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Biomedical subjects

J Goudsmit

Publications and source records attributed to J Goudsmit.

At least 361 records · Page 20Linked to original sources

Spread of human T-cell leukemia virus (HTLV-I) in the Dutch homosexual community.

Sequential sera of 697 homosexual men, participating in a prospective study (1984-1986) of the risk to acquire human immunodeficiency virus (HIV) or AIDS, were tested for antibodies to human T-cell leukaemia virus (HTLV-I) by particle agglutination and immunoblotting. No intravenous drug users were included in this trial. Three men (0.4%) were HTLV-I antibody positive at intake and an additional 2 at the end of the observation period, resulting in an attack rate of approximately 0.3%. One of the 3 men with HTLV-I antibodies at intake was a Brazilian. One man had an acute HTLV-I infection after sexual intercourse with a Brazilian during holiday in Brazil. No serological cross-reactivity with HIV was observed nor a relationship with other sexually transmissible viral or bacterial infections. In contrast to HIV no relationship with anogenital intercourse was noted; both primary HTLV-I infected men practiced only orogenital intercourse. This suggests that HTLV-I was imported in the Dutch homosexual community after HIV was introduced in the Netherlands. HTLV-I appears to spread slower within the homosexual community than HIV and possibly by other routes.

Adult↗

Pathogenesis of HIV and its implications for serodiagnosis and monitoring of antiviral therapy.

Human immunodeficiency virus (HIV) is lymphotropic and neurotropic. In vivo clinical and immunological abnormalities develop in a large proportion of long-term HIV antibody seropositive persons. 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 wk prior to HIV antibody (HIV-Ab) seroconversion and lasting 3-4 mth is generally seen in acute infection. IgM antibodies predominantly to core proteins may occasionally be detectable when, or just before, IgG antibodies appear. If IgG antibodies to both envelope and core proteins 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. IgG2 and IgG4 antibodies to HIV, which are mainly directed to p24, disappear most dramatically. Titers of antibodies to HIV p24 below 64 are strongly associated with the presence of HIV antigen and a poor clinical outcome. HIV antigen was detected frequently in sera from children in all stages of infection in contrast to adults whose sera were generally HIV-Ag negative when asymptomatic and positive when AIDS was apparent. 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. Persistence of HIV-Ag in cerebrospinal fluid (CSF) appears to be pathognomonic for progressive encephalopathy, particularly in children. Levels of HIV-Ag in serum, and possibly in CSF, can be decreased by nucleoside analogues, such as 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↗

Circulation of HIV antigen in blood according to stage of infection, risk group, age and geographic origin.

Human immunodeficiency virus antigen (HIV-ag) was determined by enzyme immunoassay (EIA) in HIV-antibody (anti-HIV) positive as well as pre-anti-HIV seroconversion sera and the results analysed according to stage of infection, risk group, age and geographic origin. Eleven (19%) of 58 homosexual men tested showed HIV-ag in a serum taken 3-4 months before or one at the time of anti-HIV seroconversion. In another eight (14%) HIV-ag persisted after seroconversion and half of them developed AIDS or AIDS-related complex (ARC) in contrast to none of the other 50 anti-HIV seroconversions. Two (13%) of 16 haemophiliacs tested had HIV-ag only in the first anti-HIV seropositive sample. HIV-ag was present in 86% (30/35) of Dutch homosexual men with AIDS, in 32% (7/22) of men with ARC and in 17% (24/145) of men with persistent generalized lymphadenopathy (PGL) or without symptoms. Three percent (2/60) of sera of asymptomatic i.v. drug users from Amsterdam were HIV-ag positive. Ten percent (1 of 10) of sera from Central Africans with 'Slim Disease' were HIV-ag positive. Among infected children from the USA or Europe 89-100% (8/9 and 2/2) of AIDS cases, 67-100% (6/9 and 3/3) of children with ARC and 75% (3/4) of asymptomatic children were HIV-ag positive. The HIV-ag EIA appears to be able to identify HIV infection earlier than the available anti-HIV assays in a significant number of cases. Since persistence of HIV-ag, except possibly in African cases, is strongly associated with clinical deterioration, HIV-ag appears to be a suitable marker for, independent of their clinical status, selecting individuals for antiviral therapy and also for monitoring the efficiency of such therapy.

AIDS-Related Complex↗

Intra-blood-brain barrier synthesis of human immunodeficiency virus antigen and antibody in humans and chimpanzees.

The presence of human immunodeficiency virus (HIV) antigens in cerebrospinal fluid (CSF) was associated with progressive encephalopathy in adult and pediatric patients with acquired immunodeficiency syndrome (AIDS). HIV antigen was detected in CSF from 6 of 7 AIDS patients with progressive encephalopathy. By contrast, HIV antigen, whether free or complexed, was detected in CSF from only 1 of 18 HIV antibody seropositive patients without progressive encephalopathy and from 0 of 8 experimentally infected chimpanzees without clinical signs. Intra-blood-brain barrier synthesis of HIV-specific antibody was demonstrated in the majority of patients with AIDS (9/12) or at risk for AIDS (8/13) as well as in the experimentally infected chimpanzees, indicating HIV-specific B-cell reactivity in the brain without apparent neurological signs. In 6 of 11 patients with HIV infection, antibodies synthesized in the central nervous system were directed against HIV envelope proteins. Active viral expression appears to be necessary for both the immunodeficiency and progressive encephalopathy associated with HIV infection.

AIDS-Related Complex↗

Risk factors and prevalence of HIV antibodies in homosexual men in the Netherlands.

As part of the prospective AIDS study in Amsterdam, blood samples were collected from 741 healthy homosexual men with multiple sexual partners, between October 1984 and May 1985. Samples were analyzed for the presence of antibodies to the human immunodeficiency virus (anti-HIV). Anti-HIV was demonstrated in 233 (31%) of the respondents. Seropositive respondents engaged in anal receptive sexual techniques with more sexual partners than did seronegative respondents, whereas seronegatives engaged in manual sexual techniques with more sexual partners than did seropositives. As far as it was possible to control for the interrelations between the measured variables, a direct relation with anti-HIV was established. This leads to the conclusion that when the number of sexual partners is considered a risk factor for HIV, a clear distinction should be made between the sexual techniques practiced with these partners. Two other risk factors for the presence of anti-HIV were the use of cannabis and of nitrite.

Acquired Immunodeficiency Syndrome↗

Detection of early anti-p24 HIV responses in EIA- and immunoblot-negative individuals. Implications for confirmatory testing.

A sensitive and specific radioimmunoprecipitation assay was developed for the detection and analysis of anti-HIV antibody response in human sera with the use of 125I-labelled purified HIV proteins with subsequent sodium-dodecylsulfate gel electrophoresis (125I-RIPA). The 125I-RIPA was shown to be as specific but at least 1 log more sensitive with respect to the detection of gp41env and p24gag than the immunoblot analysis as tested in serum samples from several risk groups. Sequential sera were obtained from 9 individuals who seroconverted for HIV antibodies. In 4 individuals, antibody to p24gag was detected in earlier serum samples by the 125I-RIPA than by EIA or immunoblot; in the other 5 individuals, the detection of p24gag concorded in enzyme-linked immunosorbent assay (EIA), immunoblot and 125I-RIPA. Moreover, in one of 78 randomly chosen EIA-negative sera from individuals at high risk, antibodies to p24gag could be detected by the 125I-RIPA. This early seroconversion was confirmed 3 months later by means of immunoblotting and EIA. The specificity of the 125I-RIPA was further demonstrated by analyzing sequential EIA-negative serum samples from 10 individuals at risk for AIDS, collected during 2 years at 3-monthly intervals. All 80 serum samples were found to be negative in the 125I-RIPA and the individuals revealed no signs of HIV infection. The 125I-RIPA technique may be a valuable confirmatory assay in the serology of HIV infections. The sensitivity of this test provides a reliable measure of effective sensitivity when new-generation screening tests are evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Serum antibodies to HTLV-I in human demyelinating disease.

Serum HTLV-I antibodies were measured in 17 MS patients and 2 closely matched control groups by 2 different independent assays. A highly sensitive particle agglutination test was used to detect HTLV-I core protein antigens and an immunoblot assay with E. coli-expressed P21E transmembrane protein was employed to detect antibodies to HTLV-I evelope antigens. No serologic evidence of prior HTLV-I infection in our population of multiple sclerosis (MS) or Guillain-Barré Syndrome (GBS) patients was found.

Adult↗

Viral gene expression, antibody production and immune complex formation in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) antigen (HIV-Ag) in polyethylene glycol (PEG) precipitates and supernatants and HIV antibodies (HIV-Ab) to core and envelope antigens were studied in serial serum samples of three HIV-Ab seroconverters and 11 HIV-Ab seropositive men with a mean follow-up time of 16.1 months. In five men not progressing beyond persistent generalized lymphadenopathy (PGL) and two progressing to AIDS, HIV-Ag was detected once in 'free' configuration before HIV-Ab seroconversion and persistently or intermittently 'complexed' thereafter; in six of these men HIV core antibodies were continuously present with a declining level in one. In two men not progressing beyond PGL and five progressing to AIDS HIV-Ag was detected 'complexed' before HIV-Ab seroconversion once and persisted predominantly in 'free' configuration thereafter, while no HIV core antibody was detected in six of these men and a declining level in one. HIV-Ag was detected in 37% (14 out of 38) of HIV core antibody seropositive samples, mostly in 'complexed' form, while HIV-Ag was detected in 86% (43 out of 50) of HIV core antibody seronegative samples, mostly in both 'complexed' and 'free' configuration. Antibodies to HIV envelope antigen were detected in all HIV-Ab seropositive samples. These results indicate that the level of HIV-Ag expression is the primary determinant of detectability of HIV core antigens as well as antibodies. Enhancement of HIV-Ag expression, in a significant number of cases associated with clinical deterioration, appears to lead to clearance of HIV core antibodies in immune complexes, while HIV envelope antibody levels remain relatively unaffected.

Acquired Immunodeficiency Syndrome↗

Decline of antibody reactivity to outer viral core protein p17 is an earlier serological marker of disease progression in human immunodeficiency virus infection than anti-p24 decline.

Using a modified immunoblot procedure we looked for early serological markers of disease progression in sequential serum samples from 30 initially symptomless HIV-infected homosexual men. Sixteen men who did not progress beyond persistent generalized lymphadenopathy (PGL) and did not develop HIV antigenaemia showed persistent strong immunoglobulin G (IgG) reactivity to all initially recognized HIV proteins. Three out of four men who did not progress beyond PGL but did develop HIV antigenaemia showed declining or absent IgG reactivity to the outer HIV core protein p17, whereas reactivity to other initially recognized HIV proteins persisted in all four; in one of these subjects a striking decline in anti-p17 reactivity occurred 1 1/2 months after HIV antibody seroconversion and 7 1/2 months before HIV antigenaemia developed. In nine out of 10 men who developed constitutional disease [Centers for Disease Control (CDC) group IV A] or AIDS (CDC groups IV C1 and IV D), a decline in anti-p17 reactivity was seen preceding or at disease development; in two of these men a concomitant decline in anti-p24 reactivity was seen. In the only individual without HIV antigenaemia who developed CDC group IV disease, anti-p17 reactivity declined 10 months before disease development, whereas no similar decline in anti-p24 reactivity was seen. Decline in IgG antibody reactivity to HIV core protein p17 appears to be an earlier marker of disease progression than the previously reported decline in anti-p24 reactivity, and may be of value in selecting individuals for secondary prevention of HIV-related disease development.

AIDS-Related Complex↗

Extrathecal and intrathecal IgG response to the AIDS virus LAV/HTLV-III in experimental infection of chimpanzees.

Seven of seven chimpanzees inoculated with LAV/HTLV-III and three of three chimpanzee-to-chimpanzee passages seroconverted for LAV/HTLV-III as tested by ELISA and immunoblotting. Serum IgG reactivity to gag-gene products emerged between 3 and 6 weeks after inoculation, p24gag reactivity always reaching maximum titers first. Serum IgG antibodies to env-related proteins occurred 11-21 weeks after inoculation. Throughout the observation period (greater than 36 weeks), IgG reactivity to gag, pol, and env gene products persisted. Matched serum and cerebrospinal fluid (CSF) from three LAV/HTLV-III-infected chimpanzees were available in the chronic phase of infection and titers of viral antibody and albumin and IgG content were determined. By calculation of antibody/albumin indices, evidence was obtained for intrathecal synthesis of IgG antibodies to LAV/HTLV-III in one animal.

Acquired Immunodeficiency Syndrome↗

Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS.

Sequential serum samples from 13 homosexual men who seroconverted for antibodies to human immunodeficiency virus (HIV) were tested for HIV antigen. In one of these men, who developed the acquired immune deficiency syndrome (AIDS), HIV antigenaemia preceded the onset of AIDS by more than a year and persisted throughout the course of the disease. This antigenaemia was accompanied by the disappearance of IgG antibody reactivity to the major HIV core protein p24. In none of the 12 others, who all remained without serious disease, were serum concentrations of HIV antigen detected, except on one occasion in one man. All their serum samples showed strong IgG antibody reactivity to p24. Nine children who were infected with HIV in 1981 by plasma transfusion from a single donor were also followed up for HIV antigenaemia. HIV antigen was almost constantly present in the serum (26 of 28 samples) of five children who developed AIDS related complex or AIDS and less often in the serum (four of 10 samples) of four children who remained free of symptoms. The two children who developed AIDS showed a virtual absence of antibody reactivity to p24. These results indicate that increased HIV gene expression is a contributing factor to the development of AIDS and also provide evidence for a switch from latent to active HIV infection.

Acquired Immunodeficiency Syndrome↗

Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection.

Human immunodeficiency virus antigen (HIV-Ag) was detected in the serum of most adult (13/16) and paediatric (6/6) AIDS patients and rarely in the serum of symptomless seropositive controls (1/13). It was present in the cerebrospinal fluid (CSF) of all 5 children and most (5/9) adults with AIDS-related encephalopathy, but not in the CSF of 13 symptomless seropositive controls, of whom 8 had antibody in the CSF. A longitudinal study of 1 of the controls with antibody in the CSF showed that HIV-Ag in CSF was present transiently before the occurrence of antibody in the CSF. In serial samples of serum from 35 men who seroconverted HIV-Ag was detected in 11 persons--in 5 before seroconversion and in 6 after. 3 of the 6 who became antigenaemic after seroconversion remained so for the rest of the follow-up. AIDS was diagnosed in 1 patient, 3 months after HIV-Ag was first detected in serum and 6 months after seroconversion. The findings suggest that HIV-Ag appears early and transiently in primary HIV infection. Antibody production follows, after which HIV-Ag may disappear. Its persistence or reappearance seems to correlate with clinical, immunological, and neurological deterioration.

Acquired Immunodeficiency Syndrome↗

Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex.

De novo synthesis in the central nervous system of IgG antibodies to human T cell lymphotropic virus type III (HTLV-III) (lymphadenopathy associated virus) was shown in seven of 10 seropositive men who had syphilis but not the acquired immune deficiency syndrome (AIDS) or AIDS related complex. None of these men showed neurological symptoms when the serum and cerebrospinal fluid were collected. Pleocytosis was present in all 10. Of the seven men who showed evidence of intrathecal synthesis of antibodies, five had increased total concentrations of IgG and four had oligoclonal IgG bands in their cerebrospinal fluid. Oligoclonal bands were also present in one man who did not have any antibodies. Longitudinal study of one man showed that seroconversion preceded intrathecal synthesis of antibody specific to HTLV-III. The appearance of antibody in the cerebrospinal fluid was accompanied by a transient rise in mononuclear cell count and the appearance of oligoclonal bands. The presence of clones of B cells specific to HTLV-III in the central nervous system of these patients without persisting neurological symptoms suggests that HTLV-III enters the central nervous system in the early stages of infection.

Acquired Immunodeficiency Syndrome↗