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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
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↗
PubMed1979

Studies on the contact sensitization of man with simple chemicals: V. Clonal priming allows direct in vitro assessment of autologous HLA-associated factors required for immune response to dinitrochlorobenzene.

Human lymphocytes from dinitrochlorobenzene (DNCB)-sensitized human subjects primed in first culture with dinitrophenylated-antigens yield a population of cells which respond in an accelerated manner to the same or similar antigen in second culture. Using this "clonal priming" approach, we have demonstrated that such a primed population showed maximal proliferative response to dinitrophenylated autologous cells. These DNP primed clones also showed responses to some dinitrophenylated allogeneic leukocytes. The magnitude of the accelerated blastogenic response with allogeneic leukocytes varied in most instances in relation to the degree of sharing of HLA-A, B, and DRw antigens with the original autologous stimulator. These findings show that the self-specific factors recognized in conjunction with the dinitrophenyl antigen are closely but not invariably associated with established major histocompatibility (MHC)-associated serologic typing results. While DNP primed clones fail to respond to unmodified autologous leukocytes, they often show significant responses to unmodified allogeneic leukocytes. If such accelerated responses to unmodified allogeneic leukocytes are not the result of nonspecific activation of allogeneic responding lymphocyte clones, these findings further indicate that DNP modified self can resemble some alloantigens.

Dermatitis, Contact↗
PubMed1979

Selective defects in T cell function in ataxia-telangiectasia.

We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function.

Antigens↗
PubMed1978

Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors.

The syndrome of ataxia telangiectasia is associated with glucose intolerance and insulin resistance. We examined the status of insulin receptors on circulating monocytes and on cultured fibroblasts from two siblings with ataxia telangiectasia and severe insulin resistance. 125I-insulin binding to monocytes of the two patients consistently demonstrated an 80 to 85 per cent decrease in receptor affinity. In contrast, the defect in receptor affinity was not expressed on the patients' cultured fibroblasts or on monocytes or fibroblasts obtained from unaffected family members. Whole plasma and immunoglobulin-enriched fractions of plasma from the patients inhibited the normal binding of insulin to its receptors on cultured human lymphocytes (IM -9 line) and on human placental membranes. We conclude that the insulin resistance in the two siblings with ataxia telangiectasia was associated with defects in the affinity of the receptors for insulin, probably caused by circulating inhibitors of insulin binding.

Acanthosis Nigricans↗
PubMed1978

Clonal priming of human lymphocytes with soluble microbial antigens: high-dose paralysis, restoration, and autologous leukocyte preference.

Lymphocytes stimulated in appropriate leukocyte cultures undergo blastogenesis and proliferation for a finite period of time. With specific antigens the proliferative response peaks usually between 4 and 8 days, after which the blastoid cells revert to small lymphocytes. Lymphocytes "primed" in this manner can be restimulated to proliferate only by the same antigen with which they were incubated and only with an adequate amount of a self-specific, autologous, somatic product(s). First or "primary" leukocyte cultures stimulated by optimal or supraoptimal concentrations of soluble protein antigens (purified protein derivative (PPD), tetanus toxoid, Candida albicans) will undergo proliferation in the first culture, but the increased number of small lymphocytes that can be visualized after 10--14 days often fail to respond to any stimulus in second (secondary) or "primed" cultures. However, when fresh X-irradiated autologous cells are re-added in appropriate amounts, vigorous accelerated proliferation takes place. Addition of allogeneic cells to antigen-primed populations has one of three effects: (1) no effect (complete restriction); (2) in some instances allogeneic cells restore a significant response to the specific antigen but almost never to the same degree as autologous cells; and (3) allogeneic cells can also induce high levels of accelerated responsiveness without added antigen. These findings are discussed in the context of a working hypothesis that self-specific factors are involved in all specific immune responses. The combination of antigen and self-specific factors may lead to a quantitatively unique immune response to all antigens in each individual. The preferential response to antigen in conjunction with autologous rather than allogeneic leukocytes suggests that self-specific products are required for recognition of soluble microbial antigens.

Antigens, Bacterial↗