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Biomedical subjects

V Schauf

Publications and source records attributed to V Schauf.

At least 19 recordsLinked to original sources

Thalidomide inhibits the replication of human immunodeficiency virus type 1.

Thalidomide, a selective inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, suppresses the activation of latent human immunodeficiency virus type 1 (HIV-1) in a monocytoid (U1) line. The inhibition is dose dependent and occurs after exposure of the cells to recombinant TNF-alpha, phorbol myristate acetate, lipopolysaccharide, and other cytokine combinations. Associated with HIV-1 inhibition is a reduction in agonist-induced TNF-alpha protein and mRNA production. Thalidomide inhibition of virus replication in the phorbol myristate acetate- and recombinant TNF-alpha-stimulated T-cell line ACH-2 is not observed. The presence of thalidomide also inhibits the activation of virus in the peripheral blood mononuclear cells of 16 out of 17 patients with advanced HIV-1 infection and AIDS. These results suggest the use of thalidomide in a clinical setting to inhibit both virus replication and the TNF-alpha-induced systemic toxicity of HIV-1 and opportunistic infections.

Acquired Immunodeficiency Syndrome↗

Cytokine gene activation and modified responsiveness to interleukin-2 in the blood of tuberculosis patients.

Selected parameters of cellular immunity relating to cytokine gene activation and responsiveness to interleukin-2 (IL-2) were analyzed in 27 patients with active pulmonary tuberculosis and no human immunodeficiency virus type 1 infection. Cytokine mRNAs were not expressed by peripheral blood mononuclear cells (PBMC) of normal controls. In PBMC of tuberculosis patients, messages for IL-1, IL-8, and tumor necrosis factor-alpha were uniformly expressed, whereas PBMC of only 5 of 18 patients expressed IL-6. PBMC of 7 patients (all of those with systemic symptoms) expressed interferon-gamma mRNA and none expressed IL-2 mRNA. Most patients' cells demonstrated IL-4 mRNA. Limiting dilution analysis of IL-2-responsive cells in PBMC revealed that tuberculosis patients had 10-fold fewer IL-2-responsive cells than did controls.

Cytokines↗

Presentation of mycobacterial antigens by human dendritic cells: lack of transfer from infected macrophages.

When exposed to a challenge of 10 Mycobacterium bovis BCG cells per antigen-presenting cell, most human monocytes engulf several organisms. In contrast, blood dendritic cells which are potent antigen-presenting cells for several antigens are not detectably phagocytic for mycobacteria. We investigated the possibility that infected macrophages might regurgitate antigens for presentation by populations of human blood dendritic cells. Macrophages were infected with M. bovis BCG, mixed with uninfected dendritic cells, and added to immune T cells, either bulk T cells or cloned populations from BCG vaccinees or patients recovering from tuberculosis. The macrophages were from donors who were mismatched to the T cells so that transfer of antigen to major histocompatibility complex-matched dendritic cells could be evaluated. As we describe, there was no evidence for the transfer of mycobacterial antigens from macrophages to dendritic cells in a form that was stimulatory for the T cells.

Amino Acid Sequence↗

Sensitization in vitro of human peripheral blood mononuclear cells to phenolic glycolipid 1 of Mycobacterium leprae in liposomes.

Study of primary immune responses in leprosy has been limited, since disease becomes manifest long after infection or is not detectable. To study primary immune responses, we immunized in vitro human peripheral blood mononuclear cells from unexposed individuals using phenolic glycolipid 1 (PGL-1), an important water-insoluble antigenic constituent of Mycobacterium leprae. PGL-1, encapsulated in liposomes, induced lymphoproliferation or, less frequently, suppression of lymphoproliferation in 11-day lymphocyte cultures. The primary lymphocyte responses resembled those elicited with keyhole limpet hemocyanin (KLH). HLA-DR2 expression, associated with tuberculoid leprosy, did not influence the outcome of in vitro sensitization. The association of HLA-DR2 and tuberculoid leprosy is not explained by differential ability to generate primary lymphoproliferative responses to PGL-1 or KLH. We have extended in vitro sensitization methodology to include a water-insoluble antigen in antigen-bearing liposomes. This methodology is potentially useful for studies of immunogenetics and immunopathology, and for vaccine research.

Antigens, Bacterial↗

Enhanced killing of group B streptococci in vitro by penicillin and opsonophagocytosis with intravenous immunoglobulin.

Combined effects of intravenous immunoglobulin (IVIG) and antibiotics in killing bacteria are of interest with broadening clinical use of IVIG. Since the kinetics of killing by these agents differ and each may influence the outcome of the other, it is difficult to evaluate combination effects in vitro. Conditions were developed to measure killing of group B streptococci (GBS), type III strain M732, by an opsonic mixture with IVIG, fresh serum, and human polymorphonuclear leukocytes (PMNL) with or without penicillin. Bacterial killing was observed with the opsonic IVIG mixture, penicillin, and the opsonic IVIG mixture plus penicillin at 1 h. The effect of the combination was greater than the sum of the effects of two separate incubations. The enhanced killing was evident for up to 18 h. By 24 h, the killing by the combination was no greater than that by penicillin alone. A similar pattern of GBS killing was observed with cord blood PMNL, six different GBS type III strains, and pretreatment of GBS with either IVIG or penicillin. These effects suggest that the combination of IVIG and penicillin has potential for use in the treatment of neonatal GBS infections.

Humans↗

Segregation analysis of leprosy in families of northern Thailand.

Sixty-three families with multiple instances of leprosy were identified through a major leprosy treatment center in northern Thailand. Complex segregation analyses for single major genes or polygenic inheritance were performed using the maximum-likelihood routine POINTER to determine the most likely etiologic model of genetic susceptibility. Liability differences between men and women were considered in these models. When individuals were considered to be affected because they had any form of leprosy, a generalized major gene model with nearly dominant parameters on the liability scale, but additive penetrances, was found to be the most likely. When only those individuals who had tuberculoid forms of leprosy were considered to be affected, a recessive model was found to be the most likely; however, the discrimination between various models was poor. Further analyses are necessary to delineate genetic mechanisms to explain these apparently divergent results. In particular, methods of testing two locus models should be considered.

Adult↗

Illness beliefs of leprosy patients: use of medical anthropology in clinical practice.

Illness beliefs of 61 patients identified as having leprosy were assessed by Kleinman's Explanatory Model Format. Our patients used a wide variety of etiologic theories which were grouped in categories such as venereal disease, heredity, dangerous food, sin, karma, and humoral disorders. Despite efforts at patient education, very few patients adopted the concept of bacterial infection to explain their illness. The patients identified their illness with a variety of different labels, some of which had associations with particular symptoms. Leprosy was perceived and experienced more as a series of acute disorders not necessarily related to one another. The various theories of illness were instrumental in directing treatment choices which included a number of indigenous healing practices. Such information may be useful in improving patient care and compliance by providing practitioners with interpretive strategies for communicating with their patients.

Adolescent↗

Soluble serum interleukin 2 receptor levels in leprosy patients.

Soluble interleukin 2 receptors (IL-2R) in sera of leprosy patients from Chiang Mai, Thailand, were quantified with a solid phase enzyme immunoassay using two monoclonal antibodies to the IL-2R. The IL-2R levels of untreated lepromatous, borderline lepromatous or midborderline patients and treated lepromatous and borderline lepromatous or treated borderline tuberculoid and tuberculoid patients were comparable to those of the Thai household or nonhousehold contacts; and they were significantly higher than the levels of USA control subjects. In contrast, IL-2R of untreated tuberculoid or borderline tuberculoid patients were significantly reduced. Patients with ongoing reversal reaction had very high circulating IL-2R, the levels of which correlated with fever and extent of skin lesions. Although erythema nodosum leprosum patients also had elevated IL-2R levels, they were significantly below those of patients with reversal reaction. When treated with corticosteroid, precipitous reduction of IL-2R was noted in all patients with reversal reaction but not in patients with erythema nodosum leprosum.

Enzyme-Linked Immunosorbent Assay↗

Lymphocyte transformation in lepromatous leprosy: a study of the influence of disease activity and symptom duration.

The lymphocyte hyporesponsiveness to M. leprae of patients with active lepromatous leprosy has been well described. This immune defect is less well understood in terms of its time of origin, possible reversibility and specificity. To further examine the persistence and specificity of this abnormality, lymphocyte transformation tests of 93 leprosy patients to lepromin, BCG and PHA were studied. Among lepromatous patients, a decreased response to M. leprae was seen, whether the disease was active or inactive. Decreased responses to BCG were found in lepromatous patients with active disease, but not in those with inactive disease. The duration of patient symptoms was not associated with differences in LTT responses among the active lepromatous patients.

Adolescent↗

Leprosy associated with HLA-DR2 and DQw1 in the population of northern Thailand.

A study of the frequency of HLA-DR2 and DQw1 was performed in leprosy patients and controls in northern Thailand. HLA-DR2 was found in 100% (17/17) of patients with sporadic tuberculoid leprosy and in over 90% (30/32) of all tuberculoid leprosy patients, as compared to 62% (20/32) of controls (p = .02). These strong associations had relative risks of 21.4 for sporadic and 7.4 for all tuberculoid leprosy, and etiologic fractions of 1.0 and 0.84, respectively. There was also a statistically significant and strong association between tuberculoid leprosy and DQw1. These data add to the growing body of evidence that products of HLA class II determinants or closely linked genes may play a role in determining the clinical manifestations of M. leprae infection.

Adult↗

Interleukin 1 production by peripheral blood mononuclear cells from leprosy patients.

Quantitation of interleukin 1 production by adherent mononuclear cells from peripheral blood was performed in patients with tuberculoid and lepromatous forms of leprosy. Cells from patients with tuberculoid leprosy either secreted interleukin 1 spontaneously or produced amounts within the normal range in response to lipopolysaccharide stimulation. Conversely, stimulated cells from lepromatous patients failed to produce interleukin 1 in 5 of 13 (38.5%) cases.

Adult↗

Chloramphenicol kills Haemophilus influenzae more rapidly than does ampicillin or cefamandole.

The bactericidal effects of chloramphenicol and three beta-lactams (ampicillin, cefamandole, and penicillin G) were measured for 27 strains of Haemophilus influenzae type b isolated from the blood or cerebrospinal fluid of infected infants. Of the ampicillin-susceptible strains, 75% were killed by less than 2.0 micrograms of each antibiotic per ml; however, the concentration of the beta-lactam agents required for bactericidal activity was higher than that required for inhibitory activity. Chloramphenicol was the only agent which had no marked discrepancy between inhibitory and bactericidal concentrations regardless of beta-lactamase production. Importantly, chloramphenicol was more rapidly bactericidal than either ampicillin or cefamandole. The bactericidal requirement of ampicillin was increased by the presence of chloramphenicol for about one-third of the isolates examined. Neither the inhibitory nor the bactericidal activity of chloramphenicol was influenced by ampicillin. Synergy occurred for only two beta-lactamase-positive isolates. The more rapid bactericidal action of chloramphenicol persisted even in the presence of ampicillin. The rapid bactericidal action of chloramphenicol with or without ampicillin supports the use of chloramphenicol alone or with ampicillin for H. influenzae infections.

Ampicillin↗