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R A Finkelstein

Publications and source records attributed to R A Finkelstein.

At least 109 records · Page 6Linked to original sources
PubMed1975

Pathogenesis and immunology of experimental gonococcal infection: role of iron in virulence.

Addition of iron componds to inocula of the relatively avirulent T3 or T4 colony types of gonococci increased their lethality for chicken embryos after intravenous inoculation but had little or no effect on the highly virulent T1 or T2 types. The toxicity of nonviable inocula, killed cells or sonicates, was not significantly affected by ecogenous iron. Addition of the iron-binding protein conalbumin reduced or delayed the lethal effect of T1, but not T3, gonococci although growth of both colony types in the allantoic cavity of the embryo was inhibited by this protwin. This effect can be attributed specifically to deprivation of iron since the iron-complexed form of conalbumin had no apparent influence on growth or virulence. The results indicate that the ability to acquire iron in vivo is a significant factor in gonococcal virulence. The virulent colony types appear to have enhanced ability to compete with the host for iron and this may be related to the presence of pili, other surface components, or the synthesis of iron-chelating compounds.

Animals↗
PubMed1975

Studies on toxinogenesis in Vibrio cholerae. III. Characterization of nontoxinogenic mutants in vitro and in experimental animals.

Spontaneous and chemically induced mutants with reduced ability to produce cholera enterotoxin (choleragen) as an extracellular protein were isolated from Vibrio cholerae strains 569B Inaba, a classical cholera vibrio, and 3083-2 Ogawa, an El Tor vibrio. By qualitative and quantitative immunological assay in vitro such mutants could be separated into different classes characterized either by production of no detectable choleragen (tox minus), or of small quantities of extracellular choleragen, or of large quantities of cell-associated choleragen but little extracellular choleragen. Analysis of proteins in concentrated culture supernates by electrophoresis in polyacrylamide gels showed that cultures from tox minus strains lacked proteins with electrophoretic mobilities corresponding with choleragen or the spontaneously formed toxoid (choleragenoid). Infant rabbits infected with the tox minus strains remained asymptomatic or developed milder symptoms than rabbits infected with the tox+ parental strains. When symptoms of cholera developed after inoculation with tox minus mutants, detectable numbers of tox+ revertants could be isolated from the intestines of the infected animals. Two tox minus strains, designated M13 and M27, caused no sumptoms and showed no evidence of reversion to tox+ during single passage in infant rabbits, and mutant M13 also remained avirulent and stably tox minus during six cycles of serial passage in infant rabbits. Strains M13 and M27 were also noncholeragenic in acult rabbit ileal loops. Quantitative cultures of the intestines from infected infant rabbits demonstrated that the avirulent mutant M13 can multiply in vivo and can persist in the intestinal tract for at least 48 h.

Animals↗
PubMed1975

Inhibition of mitogen stimulation of human peripheral blood leukocytes by Vibrio cholerae enterotoxin.

It has been found that the enterotoxin (choleragen) of Vibrio cholerae, strain 569B, can interfere with Phytohemagglutinin-P, pokeweed mitogen and concanavalin A stimulation of human peripheral blood leukocytes. The viability of cultured cells was not affected by the toxin. The toxin does not interfere with stimulation by direct competition for mitogen receptor sites. The ability of choleragen to inhibit stimulation by mitogens declines with time after initiation of stimulation. The biologically inactive, spontaneously formed, derivative of choleragen, choleragemoid, did not inhibit mitogen stimulation. However, choleragenoid did block the inhibition of stimulation caused by choleragen. Choleragenoid did not block inhibition of mitogen stimulation by a lymphocyte chalone preparation indicating that a different mechanism may be involved with the chalone. Since the diverse biological effects of choleragen are all believed to result from its interaction with cell membrane receptors followed by activation of adenyl cyclase, the results add to evidence which suggests that increases in the intracellular concentrations of 3',5'-adenosine cyclic monophosphate diminishes the mitotic activity of cells.

Animals↗
PubMed1973

Pathogenesis and immunology of experimental gonococcal infection: virulence of colony types of Neisseria gonorrhoeae for chicken embryos.

The virulence of gonococcal strains and colony types was evaluated in embryonated hen eggs of various ages inoculated by different routes. Striking differences in virulence of colony types were revealed by intravenous inoculation of 11-day embryos. T1 and T2 colony types were found to have high virulence for embryos, whereas T3 and T4 colony types were relatively avirulent. These observations are in accord with previous studies in volunteers. The differences in virulence were not related to differences in toxicity of killed gonococci, sonic lysates, or to the susceptibility of gonococci to cidal effects of chicken embryo blood. Rather, they appeared to involve differences in clearance of gonococci from the blood stream and subsequent multiplication of the virulent colony types. Infection with virulent colony types appears to be primarily bacteremic in this model. Preliminary experiments indicated that chicken embryos may be protected against the lethal infection by prior treatment of the inoculum with normal and immune rabbit serum. This protective effect was not associated with bactericidal activity. The chicken embryo model is potentially useful as a means of investigating attributes of virulence of gonococci and factors in immunity against gonorrhea.

Animals↗
PubMed1972

Crystalline cholera toxin and toxoid.

The exo-enterotoxin of Vibrio cholerae has been obtained in crystalline form. A solution of the crystalline protein was equal in potency to the parent pure toxin in both choleragenicity and skin reactivity. Crystals of the natural toxoid, choleragenoid, resemble those of the toxin in appearance. A solution of crystalline choleragenoid was equivalent to the parent preparation in the flocculation test.

Animals↗
PubMed1972

Properties of the cholera exo-enterotoxin: effects of dispersing agents and reducing agents in gel filtration and electrophoresis.

Initial studies, by using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS), led to the attractive hypothesis that the cholera exo-enterotoxin (choleragen) consisted of two noncovalently linked peptides of 56,000 and 28,000 molecular weight. The spontaneous toxoid (choleragenoid) appeared to be identical with the 56,000 molecular weight piece. The results appeared to be very similar to those obtained recently with diphtheria toxin. However, they did not agree with earlier studies which indicated that both the toxin and the toxoid consisted of subunits of approximately 14,000 molecular weight. More extensive investigation, by using gel filtration with (3)H-labeled toxin, ultracentrifugation, and immunologic studies, failed to support the observations of SDS-gel electrophoresis, suggesting the existence of a 28,000 molecular weight fragment which is unique to the toxin. The results were more compatible with our earlier observations regarding subunit composition. It is concluded that these proteins are relatively resistant to dissociation by SDS and need to be unfolded by prior treatment for more complete dissociation into subunits. Indirect evidence suggests that the 28,000 fragment may be a dimer, or larger aggregate, of a smaller subunit which can be integrated in the formation of choleragenoid. It is also evident that caution should be exercised in the interpretation of results, however pleasing, obtained only by SDS-gel electrophoresis.

Cholera↗
PubMed1971

Enteropathogenicity of Escherichia coli. I. Evaluation of mouse intestinal loops.

A ligated mouse intestinal loop assay has been introduced to evaluate the enteropathogenicity of strains of Escherichia coli. When inoculated as whole cultures, 19 (34%) of 55 strains isolated from diarrheic infants, each of 4 strains associated with diarrhea in human adults, and 5 of 7 strains associated with porcine coli bacillosis were found capable of causing fluid accumulation in this model. In contrast, only 1 of 28 strains isolated from normal individuals was positive in this test. Sterile concentrated filtrates of positive strains cultivated in Brain Heart Infusion broth or syncase broth were also positive, whereas filtrates of negative strains did not cause fluid accumulation. All of the strains associated with diarrhea in human adults and 16 of the 19 positive strains from diarrheic children were also found capable of causing hemagglutination of chicken erythrocytes in a slide test used to evaluate the "adhesiveness" of the bacteria, a property which may enable them to stick in the small bowel and avoid the normally efficient peristaltic clearance mechanism. Few of the nonenteropathogenic strains were positive in this test. The slide hemagglutination test may be a useful, rapid means of screening potentially enteropathic E. coli strains and merits further evaluation and study. Although not ideal, the mouse intestinal loop model offers some advantages over the rabbit ileal loop assay.

Adult↗
PubMed1971

Ion transport during cholera-induced ileal secretion in the dog.

To assess the ion transport mechanism by which cholera causes the small bowel to secrete, ion transport rates and electrical potential difference (PD) were determined simultaneously in the normal and choleragen-treated dog ileum in vivo. The results indicate that, during cholera, HCO(3) is actively secreted (i.e., against both an electrical and a concentration gradient); Cl is also actively secreted, against a modest electrochemical gradient. Electrogenic pumping of one or both of these anions is probably responsible for an observed PD change of approximately 13 mv (lumen negative). Na secretion can be accounted for entirely by passive ion movement. K secretion can be partly explained by passive diffusion secondary to the negative intraluminal PD; however, its concentration in the secreted fluid is two to three times higher than expected on the basis of passive forces, suggesting a component of active K secretion. The PD response of the choleragen-treated ileum is normal in response to glucose, but there was no PD response to saline-free mannitol perfusion. This suggests that the normal differential permeability of the ileum to anions and cations may be altered by choleragen, although other explanations of this finding are also possible.

Animals↗