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Biomedical subjects

M S Murthy

Publications and source records attributed to M S Murthy.

At least 19 recordsLinked to original sources

Inhibition of tumor implantation at sites of trauma by Arg-Gly-Asp containing proteins and peptides.

We report on the inhibition of wound implantation by TA3Ha mammary carcinoma cells by Arg-Gly-Asp containing proteins and peptides using a hepatic wedge resection model. Intravenously injected TA3Ha cells rarely form tumor in the liver of syngeneic mice, but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Hepatic wound implantation is significantly (P = 0.01) inhibited by pretreating the cells with whole mouse plasma, but not with fibrinogen-depleted plasma or serum. Tumor inhibition is also achieved by pretreatment of cells with fibrinogen (P = 0.05-0.0004), fibronectin (P = 0.007) and laminin, but not by albumin. The active domain appears to be the RGDS sequence since the deca- and tetrapeptides containing RGDS inhibit wound implantation (P less than 0.05). However, the tetrapeptide Arg-Gly-Glu-Ser has no such activity. None of these agents affects ascites tumor formation by the intraperitoneally injected cells, suggesting that anchorage independent growth of cells is not affected. We propose that proteins and peptides containing RGD occupy the binding sites and prevent the cells from interacting with cell adhesion proteins in healing wounds. Proteins and/or peptides containing RGD may be useful for preventing local recurrence in postsurgical cancer patients.

Animals

Tuberculous infection in a rural population of south India: 23-year trend.

A survey was conducted in Bangalore district of south India between February 1984 and January 1986 to study the tuberculosis infection rate. The data from this survey, along with the information derived from the earlier ones in the same area conducted between 1961-1968, have been used in the report to study the trend of tuberculosis. Tuberculin test results in 0- to 14-year-old unvaccinated children from each survey were distributed, and based on the antimode, infected persons were identified. The standardized prevalence rates in population from the surveys were converted into risk rates by using the TSRU methodology and compared. The average annual risk of infection of 1.1% observed in 1961 declined to 0.61% in 1985, representing a decline of approximately 37% in nearly 23 years. This amounted to an average decline of 3.2% per annum over the period. The trend probably represented a natural dynamics. Whether organized intervention played some role could not be commented upon. Similar studies in other parts of the country are recommended in order to have information on the trend in the country as a whole.

Adolescent

Purification of the medium-chain/long-chain (COT/CPT) carnitine acyltransferase of rat liver microsomes.

A procedure for the purification of the rat liver microsomal carnitine octanoyltransferase (COT) that catalyzes the reversible formation of medium-chain and long-chain acylcarnitines from acyl-coenzyme A is described. The K0.5 for L-carnitine is 0.6 mM and the K0.5 for both decanoyl-CoA and palmitoyl-CoA is 0.6 microM. The Vmax with decanoyl-CoA is approximately fourfold greater than the Vmax with palmitoyl-CoA. The enzyme is monomeric, sodium dodecyl sulfate-polyacrylamide gel electrophoresis gives a molecular weight of 50,100, and molecular sieving gives a molecular weight of 54,300. Purified COT does not cross-react with either antimitochondrial carnitine palmitoyltransferase or antiperoxisomal COT antibodies. It also does not form a covalent adduct when incubated with etomoxiryl-CoA. Microsomal COT is a different protein than either mitochondrial carnitine palmitoyltransferase or peroxisomal COT.

Acyl Coenzyme A

Probability of causation for radiation-attributable cancer in the Indian population.

Once a cancer is diagnosed in an individual with a history of radiation exposure, it may be required to know the probability that radiation exposure was the cause of the disease. The National Institute of Health, U.S., has generated radio epidemiological tables giving probability of causation for various radiogenic cancers for the population of the U.S. In this paper, the probability of causation has been calculated for the Indian population using two models: (1) the original National Institute of Health model, and (2) direct use of Japanese constant relative risk coefficients for solid tumors. In both cases, new risk coefficients based on DS86 dosimetry and extended follow-up for 35 y have been used. Calculations with new coefficients, based on the National Institute of Health model have been extended to the American population and compared with the results for the Indian population. These values are generally higher for the Indian population than for Americans because of the lower baseline incidence rates in India. Probability of causation values based on the constant relative risk model are independent of population characteristics.

Adolescent

Inhibition of tumor implantation at sites of trauma by plasminogen activators.

The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B-SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p-nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment.

Adenocarcinoma

Influence of anoxia and respiratory deficiency on the genotoxicity of some direct-acting alkylating agents in yeast.

We have studied the influence of anoxia and respiratory deficiency (RD) in yeast on the cytotoxic and recombinogenic effects of 5 direct-acting alkylating agents, namely N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methylnitrosourea (MNU), ethylnitrosourea (ENU), methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS). We found that the effects of both conditions parallel each other for MMS, MNNG, MNU and ENU. Both anoxia and RD did not modify the effects of MMS to any significant extent. On the other hand, anoxic and respiratory-deficient cells were found to be more resistant than euoxic and respiratory-proficient cells respectively for MNNG, MNU and ENU. In the case of EMS, which is similar to MMS in its chemical reaction with DNA, the respiratory-deficient cells were found to be more sensitive than the respiratory-proficient ones. These studies indicate that the response of anoxic and respiratory-deficient cells cannot be predicted solely on the basis of the chemical reactivity pattern of the alkylating agents. The physiological state which exists under these conditions may exert considerable influence on the cellular response.

Alkylating Agents

Tritium metabolism in man.

Tritium metabolism in human beings was studied in volunteers who had exposure to tritiated water accidentally, by measuring the organically bound tritium with liquid scintillation counter, in sperms and plasma proteins. 2% of the initial urinary tritium specific activity was incorporated as bound tritium in sperms. In plasma proteins, on the 20th day of exposure, tritium bound in globulin was 3 times higher than that of albumin, tritium bound in globulin was 3 times higher than that of albumin.

Adult

Naphthol and lens.

Alpha and beta naphthols, the metabolites of naphthalene, a cataractogenic agent, was tested for it's effect on sheep lens proteases and their inhibitors. It reduced protease activities, not that of inhibitor activities of lens proteins. It also increased the efflux of free amino acid from lenses which was retarded by a high concentration of tissue galactose.

Amino Acids

Delayed-type skin hypersensitivity reaction (DTH) to Thomsen-Friedenreich (T) antigen as diagnostic test for human breast adenocarcinoma.

One intradermal (i.d.) injection of human erythrocyte T antigen in the upper outer arm contralateral to any breast lesion elicits a delayed tuberculin-type hypersensitivity reaction (DTH) in breast carcinoma patients. It is necessary to inject simultaneously but separately the same quantity of MN antigen (about 6--8 cm apart), from which the T Antigen has been prepared, since particularly patients with Stage I breast carcinoma (Internatl. nomenclature) and those with benign breast disease may significantly react to it. The extent of reaction to MN antigen must be subtracted from the reaction to T antigen before interpreting results. DTH response to T antigen was 85% accurate among 67 patients with ductal breast carcinoma of all Stages (including non-invasive), 95% accurate (5% so far falsely positive) among 95 patients with benign breast disease and it was 100% accurate (no false positives) among 36 "healthy" persons tested. Among 18 patients with the comparatively rare and less ominous lobular and tubular breast carcinomata, the DTH reaction was positive in 8 of 16 (50%) patients with lobular, and in none of 2 patients with tubular breast carcinoma.

Adolescent

Human carcinoma-associated precursor antigens of the NM blood group system.

Blood group NM specificities occur in healthy, benign and carcinomatous breast glands and those of the gastrointestinal (G.I.) tract, but the precursors in their biosynthesis, T (Thomsen-Friedenreich) and Tn, are found in adenocarcinomata and not in benign or healthy tissues. T- and Tn-antigenic specificities are thus human carcinoma-associated. All humans possess anti-T and anti-Tn antibodies. Patients with breast or G.I. tract carcinoma show statistically significant alteration of anti-T titer levels when compared to patients with benign disease and to healthy controls. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vitro and in vivo. Most striking was the delayed-type hypersensitivity reaction, which was positive in over 90% of ductal breast carcinoma patients tested and negative in all presumably healthy individuals. T antigen is readily prepared from healthy human red blood cells in uncontaminated form, and free of HL-A and Au antigens. T antigen and anti-T antibodies may be useful in combating some human adenocarcinomata.

Adenocarcinoma

Induction of gene conversion in diploid yeast by chemicals: correlation with mutagenic action and its relevance in genotoxicity screening.

More than 200 chemicals, comprising drugs, pesticides, herbicides, industrial chemicals, food additives, etc. tested by various workers for their ability to induce gene conversion in diploid yeast, have been reviewed. This review shows that a strong correlation exists between the convertogenic and mutagenic abilities of these chemicals. This conclusion confirms the earlier one by Zimmermann which was based on fewer mutagenic chemicals. Published data have further been analysed to confirm quantitatively Zimmermann's other important conclusion that gene conversion is not mutagen-specific. This is a positive advantage in using gene conversion in preliminary screening of chemicals because it reduces the chances of false negatives.

Alleles

Testing of some permitted food colours for the induction of gene conversion in diploid yeast.

12 permitted food colours in use were screened for geno-toxicity. Mitotic gene conversion in Saccharomyces cerevisiae was used as the end-point. Each food colour was tested in stationary-phase as well as log-phase cells but without microsomal activation. These food colours did not cause any increase in mitotic gene conversion in diploid yeast BZ 34.

Drug Evaluation, Preclinical

Hyperthermic inactivation of diploid yeast and the interaction of damage caused by hyperthermia and ionizing radiation.

Inactivation of diploid yeast by hyperthermia has been studied. DO and Dq decrease with temperature for euoxic and anoxic conditions. The Arrhenius plot shows a break at 52 degrees C; the inactivation energies above and below this temperature are 153 and 94kcal/mol respectively. Hyperthermia (20 min at 51 degrees C) also potentiates the lethal action of gamma rays in diploid yeast cells under both euoxic and anoxic conditions. The interaction between hyperthermic and radiation damage appears to be largely at the sublethal level. The euoxic cells, the hyperthermic potentiation decreases with increasing time between the application of hyperthermia and radiation, being completely lost after 24 hours. However, in the anoxic cells there was no decrease in the hyperthermic potentiation with increasing time interval. These results suggest that yeast cells are capable of repairing hyperthermic sublethal damage, but require oxygen to do so. Thus there is a similarity in the process of repair of sublethal damage caused by ionizing radiation on the one hand and hyperthermia on the other.

Animals

Modification of high LET radiation-induced damage and its repair in yeast by hypoxia.

The lethal response of a diploid yeast strain BZ34 to densely ionizing radiations from the reaction 10B(n, alpha)7 Li was studied. The values for relative biological effectiveness (r.b.e.) and oxygen enhancement ratio (o.e.r.) for this radiation compare favourably with the data obtained with charged particles on the same strain of yeast. Recovery from potentially lethal damage was also studied by post-irradiation holding under non-nutrient conditions. In order to understand the role of oxygen in the recovery process, the investigation covered the following treatment regimens: (a) aerobic irradiation and aerobic holding (A-A), (b) aerobic irradiation and hypoxic holding (A-H), (c) hypoxic irradiation and hypoxic holding (H-H) and (d) hypoxic irradiation and aerobic holding (H-A). It has been found that the presence of oxygen is essential for recovery from the damage induced by both gamma rays and high linear energy transfer (LET) radiations. The extent of recovery was larger for gamma-induced damage than for damage induced by high LET radiation (alpha + 7Li) for the A-A condition. In the H-H condition, while only a slight recovery was seen for gamma-induced damage, it was totally absent for high LET damage. For the modality A-H, it was found that there is not recovery from the sparsely ionising gamma radiation-induced damage. The implications of these results for the treatment of malignant tumours by radiotherapy are briefly discussed.

Alpha Particles