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Biomedical subjects

R Shah

Publications and source records attributed to R Shah.

At least 55 records · Page 3Linked to original sources

Effects of age, sex, race, diagnosis-related group, and hospital setting on lipid management in patients with coronary artery disease.

Among 1,211 patients hospitalized with documented CAD at either a university hospital or a large suburban community hospital, 36% failed to receive appropriate evaluation and treatment for dyslipidemia. Younger patients, those admitted to a university hospital, and those undergoing percutaneous coronary intervention were substantially more likely to receive appropriate lipid management than other subgroups.

Adult↗

Evidence linking chondrocyte lipid peroxidation to cartilage matrix protein degradation. Possible role in cartilage aging and the pathogenesis of osteoarthritis.

Reactive oxygen species (ROS) are implicated in both cartilage aging and the pathogenesis of osteoarthritis. We developed an in vitro model to study the role of chondrocyte-derived ROS in cartilage matrix protein degradation. Matrix proteins in cultured primary articular chondrocytes were labeled with [(3)H]proline, and the washed cell matrix was returned to a serum-free balanced salt solution. Exposure to hydrogen peroxide resulted in oxidative damage to the cell matrix as established by monitoring the release of labeled material into the medium. Calcium ionophore treatment of chondrocytes, in a dose-dependent manner, significantly enhanced the release of labeled matrix, suggesting a chondrocyte-dependent mechanism of matrix degradation. Antioxidant enzymes such as catalase or superoxide dismutase did not influence matrix release by the calcium ionophore-activated chondrocytes. However, vitamin E, at physiological concentrations, significantly diminished the release of labeled matrix by activated chondrocytes. The fact that vitamin E is a chain-breaking antioxidant indicates that the mechanism of matrix degradation and release is mediated by the lipid peroxidation process. Lipid peroxidation was measured in chondrocytes loaded with cis-parinaric acid. Both resting and activated cells showed constitutive and enhanced levels of lipid peroxidation activity, which were significantly reduced in the presence of vitamin E. In an immunoblot analysis, malondialdehyde and hydroxynonenal adducts were observed in chondrocyte-matrix extracts, and the amount of adducts increased with calcium ionophore treatment. Furthermore, vitamin E diminished aldehyde-protein adduct formation in activated extracts, which suggests that vitamin E has an antioxidant role in preventing protein oxidation. This study provides in vitro evidence linking chondrocyte lipid peroxidation to cartilage matrix protein (collagen) oxidation and degradation and suggests that vitamin E has a preventive role. These observations indicate that chondrocyte lipid peroxidation may have a role in the pathogenesis of cartilage aging and osteoarthritis.

Aldehydes↗

Expression of the multidrug resistance gene in human prostate cancer.

Prostate cancer has become the most common cancer in males and the second most common cause of male cancer death in England and Wales. Death rates have doubled over the last 20 years. Prostate cancer is characterized by a high initial response rate to hormonal therapy. Drug-resistance is a significant cause of relapse in cancer. The multidrug resistance genes (MDR) encode resistance to a diverse family of cytotoxic chemotherapy agents. There are four known MDR genes, two of which are present in humans. MDR1 encodes for P-glycoprotein, a 170-kDa transmembrane calcium-dependent efflux pump. We examined P-glycoprotein expression by immunocytochemistry in 96 patients with prostate cancer and 20 patients with benign prostatic hypertrophy. A direct correlate was found between tumor grade, stage, and prostate specific antigen levels, indicating the possible significance of this protein in recurrent prostate cancer.

Journal Article↗

Parental style and vulnerability to depression: the role of core beliefs.

This study considers the potential role of core beliefs (unconditional schema-level representations) in the relationship between recalled parenting in childhood and major depression in adulthood, comparing a group of depressed outpatients (N = 60) with a healthy community sample (N = 67). The depressed group were differentiated by poorer perceived parenting (low care and high overprotection) and by three unhealthy core beliefs (defectiveness/shame, self-sacrifice, and insufficient self-control). Among nonclinical participants, it appears that vulnerability to harm beliefs act as a partial mediator of the relationship between poor paternal care and the development of depressive features. In contrast, a broader set of core beliefs appears to mediate the relationship of maternal bonding and paternal overprotection with depressive symptoms among the depressed group. The findings suggest that clinical work with adults with major depression might need to take account of parental style. Where parents are reported to be uncaring or overprotective, cognitive-behavioral therapy might need to include a schema-focused component.

Adolescent↗

Slow-release 5-fluorouracil and triamcinolone reduces subglottic stenosis in a rabbit model.

A previous pilot study suggested that a sustained-release conjugate that provided a slow release of 5-fluorouracil and triamcinolone acetonide injected into the tracheal and paratracheal tissues of rabbits at the time of subglottic surgery reduced the formation of subglottic stenosis. Our study was undertaken to confirm the effect. Ten milligrams of the compound suspended in hyaluronic acid was injected at the time of injury via a laryngofissure approach. The results showed that the control group had a mean stenosis of 52%, whereas the treated group had a mean stenosis of 32%. There was a significant difference between the treated and untreated groups (p = .003). It is hoped that this co-drug ultimately can be used in humans to reduce stenosis formation after laryngotracheal surgery and in other forms of otorhinolaryngological surgery.

Animals↗

Women and HIV--revisited ten years on.

This article compares how women and their relationship to HIV has changed since the original publication of this article in 1990. The number of women infected with HIV has continued to rise, but, in contrast, there have been few changes in their management. We review transmission risks and manifestations of the infection, and also discuss the issues faced by women with HIV.

AIDS-Related Opportunistic Infections↗

Nasal toxicity of cocaine: a hypercoagulable effect?

Nasal insufflation of cocaine injures the nasal mucosa and can perforate the septum. Cocaine-induced vasoconstriction resulting in ischemia is one of the methods that may be responsible for this damage. We are determining whether cocaine also produces a hypercoagulable state that may compound factors which have been previously established to cause damage to the nasal mucosa and septum. This study uses Modified Recalcification Time (MRT), a test developed in our laboratory that has the ability to measure the overall coagulation process. Our study revealed no connection between cocaine and enhanced platelet function or monocyte-released tissue factor. The coagulation process was unaffected by the addition of the drug, so we conclude that cocaine does not cause a hypercoagulable state and cannot assist in the explanation regarding the ischemic changes of the nasal septum.

Blood Coagulation↗

Protecting the rights of sex workers: the Indian experience.

Although India is a signatory to numerous international agreements on the rights of women and has a constitution that prohibits discrimination and exploitation by gender, as well as a plethora of related legislation, it has failed to satisfactorily protect the human rights of women, particularly those of sex workers. This is manifested in high levels of violence in the sex industry, child sex workers, lack of access to health care, and high levels of HIV infection. Policies that revolve around rescue and rehabilitation, or are based on the premise that sex work is immoral, are unlikely to effectively promote the well-being of sex workers. An alternative paradigm, which revolves around an explicit recognition of the human rights of sex workers together with an activist approach to achieve them, involving a collaboration between NGOs and collectives of sex workers, has worked well to protect the human rights and health of sex workers in India.

AIDS Serodiagnosis↗

Preferential perinuclear localization of poly(ADP-ribose) glycohydrolase.

The transient nature of poly(ADP-ribosyl)ation, a posttranslational modification of nuclear proteins, is achieved by the enzyme poly(ADP-ribose) glycohydrolase (PARG) which hydrolyzes the poly(ADP-ribose) polymer into free ADP-ribose residues. To investigate the molecular size and localization of PARG, we developed a specific polyclonal antibody directed against the bovine PARG carboxy-terminal region. We found that PARG purified from bovine thymus was recognized as a 59-kDa protein, while Western blot analysis of total cell extracts revealed the presence of a unique 110-kDa protein. This 110-kDa PARG was mostly found in postnuclear extracts, whereas it was barely detectable in the nuclear fractions of COS7 cells. Further analysis by immunofluorescence revealed a cytoplasmic perinuclear distribution of PARG in COS7 cells overexpressing the bovine PARG cDNA. These results provide direct evidence that PARG is primarily a cytoplasmic enzyme and suggest that a very low amount of intranuclear PARG is required for poly(ADP-ribose) turnover.

Animals↗

Poly(ADP-ribose) glycohydrolase is present and active in mammalian cells as a 110-kDa protein.

Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. Purification of PARG from many tissues revealed heterogeneity in activity and structure of this enzyme. To investigate PARG structure and localization, we developed a highly sensitive one-dimensional zymogram allowing us to analyze PARG activity in crude extracts of Cos-7, Jurkat, HL-60, and Molt-3 cells. In all extracts, a single PARG activity band corresponding to a protein of about 110 kDa was detected. This 110-kDa PARG activity was found mainly in cytoplasmic rather than in nuclear extracts of Cos-7 cells.

Animals↗

H2-E transgenic class II-negative mice can distinguish self from nonself in susceptibility to heterologous thyroglobulins in autoimmune thyroiditis.

Susceptibility to experimental autoimmune thyroiditis (EAT) is linked to H2-A class II genes; k and s haplotypes are susceptible, while b and f are resistant. EAT is inducible with thyroglobulins (Tgs) from several mammalian species which share portions of identical sequences. But cross-activation and cross-tolerance studies with mouse (m), human (h), and porcine (p) Tg have indicated mTg-unique T-cell epitope(s), in addition to conserved, in EAT induction. The recent introduction of the HLA-DRB1*0301 (DR3) transgene rendered major histocompatibility complex (MHC) class II-negative (Ab(0)) mice susceptible to EAT induction by both hTg and mTg, suggesting usage of conserved epitopes. Here, we introduced the H2-Ea(k) transgene into resistant B10 (H2(b)) or Ab(0) mice with a defective Ea gene to provide functional surface H2E (b haplotype) expression. Surprisingly, both transgenic strains showed severe inflammation only after hTg, but not mTg, immunization, although the moderating influence of the A(b) gene in B10 was evident. In proliferative assays, hTg-primed cells did not respond to mTg, nor to conserved 12mer peptides from three primary hormonogenic sites, two of which can activate T cells for thyroiditis transfer and cytotoxicity. The vigorous response to hTg stimulation was reduced only by Ebeta(b)-specific monoclonal antibody. EAT induction with bovine and pTg showed responses similar to hTg, suggesting thyroiditogenic epitopes shared with hTg, but not mTg. This is the first demonstration of: (1) nonpermissiveness for EAT induction with mTg, normally the most thyroiditogenic Tg and the one with unique epitopes for susceptible mice, and (2) the separation of hTg from mTg in EAT induction in H2-E-transgenic mice.

Animals↗