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Biomedical subjects

M Wani

Publications and source records attributed to M Wani.

8 recordsLinked to original sources
PubMed2004

Low birth weight and its implication in renal disease.

It has been demonstrated that intrauterine growth retardation, defined as birth weight below the 10th percentile, gives rise to a reduction in nephron number. Oligonephropathy has been suggested to increase the risk for systemic and glomerular hypertension in adult life as well as enhance risk for expression of renal disease after exposure to potentially injurious renal stimuli. Diseases, such as diabetes, that damage the kidney, may enhance this risk. In addition, it has been hypothesized that the same factors affecting kidneys in utero also impact on pancreatic tissue development, thus predisposing infants of low birth weight to an increased risk for the subsequent development of diabetes and diabetic nephropathy, consistent with the so-called "thrifty phenotype" hypothesis. Impact of low birth weight on nondiabetic renal disease has also been shown in some studies. In the current scenario, chronic kidney disease is increasing all over the world and the major two causes are diabetes and hypertension. Once the issues are shifting from management of end-stage renal disease to prevention of chronic kidney disease, prevention of low birth weight is likely to be an issue for the nephrologists in future.

Child Development↗
PubMed2002

Pneumocystis carinii pneumonia: role of high resolution computed tomography.

Pneumocystis carinii (PC) is a common opportunistic infection in renal transplant recipients and requires an early diagnosis for its successful treatment. For its definitive diagnosis PC needs to be demonstrated in bronchoalveolar lavage (BAL) fluid. At times BAL may not be possible or get delayed. In such conditions typical appearances seen on high resolution CT of the chest help in early diagnosis of PC pneumonia (PCP). This easily performed procedure helped in early diagnosis of PCP in two patients.

Adult↗
PubMed2001

Dual role of glutathione in modulating camptothecin activity: depletion potentiates activity, but conjugation enhances the stability of the topoisomerase I-DNA cleavage complex.

Depletion of glutathione (GSH) in MCF-7 and MDA-MB-231 cell lines by pretreatment with the GSH synthesis inhibitor buthionine sulfoximine potentiated the activity of 10,11-methylenedioxy-20(S)-camptothecin, SN-38 [7-ethyl-10-hydroxy-20(S)-camptothecin], topotecan, and 7-chloromethyl-10,11-methylenedioxy-20(S)-camptothecin (CMMDC). The greatest potentiation was observed with the alkylating camptothecin CMMDC. Buthionine sulfoximine pretreatment also increased the number of camptothecin-induced DNA-protein crosslinks, indicating that GSH affects the mechanism of action of camptothecin. We also report that GSH interacts with CMMDC to form a stable conjugate, 7-(glutathionylmethyl)-10,11-methylenedioxy-20(S)-camptothecin (GSMMDC), which is formed spontaneously in buffered solutions and in MCF-7 cells treated with CMMDC. GSMMDC was synthesized and found to be nearly as active as 10,11-methylenedioxy-20(S)-camptothecin in a topoisomerase (topo) I-mediated DNA nicking assay. The resulting topo I cleavage complexes were remarkably stable. In cell culture, GSMMDC displayed potent growth-inhibitory activity against U937 and P388 leukemia cell lines. GSMMDC was not active against a topo I-deficient P388 cell line, indicating that topo I is its cellular target. Peptide-truncated analogues of GSMMDC were prepared and evaluated. All three derivatives [7-(gamma-glutamylcysteinylmethyl)-10,11-methylenedioxy-20(S)-camptothecin, 7-(cysteinylglycylmethyl)-10,11-methylenedioxy-20(S)-camptothecin, and 7-(cysteinylmethyl)-10,11-methylenedioxy-20(S)-camptothecin] displayed topo I and cell growth-inhibitory activity. These results suggest that 7-peptidyl derivatives represent a new class of camptothecin analogues.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Mitotic and post mitotic consequences of genomic instability induced by oncogenic Ha-ras.

Induced expression of a mutant human Ha-ras oncogene in NIH3T3 cells leads to the rapid production of multicentric chromosomes, acentric chromosome fragments, double minute chromosomes, increased heteroploidy, and increased capacity to undergo gene amplification. In this study we have used fluorescent-in-situ hybridization (FISH) to demonstrate that induction of the Ha-ras oncogene also leads to disruption of the mitotic machinery, resulting in aberrant mitoses and abnormal daughter cells. Cells induced to express an oncogenic Ha-ras transgene accumulate chromosomes that lag outside of the rest of the chromosomal architecture, chromosomes that form bridges between daughter nuclei at anaphase, and that form micronuclei. Many of these mitotic aberrations contain structurally abnormal chromosomes. These ras-induced changes were suppressed by the introduction of a gene encoding the dominant negative effector of ras, raf 301. Expression of raf301 in cells induced to express Ha-ras reduced the level of growth in soft agar, chromosome aberrations, mitotic aberrations, and frequency of gene amplification. These data provide evidence for an association between Ha-ras induced transformation, chromosome aberrations and gene amplification. Furthermore they offer insight into how the cell responds to the formation of aberrant chromosomes, and how disrupting chromosomal architecture could lead to further imbalances in the distribution of genetic material between daughter cells.

3T3 Cells↗
PubMed1994

Therapeutic efficacy of camptothecin derivatives against human malignant melanoma xenografts.

Camptothecin (CPT) and some of its derivatives are currently used in several clinical studies with patients bearing leukaemias, lymphomas, and malignancies of various solid tissues. Therefore, it is important to establish parameters and conditions that will allow the drugs to exhibit maximal anti-cancer effectiveness with minimal toxic effects. We tested several water-insoluble CPT derivatives for their ability to inhibit growth of human melanoma tumours xenografted in nude mice. We found that anti-tumour effectiveness and drug-induced toxicity depended on (a) the CPT derivative; (b) the drug dose administered; (c) the mode of administration; and (d) the scheduling of drug administration. For all practical purposes, oral administration of the CPT derivative, 9-nitrocamptothecin, has produced the best overall results.

Animals↗
PubMed1990

ECG record during changes in oesophageal pH.

Seventeen patients with non-cardiac chest pain were investigated by simultaneous ambulatory 24 hour ECG and oesophageal pH monitoring. While 11 patients lowered their oesophageal pH below 4 for a significant percentage, (3.4%) of recorded time and experienced chest pain, no simultaneous ECG changes occurred. In 10 patients chest pain was reproduced by an oesophageal acid perfusion test (Bernstein test). No changes in ECG record during the test were shown. We conclude that although reflux oesophageal pain may be difficult to differentiate from cardiac pain, clinically oesophageal pH changes do not produce any ECG changes.

Adult↗
PubMed1989

Methotrexate resistance in NIH3T3 cells expressing polyoma virus oncogenes.

NIH3T3 cell lines expressing different polyoma virus oncogenes were found to differ by almost three orders of magnitude in frequencies of methotrexate-resistant (MTXr) cells in single-step selections. Cells expressing the polyoma small T antigen showed the highest frequencies of MTX resistance, whereas cells expressing the polyoma middle T antigen showed the lowest frequencies of MTX resistance. Amplification of the dihydrofolate reductase (dhfr) gene was not a mechanism of MTX resistance in these cell lines. Cells expressing large T antigen also showed a high frequency of MTXr colonies with only two of 20 such colonies showing evidence of marginal (less than threefold) dhfr gene amplification. Cells carrying the cloning vector without an oncogene showed intermediate frequencies of MTX resistance, and in contrast to the oncogene expressing lines, two-thirds of these MTXr colonies showed marked dhfr gene amplification. The results suggest that the plasticity of the genome as measured by frequency or extent of dhfr gene amplification is not increased by expression of either immortalizing or transforming polyoma oncogenes. These oncogenes may, however, influence MTX resistance through epigenetic mechanisms. In addition, there appears to be no relationship between frequency of methotrexate resistance and frequency of dhfr gene amplification. It is clear that mechanisms of resistance other than dhfr gene amplification can be exclusively associated with either very high or very low frequencies of resistance.

Animals↗