Search PubMed⌕ Search

Biomedical subjects

M S Murthy

Publications and source records attributed to M S Murthy.

At least 19 recordsLinked to original sources
PubMed1998

Secondary membranoproliferative glomerulonephritis due to hemolytic uremic syndrome: an unusual presentation.

Secondary membranoproliferative glomerulonephritis is an uncommon disorder. A six year old girl presented to us with microangiopathic hemolytic anemia and nephrotic syndrome and the renal biopsy showed membranoproliferative glomerulonephritis. Demonstration of fibrin thrombus in one glomerulus pointed to hemolytic uremic syndrome as the cause of membranoproliferative glomerulonephritis. Institution of plasma exchange quickly reversed both the microangiopathic hemolytic anemia and the nephrotic syndrome. The relationship between HUS and glomerular disease is discussed.

Child↗
PubMed1996

Pre-, peri-, and postoperative chemotherapy for breast cancer: is one better than the other?

The purpose of the present study was to determine the relative efficacy of pre-, peri-, and postoperative chemotherapy in the prevention of breast cancer relapse and prolongation of host survival. The studies were performed using an experimental mouse breast cancer model. TA3Ha mouse mammary adenocarcinoma was transplanted into the mammary fat pad of syngeneic mice to obtain tumors in their natural organ. The tumors were surgically excised with a "curative" intent. A single treatment with 10 mg/kg doxorubicin was given intravenously pre-, peri-, or postoperatively. Among 74 mice whose tumors were resected but no doxorubicin was given, local recurrence, axillary metastasis, and lung metastasis were seen in 43%, 37%, and 16% of the mice, respectively. Seventeen (23%) mice had no evidence of disease. Doxorubicin given 4 days preoperatively reduced the rate of growth of primary tumor. Local recurrence was reduced in these mice by 30% and metastasis to the axillary lymph nodes and lung was completely prevented. Disease-free survival was increased to 70% (P < 0.01). Similar beneficial effects were obtained when chemotherapy was administered 2 days prior to surgery. The peri-operative chemotherapy group showed 8% (2/26) local recurrence, 4% axillary metastasis, and 0% lung metastasis. Proportion of mice without any evidence of disease increased to 92% (P < 0.00001). Chemotherapy given 4 days postoperatively resulted in 63% (10/16) local recurrence, 38% axillary metastasis, and 6.3% lung metastasis. Only 38% of the mice were disease-free. Thus in the model studied, perioperative chemotherapy offers the best chance for reduced recurrence and for improved disease-free survival.

Adenocarcinoma↗
PubMed1996

The potential role of integrin receptor subunits in the formation of local recurrence and distant metastasis by mouse breast cancer cells.

BACKGROUND: The mechanisms by which surgical injury fosters tumor growth are examined. METHODS: TA3Ha mouse breast tumor line and its subline (TA3AD) differing in their metastatic abilities as tested by two models were used. In model a, TA3Ha/TA3AD tumors were grown in the mammary fat pads of mice and then surgically removed with a curative intent. In model b, TA3Ha/TA3AD cells were injected intravenously into mice subjected to liver or spleen wedge resection. Frequency of tumor formation at various sites was assessed. Expression of integrin, immunoglobulin, and proteoglycan cell adhesion receptors on TA3Ha and TA3AD cells was examined by flow cytometry. The roles of these receptors in metastasis were examined by blocking them by selected ligands and/or antibodies. RESULTS: Frequencies of local recurrence and axillary metastasis after surgical resection, were 43% (32/74), and 37% (27/74) with TA3Ha tumors and 4% (1/29) at both sites with TA3AD tumors. Tumors at surgically injured spleen and the liver were seen in 75% (141/189) and 45% (107/240) of the mice with TA3Ha cells and in 8% (3/38) and 10% (4/42) of the mice with TA3AD cells. alpha 5 and CD44 receptors were expressed by TA3Ha cells but not by TA3AD cells. Other receptors examined were similarly expressed by both cell lines. Blocking of alpha 5 receptor by fibronectin reduced tumor implantation in a dose-dependent manner. CONCLUSIONS: The data suggest a correlation among the ability to implant at surgically injured sites, to form local recurrence, and to express the fibronectin receptor subunit.

Animals↗
PubMed1996

Role of cytokines and growth factors in promoting the local recurrence of breast cancer.

The pathogenesis of local recurrence in breast cancer is not well understood. Breast-conserving surgery is particularly prone to local recurrence as it leaves behind breast tissue that may harbour occult cancer, and lends itself to enhanced intraoperative shedding of cancer cells due to narrower resection margins and transection of lymphatic channels. A review of clinical breast cancer studies as well as experimental research strongly suggests that these persisting cancerous cells are unlikely to develop into clinically evident disease if their environment remains unstimulated. However, an inordinately high local recurrence rate occurs at the surgical scar, and such recurrence must be triggered by the release of growth factors and cytokines into the healing wound. These factors can stimulate any available cancer cells which express the proper growth factor receptors. Perioperative strategies to neutralize this tumour cell-growth factor interaction should maximize local control.

Breast Neoplasms↗
PubMed1996

Endocrine and paracrine hormones in the promotion, progression and recurrence of breast cancer.

Both normal and neoplastic breast tissues are stimulated by endocrine and paracrine hormones. Epidemiological studies have demonstrated the significant role that hormones, growth factors and cytokines have in the promotion, progression and recurrence of breast cancer. Significant variations in the hormonal environment occur based on age, the cyclical changes occurring during the menstrual cycle and (mammographically determined) variations in breast composition. These variations have a significant influence on rates of local recurrence of breast cancer and survival. This review analyses data relevant to these issues and suggests means by which operative results may be improved.

Adult↗
PubMed1995

Growth and metastasis of human breast cancers in athymic nude mice.

To evaluate critically the merit of utilizing a wound model for growing human tumors, a series of increasingly difficult human tumor types were tested for growth at sites of trauma in athymic nude mice. In vitro tumor lines as well as fresh tumors from the breast, colon, rectum, lung, and a metastasis from an unknown primary were intraperitoneally injected into mice subjected to intra-abdominal organ injury. Successful xenografts were obtained from nine of 10 cell lines and 14 of 24 fresh tumors. The latter included five of six (83%) colon cancers, one lung tumor, metastatic tumor of unknown primary, three of four (75%) metastatic breast cancers and four of six (67%) estrogen receptor (ER)-negative breast primary tumors. Six ER-positive breast tumors tested failed to grow in mice without estrogen supplementation. Xenografts from two breast, two colon and the lung cancers formed spontaneous metastases and all xenografts tested were able to yield serial transplants in the surgical wound model. Histologically, all xenografts and their metastases were identical to their respective donor tumors. Transplantability in mice without exogenous estrogen supplementation was linked to the absence of estrogen and progesterone receptors in breast tumors. Transplantability of the cell lines was associated with the expression of cell surface receptors for fibronectin and hyaluronic acid. Receptors for other extracellular matrix components, namely, laminin, vitronectin, collagen, fibrinogen or von Willebrand factor were not associated with transplantability. These results demonstrate that a large proportion of human tumors, including the breast tumors, can be successfully xenografted into athymic mice by providing them with a healing wound environment, and that such xenografts grown at ectopic sites exhibit metastatic ability.

Animals↗
PubMed1995

Prevalence of tuberculosis in a rural area by an alternative survey method without prior radiographic screening of the population.

SETTING: Mass miniature radiography (MMR) is the usual tool for population screening in tuberculosis case prevalence surveys. However, this facility is not available at most centres in India. OBJECTIVE: The feasibility of conducting a survey without MMR screening was therefore investigated. DESIGN: The study was carried out in Bangalore rural district during 1984-1986. The area was the same as for six earlier prevalence surveys conducted since 1961. The population aged up to 44 years was tuberculin tested. Persons with test induration size of > or = 10 mm were eligible for sputum examination, besides all those aged over 45 years who were eligible without discrimination. RESULTS: Reduction of workload was not adequately achieved through screening, as 78.4% of the registered population (29,400) was still eligible for sputum examination. The changed screening procedure in this survey also made comparison with earlier data difficult. In spite of more liberal and comprehensive screening, the observed prevalence rate of cases (438/100,000 population aged 10+ years) was similar to earlier surveys. The prevalence rate of smear-positive cases, however, was much lower (68/100,000 population aged 10+ years). CONCLUSION: In conclusion, the candidate screening procedure was not suitable. The findings nevertheless conformed to the overall declining trend for the area, as reported earlier.

Adolescent↗
PubMed1994

A stress-regulated protein, GRP58, a member of thioredoxin superfamily, is a carnitine palmitoyltransferase isoenzyme.

We recently noted the association of carnitine palmitoyltransferase (CPT) activity with a 54 kDa microsomal protein [Murthy and Pande (1993) Mol. Cell Biochem. 122, 133-138] that, based on amino-acid-sequence identity, seemed to be the protein previously described as a 'glucose-regulated protein-58' (GRP58), phosphoinositide-specific phospholipase C, hormone-induced protein-70, endoplasmic-reticulum protein-61 (ERp61), protein disulphide-isomerase, thiol protease, a protein affected in halothane anaesthesia and one that affects renal-tubular functions and the transcriptional activation of the interferon-alpha inducible genes. To ascertain the catalytic identity of this protein unambiguously, we have expressed the corresponding cDNA transiently and stably in human kidney 293 cells as well as in HeLa cells. In each case we found that expression led to an increase in assayable and immunoreactive 54 kDa CPT activity, whereas the protein disulphide-isomerase activity was not increased. In vitro expression in a cell-free transcription and translation system led to the synthesis of a approximately 57 kDa (precursor) protein that was processed to a approximately 54 kDa (mature) protein when microsomes were present; in both these experiments again a large increase in CPT activity was seen. Thus the present data provide compelling evidence that the 54 kDa protein in question is a CPT isoenzyme. It remains to be seen now how the ability of this protein to interconvert acyl-CoA and acylcarnitine would relate to the diverse functions indicated for this protein in vivo.

Blotting, Western↗
PubMed1994

Malonyl-CoA-sensitive and -insensitive carnitine palmitoyltransferase activities of microsomes are due to different proteins.

A carnitine palmitoyltransferase (CPT), extracted from microsomes with octyl glucoside, was purified and characterized as a 54-kDa protein and was found to show no malonyl-CoA inhibition (Murthy, M. S. R., and Bieber, L. L. (1992) Protein Exp. Purif. 3, 75-79). We show here that the malonyl-CoA-sensitive CPT of microsomes associates with their membrane, whereas the above 54-kDa CPT is a soluble luminal protein. Western blot probing with antibody to the 54-kDa CPT was found to show a positive response with the soluble microsomal fraction but not with their membranes. 2-Tetradecylglycidyl-CoA inhibited the membrane-associated CPT activity irreversibly, whereas the inhibition of the soluble CPT was largely reversible. Exposure of microsomes to [3H]etomoxir, ATP, and CoA led to the labeling of a approximately 47-kDa peptide that associated with membranes, whereas no such peptide labeling was seen with the soluble microsomal fraction. These and other results show (a) that microsomes have malonyl-CoA-sensitive, as well as malonyl-CoA-insensitive, CPT activities, (b) that these two activities are due to distinct proteins, (c) that the malonyl-CoA-sensitive CPT of microsomes is a previously uncharacterized CPT isoform, and (d) that the [3H]etomoxir-labeled approximately 47-kDa peptide is a likely candidate for the microsomal malonyl-CoA-sensitive CPT or its regulatory subunit.

Animals↗
PubMed1994

Some properties of the malonyl-CoA sensitive carnitine long/medium chain acyltransferase activities of peroxisomes and microsomes of rat liver.

1. An increase in the ionic strength of the assay medium markedly increased the basal activity of the malonyl-CoA-sensitive carnitine medium/long chain acyltransferases in peroxisomes and microsomes and decreased the malonyl-CoA inhibition. 2. ATP-Mg largely reversed the salt mediated stimulation of both the peroxisomal and the microsomal activities. 3. The octylglucoside solubilization of the peroxisomes and microsomes caused only marginal losses of their catalytic activity but the malonyl-CoA inhibition was nearly fully abolished. 4. Starvation increased the above activity of peroxisomes and microsomes and decreased their sensitivity to malonyl-CoA inhibition. Tritiated etomoxir labeled a approximately 47 kDa peptide in these organelles, the intensity of which was decreased on starvation. Collectively these findings strengthen the notion that the malonyl-CoA sensitive carnitine acyltransferases in mitochondria, microsomes, and peroxisomes are distinct proteins.

Acyl Coenzyme A↗
PubMed1993

Carnitine medium/long chain acyltransferase of microsomes seems to be the previously cloned approximately 54 kDa protein of unknown function.

A microsomal protein having N-terminal amino acid sequence SDVLELTDEN, was initially described as a phosphatidyl inositol-specific phospholipase C alpha when its cDNA was cloned (Bennett et al., Nature, 334, 268, 1988). Later, this protein, with an estimated molecular mass of 54 to 60 kDa, was shown to lack the phospholipase activity and instead a protein disulfide oxidoreductase and a thiol protease activities were ascribed to it. Following evidences indicated that the protein in question is the carnitine medium/long chain acyltransferase (CPT) of microsomes that was recently purified as a approximately 54 kDa protein (Murthy and Bieber, Protein Exp. Purif. 3, 75, 1992). First, the N-terminal amino acids of the microsomal CPT showed 100% homology to the sequence described above. Second, during purification of this CPT, the oxidoreductase and the thiol protease activities of the microsomes became separated from the CPT and these other activities were not found in the approximately 900 fold enriched CPT preparations. Third, an antibody to this protein did not immunoprecipitate oxidoreductase of the solubilized microsomal extract but precipitated the CPT. This same protein has been studied by others as the ERp61 (endoplasmic reticulum protein), GRP58 (glucose regulated protein), and HIP-70 (hormone induced protein) but its function was not identified.

Amino Acid Sequence↗
PubMed1993

The role of fibronectin in tumor implantation at surgical sites.

Fibronectins are a family of glycoproteins with modular functional domains. They mediate cell-cell and cell-matrix interactions which are important in embryogenesis, wound healing, metastasis and other processes. We present data on the influence of fibronectin on wound implantation of a murine mammary carcinoma line, TA3Ha. Fibronectin used in these studies was derived from bovine plasma, human serum, human foreskin fibroblasts, and mouse embryo cultures. TA3Ha cells rarely form tumors in the liver of syngeneic mice when injected intravenously but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Wound implantation is markedly reduced when the cells are pre-exposed to 200 micrograms/ml bovine plasma fibronectin (13%, P = 0.007), human serum fibronectin (0%, P = 0.02), human cellular fibronectin (0%, P = 0.02), or mouse cellular fibronectin (0%, P = 0.04). Lung colonization is also reduced by these fibronectins. These effects are not due to a cytotoxic action of fibronectin, since intraperitoneally injected fibronectin-treated cells form ascites tumor as effectively as do control untreated cells. Local application of a solution containing 0.25 mg/ml mouse cellular fibronectin to the hepatic wound reduces the frequency of tumor implantation from 45% to 5% (1/21, P = 0.001). No tumor implantation inhibition is seen when only suspending medium or albumin in suspending medium is used. The mechanism by which topical application of fibronectin reduces hepatic wound implantation of tumor cells is unclear, but this finding raises an exciting possibility of preventing local recurrence of cancer.

Adenocarcinoma↗
PubMed1992

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↗
PubMed1992

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↗