Search PubMed⌕ Search

Biomedical subjects

A M Prince

Publications and source records attributed to A M Prince.

At least 181 records · Page 10Linked to original sources

An open air holding system for chimpanzees in medical experiments.

Chimpanzee models often impose severe mental and physical suffering on these animals. We have developed an alternative system which provides for considerably more three dimensional movement and animal-to-animal interaction. It has been used for a period of 20 months in nonexperimental and 8 months in experimental animals. Presently 24 experimental animals, previously held in isolation cages for up to 4 years, are held on outside pads. Animals were transferred from isolation to large outdoor cages for readjustment prior to being put out on pads. Animals that had acquired behavioral abnormalities during their stay in isolation had a longer period of adjustment but now appear happy and are capable of normal interaction with their companions. Chimpanzees approaching sexual maturity and individuals over 5 years that have undergone hepatitis B and non-A, non-B infections are being transferred to a 6 hectare island situated in a river 10 km from the laboratory. Six animals present on the island since October 1978 are in good physical health and are the beginning of a future semi-free-ranging colony. They are fed daily on the same regimen as the main colony and receive monthly anthelmintic treatment in milk. There are presently no caged animals in the colony.

Animals↗

Detection of virus-associated antigen in serum and liver of patients with non-A non-B hepatitis.

In a search for serological markers of non-A non-B(NANB) hepatitis, sera from repeatedly transfused and convalescent patients were assayed by immunodiffusion against sera from 12 patients with early acute NANB hepatitis. A new antigen/antibody system distinct from HBsAg was demonstrated in 8 cases. To assess the specificity of the test, serial sera from 17 patients with acute hepatitis of known aetiology (10 due to hepatitis-B virus, 4 to hepatitis-A virus, 3 to drugs) were tested twice a month, together with sera from 14 NANB patients obtained during a prospective post-transfusion study. NANB antigen (Ag) was detected in at least one sample from 12 of the 14 NANB patients (86%) but in none of the other groups. NANB Ag appeared after or just before elevation of transaminase levels and was cleared before they fell to normal. 4 of 5 patients who showed seroconversion to NANB antibody (Ab) had transient hepatitis. In contrast, the alanine adminotransferase value returned to normal in only 1 of the 5 with persistent NANB antigenaemia during 6 months' follow-up. NANB Ag was also demonstrated by immunodiffusion in liver extracts from patients with chronic NANB hepatitis with antigenaemia. Fluorescein-isothiocyanate-labelled gammaglobulins with strong NANB Ab activity revealed specific nuclear fluorescence in foci of hepatocytes on cryostat sectons of these livers but in none of 6 control human livers. The results suggest that the antigen and antibody are specifically linked to NANB hepatitis of long incubation period.

Acute Disease↗

Cryptic association of e antigen with different morphologic forms of hepatitis B surface antigen.

When highly purified HBsAg particles, separated by rate zonal centrifugation into populations differing in predominant size, were tested for HBeAg, the e1 specificity was detected preferentially in association with particle fractions containing large filaments and Dane particles. These results were obtained both by agar gel diffusion and by radioimmunoassay for e antigen. The e antigen activity present in these fractions was potentiated by prior treatment of particles with Tween 80, suggesting cryptic localization of e1 specificity within or under the outer membrane. The HBeAg released by detergent treatment from a purified preparation composed predominantly of small-particle forms of HBsAg was separated by electrofocusing into a peak of nonparticulate e antigen in the pH range of 5.7--6.0. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed three major polypeptides in this preparation with approximate molecular weights of 25,000, 55,000, and 70,000. Furthermore, two additional peaks of e antigen activity were detected which migrated in association with HBsAg particles at isoelectric points of 4.4 and 5.5--5.6. The major portion of e antigen remained in association with particles after further purification by rate zonal centrifugation.

Animals↗

Immunopathologic aspects of the HBsAg carrier state in chimpanzees.

The tissue distribution of hepatitis B virus antigens was correlated with the distribution of immunoglobulins and complement and with histopathological changes. Although no circulating antibody was detected, the participation of humoral immune mechanisms in the elimination of HBsAg from the circulation was suggested by presence of HBsAg, immunoglobulins, and C'3 in germinal centers of mesenteric lymph nodes and HBsAg mixed with immunoglobulins in the mesangium of kidney glomeruli. The results support the hypothesis that the immune status of HBV chimpanzee carriers is associated with hyporesponsiveness rather than tolerance.

Animals↗

Large-scale purification of hepatitis B surface antigen using affinity chromatography.

Large-scale purification of hepatitis B surface antigen, applicable to the preparation of potential vaccines for prevention of hepatitis B, is described. The method involves the following steps: precipitation of serum with polyethylene glycol 6000, affinity chromatography on concanavalin A-Sepharose and on omega-aminononyl-Sepharose, and isopycnic centrifugation.

Centrifugation, Isopycnic↗

Antigenic sites related to human serum proteins in HBsAg: isolation from normal human serum of a high-molecular-weight glycoprotein reacting with antialbumin.

A novel minor constituent was isolated from normal human serum by affinity chromatography on columns of insolubilized concanavalin A and antibodies to albumin, followed by rate zonal centrifugation. This component has the following properties: a sedimentation coefficient of approximately 31; a diameter of 14--22 nm, and a buoyant density of 1.302 gm/cu cm. It contains about 1% neutral sugars and is electrophoretically heterogeneous, since two populations of particles with isoelectric points of pH 4.95 and 5.75 were separated by isoelectric focusing. It contains a single major glycopeptide with an apparent molecular weight of 72,000 daltons. Its amino acid composition is distinct from that of albumin. It elicited the formation of antibodies that also reacted with HBsAg.

Antibody Specificity↗

Association of normal serum protein antigens with chimpanzee hepatitis B surface antigen particles.

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.

Aged↗

Hepatitis B immune globulin: final report of a controlled, multicenter trial of efficacy in prevention of dialysis-associated hepatitis.

In a randomized, double-blind multicenter trial, 284 patients and 282 staff members of renal dialysis units who lacked detectable hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) were randomly assigned to receive two 3-ml injections of immune serum globulin with high, intermediate, or low titers of anti-HBs four months apart. The incidence of infection with hepatitis B and of development of HBsAg was significantly lower in both patients and staff who received the high-titer material than in subjects who received the low-titer preparation eight but not 12 months after randomization (P less than 0.01 for patients and P less than 0.04 for staff, low-titer vs. high-titer at eight months). The high-titer hepatitis B immune globulin preparation did not appear to affect the severity of the cases of hepatitis that did occur, the proportion of subjects who developed persistent antigenemia, or the magnitude or timing of primary anti-HBs responses.

Antibodies, Viral↗

Our last vaccine.

Explore the source record for details and available documents.

Jurisprudence↗

Heterogeneity of hepatitis B surface antigen-associated particles isolated from chimpanzee plasma.

Hepatitis B surface antigen (HBsAg) was purified from approximately 8 liters of pooled plasma from a carrier chimpanzee. Precipitation of HBsAg with polyethylene glycol resulted in more than 20-fold purification, with about 80% recovery of antigenic activity. The sample was separated by further purification and fractionation into three populations of HBsAg-associated particles by column chromatography on hydroxylapatite: the first contained short filaments and 22- to 28-nm spheres, the second was composed of larger filaments and variable-sized spheres, and the third contained mostly 16- to 22-nm spherical particles. A large volume of the polyethylene glycol precipitate passed through hydroxyl-apatite twice yielded over 650 mg of partially purified HBsAg. A pooled preparation of purified HBsAg was separated by zone-convection electrofocusing into five peaks of antigenic activity within the pH range of 4.7 to 5.7.

Animals↗

Hepatitis type A and hemodialysis: a seroepidemiologic study in 15 U.S. centers.

Four hundred sixty patients and staff from 15 U.S. dialysis centers were surveyed by the immune adherence hemagglutination technique for antibody to hepatitis A antigen (anti-HA). The age-standardized anti-HA prevalence was 42.9% in patients and 42.1% in staff. These rates are almost identical to those of socioeconomically comparable urban volunteer blood donors never exposed to dialysis settings. There was no correlation between anti-HA prevalences and duration of dialysis treatment or employment. Among 100 patients and staff followed for 1 year 92% to 94% did not change their anti-HA status. The prevalence of anti-HA was identical in subjects with past histories of multiple blood transfusions or accidental inoculations with blood-contaminated instruments and in those without such histories. We conclude that hepatitis A virus rarely if every spreads by parenteral mechanisms, that there is no epidemiologic evidence confirming the existence of chronic hepatitis A viremic carrier states, and that hemodialysis does not play a significant role in the spread of type A hepatitis.

Adolescent↗

Antibody against the hepatitis type B core antigen. A new tool for epidemiologic studies.

Four random samples representing populations at low (volunteer blood donors), intermediate, (VD clinic patients), high (family contacts of chronic antigen carriers) and very high (male homosexuals) risk of exposure to HBV were surveyed. Among HBsAg and anti-HBs negative individuals an average of 3.3% were found to be anti-HBc positive, and among those with anti-HBs, 19.4% were anti-HBc positive. Anti-HBc, with concurrent anti-HBs and without, was detected more frequently in the high risk samples than in the low risk. Individuals was a past history of acute viral hepatitis were more frequently anti-HBc positive than those without such a history, and anti-HBc positivity was frequently accompanied by serum transaminase elevation. Anti-HBc may persist for many years after an episode of acute hepatitis. In households of carriers, the highest frequency of anti-HBc was observed among spouses, which would argue for the possibility of sexual transmission. A significant excess of females with both types of antibody was observed in families of carriers. Anti-HBc determinations in conjunction with other HBV markers, provide a useful new tool for epidemiologic studies.

Adolescent↗

Identification of additional antigenic sites on Dane particles and the tubular forms of hepatitis B surface antigen.

Additional antigenic sites, distinct from those present on spherical 20 nm diam. particles of hepatitis B surface antigen (HBsAg), are exposed on the surface of Dane particles and tubular forms of HBsAg. The immunological relationship of these sites to e-antigen, an antigen detected earlier in HBsAg-positive sera from patients with chronic hepatitis, cirrhosis or acute hepatitis but not in healthy HBsAg-carriers, was established by immune electron microscopy and affinity chromatography. These findings suggest that e-antigen may be potentially useful in active immunization against hepatitis B.

Acute Disease↗

Large-scale purification of hepatitis B surface antigen.

Hepatitis B surface antigen was concentrated and purified from plasma by two simple steps of purification. In the first step the antigen was purified 24-fold by polyethylene glycol precipitation. An additional 10-fold purification was achieved by batchwise adsorption to hydroxylapatite and subsequent elution with 0.02 M sodium phosphate buffer.

Adsorption↗