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a mycobacterial extracytoplasmic function sigma factor involved in survival following stress.the extracytoplasmic function (ecf) sigma factors constitute a diverse group of alternative sigma factors that have been demonstrated to regulate gene expression in response to environmental conditions in several bacterial species. genes encoding an ecf sigma factor of mycobacterium tuberculosis, mycobacterium avium, and mycobacterium smegmatis, designated sige, were cloned and analyzed. southern blot analysis demonstrated the presence of a single copy of this gene in these species and in mycoba ...19979139909
igm anti-phenolic glycolipid i and igg anti-10-kda heat shock protein antibodies in sera and immune complexes isolated from leprosy patients with or without erythema nodosum leprosum and contacts.the aim of the present work was to evaluate the levels of anti-pgl-i and anti-10-kda heat shock protein antibodies in serum and immune complexes isolated from leprosy patients, convivients and controls. leprosy patients with erythema nodosum leprosum or without it were included and a comparative study was done to investigate intergroup differences. immune complexes were precipitated from serum by polyethylene glycol 3.5%; antibody levels were measured in sera and in dissociated immune complexes ...19979322070
cytokine gene expression in the foot pad and spleen of balb/cajcl mice infected with m. leprae.the cytokine mrnas expressed in the foot pads and spleens of balb/cajcl mice infected with mycobacterium leprae were studied by the reverse transcriptase-polymerase chain reaction (rt-pcr) method using cytokine-specific primers for interleukin-1 alpha (il-1 alpha), -2, -4, -6, -10, -12-(p40), gamma interferon (ifn-gamma), tumor necrosis factor-alpha (tnf-alpha), and tnf-beta, and then for cd4 and cd8 markers. the pattern of cytokine gene expression in the foot pad which supports m. leprae growth ...19979207757
influence of ddt exposure on susceptibility to human leprosy bacilli in mice. 19979207760
lymphostimulatory and delayed-type hypersensitivity responses to a candidate leprosy vaccine strain: mycobacterium habana.lymphostimulatory and delayed-type hypersensitivity (dth) immune responses to a candidate antileprosy vaccine mycobacterium habana have been quantified in inbred akr mice. m. habana vaccine in three physical states, live, heat-killed and gamma-irradiated, was given intradermally to separate groups of mice and after 28 days these mice were given subcutaneous challenge with heat-killed m. leprae and heat-killed m. habana in the left hind footpad. live bcg vaccine alone and in combination with gamm ...19979217351
higher incidence of viable mycobacterium leprae within the nerve as compared to skin among multibacillary leprosy patients released from multidrug therapy.as identified by a significant growth in the footpads of immunosuppressed mice, the incidence of viable bacteria in a group of 26 multibacillary (bl-ll) patients released from multidrug (mdt) treatment was found to be two times more in the nerves (46%) as compared to skin (23%). evidently there was a positive correlation between the overall bacterial load and the incidence of viable organisms. bacterial growth was also observed in two out of five cases where neither the skin nor the nerve homoge ...19979217352
a novel mycobacterial antigen relevant to cellular immunity belongs to a family of secreted lipoproteins.the gene sequence of a novel 24.1 kda mycobacterium tuberculosis protein was identified within the sanger centre (uk) m. tuberculosis genome database (cosmid mtcy24g1) by searching with a 126 bp dna sequence isolated from a genomic m. leprae lambda gt11 library with m. leprae reactive human t cell clones as probes. the 24.1 kda antigen is common to the vaccine strain mycobacterium bovis bcg, as well as mycobacterium leprae. the 699 bp open reading frame encodes a 233 amino acid long precursor pr ...19979393626
transepidermal elimination of lepromatous granuloma: a mechanism for mass transport of viable bacilli.a 35-year-old male with lepromatous leprosy showed significant progression of the disease on initial examination. along with typical lepromatous skin lesions, many scar-forming lesions were present, mainly on his extremities. some lesions showed erosive surfaces. from clinicopathological findings, these lesions were suspected to be due to the partial excretion of intradermal lepromatous granulomata by 'transepidermal elimination'. increased local volume, which might be due mainly to rapidly grow ...19979217357
il-2 and il-12 act in synergy to overcome antigen-specific t cell unresponsiveness in mycobacterial disease.il-12 secretion by apc is critical for the development of protective th1-type responses in mycobacterial (mycobacterium avium and mycobacterium tuberculosis) infections in mice. we have studied the role of il-12 and il-2 in the generation of mycobacterium leprae-specific t cell responses in humans. leprosy patients were defined as low/nonresponders or high responders based on the level of t cell proliferation in m. leprae-stimulated pbmc. in high responders, m. leprae-induced proliferation was m ...19979218596
association of polymorphism at col3a and ctla4 loci on chromosome 2q31-33 with the clinical phenotype and in-vitro cmi status in healthy and leprosy subjects: a preliminary study.two genetic loci, viz. col3a and ctla4, located within the chromosome 2q31-33 region in the vicinity of the proposed syntenic site of the mouse "bcg" locus were genotyped by the polymerase chain reaction in leprosy patients and healthy individuals. all the subjects studied were assessed as in-vitro responders/non-responders to mycobacterial antigens. simple sequence length polymorphism analysis revealed five (236 to 312 bp) and eight (84 to 120 bp) allelomorphs for col3a and ctla4, respectively. ...19979225967
a eukaryotic xpb/ercc3-like helicase in mycobacterium leprae? 19979397681
protection against tuberculosis by a plasmid dna vaccine.past attempts to use fractions of mycobacteria as an alternative to bcg have given disappointing results. the availability of cloned genes and suitable vectors has now opened a new avenue in which individual mycobacterial protein antigens are synthesised within transfected mammalian cells. in an ex vivo transfection approach with a retroviral vector we found that even a single antigen (hsp65) could evoke strong protection when expressed as a transgene and that expression of protection was largel ...19979234527
humoral and cellular immune reactivity to recombinant m. leprae antigens in hla-typed leprosy patients and healthy controls.in our search for mycobacterium leprae antigens that might specifically induce immunity or immunopathology, we have tested both humoral and cellular immune reactivity against purified recombinant m. leprae antigens in 29 paucibacillary (pb), 26 multibacillary (mb) leprosy patients, and 47 matched healthy contacts. the following m. leprae antigens were tested: 2l-1 (65l-1, groel-1), 2l-2 (65l-2, groel-2), 4l (soda), 43l, 10l (b) and 25l (sra). the individuals were also typed for hlad-rb1 and dqb1 ...19979251589
associations between hla-drb1 alleles and leprosy in an indonesian population.to investigate whether the susceptibility to leprosy (type), subclinical infection with mycobacterium leprae and the antibody response against m. leprae-specific antigens are associated with hla-dr phenotypes sequence-specific oligonucleotide hla-drb1 and dqa1 typing and antibody assays have been performed in 79 leprosy patients (41 tt/bt and 38 ll/bl) and 50 healthy controls from a javanese population in yogyakarta, indonesia. drb1*02 was associated with ll/bl [odds ratio (or) 2.54, 95% confide ...19979251590
comparison of bacillary indexes in slit-skin smears, skin and nerve biopsies; a study from malawi.data analyzed in this paper were collected within the framework of the lepra evaluation project, an epidemiological study of leprosy in karonga district, northern malawi. for 212 patients information on the number of skin lesions, slit-skin smear and skin biopsy results were available. among 61 patients with a single lesion none were slit-skin-smear positive and two had bacilli detected in skin biopsies. in contrast, among 119 patients with four or more lesions 34 (28.6%) versus 59 (49.6%) had b ...19979251593
the clinical use of fluoroquinolones for the treatment of mycobacterial diseases.mycobacterial diseases often require prolonged therapy with multidrug regimens. fluoroquinolones have excellent bactericidal activity against many mycobacteria; achieve effective serum, tissue, and intracellular levels following oral administration; and produce few adverse effects. these properties have led to the increasing use of fluoroquinolones for the treatment of mycobacterial infections. we reviewed clinical studies and reports involving the use of fluoroquinolones for mycobacterial disea ...19979402384
a macrophage invasion mechanism of pathogenic mycobacteria.tuberculosis is the leading cause of death due to an infectious organism, killing an estimated 3 million people annually. mycobacterium tuberculosis, the causative agent of tuberculosis, and other pathogenic mycobacteria require entry into host macrophages to initiate infection. an invasion mechanism was defined that was shared among pathogenic mycobacteria including m. tuberculosis, m. leprae, and m. avium but not by nonpathogenic mycobacteria or nonmycobacterial intramacrophage pathogens. this ...19979262476
multiplex sequencing of 1.5 mb of the mycobacterium leprae genome.the nucleotide sequence of 1.5 mb of genomic dna from mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. this brings the 2.8-mb m. leprae genome sequence to approximately 66% completion. the sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 trnas, and 15 trnas. the gene density of one per 1.4 kb is slightly lower than that of mycoplasma (1.2 kb). of the protein coding genes, 44% have sign ...19979267804
characterization of the rpoc gene of streptomyces coelicolor a3(2) and its use to develop a simple and rapid method for the purification of rna polymerase.the streptomyces coelicolor rpoc gene, that encodes the beta' subunit of rna polymerase, was isolated using the escherichia coli rpoc gene as a hybridization probe. comparison of the predicted amino acid sequence of the s. coelicolor beta' subunit to those characterized from other bacteria revealed three distinct subfamilies of beta' subunits, one of which consists of the s. coelicolor subunit and those from mycobacterium leprae and mycoplasma genitalium. using site-directed mutagenesis, the car ...19979322738
whither short-course chemotherapy for leprosy? 19979290962
mycobacterium leprae: biochemical studies of clinical relevance. 19979290969
characterization of leprosy based on the nasal lipid profile.while extracting the m. leprae from the nasal flushings of leprosy patients it was found that these organisms were trapped in the waxy layer, between the aqueous and the chloroform layers. thin layer chromotography (tlc) analysis of this layer, using chloroform-methanol-water system, revealed different spots when sprayed with acid alcohol and heated at 160 degrees c. the tlc profile of lipids of lepromatous and borderline (mb according to the who terminology) leprosy patients was distinctly diff ...19979290970
preparation of thymectomized irradiated (t900r) mice: a modification. 19979290979
[many undefined problems in hansen's disease]. 19979301204
[micro-cytology of leprosy bacilli in-situ]. 19979301205
regional lymphadenitis following antileprosy vaccine bcg with killed mycobacterium leprae.phase-ii and extended phase-ii studies were conducted in three different sets of the population in thiruthani taluk, chengalpattu district, south india, involving bcg and killed mycobacterium leprae (kml) combination vaccines to ascertain the acceptability of the vaccines. in the phase-ii study, 997 healthy volunteers were vaccinated on individual randomization with one of the vaccines arms: bcg 0.1 mg + 6 x 10(8) kml, bcg 0.1 mg + 5 x 10(7) kml, bcg 0.1 mg + 5 x 10(6) kml, bcg, 0.1 mg or normal ...19979207749
high relapse rate among lepromatous leprosy patients treated with rifampin plus ofloxacin daily for 4 weeks.fifty-one lepromatous leprosy patients, all of whom had relapsed after previous dapsone (dds) monotherapy, were treated between 1990 and 1991 with 600 mg of rifampin (rmp) plus 400 mg of ofloxacin (oflo) daily for 4 weeks, and the great majority of the patients were followed up at least once a year after completion of the treatment. after only 173 patient-years of follow-up, 5 relapses had been detected; the overall relapse rate was 10.0% (confidence limits, 1.7 and 18.3%), or 2.9 relapses (conf ...19979303392
dharmendra antigen but not integral m. leprae is an efficient inducer of immunostimulant cytokine production by human monocytes, and m. leprae lipids inhibit the cytokine production.killed integral mycobacterium leprae, mitsuda antigen, and chloroform-treated m. leprae, dharmendra antigen (dh-ag), have been used for the classification of leprosy patients based on cell-mediated immunity. heat-killed m. leprae also were used as a component of the convit vaccine. human blood monocytes were stimulated with m. leprae or dh-ag and their cytokine-inducing ability was compared. monocytes were cultured in the presence of fresh human serum because of the efficiency of cytokine induct ...19979207755
schwann cell extracellular matrix protein production is modulated by mycobacterium leprae and macrophage secretory products.extracellular matrix (ecm) protein deposition is an important feature of leprous nerves, where schwann cells (scs) and macrophages are the main hosts for mycobacterium leprae. since, scs are involved in the synthesis of ecm proteins and its production is regulated by macrophage secretory factors, the present study aimed to determine in vitro, the effect of m. leprae infection and macrophage secretory products on secretion of ecm proteins by scs in two strains of mice, swiss white (sw) and c57bl/ ...19979335004
interactions between cationic liposomes and an antigenic protein: the physical chemistry of the immunoadjuvant action.the 18 kda antigenic protein from mycobacterium leprae (p) or its n-acyl derivative (ap) was incorporated in dioctadecyldimethylammonium bromide (dodab) liposomes in water or in phosphate-buffered saline (pbs). in water, 100% p incorporation in liposomes contrasts with 65% in pbs. there is 75-80% ap incorporation to liposomes in water against 55-65% in pbs, showing that attachment of hydrophobic residues to the protein, instead of increasing, further decreases incorporation to the liposomes. fro ...19979374123
reversal reaction in borderline leprosy is associated with a polarized shift to type 1-like mycobacterium leprae t cell reactivity in lesional skin: a follow-up study.borderline leprosy patients often undergo acute changes in immune reactivity that manifest as reversal reaction (rr) in the course of the disease. rr is associated with an exacerbated local delayed-type cellular immune response to mycobacterium leprae and is responsible for severe tissue damage. we investigated whether rr episodes are associated with a change in t cell subsets in the lesional skin with regard to their cytokine secretion profiles. m. leprae-responsive t cell lines and thereafter ...19979379047
down-regulatory effect of mycobacterium leprae cell wall lipids on phagocytosis, oxidative respiratory burst and tumour cell killing by mouse bone marrow derived macrophages.the authors have previously demonstrated that lipids from mycobacterium leprae cell walls inhibit macrophage functions and are endowed with anti-inflammatory properties in vivo. to investigate these observations further, the authors describe here the influence of dead m. leprae or of the lipids extracted from the cell wall of the mycobacterium, enclosed in liposomes, on the phagocytic, oxidative respiratory burst and tumouricidal ability of bone marrow derived macrophages in vitro. dead m. lepra ...19979393633
ccs1, a nuclear gene required for the post-translational assembly of chloroplast c-type cytochromes.nuclear genes play important regulatory roles in the biogenesis of the photosynthetic apparatus of eukaryotic cells by encoding factors that control steps ranging from chloroplast gene transcription to post-translational processes. however, the identities of these genes and the mechanisms by which they govern these processes are largely unknown. by using glass bead-mediated transformation to generate insertional mutations in the nuclear genome of chlamydomonas reinhardtii, we have generated four ...19979395519
a follow-up study of multibacillary hansen's disease patients treated with multidrug therapy (mdt) or mdt + immunotherapy (imt).multibacillary (mb) leprosy patients treated with multidrug therapy (mdt) or mdt + immunotherapy (imt) with bcg + heat-killed mycobacterium leprae were tested annually for their ability to proliferate in vitro to the mycobacterial antigens bcg, m. leprae soluble extract, and intact m. leprae. igm antibody responses to phenolic glycolipid i (pgl-i) were measured, as well as serum nitrite levels in patients' sera, before, during and after treatment. patients who received only mdt did not present c ...19979401484
studies on therapeutic activity of benzoxazinorifamycin krm-1648 in combination with other antimicrobial agents and biological response modifiers interferon-gamma and granulocyte-macrophage colony-stimulating factor against m. leprae infection in athymic nude mice.in the present study, we evaluated the in vivo anti-mycobacterium leprae activities of krm-1648 (krm) given at long intervals in combination with ofloxacin (oflx), clofazimine (cfz), and dapsone (dds). we also examined the combined effects of two biological response modifiers (brms), gamma interferon (ifn-gamma) and granulocyte-macrophage colony-stimulating factor (gm-csf), on the therapeutic efficacy of krm. krm exhibited potent therapeutic efficacy against m. leprae infection in mice even when ...19979401487
m. leprae binds to a 28-30-kda phosphorylated glycoprotein of rat peripheral nerve.to understand mycobacterium leprae-peripheral nerve interaction, we have investigated the binding of m. leprae to rat peripheral nerve proteins in an in vitro model using 32p-phosphorylated proteins of the peripheral nerve. intact m. leprae binds to a major phosphorylated protein of 28-30 kda and, to a minor extent, to a few proteins of molecular weight 45-55 kda. this binding was more specific for m. leprae since only insignificant binding was observed with other bacteria, such as m. bovis or e ...19979401488
a single point mutation in the embb gene is responsible for resistance to ethambutol in mycobacterium smegmatis.ethambutol [emb; dextro-2,2'-(ethylenediimino)-di-1-butanol] is an effective drug when used in combination with isoniazid for the treatment of tuberculosis. it inhibits the polymerization of arabinan in the arabinogalactan and lipoarabinomannan of the mycobacterial cell wall. recent studies have shown that arabinosyltransferases could be targets of emb. these enzymes are encoded by the emb locus that was identified in mycobacterium smegmatis, mycobacterium leprae, mycobacterium avium, and mycoba ...19979420031
mtc28, a novel 28-kilodalton proline-rich secreted antigen specific for the mycobacterium tuberculosis complex.proteins that are actively secreted by mycobacterium tuberculosis serve as major targets of immune responses in the infected host. to identify and purify novel proteins in the filtrates of m. tuberculosis cultures, a bacteriophage lambda library of m. tuberculosis h37rv dna was immunoscreened by using an anti-culture filtrate rabbit antiserum. of 20 positive clones isolated, 6 were analyzed and found to express the genes for two known components of the early culture filtrate, the secreted 45/47- ...19979393781
a genomic study on the cultivable and nerve invading mycobacterium hi-75 after the recovery 3 months of the inoculation to nude mice.the sequence of the polymerase chain reaction (pcr) product of 16s ribosomal rna (16s rrna) of the leproma-derived and cultivable mycobacterium hi-75 (m. hi-75) which was obtained from the infected regions of inoculated mice, was examined and compared with that of the cultured bacteria by the direct sequencing techniques. the sequence was completely consistent with the cultured bacilli in the comparable 837 bases of 16s rrna. the mycobacterium examined in this study was originally isolated as m. ...19979513348
pathological investigation of armadillos infected with mycobacterium leprae.an infection experiment with m. leprae was carried out using 20 nine-banded armadillos. as a result, the development of leprous lesions and a marked multiplication of afb were confirmed in a high rate of 13 out of 15 cases (86.8%) in the inoculated groups. these changes were found to be progressing at post mortem of one case even with the shortest life period for 7.5 months and were very serious in one case with the longest life period for 33 months, suggesting the continuation of symptoms, thou ...19979513349
mycobacterium tuberculosis efpa encodes an efflux protein of the qaca transporter family.the mycobacterium tuberculosis h37rv efpa gene encodes a putative efflux protein, efpa, of 55,670 da. the deduced efpa protein was similar in secondary structure to pur8, mmra, tcma, lfra, emrb, and other members of the qaca transporter family (qaca tf) which mediate antibiotic and chemical resistance in bacteria and yeast. the predicted efpa sequence possessed all transporter motifs characteristic of the qaca tf, including those associated with proton-antiport function and the motif considered ...19979008277
presence of f420-dependent glucose-6-phosphate dehydrogenase in mycobacterium and nocardia species, but absence from streptomyces and corynebacterium species and methanogenic archaea.a range of organisms known to contain f420 or to be relatives of mycobacteria were examined for f420-dependent glucose-6-phosphate dehydrogenase (fgd) and nadp-dependent glucose-6-phosphate dehydrogenase (nadp-g6pd) activities. all free-growing mycobacterium species examined (including a virulent mycobacterium tuberculosis strain) had fgd activities of 0.014-0.418 mumol min-1 mg protein-1, and nadp-g6pd activities of 0.013-0.636 mumol min-1 mg-1. armadillo-grown mycobacterium leprae had fgd acti ...19978997717
il-15, an immunomodulator of t cell responses in intracellular infection.il-15 is a novel cytokine with potent t cell growth factor activity. here, we investigated the role of il-15 in the human immune response to intracellular infection by studying patients leprosy. we found that il-15 mrna and protein were more strongly expressed in immunologically resistant tuberculoid patients than in with unresponsive and susceptible lepromatous patients. in vitro, mycobacterium leprae induced il-15 secretion from peripheral blood monocytes. furthermore, ril-15 by itself and in ...19978992997
multidrug-resistance to dapsone, rifampicin, and ofloxacin in mycobacterium leprae. 19978996430
hla-dr polymorphism modulates the cytokine profile of mycobacterium leprae hsp-reactive cd4+ t cells.in the present study, in vitro attempts have been made to define the cytokine profile of cd4+ t cells from polar leprosy patients and healthy individuals against mycobacterium leprae-derived heat shock proteins (hsps), hsp65 and hsp18, and their trypsin-digested fragments, relating to hla-dr polymorphism. while all tryptic fragments of optimal digestion and undigested hsps could stimulate cd4+ t cells from tuberculoid (tt) leprosy patients and healthy contacts (stimulation index, si > 2.0), only ...19979000043
reactivity of a population of armadillo lymphocytes with an antibody to human gamma,delta t-cells.reactivity of lymphocytes from the nine-banded armadillo (dasypus novemcinctus) was examined by flow cytometry using a panel of 16 commercially available fluorochrome-conjugated monoclonal antibodies raised against human or murine leukocyte antigens. the only reactivity observed was with antibody tcrdelta1, directed against a common determinant on the delta chain of the human gamma,delta t-cell receptor. using this antibody, a distinct, bright population of lymphocytes was seen in the peripheral ...19979000044
use of the polymerase chain reaction in the diagnosis of leprosy.one of the main limitations for successful epidemiological control of leprosy is the lack of a method for its diagnosis in subclinical cases. because of the long incubation period of the disease, liberation and spread of mycobacterium leprae during subclinical stages-principally in cases of untreated multibacillary forms of leprosy-constitute the main source of infection. this report describes the use of the polymerase chain reaction (pcr) for the detection of m. leprae in different types of tis ...19979060878
interferon-gamma differentially regulates interleukin-12 and interleukin-10 production in leprosy.the ability of monocytes to influence the nature of the t cell response to microbial pathogens is mediated in part by the release of cytokines. of particular importance is the release of il-12 and il-10 by cells of the monocyte/macrophage lineage upon encountering the infectious agent. il-12 promotes cell mediated immunity (cmi) to intracellular pathogens by augmenting t-helper type 1 responses, whereas il-10 downregulates these responses. the ability of ifn-gamma to modulate the balance between ...19979006002
experimental evaluation of possible new short-term drug regimens for treatment of multibacillary leprosy.groups of nude mice, with both hind footpads infected with 10(8) mycobacterium leprae organisms, were treated with 4-week courses of different drug combinations. the effect treatment on each group was evaluated by subinoculating footpad homogenates from the treated mice into groups of normal and nude mice for subsequent regrowth, assessed 1 year later. a combination of rifampin (rmp) with clarithromycin (clari), minocycline (mino), and ofloxacin (oflo) resulted in the complete killing of m. lepr ...19979021187
detection of mycobacterial dna in formalin-fixed, paraffin-embedded tissue specimens by duplex polymerase chain reaction: application to histopathologic diagnosis.granuloma is a chronic inflammatory process associated with noninfectious agents or infectious diseases such as tuberculosis. determination of the causative agent might be occasionally difficult in histopathologic sections. in this study, we examined 60 specimens of granuloma or inflammatory lesions that were originally diagnosed as 51 cases of granulomatous inflammation, 6 of leprosy, and 3 of atypical mycobacteriosis. the diagnoses in the last two categories were made both histologically and c ...19979021730
release of reactive nitrogen intermediates from the peripheral blood-derived monocytes/macrophages of leprosy patients stimulated in vitro by tuftsin.the production of reactive nitrogen intermediates (rni) by macrophages is critical to host defence, particularly for exerting the bactericidal and tumoricidal properties. nitric oxide (no) were measured in the peripheral blood-derived monocytes/macrophages of normal and leprosy patients (bt/tt and bl/ll) in the presence and absence of 'tuftsin' as a function of in vitro culture age (on 1, 3, 7 days). macrophages from both groups of leprosy patients were able to produce no during the unstimulated ...19979121327
molecular characterization of the aspergillus nidulans trea gene encoding an acid trehalase required for growth on trehalose.aspergillus nidulans conidiospores contain high levels of the non-reducing disaccharide trehalose. we show that upon induction of conidiospore germination, the trehalose pool is rapidly degraded and a glycerol pool is transiently accumulated. a trehalase with an acidic ph optimum was purified from conidiospores. characterization of the trea gene encoding this trehalase shows that it is homologous to saccharomyces cerevisiae vacuolar acid trehalase, the product of the ath1 gene, and to two relate ...19979140977
on the catalase-peroxidase gene, katg, of mycobacterium leprae and the implications for treatment of leprosy with isoniazid.the toxicity of the potent tuberculocidal agent, isoniazid, is mediated by the heme-containing enzyme, catalase-peroxidase, encoded by the katg gene. although isoniazid has been used for the treatment of leprosy, it is shown here that the katg gene of mycobacterium leprae is a pseudogene, which has probably been inactivated by multiple mutations. inactive genes were detected by the polymerase chain reaction in several isolates of m. leprae, of different geographical origins, and attempts to comp ...19979141669
catalytic properties of lipoamide dehydrogenase from mycobacterium smegmatis.lipoamide dehydrogenase from mycobacterium smegmatis was purified to homogeneity over 60-fold. of 20 amino acid residues identified at the amino terminus of the enzyme, 18 and 17 were identical to the sequences of mycobacterium leprae and pseudomonas fluorescens lipoamide dehydrogenases, respectively. the visible spectrum of the isolated enzyme was characteristic of a flavin in apolar environment. reduction of the enzyme with dithionite results in the appearance of an absorbance shoulder at 530- ...19979143318
pregnancy in patients with hansen disease.three pregnancies occurred in a cohort of 40 patients with hansen disease during a 6-year period. there are few recent reports in the english literature that deal with pregnancy in patients with hansen disease. these 3 cases are presented in the context of previously reported cohorts.19979158416
increased intracellular survival of mycobacterium smegmatis containing the mycobacterium leprae thioredoxin-thioredoxin reductase gene.the thioredoxin (trx) system of mycobacterium leprae is expressed as a single hybrid protein containing thioredoxin reductase (tr) at its n terminus and trx at its c terminus. this hybrid trx system is unique to m. leprae, since in all other organisms studied to date, including other mycobacteria, both tr and trx are expressed as two separate proteins. because trx has been shown to scavenge reactive oxygen species, we have investigated whether the tr-trx gene product can inhibit oxygen-dependent ...19979199416
human t-cell clones to the 70-kilodalton heat shock protein of mycobacterium leprae define mycobacterium-specific epitopes rather than shared epitopes.the mycobacterial 70-kda heat shock protein (hsp70) is a dominant antigen during the human t-cell response to mycobacterial infection despite the conserved sequence with the human homolog. to determine whether this response is pathogen specific, cd4+ t-cell clones were isolated from mycobacterium leprae hsp70-reactive individuals. the cytokine profile of the clones was mixed, with all of the clones releasing interferon gamma and half releasing interleukin-4 on stimulation, while six demonstrated ...19979038316
the mannose receptor delivers lipoglycan antigens to endosomes for presentation to t cells by cd1b molecules.we have characterized the cd1b-mediated presentation pathway for the mycobacterial lipoglycan lipoarabinomannan (lam) in monocyte-derived antigen-presenting cells. the macrophage mannose receptor (mr) was responsible for uptake of lam. antagonism of mr function inhibited both the internalization of lam and the presentation of this antigen to lam-reactive t cells. intracellular mrs were most abundant in early endosomes, but they also were located in the compartment for mhc class ii antigen loadin ...19979047240
nerve growth factor production and expression of p75 by schwann cells and neurofibroblasts in response to m. leprae infection and macrophage secretory products.this study describes the changes occurring in vitro in nerve growth factor (ngf) production and expression of p75 by murine schwann cells and neurofibroblasts, following infection with mycobacterium leprae and in the presence of macrophage secretory products, using a semiquantitative elisa. these parameters are compared in two strains of mice, swiss white (sw) and c57b1/6, as they differ in their response to m. leprae infection; c57b1/6 is the 'resistant' strain. on infection, ngf levels remaine ...19979061691
household and dwelling contact as risk factors for leprosy in northern malawi.data on household and dwelling contact with known leprosy cases were available on more than 80,000 initially disease-free individuals followed up during the 1980s in a rural district of northern malawi. a total of 331 new cases of leprosy were diagnosed among them. individuals recorded as living in household or dwelling contact with multibacillary patients at the start of follow-up were at approximately five- to eightfold increased risk of leprosy, respectively, compared with individuals not liv ...19979215227
subcellular localization of the 65-kda heat shock protein in mycobacteria by immunoblotting and immunogold ultracytochemistry.the 65-kda heat shock protein (hsp65) is an immunodominant antigen in mycobacterial infections and also the key etiologic factor in mycobacteria-induced autoimmune arthritis. because the subcellular distribution of hsp65 in the mycobacteria may be relevant to understand its immunoreactivity, we have investigated the presence of hsp65 in the envelope and cytoplasmic compartments of the bacilli. anti-hsp65 antibodies were used in western blottings to investigate the presence of hsp65 in cell fract ...19979066146
the rlep-flanked pola gene from mycobacterium leprae is not transcribed in mycobacterium smegmatis.a pola mutant of mycobacterium smegmatis (ms) lacking dna polymerase activity could not support the replication of a pal5000-derived plasmid or a derivative harbouring the rlep-flanked pola gene from m. leprae (mlep). in contrast, the plasmid containing the m. tuberculosis pola gene transformed the mutant with high efficiency and complemented its damage-sensitive phenotype suggesting that the replication of the pal5000 origin is dependent on host poli function and that the rlep-flanked mlep pola ...19979073067
expression of mycobacterial antigens on murine dissociated schwann cells infected with mycobacterium leprae.mycobacterial antigens were detected in a cell surface elisa on murine dissociated schwann cells infected with mycobacterium leprae. the time kinetics of expression and its refractoriness to modulation with monensin suggests that the antigens are likely to be integrated into the membrane during bacterial entry. this may be partially responsible for the defective schwann cell functions leading to subsequent peripheral nerve damage.19979075220
interactions of oxyr with the promoter region of the oxyr and ahpc genes from mycobacterium leprae and mycobacterium tuberculosis.in contrast to the intact oxyr gene (a homolog of the central regulator of peroxide stress response in enteric bacteria) in mycobacterium leprae, this gene is inactive in all strains of m. tuberculosis. in both species, oxyr is divergently transcribed from ahpc, which encodes a homolog of alkyl hydroperoxide reductase. to initiate investigations of the regulation of oxidative stress in mycobacteria and consequences of the elimination of oxyr in m. tuberculosis, in this work we tested the hypothe ...19979079928
dual multimodular class a penicillin-binding proteins in mycobacterium leprae.the pona gene of cosmid l222 of the mycobacterium leprae genome library encodes a multimodular class a penicillin-binding protein (pbp), pbp1. the pbp, labelled with a polyhistidine sequence, has been produced in escherichia coli, extracted from the membranes with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane-sulfonate (chaps) and purified by ni2(+)-nitrilotriacetic acid-agarose chromatography. in contrast to the pon1-encoded class a pbp1, pbp1 undergoes denaturation at temperatures higher t ...19979226276
cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis.distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (hiv) infection, and gram-negative sepsis. cytokine profiles are determined to some extent by two functional subsets of t lymphocytes, th1 and th2. the th1 cytokines (interferon gamma, int ...19979085311
neural targeting of mycobacterium leprae mediated by the g domain of the laminin-alpha2 chain.we report that the molecular basis of the neural tropism of mycobacterium leprae is attributable to the specific binding of m. leprae to the laminin-alpha2 (ln-alpha2) chain on schwann cell-axon units. using recombinant fragments of ln-alpha2 (rln-alpha2), the m. leprae-binding site was localized to the g domain. rln-alpha2g mediated m. leprae binding to cell lines and to sciatic nerves of dystrophic dy/dy mice lacking ln-alpha2, but expressing laminin receptors. anti-beta4 integrin antibody att ...19979118224
effects of essential fatty acid deficiency on prostaglandin e2 production and cell-mediated immunity in a mouse model of leprosy.results from animal and in vitro studies suggest that essential fatty acid (efa) deficiency enhances cell-mediated immunity by reducing production of prostaglandins with immunosuppressive actions. however, direct experimental evidence that efa deficiency enhances t-lymphocyte function in vivo has not been obtained. in this study, athymic (nu/nu) mice were infected in the footpads with mycobacterium leprae and fed a linoleic acid-free diet. these mice, and infected nu/nu mice on control diets, we ...19979119445
field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first results.in 1995, a field trial was implemented in senegal in order to evaluate the efficacy of a regimen based on the monthly supervised intake of rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. during the first year of the trial, 220 patients with active leprosy (newly detected or relapsing after dapsone monotherapy) were recruited: 102 paucibacillary (pb) (60 males and 42 females) and 118 multibacillary (mb) (71 males and 47 females). all of them accepted the new treatment ( ...19979251595
bacillary and histopathological findings in the peripheral nerves of armadillos experimentally infected with m. leprae. 19979251602
further sequence analysis of the dna regions with the rhodococcus 20s proteasome structural genes reveals extensive homology with mycobacterium leprae.the sequence of the respective dna regions downstream of the 20s proteasome structural genes prcb1a1 (6 kb) and prcb2a2 (3.3 kb) of rhodococcus erythropolis ni86/21 were determined. a highly conserved gene organization was observed between the two clusters which differed significantly in g + c content (68.8% versus 62.6%). several orfs were homologues of putative genes previously identified by genomic sequencing of the equivalent dna in the related nocardioform actinomycete, mycobacterium leprae ...19979254018
[regulation of the immune response: the th1/th2 concept].the immune system has different possible ways of reacting to an antigen. the choice of an appropriate immune response is determined by the manner of antigen presentation, the amount of antigen, the localization of antigen uptake, the type of antigen presenting cell, the genetic predisposition of the individual and the presence of certain cytokines released by antigen presenting or other inflammatory cells. an immune response which is not not appropriate can lead to clinical symptoms or insuffici ...19979132932
nucleotide sequence of the mycobacterium leprae katg region.synthetic oligonucleotide primers based on the dna sequence data of the escherichia coli, mycobacterium tuberculosis, and mycobacterium intracellulare katg genes encoding the heme-containing enzyme catalase-peroxidase were used to amplify and analyze the mycobacterium leprae katg region by pcr. a 1.6-kb dna fragment, which hybridized to an m. tuberculosis katg probe, was obtained from an m. leprae dna template. southern hybridization analysis with a probe derived from the pcr-amplified fragment ...19979139928
borderline tuberculoid leprosy: clinicopathological evaluation of multidrug therapy.efficacy of multi-drug therapy as per who recommendation in 125 fresh cases of borderline tuberculoid (bt) leprosy was evaluated. there were 116 (92.8%) male and 9 (7.2%) female patients. age of the patients ranged from 18-50 years but the majority (80.8%) were young adults in the age group 21-35 years. the commonest site of lesion was the upper extremity in 65 (52%) cases. skin smear for acid fast mycobacterium leprae was positive in 11 (8.8%) patients. all patients were given multidrug therapy ...199728769451
leprosy resistant to multi-drug-therapy (mdt) successfully treated with ampicillin-sulbactam combination--(a case report).a 50 year male developed a discoid lesion of leprosy on the face. inspite of dapsone 100 mg/day and rifampicin 600 mgm per day the disease spread to both sides of the face and forehead. it became worse with prednisolone and clofazimine. it cleared completely when sultamicillin was added to the latter. this seems to be the first patient of leprosy to be treated with this combination and reported.19969141351
anti-pgl-1 antibody levels in thai leprosy patients.phenolic glycolipid - 1 (pgl-1) is a mycobacterium leprae specific cell wall component. it is an immunodominant antigen and can induce a strong humoral immune response. igm antibody levels against pgl-1 were measured in thai leprosy patients between october 1992-april 1994 by a commercially available m. leprae particle agglutination test (mlpa). the percentage of seropositivity was much higher in newly untreated multibacillary (mb) patients (83.9%) than in paucibacillary (pb) patients (17.8%). a ...19969253875
immunological status of enl (erythema nodosum leprosum) patients: its relationship to bacterial load and levels of circulating il-2r.recent data suggest that the clinical course of reactional states in leprosy is closely related to the cytokine profile released locally or systemically by the patients. in the present study, patients with erythema nodosum leprosum (enl) were grouped according to the intensity of their clinical symptoms. clinical and immunological aspects of enl and the impact of these parameters on bacterial load were assessed in conjunction with patients' in vitro immune response to mycobacterial antigens. in ...19969071029
[an experimental nerve lesion simulating leprous neuropathy produced in the nude mice by the inoculation of a leproma-derived and cultivable mycobacterium hi-75].among the lesions caused by mycobacteriosis, peripheral neuropathy has been regarded as the pathognomonic one peculiar to leprosy which is caused only by m. leprae (ml) which can not be cultivated. if that whole sentence is correct, no past report should be in existence concerning the peripheral neuropathy caused by the experimental inoculation of certain cultivated mycobacterium and not of ml. there was, however an exception challenging to that theory which was done by sasaki et al. in 1985. th ...19969050357
a genomic study of the leproma-derived and cultivable mycobacterium hi-75. the direct dna sequencing of pcr product of 16s ribosomal rna. 19969050358
vaccination against leprosy--the view from 1996. 19969033195
primary resistance to single and multiple drugs in leprosy--a mouse footpad study.skin biopsy homogenates obtained from three cases of lepromatous leprosy with no prior history of antileprosy treatment were tested in the mouse footpad for the sensitivity of mycobacterium leprae to multiple drugs. one of the inocula was sensitive to all the three drugs tested using the highest concentration each of dds 0.01 g%, rfp 0.03 g% and clf 0.01 g%. the 2nd inocula showed growth in the presence of 0.01 g% dds only. while the 3rd inocula (pt. ku) tested resistant to all the three drugs i ...19969033198
borderline--tuberculoid leprosy: clinical and immunological heterogeneity.the authors analysed some immunological criteria in leprosy patients diagnosed as borderline tuberculoid by the presentation of different grades of skin lesions as well as different grades of nerve involvement. only 50% of the patients presented a single skin lesion and 58% had none or only one affected nerve. nineteen patients (39.6%) showed a positive lepromin reaction (induration > or = 5 mm). patients with a positive skin test had a greater number of skin lesions when compared with patients ...19969033199
suppression of lymph node lymphoproliferation to viable mycobacterium leprae by peripheral blood-derived monocytes. 19969033205
enzyme-linked immunosorbent assay (elisa) with mycobacterial crude antigens for the sero-epidemiological diagnosis of active tuberculosis.in search for reliable, nonexpensive procedures for tuberculosis diagnosis suitable for seroepidemiological studies in leprosy-endemic areas, enzyme-linked immunosorbent assays (elisas) with whole intact bacilli, whole lipid-free bacilli and protein-enriched soluble extracts from the h37rv mycobacterium tuberculosis strain were evaluated. sera tested came from 47 active, pulmonary tuberculosis adult cases, 60 household contacts of active tuberculosis cases, 20 lepromatous leprosy adult patients, ...19969030108
detection of m. leprae by gene amplification; combined ethidium-bromide staining and probe hybridization.biopsy and skin-scraping specimens from 130 leprosy cases across the disease spectrum (56 tt/bt/i, 73 bb/bl/ll, and 1 neuritic case) and 50 healthy contacts were studied to assess the application of gene amplification. the nucleic acids from these clinical specimens were extracted by an integrated freeze-thawing--optimized lysozyme-/proteinase-k treatment-purification and fractionation procedure. the nucleic acids from cultured organisms were isolated by the stepwise procedure earlier standardiz ...19969030107
use of nasba rna amplification for detection of mycobacterium leprae in skin biopsies from untreated and treated leprosy patients.this study was performed to assess the value of nasba rna amplification of a 16s rrna target for the detection of presumably viable mycobacterium leprae in sections of skin biopsies from leprosy patients. the nasba positivity rate was 90.4% (84/93) for untreated multibacillary (mb) patients [bacterial index (bi) > or = 2] and 16.7% (8/48) for the untreated paucibacillary (pb) patients (bi < 2). nasba positivity showed a good concordance with the presence of solidly stained m. leprae [morphologic ...19969030105
polymerase chain reaction of nasal swabs from tuberculosis patients and their contacts.previous studies have found mycobacterium leprae in nasal swabs from leprosy patients, their contacts, and persons living in endemic areas. it might be expected that m. tuberculosis would be present on nasal mucosa of pulmonary tuberculosis patients, but whether they can be detected in patients or contacts is unknown. we used the polymerase chain reaction (pcr) technique on nasal swabs from tuberculosis patients, contacts of tuberculosis patients, leprosy patients, and london controls to look fo ...19969030106
susceptibility of severe combined immunodeficient mice to mycobacterium leprae.the susceptibility of severe combined immunodeficient (scid) mice to human leprosy bacilli was investigated. nude mice were used as controls. scid mice were found to be highly susceptible to mycobacterium leprae and the progress of infection was comparatively 2-3 months earlier than observed in the nude mice. after reaching a maximum of approximately 1 x 10(9) acid fast bacilli/foot pad at about 8 months postinfection the number of bacilli gradually decreased. the progress of infection in nude m ...19969121376
short-term follow up of patients with multibacillary leprosy and hiv infection.during a period of 9 years, four male patients with hiv and hansen's disease were detected in tamil nadu, south india. the sequence as to which infection came first is not known. all had high-risk sexual behavior with commercial sex workers and a past history of genital ulcer disease. their spectrum of leprosy was multibacillary. patient no. 1 had pure neural leprosy of the lepromatous type, which is rare. he also had a single episode of type 1 reaction which did not require steroid therapy. des ...19969030104
lipids from mycobacterium leprae cell wall are endowed with an anti-inflammatory property and inhibit macrophage function in vivo.in general, the majority of bacteria are pre-inflammatory when injected in experimental animals. however, mycobacterium leprae has no inflammatory effect when injected into mouse footpad, but using the delipidated mycobacteria we observed a mild significant increase in footpad oedema. other mycobacteria, mycobacterium bovis-bcg or m. tuberculosis induce a strong paw oedema. furthermore, m. leprae reduced locally the bcg-induced inflammatory reaction in mouse footpad, whereas delipidated m. lepra ...19969014830
cloning and expression of transaldolase from potato.we have isolated a cdna encoding transaldolase, an enzyme of the pentose-phosphate pathway, from potato (solanum tuberosum). the 1.5 kb cdna encodes a protein of 438 amino acid residues with a molecular mass of 47.8 kda. when the potato cdna was expressed in escherichia coli a 45 kda protein with transaldolase activity was produced. the first 62 amino acids of the deduced amino acid sequence represent an apparent plastid transit sequence. while the potato transaldolase has considerable similarit ...19968980493
sensitization and reactogenicity of two doses of candidate antileprosy vaccine mycobacterium w.m.w vaccine is one of the antileprosy vaccines under test in an ongoing comparative vaccine trial in south india. the objective of the present study was to examine the sensitizing ability, as measured by skin test reactions to rees' mlsa and lepromin, and reactogenicity of m.w vaccine in the local population. two doses of m.w, 1 x 10(9) bacilli and 5 x 10(9) bacilli, were used, in two separate studies of 395 and 400 "healthy" individuals aged 1-65 years. in each study, the study subjects receive ...19969001899
antibody production to heat shock proteins with mr 65 kd (hsp65) in cutaneous inflammation: a possible relation to focal infection.in order to correlate the immunomodulatory roles of homologous heat shock proteins with mr 65 kd (hsp65) to skin diseases, antibody level to recombinant-hsp65 of mycobacterium leprae was quantified with enzyme-linked immunosorbent assay (elisa) in the sera of patients. in psoriasis, an insignificant increase was observed in anti-hsp65 igg (0.111 +/- 0.053, mean +/- sd in 0d492 nm, n = 22), compared with a normal group (0.080 +/- 0.032, n = 9). however, psoriasis of acute guttate-type (pga), whic ...19969082780
microbial colonizers in leprosy skin ulcers and intensity of inflammation.the microflora of 55 patients with leprosy skin ulcers was studied and related to a weighted inflammatory score (is). the control group consisted of 18 ulcers with different underlying pathology. leprosy ulcers were characterized by the exclusive presence of two types of branching gram-positive rods; a particular interesting proposal is that mycobacterium leprae share common antigens with these unusual "leprosy ulcer associated" organisms and group g beta-hemolytic streptococci. in the leprosy g ...19968862261
investigation of anti-mycobacterium leprae antibodies in leprosy patients' sera by an a60 antigen immunoassay. 19968862270
antibodies to phenolic glycolipid-i and sulfatide-i in leprosy and tuberculosis. 19968862271
effect of mycobacterium leprae on peripheral nerve protein phosphorylation; a preliminary study. 19968862273
bactericidal activities of combinations of new drugs against mycobacterium leprae in nude mice.the bactericidal activities of 12 regimens with various combinations of new drugs (clarithromycin [clari], minocycline [mino], and ofloxacin [oflo]) and the standard antileprosy drugs, especially rifampin (rmp), were compared in nude mice with established mycobacterium leprae infection. the longest duration of treatment was 24 weeks for intermittent (once every 4 weeks) therapy and 8 weeks for daily therapy. bactericidal effects were monitored by titrating the proportion of viable m. leprae isol ...19968834886
recombination in mycobacteria.mycobacterium tuberculosis, the causative agent of tuberculosis (tb) is thought to infect a quarter of the world's population and accounts for 3 million deaths each year. leprosy, caused by mycobacterium leprae continues to afflict millions. in many countries, the incidence of tb is increasing due to its association with acquired immune deficiency syndrome (aids) and the emergence of multidrug resistance strains of tubercle bacilli. genes that encode major antigens, enzymes, potential virulence ...19968858576
the cellular and molecular basis of immunity against mycobacterial diseases. 19968972118
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