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Biomedical subjects

W R Levis

Publications and source records attributed to W R Levis.

At least 37 records · Page 2Linked to original sources
PubMed1987

Mycobacterial carbohydrate antigens for serological testing of patients with leprosy.

To determine whether quantitation of antibodies to mycobacterial carbohydrate determinants would be valuable in serodiagnosis and monitoring of leprosy, we tested serum IgM antibody to Mycobacterium leprae phenolic glycolipid I and IgM and IgG antibodies to Mycobacterium tuberculosis and M. leprae lipoarabinomannan (LAM) by enzyme-linked immunosorbent assay. Seventy-one percent of patients with paucibacillary disease and 85.5% of patients with multibacillary disease were positive for at least one of the three antibodies. The 15% of antibody-negative patients with multibacillary disease were mostly long-term-treated patients, with inactive disease by biopsy. There was excellent agreement between M. tuberculosis LAM and M. leprae LAM in detection of antibodies. Bacillary index and levels of both IgG and IgM antibodies to LAM were positively correlated when all patients were analyzed. When patients with a history of erythema nodosum leprosum (ENL) were analyzed separately, there was no correlation between IgM or IgG antibody to LAM and bacillary index, a result suggesting a possible role for LAM in the pathogenesis of ENL.

Antibodies, Bacterial↗
PubMed1987

Defective monocyte chemotaxis in active lepromatous leprosy.

This study of monocyte chemotaxis in leprosy patients showed a significant inverse correlation (p less than 0.05) of chemotaxis and the bacterial index (BI) (N = 22). In addition, there was a significant inverse correlation (p less than 0.05) between chemotaxis and the serum levels of anti-phenolic glycolipid-I IgM antibodies (N = 20). Patients taking thalidomide who had a BI greater than or equal to 1 had a significantly greater (p less than 0.001) chemotaxis response than that of patients with the same BI who were not taking thalidomide. No significant decrease in chemotaxis of monocytes from healthy donors was observed when the cells were pre-incubated with serum from 18 leprosy patients. We conclude that monocytes from patients with active lepromatous leprosy not receiving thalidomide have an intrinsic abnormality when assessed by chemotaxis.

Antibodies, Bacterial↗
PubMed1986

Effect of recombinant interferon-gamma on hydrogen peroxide-releasing capacity of monocyte-derived macrophages from patients with lepromatous leprosy.

Monocyte-derived macrophages from 14 patients with lepromatous leprosy respond to rIFN-gamma with an enhanced secretion of H2O2 in a fashion similar to that of cells obtained from normal donors. The activation is not dependent on the cutaneous bacterial index, the length of treatment, or the stage and activity of the disease. H2O2 release can be triggered in these cells both by phorbol myristate acetate and by intact irradiated Mycobacterium leprae. Uptake of M. leprae by both normal donors' and patients' macrophages is proportional to the number of bacilli added. Prior ingestion of M. leprae does not interfere with the ability of macrophages to respond to IFN-gamma by the production of oxygen intermediates. We conclude that the immune defect in lepromatous leprosy probably results from a lack of response to M. leprae by the patients' T cells rather than an inability of mononuclear phagocytes to respond to IFN-gamma.

Adolescent↗
PubMed1986

Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy.

Evidence that interferon-gamma may be a physiologic macrophage-activating factor, and that macrophage activation may be defective in lepromatous leprosy, led us to test the effects of intradermal injection of low doses of recombinant interferon-gamma in six patients with this disease. Interferon-gamma, 1 or 10 micrograms, was administered daily by jet gun for three days into a single cutaneous lesion. A biopsy specimen was taken from the injection site on the sixth study day and compared with specimens obtained previously from a site where no injection had been made or where excipient alone had been injected in the same way as the interferon. Interferon-gamma elicited local effects similar to certain features of delayed-type hypersensitivity reactions or tuberculoid leprosy, including induration, T-cell and monocyte infiltration, keratinocyte proliferation, diminution of epidermal Langerhans cells, and dermal and epidermal cell HLA-DR (Ia) antigen expression. At some of the sites of interferon-gamma injection, there was also an apparent decrease in acid-fast bacilli. Before treatment, monocytes from patients with lepromatous leprosy released 48 percent as much hydrogen peroxide as did monocytes from controls in response to phorbol myristate acetate, and 36 percent as much as those from controls in response to Mycobacterium leprae. When recombinant interferon-gamma was injected, these responses became normal. No toxic effects were observed. These observations suggest that interferon-gamma can mediate certain manifestations of delayed-type hypersensitivity or cell-mediated immunity in vivo, and that recombinant interferon-gamma should be tested for possible therapeutic effects in certain nonviral infectious diseases.

Adult↗
PubMed1986

IgM and IgG antibodies to phenolic glycolipid I from Mycobacterium leprae in leprosy: insight into patient monitoring, erythema nodosum leprosum, and bacillary persistence.

Serum IgM and IgG antibodies against Mycobacterium leprae-derived phenolic glycolipid I (PG) were determined in leprosy patients, contacts, and controls by enzyme-linked immunosorbent assay (ELISA). Anti-PG IgM levels increased from the tuberculoid (TT) to the lepromatous (LL) pole of the disease spectrum. There was a positive linear correlation between anti-PG IgM and bacillary index (BI). Patients with erythema nodosum leprosum (ENL) had lower levels of serum anti-PG IgM than non-ENL patients of comparable BI, suggesting that anti-PG IgM is involved in the pathogenesis of ENL. Initial observations indicate that high anti-PG IgM levels in bacillary-negative patients might reflect bacillary persistence. A study of 2 different substrate reagents in the ELISA [2,2'-azino-di(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 0.1 mM H2O2, serum diluted 1:20, and o-phenylenediamine (OPD), 5 mM H2O2, serum diluted 1:300] showed generally good correlation in detection of anti-PG IgM. However the OPD system detected more paucibacillary disease (BT), while the ABTS system detected the significant effect of ENL on the relationship between BI and anti-PG IgM. Anti-PG IgM was clearly dominant over anti-PG IgG. However, certain patients, including several patients who had upgraded from LL and borderline lepromatous leprosy (BL), showed high levels of anti-PG IgG. Since studies have shown that LL patients are selectively deficient in cell-mediated immunity, T-cell products may be required for the IgM to IgG isotype switch. We conclude that anti-PG IgM is useful for monitoring the bacillary load in individual patients and should prove useful for leprosy control strategies.

Antibodies, Bacterial↗
PubMed1986

Serodiagnosis of leprosy: relationships between antibodies to Mycobacterium leprae phenolic glycolipid I and protein antigens.

Sera from leprosy patients and controls were assayed for immunoglobulin M (IgM) and IgG antibodies to the Mycobacterium leprae-specific phenolic glycolipid I antigen (PG) by enzyme-linked immunosorbent assay, for IgG antibodies to M. leprae protein antigens by Western immunoblot, and for antibodies to a 65-kilodalton (kDa) protein antigen of M. leprae by a competition antibody binding assay. Elevated levels of anti-PG IgM were seen in lepromatous and borderline lepromatous patients, and elevated levels of anti-PG IgG were seen in borderline lepromatous patients. There was a significant correlation between the bacillary index (BI) and anti-PG IgM whether all leprosy patients or only multibacillary patients were analyzed. A significant correlation was seen between anti-PG IgG and BI when all leprosy patients were used for analysis, but not when only multibacillary patients were used. IgG antibodies to protein antigens of M. leprae, as detected by Western immunoblot, were more prevalent in lepromatous and borderline lepromatous patients than in borderline tuberculoid patients, while one of eight controls showed one weak band. There were significant correlations between the number of M. leprae protein antigens detected by the sera of patients and both BI and the level of anti-PG IgM. The 65-kDa competition antibody binding assay detected active multibacillary leprosy. Patients positive for antibody to the 65-kDa antigen had a significantly higher BI and levels of anti-PG IgM and anti-PG IgG than did patients that were negative. In addition, the level of antibody to the 65-kDa antigen correlated with both the BI and anti-PG IgM. We conclude that testing for antibodies to protein antigens of M. leprae may provide a useful adjunct to testing for antibodies to PG.

Animals↗
PubMed1986

ELISA detection of IgM antibodies against phenolic glycolipid-I in the management of leprosy: a comparison between laboratories.

IgM antibodies to the phenolic glycolipid-I (PGL-I) antigen of Mycobacterium leprae were detected by different ELISA techniques in three laboratories (in New York, Colorado, Seattle, U.S.A.). The agreement on seropositivity and overall correlation between techniques was excellent. A positive linear correlation between the bacterial index (BI) and anti-PGL-I IgM, previously reported by the New York laboratory, was detected by all techniques. The role of erythema nodosum leprosum in decreasing the relationship of BI versus anti-PGL-I IgM was seen by the New York laboratory with sera diluted 1:20 and ABTS substrate solution and by the Colorado laboratory but not by New York with sera at 1:300 and OPD substrate or by the Seattle laboratory.

Antibodies, Bacterial↗
PubMed1985

An analysis of in vitro T cell responsiveness in lepromatous leprosy.

In lepromatous leprosy, there is extensive replication of Mycobacterium leprae (M. leprae) within dermal macrophages. This lack of microbial resistance has been attributed to a defective cell-mediated immune response to M. leprae antigens. We have examined the in vitro response of T cells to M. leprae to determine if hyporesponsiveness could be reversed. The study included 40 unselected patients from New York and from Colombia, most with the severe lepromatous form of the disease. We first noted that lepromatous leprosy patients were of two types: those unable to respond, as assessed by T cell proliferation and immune (gamma) interferon (IFN-gamma) release, and a second group, exhibiting low but detectable responses relative to tuberculoid controls. When the effect of exogenous recombinant interleukin-2 (IL-2) on the response to M. leprae antigens was compared in the two groups, many of the low responders, but not the nonresponders, showed enhanced proliferation and IFN-gamma release. To evaluate a possible suppressive effect of monocytes, these cells were eliminated with a cell-specific monoclonal antibody and complement. Depletion of monocytes often expanded preexisting weak responses but did not reverse the anergy of the M. leprae nonresponders. The enhancement was not M. leprae-specific, since it was also observed when bacillus Calmette-Guerin was the antigenic stimulus for proliferation and IFN-gamma production. Removal of the suppressor T cell subset, with OKT8 antibody and complement, also did not restore responses in nonresponder patients. We conclude that a sizable number of lepromatous leprosy patients exhibit a low degree of responsiveness to M. leprae and that the responses can be enhanced in vitro with IL-2 or with monocyte depletion. Nonresponsiveness, however, cannot be reversed. Since currently available assays measure the function of previously sensitized T cells, suppressor mechanisms may yet contribute to defective cell-mediated immunity by impairing the initial sensitization to M. leprae antigens.

Adult↗
PubMed1984

Defective production of monocyte-activating cytokines in lepromatous leprosy.

We have examined the capacity of monocytes from patients with leprosy to undergo activation and the capacity of mononuclear cells from these patients to incorporate [3H]thymidine and produce monocyte-activating cytokines. Monocytes from patients with either lepromatous or tuberculoid leprosy were activated by concanavalin A (Con A)-induced mononuclear cell supernatants generated from the leukocytes of a normal person. Monocytes activated by these supernatants strongly inhibited L. pneumophila multiplication, and the degree of inhibition was comparable in both groups of patients. Mononuclear cells from patients with either form of leprosy responded comparably to Con A with vigorous [3H]thymidine incorporation. Mononuclear cells from patients with tuberculoid leprosy also vigorously incorporated [3H]thymidine in response to M. leprae antigens. In contrast, mononuclear cells from patients with lepromatous leprosy did not exhibit significant [3H]thymidine incorporation in response to M. leprae antigens. The capacity of mononuclear cells to generate monocyte-activating cytokines generally paralleled their capacity to incorporate [3H]thymidine in response to Con A and M. leprae. Mononuclear cells from patients with either form of leprosy responded to Con A with the production of cytokines (supernatants) able to activate normal monocytes, expressed by inhibition of L. pneumophila multiplication. However Con A-induced supernatants from patients with lepromatous leprosy were less potent than Con A-induced supernatants from patients with tuberculoid leprosy. Mononuclear cells from patients with tuberculoid leprosy responded to M. leprae antigens with the production of potent monocyte-activating supernatants. In contrast, mononuclear cells from patients with lepromatous leprosy did not produce monocyte-activating cytokines in response to M. leprae antigens. These studies support the hypothesis that the immunological defect in lepromatous leprosy results from a failure to activate mononuclear phagocytes rather than from an intrinsic inability of these cells to be activated. We suggest that the failure to activate mononuclear phagocytes stems from defective production of monocyte-activating cytokines in response to M. leprae antigens.

Adult↗
PubMed1984

Common and uncommon cutaneous findings in patients with ataxia-telangiectasia.

This series describes some common and uncommon cutaneous findings in twelve patients with ataxia-telangiectasia (A-T). All patients had the characteristic telangiectasia as described previously. However, the telangiectases did not conform to a classic photodistribution . Our series did include one patient with a pathologic reaction to light-simulating hydroa aestivale or vacciniforme . In addition, there were three patients with acanthosis nigricans in two unrelated families. Vitiligo, impetigo, recurrent herpetic gingivostomatitis, hirsutism, lipoatrophy, gray hair, progeroid changes and hyper- and hypopigmented macules were noted in our patients. Many of our patients had one or more caf'e au lait like-lesions in a dermatomal distribution. In addition, several of the family members showed one or more café au lait-like lesions, suggesting the possibility that this finding may represent a phenotypic expression in the skin of carriers of this cancer-prone syndrome.

Acanthosis Nigricans↗
PubMed1982

The cutaneous infiltrates of leprosy: cellular characteristics and the predominant T-cell phenotypes.

We report on the characteristics of cells in the cutaneous lesions and blood of 21 patients with lepromatous, tuberculoid, and intermediate forms of leprosy. A large proportion of the infiltrates in lepromatous lesions consist of macrophages heavily parasitized with Mycobacterium leprae. The T cells in the lesions are devoid of OKT4/Leu 3a-positive ("helper") cells and consist almost exclusively of OKT8/Leu 2a-positive ("suppressor") populations. In contrast, the tuberculoid infiltrates contain well-organized epithelioid and giant-cell granulomas and only remnants of bacilli, and the predominant T cell is from the OKT4/Leu 3a-positive subset. In both tuberculoid and lepromatous infiltrates, T cells and macrophages expressed HLA-DR antigen. No marked alteration in the distribution of blood T-cell phenotypes was noted. We conclude that there is a marked difference between T-cell subsets in lepromatous and tuberculoid infiltrates, which may influence the microbicidal activity of macrophages in the lesions.

Antibodies, Monoclonal↗
PubMed1982

An epidemiologic evaluation of leprosy in New York City.

Leprosy is a transmissible disease that is propagated from human to human. At the US Public Health Service hospital, New York City, the number of new leprosy cases per year during the 1970s was about three times greater than in the previous decade. This review of our 100 most recent leprosy patients shows that 60% were of the lepromatous and borderline lepromatous type. Ninety-nine of the patients were foreign born, originating in more than 26 countries. This emphasizes that, at this time, the leprosy problem in New York City is almost exclusively a reflection of immigration patterns. The majority of the patients were asymptomatic at the time of entering the United States. The average latent period from entering the United States until onset of symptoms was 4.8 years, with a range of 0 to 38 years. These figures emphasize the need for physicians to be aware that leprosy can occur as long as five to 40 years after emigration from endemic areas. For all types of leprosy, the average lag from the onset of symptoms to the time of diagnosis was 29.0 months (range, 0 to 245 months). Our experience indicates that a program of urban leprosy treatment using available drugs and supportive care is feasible.

Diagnosis, Differential↗
PubMed1982

Chromosomal instability in ataxia telangiectasia.

We have examined various aspects of lymphocyte chromosomal instability in three families comprised of five individuals affected with ataxiatelangiectasia (AT), their obligate heterozygous parents, and their unaffected sibs. We found that neither baseline sister chromatid exchanges (SCEs) nor mitomycin-C-induced increments in SCEs showed any significant differences among family members or between AT heterozygotes or homozygotes. Chromosome breakage in first-division metaphases was found to be moderately elevated in three of the five AT homozygotes (range 1-12%); breakage in the six AT obligate heterozygotes was within normal limits (0-4%). Analysis of Giemsa-banded metaphases indicated the presence of a clone bearing a paracentric inversion of chromosome #14 in addition to other chromosome #14 abnormalities in one AT homozygote. The same inversion was also found in this individual's affected sister and his obligate heterozygous father. A discussion regarding the relationship of the specificity of breakage and reunion of bands q12 and q23 on chromosome #14 and the high incidence of malignancy in AT is included.

Ataxia Telangiectasia↗
PubMed1982

Sperm priming reveals specific autoreactive lymphocyte clones.

Human spermatozoa from 18 donors were used to prime lymphocytes from 15 donors in a total of 60 different combinations. The sperm primed lymphocytes were tested in second culture against a total of 60 autologous and 180 allogeneic x-ray irradiated cells. We found that lymphocytes primed for 10-12 days in first culture with allogeneic spermatozoa showed highly significant responses in second culture to leukocytes autologous to the responder. The degree of autologous reactivity between specific subjects ranged from weak to significantly higher than the usual preferential primed lymphocyte typing reaction seen in a secondary mixed leukocyte culture reaction. These findings indicate that healthy human volunteers possess a set of self-reactive lymphocytes that can be detected by priming with allogeneic sperm in specific combinations.

Autoantibodies↗