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Biomedical subjects

M Pittman

Publications and source records attributed to M Pittman.

At least 55 records · Page 3Linked to original sources

Immunization against neonatal tetanus in New Guinea. 3. The toxin-neutralization test and the response of guinea-pigs to the toxoids as used in the immunization schedules in New Guinea.

The mouse toxin-neutralization test procedure described has been used for antitoxin titration of sera of New Guinea women following primary immunization with plain and adjuvant tetanus toxoids and following booster immunization, and for titration of guinea-pig sera.The responses of guinea-pigs immunized with the same toxoids and immunization schedule to simulate the human field trial studies were observed for 6 months. The relative antitoxin responses of guinea-pigs to the different toxoids were similar to those of the women.

Animals↗

Immunization against neonatal tetanus in New Guinea. 4. Comparison of tetanus antitoxin titres obtained by haemagglutination and toxin neutralization in mice.

Haemagglutination (HA) has been used frequently for the titration of tetanus antitoxin but published results have varied in relation to the "unitage" determined by the mouse toxin-neutralization test (TN). This report gives the results of the titration of a group of sera by haemagglutination and compares them with the results obtained by toxin neutralization. Although there was marked variation between HA and TN titres of individual sera, results indicated that haemagglutination is a useful procedure for the over-all evaluation of the antitoxin responses to tetanus toxoids in field studies.

Animals↗

Immunization against neonatal tetanus in New Guinea. 5. Laboratory assayed potency of tetanus toxoids and relationship to human antitoxin response.

Previous papers in this series have shown that plain toxoids induced early primary antitoxin levels in women in New Guinea that were not significantly different from those induced by adsorbed toxoids but that at the end of 1 year the antitoxin levels differed significantly. Protective levels (not less than 0.01 unit/ml) induced by adsorbed toxoids persisted for more than 3 years. Results of laboratory assays of the toxoids reported in this paper show that per total human immunizing dose, the plain toxoids had 72 or less international units (IU) whereas the adsorbed toxoids had approximately 200 IU. The international "unitage" of these toxoids reflected the persistence of the human protective antitoxin level but not the early primary response. The assay results were in agreement with findings of other workers that the mouse as well as the guinea-pig may be satisfactory for potency assay of adsorbed toxoids. The need for determination of the international unitage of tetanus toxoids used in human studies and the confirmation of relationship of this value to persistence of antitoxin levels is emphasized.

Animals↗

Immunological response of three mouse strains to typhoid vaccine and Vi antigen.

Vi-agglutinin, active cutaneous anaphylaxis and protective responses (ed(50)) of three mouse strains (CFW, NIH, and Balb/cAnN) to acetone-inactivated typhoid vaccine and soluble Vi antigen were compared. Seven days after immunization with either typhoid vaccine or Vi antigen the three strains of mice differed with respect to Vi-antibody titers. Significant differences were observed in the protective responses. Each mouse strain was significantly better protected by the intraperitoneal than by subcutaneous route of immunization. Active cutaneous anaphylaxis was more pronounced in showing strain differences in response to Vi antigen. The serological responses to Vi antigen of the strains of mice did not correlate with their protective response.

Agglutination Tests↗

Laboratory assays of different types of field trial typhoid vaccines and relationship to efficacy in man.

Pittman, Margaret (National Institutes of Health, Bethesda, Md.), and Howard J. Bohner. Laboratory assays of different types of field trial typhoid vaccines and relationship to efficacy in man. J. Bacteriol. 91:1713-1723. 1966.-Antibody responses of rabbits to H, O, and Vi antigens did not differentiate vaccine K (acetone-killed and dried) from vaccine L (heat-phenolized and dried) relative to human efficacy. A mouse protection assay in which intraperitoneal vaccination and challenge suspended in mucin were used showed vaccine K to be 3.69 times more potent than vaccine L; with subcutaneous vaccination, vaccine K was only 0.78 as potent. With the challenge suspended in saline, the effect of the route of vaccination was accentuated. An old U.S. reference vaccine, heat-phenolized, induced the same types of response as vaccine L. In the assay with intraperitoneal vaccination and mucin-suspended challenge, the potency of vaccine K relative to vaccine L and the potencies of Polish vaccines, P, N, and T, relative to vaccine K were directly correlated with the efficacies of the vaccines for man, as reported for the recent World Health Organization cooperative field trials in British Guiana, Yugoslavia, and Poland. This assay gave a high potency for alcohol-treated vaccine V relative to vaccine L, but the values did not reflect relative efficacy in the USSR field trial; the subcutaneous vaccination assay more closely reflected their human efficacy. An analysis suggested that vaccine K had a mouse protective factor not present in vaccine L and that vaccine V may have had a third factor. The influence of a few variable factors on the assay with intraperitoneal vaccination and mucin-suspended challenge was studied briefly.

Agglutination Tests↗

Immunization against neonatal tetanus in New Guinea. Antitoxin response of pregnant women to adjuvant and plain toxoids.

Immunization of pregnant women in New Guinea with three injections of plain toxoid had previously been shown to prevent neonatal tetanus. In the present study antitoxin levels induced by two oil-adjuvant toxoids (one injection), one AlPO(4) toxoid (two injections) and one plain toxoid (three injections) were compared with those induced by the same plain toxoid as used in the earlier study. At term there was no significant difference in the levels for the five toxoids, but those for the plain toxoids later declined rapidly. AlPO(4)-toxoid titres were significantly higher than the titres for the plain toxoids at the end of a year, but lower than the oil-adjuvant titres, which were the highest and most persistent. However, unacceptable side-effects (induced by subsequent lots of oil-adjuvant toxoids) preclude their routine use at present.The results indicate that a maternal antitoxin level at delivery of 0.01 unit/ml is protective. Aluminium-compound toxoid rapidly achieved titres that were better than this for at least a year, with minimal side-effects. Hence such toxoids are recommended for maternal immunization to prevent neonatal tetanus.

Female↗

Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis.

The nature of the pathogenesis and of the prolonged immunity of whooping cough has not been clearly defined. The literature of Bordetella pertussis indicated that only the antigen that induces histamine sensitization, lymphocytosis, and other biological reactions in mice is the cause of the harmful effects and prolonged immunity of whooping cough. This antigen has the general characteristics of bacterial protein exotoxins that cause the harmful effects of infectious diseases such as diphtheria and tetanus. It is proposed that this antigen, which is histamine-sensitizing, lymphocyte-leukocyte-promoting, and islets-activating (HSF-LPF-IAP), be designated pertussis toxin. Agglutinogen, hemagglutinin, and heat-labile (at 56 C) and heat-stable (at 100 C) toxins are no doubt interrelated with the immunologic and/or toxic reactions of whooping cough. It appears that the first defense against the disease is the antibody that prevents adhesion of the bacteria to the cilia of the respiratory epithelium and that the second defense is the antitoxin against pertussis toxin (HSF-LPF-IAP).

Agglutinins↗

The healthy communities movement and the coalition for healthier cities and communities.

Part One of this article describes the principles and origins of the Healthy Communities movement. Part Two describes the Coalition for Healthier Cities and Communities, a national network of partnerships and organizations. The authors argue (a) that to sustain community initiatives, practitioners must move from projects that address symptoms of social problems to changing the underlying community cultures, incentives, and settings that give rise to these symptoms, and (b) that the Coalition's continued relevance depends on its ability to help leaders make that transition.

Community Health Planning↗

The concept of pertussis as a toxin-mediated disease.

Pertussis (whooping cough), a two-stage process of disease (respiratory colonization and toxin-mediated disease) is caused by B. pertussis. The bacterium is unique. It is a pathogenic parasite with habitat only in human beings. Growth in the pathogenic form, both in in vitro and in vivo, requires conditions that permit the expression of pertussis toxin (PT) (also known as histamine-sensitizing factor, lymphocyte-leukocyte-promoting factor, islet-activating factor and pertussigen). The expression of growth and PT appear to be genetically interrelated. For multiplication in vitro the medium must be free of substances, such as fatty acids, that inhibit the enzymatic action required for elaboration of PT. In vivo the bacteria are uniquely localized to the cilia of the respiratory epithelium where they multiply. In situ the bacteria inhibit natural defenses of the respiratory tract (cilial, phagocytic and other activities); they tend not to spread and do not invade the underlying tissue. The extent of the areas of colonization, directly related to the number of bacteria in the infecting inoculum, influences the amount of toxin elaborated and consequently the intensity of the clinical symptoms. Other factors that influence the clinical disease are the inordinate susceptibility of the infant and genetically controlled susceptibility. A specific role for PT in the initial establishment of the infection is not clear, but it seems definite that PT-specific immunity influences the clearance of colonization in about 4 to 5 weeks. The clinical symptoms become manifest when the bacteria are waning. This clearance is influenced by the synthesis of IgA antibodies and pertussis toxin antibodies that may act by inhibiting the "enzyme" required for growth or by another mechanism. The pathology of the disease is the result of altered cellular functions of toxin-sensitized cells, not by histologic damage. PT is composed of two functional components like other exotoxins that cause infectious disease (e.g. diphtheria, cholera). Certain sites on one component enable PT to bind to specific receptors on tissue cells and enter the cell. The toxin ADP ribosylates a regulatory protein of the cytoplasmic membrane and thereby alters the function of the cell. Affected (sensitized) cells are insulin-secretory islets of the pancreas, lymphocytes and leukocytes, heart cells and others that have not been clearly identified, e.g. those that effect paroxysms and neurologic disturbances. The altered function of the cell in vitro is irreversible, and the restoration of the function of a particular tissue in vivo appears to be dependent on the renewal of the cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗