association (nominally P‐value = 0.16) When the estimated haplotype counts of both samples were combined, the global χ2 was significant (P‐value = 0.00085) and the nominal P‐value for the haplotype −800C/−48G/1403T was 0.01. The fact that the same haplotype shows a similar trend for association in samples originating from different ethnic backgrounds seems to imply that the −800C/−48G/1403T haplotype may be considered as a risk factor for BP I disorder. © 2006 Wiley‐Liss, Inc.
Backbone dynamics determined by electron paramagnetic resonance to optimize solid‐phase peptide synthesis of TOAC‐labeled phospholamban
Authors: Zhang Zhiwen , Remmer Henriette A. , Thomas David D. , Karim Christine B.
Published: October 2006

Electron paramagnetic resonance (EPR) was used to optimize the solid‐phase peptide synthesis of a membrane‐bound peptide labeled with TOAC (2,2,6,6‐tetramethyl‐piperidine‐1‐oxyl‐4‐amino‐4‐carboxylic acid). The incorporation of this paramagnetic amino acid results in a nitroxide spin label coupled rigidly to the α‐carbon, providing direct detection of peptide backbone dynamics by EPR. We applied this approach to phospholamban, which regulates cardiac calcium transport. The synthesis of this amphipathic 52‐amino‐acid membrane peptide including TOAC is a challenge, especially in the addition of TOAC and the next several amino acids. Therefore, EPR of synthetic intermediates, reconstituted into lipid bilayers, was used to ensure complete coupling and 9‐fluorenylmethoxycarbonyl (Fmoc) deprotection. The attachment of Fmoc‐TOAC‐OH leads to strong immobilization of the spin label, whereas Fmoc deprotection dramatically mobilizes it, producing an EPR spectral peak that is completely resolved from that observed before deprotection. Similarly, coupling of the next amino acid (Ser) restores the spin label to strong immobilization, giving a peak that is completely resolved from that of the preceding step. For several subsequent steps, the effect of coupling and deprotection is similar but less dramatic. Thus, the sensitivity and resolution of EPR provides a quantitative monitor of completion at each of these critical steps in peptide synthesis. Mass spectrometry, circular dichroism, and Edman degradation were used in concert with EPR to verify the chemistry and characterize the secondary structure. In conclusion, the application of conventional analytical methods in combination with EPR offers an improved approach to optimize the accurate synthesis of TOAC spin‐labeled membrane peptides. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88:29–35, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.
The importance of addressing the unfolding TB‐HIV stigma in high HIV prevalence settings
Authors: Bond Virginia , Nyblade Laura
Published: October 2006

In the context of high HIV prevalence, tuberculosis is proving hard to control, becoming an increasingly prevalent disease and forcing a more integrated public health approach to the dual epidemics. Yet this integrated approach often overlooks the implications of how intertwined TB and HIV have become in the social reality of people living in high HIV prevalence settings. In this context, TB, the most common and serious of HIV's opportunistic infections in Sub‐Saharan Africa, has become progressively more stigmatised, and this paper argues, a new disease stigma has unfolded—namely TB‐HIV stigma. Rooted partly in judgement, blame and shame; fears of TB transmission; and public health practice and policy, TB‐HIV stigma has serious implications for TB outcomes and for management of HIV. The paper demonstrates the strength of the association between TB and HIV in urban and rural Zambia, how visible signs of TB become a trigger for TB‐HIV stigma, and explores three key causes of this stigma that could be addressed by integrated TB‐HIV services. Copyright © 2006 John Wiley & Sons, Ltd.
Pollution, peril and poverty: a British study of the stigmatization of smokers
Authors: Farrimond Hannah R. , Joffe Helene
Published: October 2006

This paper considers the symbolic, experiential and institutional basis of the stigmatization of British smokers, particularly in the context of the higher rates of smoking in lower socio‐economic status (SES) groups. Interviews based on a free association task were conducted with 40 smokers and non‐smokers from higher and lower SES groups. Thematic analysis identified several areas of stigmatization of British smokers by non‐smokers: identification of negative aesthetic ‘marks’ of smoking and of smokers as ‘polluters’ who harm others; the display of direct and indirect social disapproval; and the association of smokers with out‐groups such as single mothers. Higher SES smokers tend to challenge the ‘facts’ on which this stigmatization is based, whereas lower SES smokers internalize the stigmatized aspersions. Recent British Tobacco Control campaigns, which play on the negative aesthetic of the smoker and the ‘peril’ which they represent, may exacerbate stigmatization. This may have de‐motivating effects on lower SES smokers for reasons explored in the paper. Copyright © 2006 John Wiley & Sons, Ltd.
Unravelling the contexts of stigma: from internalisation to resistance to change
Authors: Campbell Catherine , Deacon Harriet
Published: October 2006

This special edition on ‘Understanding and Challenging Stigma’ seeks to further our understandings of the types of representations and practices through which stigma is perpetuated, the social contexts within which they are produced and reproduced, and the possibilities for agency, resistance and intervention. In this introductory piece, we outline three broad approaches to stigma in the existing literature—individual, macro‐social and multi‐level. Aligning ourselves with the latter, we discuss how social effects become sedimented in the individual psyche in ways that often make it difficult for stigmatised group members to resist their devalued social status. This insight frames our discussion of the papers in this volume—which cover various types of stigma, drawing on research in six countries. We focus on the ways in which the papers contribute to our understandings of (i) the material, political, institutional and symbolic contexts of stigma; (ii) the possibility of resistance to stigma; and (iii) the types of interventions most likely to facilitate such resistance. We conclude that the fields of social and community psychology have a central role to play in advancing the types of understandings that are so urgently needed to inform effective multi‐level stigma‐reduction interventions. Copyright © 2006 John Wiley & Sons, Ltd.
Thermotropic Lipid Phase Transition and the Behavior of Hydrolytic Enzymes in the Kidney Cortex Brush Border Membrane
Authors: Sanyal Sankar N. , Singh Gurdeep , Kanwar Shailender S.
Published: October 2006

Functional interactions of lipids and proteins were examined in brush‐border membranes isolated from the kidney cortex by studying the temperature dependence of the hydrolytic enzyme activities. A close relationship was observed for the membrane proteins and the thermotropic lipid phase transitions. Three lines of evidences were provided for such dependence: a) Arrhenius relationship of the membrane‐bound enzyme activities, and the effect of temperature in native and partially delipidated membranes, b) differential scanning calorimetric study of the membrane lipid phase transitions in the native and delipidated membranes, multilamellar vesicles prepared from the membrane extracted lipids, and in vesicles from dimyristoyl phosphatidylcholine, and c) the excimer (dimer)‐formation studies of the membrane extrinsic fluorescent probe, pyrene, and the resultant membrane microviscosity. The brush‐border membranes were partially delipidated with BuOH and 2,2,2‐trifluoroethanol. The functional interactions of the delipidated membranes, which were greatly lost on lipid removal, were largely restored by the addition of exogenous lipids in the reconstitution process, which indicate the critical dependence of the membrane integral proteins on the neighboring lipid molecules in the bulk lipid phase.
The Essential Oil of Lippia alba: Analysis of Samples from French Overseas Departments and Review of Previous Works
Authors: Hennebelle Thierry , Sahpaz Sevser , Dermont Charles , Joseph Henry , Bailleul François
Published: October 2006

This paper contains new data on the chemical composition of the essential oil of Lippia alba (Mill.) N. E. Brown, as well as an overview of the available literature. Although the composition of the essential oil of this species is well‐documented, discrepancies between the reported results suggest that many chemotypes and morphotypes exist. The analysis of essential oils obtained from the leaves of samples from three different locations in the French Overseas Departments (French Guiana, Martinique, and two different places in Guadeloupe) have shown that the composition of each one is quite different. This new data, along with a review and discussion of published studies, enabled us to establish seven distinct chemotypes (Tables 2 and 3). Possible connections between these chemotypes and morphotypes already described were also investigated.
Two New Taxanes from the Needles and Branches Bark of Taxus cuspidata
Authors: Cao Cong‐Mei , Zhang Man‐Li , Wang Yu‐Fang , Shi Qing‐Wen , Yamada Teiko , Kiyota Hiromasa
Published: October 2006

Two new taxanes were isolated from the MeOH extract of the needles and branches bark of the Japanese yew, Taxus cuspidata. The structures were established as (2α,5α,7β,9α,10β,13α)‐5,10,13,20‐tetraacetoxytax‐11‐ene‐2,7,9‐triol (1) and (2α,5α,9α,10β)‐2,9,10‐triacetoxy‐5‐[(β‐D‐glucopyranosyl)oxy]‐3,11‐cyclotax‐11‐en‐13‐one (2) on the basis of in‐depth 1D‐ and 2D‐NMR analyses (Tables 1–3, Fig. 1). Compound 2 is the first example of a transannular taxane glycoside isolated from a natural source.
An Efficient Hybrid, Nanostructured, Epoxidation Catalyst: Titanium Silsesquioxane–Polystyrene Copolymer Supported on SBA‐15
Authors: Zhang Lei , Abbenhuis Hendrikus C. L. , Gerritsen Gijsbert , Bhriain Nollaig Ní , Magusin Pieter C. M. M. , Mezari Brahim , Han Wei , van Santen Rutger A. , Yang Qihua , Li Can
Published: October 2006

A novel interfacial hybrid epoxidation catalyst was designed with a new immobilization method for homogeneous catalysts by coating an inorganic support with an organic polymer film containing active sites. The titanium silsesquioxane (TiPOSS) complex, which contains a single‐site titanium active center, was immobilized successfully by in‐situ copolymerization on a mesoporous SBA‐15‐supported polystyrene polymer. The resulting hybrid materials exhibit attractive textural properties (highly ordered mesostructure, large specific surface area (>380 m2 g−1) and pore volume (≧0.46 cm3 g−1)), and high activity in the epoxidation of alkenes. In the epoxidation of cyclooctene with tert‐butyl hydrogen peroxide (TBHP), the hybrid catalysts have rate constants comparable with that of their homogeneous counterpart, and can be recycled at least seven times. They can also catalyze the epoxidation of cyclooctene with aqueous H2O2 as the oxidant. In two‐phase reaction media, the catalysts show much higher activity than their homogeneous counterpart due to the hydrophobic environment around the active centers. They behave as interfacial catalysts due to their multifunctionality, that is, the hydrophobicity of polystyrene and the polyhedral oligomeric silsesquioxanes (POSS), and the hydrophilicity of the silica and the mesoporous structure. Combination of the immobilization of homogeneous catalysts on two conventional supports, inorganic solid and organic polymer, is demonstrated to achieve novel heterogeneous catalytic ensembles with the merits of attractive textural properties, tunable surface properties, and optimized environments around the active sites.
Preparation and Use of Microarrays Containing Synthetic Heparin Oligosaccharides for the Rapid Analysis of Heparin–Protein Interactions
Authors: Noti Christian , de Paz Jose L. , Polito Laura , Seeberger Peter H.
Published: October 2006

Heparin is a highly sulfated, linear polymer that participates in a plethora of biological processes by interaction with many proteins. The chemical complexity and heterogeneity of this polysaccharide can explain the fact that, despite its widespread medical use as an anticoagulant drug, the structure–function relationship of defined heparin sequences is still poorly understood. Here, we present the chemical synthesis of a library containing heparin oligosaccharides ranging from di‐ to hexamers of different sequences and sulfation patterns. An amine‐terminated linker was placed at the reducing end of the synthetic structures to allow for immobilization onto N‐hydroxysuccinimide activated glass slides and creation of heparin microarrays. Key features of this modular synthesis, such as the influence of the amine linker on the glycosidation efficiency, the use of 2‐azidoglucose as glycosylating agents for oligosaccharide assembly, and the compatibility of the protecting group strategy with the sulfation‐deprotection steps, are discussed. Heparin microarrays containing this oligosaccharide library were constructed using a robotic printer and employed to characterize the carbohydrate binding affinities of three heparin‐binding growth factors. FGF‐1, FGF‐2 and FGF‐4 that are implicated in angiogenesis, cell growth and differentiation were studied. These heparin chips aided in the discovery of novel, sulfated sequences that bind FGF, and in the determination of the structural requirements needed for recognition by using picomoles of protein on a single slide. The results presented here highlight the potential of combining oligosaccharide synthesis and carbohydrate microarray technology to establish a structure–activity relationship in biological processes.
The role of FDG‐PET/CT in suspected recurrence of breast cancer
Authors: Radan Lea , Ben‐Haim Simona , Bar‐Shalom Rachel , Guralnik Luda , Israel Ora
Published: October 2006

BACKGROUND.

Early diagnosis of recurrent breast cancer is crucial to selection of the most appropriate therapy. The current study evaluated the role of FDG‐PET/CT in the assessment of suspected recurrent breast cancer in patients who presented with elevated serum tumor markers.

METHODS.

Forty‐seven consecutive FDG‐PET/CT studies of 46 women (aged 32–79 years; mean, 59.9 years) with a history of breast cancer presented with elevated serum tumor markers 1–21 years (mean = 6.2 years) after their initial diagnosis and were retrospectively evaluated. PET/CT results were confirmed by pathology (n = 11), further imaging, and follow‐up (mean = 17.2 months; n = 36). Changes in further management based on PET/CT were recorded.

RESULTS.

Thirty (65%) patients had tumor recurrence, and 16 (35%) patients showed no further evidence of disease. Thirty‐one patients had 32 abnormal PET/CT studies, and 15 patients had normal studies with an overall sensitivity, specificity, and accuracy of 90%, 71%, and 83%, respectively. In 37 patients, PET/CT was compared with contrast‐enhanced CT and had a higher sensitivity (85% vs 70%), specificity (76% vs 47%), and accuracy (81% vs 59%). PET/CT had an impact on the management of 24 (5l%) patients. Of these, chemotherapy or radiotherapy was started in 16 patients, treatment was modified in 2 patients, and 6 patients were referred to biopsy, followed by referral to surgery for 2 patients.

CONCLUSIONS.

In patients with breast cancer and rising tumor markers, FDG‐PET/CT had high performance indices and was superior to CT for diagnosis of tumor recurrence, which led to changes in the subsequent clinical management of 51% of these patients. Cancer 2006. © 2006 American Cancer Society.
The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis
Authors: Rosen Daniel G. , Mercado‐Uribe Imelda , Yang Gong , Bast Robert C. , Amin Hesham M. , Lai Raymond , Liu Jinsong
Published: October 2006

BACKGROUND.

Signal transducer and activator of transcription 3 (Stat3), which is a latent transcription factor that participates in the transcriptional activation of apoptosis and cell cycle progression, has been implicated as an oncogene in several neoplastic diseases. However, the specific role of Stat3 in ovarian carcinogenesis remains poorly understood. The objectives of the current study were to examine the effect of Stat3 activation on the phenotypic transformation of an immortalized, nontumorigenic ovarian epithelial cell line and to evaluate the expression of tyrosine‐activated Stat3 (pStat3) in tissue microarrays from 303 ovarian carcinomas to determine its prognostic relevance and to correlate its expression with several upstream oncogenes of Stat3 and with the oncogenes involved in apoptosis and proliferation.

METHODS.

Overexpression of pStat3 was weakly tumorigenic and produced measurable tumors in mice in 1 of 3 clones. Using tissue microarrays from a large group of patients with primary ovarian carcinoma, the expression of pStat3 was correlated with the expression of growth factor receptors (HER‐2/neu and epidermal growth factor receptor [EGFR]), interleukin 6, and the proliferation and apoptosis markers Ki‐67, Bcl‐2, and Bcl‐xL and with clinicopathologic variables and patient survival.

RESULTS.

High pStat3 expression in the tumor tissue microarray was associated with high levels of HER‐2/neu, EGFR, and Ki‐67. No correlation was observed between overall pStat3 levels and any other clinicopathologic variables tested. High nuclear expression of pStat3 (>10% of positive‐stained cells) was linked with poor overall survival.

CONCLUSIONS.

The activation and translocation of pStat3 to the nucleus are frequent events in ovarian carcinoma that are associated with a poor prognosis. Further studies are needed to elucidate the mechanism of activation of Stat3, its effects on downstream targets, and its role in the neoplastic transformation of epithelial ovarian cells. Cancer 2006. © 2006 American Cancer Society.
True monolayer cell culture in a confined 3D microenvironment enables lineage informatics
Authors: Ramunas John , Illman Meredith , Kam Angela , Farn Kristen , Kelly Liam , Morshead Cindi M. , Jervis Eric J.
Published: October 2006

Background:

There is a need for methods to (1) track cells continuously to generate lineage trees; (2) culture cells in in vivo‐like microenvironments; and (3) measure many biological parameters simultaneously and noninvasively. Herein, we present a novel imaging culture chamber that facilitates “lineage informatics,” a lineage‐centric approach to cytomics.

Methods:

We cultured cells in a confined monolayer using a novel “gap chamber” that produces images with confocal‐like qualities using standard DIC microscopy. Lineage and other cytometric data were semiautomatically extracted from image sets of neural stem and progenitor cells and analyzed using lineage informatics.

Results:

Cells imaged in the chamber every 3 min could be tracked for at least 6 generations allowing for the construction of extensive lineage trees with multiparameter data sets at hundreds of time points for each cell. The lineage informatics approach reveals relationships between lineage, phenotype, and microenvironment. Mass transfer characteristics and 3D geometry make the chamber more in vivo‐like than traditional culture systems.

Conclusions:

The gap chamber allows cells to be cultured, imaged, and tracked in true monolayers permitting detailed informatics analysis of cell lineage, phenotype, and fate determinants. The chamber is biomimetic and straightforward to build and use, and should find many applications in long‐term cell imaging. © 2006 International Society for Analytical Cytology
Interactions of hydrophobic and hydrophilic solvent component degradation in an air‐phase biotrickling filter reactor
Authors: Paca Jan , Klapkova Eva , Halecky Martin , Jones Kim , Webster Todd S.
Published: October 2006

Interactions amongst the degradation rates of toluene, xylenes, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), and n‐butyl acetate (n‐BA) were investigated. Experiments were performed in a biotrickling filter reactor packed with polypropylene Pall rings in a counter‐current air–water mode of operation. Under pseudo‐steady‐state conditions, the removal efficiency (RE) of the individual components in the middle of and at the effluent above the reactor bed was evaluated. By using a mixed microbial culture as the biocatalyst, the results revealed that an increased loading of toluene and xylene had a competitive effect on the RE of MIBK. After reaching a saturation point of the overall catabolic capacity of the biocatalyst, variations of RE were observed for the different components. This was most pronounced under conditions of overloading with the water‐soluble components mixture. Despite such variations, the system was able to efficiently degrade this complex pollutant mixture for a period of 1 yr. © 2006 American Institute of Chemical Engineers Environ Prog, 2006
Two novel applications of ion exchange fibers: Arsenic removal and chemical‐free softening of hard water
Authors: Greenleaf John E. , Lin Jin‐cheng , Sengupta Arup K.
Published: October 2006

Separation processes using ion exchange materials are ubiquitous regarding the selective removal of contaminants of environmental concern. Recently, highly regulated contaminants, such as arsenic, have gained notoriety on account of carcinogenic effects and subsequent promulgation of new drinking water standards by the United States Environmental Protection Agency. Other nonregulated compounds such as hardness (e.g., Ca2+, Mg2+), pose a particular concern to avoid scaling in heat‐transfer equipment, foulingz in membranes, and high consumption of detergents and sequestering chemicals in cooling and wash water. In general, ion exchange processes used to remove hardness generate concentrated brine or mineral acid as a waste regenerant stream. Residuals management and long‐term sustainability issues will continue to be major concerns with these processes. The subject paper reports and discusses the results and attributes of two new separation processes using ion exchange fibers (IX‐fibers). The first process involves the selective removal of arsenic using hybridized IX‐fibers that contain dispersed hydrated ferric oxide (HFO) nanoparticles. Anion‐exchanger‐supported HFO particles offered a high arsenic removal capacity; less than 10% of influent arsenic broke through after 30,000 bed volumes. Hybrid fibers were also amenable to efficient regeneration with 2% NaOH and 2% NaCl and capable of simultaneous removal of both arsenic(V) and arsenic(III). The second process involves the environmentally benign removal of hardness. Most importantly, this process uses harvested snowmelt (or rainwater) sparged with carbon dioxide as the regenerant. Consequently, the spent regenerant does not contain a high concentration of aggressive chemicals such as sodium chloride or acid like traditional ion‐exchange processes nor does the process produce voluminous sludges as does lime softening. The bulk of carbon dioxide consumed during regeneration remains sequestered in the aqueous phase as alkalinity. For both treatment strategies, IX‐fibers form the heart of the process. They are essentially thin cylindrical polymeric strands 10–20 μm in diameter with functional groups residing near to the fiber surface. Low intraparticle diffusional resistance is the underlying reason why calcium loaded weak acid IX‐fibers are amenable to efficient regeneration using either snowmelt or rainwater sparged with carbon dioxide. Additionally, for hybrid IX‐fibers, enhanced adsorption kinetics may offer the possibility for certain point of use applications, which are unavailable to their resin counterparts. © 2006 American Institute of Chemical Engineers Environ Prog, 2006