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Biomedical subjects

J M Varga

Publications and source records attributed to J M Varga.

At least 37 records · Page 2Linked to original sources
PubMed1983

Inhibition of transplantable melanoma tumor development in mice by prophylactic administration of Ca-ascorbate.

Hemicalcium ascorbate (Ca-Asc, 51 mM, 1% wt/vol), added to the drinking water, had the following effects in DBA/2 mice inoculated with 10(5) S91 (Cloudman) melanoma cells: 1) it delayed the appearance of visible tumors by 2-4 weeks; 2) it increased the survival rate at three months after tumor challenge by 12-50%; 3) it had no significant effect on the rate of tumor growth once the size of the tumors had reached 10 mm3; 4) the inhibition was maximal when the treatment with Ca-Asc was started at least one week prior to the inoculation of cells 5) when free ascorbic acid was used instead of Ca-Asc, the animals consumed 50% less water, they became dehydrated and the treatment was less effective; 6) Ca++ (51 mM) alone had no significant inhibitory effect.--Since Ca Asc (1 mM) was not toxic to S91 melanoma cells in vitro, we suggest that prophylactic treatment of the animals with Ca-Asc inhibited tumor development by increasing the resistance of the host.

Animals↗
PubMed1982

Iodination of beta-melanotropin. Time course analysis of reaction mixtures by high pressure liquid chromatography and characterization of biologically active mono- and diiodo-beta-melanotropin.

The production of highly purified, chemically well defined, iodinated beta-melanotropin possessing full biological activity is described. beta-Melanotropin, purified by high pressure liquid chromatography, was iodinated using Iodogen as the oxidizing agent. Biological activity was recovered, following iodination, by incubating the iodinated peptide mixture in 0.75 M dithiothreitol at 37 degrees C for 18-24 h. The qualitative and quantitative effects of dithiothreitol and the changes that occurred in the iodination mixture with time were examined using high pressure liquid chromatography. This separation technique has proved to be a useful tool both for optimizing the iodination procedure and for the rapid, efficient purification of mono- and diiodinated beta-melanotropins. Amino acid analysis of these two peptides revealed modifications only of the one tyrosine residue (Tyr 5): the expected incorporation of iodine to form mono- or diiodo tyrosine. Monoiodo-beta-melanotropin had full biological activity, as measured by tyrosinase stimulation in Cloudman S91 melanoma cells, while diiodo-beta-melanotropin was an order of magnitude less active.

Animals↗
PubMed1982

Dose-related effects of psoralen and ultraviolet light on the cell cycle of murine melanoma cells.

Cloudman (S91) murine melanoma cells were treated with 4'-hydroxymethyltrioxsalen (HMT), a bifunctional psoralen and exposed to long-wavelength (365 nm) ultraviolet light. DNA content of the cells stained with propidium iodide was measured by flow cytometry, and cell cycle phases were delineated from the DNA histograms by using a curve-fitting routine. We found that HMT in combination with long-wavelength (365 nm) ultraviolet irradiation blocked melanoma cells in different phases of the cell cycle, depending on the dose of long-wavelength (365 nm) ultraviolet light and the concentration of HMT. The binding of [3H]HMT to DNA was measured parallel with cell cycle analyses. Treatments with HMT at concentrations corresponding to about 1 HMT bound per 10(6) base pairs of DNA led to the accumulation of cells with predominantly G2 DNA content. At higher concentrations (2 to 3 HMT/10(6) base pairs), the cells were blocked in the S and G1 phases. In conclusion, we have shown that extremely sparse substitution of HMT to DNA blocks melanoma cells in the G2 phase or other phases of the cell cycle in a dose-dependent manner.

Animals↗
PubMed1981

Cell cycle analysis of cultured mammalian cells after exposure to 4,5',8-trimethylpsoralen and long-wave ultraviolet light.

Cell cycle analysis was used to study the the effect of 4,5'8-trimethylpsoralen (TMP) and long-wave ultraviolet light (UV-A) on cultured mammalian cells. DNA distribution patterns were measured for murine melanoma cells (a cloned line of Cloudman S91) and a strain of diploid human skin fibroblasts (CRL 1295) using both a microfluorimetry procedure and flow cytometry. The untreated cells and those receiving TMP along and UV-A alone had identical DNA content as assessed at several posttreatment intervals (0-72 hr). The majority of cells in control groups contained a G1 DNA content, whereas exposure to TMP (2 x 10(-7) M) plus UV-A (1 Joule/cm2) led to the accumulation of cells in the G2 phase. These observations were similar for each cell type and both analytical techniques were in excellent agreement. The finding that psoralen plus UV-A induces a phase-specific G2 blockade in cultured cells has important implications for understanding the mechanisms which account for enhanced pigmentation and suppression of cellular proliferation following exposure to these agents in vivo.

Animals↗
PubMed1977

The number of receptors for beta-melanocyte stimulating hormone in Cloudman melanoma cells is increased by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin.

Cultured Cloudman melanoma cells exposed either to dibutyryl 3':5'-cyclic AMP and theophylline or to cholera toxin bind significantly more 125I-labeled beta-melanocyte stimulating hormone (MSH) and fluorescein-labeled MSH than untreated cells. MSH binds to melanoma cells in the G2 phase of the cell cycle. The stimulation of MSH binding by dibutyryl cyclic AMP results from an increase in the number of MSH receptors per G2 cell and, to a lesser extent, from an increase in the number of G2 cells. The affinity of the receptors for MSH is not influenced by dibutyryl cyclic AMP.

Bacterial Toxins↗
PubMed1977

Multispecific lymphoid cell surface receptors.

When mice are sequentially immunized with two antigens to give an oligoclonal "double-binding" antibody response, there is a concomitant increase of "double-binding" cell surface receptors on their splenic lymphocytes. Competition studies suggest that the capacity to bind the two ligands, bovine pancreatic ribonuclease (EC 3.1.4.22) and a 2,4-dinitrophenyl (DNP) derivative, is a function of the same molecules. In ribo-nuclease-primed mice, an early response to bovine gamma globulin containing an average of 60 Dnp groups per molecule is the appearance of an increasing number of cells bearing surface receptors binding both ribonuclease and Dnp. Later, these double-binding cells are diluted by cells that bind Dnp, but not ribonuclease. The analogous phenomenon is observed when the two antigens are used in reverse order. While other reports suggest that there may be several different receptors in relatively undifferentiated cells from unimmunized mice, it seems likely that cells committed to antibody production carry a predominant multispecific cell surface immunoglobulin receptor.

Animals↗
PubMed1976

Nonrandom distribution of receptors for melanocyte-stimulating hormone on the surface of mouse melanoma cells.

An improved bubble method was developed for applying an ultrathin layer of nuclear track emulsion on the surface of cells labeled with I125-MSH. The autoradiographs of I125-MSH binding indicate a nonrandom distribution of receptors on the surface of mouse melanoma cells. It is suggested that MSH receptors are displayed in clusters previous to and independently of their exposure to the hormone.

Acetone↗
PubMed1976

Association of cell surface receptors for melanotropin with the Golgi region in mouse melanoma cells.

Binding of beta-melanotropin (betal-melanocyte stimulating hormone) to mouse melanoma cells occurs in a region on the cell surface overlying the Golgi complex. This association was demonstrated by labeling cells with fluorescein isothiocyanate hormone and by locating the Golgi complex with a histochemical test for thiamine pyrophosphatase activity. The biologically active fluorescent hormone appears on the surface and later in vesicles in the malanized cells, as judged by fluorescence microscopy. It is conceivable that internalization of the hormone is instrumental in the process of hormonally induced melanization. Because initial and late events of hormonally induced pigmentation are related to the Golgi complex, it is likely that instructions that follow the attachment of melanotropin to receptors are carried out in a compartmentalized manner.

Cell Line↗
PubMed1976

Melanocyte-stimulating hormone receptors on cultured guinea-pig melanocytes.

Guinea-pig melanocytes in mixed epidermal cell cultures bind melanocyte-stimulating hormone in a distinct focal surface area in their perinuclear field and thus follow the same pattern previously described for Cloudman melanoma cells. The labeling index ranged from 18 to 34%. Pretreatment of cultures with trypsin leads to destruction of melanocyte-stimulating hormone receptors whereas neuraminidase has no such effect.

Cell Line↗
PubMed1975

Melanoma cells resistant to inhibition of growth by melanocyte stimulating hormone.

Melanocyte stimulating hormone (MSH) enhances melanization but inhibits proliferation of Cloudman S91 melanoma cells in culture. We have isolated variants of these cells that can grow in the presence of MSH. The conclusions we have reached from analyses of these cells are the following: (1) Basal tyrosinase activity (monophenol monooxygenase; monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1), i.e., the activity that is present in the absence of added MSH, is related through a common biochemical pathway to MSH-mediated control of growth. (2) MSH-inducible tyrosinase activity does not appear to be related to MSH control of growth. (3) The morphological changes that occur following the addition of MSH or cAMP are related to controls of growth and not to those of melanization.

Animals↗
PubMed1974

The three dimensional structure of a combining region-ligand complex of immunoglobulin NEW at 3.5-A resolution.

IgG New binds ligands such as orceine, menadione, and uridine with a low affinity (K(0) about 1 x 10(3) liter/mol) and a gamma-hydroxy derivative of vitamin K(1) with a higher affinity (K(0) = 1.7 x 10(5) liter/mol). Binding studies indicate that both the 2-methylnaphthoquinone rings and the phytyl tail of the vitamin K(1) hapten contribute to the total binding energy. The binding of these ligands in the crystalline state has been investigated by difference Fourier maps of Fab' New-ligand complexes at 6-A resolution. A 3.5-A resolution difference Fourier map obtained for the gamma-hydroxy derivative of the vitamin K(1)-Fab' complex shows that this hapten is bound in a shallow groove or crevice between the light and the heavy chains, in close proximity to the polypeptide segments containing the hypervariable regions. At least 12 amino-acid residues from both the light and the heavy chains appear to be in close contact with the ligand. No major conformational changes were detected in the Fab' fragment after ligand binding.

Antigen-Antibody Complex↗