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Biomedical subjects

A M Prince

Publications and source records attributed to A M Prince.

At least 127 records · Page 7Linked to original sources
PubMed1987

Prevalence, clinical significance, and strain specificity of neutralizing antibody to the human immunodeficiency virus.

A semiautomated microtiter assay has been developed to quantitate neutralizing antibody to the human immunodeficiency virus. This assay has been found to be highly specific. Forty-four sera that were negative by enzyme-linked immunosorbent assay (ELISA) were tested under code: 42 were negative (less than 1:2), and 2 had titers of 1:2. By contrast, of 178 sera positive by western blot, 92.7% had detectable neutralizing antibody, and 12.5% had titers greater than or equal to 1:128. Neutralizing antibody titers correlated poorly with clinical diagnosis and T4/T8 ratios. Different isolates differed quantitatively in their sensitivity to neutralization by antibodies obtained from different patients; however, all strains tested so far have been neutralizable by all the sera tested. Neutralizing antibody titers correlated weakly, if at all, with direct or competition ELISA titers.

Antibodies, Viral↗
PubMed1987

Laboratory and preclinical evaluation of the virus safety of coagulation factor concentrates.

Studies of virus sterilization of coagulation factor concentrates using marker viruses, AIDS, hepatitis B (HBV) and non-A, non-B hepatitis (NANBHV) viruses indicate the following: Strategies adopted to stabilize coagulation factors to heat denaturation, including addition of high concentrations of solutes or lyophilization, stabilize virus. At 60 degrees C, heating in the liquid state provides more rapid virus kill than heating in the lyophilized state with 2% residual moisture. To achieve the same virucidal potency as achieved on heating albumin at 60 degrees C for 10 hours, stabilized coagulation factor concentrates would require a substantial increase in the dose of heat. The rate of inactivation by either thermal or solvent/detergent methods slows with time. Improved virus kill is attained more easily by increasing the temperature than by extending the duration of exposure. Viruses vary widely in their sensitivity to thermal denaturation or solvent/detergent action. Because studies on the rate of inactivation of HBV and NANBHV are not feasible, assessment of their sensitivity is at best approximate. Sensitivity to thermal inactivation appears to follow the order HTLV-III greater than VSV, EMC greater than NANBHV?, Sindbis much greater than HBV. Sensitivity to organic solvent/detergent mixtures appears to follow the order HTLV-III greater than Sindbis, Sendai, HBV?, NANBHV? greater than VSV much much greater than EMC. Protein enveloped forms of NANBHV must occur rarely or not at all. Use of marker viruses to compare virucidal potency of methods that inactivate by different mechanisms may lead to erroneous conclusions; however, marker virus data probably provide useful comparisons of related sterilization methods or of a single method applied to different protein mixtures. If virus sterilization processes are to be validated in a manner which enables a meaningful comparison between laboratory and clinical results, higher titers of virus will be required.

Blood Coagulation Factors↗
PubMed1986

Sterilisation of hepatitis and HTLV-III viruses by exposure to tri(n-butyl)phosphate and sodium cholate.

Blood product sterilisation with 0.3% tri(n-butyl)phosphate (TNBP)/0.2% sodium cholate (CA), a combination known to permit high recovery of factor VIII and factor IX, was evaluated for its effect on hepatitis B (HBV), non-A, non-B (NANB), and human T-lymphotropic type III (HTLV-III) viruses. 2 chimpanzees received factor VIII preparations contaminated with 10(4) chimpanzee infectious doses (CID50) of HBV and treated with TNBP/CA; neither had evidence of HBV infection during 9 months follow-up, but hepatitis B surface antigen (HBsAg) developed 5 and 6 weeks, respectively, after challenge with untreated inoculum. 2 chimpanzees were similarly exposed to 10(4) CID50 of Hutchinson NANB inoculum treated with TNBP/CA; neither became infected during 26 weeks of follow-up but both had characteristic NANB-associated ultrastructural changes 3-5 weeks after exposure to untreated inoculum. 2 chimpanzees inoculated with 80 ml of TNBP/CA-treated factor VIII derived from a pool of thirteen lots obtained from five US manufacturers remained free of any evidence of NANB infection during 32 weeks of follow-up. Subsequently, NANB infection developed in both animals 3-4 weeks after exposure to untreated inoculum. Exposure of HTLV-III diluted into a factor VIII preparation to TNBP/CA inactivated greater than or equal to 10(4.2) tissue culture infective doses within 20 min at 24 degrees C.

Animals↗
PubMed1986

Detection of serum antibodies and circulating antigens in a chimpanzee experimentally infected with Onchocerca volvulus.

The course of the humoral immune response was followed in a chimpanzee experimentally infected over 27 weeks with a total of 168 Onchocerca volvulus 3rd-stage larvae obtained from naturally infected wild-caught blackflies. Antibodies against an adult worm extract could be detected by ELISA from week 16 onwards (after the inoculation of 44 larvae). Peak antibody levels were observed between weeks 66 and 74 (about one year after the last larval injection). Thereafter, antibody levels markedly decreased but rose again after week 120. First microfilariae could be detected from week 124 onwards. Microfilarial counts remained low (not more than two microfilariae per skin snip) until the end of the observation period. High levels of IgM antibodies against adult O. volvulus antigens were detectable between weeks 26 and 80 by ELISA. Total IgE levels were found to be only marginally elevated during the course of the infection. Circulating parasite antigens were only detectable for a short time (weeks 34 to 44) of the prepatent period by immuno-radiometric assays (IRMAs) using monoclonal antibodies which were raised against O. gibsoni eggs. Competitive radio-immuno-assays detected host antibodies inhibiting binding of 125I-labelled monoclonal antibodies to parasite antigens from week 28 onwards. Host antibodies clearly interfere later in infection with the detection of circulating antigens.

Animals↗
PubMed1986

Passive hemagglutination for cytomegalovirus antibody: specificity and stability of reagents.

Glutaraldehyde fixed red cells coated with CMV antigen were lyophilized in the presence of stabilizers such as glycerol, lactose, sorbitol and sucrose. These cells maintained their sensitivity for anti-CMV detection for at least 6 mth when held at 4 degrees C. Some rheumatoid factors containing sera react non-specifically with crude CMV antigen coated cells. The agglutinins in these sera could be effectively removed by adsorption with red cells coated with polymerized IgG.

Adsorption↗
PubMed1986

Clinical signs of the pseudoexfoliation syndrome.

Pseudoexfoliation syndrome (PXS) is a common cause of glaucoma throughout the world. It is most commonly diagnosed after the observation of pseudoexfoliation material (PXM) on the anterior lens surface. However, there are numerous clinical signs of PXS that should alert the examiner to search carefully for PXM on the anterior lens surface. These include pupillary ruff defects, iris sphincter transillumination, a characteristic whorl-like pattern of particulate pigment deposition on the iris sphincter, particulate pigment deposition on the peripheral iris and trabecular meshwork, and exfoliation material on the zonules and ciliary body. Accuracy of diagnosis is important for purposes of treatment, prognosis, and basic research in he mechanisms of glaucoma, particularly tissue culture.

Anterior Chamber↗
PubMed1986

Antibodies to a synthetic peptide from the preS 120-145 region of the hepatitis B virus envelope are virus neutralizing.

Studies with synthetic peptides have provided evidence for the presence of preS coded sequences in the envelope (env) proteins of hepatitis B virus (HBV) and indicated that these sequences are involved in the specific attachment of HBV to liver cells. Scanning of the preS sequence for immunodominant continuous epitopes identifies the sequence within residues preS (120-145) as the most immunogenic in eliciting antibodies recognizing HBV and as the most efficiently binding antibodies from sera of rabbits and humans immunized with HBV env proteins. To assess the potential of preS (120-145) as a synthetic vaccine against hepatitis B, in vitro neutralization of the virus by rabbit antiserum to the peptide was assayed in chimpanzees. The animals, subsequently proven to be susceptible to HBV infection, did not develop hepatitis B as judged by negative serological tests for HBV-associated antigens and antibodies and by normal serum alanine aminotransferase levels and normal liver biopsies. These results establish the role of preS domains in the process of virus neutralization and the potential of synthetic preS analogues for hepatitis B vaccination.

Animals↗
PubMed1986

Inactivation of the AIDS-causing retrovirus and other human viruses in antihemophilic plasma protein preparations by pasteurization.

Heat treatment at 60 degrees C for 10 h in solution (pasteurization) was introduced into the manufacturing process of antihemophilic cryoprecipitate (AHC) and factor VIII concentrates (F VIII) to reduce the risk of transmission of hepatitis to hemophiliacs. Since the acquired immunodeficiency syndrome (AIDS) may also be transmitted to hemophiliacs by antihemophilic plasma protein preparations, we have investigated inactivation of the AIDS virus HTLV III by pasteurization in AHC or F VIII and included in this study cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), poliovirus and vaccinia virus. Each of these viruses was efficiently inactivated by pasteurization although considerable differences were observed between the different viruses HTLV III was rapidly inactivated, becoming nondetectable within 30-60 min. Our findings indicate that pasteurized AHC or F VIII should have a high margin of safety regarding the transmission of AIDS or any other infectious disease caused by viruses such as those tested.

Acquired Immunodeficiency Syndrome↗
PubMed1985

A final report on safety and immunogenicity of a bivalent aqueous subunit HBV vaccine.

The bivalent form of an aqueous formalin-inactivated hepatitis B vaccine was evaluated for safety and immunogenicity in chimpanzees. To evaluate safety five animals were inoculated intravenously with vaccine containing 500 micrograms HBsAg and two animals with 50 micrograms. None of these animals developed hepatitis or any serologic marker indicative of the presence of residual live virus in the vaccine. Twenty-four animals were used to evaluate immunogenicity and protective efficacy. Seven of these immunized animals produced weak or no anti-HBs responses. Two doses of 50 micrograms HBsAg given subcutaneously 1 month apart protected each of four animals that were challenged with 10(3.5) CID50 HBV at 6 and 12 months after immunization and protected three of four animals challenged at 24 months against development of hepatitis or HBsAg. Three of 4 animals in each group immunized with two doses of 20, 10, or 5 micrograms HBsAg were similarly protected when challenged 6 months after immunization. Thirteen of 20 immunized animals that did not develop HBsAg after challenge with HBV developed anamnestic anti-HBs or anti-HBc responses between 2 and 18 months after challenge, indicating minimal replication of challenge virus. The time of onset and frequency of occurrence of these delayed responses was related to the titer of anti-HBs at the time of challenge. False positive Ausab test results were observed in quarantined chimpanzees. These were neither preceded by appearance of HBsAg nor accompanied by development of anti-HBc. In most cases these reactions were due to a reactant having a sedimentation coefficient and an electrophoretic mobility resembling that of IgM. This reactant generally did not appear to confer resistance to challenge with HBV. The humoral immune response was characterized as being entirely of the IgM class 2 weeks after immunization and switched entirely into the IgG class by 10-12 weeks after vaccine administration. At the time of challenge all animals with antibody had anti-HBs of subtype a.

Animals↗
PubMed1985

Incidence of hepatitis A virus (HAV) infection in rural Liberia.

To provide background for future hepatitis A vaccine trials, sera were collected from 0- to 4-year-old Liberian infants and their mothers on two occasions an average of 14.75 months apart and tested for antibody to hepatitis A virus (anti-HAV). The prevalence of anti-HAV rose from 2.5% in infants 0-6 months of age to 70% in children 3-4 years of age and did not differ between male and female infants. The annual incidence of new infections was slightly lower in the first year of life (35%) than in the subsequent 3 years, when it averaged 45%. The presence of HBV infection did not affect the incidence of HAV seroconversion. No clinical hepatitis was recognized in the subjects who seroconverted. Dual hepatitis A and B virus infection were observed; these were all clinically inapparent. The extraordinary incidence of HAV infection documented in the present study offers an opportunity for vaccine efficacy trials requiring minimal numbers of subjects.

Adolescent↗
PubMed1985

Inactivation of the Hutchinson strain of non-A, non-B hepatitis virus by combined use of beta-propiolactone and ultraviolet irradiation.

A beta-propiolactone/ultraviolet irradiation procedure (beta PL/UV) has been evaluated for its ability to inactivate 30,000 chimpanzee infectious doses of the Hutchinson strain of non-A, non-B (NANB) virus. The chimpanzees were inoculated with plasma to which this dose of the titrated virus had been added prior to application of the beta PL/UV process in accordance with a procedure used for licensed blood derivatives in Germany. Neither animal developed hepatitis. When subsequently challenged with the same contaminated plasma, which had not been sterilized, both animals promptly developed typical NANB hepatitis. This study extends the high (approximately 10(7)-fold) process efficiency of the beta PL/UV procedure previously reported for hepatitis B virus to a blood-borne NANB virus.

Animals↗
PubMed1985

Prevention of perinatal transmission of hepatitis B virus: a comparison between the efficacy of passive and passive-active immunization in Korea.

In a study to compare the prophylactic efficacy of passive and passive-active immunization against hepatitis B virus (HBV) among newborn infants of HBV carrier mothers positive for hepatitis B e in Korea, both regimens resulted in effective protection against development of hepatitis B surface antigen (HBsAg): 10 of 12 recipients of hepatitis B immune globulin (HBIG) and 25 of 29 recipients of HBIG and vaccine during nine months of follow-up. Among untreated controls in the same population just before the present study, 12 of 16 developed HBsAg within nine months of birth. Seven recipients of HBIG and vaccine and four untreated infants who had HBsAg in their blood at birth were excluded. The declining antibody levels in infants who received only HBIG as compared with the rising antibody levels in infants who received HBIG followed by three doses of HBV vaccine suggest that long-term protection will be seen only in the latter group.

Female↗
PubMed1985

Non-A, non-B hepatitis: is there more than a single blood-borne strain?

Fourteen chimpanzees were challenged with the Hutchinson strain inoculum that has been shown by many workers to produce non-A, non-B (NANB) hepatitis associated with characteristic cytoplasmic ultrastructural changes observable by electron microscopy. Nine of these animals had a history of definite NANB hepatitis induced by seven different human viral isolates; all of these animals resisted rechallenge. The five animals without a history of NANB hepatitis all developed definite histological changes associated with NANB hepatitis after challenge. Homologous rechallenge with a 100-fold higher infectivity titer was carried out in five of the nine chimpanzees. Cytoplasmic ultrastructural changes developed after challenge in two of these animals; the remaining three had evidence of possible mild reinfection on the basis of liver histopathology or mild elevations of transaminase or both. We conclude that most, if not all, blood-borne NANB isolates belong to a single class of agents and that this virus produces immunity to rechallenge, but this immunity may be overwhelmed by high-dose inocula.

Animals↗
PubMed1985

Removal of non-A, non-B hepatitis virus from a concentrate of the coagulation factors II, VII, IX and X by hydrophobic interaction chromatography.

The efficacy of a chromatographic procedure based on hydrophobic interaction chromatography to remove non-A, non-B (NANB) infection from a concentrate of coagulation factors II, VII, IX and X (Preconativ, KabiVitrum AB) was evaluated in chimpanzees. For this purpose, NANB infective human plasma (H-strain) was deliberately added to a solution of Preconativ (45 IU factor IX:C/ml) to reach a titre of NANB virus of greater than or equal to 10(2) chimpanzee infectious doses (CID)/ml. The NANB-contaminated preparation was chromatographed on octanohydrazide-Sepharose 4B at a high salt concentration. Groups of 2 chimpanzees were each inoculated intravenously with 45 IU factor IX:C of Preconative before and after this virus adsorption chromatographic step. The experimental animals remained free of any serological and biochemical evidence of hepatitis during a 12-month follow-up period. One of the two control animals developed clear evidence of NANB hepatitis.

Animals↗