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Biomedical subjects

W R Levis

Publications and source records attributed to W R Levis.

At least 19 recordsLinked to original sources
PubMed2001

Pentoxifylline downregulates nitric oxide and tumor necrosis factor-alpha induced by mycobacterial lipoarabinomannan in a macrophage cell line.

Pentoxifylline (PTX), a phosphodiesterase inhibitor, is known to downregulate tumor necrosis factor-alpha (TNF-alpha) secretion induced by lipopolysacchride (LPS) and gamma interferon (IFN-gamma). We have had limited success in treating leprosy reactions, including erythema nodosum leprosum (ENL), in which TNF-alpha has been identified as a major proinflammatory cytokine. PTX inhibited production of NO (IC50 approximately equal to 1.0 mg/ml) and TNF-alpha (IC50 approximately equal to 0.05 mg/ml) in a dose-dependent fashion. As little as 0.5 mg/ml of PTX decreased NO production and 0.01 mg/ml of PTX inhibited TNF-alpha production. Western blot analyses demonstrated that iNOS was suppressed by PTX. Northern blot analyses showed significant reduction of TNF-alpha mRNA. We conclude that PTX is an effective inhibitor of lipoarabinomannan (LAM)-induced TNF-alpha production at both the product and transcriptional levels in our macrophage cell line. PTX also showed moderate inhibition of NO at the product level as well as translation of iNOS.

Animals↗
PubMed2000

Regulation of nitric oxide induced by mycobacterial lipoarabinomannan in murine macrophages: effects of interferon-beta and taurine-chloramine.

We examined the effects of interferon beta (IFN-beta) on the production of liporabinomannan (LAM)-induced nitric oxide (NO) in peritoneal macrophages from low-responder and high-responder (C3H/HeJ and C3H/OuJ) mice. NO was produced in a dose response when induced by lipo-polysaccharide (LPS) or LAM plus interferon gamma (IFN-gamma) or IFN-beta in both high- and low-responder mice. In contrast to IFN-gamma, both high- and low-responder mice failed to induce nitrite production when IFN-beta was added, except at a high concentration of IFN-beta. Tau-Cl (0.5 mM) inhibited NO production about 50% in the high-responder strain when cells were activated with LPS or LAM in combination with either IFN-beta or IFN-gamma, and almost abolished NO production at 1.0 mM. In the low-responder strain, Tau-Cl (0.5 mM) significantly inhibited NO production when cells were activated with IFN-gamma or IFN-beta in addition to LPS or LAM, but did not completely inhibit NO production at 1.0 mM. Tau-Cl appears to play a potent role in regulating inflammatory reaction-induced bacterial or mycobacterial organisms. These data indicate a pivotal role for IFN-gamma and IFN-beta for the production of LPS and LAM initiated NO in peritoneal macrophages from low-responder (C3H/HeJ) mice.

Animals↗
PubMed1994

Prevalence of human T cell lymphotropic virus (HTLV) types I and II and human immunodeficiency virus type 1 infections among persons with Hansen's disease in New York City.

One-hundred seven consecutive patients attending a New York Hansen's disease clinic from November 1990 through June 1991 were tested for retroviruses. This cohort included 58 patients diagnosed with Hansen's disease after the onset of the AIDS epidemic, 54 of whom immigrated to the United States before diagnosis of Hansen's disease (median, 7 years). The overall rate (1.9%) of human T cell lymphotropic virus (HTLV) type I infection was low. Two (3.6%) of 55 Caribbean-born patients had polymerase chain reaction (PCR)-documented HTLV-I infection, but this incidence was not higher than expected in persons without Hansen's disease. No patient had PCR-documented evidence of either HTLV-II or human immunodeficiency virus (HIV) type 1 infection. The low rate of HIV-1 among those studied was likely related to an absence of classic HIV risk behavior because about half of the cohort could have incubated Mycobacterium leprae for a prolonged period while infected with HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Mycobacterial lipoarabinomannan induces nitric oxide and tumor necrosis factor alpha production in a macrophage cell line: down regulation by taurine chloramine.

Avirulent mycobacterium H37Ra lipoarabinomannan (LAM) elicited nitric oxide (NO) and tumor necrosis factor alpha in a dose-dependent manner in a murine macrophage cell line, RAW 264.7 cells. H37Ra LAM and recombinant gamma interferon were highly synergistic for NO production. The production of NO and the release of tumor necrosis factor alpha stimulated by H37Ra LAM plus recombinant gamma interferon in RAW 264.7 cells are inhibited by taurine chloramine.

Animals↗
PubMed1992

Specific inhibition of mRNA accumulation for lymphokines in human T cell line Jurkat by mycobacterial lipoarabinomannan antigen.

The immunomodulatory effect of Mycobacterium tuberculosis-derived lipoarabinomannan (LAM) on mitogen/antigen-induced expression of mRNAs for a number of cytokines in human monocytic cell line Mono-Mac-6 and in T cell line Jurkat was investigated. Interestingly, LAM exhibited a down-regulatory effect on the accumulation of mRNAs for IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2 receptor alpha (IL-2R alpha) in T cells co-stimulated with phytohaemagglutinin-P (PHA) and 4 beta-phorbol-12-myristyl-13-acetate (PMA). In human Mono-Mac-6 cells. LAM has a weak inhibitory effect on the lipopolysaccharide (LPS)-induced mRNA accumulation for IL-1 beta, a slight stimulatory effect on mRNAs accumulation for IL-8 and tumour necrosis factor-alpha (TNF-alpha), but clearly no effect on mRNA accumulation for intercellular adhesion molecule-1 (ICAM-1). These findings imply that LAM may contribute to the immunologic defects associated with a number of mycobacterial infections by modulating these mediators.

Antigens, Bacterial↗
PubMed1991

Serum antibodies against peripheral nervous system antigens in leprosy.

Since antibodies against peripheral nervous system (PNS) antigens may play a pathogenetic role in the mechanism of nerve damage in leprosy, sera from leprosy patients and contacts were investigated for anti-PNS antibodies by ELISA and immunoblot. In ELISA, elevated anti-PNS antibody levels were detected in 4 of 98 (4.1%) leprosy patients (4 of 52, 7.7%, lepromatous leprosy patients), in 1 of 28 (3.6%) contacts, and in 1 of 18 (5.6%) normal controls. There was no correlation between anti-PNS antibody levels and the bacterial index or neuropathy in leprosy. Immunoblot with a sample of six leprosy and five control sera showed that the antigenic binding pattern (mainly within the 100-200-kDa region) was very similar in patients and controls. Staining intensity, however, appeared to be higher with the leprosy sera than with the control sera. IgM and IgG were found to contribute to the staining pattern: IgM in the 150-200-kDa range, IgG with multiple bands between 25 kDa and 200 kDa. Thus, the presence and levels of serum anti-PNS antibodies in leprosy appear to be unrelated to parameters of disease activity, neuropathy in particular, and do not seem to be critically involved in the pathogenesis of nerve damage.

Antibody Specificity↗
PubMed1991

Serum IgA1 and IgM antibodies against Mycobacterium leprae-derived phenolic glycolipid-I: a comparative study in leprosy patients and their contacts.

In order to evaluate the potentials of IgA1 versus IgM as well as of native phenolic glycolipid-I (PGL-I) versus PGL-I-disaccharide coupled to bovine serum albumin (D-BSA) as antigens in the serodiagnosis of leprosy, anti-D-BSA IgA1 and anti-PGL-I IgM were investigated and compared to anti-PGL-I IgA1 in sera from patients and contacts. Anti-D-BSA and anti-PGL-I IgA1 significantly correlate in patients and contacts. The higher IgA1 positivity rates obtained with D-BSA as compared to PGL-I may suggest D-BSA as the favorable antigenic material. In patients but not in contacts anti-PGL-I IgM and IgA1 correlate, IgM predominating over IgA1. In all three antibody systems, the mean values as well as the positivity rates increased from the tuberculoid toward the lepromatous disease pole. Also, the levels of all three antibodies significantly increased with the bacterial index (BI). However, anti-D-BSA (PGL-I) IgA1 appears to be preferable to IgM with respect to sensitivity, i.e., detection of disease activity, in paucibacillary or BI-negative patients. A number of contacts were detected as seropositive with anti-D-BSA and/or anti-PGL-I IgA1 but not with anti-PGL-I IgM. This suggests that IgA1 is a better tool than IgM for the detection of leprosy in its subclinical stage.

Antibodies, Bacterial↗
PubMed1990

Suppression of T-cell proliferation by Mycobacterium leprae and its products: the role of lipopolysaccharide.

Addition of soluble molecules obtained from sonicated Mycobacterium leprae markedly suppressed the proliferative response to the mitogen anti-CD3 of peripheral blood mononuclear cells and isolated T cells. Suppression was nonspecific and occurred with cells from lepromatous and tuberculoid leprosy patients as well as control donors. The purified lipoarabinomannans from M. leprae and Mycobacterium tuberculosis had a similar spectrum of inhibition whereas their deacylated derivatives were without effect. All mycobacterial preparations of either a crude or purified state, which suppressed cellular responses, contained appreciable quantities of bacterial lipopolysaccharide by the Limulus amebocyte assay. Contamination with lipopolysaccharide could account for the extent and nonselectivity of the T-cell suppression. Suppression was also monocyte-dependent and in part due to the release of arachidonate metabolites of the cyclooxygenase pathway.

Antibodies, Monoclonal↗
PubMed1990

Histoid lepromas of lepromatous leprosy.

Histoid lepromas are a rare eruption in patients with lepromatous leprosy. A 59-year-old man from India with lepromatous leprosy who developed histoid lepromas and who was dapsone resistant was studied. These tumors resembled cutaneous metastases. This Indian man is to our knowledge the first patient to be reported with this rare disorder in the continental United States.

Dapsone↗
PubMed1990

Antibodies to lipoarabinomannan antigen in sooty mangabey monkeys experimentally inoculated with Mycobacterium leprae.

IgG and IgM antibody levels to mycobacterial lipoarabinomannan (LAM) antigen were determined by ELISA in eight sooty mangabey monkeys (Cercocebus atys) prior to and at intervals after experimental inoculation with Mycobacterium leprae. High levels of anti-LAM IgG were present before inoculation and increased thereafter in the five mangabeys that developed lepromatous (LL) forms of leprosy; lower levels of anti-LAM IgG were observed in two mangabeys that developed indeterminate leprosy and tuberculoid/neuritic leprosy, respectively, and in a mangabey that was leprosy resistant. IgM anti-LAM levels were near zero before M. leprae inoculation in all eight animals, rose significantly in only three LL-leprosy-susceptible animals after inoculation, and returned to near zero in all animals within 3 years. Anti-LAM antibody levels appear to be potentially valuable as an indicator of leprosy susceptibility, and when measured longitudinally together with antibody levels to M. leprae-specific phenolic glycolipid-I antigen, as a means to detect preclinical M. leprae infections in high-risk individuals.

Animals↗
PubMed1990

Sequential monitoring of leprosy patients with serum antibody levels to phenolic glycolipid-I, a synthetic analog of phenolic glycolipid-I, and mycobacterial lipoarabinomannan.

Sequential serum samples from leprosy patients at various stages of antibacterial treatment were tested by an ELISA for antibodies to phenolic glycolipid I (PGL-I), a synthetic PGL-I analog (ND-BSA), and lipoarabinomannan (LAM) from Mycobacterium tuberculosis to determine if these antibodies could be useful in monitoring response to therapy. Among patients with positive initial anti-PGL-I IgM, a significant decrease in this antibody was seen over time (p less than 0.01), whether assayed by PGL-I or ND-BSA. The two antigens showed good agreement in the detection of decrease in anti-PGL-I IgM. The greatest decrease was seen in patients with a high initial anti-PGL-I IgM and a high bacterial index (BI). Patients with a declining BI were seen to have generally declining antibody levels to PGL-I and to LAM; in those patients with a fluctuating BI, antibody levels were less predictable. We conclude that antibodies to PGL-I and LAM can be useful in following response to therapy in leprosy patients and that either the native PGL-I or ND-BSA can serve as antigen for the ELISA.

Antibodies, Bacterial↗
PubMed1989

IgA antibodies against phenolic glycolipid I from Mycobacterium leprae in serum of leprosy patients and contacts: subclass distribution and relation to disease activity.

The anti-PGL-I IgA response against phenolic glycolipid I (PGL-I) a specific surface antigen of Mycobacterium leprae, was demonstrated to be essentially of the IgA1 subclass in sera from leprosy patients and contacts. Anti-PGL-I IgA1 mean levels were found to increase significantly from the tuberculoid toward the lepromatous pole of the leprosy disease spectrum, thus resembling the predominating anti-PGL-I IgM response. Furthermore, anti-PGL-I IgA1 values were shown to increase significantly with increasing bacillary load, measured as bacillary index (BI) from skin biopsies. However, a number of BI negative leprosy patients recorded elevated anti-PGL-I IgA1 levels possibly reflecting a persistence of disease activity. Three of 28 household or family contacts of leprosy patients were detected seropositive for anti-PGL-I IgA1. Thus, our results suggest that anti-PGL-I IgA1 may be considered as an additional parameter for the early detection of infection with M. leprae.

Antibodies, Bacterial↗
PubMed1989

Analysis of human antibody epitopes on the 65-kilodalton protein of Mycobacterium leprae by using synthetic peptides.

In order to study antibody reactivity to the Mycobacterium leprae 65-kilodalton (kDa) antigen, peptides representing overlapping sequences of the 65-kDa protein were synthesized, and a recombinant protein expression system for r65-kDa was constructed. Mouse monoclonal antibodies and leprosy patient seroreactivity to peptides and r65-kDa were tested by an enzyme-linked immunosorbent assay. All seven of the monoclonal antibodies used in this study reacted with their previously defined epitopes when tested against peptides. All monoclonal antibodies also reacted with r65-kDa. Leprosy patient seroreactivity to peptides and r65-kDa was seen in about one-third of active multibacillary cases. Specimens from patients positive for antibodies to peptides were seen to recognize different epitopes than did mouse monoclonal antibodies used in this study. It is concluded that substantial differences exist between mouse monoclonal antibodies and human leprosy patient reactivity to the 65-kDa antigen and that human seroreactivity to the 65-kDa antigen is indicative of a highly elevated bacillary load.

Amino Acid Sequence↗
PubMed1989

Testicular dysfunction in leprosy: relationships of FSH, LH and testosterone to disease classification, activity and duration.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were determined by radioimmunoassay (RIA) in leprosy patients and analysed for effect of disease classification, disease activity and duration of disease. LH and FSH levels were found to be significantly elevated in lepromatous patients compared to borderline-lepromatous, midborderline and borderline-tuberculoid patients. A positive correlation was seen between LH and FSH and a negative correlation was seen between testosterone and both LH and FSH. No correlation was seen between hormone levels and measures of disease activity: bacillary index and IgM to phenolic glycolipid I, a Mycobacterium leprae antigen. A significant correlation was seen between duration of disease and FSH when age was taken into account, indicating that testicular dysfunction is probably cumulative and irreversible. It is recommended that LL patients be routinely screened for hypogonadism using FSH, LH and testosterone levels.

Follicle Stimulating Hormone↗
PubMed1988

A patient with lepromatous leprosy and anticytoskeletal antibodies.

Sera from 34 patients with lepromatous leprosy were screened for the presence of autoantibodies by indirect immunofluorescence using two epithelial cell lines, PTK2 and HEp2, as substrates. Indirect immunofluorescence staining of both substrates with the serum of a patient with lepromatous leprosy revealed a cytoplasmic intermediate filament staining pattern. After exposure of PTK2 cells to colchicine, the filaments collapsed into thick perinuclear coils, confirming the presence of intermediate filament reactivity. Immunofluorescence of rat fibroblasts with the same serum also revealed an intermediate filamentous staining pattern. Human keratinocytes exposed to the patient's serum revealed a diffuse cytoplasmic staining pattern. Our study suggests the presence of autoantibodies to cytoskeletal intermediate filaments or to molecules associated with vimentin and possibly keratin subunit proteins in the serum of a patient with lepromatous leprosy.

Adult↗
PubMed1987

Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro.

The extent to which M. leprae and its products induced suppression of T lymphocyte proliferation in vitro was evaluated. M. leprae antigens suppressed T cell proliferation in response to mitogens and antigens in both lepromatous and tuberculoid patients, as well as controls never exposed to M. leprae or M. leprae endemic areas. Both soluble and particulate fractions of M. leprae were found to suppress proliferation in a dose-dependent manner. The extent of suppression was inversely related to the proliferative response of the donors mononuclear cells to M. leprae. Evidence indicates that M. leprae contains both stimulatory and suppressive molecules for T cells. One such suppressive antigen, Lipoarabinomannan (LAM)-B of M. leprae, also suppressed the proliferative response of tuberculoid patients. Suppression was also observed with the LAM-B of M. tuberculosis. The suppressive effects observed were not due to the toxicity of the antigen. Some of the suppressive activity was mediated by T8+ suppressor cells and was expressed in both lepromatous and tuberculoid patients. We suggest that previous sensitization to M. leprae and other cross-reactive mycobacterial antigens determines the sensitivity of T cells to the suppressive effects of M. leprae antigens.

Antigens, Bacterial↗