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Biomedical subjects

P Reddy

Publications and source records attributed to P Reddy.

At least 55 records · Page 3Linked to original sources
PubMed2000

Molecular genetic diversity in 5 populations of Madhya Pradesh, India.

This paper presents data on the distribution of 3 amplified fragment length polymorphisms (D1S80, APOB, and YNZ22) in 5 populations of Central India. Using the polymerase chain reaction technique, 3 caste (Brahmin, Khatri, and Dhimer) and 2 tribal (Gond and Baiga) populations were studied for the 3 loci. The allelic variations observed in the caste populations are compatible with those of many Caucasian populations, but the caste populations showed significant overall and interpopulation variability within the region. D1S80 allele *24 varied from 32% (Dhimers) to 42% (Brahmins). Allele *18 was not observed in Baiga tribal populations, but in caste populations it varied from 11% (Dhimers) to 24% (Brahmins). Both tribal populations showed higher frequencies of allele *31 (17%-18%). For APOB, caste populations again showed bimodal distribution of alleles *35 and *37, but in tribal populations higher allele numbers (*47, *49) were also frequent. For YNZ22, extensive variation was observed for all populations studied. Allele *4 was the most common in caste populations, while alleles *2, *7, and *10 were prominent in tribal populations. The level of gene differentiation is not very high for the 3 systems studied in the 5 populations. Overall, allele frequency distribution, heterozygosity, and genetic diversity analysis show that the genetic diversity observed is socially and geographically structured.

Alleles↗
PubMed2000

Synovial cyst of lumbar spine presenting as disc disease: a case report and review of literature.

Synovial cysts most commonly involve the joints of the extremities. These cysts are rarely found in the spinal canal or the vertebral facet joints. However, if manifested as such, they can pose serious diagnostic and therapeutic problems due to the presentation, which most often resembles nerve root or spinal cord compression. Acute low back pain and radiculopathy are often attributed to a herniated nucleus pulposus. This paper presents a case of synovial cyst in a 62-year-old woman with a 2-year history of refractory low back pain with distal radiation. A facet joint cyst was encountered upon neuroimaging, resulting in excision of the cyst. In this report, we discuss the differential diagnosis of synovial cysts, the role of computed tomography and magnetic resonance imaging in the diagnosis, and treatment options for this uncommon entity.

Diagnosis, Differential↗
PubMed1999

Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation in coronary artery bypass surgery.

The cost-effectiveness of amiodarone prophylaxis of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) was determined. A decision analysis using current hospital data and values from the literature was conducted. Under the base-case scenario, CABG patients received usual care (no prophylaxis) or 2 g of oral amiodarone hydrochloride over one to three days before surgery and 400 mg daily for seven days after surgery. Costs of hospitalization in the intensive care unit (ICU) and the cardiac step-down unit (SDU), cardioversion costs, electrocardiogram costs, drug costs, nursing administration charges, and pharmacy i.v. admixture charges were included. A sensitivity analysis using a Monte Carlo simulation and a one-way sensitivity analysis were performed. The mean cost per AF event avoided was lower in the amiodarone group ($15,750, 95% confidence interval [CI]: $15,591-$15,999) than the control group ($17,426,95% CI: $17,252-$17,600). A majority of the cost difference was due to the cost of hospitalization for patients without AF, the frequency of AF, and the cost of hospitalization in the SDU for patients with AF. For patients treated with amiodarone who did not develop AF, the cost difference was sensitive to changes in the cost of hospitalization and the efficacy of amiodarone. For patients who did develop AF, the cost difference was robust. Prophylaxis of AF with amiodarone in CABG patients was more cost-effective than usual care in the short term from a hospital perspective; the results were sensitive to changes in the cost of hospitalization of patients who did not develop AF and the efficacy of amiodarone.

Amiodarone↗
PubMed1999

cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype.

We have previously demonstrated decreased Jun/AP-1 activity in the breast cancer cell line MCF-7 when compared to normal or immortalized mammary epithelial cells. In this paper, we overexpress Jun in MCF-7 cells (MCF7Jun) and demonstrate that it results in diverse biologic and biochemical changes, which mimic those seen clinically in breast cancer. Overexpression of Jun causes significant alterations in the composition of AP-1, decreased junB and increased fra-1 expression and results in an increased biologic aggressiveness. MCF7Jun cells exhibit increased cellular motility, increased expression of a matrix degrading enzyme MMP-9, increased in vitro chemoinvasion and tumor formation in nude mice in the absence of exogenous estrogens. Furthermore, MCF7Jun cells are unresponsive to the growth stimulating effects of estrogen and growth inhibitory effects of tamoxifen. Analysis of the estrogen receptor (ER) expression and activity showed that the MCF7Jun cells have no detectable ER. MCF-7 cells overexpressing mutant forms of cJun were responsive to the growth stimulatory effects of estrogen indicating that full-length cJun is required to acquire the estrogen-independent phenotype in breast cancer cells.

Animals↗
PubMed1999

Unaltered cleavage and secretion of angiotensin-converting enzyme in tumor necrosis factor-alpha-converting enzyme-deficient mice.

Mammalian angiotensin-converting enzyme (ACE) is one of several biologically important ectoproteins that exist in both membrane-bound and soluble forms as a result of a post-translational proteolytic cleavage. It has been suggested that a common proteolytic system is responsible for the cleavage of a diverse group of membrane ectoproteins, and tumor necrosis factor-alpha-converting enzyme (TACE), a recently purified disintegrin-metalloprotease, has been implicated in the proteolytic cleavage of several cell surface proteins. Mice devoid of TACE have been developed by gene targeting. Such mice could provide a useful system to determine if TACE is responsible for the cleavage of other ectoproteins. Cultured fibroblasts without TACE activity, when transfected with cDNA encoding for the testicular isozyme of ACE (ACET), synthesized and secreted ACET normally after a proteolytic cleavage near the C terminus. In addition, similar quantities of the soluble, C-terminally truncated somatic isozyme of ACE (ACEP) were present in the serum of wild-type and TACE-deficient mice. These results demonstrate that TACE is not essential in the generation of soluble ACE under physiological conditions. Finally, we also report solubilization of ACE-secretase, the enzyme that cleaves ACE, from mouse ACE89 cells and from rabbit lung. We demonstrate that soluble ACE-secretase from both sources failed to cleave its substrate in solution, suggesting a requirement for anchoring to the membrane.

ADAM Proteins↗
PubMed1999

The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter.

Inherited mutations in the breast and ovarian cancer susceptibility gene BRCA1 are associated with high risk for developing breast and ovarian cancers. Several studies link BRCA1 to transcriptional regulation, DNA repair, apoptosis and growth/tumor suppression. BRCA1 associates with p53 and stimulates transcription in both p53 dependent and p53-independent manners. BRCA1 splice variants BRCA1a (p110) and BRCA1b (p100) associates with CBP/p300 co-activators. Here we show that BRCA1a and BRCA1b proteins stimulate p53-dependent transcription from the p21WAF1/CIP1 promoter. In addition, the C-terminal second BRCA1 (BRCT) domain is sufficient for p53 mediated transactivation of the p21 promoter. Previous studies emphasized the importance of the BRCT domain, which shows homology with p53 binding protein (53BP1), in transcriptional activation, growth inhibition and tumor suppression. Our findings demonstrate an additional function for this domain in protein-protein interaction and co-activation of p53. We also found that BRCA1a and BRCA1b proteins interact with p53 in vitro and in vivo. The p53 interaction domain of BRCA1a/1b maps, in vitro, to the second BRCT domain (aa 1760-1863). The BRCT domain binds to the central domain of p53 which is required for sequence specific DNA binding. These results demonstrate for the first time the presence of a second p53 interaction domain in BRCA1 proteins and suggests that BRCA1a and BRCA1b proteins, like BRCA1, function as p53 co-activators. This BRCT domain also binds in vitro to CBP. These results suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP/p300 associated HAT/FAT activity for acetylation of p53 to specific promoters resulting in transcriptional activation.

Animals↗
PubMed1999

Establishing networks for health promoting schools in South Africa.

South African schools were segregated by years of discriminatory practice. Apartheid policies adversely affected the health and social status of children in South Africa. The conceptual framework suggested by the health promoting schools movement was adopted in South Africa to address school health comprehensively. This approach provides a useful framework because it focuses not on the curriculum but on the school environment, community involvement, policy development, and appropriate health and social services. Currently, several initiatives in South Africa focus on developing networks of health promoting schools. Initiatives seen as a mechanism to address the historical inequities among children in South Africa are described.

Child↗
PubMed1999

Dental and craniofacial features of Aarskog syndrome: report of a case and review of literature.

Aarskog syndrome is a rare syndrome with a typical triad of facial, digital and genital characteristics. The characteristic cephalometric finding in this patient was the unusually large upward slant of SN plane and a steep Ba-N plane. Though the patient presented with a class I skeletal pattern, both the maxilla and mandible were hypoplastic and retruded with respect to the cranial base. Other characteristic features regarding the mandibular morphology were a large FMA (37 degrees) and Sn-GoGn (44 degrees) angles, a large gonial angle (138 degrees), an increase in total anterior facial and lower anterior facial height.

Abnormalities, Multiple↗
PubMed1999

Helminth control as an entry point for health-promoting schools in KwaZulu-Natal.

OBJECTIVES: To use a health promotion model to investigate the risk factors (predisposing, enabling and reinforcing) for geohelminth and schistosomiasis infections, in order to develop and implement effective intervention strategies. DESIGN: Phase 1: Qualitative study using focus group discussions (FGDs) with parents, pupils and teachers; and interviews with health workers. Phase 2: Quantitative study using a semi-structured questionnaire to investigate whether the determinants identified in phase 1 were generalisable. SETTING: Rural primary schools in Vulamehlo magisterial district, southern KwaZulu-Natal. STUDY POPULATION: Qualitative study: 9 schools with 179 pupils, 93 parents and 82 teachers; and local clinics (4 fixed, 1 mobile), with 7 professional nurses. Quantitative study: 2 other schools, with 730 pupils. RESULTS: Predisposing factors: Respondents were familiar with symptoms, but did not know the cause or mode of transmission of helminth infections. Many respondents perceived food to be the cause of geohelminth infection and swimming in the river to be the cause of schistosomiasis. Although 649 (88.9%) pupils had toilets at home and at school, only 218 (29.9%) were motivated to 'always' use the toilet for faecal disposal (rural communities previously did not have toilets). Six hundred and seventy-eight pupils (92.9%) understood that it was necessary to wash their hands after using the toilet, but many schools lacked water. Personal cleanliness was a problem despite the emphasis on hygiene by health workers and teachers. Few pupils admitted to eating soil, but it was agreed that geophagia affected young children between the ages of 8 months and 6 years. Enabling factors (positive/negative): Barriers to health promotion frequently included inadequate toilet facilities at school and home, and river-water contact resulting from a lack of clean water. A dearth of recreational facilities resulted in children swimming and playing in the river. Positive factors were the health-seeking behaviour of the majority of the target group, who identified helminth infections as a health problem and sought treatment. Parents and pupils in the FGDs unanimously supported health education and 655 (89.8%) questionnaire respondents indicated that they wished to learn how to avoid helminth infections. CONCLUSIONS: Although the Government strategy is to provide clean water and adequate sanitation, provision of services does not necessarily ensure usage. A comprehensive approach to health promotion is required and the complementary development of the 'health-promoting school' would support, reinforce and sustain a helminth control programme.

Adolescent↗
PubMed1999

STD-related knowledge, beliefs and attitudes of Xhosa-speaking patients attending STD primary health-care clinics in South Africa.

The primary aim of this study was to describe patients at sexually transmitted disease (STD) clinics in Cape Town, South Africa, in terms of gender, education and age differences relative to their STD knowledge and beliefs, their condom use, as well as their attitudes towards condom use and their condom-use behaviour. The information was collected with a view to developing a health education intervention. Structured interviews were conducted with 2978 randomly sampled Xhosa-speaking STD clinic attenders about their knowledge, beliefs and practices regarding STDs and related behaviours. More males (75%) than females (25%) presented for STD treatment. The majority of patients (92%) were younger than 35 years. Female patients were found to be more aware than male patients of the sexual nature of STD transmission, valued personal autonomy in sexual behaviour and expressed a greater need to use condoms. Males perceived STD symptoms to be more serious, had more misconceptions about the cause of STDs and also more negative beliefs and attitudes towards condom use. Only 34.9% of the patients reported using condoms in the last 6 months while only 24.5% reported regular use. Those who reported condom use were more knowledgeable about the sexual transmission of STDs and the effects of STDs on the neonate. They also had fewer misconceptions about the causes of STDs and perceived STD symptoms to be more serious, attached greater value to personal autonomy in sexual behaviour and condom use and had more positive outcome expectancies of refusing sex than those who never used condoms. The data suggest that targeted interventions directed at males will have to address their inadequate knowledge regarding STDs in terms of transmission, causes, consequences, prevention and cure. Their negative beliefs and attitudes towards condoms will need special attention, especially in view of their multiple partner behaviour. Interventions directed at females will need to improve their knowledge regarding STD consequences, causes, recognition of symptoms as well as improve their knowledge of aspects of prevention and cure. All interventions must facilitate personal autonomy in decision making about sexual behaviour and condom use for both men and women, through skills development programmes that promote self-efficacy in the individual and instil a culture of mutual respect of such in the community.

Adult↗
PubMed1998

An essential role for ectodomain shedding in mammalian development.

The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.

ADAM Proteins↗
PubMed1998

Pro-tumor necrosis factor-alpha processing activity is tightly controlled by a component that does not affect notch processing.

The extracellular domain of a heterogeneous group of transmembrane proteins can be proteolytically released from the cell surface, a process known as protein ectodomain shedding. Despite the biomedical importance of several substrates of the shedding system, such as the beta-amyloid precursor protein (betaAPP), little is known about the regulation of protein ectodomain shedding, and the only protease known to be involved is the metalloprotease disintegrin, tumor necrosis factor-alpha converting enzyme (TACE). Here, we show that previously described pro-transforming growth factor-alpha shedding-defective cell mutants (M2 cells), known to be defective in ectodomain shedding of several molecules, that include betaAPP, fail to shed the ectodomain of pro-TNF-alpha. The target of the mutation is a component required for TACE activity, since transfection of TACE into M2 cells has no effect on the shedding of pro-TNF-alpha and somatic cell fusions between M2 cells and TACE null cells recover the ability to shed pro-TNF-alpha, pro-transforming growth factor-alpha, and betaAPP. Furthermore, we show that TACE is also necessary for the shedding of betaAPP since TACE null cells show defective betaAPP shedding. Biochemical evidence shows that the component that controls TACE is different from protein kinase C, the only known activator of protein ectodomain shedding, and that this component does not affect biosynthesis or processing of TACE or other metalloprotease disintegrins. The component mutated in M2 cells is likely to control only a subset of metalloprotease disintegrins involved in regulated ectodomain shedding, since Notch processing, a process known to be dependent on the activity of another metalloprotease disintegrin, Kuzbanian, is normal in M2 cells.

ADAM Proteins↗
PubMed1998

Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme.

Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective inflammatory reactions and kills tumor cells but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha is released from its membrane-bound precursor by a membrane-anchored proteinase, recently identified as a multidomain metalloproteinase called TNFalpha-converting enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This structure reveals a polypeptide fold and a catalytic zinc environment resembling that of the snake venom metalloproteinases, identifying TACE as a member of the adamalysin/ADAM family. However, a number of large insertion loops generate unique surface features. The pro-TNFalpha cleavage site fits to the active site of TACE but seems also to be determined by its position relative to the base of the compact trimeric TNFalpha cone. The active-site cleft of TACE shares properties with the matrix metalloproteinases but exhibits unique features such as a deep S3' pocket merging with the S1' specificity pocket below the surface. The structure thus opens a different approach toward the design of specific synthetic TACE inhibitors, which could act as effective therapeutic agents in vivo to modulate TNFalpha-induced pathophysiological effects, and might also help to control related shedding processes.

ADAM Proteins↗
PubMed1998

The learning curve: health education in STI clinics in South Africa.

This qualitative study aims to assess health education practice in sexually transmitted infection (STI) clinics in South Africa with a view to develop improved health education programs in such clinics. Health workers' knowledge of and attitudes towards health education practice, their perceived health education skills, the content of health education in STI clinics and the organizational structure as context for health education were investigated. In-depth interviews were conducted with 18 health care workers practicing in the area of STI control. A lack in knowledge and skills required for effective health education practice was reported. The constraints posed by health workers' current knowledge and skills around health education and the organizational structure in terms of the absence of policy and protocols to govern health education, limited time, space and resources, impede on the actual practice of health education. It seems that these obstacles to health education facilitate a biomedical approach to STI management. This approach is further portrayed in the power dynamics between the health workers as well as between health workers and patients. The data suggest that a health education intervention needs to be directed at an individual level namely at health workers and at the organizational level, i.e. the clinic that provides the context for health education. The newly adopted district health system which equally embraces medical care and health promotion augers well for a holistic management of STIs in South Africa. This would ensure the recognition of all categories of health workers' contributions to health education within their own functions, strengths and time limitations.

Community Health Services↗