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Biomedical subjects

R A Finkelstein

Publications and source records attributed to R A Finkelstein.

At least 127 records · Page 7Linked to original sources
PubMed1970

In vitro detection of antibody to cholera enterotoxin in cholera patients and laboratory animals.

Two new in vitro microtests for anticholeragen (cholera exo-enterotoxin) antibodies are described and compared. In both tests, choleragen and choleragenoid, antigenically identical purified moieties which differ in size, charge, and toxicity, may be used as sensitizing antigens with apparently equal facility. The passive hemagglutination (PHA) test in which sensitized tanned chicken erythrocytes are used was found to be more sensitive than the sensitized bentonite flocculation test. Tests with sera from cholera patients almost invariably demonstrated a rise in titer on convalescence. Results with the PHA test were directly correlated with results derived from in vivo toxin neutralization assays involving inhibition of skin reactivity and the ileal loop reaction. These observations strengthen the hypothesis that choleragen is involved in the pathogenesis of cholera in man and support the unitarian concept that skin reactivity and choleragenesis are manifestations of the same toxin acting in different tissues. Both of the tests described have been modified and used as inhibition tests in the detection and assay of choleragen antigen.

Journal Article↗
PubMed1970

Antitoxic immunity in experimental cholera: observations with purified antigens and the ligated ileal loop model.

Rabbits immunized with purified antigens, choleragen and choleragenoid (cholera exo-enterotoxin and natural toxoid), were found to resist intra-intestinal challenge with a variety of strains of cholera vibrios. The resistance occurred in the absence of a significant antibacterial antibody response. In fact, the antigens were incapable of protecting mice against the septicemic infection of the standard mouse protection test used for bioassay of conventional cholera vaccines. The immunized rabbits did, however, develop a significant antitoxin titer demonstrable by passive hemagglutination, although the presence of antitoxic coproantibody could not be established conclusively. The results suggest the potential value of antitoxic immunity in cholera and are consistent with the existence of only one serological type of cholera exo-enterotoxin.

Journal Article↗
PubMed1970

Antitoxic immunity in experimental cholera: observations with purified antigens and the rat foot edema model.

The recently introduced choleragen-induced rat foot edema model has been employed as a bioassay for evaluating the immunogenicity of three purified preparations containing cholera exo-enterotoxin antigen, choleragen, choleragenoid, and Formalin-treated choleragen (formagen). The results indicated that choleragen evoked antitoxic immunity. Both the degree of resistance to challenge and the serum antibody levels of immunized animals were found to be related to the immunizing dose. Responses to the natural toxoid, choleragenoid, were erratic: some animals responded well and some failed to respond with either serum antibody or resistance to challenge. On the other hand, the artificially prepared toxoid, formagen, was found to be superior to the parent toxin in immunogenicity. Resistance to the choleragen-induced rat foot edema could be transferred passively by means of antibody-containing serum from previously immunized animals. Each of the antigens induced a state of hypersensitivity manifested by an immediate edematous response to challenge with either choleragen or choleragenoid. This condition, which was also passively transferable, suggests that untoward reactions should be anticipated in people receiving multiple doses of immunogens containing the cholera exo-enterotoxin antigen. Some of these observations were repeated, in a preliminary fashion, in an apparently equally suitable mouse foot edema model.

Journal Article↗
PubMed1970

Monospecific equine antiserum against cholera exo-enterotoxin.

An antiserum specific for Vibrio cholerae exo-enterotoxin was produced by immunization of a horse with purified choleragenoid, a natural cholera toxoid. The serum has a high titer against the toxin antigen in passive hemagglutination tests and a respectable antipermeability factor activity. It also passively protected against choleragen-induced mouse foot edema. The serum was found to be useful for assaying toxin antigen in crude and refined products by in vitro tests such as radial immunodiffusion, Lf, and quantitative precipitin titrations. Based upon experimental observations, the serum was defined as containing 1,000 flocculating units of anticholera toxin antibody per ml. A flocculating dose, or Lf, of choleragen approximates 1 mug, and that of choleragenoid is 0.625 mug. Formalin toxoids behaved like the parent toxin in these tests. The serum contains approximately 2.2 mg of antibody protein per ml, which appears to be largely, if not entirely, of the Ig(T) type. It is suggested that this serum, which is available in considerable supply, be considered for use as a reference cholera antitoxin. The horse developed symptoms of anaphylactic shock during immunization, suggesting the need for caution in projected studies on toxoid-induced immunity in man.

Journal Article↗
PubMed1969

Pathogenesis of experimental cholera. Preparation and isolation of choleragen and choleragenoid.

Choleragen, a diarrheagenic protein enterotoxin elaborated by Vibrio cholerae, has been isolated from the supernate of fermenter cultures by steps involving ammonium sulfate precipitation, DEAE cellulose, Sephadex G-75, and Agarose A-5m chromatography. The resulting product appears to be pure according to immunoelectrophoretic, disc electrophoretic, ultracentrifugal, and immunologic criteria. Sephadex gel filtration and membrane filtration studies suggest a molecular size of 61,000. The isolated product is highly active in inducing experimental cholera in infant and adult rabbit models. It also elicits, in small dosage, an increased vascular permeability in skin. These observations indicate that choleragenicity and increased vascular permeability are intimately associated phenomena and may be manifestations of the same basic mechanism. An additional, antigenically identical, protein has also been isolated by the same procedures. The latter substance, termed "choleragenoid", lacks the permeability effect and choleragenicity of the choleragen moiety. Its size (estimated from Sephadex gel filtration at 42,000) is smaller than that of choleragen and it also differs in charge. Choleragenoid may prove useful as a nontoxic immunogen to protect against pathologic effects of V. cholerae infection.

Animals↗
PubMed1968

A test of antigenicity for the selection of strains for inclusion in cholera vaccines.

The antigenicity of a large number of cholera vibrio strains was compared, in groups of rabbits, by evaluating the serological responses to single limited doses of vaccines prepared from the strains. On the basis of these tests, it was possible to construct 2 quadrivalent (El Tor and classical, Inaba and Ogawa) vaccines which differed significantly in antigenicity for rabbits but which were indistinguishable in the "standard" mouse-protection test. The advisability of using a test of antigenicity for selection of strains and laboratory evaluation of vaccines is considered. Application of the proposed antigenicity test would depend on further comparisons of human response to vaccines which differ in antigenicity for the rabbit.

Agglutination Tests↗
PubMed1967

Colonial recognition, a "new" approach for rapid diagnostic enteric bacteriology.

The morphology, on MacConkey's agar, of colonies of the bacteria commonly found in enteric specimens is sufficiently characteristic and distinctive, when observed with transmitted oblique illumination and a low-power stereoscopic microscope, to enable identification at the generic (and occasionally the species) level with over 97% accuracy. Application of this technique resulted in great savings of time, manipulative steps, and media compared with the usual procedures of diagnostic enteric bacteriology, and there was an increase in sensitivity without sacrificing accuracy.

Bacteriological Techniques↗
PubMed1966

Virulence of Escherichia coli strains for chick embryos.

Powell, Calvin J., Jr. (Walter Reed Army Institute of Research, Washington, D.C.), and Richard A. Finkelstein. Virulence of Escherichia coli strains for chick embryos. J. Bacteriol. 91:1410-1417. 1966.-Fifty-three strains of Escherichia coli, freshly isolated from patients at Children's Hospital, Washington, D.C., were tested for virulence for 13-day chick embryos by allantoic inoculation of serial dilutions of viable cell suspensions. No clear-cut relationship could be demonstrated between inoculum size and response (death of the embryos) which would permit comparisons of virulence based on ld(50) determinations. However, the strains were classified into three groups according to the proportion of embryos which succumbed, regardless of inoculum size. There was no association between enteropathogenicity and embryo virulence, although there was high correlation between hemagglutinative activity for chicken erythrocytes and virulence of strains for embryos. Differences in virulence were not related to ability to multiply in the allantoic cavity nor did bacteremia appear to be essential for death of the embryos. Serial passage in eggs failed to alter virulence. Both the route of inoculation and the age of the embryos had a marked effect on the outcome of challenge with strains of varying virulence. The embryos were most susceptible to challenge by the intravenous route. The susceptibility of younger embryos decreased with increasing embryonic maturity, although some reversal of this trend was noted with 19-day embryos. The toxicity of culture filtrates and filtrates of allantoic fluid from infected embryos seemed to be related to strain virulence, suggesting that elaboration and availability of toxic factors may have an important bearing on the lethality of E. coli strains for chick embryos.

Animals↗