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Biomedical subjects

M T Roos

Publications and source records attributed to M T Roos.

At least 19 recordsLinked to original sources
PubMed1996

Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue syndrome.

Whether immunologic abnormalities correlate with fatigue severity and functional impairment in chronic fatigue syndrome (CFS) was investigated. Blood mononuclear cells were immunophenotyped and circulating ex vivo-produced cytokines were measured in 76 CFS patients and 69 healthy matched controls. Expression of CD11b on CD8 cells was significantly decreased in CFS patients. However, the previously reported increased expression of CD38 and HLA-DR was not confirmed. There was no obvious difference in apoptosis in leukocyte cultures, circulating cytokines, and ex vivo production of interleukin (IL)-1 alpha and IL-1 receptor antagonist. Endotoxin-stimulated ex vivo production of tumor necrosis factor-alpha and IL-beta was significantly lower in CFS. The immunologic test results did not correlate with fatigue severity or psychologic well-being was measured by Checklist Individual Strength, Beck Depression Inventory, and Sickness Impact Profile. Thus, these immunologic tests cannot be used as diagnostic tools in individual CFS patients.

ADP-ribosyl Cyclase↗
PubMed1995

T cell function in vitro is an independent progression marker for AIDS in human immunodeficiency virus-infected asymptomatic subjects.

The predictive value of low T cell reactivity to CD3 monoclonal antibodies for development of AIDS was evaluated and compared with low CD4+ cell numbers and the presence of syncytium-inducing human immunodeficiency virus (HIV) variants in 122 seropositive asymptomatic homosexual men for 4.5 years. Low T cell reactivity was a strong predictor for progression to AIDS in a multivariate proportional hazards analysis using these markers as covariates at entry and as time-dependent covariates. The combination of the three markers was associated with development of AIDS in 6 of 7 men within 15 months. In contrast, the group that lacked any of these markers had a very low risk (11%) for developing AIDS. In groups with one or two of these three markers, progression rates were 33% and 66%, respectively. These data demonstrate that measurement of T cell function in vitro is of value for staging of HIV infection and may be useful for monitoring therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Immunologic and virologic markers determining progression to AIDS.

Infection with the human immunodeficiency virus type 1 (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 provided insight into immunopathologic mechanisms responsible for the eventual development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Relationship between patterns of engraftment in peripheral blood and immune reconstitution after allogeneic bone marrow transplantation for (severe) combined immunodeficiency.

We report the outcome of allogeneic bone marrow transplantation (BMT) as treatment for severe combined immunodeficiency disease (SCID) in 31 patients grafted from 1968 until 1992. The patients received a graft from an HLA-identical related (n = 10), an HLA-haplo-identical related (n = 19), or a closely HLA-matched unrelated (n = 2) donor that resulted in the long-term survival of 6 of 10, 9 of 19, and 0 of 2 children, respectively. Major complications included failure of engraftment and early death caused by respiratory failure. The chimerism pattern and immunologic reconstitution were evaluated in 15 children who survived more than 1 year with sustained engraftment. The pattern of engraftment was investigated within flow-sorted peripheral blood (PB) T- and B-lymphoid, natural killer (NK), and myelomonocytic cell populations using the amplification of variable number of tandem repeats by the polymerase chain reaction. The immunologic reconstitution was assessed by various in vitro and in vivo parameters. Although the number of PB T cells and the in vitro T-cell proliferative response was in the lower region of normal in the majority of cases and even subnormal in some, in all cases donor T-cell engraftment and reconstitution of T-cell immunity was observed. Residual host-type T cells (1% to 5%) were detected in eight cases at multiple occasions. All children showed normal serum IgM and IgG subclass levels and produced specific IgG antibodies after vaccination, irrespective of donor B-cell engraftment. However, three HLA haplo-identical graft recipients with host-type B lymphoid and myeloid cells have a persistent selective IgA deficiency. NK cells were either of donor, host, or mixed origin. Donor NK cell engraftment restored defective in vitro NK cell function of the recipient. We conclude that determination of lineage-specific engraftment patterns provides valuable information for the understanding of the immunologic reconstitution after allogeneic BMT for SCID.

Antibody Formation↗
PubMed1994

Viro-immunological studies in acute HIV-1 infection.

OBJECTIVE: To monitor a patient who presented with symptomatic HIV-1 infection for virological and immunological parameters in relation to the clinical course. METHODS: Virological studies included determination of frequency of productively HIV-1-infected peripheral blood mononuclear cells (PBMC) and viral RNA load in plasma and p24 antigenaemia. Immunological studies included the analysis of T-cell subsets, the expression of activation markers, CD45RO and CD45RA antigens, the frequency of cells programmed for death, and T-cell function. RESULTS: During the first week post onset of primary HIV-1 infection symptoms high plasma titres of p24 and HIV-1 RNA were observed. The number of productively HIV-1-infected PBMC peaked, coinciding with CD4+ T lymphocytopaenia, during week 2 when clinical improvement started. CD8+ T lymphocytosis was observed 10 days post onset of clinical symptoms, the expanded cell population being of the CD8+CD38+, CD8+CD27+ and CD8+CD28- phenotype. CD8+ T lymphocytosis was paralleled by a high percentage of cells undergoing programmed cell death on in vitro culture. In vitro T-cell function was severely depressed during the first 10 days post onset of clinical symptoms. Within about 3 weeks, following resolution of clinical symptoms, phytohaemagglutinin-induced proliferation was restored to normal levels while responses to the CD3 monoclonal antibody only showed a partial restoration. During follow-up, concomitant with the rise of activated CD8+ T cells, p24 antigen levels and viral RNA load in serum as well as the number of HIV-producing PBMC steeply declined after 2 weeks. CONCLUSION: These findings demonstrate HIV-1-induced abnormalities during severe clinical symptoms of primary HIV-1 infection. The subsequent strong immune response, which is believed to be responsible for efficient control of viral replication, appears to precede clinical improvement.

Acquired Immunodeficiency Syndrome↗
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

Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease.

Programmed death of T cells has been proposed as one of the mechanisms by which HIV affects immune functions in stages of infection where the number of infected cells is low. Indeed, in HIV-infected individuals both CD4+ and CD8+ T cells are primed for programmed cell death, which can be enhanced by polyclonal stimulation. Here, we investigated programmed death of T cells in all stages of HIV infection, including acute infection. In individuals with primary infection the number of T cells dying due to apoptosis was much higher than in the asymptomatic phase of infection and paralleled increased numbers of CD8+ cells. In asymptomatic HIV-infected individuals, cells were dying in increased percentages compared with noninfected controls, although at much lower numbers than during acute infection. Death of T cells was not quantitatively correlated with CD4+ T cell numbers or appearance of more cytopathic, syncytium-inducing HIV variants. Analysis of the phenotype of cells undergoing apoptosis revealed that cell death was not confined to a specific T cell subset nor correlated with expression of certain T cell activation markers. Our results imply that the extent of programmed cell death of T cells in HIV infection does not correlate with progression to disease.

Antigen-Presenting Cells↗
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

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

Cervical HPV infection among HIV-infected prostitutes addicted to hard drugs.

An investigation into the prevalence of human papilloma virus (HPV) infection, abnormal cervical cytology and the relationship between HIV- and HPV infection was done in a group of intravenously (IV) and non-IV drug-using prostitutes. From July 1991 through May 1992, hard drug-addicted prostitutes attending a sexually-transmitted-disease (STD) clinic in Amsterdam were recruited. A questionnaire was administered to obtain demographic characteristics, and medical and STD history. Apart from routine STD examination, cervical scrapes for cytology and samples for HPV DNA detection by polymerase chain reaction (PCR) were collected. Some of the women included in this study also participated in HIV studies among drug users. Their data on HIV- and immunologic status could be combined. A total of 121 women entered the study; 25 women were HIV-seropositive, 44 women were HIV-negative, and the HIV status of 52 women was unknown. All 25 HIV-positive women had normal Pap smears, two of the 44 HIV-negative women had a Pap smear III A, and in the HIV-unknown group, two women with Pap III A and one with Pap III B were found. Eight of the 25 (32%) HIV-positive women were HPV DNA-positive, three of the 44 (7%) HIV-negative women and 10/52 (19%) of the HIV-unknown group. Logistic regression analysis showed that in the total group, presence or cervical HPV DNA was associated with HIV infection (order ratio [OR] for HIV-positives 7.8, 95% confidence interval [CI] 1.8 to 34.6) and with diagnosis of condylomata acuminata at entry to the study (OR 7.5, 95% CI 1.5 to 36.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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

Use of competitive polymerase chain reaction to determine HIV-1 levels in response to antiviral treatments.

OBJECTIVE: To develop a competitive polymerase chain reaction technique with which to evaluate the usefulness of HIV-1 level as a marker of response to antiviral treatment. DESIGN: HIV-1 sequences were assessed by competitive polymerase chain reaction in four subjects participating in a double-blind study of monotherapy versus combination therapy with nucleoside analogues. METHODS: We inserted a mutant construct of the HIV-1 pol sequence into a commercial vector, enabling us to generate known amounts of mutant DNA and RNA for competitive polymerase chain reaction. To measure HIV-1 DNA copies in cells, the mutant DNA fragments were allowed to compete in a 10-fold dilution series with a constant amount of nucleic acid from the subject. To measure HIV-1 RNA copies in plasma, in vitro synthesized mutant RNA was added in a 10-fold dilution series to a constant amount of subject RNA and copy DNA was synthesized. DNA and copy DNA were used as the input for nested pol polymerase chain reaction. Mutant and wild-type amplimers were discriminated by size. RESULTS: The competitive polymerase chain reaction technique has been validated in model experiments and can be used over a broad range (at least 6 logs) of levels. Three of the four subjects showed a decline of 1 log in proviral DNA levels in cells after beginning antiviral treatment. All four showed a decline of at least 1 log in viral RNA levels in plasma, but this decline was transient in one subject. CONCLUSION: The HIV-1 sequence level is a useful marker in antiviral treatment studies.

Antiviral Agents↗
PubMed1992

A combined immunodeficiency with oligoclonal CD8+, V beta 3-expressing, cytotoxic T lymphocytes in the peripheral blood.

The diagnosis severe combined immunodeficiency was made in a male infant at the age of 18 wk. Known causes of severe combined immunodeficiency were excluded. The activity of total 5'-nucleotidase (E.C. 3.1.3.5) in the PBMC was found to be strongly decreased. Analysis of the peripheral blood revealed a lymphocytosis, mainly of CD8+ T cells. These lymphocytes expressed high levels of CD29, CD38, CD45RA, and MHC class II molecules but no CD25, CD26, CD27, or CD28 Ag. The cells proliferated poorly to all T cell stimulants tested and no helper activity for IgM secretion could be induced. In contrast to the poor proliferative responses, high levels of TCR-induced cytolytic activity, without lymphokine-activated killer-cell outgrowth, were induced by CD3 mAb. Analysis of TCR-beta gene rearrangements indicated that two clonal populations constituted the majority of the E-rosette+ peripheral blood fraction. Moreover, the vast majority of the CD8+ cells were found to react with a mAb to V beta 3. Polymerase chain reaction on cDNA from peripheral blood cells with primers that amplify TCR V beta elements showed, in agreement with the fluorescence data, an overrepresentation of V beta 3 but absence of usage of approximately 50% of the other V beta elements. Thus, in a severe combined immunodeficiency patient, CD8+ T cells with limited T cell receptor usage and restricted effector functions were found. The observed alterations in the 5'-nucleotidase levels may be secondary to the outgrowth of this population.

5'-Nucleotidase↗
PubMed1992

Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection.

Nineteen individuals were studied for virologic and immunologic events during primary human immunodeficiency virus type 1 (HIV-1) infection. In 16 individuals only non-syncytium-inducing (NSI) isolates were detected; syncytium-inducing (SI) isolates were obtained from 3. Studies of transmitter-recipient pairs indicated that both NSI variants and SI variants were transmitted and that SI variants may be suppressed in the recipient. CD4+ T cells remained in the normal range in 15 of 16 individuals with NSI isolates but rapidly declined in all 3 individuals with SI variants, 1 of whom was treated with zidovudine. The most marked increase in CD8+ T cells and activated CD8+ T cells was observed in individuals with the most pronounced clinical signs of acute HIV-1 infection. Activated CD8+ T cells were only transiently elevated in individuals with SI variants, suggesting that an impaired cellular anti-HIV-1 immune response plays a role in the rapid progression to AIDS.

CD4-Positive T-Lymphocytes↗
PubMed1992

Concordance of human immunodeficiency virus detection by polymerase chain reaction and by serologic assays in a Dutch cohort of seronegative homosexual men.

In three subgroups of a clinically and socially well defined group of Dutch homosexual men, the prevalence of human immunodeficiency virus type 1 (HIV-1) sequences in seronegative blood samples was studied using the polymerase chain reaction (PCR). In 19 seronegative partners of seropositive persons, no HIV-1 sequences were found by PCR in either early (1984/1985) or more recent (1987) samples. In 42 seronegative persons selected by their high risk for HIV-1 infection, none harbored HIV-1 sequences in either early (1985/1986) or late (1989) samples. In 15 people who seroconverted for HIV-1, only 2 samples collected 3 months before seroconversion were PCR-positive. These persons were also HIV antigen-positive at this time. These data suggest that a latent infection greater than 6 months does not occur and that the combination of HIV antibody and HIV antigen tests is appropriate and conclusive in most cases of HIV-1 infection.

Base Sequence↗