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W Solbach

Publications and source records attributed to W Solbach.

86 records · Page 5Linked to original sources
PubMed1984

Dissociation of helper/inducer T-cell functions: immunodeficiency associated with mycobacterial histiocytosis.

Mycobacterial histiocytosis is a generally fatal disease characterized by abundant amounts of undigested atypical mycobacteria present within tissue macrophages that diffusely infiltrate the affected lymph nodes. The immune functions of a 22-year-old man with infection due to Mycobacterium avium were investigated. Although the patient had a marked increase in serum immunoglobulin levels and detectable antibodies toward mycobacterial antigens, he had no cellular response to these antigens both in vivo and in vitro. There was an elevated proportion of blood cells with the helper/inducer (T4+) phenotype, but these cells showed a markedly decreased response to several T-cell mitogens, as well as to autologous and allogeneic cells. The patient's lymphocytes produced diminished amounts of immune interferon, and there was no detectable interleukin 2 (IL-2) activity after stimulation with phytohemagglutinin (PHA). The proliferative response of T4+ cells to pokeweed mitogen (PWM), however, was normal; 47% of these cells bore the Tac antigen, and the production of IL-2 using PWM was within the normal range. No phenotypical or functional abnormalities were found in peripheral blood monocytes. These findings suggest a dissociation of helper/inducer T-cell functions with intact B-cell help, but an impaired ability to activate tissue macrophages or to produce immune mediators.

Adult↗
PubMed1984

Frequency analysis of cyclosporine-sensitive cytotoxic T lymphocyte precursors.

The influence of the immunosuppressant cyclosporine (CsA) on the antigen-driven activation of resting cytotoxic T lymphocyte precursors (CTL-p) and on the reactivation of mixed-lymphocyte-reaction-primed CTL, is analyzed at the clonal level. Using the limiting-dilution culture approach, we show that the majority (60-90%) of clones of CTL-p with specificity for given antigens are not activated in the presence of CsA; a minority (10-40%) of CTL-p are CsA-resistant. This is so for alloantigen-reactive CTL-p and major-histocompatibility-complex-restricted CTL-p with hapten specificity. In contrast, the frequency of CTL grown out of primed mixed lymphocyte culture cells is not influenced by CsA. Although CsA does not interfere with the short-term growth of I1-2-driven activated T cells, it may influence the expression of their cytolytic potential.

Animals↗
PubMed1984

Growth, interleukin-2 production, and responsiveness to IL-2 in T4-positive T Lymphocyte populations from malignant cutaneous T cell lymphoma (Sézary's syndrome): the effect of cyclosporin A.

Functional analysis and surface phenotyping using monoclonal antibodies have revealed that malignant T lymphocyte populations in the peripheral blood of patients with Sézary's syndrome resemble the T helper cell populations from normal individuals. In this article we have studied the effects of the immunosuppressive drug cyclosporine A (CsA) on growth, interleukin-2 (IL-2) production, and the induction of IL-2 responsiveness of peripheral blood monocytes (PBMs) from five patients with Sézary's syndrome in vitro, using the lectin phytohemagglutinin (PHA) and the phorbol ester phorbol myristate acetate (PMA) as stimuli. The following results were obtained: PHA-induced cell proliferation was significantly more sensitive to inhibition by CsA than that induced by PMA or a combination of PMA and PHA (P less than .005). Sézary PBMs produced only small amounts of IL-2 in response to PHA. Stimulation with PMA, however, resulted in significant IL-2 production. PMA and PHA, when given in combination, acted synergistically. The low levels of IL-2 production induced by PHA or PMA were more sensitive to CsA-mediated suppression than those induced by a combination of PHA and PMA (75% and 55% suppression, respectively). CsA-mediated growth suppression could be overcome if the cultures were supplemented with appropriate amounts of exogenous IL-2. We conclude from our data, that CsA in Sézary PBMs inhibits T cell growth indirectly as a consequence of suppression of IL-2 growth indirectly as a consequence of suppression of IL-2 production. Moreover, like normal T lymphocytes, Sézary PBMs do not express the IL-2 receptor spontaneously, but can be induced to do so. CsA does not interfere with intracellular events leading to the expression and the biologic function of the IL-2 receptor.

Cyclosporins↗
PubMed1984

Interleukin-2 production in peripheral blood mononuclear cells of patients with gastrointestinal tumors.

Peripheral blood mononuclear cells of patients with different tumors of the gastrointestinal tract (esophagus, stomach, colon, rectum), with Crohn's disease and healthy controls were analyzed for their capacity to produce mitogen induced interleukin-2 (I1-2). Tumor patients could be divided into two groups, one group exhibiting a nearly normal and a second group showing a significantly decreased production of I1-2. Most of the patients with a carcinoma of the colon were found in the low-producer group. Patients with Crohn's disease did not significantly differ from the relevant controls. Tumor patients with proven metastasis produced less I1-2 as compared to those with localized disease although the differences are not significant. When I1-2 containing supernatants of patients with tumors were additionally analyzed for the presence of prostaglandin E2, an inverse relationship could be demonstrated. Supernatants showing a suppressed activity of I1-2 exhibited increased amounts of PGE2, indicating a modulation of I1-2 production by prostaglandin E2.

Adolescent↗
PubMed1982

Tumor-promoting phorbol esters selectively abrogate the expression of the T4 differentiation antigen expressed on normal and malignant (Sézary) T helper lymphocytes.

12-O-tetradecanoylphorbol-13-acetate (TPA) selectively abrogates, in nanomolar concentrations, the expression of the T4 differentiation antigen, as defined by the monoclonal anti-T4 antibody (1) on Il-2-producing T helper lymphocytes from normal donors and on T helper lymphocytes from a patient with malignant T cell lymphoma (Sézary's syndrome); this compound does not affect the expression of cell surface antigens as defined by the antibodies anti-OKT3, -T6, -T8, -T11, Ia, or anti-surface immunoglobulin. Abrogation of the T4 antigen expression is concentration dependent, completed within 8 h of incubation at 37 degrees C, does not occur at 4 degrees C, and is reversible. Only those phorbol-esters known to have tumor-promoting activity in vivo (2) affect the T4 antigen, whereas nonpromoting compounds are ineffective.

Antibodies, Monoclonal↗
PubMed1982

Interactions of human T cell subsets during the induction of cytotoxic T lymphocytes: the role of interleukins.

In this work we study the role of subsets of human T cells, detectable by the OKT series of monoclonal antibodies, in the production of and the response to the lymphokine interleukin-2 (Il-2) during the course of an allogeneic cytotoxic T lymphocyte response in vitro. The results obtained establish that the Il-2 producer cells reside within the OKT4 positive T cell subset. Once produced, Il-2 mediates the clonal expansion of alloantigen-activated cytotoxic T killer cells which reside in the OKT8 positive T cell subset. Il-2 appears to have no mitogenic activity on the activated OKT4 positive T cells which produce the lymphokine. In order to release Il-2, the OKT4 positive T cell requires a stimulus, such as allogeneic cells or the lectin phytohaemagglutinin A (PHA). Macrophages are also required for Il-2 production, but the macrophage requirement can be bypassed by a soluble macrophage product as found in supernatants of lymphocyte cultures stimulated with lipopolysaccharide (LPS), the biological activity presumably representing Interleukin-1 (Il-1).

Antibodies, Monoclonal↗
PubMed1978

Effect of niridazole in cellular immunity in vivo and in vitro.

The influence of niridazole, an anti-helminthic drug, on cell-mediated immune responses was investigated. Allograft rejection in mice as well as the in vitro induction of cytotoxic T lymphocytes (CTL) against murine alloantigen were used as the test system. Repeated daily oral treatment of host mice with niridazole (100 mg/kg) prior to and during allotransplantation resulte in the postponement of graft rejection, inducing a transitory functional state of allograft tolerance. The time interval between the termination of niridazole administration and onset of graft rejection was estimated to be 5-7 days. In order to test the effect of niridazole or its derivatives on the in vitro induction of alloreactive CTL, the serum or urine of mice which were treated with niridazole were added to the cultures, instead of adding niridazole directly to the cultures. Such serum and urine were found to be inhibitory for in vitro induction of CTL. The serum and urine had no effect on the effector phase of CTL.

Administration, Oral↗
PubMedDate not supplied

Detection of cutaneous Leishmania infection in paraffin-embedded skin biopsies using the polymerase chain reaction.

In this study the polymerase chain reaction (PCR) with previously developed oligonucleotide primers was used to detect Leishmania aethiopica in paraffin-embedded skin biopsy specimens. The Leishmania-specific 120 base pair fragment of the kinetoplast deoxyribonucleic acid (kDNA) minicircles has been amplified from all parasitologically or histologically confirmed cases of cutaneous leishmaniasis (CL), as demonstrated by gel electrophoresis and hybridization with L. aethiopica kDNA. Control specimens from patients with skin diseases other than CL were all negative. Using PCR, Leishmania were demonstrated in the skin lesions of 7 cases in a group of 40 patients in whom the parasites could not be demonstrated by histopathology or culture in vitro although lesions were clinically suggestive of CL. These data indicate that PCR, carried out on DNA extracted from formalin-fixed and paraffin-embedded tissue specimens, is a valuable method for the diagnosis of CL, especially in chronic cases where the parasite load in the lesion is low.

Animals↗
PubMedDate not supplied

[Aminoglycosides in patients with mucoviscidosis and pulmonary exacerbation. Comparison of once or three times daily administration].

Twenty-six patients with cystic fibrosis and pulmonary exacerbations were enrolled in a prospective randomized study to compare the efficacy of aminoglycosides (tobramycin or netilmicin) administered once daily (21 episodes, 5 with netilmicin, 16 with tobramycin) and thrice daily (23 episodes, 2 with netilmicin, 21 with tobramycin), respectively. In addition, the patients received an anti-pseudomonal beta-lactam antibiotic. In the single-dose group the total daily dosage was 4.97 +/- 1.12 mg/kg (total dosage per exacerbation: 74.55 mg/kg), compared to 9.60 +/- 2.70 mg/kg in the triple-dose group (total dosage per exacerbation: 165.12 mg/kg). The mean peak and trough serum levels of the aminoglycoside were 8.31 +/- 1.76 mg/l and 0.18 +/- 0.10 mg/l, respectively in the single dose group compared to 6.12 +/- 1.30 mg/l and 0.58 +/- 0.31 mg/l in the triple dose group. Success of treatment, defined as decrease in leucocyte counts, normalization of elevated CRP-values, number of days in hospital and interval until next admission to hospital, was not different between both groups. We conclude that single daily dose of aminoglycosides was as efficacious as triple dose in our patients.

Adolescent↗