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Biomedical subjects

R Vyas

Publications and source records attributed to R Vyas.

At least 19 recordsLinked to original sources
PubMed1999

Suppression of tumorigenicity in human ovarian cancer cell lines is controlled by a 2 cM fragment in chromosomal region 6q24-q25.

Multiple distinct regions of chromosome 6 are frequently affected by losses of heterozygosity in primary human ovarian carcinomas. We introduced a normal human chromosome 6 into HEY and SKOV-3 ovarian carcinoma cell lines using microcell-mediated chromosome transfer techniques to further investigate the role of this chromosome in ovarian tumorigenesis. The exogenous chromosome was stably propagated in the recipient cells based on fluorescence in situ hybridization (FISH) analyses with a chromosome 6 painting probe. The tumorigenicity of HEY and SKOV-3 cells was completely suppressed after transfer of chromosome 6, but not after transfer of a chromosome 11q13-qter fragment used as control. Using 46 polymorphic microsatellite markers, the region bounded by D6S1649 and D6S1564 was found to be commonly deleted in HEY: chromosome 6 tumorigenic revertant clones. The boundaries of the commonly deleted region could be further narrowed down to a 2 cM (based on the Whitehead genetic map) or 0.36 megabase (based on gdb mapping data) region between D6S1637 and D6S1564 after transferring the exogenous chromosome from revertants into mouse L cells and performing allelic deletion mapping studies against this mouse background. We conclude that this region contains a tumor suppressor gene important for the control of ovarian tumor development.

Animals↗
PubMed1996

Toxoplasmosis of the spinal cord in a patient with AIDS: case report and review.

We present the case of a patient whose acute myelopathy almost completely resolved with empirical therapy for toxoplasmosis, and we review thirteen previously reported cases of myelopathy thought to have been caused by Toxoplasma gondii in patients with AIDS. The most common symptoms and abnormal physical findings were motor loss (usually paraparesis), bilateral sensory loss, urinary bladder dysfunction, and local pain. The majority of patients had magnetic resonance images that showed abnormalities of the spinal cord and brain in association with positive serology for Toxoplasma. Therapy for toxoplasmosis, when administered soon after the onset of symptoms, has resulted in clinical and radiographic improvement in the conditions of patients with toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1991

Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid).

BACKGROUND AND METHODS: Patients with acute promyelocytic leukemia have a characteristic (15;17) translocation, with a breakpoint on chromosome 17 in the region of the retinoic acid receptor-alpha (RAR-alpha). Since this receptor has been shown to be involved with growth and differentiation of myeloid cells in vitro, and since recent clinical studies have reported that tretinoin (all-trans-retinoic acid) induces complete remission in patients with acute promyelocytic leukemia we studied the effects of tretinoin on cellular maturation and molecular abnormalities in patients undergoing the induction of remission with this agent. RESULTS: Eleven patients with acute promyelocytic leukemia were treated with tretinoin administered orally at a dose of 45 mg per square meter of body-surface area per day. Nine of the 11 patients entered complete remission. In two patients, complete remission was preceded by striking leukocytosis that then resolved despite continued drug treatment. Serial studies of cellular morphologic features, cell-surface immunophenotypic analysis, and fluorescence in situ hybridization with a chromosome 17 probe revealed that clinical response was associated with maturation of the leukemic clone. All patients who responded to treatment who were tested by Northern blot analysis had expression of aberrant RAR-alpha. As patients entered complete remission, the expression of the abnormal RAR-alpha message decreased markedly; however, it was still detectable in several patients after complete morphologic and cytogenetic remission had been achieved. CONCLUSIONS: Tretinoin is a safe and highly effective agent for inducing complete remission in patients with acute promyelocytic leukemia. Clinical response to this agent is associated with leukemic-cell differentiation and is linked to the expression of an aberrant RAR-alpha nuclear receptor. Molecular detection of the aberrant receptor may serve as a useful marker for residual leukemia in patients with this disease.

Administration, Oral↗
PubMed1991

Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all trans-retinoic acid.

Two recent reports have described major clinical benefits from all-trans-retinoic acid (tRA) therapy of patients with promyelocytic leukemia (APL). This paper describes the first patient with a blast crisis of chronic myelogenous leukemia (CML-BC) who responded to oral tRA therapy. In vitro marrow studies, including clonogenic assays, immunopheno-typing, cytogenetics and premature chromosome condensation together with chromosome painting provided evidence for the in vivo differentiation and maturation of the malignant cells. The patient achieved a partial remission with reversal of all clinical features of disease, including normalization of peripheral blood counts, complete resolution of fever, fatigue and splenomegaly, and marked maturation of the bone marrow. This response to tRA in CML-BC is unique, and broadens the spectrum of diseases which may respond to retinoids.

Antineoplastic Agents↗
PubMed1990

A restriction fragment length polymorphism for human topoisomerase II: possible relationship to drug-resistance.

In previous studies we used Southern blotting to examine the topoisomerase II locus (on chromosome 17) in human leukemia cell lines and noted a difference in the XmnI restriction endonuclease digestion pattern between an m-AMSA-resistant line and its m-AMSA-sensitive parent line (Zwelling, L. A.; Hinds, M,; Chan, D.; Mayes, J.; Sie, K. L.; Parker, E.; Silberman, L.; Radcliffe, A.; Beran, M.; Blick, M. Characterization of an amsacrine-resistant line of human leukemia cells. Evidence for a drug-resistant form of topoisomerase II. Journal of Biological Chemistry 264:16411-16420; 1989). We now demonstrate that the variable XmnI digestion pattern represents a normal restriction fragment length polymorphism (RFLP) which is observed in subjects without malignant disease and exhibits an autosomal pattern of inheritance. These data suggest that the previously described deviation in the genomic structure of topoisomerase II in the m-AMSA-resistant cell line did not reflect a new mutation, but rather a reduction to homozygosity at the topoisomerase II locus. This reduction to homozygosity is not due to chromosomal loss, as chromosome 17-specific gene probes clearly identify two chromosome 17's in the sensitive line and four in the resistant line, using chromosome painting with a chromosome 17-specific library. Some other genetic change must be the cause of the resistance of HL-60/AMSA and its topoisomerase II to the inhibiting actions of m-AMSA.

Alleles↗
PubMed1990

Cardiovascular response to dynamic treadmill exercise in patients with essential hypertension before and after therapy with atenolol or captopril.

Thirty eight patients with essential hypertension and 20 healthy volunteers were subjected to treadmill exercise test. The hypertensives were then controlled with atenolol or captopril by randomly forming two groups of 19 patients each, and treadmill evaluation was repeated. The resting rate-pressure product (RPP) and myocardial oxygen consumption (MVO2), as well as peak RPP and MVO2 and recovery time, were increased and exercise duration decreased significantly in uncontrolled hypertensives (p less than 0.001). Control of hypertension resulted in significant improvement of exercise performance in both the groups. Atenolol, when compared to captopril, resulted in better exercise conditioning with considerable lowering of resting and peak RPP and MVO2 (p less than 0.001), though the difference in exercise duration, maximum work load and recovery time were not significant (p greater than 0.05). Thus, where myocardial oxygen consumption is an important consideration while treating hypertension, atenolol offers a better choice.

Adult↗