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Biomedical subjects

R Goldman

Publications and source records attributed to R Goldman.

At least 163 records · Page 9Linked to original sources
PubMed1978

A differential interaction of daunomycin, adriamycin and their derivatives with human erythrocytes and phospholipid bilayers.

Drug-membrane association of daunomycin, adriamycin and three of its derivatives, adriamycin-14-octanoate (AD-14-OCTA), adriamycin-14-acetate (AD-14-ACE) and N-trifluoroacetyladriamycin-14-valerate (AD32), was studied using phospholipid bilayers and human erythrocytes. The various drugs exhibited a differential affinity to membrane-lipid domains. Lipid-incorporated drugs exhibit a marked change in the shape of the emission spectrum which was utilized for the evaluation of the apparent dielectric constant, epsilon, of the environment surrounding the anthracycline moiety, as well as for the determination ofthe partitioning constant. By measuring the fluorescence polarization and the fluorescence lifetime of the incorporated drugs, rotational relaxation times of 4--8 ns were derived. These parameters provide a supportive evidence of the association of the fluorophore of the drugs with membrane-lipid domains. The anthracycline derivatives interact to a different degree with dipalmitoyl phosphatidylcholine and phosphatidylserine as reflected by changes in their thermotropic properties assessed by differential scanning calorimetry. Daunomycin was the most effective in decreasing the temperature of the phase transition and brought about a comparable reduction in the enthalpy of melting as AD32 and AD-14-OCTA. Adariamycin was the least potent of the series. AD-14-ACE and AD32 protected erythrocytes against hypotonic lysis, adriamycin and daunomycin had no significant effect on the susceptibility to hypotonic lysis, whereas AD-14-OCTA proved to be hemolytic even at low concentration (approx. 10(-7M).

Calorimetry, Differential Scanning↗
PubMed1978

Morphology of an Escherichia coli mutant with a temperature-dependent round cell shape.

Mutants of Escherichia coli capable of growing in the presence of 10 microgram of mecillinam per ml were selected after intensive mutagenesis. Of these mutants, 1.4% formed normal, rod-shaped cells at 30 degrees C but grew as spherical cells at 42 degrees C. The phenotype of one of these rod(Ts) mutants was 88% cotransducible with lip (14.3 min), and all lip+ rod(Ts) transductants of a lip recipient had the following characteristics: (i) growth was relatively sensitive to mecillinam at 30 degrees C but relatively resistant to mecillinam at 42 degrees C; (ii) penicillin-binding protein 2 was present in membranes of cells grown at 30 degrees C in reduced amounts and was undetectable in the membranes of cells grown at 42 degrees C. The mecillinam resistance, penicillin-binding protein 2 defect, and rod phenotypes all cotransduced with lip with high frequency. Thus the mutation [rodA(Ts)] is most likely in the gene for penicillin-binding protein 2 and causes the organism to grow as a sphere at 42 degrees C, although it grows with normal rodlike morphology at 30 degrees C. At 42 degrees C, cells of this strain were round with many wrinkles on their surfaces, as revealed by scanning electron microscopy. In these round cells, chromosomes were dispersed or distributed peripherally, in contrast to normal rod-shaped cells which had centrally located, more condensed chromosomes. The round cells divided asymmetrically on solid agar, and it seemed that the plane of each successive division was perpendicular to the preceding one. On temperature shift-down in liquid medium many cells with abnormal morphology appeared before normal rod-shaped cells developed. Few abnormal cells were seen when cells were placed on solid medium during temperature shift-down. These pleiotropic effects are presumably caused by one or more mutations in the rodA gene.

Amdinocillin↗
PubMed1978

A differential interaction of daunomycin, adriamycin, and N-trifluoroacetyladriamycin 14-valerate with mouse peritoneal macrophages.

The interaction of three anthracycline drugs, daunomycin, Adriamycin, and N-trifluoroacetyladriamycin 14-valerate, with mouse peritoneal macrophages was explored. As assessed by drug-specific cytofluorescence, Adriamycin and daunomycin accumulated slowly within macrophages, first staining the nucleus and then the cytoplasmic inclusions that were induced by the drug treatment. N-Trifluoroacetyladriamycin 14-valerate distributed rapidly into the cells, was excluded from the nucleus, and induced numerous cytoplasmic inclusions. Electron microscopy revealed that the cytoplasmic inclusions were vacuoles containing some amorphous material and not the classical autophagic vacuoles containing organelles and membrane lamellae. All the drugs induced cell shrinkage with time and brought about cell death within 24 hr. Loss of cell function and viability was dose and time dependent; i.e., a 6-hr incubation with daunomycin or Adriamycin, 2.5 microgram/ml, brought about a 50% reduction in the phagocytic capacity of the treated macrophages. The damaging potency towards macrophages (daunomycin greater than Adriamycin greater than N-trifluoroacetyladriamycin 14-valerate) is in the reverse order to the in vivo therapeutic efficiency.

Animals↗
PubMed1977

Differential scanning calorimetry and enzymic activity of rat liver microsomes in the presence and absence of delta1-tetrahydrocannabinol.

The thermal transitions of rat liver microsomes and isolated lipids were investigated by using differential scanning calorimetry. Endothermic transitions at approximately-5 degrees C and between approximately18 degrees and 40 degrees C were detected in the membranes and at approximately-10 degrees C and between approximately 10 degress and 20 degrees C in the extracted lipids. Interaction with delta1-tetrahydrocannabinol of microsomal membranes and of extracted lipids influences the thermotrophic behaviour as revealed by differential scanning calorimetry and eliminates the break in the Arrhenius plot of the enzymic activity of O-demethylase.

Animals↗
PubMed1977

Maintenance hemodialysis in myeloma kidney disease.

Maintenance hemodialysis and chemotherapeutic agents were used in the treatment of seven patients with end-stage myeloma kidney disease. Results indicate that with the use of such therapy life can be prolonged substantially. It appears that patients with myeloma-with or without serious extrarenal complications-are suitable candidates for maintenance hemodialysis and should not be denied the treatment even in the face of systemic neoplasm.

Adult↗
PubMed1977

Fluidity difference of membrane lipids in human normal and leukemic lymphocytes as controlled by serum components.

Lymphocytes isolated from the peripheral blood of patients with chronic lymphatic leukemia and from normal healthy donors were analyzed for fluidity of membrane lipids. The degree of lipid fluidity in normal and leukemic lymphocytes was quantitatively monitored by a method based on fluorescence polarization analysis of a fluorescent probe that is embedded in lipid regions of cellular membrances. The present studies were performed on lymphocytes isolated from 26 blood samples from 16 patients with chronic lymphatic leukemia and 36 blood samples from 36 normal health donors. A signifcant increase in the degree of fluidity of membrane lipids was found in lymphocytes isolated from leukemic patients as compared to that found for lymphocytes isolated from healthy donors. In vitro incubation of leukemic lymphocytes in normal serum resulted in a decrease in the fluidity of cellular membranes, whereas incubation of normal lymphocytes in leukemic serum resulted in an increase in the fluidity of membrane lipids. These observations suggest that normal and leukemic lymphocytes can be quantitatively characterized by monitoring degree of fluidity of cellular membrane lipids and that the fluidity difference between normal and leukemic lymphocytes is controlled by components in the blood serum.

Adult↗