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Biomedical subjects

K Kannan

Publications and source records attributed to K Kannan.

At least 91 records · Page 5Linked to original sources
PubMed1999

Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009.

Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months. Significant increases in the proportion and total number of CD56+ natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0. 001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4: CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8+ cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median follow-up 45 months) demonstrated increases in the total numbers of CD8+, CD25+, CD56+, VLA4+, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8+, CD4:CDw29, CD4: CD45RA and VLA4+ cells and minimal increases in CD56+ and CD25+ cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen for CD25+, CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy with 5FU/LMS. Many of these changes are significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy.

Adjuvants, Immunologic↗
PubMed1999

Occurrence of butyltin residues in sediment and mussel tissues from the lower-most Tennessee River and Kentucky Lake, U.S.A.

Surface sediments and mussel samples were collected at six selected locations in the lower-most Tennessee River and Kentucky Lake, U.S.A. and analyzed for butyltin (BT) derivatives. In sediments, total BT concentrations ranged from 6.8 to 356 ng g-1 dry wt. A wide range of concentrations in sediments suggested the presence of localized area of contamination. In mussel tissues, total BT concentrations varied between 26-107 ng g-1 dry wt. BT levels were comparable to the levels reported in mussels from some coastal sites as well as a few freshwater ecosystems. Leaching of tributyltin-containing anti-fouling paints in the ocean-going ships is a source of tributyltin, and discharge of municipal sewage and industrial waste waters in to this watershed may account for the presence of the monobutyltin and dibutyltin derivatives detected in the samples. To our knowledge, this is the first report on the butyltin concentrations in sediment and mussel tissues from the lower-most Tennessee River and Kentucky Lake.

Animals↗
PubMed1999

Tear secretory IgA: evaluation of usefulness as a diagnostic marker in herpetic keratitis.

In a South Indian study, an 'in-house' enzyme-linked immunosorbent assay (ELISA) was developed to evaluate the potential of herpes simplex virus (HSV)-specific tear secretory IgA (sIgA) in the diagnosis of herpes simplex keratitis (HSK). The presence of HSV-specific tear sIgA was found to be diagnostic in 20.28% of cases. The usefulness of the sIgA ELISA system was evaluated against HSV isolation, which is the 'gold standard' and HSV antigen detection, a more sensitive, commonly employed method. Analysis of HSV-specific IgG and IgM results showed their failure as reliable indicators of active or ongoing infection. Comparison of sIgA ELISA with culture as 'gold standard' showed its sensitivity, specificity, and positive and negative predictive values to be 60% (95% CI 36.4-80), 93.2% (95% CI 86.7-96.8), 60% (95% CI 36.4-80), and 93.2% (95% CI 86.7-96. 8), respectively. This study is the first report on the complete evaluation of the usefulness of tear anti-HSV sIgA in the laboratory diagnosis of HSK, taking into account both epithelial and stromal keratitis cases.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Effect of hyperketonemia on blood monocytes in type-I diabetic patients and apoptosis in cultured U937 monocytes.

Recent studies have proposed a role for a reduced number of circulating monocytes in the development of atherosclerosis and circulatory diseases in diabetes. Ketosis is frequently encountered in type-I diabetics. This study was undertaken to test the hypothesis that hyperketonemia can lower blood monocyte count in type-I diabetic patients. Blood monocyte count was significantly lower (p < 0.05) in diabetics (n = 27) compared with age-matched normal siblings (n = 22). Blood levels of acetoacetate (AA) and triglycerides were significantly higher in diabetics compared with normals. To examine whether hyperketonemia can directly alter the monocyte count in diabetics, we studied the effect of ketone bodies AA and beta-hydroxybutyrate (BHB) on U937 cells, a human-derived promonocytic cell line as an in vitro model. The cell culture studies showed a dose-dependent growth inhibition and induction of apoptosis as a result of treatment with AA in U937 cells. Furthermore, there was a significant decrease in GSH and increase in lipid peroxidation products in AA-treated U937 cells. Taken together, this study suggests that elevated levels of ketone body AA can result in oxidative damage, accelerated apoptosis, and inhibition of cell growth in monocytes, which in turn can lower monocyte count in the blood of type-I diabetic patients.

Apoptosis↗
PubMed1999

Low incidence of p53 mutations in betel quid and tobacco chewing-associated oral squamous carcinoma from India.

Mutations of the p53 tumor suppressor gene have been found to be the single most frequent event in human cancers. In India and other southeast Asian countries tobacco chewing with betel quid was attributed to be the major factor in oral carcinogenesis. We have analyzed 72 untreated primary oral squamous cell carcinomas (SCCs) for mutations in the tumor suppressor gene p53 exons 4-9 by PCR-SSCP and DNA sequencing. Sequencing analysis revealed 16 missense mutations, one silent mutation in codon 307 and four A to G substitution polymorphism in codon 213. The incidence of p53 mutation was 21% (15 of 72) excluding the polymorphism and the silent mutation. Eight mutations were clustered in codons 266-282 of exon 8. Of the total mutation events 37.5% were G to A transitions and 31.3% were G to T transversions. These results indicate the possible involvement of tobacco derived nitrosamines and their adducts in the genesis of oral cancer among Indians.

Adult↗
PubMed1999

Infrequent genetic alterations of p53, p16 genes and polymorphism in fhit gene in Indian myelodysplastic syndrome.

Alterations in the tumor suppressor genes p53, p16, and fhit were studied in myelodysplastic syndrome (MDS) samples of Indian patients. PCR-SSCP analysis showed evidence for the presence of polymorphism in fhit gene in 7 of 15 samples. We failed to get any evidence for mutation in the p53, p16, and fhit genes. These results indicate that mutational inactivation of these genes may not play a major role in the development of myelodysplastic syndrome.

Acid Anhydride Hydrolases↗
PubMed1998

Interaction of tributyltin with 3,3',4,4',5-pentachlorobiphenyl-induced ethoxyresorufin O-deethylase activity in rat hepatoma cells.

Interaction of tributyltin (TBT) with 3,3',4,4',5-pentachlorobiphenyl (PCB-126)-induced ethoxyresorufin O-deethylase (EROD) activity was examined in vitro using H4IIE rat hepatoma cells. H4IIE cells were exposed to TBT and PCB-126, individually or in combination, at different concentrations. TBT was cytotoxic at concentrations greater than 98 nM. PCB-126 was not cytotoxic in the concentration range of 49 to 3140 pM. At concentrations greater than 49 nM, PCB-126 enhanced the cytotoxicity of TBT in the 24-98 nM range. In the absence of inducers of EROD activity, TBT significantly inhibited constitutive EROD activity in H4IIE cells in a concentration-dependent manner. EROD activity in H4IIE cells was significantly increased by exposure to PCB-126 alone. This effect was potentiated by coexposure to low, noncytotoxic concentrations of TBT. The induction of cytochrome P-4501A (CYP1A) activity in the presence of both an inducer (PCB-126) and low concentrations of an inhibitor (TBT) indicates that TBT does not interfere with the Ah receptor binding, but acts at the transcriptional level. Potentiation of EROD activity and cytotoxicity as a consequence of coexposure to PCB-126 and TBT is of considerable toxicological significance, given their coaccumulation in a variety of marine organisms.

Animals↗
PubMed1998

Histidine utilisation operon (hut) is upregulated at low temperature in the antarctic psychrotrophic bacterium Pseudomonas syringae.

The antarctic psychrotrophic bacterium Pseudomonas syringae was mutagenised using a transposon Tn5-OT182 which facilitates identification of promoter fusions expressing the reporter gene (lacZ) for beta-galactosidase. Most mutants expressed beta-galactosidase both at optimal growth temperature (20-22 degrees C) and at low temperature (4 degrees C). But a small percentage of the mutants (approximately 5%) were unique in that they expressed beta-galactosidase activity predominantly at low temperature. One such mutant was found to have an insertion in the gene for urocanase (hutU) of the histidine utilisation (hut) operon. Direct assay of urocanase and histidase activity in wild-type cells of various antarctic psychrotrophic strains including P. syringae, P. fluorescens and P. putida also suggested that the hut operon is expressed at an elevated level at low temperature.

Amino Acid Sequence↗
PubMed1998

The status of human papillomavirus and tumor suppressor genes p53 and p16 in carcinomas of uterine cervix from India.

OBJECTIVES: Infection with the high-risk strain of human papillomaviruses (HPVs) and the inactivation of the tumor suppressor gene p53 through mutation are important factors in cervical carcinogenesis. To know whether such events would occur in cervical carcinomas of Indians, 43 tumors (consisting of 36 of stage III B and 6 of stage II B) were screened for p53 and p16 gene mutations. METHODS: PCR followed by single-strand conformation polymorphism (SSCP) analysis were used to detect mutations in p53 and p16 genes and PCR for the presence of human papillomavirus genome. HPV status was ascertained by PCR amplification of parts of E6 and E7 genes using primers pU-1M and pU-2R and typing was carried out by restriction analysis. RESULTS: Of the 43 samples analyzed, 4 samples (9%) showed mobility shifts for p53 mutations; PCR products of the p16 gene did not show band shifts in SSCP analysis. HPV DNA was detected in 70% of the 43 samples analyzed: HPV 16 in 23 cases (53%), HPV 18 in 4 cases (13.3%), and HPV 33 in 1 case (3.3%). Two amplified HPV DNAs that were difficult to type with various restriction enzymes were cloned and the amplified regions were sequenced. One of these was 93% close to HPV 35 and the other was 80% close to HPV 58. Three samples had both p53 mutations and HPV genome. CONCLUSIONS: Our results indicate that HPV 16 infection was more common than HPV 18, the p53 mutations and HPV infection were not mutually exclusive events in the genesis of carcinoma of uterine cervix among Indian women, and p16 gene may not play a role in Indian cervical carcinomas.

Adult↗
PubMed1998

Concentrations and hazard assessment of organochlorine contaminants and mercury in smallmouth bass from a remote lake in the Upper Peninsula of Michigan.

Concentrations of PCBs, DDTs, toxaphene, chlordanes, dieldrin, and mercury were determined in smallmouth bass (Micropterus dolomieui) collected from Fumee Lake, a remote lake in the Upper Peninsula of Michigan. An ecological hazard assessment was conducted to determine potential impacts of contaminants on bald eagles and mink eating fish from this lake. Concentrations of organochlorines, except toxaphene, and mercury in smallmouth bass were similar to those found in fish from Lake Superior, where atmospheric inputs are the primary sources. Bioaccumulation was indicated by a positive correlation between fish weight and contaminant concentrations for organochlorines, while mercury concentrations did not appear to correspond predictably to body weight. Concentrations of mercury and PCBs in smallmouth bass were sufficiently great to be of concern regarding their consumption by eagles or mink.

Animals↗
PubMed1998

Distribution of total mercury and methyl mercury in water, sediment, and fish from south Florida estuaries.

Concentrations of total mercury and methyl mercury were determined in sediment and fish collected from estuarine waters of Florida to understand their distribution and partitioning. Total mercury concentrations in sediments ranged from 1 to 219 ng/g dry wt. Methyl mercury accounted for, on average, 0.77% of total mercury in sediment. Methyl mercury concentrations were not correlated with total mercury or organic carbon content in sediments. The concentrations of total mercury in fish muscle were between 0.03 and 2.22 (mean: 0.31) micrograms/g, wet wt, with methyl mercury contributing 83% of total mercury. Methyl mercury concentrations in fish muscle were directly proportional to total mercury concentrations. The relationship of total and methyl mercury concentrations in fish to those of sediments from corresponding locations was fish-species dependent, in addition to several abiotic factors. Among fish species analyzed, hardhead catfish, gafftopsail catfish, and sand seatrout contained the highest concentrations of mercury. Filtered water samples from canals and creeks that discharge into the Florida Bay showed mercury concentrations of 3-7.4 ng/L, with methyl mercury accounting for < 0.03-52% of the total mercury. Consumption of fish containing 0.31 microgram mercury/g wet wt, the mean concentration found in this study, at rates greater than 70 g/day, was estimated to be hazardous to human health.

Animals↗
PubMed1998

Accumulation Features of Polychlorinated Biphenyls and Organochlorine Pesticides in Resident and Migratory Birds from South India

Persistent organochlorines such as DDT and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs) were determined in whole-body homogenates of resident and migratory birds collected from South India. Organochlorine contamination pattern in birds varied depending on their migratory behaviour. Resident birds contained relatively greater concentrations of HCHs (14-8,800 ng/g wet wt) than DDTs and PCBs concentrations. In contrast, migrants exhibited elevated concentrations of PCBs (20-4,400 ng/g wet wt). The sex differences in concentrations and burdens of organochlorines in birds were pronounced, with females containing lower levels than males. Inland piscivores and scavengers accumulated greater concentrations of HCHs and DDTs while coastal piscivores contained comparable or greater amounts of PCBs. Global comparison of organochlorine concentrations indicated that resident birds in India had the highest residues of HCHs and moderate to high residues of DDTs. It is, therefore, proposed that migratory birds wintering in India acquire considerable amounts of HCHs and DDTs. Estimates of hazards associated with organochlorine levels in resident and migratory birds in India suggested that Pond Heron, Little Ringed Plover, and Terek Sandpiper may be at risk from exposure to DDTs.

Journal Article↗
PubMed1998

Occurrence of butyltin compounds in tissues of water birds and seaducks from the united states and canada

Tributyltin and its breakdown products, mono- and di-butyltin, were determined in water birds collected from Lake Huron (the Great Lakes), marine coastal United States, and the west coast of British Columbia, Canada. Concentrations of butyltins in the liver of birds collected from Lake Huron were </= 27 ng/g, wet wt, whereas those from marine coastal areas contained up to 90 ng/g. Relatively higher concentrations were found in seaducks collected from coastal British Columbia, with concentrations as great as 1,100 ng/g. Mollusk-feeding seaducks seemed to accumulate greater concentrations of butyltins than predatory birds feeding on fish, other birds and small mammals. Hepatic concentration ranges of butyltins in birds from the United States and Canada were compared with those reported for the UK, Netherlands, Japan, and Poland. Exposure of birds to butyltin compounds continues to occur in harbors and marinas where TBT is used on vessels greater than 25 m in length.

Journal Article↗
PubMed1998

Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells.

Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 degrees C with ketone bodies (acetoacetate, beta-hydroxybutyrate). Acetoacetate, but not beta-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by beta-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes.

3-Hydroxybutyric Acid↗
PubMed1998

Expression of bcl-2 oncoprotein in Indian oral squamous cell carcinomas.

Thirty-nine oral squamous cell carcinomas were assessed for bcl-2 protein expression by immunostaining of tumour sections. Twenty-three per cent of these tumours showed strong nuclear staining for bcl-2 protein. Tumours of the cheek and tongue together accounted for 77% of overexpression of this protein. When bcl-2 expression was compared with p53 expression, they were found to be non-overlapping. These results suggest that overexpression of either of these genes may substitute each other in the development of oral carcinomas of Indians.

Adult↗
PubMed1998

Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs): implications for risk assessment.

Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative, and toxic contaminants in the environment. Individual PCB congeners exhibit different physicochemical properties and biological activities that result in different environmental distributions and toxicity profiles. The variable composition of PCB residues in environmental matrices and their different mechanisms of toxicity complicate the development of scientifically based regulations for the risk assessment. In this article various approaches for the assessment of risks of PCBs have been critically examined. Recent developments in the toxic equivalency factor (TEF) approach for the assessment of toxic effects due to dioxin-like PCBs have been examined. PCB exposure studies that describe non-dioxin-like toxic effects, particularly neurobehavioral effects and their effective doses in animals were compiled. A comparative assessment of effective doses for dioxin-like and non-dioxin-like effects by PCBs has been made to evaluate the relative significance of non-ortho-and ortho-substituted PCBs in risk assessment. Using mink as an example, relative merits and implications of using TEF and total PCB approaches for assessing the potential for toxic effects in wildlife was examined. There are several advantages and limitations associated with each method used for PCB risk assessment. Toxic effects due to coplanar PCBs occur at relatively smaller concentrations than those due to non-dioxin-like PCBs and therefore the TEF approach derives the risk assessment of PCBs, in the environment. The need for the refinement of TEF approach for more accurate assessment of risks is discussed.

Animals↗
PubMed1997

Organochlorine pesticides and polychlorinated biphenyls in foodstuffs from Asian and oceanic countries.

Public concern about the adverse environmental and human health impacts of organochlorine contaminants led to strict regulations on their use in developed nations two decades ago. Nevertheless, DDT and several other organochlorine insecticides are still being used for agriculture and public health programs in developing countries in Asia and the South Pacific. As a consequence, humans in this region are exposed to greater dietary levels of organochlorines. In this review, published information on organochlorine concentrations in foodstuffs from South and Southeast Asia and Oceanic countries has been compiled. Foodstuffs that contribute to human exposures and dietary intakes of organochlorines were examined, and the data compared with those reported from more developed nations. Among various developing countries in Asia, considerable information on organochlorines in foodstuffs has been available from India since the late 1960s. DDT and HCH were the major insecticides in Indian foodstuffs. Concentrations of these insecticides have declined more than two orders of magnitude in farm products, such as food grains and vegetables, in two decades. Milk and milk products are the major sources of dietary exposure to DDT and HCH in India. The residues of these insecticides in dairy products were close to or above the MRLs of the FAO/WHO. Dietary intake of DDT and HCH by Indians was > 100 fold that in more developed nations. Sporadic incidences of greater concentrations (> 1 microgram/g) of aldrin, dieldrin, and heptachlor have been measured in Indian vegetables. Untreated surface waters could be a potential source of DDT and HCH exposure. In most Southeast Asian countries DDT was the common contaminant in animal origin foodstuffs. The higher percentage of p,p'-DDT in meat and fish from Southeast Asian countries, except Japan and Korea, indicated the recent use of DDt in vector control operations. Dietary intakes of DDt and HCH in Southeast Asia were an order of magnitude less than those of Indians but 5- to 10 fold greater than in more developed nations. In addition to DDT, aldrin and dieldrin were prominent in meat collected from Thailand and Malaysia. Aquatic food products from more industrialized countries, such as Japan, South Korea, Hong Kong, and Taiwan, contained significant levels of PCBs. In South Pacific countries, particularly in Australia and New Zealand, chlordanes and PCBs were the most prevalent organochlorines in foodstuffs. Food contamination by DDT, HCH, aldrin, and dieldrin was less than in developing countries in Asia but greater than in the U.S. and Japan. Intake of PCBs in Australia was greater than in the U.S. Meat and fish were the major sources of organochlorine exposure by Australians. Human dietary intake of organochlorines has been declining more slowly in developing countries in Asia. Current intakes were at least 5- to 100 fold greater than those in more developed nations, suggesting a greater risk from organochlorine exposure. Factors such as malnutrition, common among rural poor in developing nations, can increase these risks. Of greatest concern is the magnitude of exposure to organochlorines to which infants and children are subjected through human and dairy milk. The estimated intake of DDT by infants was at least 100 fold greater than the ADI of the FAO/WHO. In addition to DDT, excessive exposures to HCH and dieldrin may cause potential health effects in infants because they are more vulnerable to toxic effects. The design and implementation of appropriate epidemiological studies and their integration with monitoring of human, food, and environmental samples would be a major step in assessing the risks of organochlorine residues in foods and controlling or eliminating them. With the continued globalization of trade in food products, and the concomitant risk that food contaminated through point-source pollution may be widely distributed, identification of sources and their control should be matters of

Asia↗