Search PubMed⌕ Search

Biomedical subjects

A M Prince

Publications and source records attributed to A M Prince.

At least 109 records · Page 6Linked to original sources

Avidin-biotin enhanced reverse passive hemagglutination method for detection of HIV antigens.

A new assay for HIV antigens, the avidin-biotin enhanced reverse passive hemagglutination (AB RPHA) test is described which is suitable for detection of infection in cell culture experiments. This assay is simple to perform and economical, and has sensitivity equal to or greater than that of commercial ELISA assays. The coated red cells used for this assay may be stored in the frozen or lyophilized state.

Avidin↗

Antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected and passively immunized chimpanzees.

Based on recent reports of antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected humans, sera from HIV-1 antibody-positive chimpanzees (Pan troglodytes) was evaluated for enhancing activity in an in vitro infection assay that uses MT-2 cells (a human lymphoblastoid cell line). Although fresh chimpanzee serum was found to have pronounced infection-enhancing properties in the absence of antibody to HIV-1, this effect was abolished by heat inactivation (57 degrees C, 1 hr) or treatment with cobra venom anticomplementary protein. Heat-inactivated, HIV-1 antibody-positive chimpanzee serum could enhance HIV-1 infection of MT-2 cells in vitro when combined with fresh, normal human serum. By serial serum samples from three HIV-1-infected chimpanzees, HIV-1 antibody-positive chimpanzees are shown to develop enhancing antibodies early in infection (2 mo postchallenge), whereas neutralizing antibodies develop later. Over the course of HIV-1 infection, this enhancing activity decreases while neutralizing activity increases, suggesting a possible role for enhancing and neutralizing activities in HIV-1 pathogenesis. The enhancing activity of an IgG fraction used to passively immunize chimpanzees against HIV-1 infection is shown to be present at dilutions as high as 1:65,000, offering an interesting possible reason for the failure of passive immunization to protect chimpanzees from HIV infection. These results suggest that serum from HIV-1-immunized chimpanzees might be tested to determine whether current HIV-1 candidate vaccines induce production of antibodies that mediate antibody-dependent enhancement of HIV-1 infection in this in vitro assay.

Acquired Immunodeficiency Syndrome↗

Appropriate conditions for maintenance of chimpanzees in studies with blood-borne viruses: an epidemiologic and psychosocial perspective.

Based on the know epidemiology of the viruses that account for the bulk of the need for chimpanzees in biomedical research--hepatitis B virus (HBV), non-A, non-B (NANB) hepatitis virus, and human immunodeficiency virus (HIV)--as well as the psychosocial needs of this species, requirements for appropriate isolation conditions for these animals have been reviewed. We believe that animals should generally be housed in groups of at least two in the same cage, and that cages encased in solid-walled isolator boxes for housing of single chimpanzees are unnecessary for virologically adequate isolation for studies of HBV, NANB and HIV, and cause sensory and psychosocial deprivation, which contravenes their psychological well-being.

Acquired Immunodeficiency Syndrome↗

Chimpanzees and AIDS research.

Pressure is mounting to relax the regulations on importation of chimpanzees for research. Such a policy is unnecessary and would deepen the plight of an already endangered species.

Acquired Immunodeficiency Syndrome↗

Spumaviruses isolated from sources containing agents of non-A, non-B (NANB) hepatitis do not cause NANB hepatitis.

Serum and liver tissue containing infective non-A, non-B hepatitis virus were shown to contain a retrovirus-like agent that replicated when inoculated into chimpanzee liver cell cultures in vitro. The virus appeared to assemble its core particles in association with tubular structures reminiscent of those characteristically seen in non-A, non-B hepatitis virus-infected chimpanzee liver in vivo, and produced syncytial cytopathic effects in a number of continuous and a primary mammalian liver cells. The agents were neutralized by acute and convalescent sera from human and chimpanzee cases of non-A, non-B hepatitis, as well as by antisera against simian spumavirus type 7, but not type 6. Aluminum chloride failed to abolish viral infectivity. There was no evidence of virus replication or hepatitis in chimpanzees inoculated with a seventh passage of one of the isolates. Thus the data suggest that the isolates are not causally related to non-A, non-B hepatitis, as was previously postulated.

Aluminum↗

Inactivation of the Hutchinson strain of hepatitis non-A, non-B virus in intravenous immunoglobulin by beta-propiolactone.

beta-propiolactone (beta-PL) treatment has been evaluated for its ability to inactivate 10(3.5) chimpanzee infectious doses (CID50) of the Hutchinson strain of hepatitis non-A, non-B virus (HNANBV). Two chimpanzees were inoculated with a beta-PL-treated immunoglobulin solution to which this dose of the titrated virus had been added prior to beta-PL treatment. beta-PL treatment was performed in accordance with the production procedure used for a licensed intravenous immunoglobulin preparation. Neither animal developed hepatitis. When subsequently challenged with the same spiked immunoglobulin solution that had not been beta-PL treated, both animals developed clear-cut hepatitis non-A, non-B. The results of this experiment demonstrate that beta-PL treatment is effective for the inactivation of hepatitis non-A, non-B virus in intravenous immunoglobulin.

Animals↗

Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.

To assess the possible efficacy of passive immunization against human immunodeficiency virus (HIV) an immune globulin was prepared from plasma of HIV-seropositive donors selected to be among those having the top 12.5% of virus-neutralizing antibody titers. The immune globulin was treated with pepsin to render it intravenously tolerable. The preparation, which we termed HIVIG, neutralized 100 tissue culture 50% infective doses (TCID50) of HIV at an average dilution of 1:1000 in neutralization tests in vitro. During preparation HIVIG was subjected to virus inactivation and removal procedures that in theory resulted in a reduction in HIV infectivity by a factor of 10(25). At a dose of 9-10 ml/kg of body weight both the virus-inactivated source plasma and the final immunoglobulin preparation were noninfective and without adverse effect in two chimpanzees. Two chimpanzees inoculated intravenously with HIVIG at 1 ml/kg and two inoculated with 10 ml/kg were challenged intravenously 1 day later with 400 TCID50 of the same strain of HIV (HTLV-IIIb) used in neutralization assays in vitro. All animals became infected. Incubation periods to virus isolation (by cocultivation with human mononuclear cells) in HIVIG recipients did not differ significantly from the incubation period seen in a control animal that received a normal anti-HIV-free immunoglobulin. These findings may have implications for understanding the failure of experimental vaccines to protect against HIV challenge in chimpanzee experiments.

Acquired Immunodeficiency Syndrome↗

Inactivation of lipid-enveloped viruses in labile blood derivatives by unsaturated fatty acids.

Virus sterilization of blood plasma derivatives by addition of several naturally occurring fatty acids was evaluated using vesicular stomatitis virus and Sindbis virus as markers for lipid-enveloped virus inactivation and human immunodeficiency virus (HIV). Inactivation of greater than or equal to 10(4) tissue culture infectious doses (TCID50) of marker viruses added to antihemophilic factor (AHF) concentrates, with 60-100% retention of AHF activity, was achieved with oleic, 11-eicosenoic, linoleic, linolenic, palmitoleic and arachidonic acids. Elaidic, gamma-linolenic, palmitic, and arachidic acids and another fat-soluble compound previously reported to inactivate virus, butylated hydroxytoluene, were less effective. A long chain mono- but not a di- or triglyceride also displayed virucidal properties. Evaluation of the inactivation of HIV added to an immune globulin solution on exposure to 0.033% sodium oleate for 20 min indicated inactivation of greater than or equal to 10(3.4) TCID50. The degree of virus inactivation depended on the sample composition. A favorable balance was achieved between degree of virus inactivation and retention of protein function for AHF concentrate, prothrombin complex concentrate, antithrombin III concentrate, and immune globulin solution on incubation with 0.033% (w/v) sodium oleate at 24 degrees C for 4-6 h. Virus inactivation in whole plasma and plasma cryoprecipitate was not complete despite use of higher concentrations of sodium oleate and/or incubation at 37 degrees C. Reduced virus kill in these less purified derivatives probably is a consequence of their endogenous lipid and/or albumin.

Antiviral Agents↗

Gamma-glutamyltransferase as a potential surrogate marker for detection of the non-A, non-B carrier state.

Alanine aminotransferase (ALT) is currently widely used as a surrogate marker for detection of blood having a higher risk of transmission of non-A, non-B hepatitis (NANBH). Studies in the chimpanzee model, in which the NANBH carrier state is well defined, have revealed gamma-glutamyltransferase to be considerably more sensitive for the detection of NANBH carrier blood. Further study is required to determine whether this marker is also more sensitive for detection of the chronic NANBH carrier state in man.

Alanine Transaminase↗

Preclinical diagnosis of pseudoexfoliation syndrome.

Although the diagnosis of pseudoexfoliation syndrome (PXS) is made by observation of pseudoexfoliation material (PXM) deposited on the anterior lens capsule, there are several additional signs related to pigment dispersion that are often present both in eyes with PXS and fellow eyes in unilateral cases. On the basis of the presence of these signs, we have categorized a group of patients as "pseudoexfoliation suspects" who demonstrated no evidence of PXM on the lens capsule in either eye. As PXM has previously been identified in the conjunctiva of affected eyes as well as fellow eyes in unilateral cases, we hypothesized that it could also be present in PXS suspect eyes. Inferior bulbar conjunctival biopsies were performed on four eyes with PXS, five fellow eyes, and 23 PXS suspect eyes, and specimens were examined by transmission electron microscopy. In eight PXS suspect eyes biopsy specimens demonstrated PXM, suggesting that PXS is more prevalent and possibly responsible for a greater proportion of glaucoma than previously suspected.

Aged↗

Inactivation of 10(15) chimpanzee-infectious doses of hepatitis B virus during preparation of a heat-inactivated hepatitis B vaccine.

The safety of a plasma-derived hepatitis-B vaccine inactivated by two heating steps (90 sec at 103 degrees C followed by 10 hr pasteurization at 65 degrees C) was validated in chimpanzees; 10(3) chimpanzee-infectious doses (CID50) of hepatitis-B virus (HBV), subjected to the purification steps during production of the vaccine, were noninfectious in two chimpanzees. Furthermore, 10(6) CID50 of HBV heated at 103 degrees C for 90 sec and another 10(6) CID50 of HBV heated at 65 degrees C for 10 hr, were also not infectious in two other chimpanzees. All animals developed hepatitis-B infection after subsequent challenge with the untreated starting material, before the respective purification and inactivation procedures. Thus, the total reduction of infectivity of HBV during production of this vaccine was established to be at least 10(15) CID50.

Animals↗

The development of virus-free labile blood derivatives--a review.

Human blood plasma derived coagulation factor concentrates carry a substantial risk of virus transmission as traditionally prepared. Intensive investigations during the past 5 years have led to the development of several virus sterilization procedures which can be applied to these concentrates as well as to other labile protein derivatives. This review summarizes detailed information which is now available establishing the virucidal potency of these procedures, particularly with regard to the contaminating viruses of most concern: hepatitis B, non-A, non-B hepatitis and the AIDS virus. Currently utilized virus sterilization procedures have greatly reduced or eliminated the transmission of AIDS virus, HIV. The transmission of non-A, non-B hepatitis virus (NANBHV) has also been greatly reduced by some but not all of these procedures. Additional virus safety data in man will be required to establish whether any of the procedures gives products which are totally safe from NANBHV transmission and to assess their impact on other blood-borne viruses.

Animals↗

Inactivation of HIV in plasma derivatives by beta-propiolactone and UV irradiation.

The inactivation of HIV in human plasma and plasma derivatives by combined treatment with beta-propiolactone and UV-irradiation was investigated. beta-propiolactone inactivated greater than or equal to 3.5 log10 and UV greater than or equal to 2.8 log10 HIV in plasma and beta-propiolactone greater than or equal to 3.5 log10 in cryoprecipitate and UV irradiation greater than or equal to 4.5 log10 in factor VIII concentrate.

Drug Contamination↗

Safety and immunogenicity of a new heat-inactivated hepatitis B virus vaccine in adult recipients.

A new heat inactivated HBV vaccine has been evaluated for safety and immunogenicity in 203 adult recipients. The vaccine was found to be safe and highly immunogenic. Three doses of 3 micrograms given at 0, 1 and 6 months, resulted in 96% seroconversion. Three doses of 3 micrograms given at 0, 1 and 2 months produced, more rapidly, seroconversion in 92% of those immunized. Antibody to a pre-S determinant developed in four of six subjects tested.

Adult↗

Pseudoexfoliative fibrillopathy in the conjunctiva. A relation to elastic fibers and elastosis.

Pseudoexfoliative (PSX) material in the conjunctiva was found to have a close association with elements of the elastic system in 13 eyes of patients with PSX disease studied ultrastructurally. Pseudoexfoliation aggregates were rare within vascular walls but frequent in proximity to the plasmalemma of stromal fibroblasts. No amyloid was found. A striking feature was the association of PSX fibers with the elastosis seen in many of the specimens. Typical PSX fibers were present in clumps of oxytalan and around small elastic fibers. In five cases with more advanced elastosis, the aggregates of PSX fibers were larger and their usual loose fibrogranular matrix was extensively replaced by a dense elastotic one. Morphology of PSX here varied from typical to thicker, fragmented, and sometimes nondiagnostic fibers. This intermingling of PSX and elastotic materials suggested that PSX fibrillopathy is itself a type of elastosis, possibly resulting from abnormal aggregation of components related to elastic microfibrils.

Actin Cytoskeleton↗