The effects of interleukin-10 depletion in vivo on the immune response to Porphyromonas gingivalis in a murine model

Background: The immune response to Porphyromonas gingivalis in the mouse abscess model is known to be dependent upon CD4 T-cell activation and the regulatory role of cytokines. The role of interleukin-10 (IL-10) in this mouse model was examined in vivo. Methods: One-week-old, female BALB/c mice were divided into 4 groups. Groups 1 and 2 were given intraperitoneal (ip) injections of phosphate buffered saline (PBS) weekly for 5 weeks. Group 3 was given an ip injection of rat immunoglobulin. Group 4 was injected with rat anti-IL-10 antibodies. At week 6, group 1 was sham-immunized with PBS, and groups 2, 3, and 4 were injected with P gingivalis lipopolysaccharide (Pg-LPS) weekly for 2 weeks. One week after the final immunization, delayed-type hypersensitivity (DTH) was assessed by footpad swelling to Pg-LPS. The level of serum antibodies to Pg-LPS and IFN-gamma (IFN-gamma) was determined by enzyme-linked immunosorbent assay. Dorsal abscess formation induced by the injection of viable P gingivalis was examined daily for 30 days. Results: The footpad swelling of the anti-IL-10-treated group (group 4) was significantly higher than that of groups 1 to 3. Similarly, the serum IFN-gamma level in group 4 was much higher than that of the other experimental groups. There was no significant difference in serum IgG antibodies to Pg-LPS in any of the experimental groups. However, the level of IgM antibodies in group 4 mice was significantly lower than that in groups 2 and 3. In addition, serum IgG1 was suppressed in group 4 mice, while IgG2a antibodies were raised. However, there was no difference observed between the levels of IgG2b and IgG3 antibodies in any group of mice. The lesions in sham-immunized mice (group 1) persisted for 30 days, and those in group 2 and 3 were undetected by day 18 and 20, respectively. In sharp contrast, lesions in group 4 had healed completely by day 13. Conclusions: This study has shown that IL-10 depletion in vivo in P gingivalis LPS-induced immune response in mice led to an elevated DTH response, an increase in serum IFN-gamma levels, and raised levels of IgG and IgG2a antibodies. Treatment with anti-IL-10 antibodies resulted in suppressed IgG I and IgM responses and a more rapid healing of abscesses than in non-IL-10-depleted mice. These results suggest that IL-10 depletion in Pg-LPS-induced immune response in mice may lead to a Th1-like immune response and provide strong protection against a subsequent challenge with live P gingivalis in an abscess model.

Gas permeation in silicon-oxide/polymer (SiOx/PET) barrier films: role of the oxide lattice, nano-defects and macro-defects

We propose a model for permeation in oxide coated gas barrier films. The model accounts for diffusion through the amorphous oxide lattice, nano-defects within the lattice, and macro-defects. The presence of nano-defects indicate the oxide layer is more similar to a nano-porous solid (such as zeolite) than silica glass with respect to permeation properties. This explains why the permeability of oxide coated polymers is much greater, and the activation energy of permeation much lower, than values expected for polymers coated with glass. We have used the model to interpret permeability and activation energies measured for the inert gases (He, Ne and Ar) in evaporated SiOx films of varying thickness (13-70 nm) coated on a polymer substrate. Atomic force and scanning electron microscopy were used to study the structure of the oxide layer. Although no defects could be detected by microscopy, the permeation data indicate that macro-defects (>1 nm), nano-defects (0.3-0.4 nm) and the lattice interstices (<0.3 nm) all contribute to the total permeation. (C) 2002 Elsevier Science B.V. All rights reserved.

The role of CD4(+) cells in vivo on the induction of the immune response to Porphyromonas gingivalis in mice

Background: It has previously been suggested that CD4(+) T cells play a pivotal role in regulating the immune response to periodontal pathogens. The aim of the present study therefore was to determine delayed type hypersensitivity (DTH), spleen cell proliferation, serum and splenic anti-Porphyromonas gingivalis antibody levels, and lesion sizes following challenge with viable P. gingiualis in CD4-depleted BALB/c mice immunized with P. gingiualis outer membrane proteins (OMP). Methods: Four groups of BALB/c mice were used. Groups 1 and 2 were injected intraperitoneally (ip) with saline for 3 consecutive days and then weekly throughout the experiment. Groups 3 and 4 were injected ip with rat immunoglobulin and a monoclonal rat anti-mouse CD4 antibody, respectively. Two days later, group 1 mice were injected ip with saline only, while all the other groups were immunized ip with P. gingiualis OMP weekly for 3 weeks. One week later following the last immunization of OMP, 3 separate experiments were conducted to determine: 1) the DTH response to P. gingiualis OMP by measuring footpad swelling; 2) the levels of antibodies to P. gingiualis in serum samples and spleen cell cultures using an enzyme-linked immunosorbent assay, as well as spleen cell proliferation after stimulation with OMP; and 3) the lesion sizes after a subcutaneous challenge with viable P. gingiualis cells. Results: In CD4(+) T-cell-depleted mice (group 4), the DTH response and antigen-stimulated cell proliferation were significantly suppressed when compared to groups 2 and 3. Similarly, the levels of serum and splenic IgM, IgG, and all IgG subclass antibodies to P. gingiualis OMP were depressed. Delayed healing of P. gingivalis-induced lesions was also observed in the CD4(+) T-cell-depleted group. Conclusions: This study has shown that depletion of CD4(+) T cells prior to immunization with P. gingiualis OMP led to the suppression of both the humoral and cell-mediated immune response to this microorganism and that this was associated with delayed healing. These results suggest that the induction of the immune response to P. gingiualis is a CD4(+) T-cell-dependent mechanism and that CD4(+) T cells are important in the healing process.

Maintaining muscle mass during extended disuse: Aestivating frogs as a model species

Prolonged muscle disuse in vertebrates can lead to a pathological change resulting in muscle wasting and a loss of muscle strength. In this paper, we review muscle disuse atrophy in the vertebrates and examine the factors that influence the magnitude of the atrophic response during extended periods of inactivity, both artificially imposed (e.g. limb immobilisation) and naturally occurring, such as the quiescence associated with dormancy (e.g. hibernation and aestivation). The severity of muscle atrophy is positively correlated with mass-specific metabolic rate, and the metabolic depression that occurs during dormancy would appear to have a protective role, reducing or preventing muscle atrophy despite periods of inactivity lasting 6-9 months. In the light of these findings, the role of reactive oxygen species and antioxidants during muscle disuse is emphasised.

Control of dimethylsulfoxide reductase expression in Rhodobacter capsulatus: the role of carbon metabolites and the response regulators DorR and RegA

Regulation of the expression of dimethylsulfoxide (DMSO) reductase was investigated in the purple phototrophic bacterium Rhodobacter capsulatus. Under phototrophic, anaerobic conditions with malate as carbon source, DMSO caused an approximately 150-fold induction of DMSO reductase activity. The response regulator DorR was required for DMSO-dependent induction and also appeared to slightly repress DMSO reductase expression in the absence of substrate. Likewise, when pyruvate replaced malate as carbon source there was an induction of DMSO reductase activity in cells grown at low light intensity (16 W m(-2)) and again this induction was dependent on DorR. The level of DMSO reductase activity in aerobically grown cells was elevated when pyruvate replaced malate as carbon source. One possible explanation for this is that acetyl phosphate, produced from pyruvate, may activate expression of DMSO reductase by direct phosphorylation of DorR, leading to low levels of induction of dor gene expression in the absence of DMSO. A mutant lacking the global response regulator of photosynthesis gene expression, RegA, exhibited high levels of DMSO reductase in the absence of DMSO, when grown phototrophically with malate as carbon source. This suggests that phosphorylated RegA acts as a repressor of dor operon expression under these conditions. It has been proposed elsewhere that RegA-dependent expression is negatively regulated by the cytochrome cbb(3) oxidase. A cco mutant lacking cytochrome cbb(3) exhibited significantly higher levels of Phi[dorA::lacZ] activity in the presence of DMSO compared to wild-type cells and this is consistent with the above model. Pyruvate restored DMSO reductase expression in the regA mutant to the same pattern as found in wild-type cells. These data suggest that R. capsulatus contains a regulator of DMSO respiration that is distinct from DorR and RegA, is activated in the presence of pyruvate, and acts as a negative regulator of DMSO reductase expression.

A role for the dominant thalamus in language? A linguistic comparison of two cases subsequent to unilateral thalamotomy procedures in the dominant and non-dominant hemispheres

Background: Thalamotomy has been reported to be successful in ameliorating the motor symptoms of tremor and/or rigidity in people with Parkinson's disease (PD), emphasising the bona fide contribution of this subcortical nucleus to the neural circuitry subserving motor function. Despite evidence of parallel yet segregated associative and motor cortico-subcortical-cortical circuits, comparatively few studies have investigated the effects of this procedure on cognitive functions. In particular, research pertaining to the impact of thalamotomy on linguistic processes is fundamentally lacking. Aims: The purpose of this research was to investigate the effects of thalamotomy in the language dominant and non-dominant hemispheres on linguistic functioning, relative to operative theoretical models of subcortical participation in language. This paper compares the linguistic profiles of two males with PD, aged 75 years (10 years of formal education) and 62 years (22 years of formal education), subsequent to unilateral thalamotomy procedures within the language dominant and non-dominant hemispheres, respectively. Methods & Procedures: Comprehensive linguistic profiles comprising general and high-level linguistic abilities in addition to on-line semantic processing skills were compiled up to 1 month prior to surgery and 3 months post-operatively, within perceived on'' periods (i.e., when optimally medicated). Pre- and post-operative language performances were compared within-subjects to a group of 16 non-surgical Parkinson's controls (NSPD) and a group of 16 non-neurologically impaired adults (NC). Outcomes & Results: The findings of this research suggest a laterality effect with regard to the contribution of the thalamus to high-level linguistic abilities and, potentially, the temporal processing of semantic information. This outcome supports the application of high-level linguistic assessments and measures of semantic processing proficiency to the clinical management of individuals with dominant thalamic lesions. Conclusions: The results reported lend support to contemporary theories of dominant thalamic participation in language, serving to further elucidate our current understanding of the role of subcortical structures in mediating linguistic processes, relevant to cortical hemispheric dominance.

The differential role of alcohol expectancies, drinking refusal self-efficacy and coping resources in predicting alcohol consumption in community and clinical samples

This study explored the relationship between coping, alcohol expectancies and drinking refusal self-efficacy in predicting drinking behaviour in both community and clinical samples. These variables were found to have differential effects in their association with frequency and volume of alcohol consumption across the two samples. Generally, drinking refusal self-efficacy was a more salient factor in relation to frequency and volume of community drinking, while coping and expectancies were more strongly associated with frequency of drinking sessions by problem drinkers. The interaction between expectancies and drinking refusal self-efficacy was related to volume of consumption in both groups, while coping and expectancies interacted in their association with frequency in the clinical group. The findings are discussed with regard to the different patterns of cognitive variables governing the decision to drink and the amount consumed in each drinking session, which may differentiate community and problem drinkers.

The martensitic transformation in ceramics - its role in transformation toughening

This paper reviews the current knowledge and understanding of martensitic transformations in ceramics - the tetragonal to monoclinic transformation in zirconia in particular. This martensitic transformation is the key to transformation toughening in zirconia ceramics. A very considerable body of experimental data on the characteristics of this transformation is now available. In addition, theoretical predictions can be made using the phenomenological theory of martensitic transformations. As the paper will illustrate, the phenomenological theory is capable of explaining all the reported microstructural and crystallographic features of the transformation in zirconia and in some other ceramic systems. Hence the theory, supported by experiment, can be used with considerable confidence to provide the quantitative data that is essential for developing a credible, comprehensive understanding of the transformation toughening process. A critical feature in transformation toughening is the shape strain that accompanies the transformation. This shape strain, or nucleation strain, determines whether or not the stress-induced martensitic transformation can occur at the tip of a potentially dangerous crack. If transformation does take place, then it is the net transformation strain left behind in the transformed region that provides toughening by hindering crack growth. The fracture mechanics based models for transformation toughening, therefore, depend on having a full understanding of the characteristics of the martensitic transformation and, in particular, on being able to specify both these strains. A review of the development of the models for transformation toughening shows that their refinement and improvement over the last couple of decades has been largely a result of the inclusion of more of the characteristics of the stress-induced martensitic transformation. The paper advances an improved model for the stress-induced martensitic transformation and the strains resulting from the transformation. This model, which separates the nucleation strain from the subsequent net transformation strain, is shown to be superior to any of the constitutive models currently available. (C) 2002 Elsevier Science Ltd. All rights reserved.

Global job satisfaction and facet description: The moderating role of facet importance

Recent research support sLocke's (1976) model of facet satisfaction in which the range of affect of objectively defined facet descriptions is moderated by subjective evaluations of facet importance (McFarlin & Rice, 1992). This study examined the utility of Locke's moderated model of face t satisfaction for the prediction of organizationally important global measures of job satisfaction. A large dataset of two groups of workers allowed testing over different time periods and across a broad range of satisfaction measures. The hypothesis derived from Locke's model, that global satisfaction would represent a linear function of facet satisfaction (i.e., facet description x facet importance), was not supported. Instead, a simple (have-want) discrepancy model (operationalized as facet description) provided the most consistent set of predictors. The results suggests that workers, when providing global measures of job satisfaction, may use cognitive heuristics to reduce the complexity of facet description x importance calculations. The implications of these data for Locke's model and directions for future research are outlined.

Cyclosporin A pretreatment in a rat model of warm ischaemia/reperfusion injury

Background/Aims: These studies investigated the role of apoptosis following ischaemia/reperfusion (I/R) injury to the liver and the effect of pretreatment with Cyclosporin A. Methods: Male Sprague-Dawley rats received 30 min of warm ischaemia followed by a period of reperfusion of 6 h. Rats were given olive oil or Cyclosporin A (30 mg/kg p.o.) the day before surgery. Neutrophil numbers were assessed in haematoxylin-eosin-stained sections of liver. In situ staining of sections using TdT-mediated dUTP-fluoreseein nick-end labelling was carried out to determine the extent of apoptosis, followed by electron microscopy. Semi-quantitative polymerase chain reaction (PCR) analysis of the transcript for Fas antigen was performed. Results and Conclusions: High levels of apoptosis were observed in I/R injury, which were greatly ameliorated in Cyclosporin A-pretreated groups. PCR analysis indicated a reduction in the level of expression of Fas transcript in Cyclosporin A-treated rats. Histological analysis showed a significant increase in the number of neutrophils infiltrating I/R-injured tissue (62 +/- 10.69, it = 16), which was markedly reduced by Cyclosporin A pretreatment (16 +/- 7, n = 6, P < 0.05). These results indicate a role of parenchymal apoptosis in the pathogenesis of I/R injury, which occurs in association with neutrophil infiltration, both of which can be significantly reduced by Cyclosporin A pretreatment. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

The role of space as both a conflict trigger and a conflict control mechanism in culturally heterogeneous workgroups

The diversity literature is replete with examples of poor outcomes in Culturally Heterogeneous Workgroups (CHWs) caused by relational difficulties. Although it is widely recognised that culture shapes people's interpretation of behavior and their style of interaction with others in the workplace, what is ill understood is what the specific conflict triggers of these conflicts are. In this paper, we argue that differences in cultural norms and views of physical and psychological space are major triggers of conflict in CHWs. Findings from a field study support the proposition that different viewpoints regarding the use of space, the inability to retreat from exposure to others, decreased interpersonal space, and privacy invasion moderate the relationship between cultural diversity in the workgroup and the type, frequency, and duration of conflict events in CHWs. The paper represents a first step in elucidating the role of space in cross-cultural interactions in the workplace and how space may be a potentially important conflict control mechanism for managers of culturally diverse workgroups.

The influence of role models on strudents' entrepreneurial intentions

The Smart State initiative requires both improved education and training, panicularly in technical fields, plus entrepreneurship to commercialise new ideas. In this study, we propose an entrepreneurial intentions model as a guide to examine the educational choices and entrepreneurial intentions of first-year University students, focusing on the effect of role models. A survey of over 1000 first-year University students revealed that the most enterprising students were choosing to study in the disciplines of information technology and business, economics and law, or selecting dual degree programs that include business. The role models most often identified for their choice of field of study were parents, followed by teachers and peers, with females identifying more role models than males. For entrepreneurship, students' role models were parents and peers, followed by famous persons and teachers. Males andfemales identified similar numbers of role models, but malesfound starting a business more desirable and more feasible, and reponed higher entrepreneurial intention. The implications of these findings for Sman State policy are discussed.

In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated. Copyright (C) 2003 John Wiley Sons, Ltd.

The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes

We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk.

In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.