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Biomedical subjects

J Goudsmit

Publications and source records attributed to J Goudsmit.

At least 343 records · Page 19Linked to original sources
PubMed1988

Decline of HIV antigen levels in cerebrospinal fluid during treatment with low-dose zidovudine.

Six HIV-antigenaemic patients with AIDS or AIDS-related complex were studied to assess the effect of treatment with low-dose zidovudine (250 mg) in 6-hourly doses on HIV antigen (HIV-Ag) levels in cerebrospinal fluid (CSF). HIV-Ag was detected in CSF of three patients before treatment. These patients became CSF HIV-Ag-negative within 8 weeks of treatment. One initially CSF HIV-Ag-negative patient became strongly CSF HIV-Ag-positive during interruption of zidovudine treatment; CSF HIV-Ag disappeared again after treatment was restarted. None of our patients showed a significant neurological improvement during the study. These results show that low-dose zidovudine can suppress viral expression in CSF. Whether suppression of viral replication can prevent future HIV-related neurological disease remains to be investigated.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Prevalence and risk factors of HIV infections among drug users and drug-using prostitutes in Amsterdam.

In December 1985 we started a study to determine the prevalence and risk factors of HIV infection among drug users and drug-using prostitutes in Amsterdam. Recruitment took place at methadone posts (not drug-free; i.e. a low-threshold programme on which some drug users continue to use hard drugs, but at a lower level) and the weekly evening sexually transmitted diseases (STD) clinic for drug-addicted prostitutes. Three hundred and ten drug users have so far been tested and interviewed. Eighty-one per cent reported intravenous drug use; 83% of the 166 females and 15% of the 144 men reported prostitution. Female prostitutes practised mainly vaginal and orogenital intercourse and reported frequent use of condoms (89% of vaginal and 64% of orogenital contact). Male prostitutes practised mainly orogenital and manual contact. At entry 88 of the 310 (28%) were HIV-antibody-seropositive; 85 of these 88 were intravenous drug users and three were male homosexuals. HIV-antigen was detected in two seropositive and one seronegative intravenous drug-user. Antibodies to HTLV-I were found in four out of 308. Risk factors independently associated with HIV-antibody seropositivity among intravenous drug users were: frequency of borrowing used needle or syringe, date of first intravenous drug use, recent intravenous drug use, time living in Amsterdam and German nationality. Of medical history data, an attack of herpes zoster in the previous 5 years had the greatest value in the prediction of the presence of HIV antibodies (relative risk 20.90; 95% confidence interval 2.41-167.27).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1988

Antibodies to soluble CD4 in HIV-1-infected individuals.

A direct enzyme immunoassay (EIA) using the recombinant soluble form of CD4 (sCD4) produced in rodent cells as antigen was applied to detect antibodies to CD4 in sera from HIV-1- and HIV-2-infected patients. High titers of antibodies to sCD4 were found in sera from 12.6% of the HIV-1-infected persons included in this study, but not in 120 normal human sera. The reactivity of these antibodies with sCD4 was confirmed by a Western blot analysis. A possible anti-idiotypic origin of those antibodies was thought to be unlikely in view of the lack of inhibition of the binding of the biotin-labeled monoclonal antibody (mAb) anti-Leu3a by sCD4 positive sera. Attempts to correlate the evolution of the disease with the presence or absence of antibodies to sCD4 in a panel of well documented HIV-1-seropositive cases did not reveal any clear correlation. Sera from HIV-2-infected people (nine sera analysed), sera from HIV-1-infected chimpanzees (10 sera analysed) and sera from humans immunized with a recombinant vaccinia virus expressing gp160 (10 sera analysed) scored negative for antibodies to sCD4. The possible origin and biological significance of the observed antibodies to sCD4 are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Heat-shock induction of the human immunodeficiency virus long terminal repeat.

Rat cell lines were established in which the bacterial chloramphenicol acetyltransferase (CAT) gene under control of the human immunodeficiency virus (HIV) long terminal repeat (LTR) was stably integrated. The cell lines showed a repressed phenotype for CAT expression, but could be induced for it by inhibition of protein synthesis, as well as by heat-shock and chemical inducers of the cellular stress response, such as sodium arsenite, 8-hydroxyquinoline and the heavy metals cadmium and copper. A decameric sequence present in the NF-kB binding sites in the HIV LTR (GGGACTTTCC) resembles the cellular heat-shock core sequence and may therefore be involved in the heat-shock response.

Animals↗
PubMed1988

Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.

To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Impact of HIV antibody testing on changes in sexual behavior among homosexual men in The Netherlands.

Between October 1984 and May 1986, 746 homosexual men, living in and around Amsterdam, The Netherlands, were surveyed at three consecutive six months periods regarding their sexual behavior. At the start of the study all subjects, of whom 234 (31 per cent) were HIV-Ab seropositive, were informed about their HIV antibody status. Seropositives initially reported more sexual partners than seronegatives; they also showed a greater reduction in the number of sexual partners and the number of partners with whom all forms of sexual practices were performed than did seronegatives. In both groups subjects were more likely to terminate orogenital intercourse than anogenital intercourse and masturbation.

AIDS Serodiagnosis↗
PubMed1988

Persistence of human immunodeficiency virus antigenemia in patients with the acquired immunodeficiency syndrome treated with a reverse transcriptase inhibitor, suramin. Ten-patient case-control study.

Ten homosexual men with the acquired immunodeficiency syndrome were included in a serologic follow-up study (duration, 40 weeks) of human immunodeficiency virus (HIV) antigenemia. Five of these men were treated with the reverse transcriptase inhibitor, suramin, for a period of 19 to 37 weeks. In contrast with reported changes in HIV antigen levels after treatment with zidovudine, HIV antigenemia persisted in the suramin-treated group, as well as in the untreated group. No clinical or immunologic improvement was seen in either group within the observation period. These data add evidence to the notion that monitoring HIV antigen levels helps to assess the efficacy of antiviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

A monocyte chemotaxis inhibiting factor in serum of HIV infected men shares epitopes with the HIV transmembrane protein gp41.

This report describes that gp41, the transmembranous envelope protein of HIV, is able to inhibit monocyte chemotaxis (measured as FMLP-induced polarization). To study the presence of such immunosuppressive HIV env proteins in the circulation of HIV-infected men, fractions were prepared from serum via ultrafiltration, yielding molecules with a relative Mr of 25-50. These fractions inhibited FMLP-induced polarization of normal human monocytes, while similar fractions of HIV-uninfected men did not. A monoclonal antibody (MoAb) to gp41 was able to adsorb the serum factor responsible for this inhibitory activity. This demonstration of the presence of a gp41-like factor in the circulation of HIV-infected men exerting immunosuppressive activities might have implications for the understanding of the pathogenesis of AIDS, as well as for the selection of HIV-encoded proteins for putative vaccines.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition.

PEPSCAN analysis, performed using 536 overlapping nonapeptides derived from the HTLV-III B nucleotide sequence of the region encoding the external envelope protein of 120 kDa (gp120), identified in the V3 region of gp120 a major binding site for antibodies of HIV-1-infected humans. The minimal amino acid sequence of this antibody binding site was demonstrated by multiple length scanning to be five to eight amino acids in length: (G)PGRAF(VT), i.e. amino acids 312-319. A peptide (Neu 21) containing this binding site for human antibodies (KSIRIQRGPGRAFVTIG) was synthesized and shown to induce HTLV-III B cell fusion-inhibiting antibodies in rabbits and mice. Antibodies binding to this HTLV-III B/LAV-1-specific peptide were shown to be primarily of the IgG 1 subclass, appeared within 6 months after HIV-1 antibody seroconversion in six out of 14 men studied, and persisted throughout the follow-up period of 10-24 months. The other eight seroconverting men did not develop antibodies to Neu 21 during the observation period. The appearance of antibodies to Neu 21 paralleled the capacity of the serum to inhibit HTLV-III B in cell fusion. HIV-1-infected men with Kaposi's sarcoma exhibited a similar frequency of antibodies to the synthetic peptide Neu 21 (14 out of 39, 36%) as asymptomatic HIV-1-infected men (112 out of 319, 35%). Adults with Pneumocystis carinii pneumonia had a significantly lower frequency (11 out of 78, 14%) of antibodies to Neu 21. Similarly, a low prevalence of antibodies to Neu 21 (8 out of 43, 19%) was observed among symptomatic HIV-1-infected children.

Amino Acid Sequence↗
PubMed1988

Expression of RNA and antigens of human immunodeficiency virus type-1 (HIV-1) in lymph nodes from HIV-1 infected individuals.

The presence of proteins (p17 and p24 core proteins, gp41 envelope protein) and mRNA (gag/pol and env gene segments) of human immunodeficiency virus type-1 (HIV-1) was analyzed on frozen tissue sections of lymph nodes from HIV-1 infected individuals. Thirty-one lymph nodes were categorized in the stages of follicle hyperplasia (n = 18), follicle degeneration (n = 5), and total depletion (n = 8). The follicle dendritic cells in germinal centers showed the presence of core proteins and, to a lesser extent, gp41. The staining patterns, being similar to those of immunoglobulins, suggested that they occur in the form of immune complexes. In addition there were solitary cells expressing viral protein, in particular gp41, and mRNA. The number of mRNA-positive cells was very low: about five positive cells were observed in a tissue section with about ten (hyperplastic) follicles. HIV-1-mRNA-positive cells were observed both in follicles and interfollicular areas and showed no differences between various stages. The extent and intensity of distinct HIV-1 proteins and HIV-1-mRNA gene segments in follicles were significantly correlated, as was their presence in interfollicular areas. No significant correlation was found between the presence of HIV-1 components in follicles and in interfollicular areas. This indicates that processes involving HIV-1 components occur in a segregated manner in both lymph node compartments. The presence of HIV-1 components did not correspond to any clinical classification (CDC criteria), nor to other histochemical characteristics. An exception was the correlation between gp41-positive cells and CD1-positive interdigitating cells in the interfollicular areas.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Serodiagnostic profiles of HIV and HIV pathogenesis in vivo.

Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies, formation of antigen/antibody complexes and clearance of such complexes. Transient HIV antigenemia appearing generally 6-8 weeks prior to HIV antibody (HIV-Ab) seroconversion and lasting 3-4 months is generally seen in acute infection. If IgG antibodies to both envelope and core protein persist in the absence of HIV-Ag the short-term prognosis is relatively good. However, HIV-Ag seroconversion may appear at any time after HIV-Ab seroconversion. Progression to AIDS is strongly associated with declining or absent levels of IgG antibodies to p24. Titers of antibodies to HIV p24 below 64 are strongly associated with the presence of HIV antigen and a poor clinical outcome. HIV antigen may be less efficiently detected with the present assays in sera from regions where the prototype strains of HIV (HTLV-III and LAV) are less prevalent, like Central Africa. Levels of HIV-Ag in serum, and possibly in CSF, can be decreased by nucleoside analogues, like AZT. This indicates HIV-Ag and possibly antibody to HIV core protein p24 as suitable markers for selecting individuals for antiviral therapy as well as monitoring the efficacy of such therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Influenza-like syndrome in homosexual men: a prospective diagnostic study.

In the course of a prospective study of the prevalence and incidence of infection with the human immunodeficiency virus (HIV) and risk factors for the acquired immune deficiency syndrome among 961 homosexual men, 97 initially HIV antibody seronegative men reported a febrile period lasting at least three days. In 60 of these men serological evidence for an infection was found: influenza A or B virus (17 men), HIV (14), Epstein-Barr virus (seven), parainfluenza virus type I, 11 or Ill (five), hepatitis A virus (three), cytomegalovirus (three), adenovirus (two), respiratory syncytial virus (two), hepatitis B virus (one) and Toxoplasma gondii (one). Combined infections were found in five men. A total of 17 men seroconverted for HIV antibody. The clinical symptoms of acute HIV infection closely resembled those of influenza A or B infection. Skin rashes also occurred frequently in men with HIV infection. HIV antibody seroconversion gives rise to a number of different symptoms and primary HIV infection should be included in the differential diagnosis of prolonged febrile illness in those at risk of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Serological markers in HIV infection.

HIV antigenaemia can be detected at or possibly before the onset of clinical symptoms of primary HIV infection. Approximately one week after the onset of HIV antigenaemia, a primary anti-HIV IgM response may occur. A week later, generally within 3 to 6 weeks after infection, anti-HIV IgG can be detected. After primary infection, most persons enter an asymptomatic stage, often with generalized lymphadenopathy of varying duration. Disease progression is associated with the appearance of persistent HIV antigenaemia and with a decline of antibody reactivity to the viral core proteins p17 and p24.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Analysis of the antigen- and mitogen-induced differentiation of B lymphocytes from asymptomatic human immunodeficiency virus-seropositive male homosexuals. Discrepancy between T cell-dependent and T cell-independent activation.

Five asymptomatic human immunodeficiency virus (HIV)-seropositive male homosexuals were immunized with the recall antigens tetanus toxoid (TT) and the three types of poliovirus present in diphtheria, tetanus, and polio vaccine. Four weeks after immunization, the in vivo response to booster immunization, the in vitro pokeweed mitogen (PWM)-induced IgG secretion, and the in vitro T cell-dependent and T cell-independent antigen-induced antibody response were assayed. Increase in serum antibody titer to TT and poliovirus was low and normal, respectively. In all five subjects studied, a high rate of spontaneous IgG production, including antibodies directed toward HIV was observed. Addition of PWM to the cultures induced suppression of the spontaneous IgG secretion. Only one donor showed a slightly increased IgG production after stimulation with PWM. Peripheral blood mononuclear cells of four of the five HIV-seropositive individuals did not produce TT, or poliovirus-specific antibodies when stimulated with the respective T cell-dependent antigens. However, stimulation of these peripheral blood mononuclear cells with TT coupled to agarose beads, which was shown to be T cell-independent, resulted in the generation of IgG anti-TT antibody-forming cells.

Adult↗
PubMed1987

Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia.

One hundred and ninety eight men seropositive for human immunodeficiency virus (HIV) antibody and 58 HIV antibody seroconverters were studied for an average of 19.3 (SEM 0.5) months to assess the relation between HIV antigenaemia and the risk of developing the acquired immune deficiency syndrome (AIDS) and AIDS related complex. Forty (20.2%) of the 198 HIV antibody seropositive men were antigen positive at entry and remained so during follow up. Eight (13.8%) of the 58 HIV antibody seroconverters and 20 (12.7%) of the remaining 158 HIV antibody seropositive men became antigen positive during follow up, resulting in an end point attack rate for HIV antigenaemia of 14.3%. AIDS related complex was diagnosed in 25 (15.8%) of the HIV antigen negative men and in 14 (20.7%) of the HIV antigen positive men. AIDS was diagnosed in 15 men, resulting in an end point attack rate for AIDS of 23.9% in the HIV antigen positive group and 1.3% in the antigen negative group. HIV antibody seropositive men without symptoms but with persistent HIV antigenaemia are at increased risk of developing AIDS and AIDS related complex.

AIDS-Related Complex↗
PubMed1987

Expression of human immunodeficiency virus in cerebrospinal fluid of children with progressive encephalopathy.

The retrovirus that causes acquired immune deficiency syndrome (AIDS) is now designated the human immunodeficiency virus (HIV). The cerebrospinal fluid (CSF) of 27 children with HIV infection was assayed for intra-blood-brain barrier (IBBB) synthesis of HIV-specific antibodies and for the presence of HIV antigen. In this cohort, 11 children had a progressive encephalopathy (PE), 9 had a static encephalopathy (SE), and 7 had normal neurological findings (N). IBBB synthesis of HIV-specific antibodies was identified (using matched serum and CSF specimens) in 7 of 11 children with PE, 4 of 9 children with SE, and 2 of 7 children with N. HIV antigen was found (using a highly sensitive solid-phase enzyme immunoassay) in the CSF of 8 of 11 children with PE, none of the children with SE, and none of the 7 children with N. On the basis of these data, we conclude that: IBBB synthesis of HIV antibodies indicates invasion of the central nervous system but may reflect prior or current infection; and HIV antigen in CSF indicates viral expression and correlates with the occurrence of PE. These findings strongly implicate HIV as the causative agent of PE in these children. The assay for HIV antigen in the CSF may be of value in determining the prognosis of children with HIV infection and for evaluating the efficacy of therapeutic agents against this retrovirus.

Acquired Immunodeficiency Syndrome↗