PubMed Health⌕ Search

Biomedical subjects

M Koot

Publications and source records attributed to M Koot.

At least 37 records · Page 2Linked to original sources
PubMed1994

Characteristics of long-term asymptomatic infection with human immunodeficiency virus type 1 in men with normal and low CD4+ cell counts.

From a cohort study of homosexual men in Amsterdam, 61 human immunodeficiency virus (HIV)-infected men who had remained asymptomatic for at least 7 years were identified. In a nested case control study, these men were compared with 142 men who progressed symptomatic HIV infection (CDC class IV) within 7 years, regarding laboratory markers, sexual behavior, psychologic coping, and drug use. Of the 61 long-term asymptomatic men, 13 had a CD4+ cell count > or = 500/mm3 after 7 years; in 2 of these 13, the CD4+ cell count had not declined during follow-up. Independent of CD4+ cell count, long-term asymptomatic HIV-1 infection was characterized by stable T cell reactivity after stimulation with monoclonal CD3 antibodies, seropositivity for antibodies to HIV core proteins, and the absence of hepatitis B markers. No association with markers of high-risk sex or the recreational use of drugs was found. Long-term asymptomatic men had a slightly lower score regarding the coping behavior active problem-solving; no other associations with coping behaviors were found.

Adult↗
PubMed1994

Associations between HLA frequencies and pathogenic features of human immunodeficiency virus type 1 infection in seroconverters from the Amsterdam cohort of homosexual men.

HLA-disease associations may be important for understanding the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. Therefore, 106 homosexual men from the Amsterdam Cohort Study on AIDS with a known date of HIV-1 seroconversion were serologically typed for HLA. Several significant associations between HLA type and pathogenic features of HIV-1 infection were observed: Subjects with fever and skin rash during primary HIV-1 infection showed an increased frequency of HLA-B62 (relative risk [RR], 5.8; P = .005). The frequency of HLA-B35 was increased in subjects with a rapid decline in CD4+ T lymphocytes (RR, 3.2; P = .021). Kaplan-Meier survival analysis revealed a significant association between HLA-B35 and a decrease in CD4+ cells to < 200/microL (P = .01). The strongest association was found between HLA-DR1 and AIDS-related Kaposi's sarcoma (RR, 22.5; P < .001), also confirmed in survival analysis (P = .001). In AIDS patients with only opportunistic infections, increased frequencies of HLA-DR3 (P = .011) and -DQ2 (P = .007) were observed. Finally, the occurrence of syncytium-inducing HIV-1 variants was significantly associated with HLA-DQ2 (P = .01).

Cohort Studies↗
PubMed1994

Predictors of disease progression in HIV-infected homosexual men with CD4+ cells < 200 x 10(6)/l but free of AIDS-defining clinical disease.

OBJECTIVE: To study progression of HIV infection in individuals who are free of AIDS-defining clinical disease with CD4+ cell counts < 200 x 10(6)/l. DESIGN: Prospective and nested case-control study. SETTING: Amsterdam cohort study on HIV infection, The Netherlands. PARTICIPANTS: Prospective study: 148 asymptomatic HIV-infected individuals with < 200 x 10(6)/l CD4+ cells. Nested case-control study: 58 men with AIDS-free follow-up more than 2 years after CD4 count < 200 x 10(6)/l, compared with 63 who progressed to AIDS within 2 years. MAIN OUTCOME MEASURES: Progression to AIDS according to the 1987 Centers for Disease Control and Prevention case definition and death. RESULTS: Median AIDS-free interval was 22 months, median interval to death 41 months. Presence of syncytium-inducing (SI) HIV variants, HIV p24 antigen, and a low T-cell response after stimulation with phytohaemagglutinin (PHA) were independent predictors of progression to AIDS. Probability of 1 year AIDS-free survival varied between 89 and 38% by the presence or absence of these additional markers. Effect of early treatment could only be detected in men with HIV p24 antigen and SI variants. Case-control analysis showed similar changes over time regarding prognostic markers in both groups although at a lower rate in the AIDS-free men. Eight men remained AIDS-free more than 4 years, SI variants were absent in seven, and all eight were p24-seronegative. CONCLUSIONS: HIV-infected individuals can remain disease-free for more than 4 years with very low CD4+ cell counts, provided that they lack other progression markers: SI variants, p24 antigen and a low PHA-induced T-cell reactivity. A beneficiary effect of early treatment may be limited to men with SI variants and/or p24 antigen.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Production of interleukin-2 by EL4 tumor cells induces natural killer cell- and T-cell-mediated immunity.

Systemic administration of recombinant interleukin (rIL)-2 to cancer patients has met with limited clinical success since, despite significant antitumor effects, its use is associated with severe toxicity. Local production of IL-2 by IL-2 gene transfected tumor cells in murine model systems has been reported to induce specific immunity--devoid of toxicity--to the parental non-IL-2-producing tumor cells. We now report enhanced resistance in nonimmunized mice to murine EL4 thymoma cells, producing murine IL-2 following gene transfer (EL4pIL-2). This effect is mediated by activated natural killer (NK) cells, since we observed the same effect in nude mice but not in NK-depleted mice. Additionally, in mice repeatedly vaccinated with irradiated EL4pIL-2 cells, we observed immunity to challenge with a tumorigenic dose of EL4 cells transfected with a control vector, EL4p. EL4-specific cytotoxic T-lymphocytes (CTLs) were detected in these mice. Mice vaccinated with irradiated EL4p cells were less protected against challenge with a tumorigenic dose of EL4p cells. This study indicates that although some IL-2-producing autologous tumor cells elicit NK-mediated responses and not CTL responses upon inoculation, tumor-specific CTL responses are generated upon repeated vaccinations with these cells. This strategy has potential application for treating a wide variety of cancer patients with autologous IL-2 producing tumor cells.

Animals↗
PubMed1994

Immunological and virological markers determining progression to AIDS.

Infection with the human immunodeficiency virus (HIV-1) results in a severe immunodeficiency characterized by a depletion of CD4+ T-helper cells. Furthermore it is well documented that in asymptomatic persons the number of CD4+ cells is also a good predictor of progression to AIDS. However, persons with similar CD4+ cell counts may differ with regard to clinical progression. For this reason the development of additional markers predictive of disease progression is of major clinical importance. In this review three additional progression markers are discussed: rate of decline of CD4+ cells, T-cell reactivity and HIV biological phenotype. Besides their usefulness as independent progression markers they also provide insight into the immunopathological mechanisms responsible for the final development of AIDS.

Biomarkers↗
PubMed1993

Relation of phenotype evolution of HIV-1 to envelope V2 configuration.

Biological variability of human immunodeficiency virus type-1 (HIV-1) is involved in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Syncytium-inducing (SI) HIV-1 variants emerge in 50 percent of infected individuals during infection, preceding accelerated CD4+ T cell loss and rapid progression to AIDS. The V1 to V2 and V3 region of the viral envelope glycoprotein gp120 contained the major determinants of SI capacity. The configuration of a hypervariable locus in the V2 domain appeared to be predictive for non-SI to SI phenotype conversion. Early prediction of HIV-1 phenotype evolution may be useful for clinical monitoring and treatment of asymptomatic infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS.

OBJECTIVE: To investigate the relation between detection of syncytium-inducing (SI), human immunodeficiency virus type 1 (HIV-1) variants, rate of CD4+ cell decline, and clinical progression. DESIGN: Prospective study during a 2.5-year follow-up period; cohort study with pairwise matched controls. SETTING: The Amsterdam cohort study on the course of HIV-1 infection in homosexual men. PARTICIPANTS: Asymptomatic HIV-1 infected men (n = 225) were tested for the presence of SI variants and were studied prospectively for CD4+ cell decline and clinical progression. In addition, 45 men with a defined moment of appearance of SI variants and 45 matched controls without SI variants were compared for CD4+ cell decline. MEASUREMENTS: Syncytium-inducing variants were detected by cocultivation of peripheral blood mononuclear cells with the MT-2 T-cell line. RESULTS: During a 30-month period, 70.8% of the men with SI variants progressed to AIDS, compared with 15.8% of men without SI variants at entry (P < 0.0001). Multivariable Cox proportional hazard analysis, controlling for CD4+ cell count and HIV-p24 antigenemia, showed a relative hazard for SI variants of 6.7 (95% Cl, 3.5 to 12.7). In the matched control study, before the appearance of SI variants, CD4+ cell counts of 45 men with SI variants and their controls were compared. Syncytium-inducing variants emerged at a mean CD4+ cell count of 0.48 x 10(9)/L(Cl, 0.42 to 0.54), coinciding with the onset of a threefold increased rate of CD4+ cell decline. Men developing AIDS with SI variants had decreased CD4+ cell counts (0.08 x 10(9)/L; 95% Cl, 0.05 to 0.12) at the time of diagnosis compared with persons progressing to AIDS without SI variants (0.25 x 10(9)/L 95% Cl, 0.15 to 0.41) (P = 0.0035]. CONCLUSIONS: The HIV-1 biological phenotype is a practical, binary marker for progression to AIDS, which is independent of decreased CD4+ cell counts and antigenemia. Appearance of SI variants, occurring 2 years before progression to AIDS on the average, is predictive for a significantly increased rate of CD4+ cell decline.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Viral phenotype and T cell reactivity in human immunodeficiency virus type 1-infected asymptomatic men treated with zidovudine.

The effect of zidovudine on disease progression in asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected men (n = 52) in relation to CD4 T cell numbers, T cell reactivity, and HIV-1 biologic phenotype was studied in a double-blind randomized trial over 2 years. CD4+ cell numbers and T cell reactivity did not differ significantly between the zidovudine- and placebo-treated groups, except for a transient improvement of both parameters in the zidovudine-treated group during the first 9 months. A marked differential efficacy of zidovudine was observed depending on the HIV-1 phenotype present. Zidovudine did not prevent the emergence of high-replicating syncytium-inducing (SI) variants, and clinical progression was observed in persons with SI variants despite zidovudine treatment. In contrast to nontreated HIV-1-infected asymptomatic persons, zidovudine-treated men who did not develop SI variants did not progress to AIDS. The beneficial effect of zidovudine during the asymptomatic phase may be mainly limited to persons who do not develop SI variants in the course of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Predictors of rapid progression to AIDS in HIV-1 seroconverters.

OBJECTIVE: To determine whether at the time of HIV-1 seroconversion rapid progressors to AIDS and a low CD4+ count can be distinguished by the clinical presentation of primary HIV-1 infection and serological and immunological characteristics. DESIGN: Prospective cohort study on HIV-1 infection in homosexual men. SETTING: The Municipal Health Service, Amsterdam, The Netherlands. SUBJECTS: One hundred and eight men who seroconverted for HIV-1 during follow-up. MAIN OUTCOME MEASURES: Progression to AIDS and progression to a CD4+ lymphocyte count < 200 x 10(6)/l. RESULTS: Symptomatic primary HIV infection with fever and skin rash, absence of anti-HIV core and transient HIV p24 antigenemia were independent predictors of progression to AIDS at the time of HIV-1 seroconversion. A low CD4+ count immediately after seroconversion and the calendar year were independent predictors of progression to a low CD4+ count at the time of HIV-1 seroconversion. CONCLUSIONS: Even in the earliest stage of HIV-1 infection a small group of individuals at high risk for rapid progression to AIDS can be recognized by the clinical presentation of primary HIV infection, the presence of HIV p24 antigenaemia and the absence of a serological response to HIV core protein.

Acquired Immunodeficiency Syndrome↗
PubMed1992

HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay.

OBJECTIVE: We have previously demonstrated that detection of syncytium-inducing (SI) HIV-1 in asymptomatic seropositive individuals is associated with rapid progression to AIDS. In the present study, we sought to develop and evaluate an HIV-1 phenotyping assay for the screening of large numbers of individuals. METHODS: Efficiency of HIV-1 isolation from patient peripheral blood mononuclear cells (PBMC) was studied with donor PBMC or seven different CD4+ T-cell lines as target cells. The biological phenotype of sequential isolates from 20 long-term asymptomatic HIV-1-seropositive individuals was determined by two different assays. RESULTS: Non-SI isolates, efficiently recovered by cocultivation with donor PBMC, were never isolated with T-cell lines as target cells. Direct cocultivation with MT-2 cells, but not with six other CD4+ T-cells, resulted in the efficient recovery of SI isolates. HIV-1 MT-2 tropism and SI capacity were shown to be coupled properties at the clonal level. SI isolates emerged in 10 out of 20 longitudinally-studied individuals. In these long-term infected individuals, appearance of SI isolates was associated with progression to AIDS. CONCLUSIONS: Direct cocultivation of patient PBMC with the MT-2 cell line is a sensitive, specific and convenient method to detect SI isolates. The availability of an assay suitable for the screening of large groups allows further study of the value of HIV-1 biological phenotyping as a prognostic marker.

Acquired Immunodeficiency Syndrome↗
PubMed1992

HIV-1 biological phenotype and the development of zidovudine resistance in relation to disease progression in asymptomatic individuals during treatment.

OBJECTIVE: To determine which parameters are associated with clinical progression during zidovudine treatment of asymptomatic HIV-1-infected individuals. METHODS: Twenty-four initially asymptomatic HIV-1-infected individuals were treated with zidovudine and followed until the development of AIDS or for approximately 3 years. HIV-1 phenotype was determined by cocultivation of patient cells with donor lymphocytes, and by a new assay of direct cocultivation with MT-2 cells. Specific mutations in the HIV-1 reverse transcriptase (RT) gene conferring resistance to zidovudine were detected using a selective polymerase chain reaction. RESULTS: Progression to AIDS was more rapid in individuals harbouring syncytium-inducing (SI) viral isolates or showing a conversion from non-syncytium-inducing (NSI) to SI viral isolates. One out of 20 patients who spent a total of 559 months harbouring an NSI phenotype progressed to AIDS, whereas eight out of 12 patients who spent a total of 223 months harbouring an SI phenotype progressed to AIDS (P < 0.001). There was no significant difference between SI and non-SI isolates in the frequency of five mutations causing zidovudine resistance. However, all SI isolates obtained after 2 years of treatment contained mutations in codons 41 and 215 of the RT gene, whereas only five out of 11 (45%) NSI isolates obtained at that time had this combination of mutations. CONCLUSIONS: Conversion to the SI phenotype cannot be prevented by zidovudine treatment. The presence or appearance of an SI virus heralded disease progression in zidovudine-treated individuals. Further research is required to investigate the relationship between virus phenotype and development of zidovudine resistance.

Cytopathogenic Effect, Viral↗
PubMed1992

Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population.

The composition of human immunodeficiency virus type 1 (HIV-1) clonal populations at different stages of infection and in different compartments was analyzed. Biological HIV-1 clones were obtained by primary isolation from patient peripheral blood mononuclear cells under limiting dilution conditions, with either blood donor peripheral blood lymphocytes or monocyte-derived macrophages (MDM) as target cells, and the biological phenotype of the clones was analyzed. In asymptomatic individuals, low frequencies of HIV-1 clones were observed. These clones were non-syncytium inducing and preferentially monocytotropic. In individuals progressing to disease, a 100-fold increase in frequencies of productively HIV-1-infected cells was observed as a result of a selective expansion of nonmonocytotropic clones. In a person progressing to AIDS within 19 months after infection, only syncytium-inducing clones were detected, shifting from MDM-tropic to non-MDM-tropic over time. From his virus donor, a patient with wasting syndrome, only syncytium-inducing clones, mostly non-MDM-tropic, were recovered. Parallel clonal analysis of HIV-1 populations in cells present in bronchoalveolar lavage fluid and peripheral blood from an AIDS patient revealed a qualitatively and quantitatively more monocytotropic virus population in the lung compartment than in peripheral blood at the same time point. These findings indicate that monocytotropic HIV-1 clones, probably generated in the tissues, are responsible for the persistence of HIV-1 infection and that progression of HIV-1 infection is associated with a selective increase of T-cell-tropic, nonmonocytotropic HIV-1 variants in peripheral blood.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Comparative observations of fever and associated clinical, haematological and blood biochemical changes after parenteral administration of poly I: poly C, interferon-alpha 2a and Escherichia coli endotoxin in goats.

The present report describes a comparative study in dwarf goats on human IFN-alpha 2a (0.5 x 10(6) IU kg-1 body weight IM), poly I: poly C (an interferon inducer; 30 micrograms kg-1 b.w. IV), and Escherichia coli endotoxin (an I1-1 inducer; 0.1 micrograms kg-1 b.w. IV). Although IFNs are considered to be species specific, human IFN-alpha 2a was very potent in dwarf goats. All 3 stimuli induced the 'acute phase response'. Among the varied physiological alterations, which together produce this response, are fever and depression, inhibition of gastric function, tachycardia, a decrease in serum alkaline phosphatase activity, leukopenia, lymphopenia and neutropenia followed by neutrophilic leukocytosis, hypoferraemia and hypozincaemia. The results suggest that, apart from I1-1, IFN-alpha also seems to mediate the systemic 'acute phase response' to certain exogenous stimuli.

Animals↗
PubMed1989

Appetite-modulating drugs in dwarf goats, with special emphasis on benzodiazepine-induced hyperphagia and its antagonism by flumazenil and RO 15-3505.

In dwarf goats fasted for 2 h, i.v. administration of the benzodiazepine (BZ) agonists diazepam (60 micrograms/kg), brotizolam (2 and 4 micrograms/kg) and climazolam (100 micrograms/kg) induced hyperphagic effects, whereas i.v. injections of the BZ-antagonist flumazenil (R degrees 15-1788; 0.5 mg/kg), the anthelmintic ivermectin (0.1 mg/kg), the 5-HT2 antagonist ritanserine (0.1 mg/kg), ACTH (10 micrograms/kg) and prednisolone (1 mg/kg) were inactive in a 30-min feeding test. Both the BZ-antagonist R degrees 15-3505 (greater than or equal to 0.1 mg/kg) and the opiate receptor antagonist naloxone (0.1 mg/kg) had anorectic effects in dwarf goats given 30 min access to a palatable pelleted concentrate. The hyperphagic effects of climazolam and brotizolam were not antagonized by flumazenil, whereas similar doses of this drug completely reversed muscle incoordination and ataxia induced by much higher doses of these BZ-agonists. In the combination experiments with naloxone and BZ-agonists, naloxone antagonized the hyperphagic effects of both diazepam and brotizolam. Similarly, in the diazepam-R degrees 15-3505 study, there was a significant effect of diazepam and a significant inhibition of this effect by R degrees 15-3505 (50 micrograms/kg). In the diazepam-ivermectin combination experiment no evidence for drug potentiation was found. These results and the mode of action of the above mentioned drugs are discussed in relation to feeding behaviour.

Animals↗
PubMed1987

Two domains within the early coding region of SV40 involved in the transformation of human fibroblasts.

The early gene products of simian virus 40 (SV40) transform human fibroblasts, whereas those of the human papovavirus BK (BKV) do not. The early gene products of both SV40 and BKV transform baby rat kidney cells. SV40-BKV chimerics were constructed which were able to transform baby rat kidney cells. Using the SV40-BKV chimerics, two domains within the SV40 large T protein were identified which are involved in the transformation of human fibroblasts.

Animals↗