Search PubMed⌕ Search

Biomedical subjects

M Rabinovitz

Publications and source records attributed to M Rabinovitz.

At least 91 records · Page 5Linked to original sources
PubMed1980

A comparative cytogenetic study of melphalan-sensitive and -resistant murine L1210 leukemia cells.

A cytogenetic analysis of melphalan-sensitive and -resistant murine L1210 leukemia cells maintained in vivo indicated that the drug-resistant tumor had a modal number of 40 chromosomes while the sensitive tumor possessed a mode of 41 chromosomes. Two marker chromosomes were present in both the sensitive and the resistant tumors. One was of medium length with secondary constrictions, and the other was a minute chromosome. A single in vitro exposure of the sensitive tumor cells to a cytotoxic concentration of melphalan was not accompanied by a change in modal number but resulted in chromatid exchange. No alterations were found in resistant tumor cells which were exposed to the same drug concentration. However, exposure of resistant tumor cells to higher doses of melphalan resulted in chromatid breaks, chromatid gaps and the formation of acentric chromosomes. The resistant tumor, transplanted once without drug injection, maintained a sharp mode of 40 chromosomes.

Animals↗
PubMed1980

Hemolysis due to human antibody-dependent cell-mediated cytotoxicity. Lysis of erythrocytes treated with anti-D serum.

Antibody-dependent cell-mediated cytotoxicity against Rh+ red blood cells was detected in human anti-D sera. We used a rapid 4-h 51Cr-release assay to show that cytotoxic activity was proportional to serum concentration, incubation time and the attacking cell concentration. Attacking cells were obtained from normal human peripheral blood by Ficoll-Hypaque separation. Incubation of these lymphoid cells on a nylon column prior to the test depleted the number of phagocytic (latex-positive) cells in the effluent concomitantly with a drop in cytotoxic activity. Enrichment of the attacking cell population in mononuclear phagocytes by albumin gradient separation led to an increase in cytotoxicity. Granulocytes separated by Ficoll-Hypaque were not active in this system. Antibody activity was found in the 7S region following Sephadex G-200 fractionation of anti-D serum. Antibody activity was also studied after its elution from antiserum-coated red blood cells by diethyl ether. The eluate contained IgG and mediated cell-dependent lysis. Cell-free antiserum did not mediate lysis of coated red blood cells in the presence of complement.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1979

Amino acid conferred protection against melphalan interference with melphalan therapy by L-leucine, a competitive substrate for transport.

Melphalan uptake by L1210 leukemia cells obtained from tumor bearing mice is reduced to one-third of control by physiological concentrations of L-leucine. Kinetic analysis revealed that melphalan and leucine compete for transport carrier sites. Administration of leucine with optimal therapeutic doses of melphalan to tumor bearing mice negated the efficacy of the drug.

Animals↗
PubMed1979

Effect of L-alpha-amino-gamma-guanidinobutyric acid on melphalan therapy of the L1210 murine leukemia.

About half the mice administered a lethal inoculum of L1210 leukemia become 60-day survivors when treated with an appropriate dose of melphalan. Leucine completely abolishes this long-term survival by interfering with melphalan uptake into the tumor cells. L-alpha-Amino-gamma-guanidinobutyric acid, the lower homolog of arginine, promotes melphalan uptake in vitro only in the presence of leucine. When administered to mice with melphalan and a dose of leucine which negates the 50% cure rate of melphalan, it reduces the therapeutic interference of leucine. However, L-alpha-Amino-gamma-guanidinobutyric acid alone does not improve melphalan therapy, suggesting that endogenous leucine can play only a minor role in interference with therapy of the L1210 leukemia.

Aminobutyrates↗
PubMed1979

Amino acid conferred protection against melphalan: comparison of amino acids which reduce melphalan toxicity to murine bone marrow precursor cells (CFU-C) and murine L1210 leukemia cells.

The effect of the naturally occuring amino acids upon melphalan (L-phenylalanine mustard, L-PAM) toxicity to a host sensitive tissue, the granulocyte and macrophage precursor cells of murine bone marrow (CFU-C), was investigated. At physiological concentrations the L isomers of leucine and glutamine were found to be the most effective of the naturally occurring amino acids in reducing drug toxicity. Tyrosine, phenylalanine and methionine also protected murine CFU-C from melphalan toxicity although the amount of protection provided by these amino acids at physiological concentrations was less than that provided by leucine and glutamine. Little difference was observed in the pattern of amino acid protection of murine CFU-C and murine L1210 leukemia cells. Murine CFU-C however were more sensitive to melphalan both in the absence and presence of amino acids.

Amino Acids↗
PubMed1978

Potentiation of chlorambucil activity by phenylbutazone.

Phenylbutazone increased the cytotoxicity of chlorambucil to L1210 and P388 leukemia cells in vitro by displacing alkylating agent bound to serum of the tissue culture medium. Administration of phenylbutazone with chlorambucil to mice bearing the P388 tumor lowers the dose of chlorambucil required to achieve maximum increase in life span, but also lowers the dose required for host toxicity. No therapeutic advantage is obtained by the combination.

Animals↗
PubMed1978

Enhancement of melphalan therapy with glutaminase:asparaginase.

Depletion of glutamine with Acinetobacter glutaminase:asparaginase promotes melphalan uptake by and cytotoxicity to murine L1210 cells in vitro. Combined treatment of tumor bearing mice with these two agents increases the therapeutic response.

Acinetobacter↗
PubMed1976

Amino acid-conferred resistance to melphalan. I. Structure-activity relationship in cultured murine L1210 leukemia cells.

Melphalan cytotoxicity to murine L1210 leukemia cells in culture was reduced in growth medium containing amino acids. Investigation of the effect of single amino acids revealed that the L-isomers of glutamine and leucine, but not the D-isomers, were the most active in decreasing cytotoxicity. Protection was concentration dependent, with maximum protection occurring at approximately 0.25 mM, a physiologic concentration. The LD90 for melphalan in the presence of 0.1 mM L-glutamine or L-leucine was increased by 7.3- and 10.8-fold respectively, under conditions where the cells had been pre-incubated with the amino acids. These results are interpreted to suggest that melphalan transport by the L1210 leukemia cell is mediated by a system also responsible for the transport of glutamine and leucine and that interaction with such a system may play a significant role in the chemotherapeutic activity of this alkylating agent.

Amino Acids↗