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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 181 records · Page 10Linked to original sources

The N-ras oncogene assigned to the short arm of human chromosome 1.

The human N-ras oncogene, isolated from the HL-60 promyelocytic leukemia cell line, is distantly related to viral oncogenes of Kirsten and Harvey sarcoma viruses. We have determined its chromosomal location by Southern blot analysis of DNAs from 37 human x rodent hybrid cell lines derived from 8 different human donors, some of whom carried balanced rearrangements of chromosome 1. The results indicate that the N-ras oncogene (RASN) is localized on the proximal part of the short arm of human chromosome 1, in region p3200 leads to cen.

Animals↗

The HL-60 transforming sequence: a ras oncogene coexisting with altered myc genes in hematopoietic tumors.

The oncogene of the HL-60 human promyelocytic leukemia cell line has been passed serially through NIH/3T3 mouse fibroblasts. Oncogene-specific probes prepared from the resulting tertiary transfectants by molecular cloning have been used to show that loss of the transfected oncogene from NIH/3T3 cells correlates with reversion to nontransformed morphology. Analysis of cells transfected by the oncogenes of other tumors and tumor cell lines indicates that the transforming gene of the HL-60 leukemia cell line is closely related to oncogenes of a Burkitt's lymphoma, an acute myelogenous leukemia, an adenocarcinoma of the colon, a neuroblastoma, and two sarcomas. This oncogene is distantly related to the viral oncogenes of Kirsten and Harvey sarcoma viruses. It has been termed N-ras. The active N-ras oncogene coexists with altered versions of the myc oncogene in the HL-60 and AW Ramos human tumors. This suggests a multistep mechanism involving both ras and myc genes in the creation of these tumors.

Animals↗

Effects of dietary zinc on melanoma growth and experimental metastasis.

These studies were designed to determine the effects of zinc on in vitro melanoma cell growth and in vivo metastasis. Cultured P51 mouse melanoma cells were larger, had longer doubling times and a decreased rate of tritiated-thymidine uptake when grown in zinc depleted compared to standard medium. Experimental metastasis was evaluated using intravenously injected, radiolabelled melanoma cells. Cell distribution and survival were determined 1, 3 and 21 days post-injection in C57BL/6 mice fed low zinc (0.5 and 4.0 mg Zn/kg) or stock diets. Altered organ distribution and survival of melanoma cells were observed in the zinc depleted dietary groups compared to the stock diet group. After 21 days of tumor growth, lungs of mice fed diets low in zinc contained up to 50% fewer labelled tumor cells than those of mice fed the stock diet. Livers of mice in the 0.5 mg Zn/kg group contained a greater percentage of tumor cells 21 days post-injection than those of mice fed the stock diet. Thus, dietary zinc can influence experimental tumor metastasis through modification in organ distribution of tumor cells and their subsequent survival.

Animals↗

Effects of supplemental zinc on melanoma metastasis in mice.

The influence of a single intraperitoneal injection of zinc (0.5, 1.5 and 4.5 mg/kg) on the metastasis and subsequent growth of radiolabelled melanoma cells was examined in mice receiving tumor cells s.c. or i.v. 24 h following zinc treatment. Parenteral zinc resulted in increased tumor cell survival in the liver, spleen and lungs of zinc-treated mice 1 day post-injection, while 21-day cell survival was enhanced in the spleens of s.c. injected, zinc-treated mice. Regardless of zinc exposure, relative numbers of s.c. injected tumor cells decreased with time in the lungs and spleen, while increasing in the liver and kidneys. A single dose of zinc can modify the organ distribution and viability of metastatic tumor cells in mice.

Animals↗

Construction and use of a dominant, selectable marker: a Harvey sarcoma virus-dihydrofolate reductase chimera.

The transcriptional promoter of the Harvey sarcoma virus long terminal repeat has been used to construct a biologically active dihydrofolate reductase chimera. The construction placed the long terminal repeat at the 5' end of a dihydrofolate reductase cDNA. This chimera mediated methotrexate resistance when introduced into wild-type NIH3T3 mouse cells by transfection. The chimeric sequences were expressed in the form of polyadenylated RNA and dihydrofolate reductase protein and were amplified when the methotrexate-resistant transfectants were selected to grow in increasing methotrexate concentrations. This chimera was dominant acting and able to confer a methotrexate-resistant phenotype on wild-type NIH3T3 cells. It has been used in cotransfection experiments with DNA from human tumor cells to obtain foci of methotrexate-resistant transformed NIH3T3 cells resulting from uptake of exogenous DNA. The transfected methotrexate-resistant cells carried double minute chromosomes that appeared to contain DNA acquired during transfection.

Animals↗

Modulation of murine lymphocyte and macrophage proliferation by parenteral zinc.

The effects of a single i.p. injection of zinc (0.7, 1.3, 4.0 or 12.0 mg/kg), 24 h prior to sacrifice, on lymphocyte blastogenesis as well as lymphocyte and macrophage progenitor cell proliferation were examined using cells from adult BALB/c mice. Splenic lymphocyte blastogenesis in response to T cell mitogens decreased for mice receiving the highest zinc dosage while responses to B cell mitogens were initially depressed, subsequently increased, and finally declined sharply as the LD50 was approached. Splenic B cell colony formation decreased linearly in relation to zinc dosage with a 50% suppression of colony formation observed at approximately 8.0 mg/kg. In contrast, bone marrow granulocyte-macrophage colonies were enhanced at higher dosages (greater than or equal to 2.5 mg/kg) of zinc. These results indicate that zinc exposure at dosages less than the LD50 can influence lymphocyte blastogenesis and clonal expansion of both B cell and macrophage progenitors.

Animals↗

Clonal proliferation of peritoneal exudate cells from New Zealand black mice: age-related changes.

Proliferation and differentiation of peritoneal exudate colony-forming cells (PE-CFC) were examined in BALB/c, C57BL/6, and NZB mice; NZB mice provided an experimental animal model for studies of autoimmunity. At 1 and 12 months of age, the number of PE-CFC from NZB mice was significantly less than the number of PE-CFC for other tested strains, whereas the number of clusters formed was reduced only in the older NZB mice. In contrast, 1- to 12-month-old BALB/c and C57BL/6 mice showed no significant age or strain-dependent alterations in PE-CFC. Although the latency period preceding colony growth remained constant for all strains and ages, significant variation in colony size was observed for NZB mice; the largest colonies were noted in the oldest group. We also observed age-associated variations in colony morphology; therefore, age- and strain-dependent differences may exist in the differentiation or functional attributes of PE-CFC subpopulations. The results specifically indicate that NZB mice have age-related alterations in PEC proliferative and differentiation capacities.

Aging↗

Three different human tumor cell lines contain different oncogenes.

We have obtained foci of transformed mouse cells after transfection of human DNA from colon and bladder carcinoma cell lines and a promyelocytic leukemia cell line. These foci can be shown to contain a large number of human DNA sequences by use of highly repetitive human DNA sequence probes. Cell DNA from primary foci can be used in a subsequent cycle of transfection resulting in secondary foci that contain relatively little human DNA. Secondary foci appear to contain only the human sequences proximal to those responsible for the transformed phenotype. A set of characteristic DNA restriction fragments is found in common among secondary foci derived from each tumor cell line DNA. Comparison of the common DNA fragments found in secondary foci derived from three different human tumor cell lines indicates that these three cell lines contain three different transforming genes.

Animals↗

The salutary effect of milk on amoebiasis and its reversal by iron.

Observations among milk-drinking African nomads showed an unusual freedom from infection with Entamoeba histolytica compared with similar nomads taking a mixed diet. A controlled study among Maasai pastoralists showed that the administration of iron to correct their dietary iron deficiency sharply increased their susceptibility to amoebiasis. Examination of the milk of their Zebu cattle showed that it not only had a concentration of iron below the minimum necessary for the growth of E histolytica but also contained partly saturated lactoferrin and transferrin, which may actively compete with the parasite in the colon for ambient iron. These observations suggest the possibility of a long-standing ecological compromise between nomads, their milk diet, and E histolytica.

Adult↗

Nitrous oxide availability.

Nitrous oxide (N2O) is marketed as an inhalation anesthetic and as a food ingredient (e.g., whipping cream propellant). In the human, inhalation has been associated with "highs," peripheral nerve damage, mitotic poisoning of bone marrow, psychosis, and mental impairment. Exposure to hypoxemic mixtures has resulted in death. The commercial N2O sources specifically studied were aerosol whipping cream containers (three brands) and 6.5-cm cylinders, or chargers (two brands). The gas content and N2O concentrations of these devices were measured. The aerosol cans, when not shaken, will dispense at least 3 liters of 87 to 90% N2O. Charger misuse may occur when they are substituted for identically designed carbon dioxide (CO2) chargers of a seltzer bottle; 4.3 to 5.0 liters of 93 to 98% N2O is expelled at a controllable rate. The toxicity of these inexpensive N2O products, their high potential for misuse, and the absence of labeling (chargers) argue that their distribution be discontinued.

Aerosols↗

Molluscum contagiosum and herpes simplex in Maasai pastoralists; refeeding activation of virus infection following famine?

An epidemic of molluscum contagiosum and oro-genital herpes simplex was observed in Maasai pastoralists of the Rift Valley. It coincided with a period of refeeding following famine, when the relief diet was different from normal milk fare. We propose that refeeding may be an important mechanism for activation of certain viral infections previously suppressed by famine.

Adolescent↗

Locating spike-initiating or spike-entry zones in a branched molluscan neuron.

A theoretical method for locating spike-initiating or spike-entry zones within a single neuron was experimentally verified using the cell RPI in the marine opisthobranch Navanax inermis. Multiple sites of spike-initiation were found to exist in RPI. Furthermore, it was demonstrated that extracellular recording alone was sufficient to map sections of cells' branching patterns and possibly locate multiple spike-initiating zones.

Animals↗

Immunoselection of mutants deficient in cell surface glycoproteins encoded by murine erythroleukemia viruses.

We have described a heterogeneously processed glycoprotein with an apparent molecular weight of 55,000 (gp55) that is encoded by the Friend spleen focus-forming virus, an acute erythroleukemia virus [Dresler, S., Ruta, M., Murray, M.J. & Kabat, D. (1976) J. Virol. 30, 564-573]. Several lines of evidence suggest that a small proportion of the gp55 in infected cells is located on the surface membranes. First, different nonproducer cell lines infected with cloned Friend spleen focus-forming virus were efficiently killed in the presence of complement by cytotoxic antisera that react with gp55. Furthermore, a clone of cells selected for resistance to the cytotoxic antibody synthesized an altered intracellular form of gp55. This immunoselection procedure appears to also be useful for isolating glycoprotein mutants of other RNA tumor viruses. Analysis of cell surface proteins labeled with [125I]iodine supported the idea that gp55 occurs on the plasma membranes. However, the cell surface gp55 had more highly processed oligosaccharides than the majority of the gp55, which occurs within the infected cells. In addition, we have found that leukemia cells from mice infected with the erythroleukemic Rauscher virus complex contain a membrane glycoprotein that appears similar to the gp55 encoded by Friend spleen focus-forming virus. The encoding of similar glycoproteins by independently isolated acute erythroleukemia viruses suggests that these glycoproteins may be important in leukemogenesis.

Animals↗

An ecological interdependence of diet and disease? A study of infection in one tribe consuming two different diets.

The nature and incidence of infections were studied in two groups of Turkana living in the same area but eating different diets; one consumed milk only and the other a combination of fish and milk. The only apparent and significant nutritional difference between the two groups was mild iron deficiency in the milk drinkers. Episodes of fever, symptomatic infection with malaria and brucellosis, molluscum contagiosum and common warts, episodes of diarrhea, and serological evidence of infection with Entamoeba histolytica were significantly increased in Turkana eating fish. We suggest that this phenomenon may result from a disruption of a long-standing ecological compromise between the all-milk diet of the Turkana and the pathogenic organisms.

Adolescent↗

A murine leukemia virus mutant with a temperature-sensitive defect in membrane glycoprotein synthesis.

Cells infected with a temperature-sensitive mutant (ts-26) of Rauscher murine leukemia virus (R-MuLV) or with wild-type virus were labeled with 35S-methionine, and cell extracts were examined for radioactive polypeptides which could be precipitated by monospecific antisera to viral proteins. When shifted from permissive (31 degrees C) to nonpermissive (39 degrees C) temperature, cells infected with ts-26 rapidly begin to accumulate gPr90enr, the glycoprotein precursor to the membrane envelope glycoprotein gp70 and to the membrane-associated protein p15E. Simultaneously, formation of these mature virion proteins ceases. In addition, lactoperoxidase-catalyzed surface labeling with 125I--iodine indicates that the plasma membrane of cells infected with ts-26 becomes depleted of gp70 antigens at 39 degrees C. Nevertheless, at 39 degrees C these cells release defective MuLVs which lack gp70 and p15E but contain an outer membrane. The released particles also contain an aberrantly processed form of the major virion core protein p30, and many of these virion cores have an unusual immature crescent shape. It has previously been reported that cells infected with the ts-26 mutant of R-MuLV process a 65,000 dalton precursor (Pr65gag) of the virion core proteins more slowly at 39 degrees C than do cells infected with wild-type virus (Stephenson, Tronick and Aaronson, 1975). Although we have confirmed these results, this effect is relatively small and it is known that various alterations of MuLV assembly can lead secondarily to inhibited processing of Pr65gag. We propose that the ts-26 mutant has a primary temperature-sensitive defect in membrane glycoprotein synthesis and that this change causes pleiotropic effects on core morphogenesis.

Genes↗