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Biomedical subjects

J N Weber

Publications and source records attributed to J N Weber.

At least 91 records · Page 5Linked to original sources
PubMed1990

HIV and AIDS.

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Acquired Immunodeficiency Syndrome↗
PubMed1989

Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells.

The CD4 antigen has been subverted as a receptor by the human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV). Several groups have reported that recombinant, soluble forms of the CD4 molecule (sCD4) block the infection of T lymphocytes by HIV-1, as CD4 binds the HIV envelope glycoprotein, gp120, with high affinity. We now report that sCD4 blocks diverse strains of HIV-1, HIV-2 and SIV, but is less effective for HIV-2. The blocking effect is apparent even after adsorption of virions to CD4 cells. Soluble CD4 prevents HIV infection of T-lymphocytic and myelomonocytic cell lines, but neither sCD4 nor anti-CD4 antibodies inhibit infection of glioma and rhabdomyosarcoma cell lines.

Antigens, Surface↗
PubMed1989

Parasite infections in AIDS.

'Illnesses no one's got' was the epidemiological clue that led to the identification of AIDS as a new disease in 1981 when a rare infectious organism Pneumocystis carinii was seen in previously healthy homosexuals. Since then a wide range of parasite infections has been recognized in AIDS patients. However, these patients are not susceptible to just any passing parasite. The human immunodeficiency virus (HIV) produces a specific immune defect and only parasites that can exploit that defect will be able to flourish. In this review Diana Lockwood and Jonathan Weber explore the spectrum of parasite diseases recognized in AIDS and also consider those parasites that occur infrequently in AIDS. Analysis of parasitic infections that AIDS patients do not suffer from will yield valuable information about immune recognition and handling of these parasites.

Journal Article↗
PubMed1989

HTLV-1 infection in Papua New Guinea: evidence for serologic false positivity.

Serum samples from 557 individuals participating in studies from four separate lowland and highland populations in Papua New Guinea exhibited consistently false-positive results for human T lymphotropic virus (HTLV) type 1 (10%) and human immunodeficiency virus (HIV) type 1 (5%) antibody in direct antiglobulin and agglutination assays. All serum samples were negative in competitive ELISAs and radioimmunoassays for HTLV-1 and HIV-1; selected samples of reactive sera were negative in an HTLV-2 competitive ELISA. Immunofluorescent antibody tests using HTLV-1 infected cells correlated poorly with ELISA results. None of the sera from Papua New Guinea neutralized vesicular stomatitis virus pseudotypes of HTLV-1. By Western blot analysis, only three serum samples were weakly reactive to HTLV-1 gag proteins. These studies suggest there is as yet no firm evidence of HTLV-1, HTLV-2, or HIV-1 infection in Papua New Guinea, although there may be a low prevalence.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Neutralizing monoclonal antibodies to the AIDS virus.

The production of neutralizing monoclonal antibodies (MAbs) will permit the exact localization of neutralizing epitopes on the AIDS virus, HIV-1. We describe the properties of seven MAbs to the envelope of the LAV-1 isolate. Five MAbs recognise the central portion of gp110, amino acids 279-472, and four of these are capable of high-titre neutralization of HIV-1, by infection inhibition, syncytial inhibition and vesicular stomatitis virus (VSV) pseudotype neutralization. One of the two MAbs to gp41 inhibits syncytium formation. Neutralization, live cell immunofluorescence and immunoprecipitation of gp110 are type-specific and restricted to HIV-1 isolates closely related to LAV-1.

Antibodies, Monoclonal↗
PubMed1988

HIV-2 antisera cross-neutralize HIV-1.

The neutralization properties of three independent HIV-2 isolates were examined in comparison with four diverse HIV-1 strains. Human sera containing antibodies specific to HIV-2 can cross-neutralize HIV-1. By contrast, HIV-1 sera are group-specific and have no neutralizing effect on HIV-2. Therefore, HIV-2 antigens may be important components for the development of broadly cross-protective AIDS vaccines.

Antibodies, Viral↗
PubMed1988

Human immunodeficiency viruses: neutralization and receptors.

The envelope glycoproteins of HIV, gp120 and gp41, contain epitopes recognized by neutralizing antibodies. Studies of human sera from infected individuals indicate that group-specific neutralization antigens common to most isolates of HIV-1 exist, and that some HIV-2 antisera cross-neutralize HIV-1. Neutralization epitopes for HIV-1 have been identified and mapped, including a group-specific antigen on gp41, and a type-specific antigen on gp120. Neutralization "escape" mutants have been selected in vitro with a neutralizing mab to the type-specific antigenic loop. The CD4 antigen binds HIV-1 gp120 with high affinity and acts as the receptor on human and simian T-lymphocytes and monocytes for all strains of HIV-1, HIV-2, and SIV tested. Following binding to the CD4 receptor, HIV becomes internalized by a pH-independent process. The principle binding domain for gp120 is located in the N-terminal V domain of CD4. Anti-idiotypic sera to CD4 mabs recognizing the same site weakly neutralize HIVs of many strains, and soluble, recombinant forms of CD4 strongly neutralize HIV. Neither anti-CD4 mabs nor sCD4 inhibit the low level of plating of HIV observed on tumour cells in culture of glial (brain) and muscle origin, indicating that CD4 is not essential for infection of these cell types.

Animals↗
PubMed1987

Association of different allelic forms of group specific component with susceptibility to and clinical manifestation of human immunodeficiency virus infection.

The distribution of phenotypes of the group specific component (Gc) was examined in 203 homosexuals at risk of infection or infected by the human immunodeficiency virus and compared with that in 50 randomly selected homosexuals and 122 healthy male heterosexual seronegative controls. 30.2% of patients with the acquired immunodeficiency syndrome (AIDS) were homozygous for Gc 1 fast (Gc 1f) compared with 0.8% of controls (p less than 0.0001); patients with other clinical manifestations of HIV infection were also more likely than controls to have Gc 1f. By contrast, seronegative symptomless homosexual contacts of AIDS patients (AH-p) lacked this phenotype but were more likely than controls to be homozygous for Gc 2 (25% vs 9%, p less than 0.05). AIDS patients lacked the homozygous Gc 2 phenotype altogether. A chi 2 trend test showed that progression to AIDS had a strong positive association with the Gc 1f allele (p less than 0.0001) and a negative one with Gc 2 (p less than 0.05). It is proposed that Gc may be involved in viral entry into host cells, the ease of which varies with different allelic forms of Gc, according to their sialic acid content.

AIDS-Related Complex↗
PubMed1987

Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis.

Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV-I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC.

AIDS-Related Complex↗
PubMed1987

Ophthalmic findings in a group of ambulatory patients infected by human immunodeficiency virus (HIV): a prospective study.

Twenty-eight patients with either the acquired immune deficiency syndrome (AIDS) or persistent generalised lymphadenopathy (PGL) were studied prospectively as outpatients for up to one year. Six patients had fundal cotton wool spots at some stage of their follow-up and all six suffered opportunistic infections associated with AIDS. We suggest that ocular abnormalities may be prognostic for opportunistic infection in AIDS and discuss the wide range of ophthalmic complications consequent to HIV infection.

AIDS-Related Complex↗
PubMed1987

Cytomegalovirus colitis and oesophageal ulceration in the context of AIDS: clinical manifestations and preliminary report of treatment with Foscarnet (phosphonoformate).

Three patients with biopsy diagnosed invasive cytomegalovirus infection of the colon have been seen in the context of the acquired immune deficiency syndrome (AIDS). Cytomegalovirus colitis presented with fever, abdominal distention, bloody diarrhoea and weight loss. Plain abdominal radiographs showed generalised large bowel dilatation in one patient. Cytomegalovirus infection was shown histologically, but the virus could not be cultured from the stool; no other gastrointestinal pathogens could be demonstrated. The patients were treated with a 14 day continuous infusion of Foscarnet 0.08 mg/kg/min (phosphonoformate, Astra Pharmaceuticals). One patient showed a partial response to therapy, but the cytomegalovirus colitis relapsed; the second patient had a symptomatic response only and the third patient died of non-cytomegalovirus opportunist infection while on treatment. Two other patients with biopsy proven cytomegalovirus ulceration of the oesophagus were seen, presenting with dysphagia, fever and weight loss. Invasive infection of the gastrointestinal tract with cytomegalovirus is now a major clinical problem in AIDS. Treatment with Foscarnet may be initially effective, but does not eliminate cytomegalovirus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Decline of anti-p24 antibody precedes antigenaemia as correlate of prognosis in HIV-1 infection.

A cohort of 84 homosexual men presenting with persistent generalized lymphadenopathy (PGL) was studied between March 1982 and March 1987. A progression rate to AIDS of 5% per year was seen in those who were infected with HIV. Certain clinical features and routine laboratory investigations were significantly associated with an increased risk of disease progression, but had only limited predictive value. Two hundred and fifty-two serial sera from 57 patients were analysed for the p24 antigen (Abbott), the principal core protein of HIV and antibody against p24 by direct enzyme-linked immunosorbent assay (ELISA). Patients who remained well retained a high titre of anti-p24 antibody compared with those who progressed to AIDS-related complex (ARC) or AIDS. HIV antigen was detectable in 40% of AIDS patients 2 years before diagnosis, but antigenaemia was preceded by loss of anti-p24 antibody by up to 18 months and preceded AIDS by up to 40 months. ARC patients tended to be negative when tested for both alpha-p24 antibody and antigen, suggesting a transitional state. Analysis of the humoral response against gag proteins appears to correlate closely with clinical status and may be an earlier and more consistent way of predicting disease progression than p24 antigenaemia, or clinical and routine laboratory investigations.

AIDS-Related Complex↗