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Biomedical subjects

A M Prince

Publications and source records attributed to A M Prince.

At least 145 records · Page 8Linked to original sources
PubMed1985

Quantitative assays for evaluation of HTLV-III inactivation procedures: tri(N-butyl)phosphate:sodium cholate and beta-propiolactone.

Human T-lymphotropic retrovirus type III (HTLV-III) can be quantitatively assayed for infectivity by inoculation of serial dilutions into cultures of the H-9 cell line and testing for reverse transcriptase in the culture supernatants. Sequential harvests revealed that 14 days of incubation of cultures fed twice weekly was sufficient to reveal maximal titers. Stocks prepared from unconcentrated H9:HTLV-IIIb supernatants have contained from 10(4.5) to 10(6.0) (TCID50)/ml. Stocks prepared by 100-fold concentration of such fluids by pelleting or by polyethylene glycol precipitation followed by pelleting onto sucrose cushions contained 10(6.0)-10(6.5) TCID50/ml. Preliminary studies are under way to utilize this system for evaluation of sterilization processes which can be applied to blood derivatives. Exposure of HTLV-III suspended in Factor VIII preparations to 0.3% tri(n-butyl)phosphate-0.2% sodium cholate resulted in inactivation of greater than or equal to 10(4.5) TCID50 in 2.5 h at 27 degrees C. Exposure of HTLV-III suspended in 4 g of gamma-globulin per 100 ml to 0.14% beta-propiolactone for 4 h at room temperature at pH 8.0 inactivated greater than or equal to 10(4.5) TCID50. However, exposure to gamma-globulin alone inactivated about 99% of HTLV-III infectivity.

Cell Line↗
PubMed1985

Onchocerca volvulus: transplantation of adult worms into chimpanzees.

Adult Onchocerca volvulus were transplanted into chimpanzees with or without complete or partial digestion of associated nodule tissue. Survival of adults worms was limited, but low level microfilarial densities remained detectable in skin over partially digested nodule transplants for 12 months. Human nodule tissue transplanted with adult worms showed enhanced survival as compared to subcutaneous tissue transplanted without worms. It is postulated that this reflects the action of an immunosuppressive factor utilized by the parasite to permit its own survival.

Animals↗
PubMed1984

Isolation of a virus from chimpanzee liver cell cultures inoculated with sera containing the agent of non-A, non-B hepatitis.

A membrane-coated virus having a diameter of 85-90 nm and containing a 40-45 nm core was found to replicate in cell cultures derived from chimpanzee liver after inoculation of serum containing infective non-A, non-B (NANB) hepatitis viruses from two independent sources. Replication of this agent was not observed when the same cells were inoculated with a chloroform-extracted inoculum or were left uninoculated. Replication involves assembly of virus cores on tubular structures similar to those seen in liver cells of chimpanzees infected with most isolates of NANB virus.

Animals↗
PubMed1984

Occurrence of AUSAB test positivity unrelated to prior exposure to hepatitis B virus.

Positive AUSAB test results in the absence of all other serological markers for hepatitis B have been seen frequently in serial serum specimens from quarantined chimpanzees. In this study the responsible reactant was found to be similar to IgM in terms of both size and charge. After the inoculation of hepatitis B virus, AUSAB-positive and AUSAB-negative chimpanzees were found to be equally susceptible to hepatitis B infection. Thus, the presence of this reactant did not confer immunity to hepatitis B or modulate the course of the disease. At present, hepatitis B virus-seronegative chimpanzees are excluded from use in research on hepatitis B because of the occurrence of this "false-positive" AUSAB test result. It is likely that humans may be denied active or passive immunization for similar reasons.

Animals↗
PubMed1984

Inactivation of hepatitis B and Hutchinson strain non-A, non-B hepatitis viruses by exposure to Tween 80 and ether.

Titrated stocks of hepatitis B virus and Hutchinson strain non-A, non-B hepatitis virus were diluted in normal serum to contain, respectively, greater than or equal to 10(6) and greater than or equal to 10(4) chimpanzee infectious doses (CID50) per milliliter and exposed to 1% Tween 80 and 20% ether at 4 degrees C for 18 h. After evaporation of the ether, the treated sera were each inoculated into two chimpanzees. The animals remained free of serologic and biochemical evidence of hepatitis during a 6-month follow-up period, and were then shown to be susceptible to infection by challenge with the original untreated inocula. To assess the effect of exposure to Tween 80/ether on coagulation factors, four lots of antihemophilic factor (AHF) concentrate and 2 lots of commercial factor IX concentrate were treated as above. For the AHF concentrate there was an average of 70% recovery of factor VIII procoagulant activity, 93% recovery of factor VIII-related antigen, and 73% recovery of fibronectin opsonin activity and no detectable change in ristocetin cofactor activity or in fibronectin antigen. Crossed immunoelectrophoresis revealed no change in migration rate of fibrinogen, fibronectin, and von Willebrand factor (vWF), although the quantity of fibrinogen was reduced. Factor VIII procoagulant activity and vWF activity remained associated during chromatography on BioGel A15.

Animals↗
PubMed1984

Inactivation of non-A, non-B virus infectivity by a beta propiolactone/ultraviolet irradiation treatment and Aerosil adsorption procedure used for preparation of a stabilized human serum.

Inoculation of chimpanzees revealed that starting material for the preparation of a pooled stabilized human serum preparation was contaminated with non-A, non-B hepatitis virus(es). This material was subjected to beta-propiolactone/ultraviolet irradiation treatment and adsorption with an insolubilized silicic acid under conditions employed for sterilization of the final product (Biseko, Biotest). The treated material did not transmit hepatitis to 2 inoculated chimpanzees. These animals were subsequently found to be susceptible to non-A, non-B infection by challenge with the untreated material. These findings demonstrate a non-A, non-B type hepatitis virus to be susceptible to inactivation by the methods employed for sterilization of this stabilized human serum preparation.

Adsorption↗
PubMed1984

Modulation of hepatitis B infection by intravenous application of an immunoglobulin preparation that contains antibodies to hepatitis B e and core antigens but not to hepatitis B surface antigen.

Repeated administration of an intravenous immunoglobulin containing antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc) but free of antibody to hepatitis B surface antigen (anti-HBs) before and after the inoculation of 10(4.9) 50% chimpanzee infective doses of hepatitis B virus (HBV) markedly prolonged the incubation period of HBV in experimentally infected chimpanzees. Similar administration of an immunoglobulin preparation containing anti-HBc but free of anti-HBe and anti-HBs or intramuscular administration of a single dose of immunoglobulin containing anti-HBe and anti-HBc 3 days before or after inoculation with HBV did not appear to modulate HBV infection. These observations suggested that anti-HBe, or an unidentified antibody associated with it, may have biological activity in the modulation of HBV replication.

Animals↗
PubMed1984

An affordable multideterminant plasma-derived hepatitis B virus vaccine.

A new vaccine is reported which contains hepatitis B virus (HBV) e antigen (HBeAg) and pre-S determinants, in addition to highly purified HBV surface antigen (HBsAg). The rationale for this approach depends on the following data indicating that anti-HBe and antibody to the core antigen (anti-HBc), and antibody to pre-S determinants may play an active role in preventing HBV infection: (1) active immunization of chimpanzees with HBeAg(s) devoid of detectable HBsAg protected against subsequent challenge with HBV; (2) passive immunization of chimpanzees with an anti-HBe/anti-HBc intravenous immunoglobulin devoid of anti-HBs significantly delayed and appeared to attenuate HBV infection following subsequent challenge with HBV; (3) antibody to pre-S determinants appears to be able to neutralize infective HBV. The purification procedure used for the production of the New York Blood Center vaccine was designed to accomplish a high degree of purification with minimal use of complex equipment. This may facilitate eventual utilization of the vaccine on a mass scale for prevention of the HBV carrier state in high-prevalence regions of the world. The procedure uses polyethylene glycol (PEG) precipitations and hydroxylapatite adsorption steps, followed by only a single isopycnic separation in a zonal rotor, to achieve a vaccine which is substantially free of serum proteins and detectable HBV DNA yet contains HBsAg, HBeAg and pre-S determinants. The original vaccine was inactivated by Tween 80 and formalin. Four lots passed chimpanzee safety tests; two of these have been tested in clinical trials. Recently an improved vaccine has been developed in which two heat inactivation steps are used instead of formalin inactivation. This has resulted in further improvement in yields of antigenicity and immunogenicity, and provides an additional margin of safety.

Animals↗
PubMed1984

Use of hepatitis B virus vaccine in Africa: rationale and practical approaches for effective utilization.

This report considers the following questions: (1) Should hepatitis B virus (HBV) vaccine be used in Africa, if and when adequate supplies become available at an affordable cost? (2) Who should receive the vaccine and when? (3) What type of HBV vaccine should be used? Answers to these questions are suggested based on a review of available knowledge of the epidemiology of HBV infections in Africa, the role of HBV in the etiology of hepatocellular carcinoma and cirrhosis, and the utilization of various currently available and experimental HBV vaccines.

Africa↗
PubMed1983

Inactivation of hepatitis B and non-A, non-B viruses by combined use of Tween 80, beta-propiolactone, and ultraviolet irradiation.

To assess the sterilization efficacy of a combined Tween 80, beta-propiolactone and ultraviolet irradiation procedure applied to a F VIII preparation to which an estimated 10(5.9) chimpanzee infectious doses (CID50) of hepatitis B virus had been added per ml, two chimpanzees were inoculated with 10 ml each of treated and untreated preparations. The untreated preparation, which was obtained from donors with normal alanine aminotransferase (ALT) levels, induced non-A, non-B hepatitis in both recipient animals, and delayed hepatitis B infection in one of these. Neither animal receiving the treated preparation developed either type of hepatitis. When subsequently challenged with the untreated material, both of the latter animals developed non-A, non-B and hepatitis B infection, proving their susceptibility to both types of infection. It was concluded that the combined procedure inactivated an estimated 10(6.9) CID50 of hepatitis B virus and an unknown quantity of a non-A, non-B virus. The finding of non-A, non-B virus infectivity in a pooled F VIII preparation despite careful ALT screening of plasma donors emphasizes the necessity of subjecting such preparations to sterilization procedures.

Animals↗
PubMed1983

Evaluation of thrombogenicity of beta-propiolactone/ultraviolet (beta-PL/UV) treated PPSB in chimpanzees.

The thrombogenicity of beta-PL/UV-treated PPSB (factor IX concentrate) was evaluated in chimpanzees. PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma was injected into chimpanzees at a dose of approximately 100 units/kg body weight. An FDA licensed PPSB preparation served as the negative control, and a preparation containing activated as well as precursor clotting factors served as the positive control. 15 minutes, 1 h, 4 h, and 24 h after the PPSB application the following parameters were determined in the chimpanzee blood: factors II, VII, IX, X, VIII, fibrinogen, AT III, thrombin coagulase, Quick value, APTT and platelet count. Neither the untreated control preparation, nor the PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma, showed signs of thrombogenicity in the chimpanzee model. The positive control indicated that the chimpanzee is a suitable model for the thrombogenicity testing of activated clotting factors.

Animals↗
PubMed1983

Interference between non-A, non-B and hepatitis B virus infection in chimpanzees.

Pre-existing chronic or concurrent acute non-A, non-B (NANB) virus infection has been found to interfere with hepatitis B virus (HBV) replication and to delay and moderate markedly the appearance of disease related to HBV infection in chimpanzees. The mechanism for this phenomenon remains unclear. These findings are of practical significance for vaccine safety testing and evaluation of methods for virus inactivation in chimpanzees. The possible occurrence of dual NANB and HBV infection requires that prolonged follow-up be carried out. Attempts to carry out inactivation studies on materials containing both types of virus may also provide misleading observations.

Alanine Transaminase↗
PubMed1983

A method for coupling cytomegalovirus antigens to aldehyde-fixed erythrocytes for use in passive hemagglutination.

A method for coupling cytomegalovirus (CMV) antigens to aldehyde-fixed erythrocytes for use in a passive hemagglutination assay for antibody to CMV is described. This method uses acid buffer instead of tannic acid for coupling CMV-complement fixation (CF) antigen to the stabilized cells. The coated cells are stable for at least 6 mth at -70 degrees C and for 5 days at 4 degrees C. This provides an inexpensive reagent having a sensitivity for anti-CMV detection which compares favorably with that of the CF test and enzyme immunoassay.

Antibodies, Viral↗
PubMed1983

Blood-borne non-A, non-B hepatitis: lack of infectivity of feces from chimpanzees infected with a strain producing cytoplasmic tubular alterations.

Fecal and serum samples from a chimpanzee with acute-phase, blood-borne non-A, non-B hepatitis were administered to four chimpanzees. Fecal material given either intravenously or orally did not result in abnormal levels of alanine aminotransferase or the occurrence of ultrastructural alterations in hepatocellular cytoplasm characteristic of non-A, non-B hepatitis during a one-year period of follow-up. Definite non-A, non-B hepatitis was later demonstrated in two of these animals four weeks after inoculation of acute-phase serum. Thus, feces do not appear to transmit this human strain of blood-borne non-A, non-B hepatitis.

Animals↗
PubMed1983

Cytomegalovirus (CMV) antibody in male homosexuals: a source for CMV immune globulin.

Male homosexuals have been found to have an extraordinarily high prevalence, and high titers, of antibodies to cytomegalovirus (CMV), as determined by complement-fixation and passive hemagglutination tests. These findings support other data suggesting that CMV may be sexually transmitted. The high titers of CMV antibody found in this population suggest that the homosexual population may be a valuable source of plasma for preparations of CMV immune globulins. CMV immune globulins may be useful in passive immunoprophylaxis or immunotherapy in immunosuppressed patients.

Antibodies, Viral↗