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Biomedical subjects

N Taneja

Publications and source records attributed to N Taneja.

At least 37 records · Page 2Linked to original sources

p56/p53lyn tyrosine kinase activation in mammalian cells treated with mitomycin C.

The present studies have examined the effects of mitomycin C (MMC), a genotoxic alkylating agent, on the activation of Src-like protein tyrosine kinases in HL-60 myeloid leukemia cells. The results demonstrate no detectable induction of p59fyn or pp60c-src activity. The response of HL-60 cells to MMC however was associated with rapid activation of p56/p53lyn. Similar findings were obtained with other alkylating agents such as nitrogen mustard and cis-platinum. Activation of p56/p53lyn was associated with increased autophosphorylation on tyrosine and sensitivity to the tyrosine kinase inhibitors herbimycin A and genistein. Studies with a glutathione S-transferase-Lyn fusion protein were performed to explore the potential significance of p56/p53lyn activation. Analysis of the adsorbates demonstrates interaction of Lyn with the cell cycle regulatory protein, p34cdc2. Coimmunoprecipitation studies further confirmed the association of p56/p53lyn and p34cdc2 in MMC-treated cells. We also demonstrate that p34cdc2 undergoes increased phosphorylation on tyrosine following MMC exposure and that p56/p53lyn phosphorylates the Tyr-15 site of p34cdc2 in vitro. These findings indicate that the cellular response to MMC includes activation of p56/p53lyn and that this event may contribute to signals transduced by the DNA damage-dependent mitotic checkpoint.

Alkylating Agents↗

Coinduction of c-jun gene expression and internucleosomal DNA fragmentation by ionizing radiation.

Previous work has demonstrated that the cellular response to ionizing radiation includes transcriptional activation of the c-jun early response gene. The present studies demonstrate that this induction of c-jun expression is temporally related to the appearance of internucleosomal DNA fragmentation. These events were maximal at 6 h and transient after exposure to lethal doses (20 Gy) of ionizing radiation. We also demonstrate that N-acetyl-L-cysteine (NAC), an antioxidant, inhibits X-ray-induced c-jun expression and endonucleolytic DNA cleavage. These findings suggested that both events are mediated at least in part through the formation of reactive oxygen intermediates (ROIs). Since ROIs damage DNA and X-ray-induced DNA damage is associated with activation of poly(ADP-ribose) polymerase (ADPRP), we studied the effects of the ADPRP inhibitors 3-aminobenzamide (3-AB), nicotinamide, and theophylline. 3-AB blocked both X-ray-induced c-jun expression and internucleosomal DNA fragmentation. Similar findings were obtained with nicotinamide and theophylline. In contrast, 3-AB had little if any effect on induction of c-jun transcripts or DNA fragmentation induced by the alkylating agent mitomycin C. While c-jun expression is restricted to cells in G1 and G1/S phases, we have found that X-ray-induced c-jun transcripts are detectable throughout all phases of the cell cycle. The induction of internucleosomal DNA fragmentation by X-rays was also detectable throughout the cell cycle. Taken together, these results support the coinduction of c-jun transcription and internucleosomal DNA fragmentation by ionizing radiation. Similar studies were performed with H2O2 since this agent also results in the production of ROIs.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗

Reactive oxygen intermediates target CC(A/T)6GG sequences to mediate activation of the early growth response 1 transcription factor gene by ionizing radiation.

The cellular response to ionizing radiation includes induction of the early growth response 1 gene (EGR1). The present work has examined the involvement of reactive oxygen intermediates (ROIs) in this response. Exposure of human HL-525 cells, an HL-60 subclone deficient in protein kinase C-mediated signaling, to both ionizing radiation and H2O2 was associated with increases in EGR-1 transcripts. These increases in EGR-1 expression were inhibited by the antioxidant N-acetyl-L-cysteine (NAC). Nuclear run-on assays demonstrate that NAC inhibits the activation of EGR1 transcription by these agents. Previous studies have shown that induction of EGR1 by x-rays is conferred by serum response or CC(A/T)6GG (CArG) elements. The present studies demonstrate similar findings with H2O2 and the finding that activation of the EGR1 promoter region containing CArG elements is abrogated by NAC. Moreover, we show that NAC inhibits the ability of a single CArG box to confer x-ray and H2O2 inducibility when linked to a heterologous promoter. Taken together, these findings indicate that ROIs induce EGR1 transcription by activation of CArG elements.

Actins↗

Dermatoglyphic patterns of patients with rheumatoid arthritis.

Finger tip and palmar dermatoglyphics were studied in 31 patients (22 females and 9 males) with rheumatoid arthritis (RA) and 38 matched controls (20 females and 18 males) from North India. While not many differences were observed in palmar patterns, a low ending of line A was found on both hands of two patients. Finger tip patterns were significantly different in patients compared to controls. No association with any dermatoglyphic feature and HLA antigens was observed.

Arthritis, Rheumatoid↗

Sister-chromatid exchanges are increased in epileptics, but not by sodium valproate.

Sister-chromatid exchange (SCE) frequency has been studied from peripheral blood lymphocyte cultures of 21 patients with epilepsy on sodium valproate, 20 patients who had not started therapy (untreated) and 20 normal healthy controls. Treated and untreated patients with epilepsy were observed to have higher SCE frequencies (mean 9.05 and 9.82 respectively) than healthy controls (mean 4.8; P < 0.001). There was no significant difference in SCE frequency between treated and untreated patients. This suggests that the disease itself may be associated with an increased frequency of SCEs.

Adolescent↗

A transsexual male with 47,XYY karyotype.

Transsexuals are usually found to have a normal chromosome complement. The literature to date documents four transsexuals with 47,XYY pattern. This paper reports a fertile male with major cell line of 47,XYY and a gender identity disorder.

Adult↗

Induction of sister chromatid exchanges in phenytoin treated & untreated patients with epilepsy.

The mutagenic potential of phenytoin (PHT) was studied using the sister chromatid exchange (SCE) assay. Twenty nine PHT treated epileptics, 32 untreated and 32 normal healthy controls were analysed. Similar SCE frequencies were observed in untreated patients and patients on PHT monotherapy. Both groups had significantly increased SCE frequency as compared to controls. No positive correlation of SCE frequency with sex and duration of therapy was observed. The results of the present study suggest the role of the disease condition in inducing genetic damage as assessed by increased SCE frequencies.

Adolescent↗

An Indian family with postaxial polydactyly in four generations.

An Indian family was observed with postaxial polycactyly in four generations. Of the twelve affected cases, eleven were male and one was female. The affected males showed postaxial polydactyly Type A in both hands and feet. The affected female showed polysyndactyly and both Types A and B postaxial polydactyly. Study of this family strongly suggests a common causal factor for postaxial polydactyly Types A and B and polysyndactyly. The observations also support an autosomal dominant pattern of inheritance and a high degree of genetic heterogeneity in ths malformation.

Abnormalities, Multiple↗