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M L Freedman

Publications and source records attributed to M L Freedman.

At least 91 records · Page 5Linked to original sources
PubMed1975

Heterogeneity of rabbit platelets. IV. Thrombocytosis with absolute megathrombocytosis in phenylhydrazine-induced hemolytic anemia in rabbits.

Intravenous injection of phenylhydrazine into intact rabbits resulted in a thrombocytosis of 1.85 fold and megathrombocytosis (large platelets) of 2.30 fold. Splenectomy markedly impaired this response. The intravenous injection of red blood cell hemolysates gave a response similar to that of phenylhydrazine in both intact and splenectomized animals. Basal data obtained from intact and splenectomized animals; as well as kinetic data obtained following apparent splenic blockade secondary to phenylhydrazine hemolysis revealed the presence of a splenic platelet pool with preferential splenic sequestration of megathrombocytes. It is suggested that the thrombocytosis and absolute megathrombocytosis of hemolysis is due to splenic blockade by red blood cell hemolysate.

Anemia, Hemolytic↗
PubMed1975

Ethanol inhibition of reticulocyte protein synthesis: the role of haem.

Ethanol, in concentrations of 0.05-0.8 M, inhibited intact human and rabbit reticulocyte protein synthesis in the presence of iron-transferrin for endogenous haem synthesis. Associated with this effect there was a conversion of polyribosomes to monoribosomes and a decreased incorporation of radioactive leucine into nascent globin chains. When physiological levels of ethanol (0.05-0.1 M) were used, these effects were prevented by incubation with 50 muM haemin and reversed by removing the alcohol and reincubating with iron-transferrin or haemin. The polyribosomal disaggregation was also prevented by stopping ribosomal movement with 5 mM cycloheximide. Neither ATP nor GSH levels were altered in the presence of ethanol. When non-physiological levels of 0.8 M ethanol were used, haemin did not prevent the inhibition of protein synthesis. Likewise, in the rabbit reticulocyte cell-free lysate system containing haemin inhibition was noted at concentrations greater than 0.05 M ethanol. The polyribosomal disaggregation in reticulocytes incubated with 0.8 M ethanol was associated with decreased dissociation of monoribosomes into subunits. Similarly, when ribosomes were directly suspended cell-free in 0.1 or 0.8 M ethanol there was a decreased percentage of subunits. These results indicate that physiological concentrations of ethanol inhibit initiation of reticulocyte protein synthesis secondary to a block in haem synthesis. When intact cells are exposed to high non-physiological concentrations of ethanol the inhibition is secondary to decreased ribosomal dissociation. The cell-free lysate inhibition is also through this effect on ribosomal dissociation. This study supports the view that alcohol is a direct toxin to developing red cell precursors via its effect on mitochondrial haem synthesis. The physiological role of the decreased dissociation of monoribosomes into subunits is not yet clear.

Acetaldehyde↗
PubMed1975

Heterogeneity of rabbit platelets. V. Preferential splenic sequestration of megathrombocytes.

Rabbits were either splenectomized or subjected to splenic blockade with phenylhydrazine in order to determine the splenic platelet and megathrombocyte (large-platelet) pools. The average splenic platelet pool calculated from both methods was 35% of total platelets. The average splenic megathrombocyte pool was 54% of total megathrombocytes. Adrenaline injection into rabbits or dogs revealed a rapid increase in both platelet count and megathrombocyte number which peaked at 2-6 min and returned toward normal in 5-10 min. The platelet volume distribution curve was shifted to the right, indicating the release of large platelets (megathrombocytes) into the circulation. The peak rise in megathrombocyte number was significantly greater than the peak rise in platelet count. Rabbits subjected to splenic massage shifted their platelet volume distribution curve to the right in the absence of a rise in platelet count. It is concluded that the spleen preferentially sequesters megathrombocytes.

Aging↗
PubMed1975

Variation in internal polysaccharide synthesis among Streptococcus mutans strains.

Five strains, representative of Streptococcus mutans genetic group III antigenic group d, synthesized and degraded less intracellular polysaccharide (IPS) then 17 strains representative of other S. mutans groups. The strains that synthesize IPS degraded it rapidly. The production of acid in titratable amounts from endogenous IPS was usually complete within 1 h. IPS synthesis in S. mutans increased abruptly at culture glucose concentrations between 0.2 and 0.5% and was quantitated as both iodine-and glucose oxidase-positive material in cell hyrolysates. IPS degradation was measured by acid production in a pH-stat maintained at 7. The existence within group III d of a strain recently shown to be cariogenic in experimental animals suggest that IPS may not be a prerequisite for virulence in these cariogenic bacteria.

Acids↗
PubMed1975

Elevated platelet count and megathrombocyte number in sickle cell anemia.

Eight adult patients with sickle cell anemia were followed over a 6-mo period. During this time all patients had elevated plateletcounts, 1.7-fold (mean, 438,398 +/- 86,223), and megathrombocyte numbers, 2.3-fold (mean, 79,535 +/- 38,907), during asymptomatic periods. These data are interpreted as suggesting that the elevated platelets and megathrombocytes in asymptomatic sickle cell patients result from lack of splenic sequestration. During three crises in two patients, both megathrombocyte number and platelet count fell significantly. It is speculated that platelets may be associated with the pathology in this disease. Platelet function studies performed during crises, therefore, must take into account the number of megathrombocytes.

Adult↗
PubMed1975

Comparison of the effects of carbamyl phosphate and sodium cyanate on protein synthesis and glutathione concentration in human sickle cell and rabbit reticulocytes.

Two carbamylating agents, carbamyl phosphate and sodium cyanate, are currently being evaluated as therapeutic drugs for the treatment of sickle cell anemia. Since the clinical usefulness of these drugs might be limited by toxicity, a comparative in vitro study of the relative inhibition of human sickle cell and rabbit reticulocyte protein synthesis was performed. Sodium cyanate was found to inhibit human sickle cell protein synthesis at concentrations one-eighth that of carbamyl phosphate. Carbamyl phosphate lowered reduced glutathione levels to a similar degree as sodium cyanate and was slightly more effective as an in vitro antisickling agent, which is evidence that carbamyl phosphate enters these cells. When rabbit reticulocyte protein synthesis was investigated, carbamyl phosphate was found to be noninhibitory at concentrations as high as 128 mol/mol of hemoglobin in the incubation medium, while cyanate was inhibitory at much lower concentrations. The effect of carbamyl phosphate on glutathione concentrations, however, was virtually identical to that of cyanate. These results show that the effect on protein synthesis does not result from the lowered glutathione levels. It is concluded that both the therapeutic and toxic effects of sodium cre, there might be differences in toxicity between animals and humans.

Anemia, Sickle Cell↗
PubMed1974

Dissociation of plaque formation from glucan-induced agglutination in mutants of Streptococcus mutans.

The traits adhesion and cohesion are manifested in Streptococcus mutans by in vitro plaque formation and glucan-mediated agglutination and have been dissociated in mutants of this caries-associated microbe. In these mutants, which differ from each other in colonial morphology, we have observed a consistent loss of ability to form adhesive microbial deposits (plaque) on wires, but only a minimal alteration from the wild type in ability to agglutinate into macroscopic clumps in the presence of exogenous glucans or sucrose. Also, when these mutants were cultured in sucrose-containing medium, there was an increase in the synthesis of water-soluble, extracellular glucans and a decrease in the synthesis of alkali-soluble, cell-associated glucans. Based on these findings, it appears (i) that in vitro plaque formation and agglutination are distinct and dissociable traits, and (ii) that adhesion but not agglutination appears related to the synthesis of alkali-soluble, cell-associated glucans.

Agglutination↗
PubMed1974

Diminished virulence of glucan synthesis-defective mutants of Streptococcus mutans.

The virulence of cell surface-associated, glucan synthesis-defective mutants of Streptococcus mutans strain 6715-13 was studied. Representatives from three groups of such mutants were tested for their pathogenicity in conventionalized, specific pathogen-free rats and gnotobiotic rats. The mutants differ from the wild-type strain in that each failed to form plaque on the smooth surfaces of the teeth and to cause smooth surface caries. Although the ability to form cell surface-associated glucans was not a strict requirement for the expression of virulence in the sulci of the teeth, it augmented virulence at such sites. However, the ability to form cell surface-associated glucans and to adhere to the teeth was clearly not the sole determinant of virulence.

Animals↗
PubMed1974

Ultrastructure of Mutants of Streptococcus mutans with Reference to Agglutination, Adhesion, and Extracellular Polysaccharide.

An electron microscopic study of S. mutans 6715-13 wild type and representatives of three distinct classes of glucan synthesis-defective mutants (which fail to form adherent microbial plaques but agglutinate normally in the presence of exogenous glucans) disclosed the presence of two sucrose-dependent, glucanase-sensitive, extracellular components. In the wild type, these extracellular glucans had predominantly fibrillar (with some globular) morphologies. However, in the mutant strains, there was a consistent reduction in or loss of the fibrillar components and dramatic increases in globular forms. A cell surface-associated fuzzy coat was consistently seen, and it was neither sucrose-dependent nor glucanase-sensitive. The data indicated that in vitro and in vivo adhesion and virulence at smooth tooth surfaces (all these properties dramatically reduced in the mutants) were causally and functionally related to the extracellular, fibrillar, glucan component, whereas in vitro glucan-mediated agglutination may be related to the cell-associated surface fuzzy coat.

Journal Article↗