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Biomedical subjects

J Goudsmit

Publications and source records attributed to J Goudsmit.

At least 307 records · Page 17Linked to original sources
PubMed1989

Antibody response to the viral negative factor (nef) in HIV-1 infection: a correlate of levels of HIV-1 expression.

Antibody responses against the nef gene product of HIV-1 were determined in sequential sera from a longitudinally studied cohort of 194 initially asymptomatic HIV-1-seropositive individuals and 72 individuals who seroconverted for antibodies to HIV-1 structural proteins (gag/env). In the majority of men, nef-specific antibodies, once detected, persisted (67.6%). In some men, nef-specific antibodies were only transiently (6.8%), or intermittently (5.3%), detectable. No nef-specific antibodies were found in the remaining men (20.3%). Nef-specific antibodies were elicited early in infection, but rarely (2/72 men) prior to seroconversion for antibodies to HIV-1 structural proteins. An absent, transient, or intermittent nef-specific antibody response was significantly associated with the absence or disappearance of antibodies to HIV-1 core proteins, with (re)appearance and persistence of HIV-1 core antigen and with the presence of low CD4+ cell numbers, i.e. profiles previously shown to be predictive of rapid disease progression. Although more cases of AIDS and AIDS-related disease (21/86 versus 28/180) occurred in the nef-specific antibody-negative group than in the nef-specific antibody-positive group, this difference did not reach significance.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Appearance of predictors of disease progression in relation to the development of AIDS.

To study the natural history of HIV-1 infection in relation to serological and immunological profiles, 199 asymptomatic HIV-1-antibody (HIV-1-core-antibody)-seropositive and 76 seroconverted homosexual men were followed prospectively for 39 months. AIDS was diagnosed in 38 men. The AIDS attack rate was 20.8% after 39 months. The AIDS attack rate in the HIV-I-core-antibody positives was 12.1, versus 30.1% in the HIV-1-core-antibody negatives (P less than 0.001), and it was 13.3% in the HIV-1-antigen (HIV-1-Ag) negatives versus 53.9% in the HIV-1-Ag positives (P less than 0.001). The AIDS attack rate after 39 months was 10.9% in men with counts greater than or equal to 0.5 x 10(9)/l and 49.9% in those with CD4+ lymphocyte counts less than 0.5 x 10(9)/l. AIDS attack rates after 30 months in the same cohort have been previously reported [1], and were as follows: 6.8% in the core-antibody positives versus 35.7% in the core-antibody negatives. 6.9% in the HIV-1-Ag negatives versus 43.9% in the HIV-1-Ag positives, and 6.1% in those with CD4+ lymphocyte counts greater than or equal to 0.5 versus 51.9% in those with CD4+ lymphocyte counts less than 0.5 x 10(9)/l. The disappearance of core antibody, the appearance of antigen and the occurrence of low CD4+ lymphocyte counts preceded AIDS by a mean (s.d.) of 21.3 (8.9), 17.7 (8.8) and 15.7 (8.9) months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Characterization of HIV-1 neutralization escape mutants.

Infection by molecularly cloned HIV-1, in the presence of a high-titre neutralizing monoclonal antibody (MAb), resulted in the selection of plaques in MT4 cells releasing HIV resistant to neutralization by the same MAb. The epitope recognized by the MAb was mapped to the V3 neutralization epitope at amino acids 305-321. The HIV-1 variants showed a reduced binding capacity for the selecting MAb as determined by immunofluorescence. Polymerase chain reaction (PCR) amplification of complementary DNA derived from viral RNA, cloning and sequencing identified a base pair (bp) change C----G at position 6663 in variant 110.5/1, predicting a change at amino acid 308 Arg----Gly. No other changes in the epitope were observed by sequencing three other variants. Differential hybridization of PCR amplified viral RNA and DNA, with oligonucleotides specific for the observed bp change or the 'wild type' sequence, indicated that the variants 110.5/1 and 110.5/7 were genotypically mixed for 308Gly/Arg. Subsequent screening of biologically 'recloned' variants 110.5/1 and 110.5/7 identified two subclones homozygous for the 308Gly change. The Arg----Gly change appears to affect the binding of the antibody to the epitope, since the linear peptide substituting 308Gly for 'wild type' 308Arg was 100 times less potent in blocking the neutralization of parental HIV. Amino-acid residue 308 thus appears to be crucial for antibody binding to the epitope. In addition, mutations distant from the monoclonal antibody binding site may also affect neutralization by antibodies recognizing the V3 loop.

Amino Acid Sequence↗
PubMed1989

Specificity and function of the individual amino acids of an important determinant of human immunodeficiency virus type 1 that induces neutralizing activity.

An important antigenic determinant of human immunodeficiency virus type 1 that induces neutralizing activity in infected humans and chimpanzees was previously mapped with nonapeptides between amino acids 307 and 320 on the external envelope glycoprotein (gp 120) of strain HTLV-IIIB (molecular clone BH10) and amino acids 320 to 330 of strain HTLV-IIIRF. Using different sera we found different reactive nonapeptides that overlapped and shared a tetrapeptide, GPGR. This tetrapeptide, which is the same in HTLV-IIIB and HTLV-IIIRF, is flanked by amino acids that vary between virus strains. Because GPGR is predicted to form a beta-turn and is flanked by two cysteine residues that may form a disulphide bridge, a hairpin-like structure is suggested for this part of gp120. The tetrapeptide GPGR and the reactive peptides are located on top of this structure, well exposed to antibodies. We determined the role of the individual amino acids in antibody binding using three sets of peptide analogues derived from three reactive nonapeptides (two of strain HTLV-IIIB which overlapped and one of strain HTLV-IIIRF). Each set contained peptide analogues in which each amino acid was replaced, one at a time, by all genetically encoded amino acids. At least five consecutive amino acids in each nonapeptide were essential for antibody binding. They include amino acids of GPGR and potentially provide the virus with ample opportunity to escape immune surveillance.

Amino Acid Sequence↗
PubMed1989

Low AIDS attack rate among Dutch haemophiliacs compared to homosexual men: a correlate of HIV antigenaemia frequencies.

A cohort of 180 haemophiliacs followed between 1983 and 1986 and a cohort of 961 homosexual men followed between 1984 and 1986 were compared for the prevalence and incidence of HIV-1 antibody (HIV-1-Ab) seropositivity, the incidence of AIDS-related complex (ARC) and AIDS and the prevalence and incidence of serological and immunological markers for HIV-related disease progression. Among the haemophiliacs 23 (12.8%) patients were HIV-1-Ab seropositive at entry and 20 (12.7%) of the remaining 157 seroconverted for HIV-1-Ab during follow-up. Of the homosexual men 238 (24.8%) were HIV-1-Ab seropositive at entry and 68 (9.4%) of the 723 at entry seronegatives seroconverted during follow-up. Clinical follow-up of the HIV-1-Ab seropositive and seroconverted men was 59 months in the haemophiliac cohort and 60 months in the homosexual cohort. Among the HIV-1-Ab seropositive and seroconverted haemophiliacs and homosexual men the cumulative ARC/AIDS incidence was 2 and 18%, respectively. Occurrence of HIV-1-antigenaemia was more frequent among seropositive and seroconverted homosexual men (28%) than among haemophiliacs (7%) (p = 0.001). The groups did not differ significantly for the absence or loss of anti-HIV core antibodies or the occurrence of low CD4+ cell numbers. These data indicate a slower progression of HIV-related disease in seropositive haemophiliacs compared to seropositive homosexual men.

AIDS-Related Complex↗
PubMed1989

Antibody response to human immunodeficiency virus type 1 protease according to risk group and disease stage.

Three groups with different routes of human immunodeficiency virus type 1 (HIV-1) transmission (homosexual men, hemophiliacs, and children) were studied for serum antibodies to a recombinant form of the HIV-1 protease using an enzyme-linked immunoassay. At 1 year after seroconversion, defined as the moment antibodies to HIV-1 proteins were first detected, 56% (34/61) of the homosexual men had antibodies to protease, and 2 years after seroconversion this percentage was 63% (24/38). Within this 2-year period these antibodies were no longer detected in 16% (9/56). A similar pattern was observed in 20 hemophiliacs who seroconverted after exposure to HIV-1-contaminated blood products. We found that 63% (160/255) of homosexual men in Centers for Disease Control stage II or III, 60% (9/15) of patients with acquired immunodeficiency syndrome (AIDS)-related complex, and 36% (14/39) of patients with AIDS had antibodies to protease. In 255 homosexual men in Centers for Disease Control stage II or III, antibodies to protease were significantly more frequently found in samples lacking HIV-1 antigen (P less than 0.001) and possessing antibodies to HIV-1 core proteins (P less than 0.001). Twenty-four persons who developed AIDS were studied longitudinally: 58% (14/24) had antibodies to protease 1 year before developing symptoms; 29% (7/24) showed a decline and 29% (7/24) showed a loss of antibodies to protease at the onset of symptoms. Within a group of 47 HIV-1-infected children, 90% (18/20) with a stable disease course were persistently protease antibody positive, versus 4 of 27 children (15%) with an unstable disease course (P = 0.0001). These data indicate that HIV-1 protease is expressed and antigenic in most HIV-1-infected individuals and that a decline or absence of antibodies to protease is strongly associated with unstable disease in children and AIDS in adults.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates.

Sequential human immunodeficiency virus (HIV) isolates, recovered from a panel of longitudinally collected peripheral blood mononuclear cells obtained from 20 initially asymptomatic HIV-seropositive homosexual men, were studied for differences in replication rate, syncytium-inducing capacity, and host range. Eleven individuals remained asymptomatic; nine progressed to acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) at the time point at which the last HIV isolate was obtained. In 16 individuals, only non-syncytium-inducing (NSI) isolates, with a host range restricted to mononuclear cells, were observed. From four individuals, high-replicating, syncytium-inducing (SI) isolates that could be transmitted to the H9, RC2A, and U937 cell lines were recovered. From two of these four individuals, SI isolates were obtained throughout the observation period. In the two others, a transition from NSI to SI HIV isolates was observed during the period of study. Three of these four individuals developed ARC or AIDS 9 to 15 months after the first isolation of an SI isolate. With the exception of the two individuals in whom a transition from NSI to SI isolates was observed, within a given individual the replication rate of sequential HIV isolates was constant. A significant correlation was found between the mean replication rate of isolates obtained from an individual and the rate of CD4+ cell decrease observed in this individual. In individuals with low-replicating HIV isolates, no significant CD4+ cell loss was observed. In contrast, recovery of high-replicating isolates, in particular when these were SI isolates, was associated with rapid decline of CD4+ cell numbers and development of ARC or AIDS. These findings indicate that variability in the biological properties of HIV isolates is one of the factors influencing the course of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

HIV infection and STD in drug addicted prostitutes in Amsterdam: potential for heterosexual HIV transmission.

To assess the potential role of drug using prostitutes in the heterosexual transmission of human immunodeficiency virus (HIV), 117 prostitutes, recruited from December 1985 to November 1987 at a weekly evening sexually transmitted diseases (STD) clinic for drug using prostitutes only, were studied for the prevalence of HIV and STD. Intravenous drug use was reported by 96 (82%) of the women. Antibody to HIV was found in 35/117 (30%) women, all but one of whom had been using drugs intravenously. Most (73, 62%) of the prostitutes reported having had more than 2000 clients each in the preceding five years. In the six months preceding enrollment to the study they had practised mainly vaginal (106/117) and orogenital (82/117) intercourse; 90% (105/117) reported frequent use of condoms in vaginal intercourse and 65% (68/105) in orogenital intercourse. Despite frequent condom use, 81% (84/104) contracted one or more STD in this period. Considering the high incidence of HIV and STD and the finding by others that the presence of STD may facilitate transmission of HIV, we conclude that the potential for HIV transmission from these prostitutes to their clients (and vice versa) was clearly present.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The thymus in acquired immune deficiency syndrome. Comparison with other types of immunodeficiency diseases, and presence of components of human immunodeficiency virus type 1.

The authors studied thymus specimens taken at autopsy from eight acquired immune deficiency syndrome (AIDS) patients and compared these with those taken from four patients with congenital immunodeficiency (unrelated to an intrinsic thymus defect) and seven patients after allogeneic bone marrow transplantation. In all cases, histology showed a severely involuted architecture, compatible with a debilitating disease before death. There were no major differences between thymus tissue in AIDS patients and in the other patients studied. This argues against the claim expressed in the literature that the epithelial microenvironment incurs particular HIV-1-induced injury in AIDS. This conclusion is substantiated by immunohistochemistry for HIV-1 gag and env proteins, and by hybridohistochemistry for gag/pol and env mRNA of HIV-1. Positive cells were observed only in low numbers, both inside the epithelial parenchyma and in the (expanded) perivascular areas. An interesting finding was the labeling of subcapsular/medullary epithelium in normal uninvoluted thymus by a number of antibodies to HIV-1 gag p17 and p24 proteins. Compatible with this labeling was the staining of epithelial stalks in hyperinvoluted thymuses irrespective of disease category. The previously reported cross-reactivity between HIV-1 core protein and thymosin alpha 1 cannot fully explain this observation, because the epithelium in the hyperinvoluted state is negative for thymosin alpha 1. This study confirms and extends previous reports on the endogenous presence of epitopes of retroviral antigens in thymic epithelium.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Specificity of chimpanzee antibodies binding a strain-specific HIV-1 neutralization epitope of the external envelope.

Sera from three chimpanzees infected with a primary lymphadenopathy-associated virus (LAV-1) or human T-lymphotropic virus type III (HTLV-IIIB) passage, from two chimpanzees infected with blood from the primary infected chimpanzees, and from one chimpanzee infected with blood from a secondary passage animal all bound the peptides 3B and 3B/RF, sharing the sequence IQRGPGR, with equally high titers. Pepscan analysis confirmed the amino acids Q, R, G, P, and G as irreplaceable in order to retain antigenicity.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cellular and humoral immunity in various cohorts of male homosexuals in relation to infection with human immunodeficiency virus.

The relationship between infection with human immunodeficiency virus (HIV) and various immunological parameters was studied in: (a) healthy controls; (b) homosexual individuals from the AIDS risk group without anti-HIV antibodies; (c) idem, but with anti-HIV antibodies; (d) patients with persistent generalized lymphadenopathy (PGL); (e) patients with AIDS-related syndrome; (f) patients with AIDS and opportunistic infections. In each group, consisting of 15-20 individuals, the following parameters were studied: absolute numbers of CD4+ and CD8+ cells; ratio CD4+/CD8+; cellular immune responses as measured in vivo by delayed-type hypersensitivity (DTH) and in vitro; and antibody response in vivo after immunization with a low dose of keyhole limpet haemocyanin. Healthy HIV antibody-positive individuals and patients with persistent generalized lymphadenopathy already showed a decreased CD4+/CD8+ ratio, mainly due to an increase in the number of CD8+ cells. The ratio in the AIDS-related syndrome and AIDS groups was even lower, but this was now due to low numbers of CD4+ cells while the number of CD8+ cells was normal. The lymphocyte proliferative response was low in the HIV antibody-positive group, normal in the group with persistent generalized lymphadenopathy and profoundly decreased in the AIDS-related syndrome and AIDS groups. DTH was enhanced in the PGL group and diminished in both ARC and AIDS. Compared to healthy controls, the antibody response upon immunization with a low dose of keyhole limpet haemocyanin was depressed (although not absent) in all groups studied, even in HIV antibody-negative homosexuals. In the HIV antibody-positive group, the severity of the impairment of the various parameters of immunocompetence was not related to the presence of HIV antigenaemia.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The prevalence of human immunodeficiency virus among pregnant women attending a hospital in the Moungo district, Cameroon.

A seroepidemiological survey conducted from January to May 1986 among 650 pregnant women from mixed rural/urban origin in the Moungo district, Cameroon, revealed a very low prevalence of antibodies to human immunodeficiency viruses (HIV). One subject appeared to be infected with HIV 2. This is remarkable since HIV 2 has been isolated predominantly from West-African subjects. Further epidemiological and antropological studies are required to explain the distribution of HIV 1 and HIV 2 throughout the African continent.

Acquired Immunodeficiency Syndrome↗