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Biomedical subjects

M Krishna

Publications and source records attributed to M Krishna.

At least 55 records · Page 3Linked to original sources

Signal transduction mechanism in response to aflatoxin B1 exposure: phosphatidylinositol metabolism.

A single dose of aflatoxin B1 (7 mg/kg body weight) to male Wistar rats significantly stimulated the hepatic activity of phosphatidylinositol kinase, a key enzyme in the cell signalling mechanism, 1-7 h following its administration. Phosphatidylinositol 4-phosphate kinase activity showed only marginal increase, whereas activities of diacylglycerol kinase and phosphatidylinositol synthetase remained unchanged. The level of diacylglycerol, however, recorded a sharp increase at 1 and 2 h after carcinogen treatment. The stimulation of phosphatidylinositol cycle with faster turnover of active second messengers might be an early step in the manifestation of toxicity and/or carcinogenicity.

1-Phosphatidylinositol 4-Kinase↗

Phosphoinositide turnover during hepatocarcinogenesis induced by N-nitrosodiethylamine.

The metabolism of phosphatidylinositol (PI) has been examined in rat liver during administration of N-nitrosodiethylamine (NDEA). The activities of PI kinase and PIP kinase were observed to be decreased as early as 7 days from the onset of NDEA administration, and remained suppressed until 60 days. PI synthetase showed a transient increase in activity at 7 days and thereafter the activity declined. The level of diacylglycerol (DAG), a key second messenger, showed a steady rise during the period of NDEA administration. A parallel increase in DAG kinase activity was also apparent. The results suggest that alterations of enzymes central to second messenger system with resulting changes in phosphoinositide turnover are important events during hepatocarcinogenesis induced by NDEA.

1-Phosphatidylinositol 4-Kinase↗

Expression of bcl-2 in reactive and neoplastic astrocytes: lack of correlation with presence or degree of malignancy.

The bcl-2 protooncogene encodes a 26-kD protein that extends cell survival by blocking apoptosis. This protein has been found to be overexpressed in neoplastic neural cell lines, although its expression in reactive and neoplastic astrocytes in vivo has not been well characterized. The authors hypothesized that bcl-2 oncoprotein expression in gliomas might be positively correlated with the tumor's degree of malignancy. Sixty-three gliomas of various subtypes and histological grades were immunostained by bcl-2 protein and the percentage of positive cells was quantitatively assessed. All tumors contained neoplastic cells that were immunoreactive for the bcl-2 protein (range of cell positivity 1%-53%). It was found that bcl-2 expression did not vary significantly as a function of tumor subtype or grade (p < 0.1, one-way analysis of variance (ANOVA) on ranks) as compared to the cell proliferation marker Ki-67 (MIB-1) in which a very significant correlation with tumor grade was noted (p < 0.0000001, one-way ANOVA on ranks). In fact, the highest percentage of bcl-2 immunoreactive cells was noted in low-grade gliomas, that is, in juvenile pilocytic astrocytomas and oligoastrocytomas. The specificity of bcl-2 overexpression was also assessed in 10 nonneoplastic lesions associated with prominent reactive astrocytosis. In nine of these cases (90%), bcl-2-positive reactive astrocytes were observed, often in large numbers, whereas relatively few Ki-67 immunoreactive cells were noted. The authors conclude that bcl-2 oncoprotein expression as assessed immunohistochemically does not correlate with glial tumor type or grade and its overexpression is not confined only to neoplastic conditions. Instead, the finding of robust bcl-2 expression in low-grade glial tumors and in reactive astrocytes warrants the inference that resistance to apoptosis is a nonspecific finding in astrocytes associated with both reactive and neoplastic conditions.

Adolescent↗

Progesterone blocks intracellular translocation of free cholesterol derived from cholesteryl ester in macrophages.

Macrophage foam cells must accommodate continuing fluxes of free cholesterol in spite of a greatly expanded store of cholesteryl ester. Though endogenous free cholesterol synthesis is suppressed, free cholesterol continues to enter the cell via endocytosis of oxidized/modified lipoproteins. It has been shown previously that this free cholesterol is released into the lysosomal compartment and rapidly transported to the plasma membrane prior to its esterification. A substantial amount of free cholesterol is also presented via the continuous hydrolysis of cholesteryl ester during the cholesteryl ester cycle. We addressed the question of whether the intracellular free cholesterol derived from the hydrolysis of cholesteryl ester formed a protected pool for rapid re-esterification. Incubation of macrophage foam cells with cyclic AMP to enhance cholesteryl ester hydrolysis, and with S58035 to inhibit acyl-CoA:cholesterol acyltransferase (ACAT) activity, led to conversion of cellular cholesteryl ester to free cholesterol and transport of this free cholesterol to the plasma membrane. Addition of progesterone, previously demonstrated to be an inhibitor of free cholesterol transport in other cell types, also led to conversion of cholesteryl ester to free cholesterol even though progesterone was only a weak inhibitor of ACAT activity. Free cholesterol in the plasma membrane was an important source of ACAT substrate to balance the constitutive hydrolysis of cholesteryl ester in cholesterol-loaded macrophages. Treatment of cells with progesterone, however, prevented free cholesterol derived from cholesteryl ester hydrolysis from moving to the plasma membrane. The sequestration of free cholesterol by progesterone could be reversed by incubation with human HDL3.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗

Expression of p53 antigen in inflamed and regenerated mucosa in ulcerative colitis and Crohn's disease.

Physiologic overexpression of p53 protein may occur in the G1 stage of the cell cycle to slow down the cell cycle and allow DNA repair in stressed or injured cells. We questioned whether there is increased expression of p53 protein in acutely inflamed mucosa (AI) and regenerated mucosa (RM) in ulcerative colitis (UC) and Crohn's disease (CD). Formalin-fixed paraffin-embedded sections of resected bowels from eight patients with UC and 20 with CD were reviewed, and blocks were selected having areas defined as follows: AI = two high-power fields (HPFs) at the edge of an ulcer, or one HPF with an inflamed crypt in the center; RM = branched or irregular glands with only mild chronic inflammation. Blocks with normal mucosa were available in 20 cases. One case of CD also had dysplasia, adenoma, and invasive carcinoma. p53 was identified with PAb1801 antibody using a labeled avidin-biotin immunoperoxidase technique. In each defined area, the positive nuclei were counted and expressed as the number of positive nuclei per 10 HPFs. Data were analyzed statistically for comparisons within and between the diseases. In normal mucosa, only rare cells expressed p53 in two cases of CD. The mean frequency of positive nuclei was 2.24/10 HPFs in AI and 0.30/10 HPFs in RM in CD, and 7.63/10 HPFs in AI and 1.14/10 HPFs in RM in UC. Differences between the means for AI and RM were statistically significant in both UC and CD. Although not significant, the frequency of positive staining in both AI and RM was greater in UC as compared with CD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

9-O-acetylated sialic acids have widespread but selective expression: analysis using a chimeric dual-function probe derived from influenza C hemagglutinin-esterase.

While 9-O-acetylation of sialic acids has been reported in some mammalian tissues, the distribution of this modification on specific cell types and molecules is largely unknown. The influenza C virus hemagglutinin-esterase is a membrane-bound glycoprotein that binds specifically to 9-O-acetylated sialic acids (hemagglutinin activity) and then hydrolyzes the O-acetyl group (receptor-destroying activity). A recombinant soluble form of influenza C virus hemagglutinin-esterase wherein the C-terminal transmembrane and cytoplasmic domains are replaced by the Fc portion of human IgG retains both its recognition and enzymatic functions. The latter activity can selectively remove 9-O-acetyl groups from bound or free sialic acids and, under specific conditions, 7-O-acetyl groups as well. Irreversible inactivation of the esterase unmasks stable recognition activity, giving a molecule that binds specifically to 9-O-acetylated sialic acids. These probes demonstrate widespread but selective expression of 9-O-acetylated sialic acids in certain cell types of rat tissues. Patterns of polarized or gradient expression further demonstrate the regulated nature of this modification. Direct probing of blots and thin-layer plates shows selective expression of 9-O-acetylation on certain glycoproteins and glycolipids in such tissues. Thus, 9-O-acetylation is more widespread than previously thought and occurs on specific molecules and cell types.

Animals↗

Maternal hemoglobin and serum albumin and fetal growth.

Four hundred and eighty four pregnant women and their offsprings were studied to determine the relationship of maternal hemoglobin and serum protein levels on the birthweight of offspring. The correlation coefficient of maternal hemoglobin as well as serum albumin level (gamma = 0.1097 and 0.0936, respectively) with birthweight were not statistically significant. However, mean birthweight of neonates born to nonanemic mothers was significantly higher than of those born to anemic mothers. The prevalence of low birthweight babies was significantly higher among anemic mothers (p < 0.01); however, no such trend was observed in relation to maternal serum albumin (p > 0.05).

Anemia, Iron-Deficiency↗

Changes in knowledge, attitudes and behavior of women participating in a community outreach education program on breast cancer screening.

A community-based intervention project on Long Island was supported by the National Cancer Institute to increase the use of mammography and breast physical examination among older women. During a 1-year period 526 women aged 50 and older attended educational sessions presented by the project staff conducted in the community in a variety of settings. Sixty-eight percent (355) of the women who participated provided identifying data and completed pre- and post-session surveys while 40% (210) also completed a mail survey 6-12 months later. Screening behavior improved subsequent to the intervention, at follow-up 61% had taken some related action. More than half of the 109 women who had a mammogram after attending the session indicated that the presentation influenced them to do so. The use of a game created a positive atmosphere for conveying information about a sensitive subject and encouraged discussion among women who had a variety of experiences with screening.

Breast Neoplasms↗

Tibial torsion measured by ultrasound in children with talipes equinovarus.

Previous clinical studies have studied tibiofibular torsion by measuring the angular difference between a proximal (often bicondylar) plane and a distal bimalleolar plane. We measured the angular difference between the proximal and distal posterior tibial planes as defined by ultrasound scans. We found no significant torsional difference between the right and left tibiae of 87 normal children, nor between their different age groups. The mean external torsion of 58 legs with congenital talipes equinovarus was 18 degrees; significantly less than the mean 40 degrees in the normal children and 27 degrees in the clinically normal legs of the 22 patients with unilateral congenital talipes equinovarus. We did not confirm the previously reported increase in external torsion with increasing age. The relative internal tibial torsion we have demonstrated in patients with congenital talipes equinovarus must be differentiated from the posterior displacement of the distal fibula observed by others and which may result from manipulative treatment. The relative internal tibial torsion we found in the clinically normal legs of children with congenital talipes equinovarus is further evidence that in this condition the pathology is not confined to the clinically affected foot.

Adolescent↗

Spatial relationship between Ph and normal chromosome 22 at somatic metaphase in chronic myelogenous leukemia.

The spatial distances between the Ph and the normal chromosome 22 in bone marrow are compared with the distances between the two normal chromosome 22s in peripheral blood. No significant differences between these two distances were found in two different tissues. The present findings indicate that length does not affect the spatial relationship between the homologous chromosomes in the nucleus, as previously postulated.

Chromosomes, Human, Pair 22↗

Comparison of two methods for detecting translocation heterozygotes in mice.

An accurate estimate of the error of misclassifying male translocation heterozygotes as normals is essential for the proper evaluation of results of the heritable translocation test in mice. The size of this error may vary from one laboratory to another depending, primarily, on the method or variation of the method used in screening for translocation heterozygotes. This report shows a way to estimate for misclassification errors involved in two methods, sequential and direct cytological analysis, of screening for translocation heterozygotes. A positive correlation was found between the degree of partial sterility of a male and the frequency of cells with multivalent configurations among his diakinesis-metaphase I cells. We interpreted this to confirm that the length of translocated chromosome segments has some influence on the proportion of unbalanced gametes in the ejaculate, presumably reflecting the frequency with which adjacent-1 and adjacent-1 segregations and 3-1 misdivisions occur.

Animals↗

Heritable translocation and dominant-lethal mutation induction with ethylene oxide in mice.

Ethylene oxide was studied for induction of dominant-lethal mutations and heritable translocations in male mice. The chemical was prepared in water and injected intraperitoneally. The dominant-lethal study was conducted using a single injection of 150 mg/kg (maximum tolerated dose); in the heritable translocation study males were injected daily on weekdays for 5 weeks with 60 or 30 mg/kg dose per day. Results clearly showed that ethylene oxide is effective in inducing dominant-lethal mutations and that the 4 stocks of untreated females used do not differ or may differ only slightly in the ability of their eggs to repair ethylene oxide-induced lesions in male germ cells. Increases in the frequencies of heritable translocations were also observed at the 2-dose levels. These frequencies did not deviate significantly from those expected on the basis of dose-square kinetics.

Animals↗

Genetic lesions induced by chemicals in spermatozoa and spermatids of mice are repaired in the egg.

Conclusive proof that the mouse egg is capable of carrying out repair of genetic lesions present in the male genome was obtained through dominant-lethal studies of chemically treated spermatozoa and spermatids and through cytological analysis of first-cleavage metaphases. The maximum difference in repair capability between stocks of females, found for isopropyl methanesulfonate treatment, was large; considerably smaller differences were found for ethyl methanesulfonate, triethylenemelamine, and benzo[a]pyrene treatments; and no difference was found for x-ray treatment.

Animals↗

Effect of pregnancy anaemia on cellular growth in the human placenta.

The effects of pregnancy anaemia on cell number and size in human placentae were investigated. Total organ weight, protein, RNA and DNA contents were determined in 54 fresh placentae from anaemic women (haemoglobin less than 110 g/l) and another 32 placentae from women without anaemia (haemoglobin greater than or equal to 110 g/l). The placental weight was significantly reduced in pregnancy anaemia. The decrease in total placental DNA in anaemic women suggested that the reduced placental weight was due to a decrease in cell number. However, these placentae also showed evidence of compensatory cellular hypertrophy as indicated by increase in both weight per cell and protein per cell.

Anemia↗