Biomedical subjects
Publications and source records attributed to N Hashimoto.
Carotid angiography was performed in our model rats with cerebral experimental aneurysms. Major vessels at the base of the brain and the cerebral aneurysms were well visualized by a single injection into one carotid artery.
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HBsAg/adw was purified from 2.6 liters of pooled plasma from a single chimpanzee carrier by polyethylene glycol (PEG) precipitation followed by isopycnic and rate zonal centrifugation. The different morphological populatilons of HBsAg separated in the final rate zonal centrifugation step were combined into seven pools: two fractions rich in filaments and Dane particles, two pools composed of filaments and 20--28-nm spheres, and three fractions containing mostly 20--28-nm spheres. The purified preparations of HBsAg analyzed for normal serum protein contaminants revealed albumin and traces of IgG. The same samples analyzed after Tween-80 treatment, revealed enhanced quantitites of the previous two contaminants, and in addition, transferrin, traces of alpha2-macroglobulin, IgM, and complement (C3/C3c). The residual contaminants were mostly removed by further purification and fractionation after detergent treatment using zone convection electrofocusing and rate zonal centrifugation. Our findings indicate that conventional purification techniques will not provide preparations of HBsAg free of traces of serum protein contaminants. Many of these are released only by detergent treatments and subsequent purification. It is not yet clear whether detergents release these contaminants from the interior of the particles or from firm association or incorporation within the membranes.
The absorption of propicillin from the rat stomach and small intestine in situ was examined as a function of recirculating solution pH. The in vitro interphase transport from an aqueous buffer of various pH values to the octanol phase was also studied for several penicillins by the use of a two-phase rolling cell. The rate--pH profiles obtained from both in situ and in vitro experiments deviated significantly from the dissociation curves. The degrees of the shifts were approximately 2 pH units for the in situ intestinal absorption of propicillin and in vitro transport of propicillin and cloxacillin, approximately 1.5 pH units for the in vitro transport of penicillin V, and 0.8 pH unit for the in situ stomach absorption of propicillin. These discrepancies from the classical pH--partition hypothesis can be interpreted by the permeation through the lipoidal barrier of the undissociated species of penicillins transported through the aqueous diffusion layer adjacent to the lipoidal surface. All in situ and in vitro experiments tend to support this theory.
Saccular cerebral aneurysms were successfully induced in rats treated with beta-aminopropionitrile, deoxycorticosterone and salt hypertension and ligation of unilateral common carotid artery. This experiment was performed on the hypothesis that if hemodynamic stresses were increased on the fragile, cerebral arterial wall of beta-aminopropionitrile-fed animals, cerebral aneurysms might be produced. Although the incidence of cerebral aneurysms was low and the contributory mechanisms of these procedures must be more clearly elucidated, the present results show that saccular cerebral aneurysms are really inducible in experimental animals.
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Experimental ileal atresia and stenosis were produced by a localized ligation of the mesenteric vessels in fetuses from 13 pregnant mongrel dogs having gestational ages of 45-55 days. The intestinal infarct in the fetus was characterized by an aseptic coagulation necrosis selectively limited to the mucosa and submucosa, and also by intense hyperemia and minimal cellular reaction in the adjacent tissue. Eleven days after the devascularization, type 2 intestinal atresia, in which there is a long cord between the blunt ends microscopically similar to that seen in humans.
Hepatitis B surface antigen was adsorbed to insolubilized sialic acid-specific haemagglutinin isolated from the haemolymph of Limulus polyphemus. Treatment of the antigen with Vibrio cholerae neuraminidase (EC 3.2.1.18) resulted in the release of sialic acid and in an increase of the isoelectric point from pH 4-35 (for subtype ad) or 4-9 (for subtype ay) to pH 5-45. Treated, but not untreated, antigen incorporated [14-C]-sialic acid when incubated at 37 degrees C with sialyl transferase (EC 2.4.99.1) and cytidine-5'-monophosphate-[14-C]-sialic acid. The major portion of [14-C]-sialic acid was linked to a glycoprotein with an apparent mol. wt. of 26 x 10-a. De-sialylated antigen had a drastically reduced in vivo life span in rabbit plasma and elicited a higher humoral antibody response than intact antigen (subtype ad). Antigen-stimulated proliferation of lymphocytes, measured 3 months after immunization, was observed only with cells from rabbits injected with neuraminidase-treated antigen.
Krugman has demonstrated that injection of heated serum containing HBsAg conferred some protection against subsequent challenge with live hepatitis B virus (HBV). It is likely that improved protection will result from injections for larger quantities of HBsAg. This can be readily done with purified antigen. We have carried out preliminary studies in mice to investigate the inactivation kinetics of HBsAg antigenicity and immunogenicity. Rates of inactivation of the two parameters by heat have been found to be parallel. Chimpanzees will be required to determine adequacy of inactivation procedures, and optimal dose and immunization schedule, prior to the initiation of human trials. The use of newly imported chimpanzees for this purpose may be hazardous. Of 27 chimpanzees recently tested in an exporter's compound in Sierra Leone, ten were found to circulate HBsAg and five additional had detectable anti-HBs, suggesting a high risk of hepatitis B transmission within the compound. Thus newly imported animals may be incubating HB infection, and could give rise to false positive results in inactivation trials, unless quarantined for a four to six month period prior to use. We have therefore established a laboratory for chimpanzee trials in West Africa, and plan to utilize only animals captured by trapping and held in strict isolation from the time of capture. It is unlikely that immunization against HBV will ever provide absolute immunity. Three chimpanzees who received a massive transfusion of infective plasma one year after resisting challenge with aliquots of the same plasma inoculated intraperitoneally, all developed severe hepatitis, accompanied in two cases by HBs antigenemia, despite strong anamnestic anti-HBs responses in all three animals.
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Attempts were made to analyze the specificity of inhibitory activities of normal bovine and equine sera to the Mahoney strain of type 1 poliovirus. A total of five inhibitory factors were postulated to explain the complicated results. Two of the three bovine inhibitors were identical in specificity to certain equine inhibitors despite differences in their mode of virus inactivation and their molecular size. In addition to this, inhibitors that could inactivate certain resistant mutants, but not the parent virus, were newly detected in a number of normal bovine and equine sera. Antigenic variation of the resistant mutants against equine sera containing an inhibitory factor h-11 was determined by means of the kinetic neutralization test by using both anti-Mahoney and anti-M-H11 sera. These results offer evidence that some inhibitors, at least in part, are indistinguishable from specific antibody.
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