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Biomedical subjects

M Gompels

Publications and source records attributed to M Gompels.

At least 19 recordsLinked to original sources
PubMed1998

Increase in dendritic cell numbers, their function and the proportion uninfected during AZT therapy.

The effects of AZT treatment on the numbers, level of infection and function of peripheral blood dendritic cells (DC) were examined in patients with HIV infection. This was a cross-sectional study of patients before AZT treatment and up to 20 months after initiation of treatment. Numbers of DC separated by density gradients were below the normal range in patients before treatment, but increased between 3 and 12 months of treatment. The numbers of DC per provirus copy rose from around 100 cells to 5000 cells and this decrease in viral load in DC was significant between 3 and 20 months of treatment. The capacity of DC to stimulate allogeneic T cell proliferation was low before treatment and significantly higher between 6 and 12 months after the start of AZT. This study indicated that AZT treatment produced beneficial effects on DC by increasing their numbers, reducing the provirus load and increasing their function in stimulating T cells. These results support the thesis that the function of these potent antigen-presenting cells is important in development of immunological defects in AIDS, and that effects of AZT treatment on DC may provide a measure of its therapeutic effect.

Anti-HIV Agents↗
PubMed1998

Serum kynurenine-to-tryptophan ratio increases with progressive disease in HIV-infected patients.

An alternative pathway of Trp metabolism involves the conversion of Trp to kynurenine by indoleamine-2,3-dioxygenase, which leads to synthesis of the neurotoxin, quinolinic acid. This study explores the relationship of indoleamine-2,3-dioxygenase activity with stages of HIV infection. Sera from 206 HIV-positive and 72 seronegative subjects were analyzed for Trp and kynurenine. The kynurenine-to-Trp (KT) ratio was calculated. The mean KT ratio of seronegative controls was 36.6 +/- 10.9, and the median ratio was 34.9. The upper limit of the seronegative KT ratio, defined as mean + 2 SD, was 58.4. Patients with HIV infection showed a reciprocal relationship between the KT ratio, the CD4 count, and the stage of the disease. The median KT ratios for asymptomatic and AIDS patients were 50.5 and 117.0, respectively. This study shows that the serum Trp concentration is markedly decreased and that the kynurenine concentration is increased with immune stimulation in HIV infection. This may lead to changes in quinolinic acid and explain some of the pathogenesis of AIDS dementia.

AIDS Dementia Complex↗
PubMed1994

Dendritic cells from HIV-1 infected individuals show reduced capacity to stimulate autologous T-cell proliferation.

Dendritic cells (DC) exposed for a short period of time (1 day) in vitro to HIV infection caused stimulation of autologous T-cells, but those exposed for a longer period (3 days) before addition to T-cells stimulate little or no proliferation [1]. Since a proportion of DC from patients who are HIV-1 seropositive is infected with HIV-1 [2] we used the same culture system to test the level of ongoing stimulation of autologous T-cells by DC. The DC from patients with HIV-1 infection showed no enhanced stimulation of autologous T-cells; they produced significantly lower levels of proliferation than those induced by DC from normal controls or from high risk seronegative individuals. However, DC stimulated production of antibodies to gp120 and p24 in cultures containing autologous B plus T-cell in the absence of any added exogenous antigens as previously described [3]. DC in asymptomatic individuals thus appear to be fuelling antibody production but not T-cell proliferation. The results suggest that a failure by DC to stimulate T-cell proliferation either to HIV-1 or to other environmental antigens may be involved in the failure of cell-mediated responses in HIV infection.

Cells, Cultured↗
PubMed1994

Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS.

The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposi's sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposi's sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1994

Dendritic cells persistently stimulate antibody responses to HIV in seropositive individuals.

OBJECTIVES: B-cell hyperactivity and hypergammaglobulinaemia with high levels of HIV-1-specific antibody occur during HIV-1 infection. We investigated the role played by antigen-presenting cells (APC) in the ongoing production of antibody. METHODS: Adherent monocytes and non-adherent low density dendritic cells were enriched from peripheral blood of patients at different stages of HIV-1 infection (Centers for Disease Control and Prevention categories II, III and IV) and from control subjects at high or low risk of HIV infection. Different concentrations of lymphocytes were cultured in 20 ml hanging drops in the presence or absence of autologous dendritic cells or monocytes. Antibodies to p24 and gp120 were assessed by enzyme-linked immunosorbent assay. RESULTS: Lymphocytes taken from asymptomatic HIV-1-seropositive subjects and depleted of APC produced low or moderate levels of antibody to gp120 or p24 in vitro. However, adding back autologous dendritic cells significantly enhanced antibody production, although fewer samples showed responses to p24 than to gp120. Less antibody production was stimulated using cells from patients with persistent generalized lymphadenopathy, or if monocytes rather than dendritic cells were added back. Little or no antibody was produced by cells from patients with AIDS and no antibody was detected in cultures of cells from seronegative individuals with low or high risk for infection. CONCLUSIONS: The evidence suggests that ongoing humoral responses to HIV-1 are fuelled by dendritic cells. Thus, the dominance of humoral over cell-mediated responses in HIV-1 infection may depend upon signalling via dendritic cells. Changes in signalling by dendritic cells could be central to the immunologic features of HIV-1 infection.

Antibody Formation↗
PubMed1993

Double-staining artefact observed in certain individuals during dual-colour immunophenotyping of lymphocytes by flow cytometry.

An unusual double-staining artefact has been repeatedly observed in certain individuals (both HIV-positive and healthy laboratory controls) during 2-colour immunophenotyping of lymphocytes by flow cytometry after red cell lysis. This artefact can falsely suggest co-expression of CD4 and CD8, as well as some of the other monoclonal antibody pairs commonly used in the typing of lymphocytes. It is caused by a serum factor associated with the ammonium-sulphate-precipitated and gamma-globulin fractions. It appears to be fairly common in the population (being found in 6 out of 105 of our healthy laboratory controls and in 42 out of 247 of our HIV-1 seropositive subjects); it may be genetically determined, but may be acquired in some. It is a potential source of error in lymphocyte immunophenotyping, which can be avoided by simple adjustments to the recommended techniques.

Antibodies, Monoclonal↗
PubMed1992

The effect of the temperature and duration of sample storage on the measurement of lymphocyte subpopulations from HIV-1-positive and control subjects.

EDTA-anticoagulated blood samples from 19 HIV-1-positive subjects and 13 healthy laboratory worker controls were analysed for three lymphocyte subpopulations (CD3, CD4, CD8 T cells) (lysed whole blood method, Becton Dickinson FACScan flow cytometer) at 0, 24, 48, 72 and 96 h after venesection, having been stored at either 4 degrees C, 12 degrees C, 16 degrees C or 21 degrees C. In samples stored at 4 degrees C and 12 degrees C there was a significant fall in both %CD3 and %CD 4, and a significant rise in %CD8. At 16 degrees C the %CD8 remained stable, while there were marginal rises in %CD3 and %CD4. At 21 degrees C, the %CD8 again remained stable, while %CD3 and %CD4 rose significantly with time. These trends were independent of HIV-1 status. At each temperature studied, the rates of change of lymphocyte subpopulations were independent of each other. These results suggest that a temperature range of 14-16 degrees C may be optimal for sample storage prior to measurement of T cell subsets. They emphasise the importance of strict control on conditions if samples are to be kept for any length of time before analysis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

T-cell receptor variable gene products and early HIV-1 infection.

To assess the hypothesis that the human immunodeficiency virus (HIV) might mimic major histocompatibility complex (MHC) allodeterminants and interact with T-cell receptors (TCRs) of alloreactive T-cells, we have done a preliminary analysis of the range of alpha beta TCR gene products in 16 HIV-1-seropositive individuals with normal CD4 counts and in 16 healthy HIV-1-negative controls. Using a panel of monoclonal antibodies with a two-colour direct immunofluorescence method, we found a significant increase in the expression of the V beta 5.3 subfamily in the HIV-positive patient group compared with controls (p less than 0.01). Selected increase in expression of V beta sequences has been described in various autoimmune conditions and our findings raise the possibility that the immunopathological damage from HIV infection may be due to the induction of autoreactivity. If HIV does mimic MHC II, the normal immune response to the virus could represent an autoimmune process similar to graft-versus-host disease.

Gene Expression↗
PubMed1992

A study of neuropathy in HIV infection.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

AIDS-Related Opportunistic Infections↗
PubMed1992

Antigen-presentation by macrophages but not by dendritic cells in human immunodeficiency virus (HIV) infection.

Dendritic cells (DC) have a potent antigen-presenting capacity for recruiting resting T cells into immune responses. They also promote expansion of already activated memory T cells. By contrast, macrophages (M phi) are only effective in stimulating memory responses. Infection and depletion of DC occur in human immunodeficiency virus (HIV)-infected individuals and recruitment of T cells into primary responses is blocked. Here comparisons between DC and M phi in stimulating secondary T-cell responses in HIV infection were made. Adherent M phi, and DC isolated by a new method, were separated from peripheral blood of patients in different stages of HIV infection and from uninfected controls and added to allogeneic lymphocytes in mixed leucocyte reactions (MLR). Some were pulsed with influenza virus or tetanus toxoid and used to stimulate autologous T cells. Responses were measured from uptake of [3H]thymidine in 20 microliters hanging drop cultures. DC, but not M phi, from normal individuals stimulated MLR but both populations stimulated secondary responses to recall antigens. DC from all HIV seropositive individuals caused little or no stimulation of any lymphocyte responses. However, M phi from HIV seropositive asymptomatic individuals and those with persistent generalized lymphadenopathy stimulated responses to recall antigens. There was no stimulation using cells from acquired immune deficiency syndrome (AIDS) patients. Blocked DC but not M phi function may underlie progressive immunological non-responsiveness in HIV infection. Without recruitment of resting T cells, loss of memory T cells may be cumulative; failure of secondary activation (e.g. by M phi) would lead to lost T-cell activity. Identification and circumvention of the defect in DC could offer new therapeutic approaches.

Antigen-Presenting Cells↗
PubMed1991

Disseminated pneumocystis carinii infection in AIDS.

Eight patients with AIDS and Pneumocystis carinii infection were studied. Protean manifestations were a feature not untypical of disseminated pneumocystosis. Aerosolised pentamidine as prophylaxis against P carinii pneumonia was ineffective at suppressing dissemination. The knowledge that extrapulmonary infection can occur has implications for the detection and treatment of, and prophylaxis against, P carinii infection. The survival of patients with disseminated pneumocystosis is particularly poor, and may be due to a lack of clinical awareness and consequent delay in diagnosis.

Acquired Immunodeficiency Syndrome↗