Outer membrane protein subtypes and biotypes of Haemophilus influenzae type b: relation between strains isolated in 1934-1954 and 1977-1980.
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Biomedical subjects
Publications and source records attributed to M Pittman.
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Previous determinations of normal valve orifice areas have been mainly from postmortem studies. In this study mitral and aortic valve orifice area were determined from two dimensional echocardiograms in 20 normal subjects and 20 patients with congestive cardiomyopathy. Mitral valve orifice area was larger than quoted in standard textbooks. Both mitral and aortic valve orifice area were reduced in patients with cardiomyopathy. Valve opening was assessed relative to left ventricular and aortic root size. The ratio of mitral valve orifice area to left ventricular cross-sectional area was markedly reduced in patients with cardiomyopathy compared with normal subjects. The ratio of aortic valve orifice area to aortic root size also was reduced in patients with cardiomyopathy. Anterior mitral leaflet E point-septal separation was similar to that in previous reports contrasting normal subjects with patients with myopathy. Among patients with cardiomyopathy, mitral E point-septal separation was primarily a function of left ventricular size and was not significantly correlated with fractional shortening or ejection fraction within this group having uniformly poor systolic function.
The influence of living Bordetella pertussis on the induction and duration of pathophysiological reactions in mice infected intranasally with graded doses of culture was studied. Lethally infected mice showed loss of body weight, spleen atrophy, pronounced hypothermia and hypoglycemia, and highly elevated levels of leukocytes and serum immunoreactive insulin. Sublethally infected mice showed normal weight gain, practically normal temperature, spleen enlargement, lesser pronounced hypoglycemia, lower but significantly elevated levels of leukocytes and serum immunoreactive insulin, and histamine sensitization. Intensity of each reaction was related to the degree of lung infectivity. Hypothermia and leukocytosis were highly correlated. Concentration of serum immunoreactive insulin was closely related to the level of leukocytosis but not to the level of glucose. The strain and age of mice significantly affected the degree and duration of the reactions. The results suggest that the intranasally infected mouse may provide a useful model for investigations on whooping cough.
Mice from 14 suppliers (breeders) responded significantly different in the mouse-weight-gain test for toxicity of pertussis vaccine. Seven-day weight gain varied by 2.4 fold (2.5 to 6.1 g) and did not correlate with normal gain. Weight gain expressed as percentage-weight gain of the control varied by two-fold (52 to 104%). The percentage-weight gain requirement of greater than 60% (The Netherlands) was more discriminatory between mouse breeds than was the requirement of greate than or equal to 3.0 g gain (U.S.A.). Percentage-weight gains greater than 60%, however, showed significant distinctions. Specifications for the mice for this test are needed. Suggestions for the selection of the mouse are given.
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Mice injected intranasally (it.n.) and intraperitoneally (i.p.) with a nonlethal dose (2.5 x 10(5) colony-forming units) of live Bordetella pertussis were examined for 50 days for infection, respiratory tract immunoglobulins (Ig), changes in serum Ig, and histamine sensitivity. With mice infected it.n., respiratory infection markedly declined between day 20 and day 30. Ig classes (A, G(1), G(2a), G(2b), but no M), which had specificity for B. pertussis, were present in tracheobronchial wash (TBW) by day 15; by day 50, TBW immunodiffusion and immunoelectrophoretic precipitin bands were more intense. A sharp rise in serum IgA after day 30 was the only significant change relative to controls among the five serum Ig examined. A high degree of histamine sensitivity developed by day 15 to 20 and persisted for the 50 days. With mice inoculated i.p., no bacteria were recovered, no Ig or only traces were found in TBW and IgA only was specific, and no significant changes in the serum Ig relative to controls occurred. Histamine sensitivity developed somewhat more slowly and to a lesser degree than in it.n.-injected mice but persisted for the 50 days. A similar small number of killed bacteria (pertussis vaccine) injected it.n. or i.p. likewise induced slowly developing histamine sensitivity in contrast to published reports of 4 to 5 day peak sensitivity and decline following i.p. injection of 10(9) or more killed bacteria.
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The assayed potency of an adsorbed tetanus toxoid C(2), relative to the international standard for tetanus toxoid (adsorbed), varied significantly with the use of different strains of mice. The unitage was highest with NIH mice, and it was not significantly different from that with CFW mice. With CDF(1) and BALB/c mice, however, the assayed potency was significantly lower than with NIH mice. C3H mice failed to respond to the dose range of the toxoids employed with the other four strains. The significance of the influence of the mouse strain on the designation of a prescribed unit requirement for tetanus toxoid, adsorbed, relative to human efficacy is discussed.
A diphtheria toxin shown to have high toxicity and avidity and to combine with antitoxin in multiple proportions was selected for the U.S. standard diphtheria toxin for the Schick test and freeze-dried. Assayed values per vial were 1.09 L(f), 1.09 L(r), 1,090 Schick test doses (STD), 33 LD(80), 38 LD(50), and 43,000 minimum skin reactive doses. One STD (L(r)/1000) is slightly more toxic than one unit of the international standard (L(f)/1,000). Experiments showed that the potency assay of Schick test toxin by guinea pig erythema toxicity, determined relative to the toxicity of the standard, was highly reproducible and significantly more reproducible than the lethal (minimum lethal dose) test and that the STD, defined as one L(r)/1000, was equivalent to approximately 1/50 minimum lethal dose. The erythema potency assay was prescribed in the U.S. standards for Schick test toxin effective in 1969.
Because of wide variations in the methods used to assay the potency of pertussis vaccine, the effect of the type of challenge used in the mouse-protection test was studied. Eight laboratories took part in a collaborative investigation and the potencies of 4 pairs of vaccines were estimated. Two methods were used, a "local method" using local strains and procedures for challenge, and a "study method" using a distributed strain and a specified procedure. For both methods the challenge level (mouse LD(50)) and the number of colony-forming units per challenge dose varied greatly between laboratories.The results of the collaborative assay show that the use of a common challenge, Bordetella pertussis strain 18-323, and a uniform method for preparing the challenge did not reduce the heterogeneity of the results. Other factors influencing the results of potency assays, such as the use of different strains of mice and the effect of levels of challenge, have still to be investigated.
THIS PAPER DESCRIBES: (1) a continuation of the study reported in 1965 of tetanus antitoxin titres among women after primary immunization with plain, AlPO(4)-adsorbed or oil adjuvant toxoids; (2) the effect of age and of abscess formation due to oil adjuvants on antitoxin response; and (3) a comparative study of titres in some women of the study groups who received either a plain or an AlPO(4) toxoid booster injection in pregnancy.The results support our previous recommendation to use aluminium adjuvant toxoid in the prevention of neonatal tetanus. Mean maternal protective antitoxin levels were maintained for 40 months but not for 54 months after 2 primary injections and booster response was higher in those immunized with this toxoid than in those immunized with plain toxoid. Also, the use of AlPO(4) toxoid as booster stimulated a higher antitoxin response than did the use of plain toxoid. Mean protective levels induced by oil adjuvant toxoids (1 injection) persisted for the same time as for the adsorbed toxoid (2 injections). Age did not significantly affect the level of antitoxin response, whereas abscess formation was associated with a higher level.Pregnancy appeared to favour the incidence of antitoxin responders to adsorbed toxoids. Failure to respond to primary immunization with 2 injections of adsorbed toxoid occurred in 7% of women while 100% responded to the oil adjuvant toxoids. Induction of abscess formation precludes use of the latter toxoids, however. Additional studies are needed on the influence of larger antigen doses on the primary response in different ethnic and ecological situations and on the influence of smaller antigen doses on the booster response where repeated booster injections are indicated.