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Biomedical subjects

S Srinivas

Publications and source records attributed to S Srinivas.

44 records · Page 3Linked to original sources
PubMed1992

Induction of c-jun protooncogene expression and transcription factor AP-1 activity by the polyoma virus middle-sized tumor antigen.

Polyoma virus middle-sized tumor (PymT) antigen is required for neoplastic cell transformation by polyoma virus. We studied changes in gene expression accompanying expression of PymT in murine fibroblasts. These experiments showed that PymT differentially affects several growth-related genes. c-jun protooncogene expression was highly increased, whereas the expression of two growth arrest-specific genes (gas) was reduced, in cells transformed by PymT. Cotransfection experiments showed that the increase in c-jun expression resulted from elevated activity of the transcription factor AP-1 and was mediated through the phorbol 12-tetradecanoate 13-acetate response element in the c-jun promoter. The degree of c-Jun/AP-1 activation by different PymT mutants correlated with their transforming capability, suggesting that regulation of c-Jun/AP-1 activity may play a role in cell transformation by polyoma virus.

Animals↗
PubMed1991

Dimethyl sulfoxide inhibits the expression of early growth-response genes and arrests fibroblasts at quiescence.

We have previously shown that dimethyl sulfoxide (DMSO) treatment of mouse embryo fibroblasts (MEF) at the early hours of mitogenic stimuli resulted in the inhibition of DNA and protein synthesis; delayed treatment of serum-stimulated cells with DMSO had little effect on the synthesis of these macromolecules. Here, we demonstrate the specific inhibition of expression of early growth response genes by DMSO in serum-stimulated MEF. The expression of interleukin 6, and of oncogenes c-myc and c-fos were inhibited when the cells were treated with 2% DMSO from the beginning of serum-stimulated growth but not after 3 h of mitogenic stimuli. Although the actin gene is an early serum-response gene, its expression was not affected by DMSO. The synthesis of another serum-induced protein, the plasminogen activator inhibitor-1 was blocked during concurrent and delayed (after 3 h of stimulation) treatment of serum-stimulated fibroblasts with DMSO. The expression of glyceraldehyde-3-phosphate dehydrogenase gene was not affected by DMSO. These results indicate that the expression of non-growth-related genes are either not affected or affected nonspecifically both at early and late stages of serum-induced growth of mouse embryo fibroblasts. The serum-induced expression of c-fos gene was abolished by DMSO treatment of MEF while the phorbol 12-myristate 13-acetate-induced expression of fos gene was not, indicating that the PMA signaling pathway was refractory to DMSO. Treatment of cells with medium containing 2% DMSO for 24-48 h prevents them from progression into cell cycle by preventing the expression of genes involved in G0-G1 transition of quiescent cells.

Actins↗
PubMed1989

Effect of dimethyl sulfoxide on mouse embryo fibroblasts: inhibition of plasminogen activator inhibitor deposition and interference with early events of serum-stimulated growth.

Quiescent and serum-stimulated cultures of Swiss mouse embryo fibroblasts (MEF) showed alterations in cell morphology including an enlargement in size upon treatment with 2% dimethyl sulfoxide (DMSO). Treatment of MEF and monkey kidney epithelial cells (MK2) with 2% DMSO at the early periods of serum-stimulated growth inhibited RNA, protein and DNA synthesis. DMSO treatment of cells at late stages of serum-stimulated growth (MEF after 1 hr and MK2 cells after 3 hr of stimulation) had little effect on DNA and protein synthesis although cell enlargement occurred in these cells. When the [35S]methionine labelled proteins of the control and the DMSO treated cells were analysed by high resolution polyacrylamide gel electrophoresis, no apparent difference was observed in the pattern of intracellular proteins of these cells. In contrast, the extracellular levels of two serum-induced secreted proteins of MEF (Mr 48,000 and 26,000) were dramatically reduced by DMSO treatment. The DMSO sensitive 48 kDa protein was found to be the major component of the extracellular matrix, while the 26 kDa protein was not. The 48 kDa protein was identified as plasminogen activator inhibitor (PAI-1). Densitometric quantitation showed a gradual accumulation of this protein in the matrix of serum-stimulated cells. The deposition of this protein in the matrix was inhibited by DMSO. Flow-cytometric quantitation of indirect immunofluorescence indicated higher intracellular levels of the 48 kDa protein in fetal calf serum (FCS) + DMSO treated cells, suggesting that the low level of this protein in the medium of DMSO treated cells is probably due to lack of transport of this protein from the cells into the medium.

Animals↗
PubMedDate not supplied

Actinomycin D revisited in testicular cancer. A case report.

BACKGROUND: Between 20-30% of patients with advanced germ cell tumors relapse or fail to achieve a complete response to conventional cisplatin based chemotherapy. Ifosphamide has been used very effectively in combination with cisplatin and etoposide (VIP) or in combination with cisplatin and vinblastine (VeIP). Actinomycin D with chlorambucil and methotrexate was widely used in the 1960s with complete responses in 20% of patients and long term survival of 6-10%. There exists no information on the use of actinomycin as a salvage in cisplatin refractory patients. METHODS AND RESULTS: One patient with metastatic germ cell tumor who failed chemotherapy with cisplatin and ifosphamide was successfully treated with an actinomycin D based regimen. CONCLUSIONS: Actinomycin D is an active agent in testicular cancer and maybe used in patients refractory to platinum.

Adult↗
PubMedDate not supplied

Efficacy and safety of carvedilol in infants with dilated cardiomyopathy: a preliminary report.

BACKGROUND: Carvedilol has proven to be beneficial in a majority of adult patients with congestive heart failure. Although the experience from adult patients may be extrapolated to older children, symptomatic infants remain a subset for whom dosage, safety and efficacy need to be established. The purpose of this study was to assess whether treatment with carvedilol is efficacious and safe for infants with dilated cardiomyopathy who do not show satisfactory clinical improvement despite treatment with conventional medications. METHODS AND RESULTS: Eight infants with dilated cardiomyopathy (ejection fraction <30%) who were symptomatic despite tailored treatment with decongestive medications, were enrolled in the study. Echocardiographic findings and heart failure symptom scores were analyzed before and after starting carvedilol. Patients were hospitalized and monitored for side-effects during up-titration of carvedilol. At a follow-up of 4.5+/-2.2 months, patients receiving carvedilol showed a significant improvement in the left ventricular ejection fraction (38.5+/-11% v. 24.4+/-5%), and heart failure symptom score (p<0.05). No adverse events related to carvedilol administration occurred. There were no deaths. CONCLUSIONS: Carvedilol is well tolerated in infants with dilated cardiomyopathy and there is significant improvement in their functional status. Optimal timing of starting therapy, dosage and long-term effects need to be investigated with multi-institutional trials.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Ross procedure in an infant.

The Ross procedure is gaining acceptance as the procedure of choice for aortic valve replacement in children. We present the case of a 4-month-old child (weight 3.2 kg) suffering from congenital valvar aortic stenosis who underwent a Ross procedure. We believe that this is the youngest patient to have undergone this procedure successfully in the Indian subcontinent.

Aortic Valve↗
PubMedDate not supplied

Antibody testing in Indian children with celiac disease.

BACKGROUND: We prospectively evaluated the usefulness of IgA tissue transglutaminase antibodies (IgA tTG) in the initial diagnosis of celiac disease (CD) and compared its diagnostic potential with that of IgA anti-endomysial antibodies (IgA EMA) and anti-IgA and IgG gliadin antibodies (AGA and AGG, respectively). METHODS: Sera of 23 untreated children fulfilling the revised ESPGHAN criteria for diagnosis of CD (Group I; mean age 10.8 y); 19 disease controls (Group II; mean age 8.5 y) presenting with chronic diarrhea, short stature or both; and 22 healthy children (Group III; mean age 8.8 y) were studied. These were tested in a blinded manner for AGA, AGG, IgA tTG (guinea pig as antigen) and IgA EMA. RESULTS: In Group I, IgA EMA was positive in 19, IgA tTG in 17, AGA in 14 and AGG in 17 patients. In Group II, these tests were positive in 1, 0, 2 and 14 patients, respectively and in Group III, in 0, 0, 0 and 1 child, respectively. Analyzing data from Group I and II, IgA EMA, IgA tTG, AGA and AGG had sensitivity rates of 83%, 74%, 61% and 74%, respectively; the specificity rates were 95%, 100%, 89% and 26%; positive predictive values were 95%, 100%, 88% and 55% and negative predictive values were 82%, 74%, 65% and 45%, respectively. CONCLUSION: IgA tTG is useful for the diagnosis of CD, with sensitivity and specificity rates comparable to those of EMA and this test is well suited for use in tropical countries like India.

Adolescent↗