Biomedical subjects
Publications and source records attributed to N S Srikanth.
Urinary isolates of Escherichia coli were studied for presence of haemolysin, adhesins, serum resistance and O serotype prevalence. Of the 144 isolates studied, 72 exhibited hemolysin, 7 were resistant to bactericidal effect of serum and 50 strains showed Mannose resistant Haemagglutination (MRHA). O101,O68,O04 and O25 were the commonest serotypes in this study.
The cytotoxicity of the potent antibiotic and antitumor agent mitomycin C (MMC) is due to its irreversible binding to DNA. Alkylating species generated by bioreductive activation of MMC are known to cause monoadducts and cross-links in DNA by specifically binding to guanine residues. To gain insight into how these lesions lead to base- and sequence-specific mutations, shuttle vector pSP189 was treated with MMC chemically reduced by treatment with sodium borohydride, replicated in human Ad293 cells, rescued in bacteria, and analyzed for mutations in the supF tRNA gene sequence. The MMC-induced mutations were predominantly base substitutions. Eighty-four percent of the base substitutions were transversions, with G:C-->T:A the major transversion. Single base deletions were the other major mutational event, and 77% of these were G:C deletions. Base positions 115, 123, and 163 were mutational hot spots based on the frequency of independent mutations. Identification of a single MMC adduct (presumed to be a modified G on the basis of its Rf value) and clustering of MMC-induced mutations at three GC-rich areas (nt 100-123, 152-163, and 168-176) suggested that the mutational spectrum we found was due to binding of MMC to guanine on either strand of the plasmid DNA.
Levels of various cytochrome P450 proteins have been reported to be decreased to varying degrees in chemically induced hepatocyte nodules and following partial hepatectomy (PH). By screening a rat liver lambda ZAP cDNA expression library with antibodies raised against a partially purified preparation of cytochrome P450 isolated from untreated male Fischer 344 rats, we have isolated a 1.1-kb cDNA. This cDNA was sequenced for 139 bases from the 5' end of the sense strand and comparison of the resulting sequence with the sequences in Gene Man DNA data bank revealed 95% homology of the sequenced portion with male-specific rat cytochrome P450 (M-1, CYP IIC11). The 32P-labeled cDNA was used as a hybridization probe on RNA blots (Northern blots) prepared with total RNA from rat livers obtained post PH, from aflatoxin B1(AFB1)-induced rat liver tumors and from rat liver nodules induced with a combination of diethylnitrosamine/acetylaminofluorene/PH (DEN/AFF/PH). At 36 and 72 hr post PH, the mRNA level was decreased by > 93%. Relative to the corresponding control livers, the mRNA level was also decreased by 97% in the liver nodules and by 57% in AFB1-induced liver tumors. The RNA blots derived from the liver nodules and AFB1-induced liver tumors were also probed with a cDNA probe (R17) that recognizes other cytochromes P450 (CYP IIB1/CYP IIB2). The mRNA corresponding to CYP IIB1/CYP IIB2 was also depressed 92% in the nodules and 65% in the tumors. These results clearly indicate that the depression of both CYP IIC11 and IIB1/IIB2 in the hepatic nodules and the tumors is related to the inhibition of transcription and/or enhanced degradation of the mRNA.
The effects of endosulfan (3 mg kg-1 body wt., i.p.) and malathion (30 mg kg-1 body wt.) and their coexposure on rat hepatic and brain xenobiotic metabolizing enzymes were investigated. Endosulfan was found to induce aminopyrine-n-demethylase (81%) and aniline hydroxylase (59%) activities significantly in liver and to a lesser extent in brain. Malathion treatment induced malathion carboxylesterase activity in both liver (50%) and brain (22%), significantly depleted liver glutathione (35%) content with stimulation of glutathione-S-transferase (50%) and inhibited the activity of mixed-function oxidases. In the coexposed animals, malathion's inhibitory influence on mixed-function oxidases and endosulfan's inhibitory effect on malathion carboxylesterase were found to dominate, while endosulfan potentiated the activity of glutathione-S-transferase significantly in liver (69%) and brain. A similar trend of alteration in coexposed brain was found, but to a lesser extent. A significant inhibition in brain acetylcholine esterase activity (42%) in the coexposed animals suggests that endosulfan may potentiate the toxicity of malathion by interfering with glutathione and carboxylesterase routes of malathion detoxification.
A new method based on linear regression of per cent modulation in enzyme activity over substrate concentration is proposed to give an interpretative base to the influence of more than one modulator/inhibitor/toxicant, a situation commonly met with in toxicological studies-toxicant interactions. Advantages of this method over the classical kinetic methods are discussed in detail using brain Mg2+ ATPase activity of the fish Tilapia mossambica under in vitro regimes of hexachlorocyclohexane and malathion.
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Endosulfan stereoisomer I (E-I) inhibited the activity of calmodulin-dependent Ca2+-ATPase to an extent of 15-55% in a concentration range of 1-20 microM under in vitro conditions without significantly affecting the basal enzyme activity. The less toxic isomer E-II produced no significant inhibition of Ca2+-ATPase activity up to a concentration of 40 microM. The inhibition of Ca2+-ATPase by E-I was noncompetitive with respect to substrate, free from the influence of calcium, and competitively inhibited calmodulin activation kinetics. Reconstitution with the exogenous addition of calmodulin (5 and 20 micrograms) restored the inhibited enzyme activity, indicating nonspecific binding of E-I with calmodulin. Both calmodulin-activated and basal enzyme activity was inhibited significantly in rats fed E-I (3 mg/kg body weight) for 15 d. These data suggest that endosulfan may modulate calmodulin-related events in neurons and result in its neurotoxicity.
400 adult unrelated individuals of both sexes were studied from two groups of Srivaishnava Brahmins residing in Tirupati, South India, for the distribution of middle phalangeal hair (MPH). The occurrence of MPH was predominantly manifested on the III, IV, and V digits of both hands in the two sexes of Vadagalai and Tengalai groups. Tengalai males showed higher frequency of presence of MPH (39.00%) than Vadagalai males (37.00%). Among the females the frequency was (36.00 %) in Tengalai and (34.00 %) in Vadagalai groups. Sex differences were not statistically significant in both the groups. Populations of Mongoloid affinity seems to have a marked increase in the frequency of individuals without MPH and the present Srivaishnava Brahmin sample reflects such a similar tendency.