Biomedical subjects
Publications and source records attributed to B Nagarajan.
Lay et al. (Research Articles, 20 May 2005, p. 1127) estimated a 600-km length for the tsunami source region. Adding tide-gauge data from Paradip, the northernmost of the Indian east-coast stations and therefore the most critical constraint on the northern extent of the source, we estimate that its length was greater by approximately 30%.
Type 1 cytokines, such as interferon gamma (IFNgamma) and interleukin-2 (IL-2), increase T cell-mediated immune responses and are considered to be beneficial for antitumour immunity. Type 2 cytokines, such as IL-4, IL-5, and IL-10, inhibit Type 1 responses and promote humoral responses. We have previously reported an association between low intratumoral IFNgamma mRNA levels and poor clinical outcome in patients with invasive cervical carcinoma. In this study, by using quantitative polymerase chain reaction (PCR), we identified a group of cervical carcinoma patients with undetectable intratumoral T cell-derived cytokine mRNAs, as IFNgamma, IL-4 and IL-17 expression could not be detected in 5, 25 and 8 of the 52 biopsies analysed, respectively. Global downregulation of Type 1 and Type 2 cytokines was observed in a subgroup of patients who more frequently presented advanced stage tumours. Biopsies of patients with no IFNgamma gene expression did not appear to be less infiltrated by T cells than control biopsies with measurable IFNgamma gene expression. These results clearly demonstrate that, in some clinical situations, the decrease in intratumoral Type 1 cytokines is not associated with a Type 2 polarisation, but rather reflects global deactivation of T cells at the tumour site. These data provide support for immunotherapy protocols designed to reverse the anergic state of T cells in cancer.
A combined 31P and 1H nuclear magnetic resonance (NMR) spectroscopic study was carried out in drug-sensitive and adriamycin- and mitoxantrone-resistant P388 murine leukemic cells. Typical spectral changes characteristic of multidrug resistance were observed in resistant cells compared to drug-sensitive cells. Quantitative comparison of phosphate metabolites ATP, phosphocreatine, phosphomonoesters and phosphodiesters revealed a significant alteration in the metabolism of resistant cells. The elevated levels of energy metabolites supported the energy-dependent process of drug efflux in resistant cells. An increased rate of glycolysis in resistant cells as indicated by the elevated lactate level further supported this. The near total loss of energy metabolites and marked decrease in phospholipid metabolites in sensitive cells upon treatment with drug compared to unaltered metabolite levels in resistant cells suggested that the spectral changes can reveal the subtle differences in tumor response between drug-sensitive and -resistant cells. The results substantiate the potential of this non-invasive method to characterize the multidrug resistance phenotype and monitor tumor response.
Previous studies from our laboratory have shown the clastogenic effects of long-term feeding on deep-fried fish and mutton in rat bone marrow cells. We report the chemopreventive action of two flavanoids, quercetin (Qn) and luteolin (Ln) against the induced mutagenicity by fish and mutton extracts. Groups of rats were treated with flavanoids through pre-, simultaneous- and post-treatment regimens and killed at the end of treatment. The bone marrow was removed and analysed for the presence of micronuclei (MN) and chromosome aberrations (CA). Pre-treatment showed most effectively a good inhibition of mutagenicity at every dose tested. Luteolin was a better protective agent than quercetin. It protected the cells against genetic damage to 93% in the micronucleus assay and to 95% in the chromosome aberrations induced by fish extract (p < 0.001 in both the groups). Mutton extract-induced micronuclei and chromosome aberrations were protected 85% and 90%, respectively, by luteolin and 79% and 76%, respectively, by quercetin. Our results tend to suggest that quercetin and luteolin are potential chemopreventive compounds.
Alterations in the activities of certain lysosomal enzymes such as beta-D-galactosidase, beta-D-glucosidase, beta-D-glucuronidase, alpha-L-fucosidase, N-acetyl-beta-D-glucosaminidase, cathepsins B and D were studied in serum and tissue homogenates of buccal mucosa of hamsters treated with 0.5%, 7,12-dimethylbenz[a]anthracene (DMBA) in liquid paraffin. Among the enzymes studied, the activities of beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase showed significant elevation both in serum and tissue homogenates fro papilloma onwards and the elevations were progressive with the development of carcinomas. The elevations in the activities of alpha-D-fucosidase and cathepsin D were found to be significant from papillomatous tissue onwards whereas in serum they showed higher activities only in carcinoma stages. The activities of beta-D-glucosidase, beta-D-glucuronidase and cathepsin B in both serum and in tissue homogenate were elevated markedly only in carcinoma stages. It is suggested that beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase may be used as diagnostic markers for premalignant and malignant lesions of oral mucosa.
Salted, sun-dried and deep-fried fish and mutton were screened for their mutagenicity by the Ames test, single cell gel electrophoresis assay (SCG), chromosomal aberrations (CA), and micronucleus test. Fish and mutton given at 20% in the diet to the rats daily for 2 months resulted in cytogenetic damage which could not be repaired on withdrawal. However, the temporary damage was reversed at a 10% dose upon withdrawal after the same period. The maximum chromatid damage, found as breaks and gaps, was in agreement with the increased number of strand breaks. Treated rats also showed DNA strand breaks in hepatocytes and lymphocytes, more so in hepatocytes. Lime and onion extracts inhibited the nitrosation of fish and mutton, and were antitoxic.
The cytogenetic and cytotoxic effects of the pesticides methyl parathion, Bayleton and Hinosan were evaluated in mammalian test systems. The frequency of chromosome aberrations and micronuclei in bone marrow cells and the arginase enzyme profile in the liver tend to show the genotoxicity of organophosphorus and organochlorine pesticides in a single-exposure response study. Methyl parathion was the most hazardous among the three, showing definite pathology in the livers of treated rats.
The changes in sialoglycoconjugates synthesis after administration of 14C-glucose to fibrosarcoma bearing rats were studied. After 1 hr treatment 14C-glucose tumor bearing rat synthesized hexosamine which contained more radioactivity when compared to sialic acid. On fractionation of lipoproteins, low density lipoproteins (LDL) contained more sialic acid. This was further confirmed by separating the lipoproteins, as more radioactivity incorporation was observed in the LDL fraction. It is noteworthy that inspite of the tumor, high density lipoproteins (HDL) did not show any change.
The cumulative cardiotoxicity of Adriamycin (ADR) is a constraint on its pharmacological use. The generation of drug induced oxygen radicals in heart cells lead to cardiac lipid membrane peroxidation. We studied the free radical scavenging potential of two compounds Oleanolic acid (OA) isolated from Eugenia jumbolana and Ursolic acid (UA) isolated from Ocimum sanctum against ADR induced lipid peroxidation both in liver and heart microsomes in vitro. In our attempt in the management of cardiotoxicity, we have identified OA as a strong protector against ADR induced lipid peroxidation and UA as a mild protector. Protection with OA was 49% and 21% in liver and heart microsomes respectively. On combined treatment, it increased to 69%. UA showed only 13% and 17% protection in liver and heart microsomes. Two methods for the microsome preparation, Calcium aggregation (CA) and Differential centrifugation (DC) were also compared. CA seems to give a better microsomal preparation though the protection was about the same.
Implantable collagen-poly(HEMA) hydrogels containing the anticancer drug 5-fluorouracil (5-FU) have been prepared and evaluated for their efficacy towards a solid tumour fibrosarcoma in Wistar rats. The tumour was developed by inoculation of a 10% tumour-cell suspension in the anterior aspect of the hind limb. Four groups were studied--untreated control, intratumoural injection of free 5-FU, subcutaneous implantation of placebo and implantation of 5-FU-bearing hydrogel pellets (10 mm diameter x 1 mm thick) containing the drug in close proximity to the tumour. The hydrogel showed an improved antitumour activity over free 5-FU as evidenced by the gross tumour weight assessments and by [3H]thymidine incorporation in-vitro. This was attributed to the controlled and slow release of 5-FU compared with free 5-FU over the same period of treatment. The implantation of hydrogel could thus be a potential alternative to free 5-FU therapy in the treatment of solid tumours such as fibrosarcoma.
In a search for plant products against cancer, the protective effect of two plant products, ursolic acid isolated from Ocimum sanctum and oleanolic acid from Eugenia jumbolana against free radical induced damage was studied. Three different standard systems viz., ascorbic acid, carbon tetrachloride, ADP/Iron were used to induce lipid peroxidation in isolated rat liver microsomes in vitro. Both oleanolic acid and ursolic acid offered remarkable protection of 90% and 60% respectively. Both the compounds did not induce lipid peroxidation by themselves that improved the therapeutic application.
Hexosaminidase, polyamines and lipid-bound sialic acid are a few tumour-associated markers which are significantly elevated both in urine and serum of patients with haematopoietic malignancy, in direct correlation to dedifferentiation. Our computer database incorporates these parameters and predicts the clinical response based on the baseline values of these tumour-associated markers. This completely menu-driven user-friendly database can be routinely applied in tumour management and can access a billion records. The results of our evaluation confirm that most clinical assessments by a physician working blind are in agreement with the computer prediction, thus encouraging the use of microcomputers in patient management.
Proliferation end products are of considerable value as tumour markers. Hexosaminidase and polyamines were significantly elevated in urine of patients with leukemia and lymphoma (p less than 0.001). Interfering low molecular weight compounds were eliminated by a microcolumn centrifuge method. Urinary polyamines were estimated by high voltage electrophoresis technique. Marked increase in these markers in untreated patients and subsequent decrease on effective chemotherapy support the use of these two tumour markers to monitor therapeutic response.
The effect of clofibrate on rat liver enzymes and metabolites was compared with that produced by partial hepatectomy and an extrahepatic tumor. Clofibrate administration produced decrease in gamma-glutamyltranspeptidase (GGT) activity with concomitant increase in glutathione concentration. The drug was able to exert its GGT-lowering effect even when fed to tumor-bearing animals. Presence of an extrahepatic neoplasm as well as administration of clofibrate resulted in marked decrease in activities of hepatic arginase and ornithine transaminase. Administration of clofibrate to the tumor-bearing rat produced a further decrease in activities of these two enzymes. These results suggest that clofibrate causes hepatic dedifferentiation and simulates an extrahepatic tumor. However, clofibrate did not induce any significant increase in polyamine profile unlike the other two experimental conditions.
Total and lipoprotein cholesterol in serum have been determined in patients with leukemia and lymphoma. Untreated patients were hypocholesterolemic with reduced lipoprotein cholesterol content. On successful chemotherapy most of the patients showed near normal total cholesterol levels with a subsequent increase in LDL cholesterol content. A rapid, sensitive and inexpensive method is reported using agarose electrophoresis and quantitation of cholesterol by Liebermann-Burchard reaction.
In diethylnitrosamine-initiated rats, administration of clofibrate for 32 weeks induced neoplastic lesions and hepatocellular carcinoma. In contrast to conventional carcinogens, clofibrate effected a marked decrease in the activity of gamma-glutamyltranspeptidase. Ornithine was selectively channeled into polyamine synthesis with concomitant repression of the urea cycle and the transamination pathway. These histological and biochemical studies suggest that clofibrate acts as a promoting agent in hepatocarcinogenesis.
Explore the source record for details and available documents.