The current study examined the psychometric properties of the Pathways to Inflated Responsibility Beliefs Scale (PIRBS; Coles & Schofield, 2008), a measure designed to assess the theoretical pathways posited to contribute to responsibility beliefs in individuals with obsessive-compulsive disorder (OCD; Salkovskis et al., 1999). The primary aim of this study was to examine the factor structure, reliability, and validity of the measure in a diverse sample as well as to compare the properties of the scale across ethnic groups. The current sample consisted of 442 university students who completed questionnaire packets or an online survey. The results of an exploratory factor analysis suggested that a four-factor model with three items removed from the original PIRBS scale best fit the data. Confirmatory factor analyses in groups of African American and Caucasian participants indicated that neither the original PIRBS model nor the EFA-derived model adequately fit the data, but the latter model demonstrated comparable indicators of validity as well as an improvement in the internal consistency of the PIRBS Overprotection subscale. Evidence of the convergent and discriminant validity of the PIRBS was obtained through its associations with OCD-relevant constructs, including OC beliefs domains and symptoms, trait anxiety and worry, depression, parenting styles, a measure of childhood responsibility, and religiosity. Some differential associations were observed in these relationships across ethnic groups. Suggestions for future research and the clinical implications of research in this area are discussed.

Made available in DSpace on 2014-06-11T19:28:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2004-02-19Bitstream added on 2014-06-13T19:57:16Z : No. of bitstreams: 1 ishi_ep_me_arafo.pdf: 346197 bytes, checksum: 6795ce77ad2dd590c6c320a2852cea60 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Tendo em vista que existem controvérsias na literatura quanto à existência de associação entre a doença periodontal e a artrite reumatóide e que as metodologias empregadas são tão diversas quanto os seus resultados e conclusões, este estudo transversal teve por objetivo avaliar a condição periodontal em portadores de artrite reumatóide e verificar se existe associação entre essas duas condições. Para isso, foram aplicados questionários de saúde geral e bucal, e foi realizado o exame periodontal em 49 portadores de artrite reumatóide e em 22 indivíduos não portadores de artrite reumatóide ou qualquer outra doença auto-imune. Fumantes e portadores de diabetes mellitus foram excluídos deste estudo. Os resultados indicaram que portadores de artrite reumatóide possuem menor número de dentes na cavidade bucal, apresentam maior extensão de placa bacteriana e maior proporção de sítios com perda de inserção periodontal avançada do que os indivíduos não portadores de artrite reumatóide Apesar da maior extensão de placa bacteriana dentre portadores de artrite reumatóide, a porcentagem de sítios que apresentaram sangramento marginal foi semelhante nos dois grupos, provavelmente devido ao uso de drogas antiinflamatórias e drogas de base, imunoreguladoras. Além disso, portadores de artrite reumatóide que utilizavam a associação de drogas de base apresentaram menor perda de inserção periodontal do que aqueles que não utilizavam a associação dessas drogas. Os resultados do estudo sugerem que existe associação entre periodontite e artrite reumatóide e que novos estudos serão necessários para identificar os fatores presentes nos portadores de artrite reumatóide que predispõem esses indivíduos a uma maior perda de inserção periodontal. / There are controversies in the literature concerning the association between periodontal disease and rheumatoid arthritis. There are no consistent methodologies and results. The aim of this cross-sectional study was to assess periodontal condition in rheumatoid arthritis patients and verify if there is an association between these two conditions. We have produced general and dental health questionnaires and periodontal examination was achieved in 49 rheumatoid arthritis patients and 22 healthy individuals. Smokers and diabetes mellitus patients were excluded of the sample. Our results indicated that rheumatoid arthritis patients had lesser remaining teeth, higher extension of dental plaque and higher proportion of sites presenting advanced attachment loss than controls. Although rheumatoid arthritis patients had higher extension of dental plaque than the control group, gingival bleeding was similar between them, maybe because of the fact that rheumatoid arthritis patients take anti-inflammatory and disease-modifying antirheumatic drugs (DMARDs) for their treatment. Rheumatoid arthritis patients who were taking an association of two or more disease-modifying antirheumatic drugs had lesser attachment loss than patients that were taking only one of these drugs. Our results suggest that there is an association between periodontitis and rheumatoid arthritis and that more studies are required to identify specific risk factors for attachment loss in rheumatoid arthritis patients.

M.Tech. / Natural occurring components in human breast milk, cow milk and soy milk have shown anticarcinogenic abilities. The human breast milk protein, -lactalbumin, was found to induce apoptosis in cancer cells, embryonic cells and rapidly growing cells, when converted from its native form to a partial denatured apoptotic-inducing form. Moreover, radiation may cause irreversible changes of protein conformation at the molecular level. Native -lactalbumin is one protein that has shown a decrease in aromatic amino acid concentration and the formation of high and low molecular weight fractions when exposed to high doses of ionizing radiation. The effect of human breast milk, cow milk, soy milk and galactose (positive control) on SNO, A549 cancer cells and normal lymphocytes were investigated. Human breast milk was irradiated with low doses of Co60 ionizing radiation (0.1Gy, 1.0Gy and 5.0Gy) in order to establish the effect of these doses on the apoptotic-inducing ability of human breast milk. The techniques used included, Trypan blue dye exclusion (cell viability), haematoxylin and eosin stain (cell morphology), modified comet assay (halo) (DNA damage) and flow cytometry (apoptosis and necrosis). Findings showed that human breast milk, irradiated human breast milk and galactose induced apoptosis in the SNO, A549 cells and lymphocytes. The cell viability, cell morphology and DNA fragmentation patterns of irradiated human breast milk were similar to that of non-irradiated human breast milk, although the flow cytometry results did not correlate. Cow and soy milk did not induce apoptosis in the SNO, A549 cells and lymphocytes. The modified comet assay (halo) detected DNA damage as apoptotic or necrotic cells. A clear distinction could not be made between the two cell populations using this assay. Flow Cytometry discriminated and quantified apoptotic cells and necrotic/late apoptotic cells using Annexin V and Propidium Iodide (PI), respectively.

No description available.

Toxic shock syndrome toxin-1 (TSST-1), an exoprotein produced by some strains of Staphylococcus aureus, is implicated in the pathogenesis of menstrual TSS. However, its role in nonmenstrual TSS is less certain. In order to study the pathogenetic role of TSST-1 in TSS, three approaches were taken: a) to develop an ELISA for detection of TSST-1 in biologic fluids in order to verify TSST-1 production in vivo in TSS patients, b) to quantitate TSST-1 specific antibodies in the serum of TSS patients and controls to determine whether such antibodies are protective, and c) to attempt to identify other staphylococcal products which may be implicated in some forms of TSS. A sensitive and specific noncompetitive enzyme-linked immunosorbent assay (ELISA) capable of detecting TSST-1 at concentrations from 0.5 to 16 ng/ml was developed. This assay did not detect other staphylococcal enterotoxins including A, B, C₁, C₂, C₃, D and E. Possible interference by protein A was readily eliminated by pretreatment of test samples with 10% nonimmune rabbit serum. The assay was adapted for rapid screening of TSST-1 production by S. aureus isolates in culture supernatants in vitro, and for the detection of TSST-1 in vaginal washings and urine of TSS patients and healthy controls in vivo. All 35 S. aureus isolates confirmed to be TSST-1 positive by Ouchterlony immunodiffusion, and 59 of 60 isolates confirmed to be TSST-1 negative, gave concordant results by ELISA. Interestingly, toxigenic S. aureus strains isolated from TSS patients quantitatively produced significantly more toxin in vitro compared to toxigenic control strains (p<0.05, Mann-Whitney rank sum test). TSST-1 could be detected by ELISA in 3 of 4 vaginal washings collected within 3 days of hospitalization from 3 women with acute menstrual TSS, compared to 0 of 17 washings from 9 TSS women collected greater than 3 days after hospitalization (p=0.003, Fisher's exact test) and 1 of 15 washings from 14 healthy control women (p=0.016). TSST-1 was not detected in the urine of 4 acute TSS patients, 2 convalescent TSS patients or in 3 control urine tested. A sensitive and reproducible ELISA was also developed for the quantitation of TSST-1 specific IgG in serum. Anti-TSST-1 was assessed in acute and convalescent sera from 16 nonmenstrual (9 female, 7 male) and 14 menstrual TSS patients, and from 87 healthy women and 66 healthy men as controls. Quantitative levels of anti-TSST-1 in the study groups were calculated as the percent of standard activity (POSA) relative to a medium titre reference serum standard. ELISA titers in acute sera from menstrual TSS (26.2 ± 5.2, mean POSA ± S.E.M.), but not nonmenstrual TSS women (71.8 ± 18.6), were significantly lower than in healthy controls (78.9 ± 7.3) (p<0.01, Mam-Whitney test). Titers from menstrual TSS patients remained low (25.2 ± 10.7) even during late convalescence (mean duration 20 months after illness onset), compared to healthy female controls (p<0.05). Acute titers in males with TSS (37.0 ± 15.6) were also significantly lower than those in control men (114.6 + 11.0) (p<0.05). An inverse relationship of recovery of toxigenic S. aureus and anti-TSST-1 titers in acute sera of TSS patients was observed. Interestingly, antibody titers in control men were significantly higher than in control women (p<0.001). No age-dependent effects or interactive effects of age and sex on ELISA titers were observed. To enable immunoblot analyses, TSST-1 was produced and partially purified using column chromatography techniques. Percent recovery of TSST-1 from culture supernatant through to the final procedure was approximately 15.5%. The relative purity of TSST-1 (TSST-l/total protein, w/w) was increased from 0.21% in culture supernatants to 94.4% in the final product. Ouchterlony immunoprecipitation against reference rabbit antitoxin demonstrated identity with reference TSST-1 as well as with TSST-1 prepared in other laboratories. Physical characterization demonstrated a molecular weight of 24 kd and a pi of 7.0. Using pooled normal human serum as a first antibody probe, several bands in addition to the 24 kd TSST-1 band were visualized by immunoblot against our partially purified toxin as well as similar preparations obtained from other investigators. To determine whether any of the additional bands might be implicated in TSS, acute and convalescent sera from TSS patients were used to probe for immunoreactive bands in our partially purified TSST-1 as well as a commercially obtained preparation. Seroconversion was demonstrated to the 24 kd TSST-1 protein in 7 of 10 TSS patients from whom toxigenic S. aureus was isolated. In addition, seroconversion was noted to a 49 kd band in 4 patients, to a 21 kd band in 3 patients, to a 28 kd band in 1 patient and to a 32 kd band in 2 patients. In conclusion: 1) the ability to measure TSST-1 in biologic fluids lends stronger support for the role of TSST-1 in menstrual TSS patients; 2) the serologic data support the etiologic role of TSST-1 in menstrual TSS and in nonmenstrual TSS patients from whom toxigenic S. aureus could be cultured, but not for nonmenstrual TSS women from whom toxigenic S. aureus was not isolated; 3) immunoblotting results with acute and convalescent sera from TSS and control patients, not only add further support to the role of TSST-1 in patients from whom toxigenic S. aureus could be isolated, but also indicate that there may be several other staphylococcal products implicated in TSS, particularly in whom antibody to TSST-1 pre-existed in acute sera. The nonresponsiveness or lack of seroconversion to TSST-1 in some patients could suggest either: a) TSST-1 was not the etiologic agent for such patients; b) TSST-1 was the etiologic agent, but the exposure was sufficient for an immune response (similar to tetanus), or; c) some immunologic defect may be present. Future studies are required to clarify these possibilities. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

No description available.

Myocardial reperfusion injury is thought to be caused by reperfusion induced i) cytosolic Ca²⁺ overload and/or, ii) the formation of oxygen derived freeradicals. At the start of this study, data implicating cytosolic Ca²⁺ overload in the genesis of reversible reperfusion injury were inconclusive. Although several workers have approached this problem by measurements of cytosolic calcium ions, it was my aim to examine the potential sources of such calcium overload. The experiments reported in this thesis were therefore designed to examine the role of altered intracellular and transsarcolemmal Ca²⁺ fluxes in the genesis of reperfusion stunning and arrhythmias. The study was also aimed at elucidating the possible sources and entry pathways contributing to this proposed cytosolic Ca²⁺ overload. In order to investigate the possible role of altered reperfusion Ca²⁺ fluxes in reperfusion injury, we exposed the isolated working, and Langendorff perfused rat heart model to ischaemia and reperfusion to induce reperfusion stunning and arrhythmias. Hearts were pre-treated (before ischaemia) or reperfused with pharmacological compounds, or by interventions known to enhance or inhibit intracellular or transsarcolemmal Ca²⁺ fluxes. The severity of reperfusion stunning (mechanical dysfunction) was measured by reperfusion aortic output, coronary flow and left ventricular pressure. The incidence of reperfusion ventricular arrhythmias was measured by the incidence of ventricular tachycardia and/ or fibrillation. In selected studies, the metabolic status of hearts was evaluated using biochemical assays performed on myocardial tissue samples. Data obtained in these studies indicate that increased Ca²⁺ fluxes through sarcolemmal L-type Ca²⁺ channels during early reperfusion exacerbate stunning, while inhibition of these fluxes with the Ca²⁺ antagonist drug nisoldipine or by Mg²⁺ or Mn²⁺ improve reperfusion function. These data also suggest that although interventions increasing Ca²⁺ fluxes early in reperfusion exacerbate reperfusion stunning, these same interventions improve reperfusion function when performed later. The data also indicate that Ca²⁺ may enter the myocyte indirectly via activation of the Na⁺/H⁺ and Na⁺/Ca²⁺ exchanger during reperfusion. Inhibition of Na⁺/H⁺ exchange activity by HOE 694 during reperfusion attenuated reperfusion stunning and arrhythmias. Both activation of the Na⁺/H⁺ (and Na⁺/Ca²⁺) exchanger and Ca²⁺ influx via the Ca²⁺ channel could contribute to reperfusion induced Ca²⁺ overload and subsequent injury. The study also showed that altered intracellular Ca²⁺ oscillations play a role in reperfusion stunning and arrhythmias as shown by the use of the SR Ca²⁺ release channel blocker, ryanodine. Inhibition of the sarcoplasmic reticulum Ca²⁺ A TP-ase pump by two novel inhibitors, thapsigargin and cyclopiazonic acid, during ischaemia and early reperfusion improved reperfusion function and reduced the incidence of ventricular arrhythmias. function when unphysiologically high concentrations of the peptide were infused into the heart during reperfusion. Taken together, these data suggest that: 1) Ca²⁺ fluxes during early reperfusion (intracellular and transsarcolemmal) play a role in reperfusion injury, 2) that both the Ca²⁺ channel and Na⁺/H⁺ exchange activity contribute to reperfusion injury by possibly contributing to cytosolic Ca²⁺ overload and that, 3) altered intracellular Ca²⁺ oscillations through the SR play a role in both stunning and arrhythmias. Thus the proposal is that modulation of Ca²⁺ fluxes through either the sarcolemma or the sarcoplasmic reticulum, lessen reperfusion injury (stunning and arrhythmias). Although these data do not provide direct evidence of reperfusion Ca²⁺ overload, they support the concept that calcium ions play a role in the genesis of reversible reperfusion injury.

No description available.

Ischaemic necrosis of bone, particularly of the femoral head appears to be an increasing cause of musculoskeletal disability in relatively young people (Hungerford 1981). The disease is usually progressive, resulting in the destruction of major weight-bearing joints requiring arthrodesis or arthroplasty. A decade ago it was hoped that joint replacement would solve most of these problems, however, failure of such arthroplasties have often been associated with catastrophic consequences (Chandler 1979).

An altered small intestinal permeability has been proposed as an important aetiological factor in the pathogenesis of inflammatory bowel disease. The relevant literature was reviewed. Intestinal permeability to Polyethylene glycol 400 in patients with Crohn' s disease, their relatives and healthy controls was examined and the data compared with studies of small bowel permeability to other similar sized probes. A new technique of analysis of urinary Polythylene Glycol 400 by High Performance Liquid Chromatography was described and compared with a previously established HPLC method. No evidence of an altered bowel permeability could be found using Polyethylene glycol 400, but the possibility that this may have been related to probe size and characteristics can not be excluded .