Publications

detection of mycobacterium leprae nasal carriers in populations for which leprosy is endemic.	in order to better understand the role of mycobacterium leprae nasal carriage in the maintenance of infection reservoirs and transmission of leprosy, we applied a polymerase chain reaction (pcr) that detected a 531-bp fragment of the pra gene of m. leprae on nasal swab specimens collected through a total population survey from individuals living in an area in which leprosy is endemic. among the total tested population of 1,228 people, 7.8% were found to be pcr positive. pcr positivity was shown ...	1993	8263180
the microbiology of mycobacterium leprae; progress in the last 30 years.	over the last 30 years, there have been dramatic changes in the way mycobacterium leprae is studied in the microbiology laboratory. the organism still has not been grown in vitro but, starting with demonstration of growth in the footpads of mice and culminating in the application of molecular biological and genetic techniques, we are now in a position to circumvent some of the difficulties arising from lack of cultivability. such studies are providing us with new insights into the basic biology ...	1993	8266397
immunology of leprosy.	the host immune response to mycobacterium leprae is critical for control of the infection but also responsible for the immunopathological damage to skin and nerves. the complex and varied immune responses to the organism are the basis for the clinical spectrum of disease ranging from tuberculoid to lepromatous leprosy. the cellular interactions underlying this spectrum are discussed and the antigenic components of the bacillus briefly reviewed. m. leprae has evolved a variety of mechanisms to av ...	1993	8266398
major structural features of the cell wall arabinogalactans of mycobacterium, rhodococcus, and nocardia spp.	the cell wall arabinogalactans of strains of mycobacterium, rhodococcus, and nocardia were per-o-methylated, partially hydrolyzed with acid, and the resulting oligosaccharides were reduced and per-o-ethylated to yield per-o-alkylated oligoglycosyl alditol fragments. analyses of these fragments by gas chromatography-mass spectrometry and of the intact solubilized polysaccharides by 1h and 13c nmr revealed the major structural features of the different arabinogalactans from representatives of the ...	1993	8275507
in vivo effect of delipidified cell component of mycobacterium leprae in relation to infection with leprosy bacteria in mice.	the delipidified cell component (dcc) of mycobacterium leprae was used as an immunomodulatory agent in swiss white mice. the peritoneal macrophages of these mice were activated to produce increased amount of reactive oxygen intermediates like hydrogen peroxide (h2o2) and superoxide. these macrophages also attained the ability to kill m. leprae in vitro as shown by several assay systems including the conventional mouse foot-pad technique. the increased levels of superoxide seem to be responsible ...	1993	8283062
bacillaemia and mycobacterium leprae cell wall antigen in paucibacillary leprosy.	a study was undertaken to estimate bacillaemia and m. leprae antigen detection in 54 paucibacillary leprosy patients (tt, bt). acid-fast bacilli were detected in the blood of 14.8% patients of borderline tuberculoid (bt) leprosy. m. leprae antigen was demonstrated in 48.2% patients of bt leprosy. slit-skin smears were negative in all these patients. at the end of treatment (6 months of who-mdt) all the follow-up blood samples were negative for both bacillaemia and m. leprae antigen in the serum.	1993	8283063
towards an evolving consensus on leprosy bacillus.		1993	8283073
an immunodominant 30-kda antigen of a candidate anti-leprosy vaccine, mycobacterium w, shares t and b cell determinants with m. leprae and m. tuberculosis.	earlier we reported that vaccination of leprosy patients with mycobacterium w induces an immune response directed predominantly against low molecular weight antigens. one of these antigens, with a molecular mass of 30-kda, was recognized by a majority of the vaccinated subjects as well as the tuberculoid leprosy patients and healthy contacts. in the present communication we report further characterization of this antigen. immunofluorescence and western blot studies with antibodies raised against ...	1993	8283960
the 19th kellersberger memorial lecture, 1993. nerve damage, disabilities and rehabilitation in leprosy.		1993	8287863
[development of hybridomas secreting monoclonal anti-idiotypic antibodies that bear the internal image of the terminal trisaccharide of pgl-i].	two hybridomas designated as f7b7 and f7b9 secreting monoclonal anti-idiotypic antibodies against terminal trisaccharide of pgl-i were developed by fusion of sp2/0 cells and spleen cells of balb/c mouse immunized with mouse monoclonal anti-trisaccharide of pgl-i (mab1-e10f1). to characterize the f7b7, the following results were obtained. first, f7b7 reacted with mab1-e10f1 specifically. secondly, the cross elisa neutralizing tests gave positive results. the binding of anti-trisaccharide positive ...	1993	8288190
[production and identification of monoclonal anti-idiotype antibodies against anti-phenolic glycolipid-i antibody of mycobacterium leprae].	hybridoma (4c4) secreting monoclone anti-idiotype antibody (mcab2) against anti-phenolic glycolipid-i (pgl-i) antibody (ab1) was produced by fusion of sp2/0 myeloma cells and spleen cells of syngeneic mice which had been previously tolerant to human igm 4c4 monoclone anti-idiotype antibody was identified with a series of experiments including competitive and neutralizing inhibition elisa. it was found that the binding of mcab2 with rabbit anti-pgl-i antibody could be competitively inhibited by n ...	1993	8288191
[the isolation of monoclonal antibodies to strains of mycobacterium leprae passed through laboratory animals].	hybridoma synthetizing monoclonal antibodies (mab) iiie4 has been obtained in hybridization of myeloma p3-x63-ag8. 653 cells and splenocytes from balb/c mice immunized with m. leprae passaged on rats. the mab specificity evaluated by enzyme immunoassay using ultrasonic disintegrates of m. leprae obtained from human, dasypus novemcinctus, rat lepromas as well as mycobacteria of 7 species and e. coli indicated that the mab reacted only with mycobacteria passaged on the rats. they had weak cross re ...	1993	8290533
use of beta-lactam/beta-lactamase-inhibitor combinations as antimycobacterial agents.	mycobacterium tuberculosis and mycobacterium leprae develop resistance against the drugs used to treat tuberculosis and leprosy, respectively. now multidrug-resistant tuberculosis is spreading in many countries, especially with the emergence of aids. multidrug treatment is being promoted at present to eradicate leprosy. since m. leprae may also become multidrug-resistant, new approaches have to be adopted for controlling mycobacterial diseases. mycobacteria usually synthesize beta-lactamase and ...	1993	8302203
water soluble complex of palmitic acid in media for cultivation of leprosy-derived psychrophilic mycobacteria from mycobacterium leprae infected tissues.	palmitic acid and palmitates were transformed into water soluble complexes with crystalline heptakis-2,6-di-0-methyl-beta-cyclodextrin. this formulation was incorporated into liquid and solid chemically well-defined media. the fatty acid served as c and energy source, ammonium thioglycolate as the sole source of n with the sh group as further source of energy. minute amount of dimethyl-sulfoxide added was used for its known effect on cell membrane permeability. the media were inoculated with hos ...	1993	8304006
two sisters with leprosy.	leprosy is a rare entity in japan, but remains quite common in developing countries. we report two sisters with leprosy from brazil but currently working in japan who presented to our clinic. the younger sister was infected with the bb type with hla-a2, a24, b51, bw52, dr2, drw8, drw52, dqw1, and dqw3. the elder sister had the tt type with hla-a2, a31, b51, cw3, drw6, drw8, drw52, dqw1, and dqw3. immunohistochemical findings revealed that cd4+, 4b4+ helper/inducer t-cells were dominant in the gr ...	1993	8315112
tumor cells transfected with a bacterial heat-shock gene lose tumorigenicity and induce protection against tumors.	the gene encoding a highly immunogenic mycobacterial heat-shock protein (hsp65) was transfected into the murine macrophage tumor cell line j774. the resulting hsp65-expressing cells (j774-hsp65) were no longer able to produce tumors in syngeneic mice. this loss of tumorigenicity was not mediated through t cells since the transfected cells did not produce tumors in athymic mice. if mice are first immunized with the j774-hsp65 cells and then challenged with the parent j774 cells, the mice do not d ...	1993	8315389
mycobacterium smegmatis rna polymerase: dna supercoiling, action of rifampicin and mechanism of rifampicin resistance.	we have isolated rna polymerase from mycobacterium smegmatis and established conditions for specific transcription initiation in vitro. the m. smegmatis enzyme has a strong dependence on supercoiling of the dna substrate for transcription from mycobacterial promoters. we also show that rna polymerase is the target for rifampicin, and that this antibiotic specifically inhibits the transition from synthesis of short oligoribonucleotides to full-length transcripts. rna polymerase isolated from a ri ...	1993	8316080
[study on subclinical infection with m. leprae--a follow-up].	in this article, we reported the results of studies on the rates of subclinical infection (si) among leprosy contacts and a follow-up using pgl-i-elisa. the results indicated that: (1) the rates of si were higher in household contacts than those in around population; (2) factors such as type of leprosy, degree of contact affected the development of si; (3) among 97 followed-up contacts, one person developed clinical leprosy in the second year; (4) acid-fast bacilli (afb) were seen in the skin or ...	1993	8324834
suppression of human monocyte cytokine release by phenolic glycolipid-i of mycobacterium leprae.		1993	8326172
effects of chemotherapy on antibody levels directed against pgl-i and 85a and 85b protein antigens in lepromatous patients.	igg antibodies against antigens 85a and 85b from mycobacterium bovis bcg, igm antibodies against phenolic glycolipid-i (pgl-i) and circulating pgl-i antigen were measured in the serum of 11 patients with lepromatous leprosy receiving multidrug therapy (mdt). before treatment, 6 patients were reactive to antigen 85a, 10 patients to antigen 85b, and 11 patients to pgl-i; circulating pgl-i was detected in the sera of all of them. after 2 years of mdt pgl-i antigen could no longer be detected in all ...	1993	8326178
serological monitoring of the response to chemotherapy in leprosy patients.	sixty-five patients initially seropositive for igm anti-phenolic glycolipid-i (pgl-i) antibodies were tested for antibody levels to pgl-i, lipoarabinomannan (lam), and the 35-kda protein of mycobacterium leprae at regular intervals for up to 30 months following the commencement of multidrug therapy (mdt). there was a steady decline in igm anti-pgl-i and anti-35-kda antibody levels to a mean of 17% and 14%, respectively, of the starting level at 24 months. the development of type 1 and type 2 rea ...	1993	8326179
circulating immune complexes in leprosy sera: demonstration of antibodies against mycobacterial glycolipidic antigens in isolated immune complexes.	circulating immune complexes (cic) were assayed in sera of leprosy patients. using an immunoassay for two mycobacterial antigens--phenolic glycolipid-i (pgl-i) and glycolipid iv (sl-iv)--sera from 65 patients with leprosy (38 lepromatous, 18 borderline, and 9 tuberculoid) were studied. the cic were isolated by polyethylene glycol (peg) precipitation, washed, treated with an acid buffer, neutralized, and tested using an enzyme-linked immunosorbent assay (elisa). we demonstrated that cic could con ...	1993	8326180
lymphocyte proliferation, ifn-gamma production and limiting dilution analysis of t-cell responses to icrc and mycobacterium leprae antigens in leprosy patients.	lymphocyte proliferative responses and interferon-gamma (ifn-gamma) production after stimulation with antigens of icrc, mycobacterium leprae, and purified protein derivative (ppd) were assessed in leprosy patients and healthy donors. the patients studied were newly diagnosed as having lepromatous leprosy (ll), multidrug therapy (mdt) responders (mdt-r ll), mdt nonresponders (mdt-nr ll), borderline lepromatous (bl), and borderline tuberculoid/tuberculoid (bt/tt) leprosy. the tuberculoid leprosy p ...	1993	8326181
clarithromycin is bactericidal against strains of mycobacterium leprae resistant and susceptible to dapsone and rifampin.	the anti-mycobacterium leprae activity of clarithromycin when administered alone and in combination with rifampin and dapsone in the diet was determined using the kinetic method of drug evaluation in mice. clarithromycin when administered at a concentration of 0.1% (w/w) in the diet completely prevented growth of 2 pan-susceptible, 3 dapsone-resistant, 2 rifampin-resistant, and 2 rifampin and dapsone double resistant strains of m. leprae. a 0.03% (w/w) concentration also completely prevented gro ...	1993	8326182
search for effective short-course regimens for the treatment of leprosy.		1993	8326183
leprosy today.	leprosy is a disease common to developing countries. it is relatively rare in europe. there are an estimated 5.5 million patients in the world, of which two-thirds are found in south east asia. currently, 3.1 million are registered for treatment. mycobacterium leprae, the causative organism of leprosy, is an intracellular acid-fast organism not cultivable in vitro. the disease is transmitted from man to man mainly through inhalation. the disease occurs in several types depending upon the immunol ...	1993	8327871
t cell unresponsiveness in lepromatous leprosy.	t lymphocytes from patients with lepromatous leprosy are anergic to m. leprae antigens. the mechanisms which induce and maintain this antigen specific t cell unresponsiveness in lepromatous leprosy have been the subject of intensive research. recent insights from work on t cell recognition of antigen, cytokines, and t cell subsets have considerably enhanced the understanding of the immunopathology of lepromatous leprosy.	1993	8336323
in leprosy the presence of mycobacteria in the nerve is an essential factor in the cycle and spectrum of mycobacterium leprae infection.	a total of 220 untreated leprosy patients who underwent parallel skin and nerve biopsies are included in this study, which is intended to evaluate the extent of previously reported differences in bacillary load between skin and nerve lesions in leprosy and to describe the response of peripheral blood lymphocytes to mycobacterium leprae antigens in such patients. in 161 patients out of the 220, the skin and nerve biopsies were diagnostic for leprosy. when patients were grouped according their ski ...	1993	8341112
pilot study to determine acceptability and ability of heat-killed mycobacterium leprae plus bcg (hkml+bcg) vaccine to induce skin test conversion.	although local reactions, including erythema, induration and ulcers, appeared in every patient after the injection of the combined hkml+bcg vaccine, they were accepted by the patients. there was no tendency for the local reaction to become aggravated after repeated vaccination. however, systemic reactions, mainly iridocyclitis and complaint of numbness of the fingers and toes, became quite common after the 5th vaccination and therefore significantly reduced the acceptability of vaccine by inject ...	1993	8341114
survey for secondary dapsone and rifampicin resistance in cuba.	a total of 1211 cuban multibacillary leprosy patients treated for at least 5 years were clinically and bacteriologically examined. they were being treated according to a 2-phase monotherapy regimen with rmp first and dadds afterwards. on skin-smear examination 50 patients were found positive, of which 9 showed a bi of 3+ or higher at any site. with regard to the clinical status the only cases found with clinical signs of relapse were 5 out of 7 long-standing patients with bi of 4+ and 5+. a 6th ...	1993	8341115
inventory of skin smear practices in 6 leprosy control programmes in nigeria.	a study of slit skin smear (sss) examination practices in 6 nigerian leprosy control programmes was undertaken to assess the quality of smearing, staining and reading. results indicated that the standard of sss practices fall below the ideal. there is a great need for training as well as supervision and support of laboratory staff if this deplorable situation is to be improved.	1993	8341118
nucleotide sequence of mycobacterium leprae elongation factor (ef-tu) gene.		1993	8341612
observations on attempted leprosy cultures in two media.	suspensions of skin tissue material collected from lepromatous leprosy patients and material from mouse foot-pad harvests were inoculated into two media, viz., a biphasic medium and a minimal basal medium. the cultures were incubated at 37 degrees c and 15 degrees c. small oval (or round) cells appeared in these cultures around the tenth day along with a few cystic structures; and they increased in number later, reaching the maximum around six-seven weeks. the above cells appeared acid-fast in s ...	1993	8345230
application of filter paper method for collection of blood for mlpa test.	the results of mlpa test using serum and filter paper eluate have been compared in this paper. testing 64 patient samples at 1:32 dilution, 31 were negative by both serum and eluate, 20 were positive by both, six were positive only by serum and one was positive only eluate. in six other cases eluate gave equivocal results while serum result was clearly positive. some eluates negative at 1:32 dilution gave weak positive agglutination at 1:16 dilution.	1993	8345234
evolving consensus on the probable nocardioform morphology of the leprosy bacillus.		1993	8345235
t-cell stimulation with purified mycobacterial antigens in patients and healthy subjects infected with mycobacterium leprae: secreted antigen 85 is another immunodominant antigen.	peripheral blood leucocytes from 9 paucibacillary and 12 multibacillary leprosy patients, from 18 healthy controls and from 34 healthy leprosy contacts were stimulated with three mycobacterial heat shock proteins with respective molecular weights of 70, 65 and 18 kda and with the secreted 30-32 kda protein, also called antigen 85. antigen 85 was found to be the most powerful t-cell antigen (as measured by lymphoproliferation and ifn-gamma secretion), eliciting a positive response in all (100%) p ...	1993	8346416
[neurotropic properties of listeria monocytogenes and mycobacterium leprae in natural and experimental infections].		1993	8351384
determination of mycobacterium leprae viability by polymerase chain reaction amplification of 71-kda heat-shock protein mrna.		1993	8354932
the mycobacterium leprae antigen 85 complex gene family: identification of the genes for the 85a, 85c, and related mpt51 proteins.	the genes for two novel members (designated 85a and 85c) of the mycobacterium leprae antigen 85 complex family of proteins and the gene for the closely related m. leprae mpt51 protein were isolated. the complete dna sequence of the m. leprae 85c gene and partial sequences of the 85a and mpt51 genes are presented. as in m. tuberculosis, the m. leprae 85a, 85c, and previously identified 85b component genes are not closely linked on the genome. however, the mpt51 genes of both species localize clos ...	1993	8359887
cross-sectional assessment of elisa reactivity in leprosy patients, contacts, and normal population using the semisynthetic antigen natural disaccharide octyl bovine serum albumin (nd-o-bsa) in cebu, the philippines.	an indirect enzyme-linked immunosorbent assay (elisa) using natural disaccharide octyl bovine serum albumin (nd-o-bsa) as antigen was used in testing leprosy patients, contacts and a normal population in cebu, the philippines, from 1985 to 1989. a total of 1413 persons were studied. the results suggested that elisa reactivity and the bacterial index (bi) correlate in a general way. in multibacillary (mb) leprosy, positivity ranges from 54.2% to 92.3% among patients with a bi of < 2+ to > 4+ on t ...	1993	8371027
development of giant reaction in response to ppd skin test in lepromatous leprosy patients.	the present study analyzes some clinical and immunological aspects of the giant reaction (gr) in lepromatous leprosy. sixteen out of a total of 147 (10.9%) lepromatous patients developed the clinical features of gr upon the intradermal administration of ppd; most (14 of 16) grs occurred in bacteriologically positive cases. gr precipitated an episode of erythema nodosum leprosum (enl) in three patients. in addition, patients with gr showed enhanced in vitro response to ppd, by the lymphoprolifera ...	1993	8371029
serologic responses to nerve antigens in sooty mangabey monkeys with experimental leprosy.	eight sooty mangabey monkeys were inoculated intravenously and intradermally with varying doses of mycobacterium leprae from 4.8 x 10(7) to 4.8 x 10(10). serum samples were obtained from the animals at intervals of about 3 months for 90 months, and were examined for igm and igg antibodies to nerve antigens, including ceramide, galactocerebroside (gc), and asialo-gm1 (agm1), using an enzyme-linked immunosorbent assay (elisa). the serological results were then compared with clinical findings, part ...	1993	8371033
in vivo antileprosy activity of the newly synthesized benzoxazinorifamycin, krm-1648.	the in vivo anti-mycobacterium leprae activity of the newly synthesized benzoxazinorifamycin, krm-1648, was studied. krm-1648 was given orally to athymic nude mice, infected subcutaneously with m. leprae in the hindfoot pad, at doses between 0.001 and 0.01 mg of the drug/mouse/day six times per week, from day 31 to day 80. krm-1648 administration markedly suppressed bacterial growth in the foot pads for 360 days. krm-1648 given daily at the dose of 0.01 mg/mouse elicited a 2-4-log decrease in th ...	1993	8371034
attempts to grow mycobacterium leprae in a medium with palmitic acid as the substrate.		1993	8371039
leprosy; another possible source of transmission.		1993	8371040
immunological and functional characterization of proteins of the mycobacterium tuberculosis antigen 85 complex using synthetic peptides.	as tuberculosis re-emerges as an important health problem worldwide, new drugs, better diagnostic tests and vaccines are being sought. in order to identify potentially useful peptides for the development of a synthetic vaccine against tuberculosis, immunological and functional studies were performed using proteins of the antigen 85 complex. western blot (immuno-blot) analysis and a lymphoproliferation study was used to investigate the b- and t-cell immune response of tuberculosis patients, healt ...	1993	8371117
in vitro synergistic activity between ofloxacin and ansamycins against mycobacterium leprae.	the antimicrobial effects of ofloxacin, alone and in combination with either rifampicin or rifabutin, were evaluated against m. leprae, using in vitro cell-free culture system. the minimum inhibitory concentration (mic) of ofloxacin against m. leprae was 1.5 micrograms/ml, while mics of rifampicin and rifabutin were 0.4 and 0.2 microgram/ml, respectively. combination of 0.375 microgram/ml ofloxacin and 0.05 microgram/ml of rifabutin exhibited synergistic bactericidal activity while the effect of ...	1993	8387790
sparfloxacin is more bactericidal than ofloxacin against mycobacterium leprae in mice.	the comparative bactericidal activities of sparfloxacin and ofloxacin against mycobacterium leprae in mice were determined using the proportional bactericidal test at doses of 12.5 mg/kg-100 mg/kg. significant bactericidal activity was found at 12.5 mg/kg sparfloxacin and 25 mg/kg ofloxacin. sparfloxacin was significantly more bactericidal than ofloxacin at all doses, and the results with 25 mg/kg sparfloxacin were nearly identical to those obtained with 100 mg/kg ofloxacin. these results, toget ...	1993	8392100
animal model to study the mechanism of nerve damage in leprosy--a preliminary report.	intraneural injection of 10-20 x 10(6) viable mycobacterium leprae into the sciatic nerve of normal, unsensitized, swiss white mice gives rise to a tuberculoid type of granulomatous response in 2 weeks. the same dose of viable m. leprae when injected into the sciatic nerves of unsensitized immunosuppressed mice (t200 x 5r) elicited a macrophage response. when macrophages were systemically immobilized using an intraperitoneal injection of silica quartz dust in normal mice, the lesion produced was ...	1993	8392101
antigen-coated latex particles as a model system for probing monocyte responses in leprosy.	to study responses to mycobacterium leprae antigens, we developed an in vitro model system in which latex particles coated with m. leprae sonic extract (mlson) antigen were presented to monocytes. uptake and oxidative response as measured by superoxide production to these antigens were investigated. phagocytosis of mlson-coated particles was greater than that of control particles in monocytes from both leprosy patients and controls from leprosy-endemic areas; uptake of mlson-coated particles was ...	1993	8395470
therapeutic efficacy of some new quinolones and a combination of ofloxacin with rifampin against mycobacterium leprae infection induced in athymic nude mice.	ofloxacin (oflx), having superior antileprosy activity among the various quinolones, was studied for its combined therapeutic efficacy with rifampin (rmp) against mycobacterium leprae infection induced in nude mice. when oflx (3 mg/mouse) was given to infected mice in combination with rmp (0.01 mg/mouse) by gavage once daily six times per week, from day 31 to day 80 postinfection, a significant combined effect was observed. this study demonstrates the possibility of using oflx in multidrug regim ...	1993	8396614
effect of recombinant interferon gamma administration on lesional monocytes/macrophages in lepromatous leprosy patients.	hydrogen peroxide (h2o2) and superoxide anion (o2-) were estimated in lesional cells from 10 lepromatous leprosy patients injected intralesionally with recombinant interferon-gamma (rifn-gamma). clinically similar contralateral lesions injected with excipient served as controls. lesional esterase-positive cells (suggestive of monocytes/macrophages) from rifn-gamma-injected sites of many subjects showed net increments in the h2o2 and o2 levels compared to controls. when these cells were exposed t ...	1993	8396615
mechanism of interaction of the 85b secreted protein of mycobacterium bovis with fibronectin.	the 85b protein of mycobacterium bovis is a member of the secreted antigen 85 complex, which has been identified in a number of pathogenic mycobacteria. the 85 complex contains three components with molecular masses of 30 to 32 kda which share the property of binding to fibronectin, a large glycoprotein present in plasma. to investigate this activity we have expressed the m. bovis 85b antigen as a recombinant protein and studied its interaction with human fibronectin. fibronectin bound to the im ...	1993	8406884
use of pcr-mediated amplification of mycobacterium leprae dna in different types of clinical samples for the diagnosis of leprosy.	dna of mycobacterium leprae, obtained by a highly efficient nucleic acid extraction procedure, was used for standardisation of the amplification of an m. leprae-specific repetitive sequence by use of the polymerase chain reaction (pcr). with pure dna, m. leprae-specific amplification was obtained with as low as 100 ag (1 ag = 10(-18) g) of target dna, a quantity equal to about one-tenth of the bacterial genome. optimal processing of different types of clinical samples such as biopsy material, bl ...	1993	8411091
lepromin skin testing in the classification of hansen's disease in the united states.	hansen's disease, or leprosy, although a relatively uncommon disease in the united states, continues to be important because of its implications--physical, psychological, and social--for the patient. prognosis and treatment of the disease are based largely on clinical classification, which ranges from the multibacillary "lepromatous" to the paucibacillary "tuberculoid" forms, depending on the patient's specific immune capabilities. traditionally, skin testing with lepromins--suspensions of the e ...	1993	8416677
leprosy, tuberculosis, and the new genetics.		1993	8416888
hla class ii+ human keratinocytes present mycobacterium leprae antigens to cd4+ th1-like cells.	in a variety of inflammatory skin diseases like leprosy, keratinocytes (kc) are induced to express mhc class ii molecules and may therefore serve as antigen-presenting cells (apc) for mhc class ii restricted t cells infiltrating the lesions. however, kc have been thought to be improper apc for mhc class ii restricted t cells and to drive t cells into an anergic rather than into an activation state. we evaluated this issue in relation to leprosy and tested whether hla-dr+ kc could present m. lepr ...	1993	8418472
selection of t lymphocytes bearing limited t-cell receptor beta chains in the response to a human pathogen.	delayed-type hypersensitivity (dth) is a classic measure of t-cell responsiveness to foreign antigen. to estimate the extent of the t-cell repertoire in the dth response to a human pathogen, we measured t-cell receptor (tcr) beta-chain variable-region (v beta) gene usage in reversal reactions in leprosy. reversal reactions represent naturally occurring dth responses in leprosy, in which augmentation of t-cell responses to mycobacterium leprae is concomitant with clearance of bacilli from lesions ...	1993	8419921
combined multidrug and mycobacterium w vaccine therapy in patients with multibacillary leprosy.	immunotherapy with mycobacterium w vaccine was attempted in patients with borderline-borderline, borderline lepromatous (bl), or lepromatous leprosy (ll) to determine whether immunization can hasten recovery and reduce treatment time by invigorating cell-mediated immunity. mycobacterium w, a nonpathogenic, rapidly growing, atypical mycobacterium, shares a number of common b and t cell determinants with mycobacterium leprae and mycobacterium tuberculosis. patients receiving the vaccine had rapid ...	1993	8421173
recent advances in cytokine therapy in leprosy.	lepromatous leprosy is characterized by a selective anergy to mycobacterium leprae and its antigens. the inadequate immune response and the resulting reduced interferon-gamma (ifn-gamma) production lead to a lack of macrophage activation and unrestricted bacterial growth. purified protein derivative of tuberculin induced a normal local immune response in many lepromatous leprosy patients. interleukin-2 induced an accelerated equivalent of an antigen response in the skin. in both, monocytes and t ...	1993	8433015
cell-mediated immunity in trachomatous scarring. evidence from a leprosy population.	there is limited understanding of the mechanisms that mediate immunity after infection by chlamydia trachomatis. since it is known that the clinical course of leprosy is related to cell-mediated immunity and that such immunity contributes to the development of trachomatous conjunctival scarring, the authors examined patients to determine if there might be an association between leprosy status and trachomatous conjunctival scarring.	1993	8433835
macrophage activation: lipoarabinomannan from avirulent and virulent strains of mycobacterium tuberculosis differentially induces the early genes c-fos, kc, je, and tumor necrosis factor-alpha.	lipoarabinomannan (lam) is a major cell-wall associated glycolipid produced by mycobacterium tuberculosis and mycobacterium leprae. previous work demonstrated that lam from avirulent (h37ra) and virulent (erdman) strains of m. tuberculosis differ in structure at their non-reducing termini. in this study the effects of the h37ra and erdman lam on the activation of murine bone marrow-derived macrophages has been investigated. their abilities to elicit immediate early gene responses at mrna (c-fos, ...	1993	8436823
lepromin responses in recipients of a candidate antileprosy bacterin vaccine (who-immlep mycobacterium leprae killed preparation) in the usa.	identification of the nine-banded armadillo as a potential source of massive numbers of mycobacterium leprae led to the development of a candidate bacterin vaccine for possible immunoprophylaxis.	1993	8444531
use of an ordered cosmid library to deduce the genomic organization of mycobacterium leprae.	in an attempt to unify the genetic and biological research on mycobacterium leprae, the aetiological agent of leprosy, a cosmid library was constructed and then ordered by a combination of fingerprinting and hybridization techniques. the genome of m. leprae is represented by four contigs of overlapping clones which, together, account for nearly 2.8mb of dna. several arguments suggest that the gaps between the contigs are small in size and that virtually complete coverage of the chromosome has be ...	1993	8446027
nucleotide sequence of the first cosmid from the mycobacterium leprae genome project: structure and function of the rif-str regions.	the nucleotide sequence of cosmid b1790, carrying the rif-str regions of the mycobacterium leprae chromosome, has been determined. twelve open reading frames were identified in the 36716bp sequence, representing 40% of the coding capacity. five ribosomal proteins, two elongation factors and the beta and beta' subunits of rna polymerase have been characterized and two novel genes were found. one of these encodes a member of the so-called abc family of atp-binding proteins while the other appears ...	1993	8446028
homologs of mycobacterium leprae 18-kilodalton and mycobacterium tuberculosis 19-kilodalton antigens in other mycobacteria.	most of the antigens of mycobacterium leprae and m. tuberculosis that have been identified are members of stress protein families, which are highly conserved throughout many diverse species. of the m. leprae and m. tuberculosis antigens identified by monoclonal antibodies, all except the 18-kda m. leprae antigen and the 19-kda m. tuberculosis antigen are strongly cross-reaction between these two species and are coded within very similar genes. studies of t cell reactivity against mycobacterial a ...	1993	8454357
a simple colorimetric assay for detection of amplified mycobacterium leprae dna.	a colorimetric assay for the detection of pcr-products is described. the assay is based on amplification of dna in the presence of digoxigenin-dutp. after immobilization of the pcr products to a microtitre plate, amplified dna could be detected colorimetrically. the sensitivity of this colorimetric assay was equal to gel-analysis allowing the detection of 100 fg of template dna. here, we show that it can be used to detect mycobacterium leprae dna in biopsy specimens from leprosy patients. the si ...	1993	8455642
foamy histiocytes and lepra bacilli in a lymph node aspirate.		1993	8455834
appearance of gamma delta t cell receptor-positive cells following alpha beta t cell receptor-positive cells in the lepromin reaction of human skin.	to elucidate the involvement of human gamma delta t cell receptor (tcr)+ cells in mycobacterial infection, we examined the kinetics of these cells in skin lesions of human lepromin reaction. the majority of cd3+ cells two days after induction of the lepromin reaction were alpha beta tcr+, while gamma delta tcr+ cells accounted for only 4.4 +/- 1.4% of the cd3+ cells. on day 21, the incidence of gamma delta tcr+ cells was greater (16.0 +/- 2.1%), although alpha beta tcr+ cells remained the predom ...	1993	8458635
polymerase chain reaction for detection of mycobacterium leprae in nasal swab specimens.	the polymerase chain reaction based on the selective amplification of a 531-bp fragment of the gene encoding the proline-rich antigen of mycobacterium leprae was applied to nasal swab specimens from leprosy patients, occupational contacts, and endemic and nonendemic controls. to prevent false-positive amplification, we used dutp and uracil-dna-glycosylase in all polymerase chain reactions. false-negative reactions were detected by using a 531-bp modified template as an internal control. amplific ...	1993	8458942
simple colorimetric microtiter plate hybridization assay for detection of amplified mycobacterium leprae dna.	the detection of amplified products resulting from polymerase chain reactions (pcrs) remains a complicated process. to simplify the detection procedures, we developed a colorimetric microtiter plate hybridization assay for the specific detection of 5'-biotinylated pcr fragments of mycobacterium leprae dna. for this assay, an m. leprae dna capture probe was made and immobilized on the wells of a microtiter plate. hybridization of the biotin-labeled pcr fragments was detected through enzymatic col ...	1993	8458960
evolutionary conservation of major histocompatibility complex-dr/peptide/t cell interactions in primates.	many major histocompatibility complex (mhc) polymorphisms originate from ancient structures that predate speciation. as a consequence, members of the mhc-drb103 allelic lineage are not only present in humans but in chimpanzees and rhesus macaques as well. this emphasizes that mhc-drb103 members must have been present in a common ancestor of these primate species that lived about 30 million years ago. due to the accumulation of genetic variation, however, alleles of the mhc-drb1*03 lineage exhi ...	1993	8459225
molecular basis of rifampin resistance in mycobacterium leprae.	rifampin is currently the most potent drug used in leprosy control programs. we show that the rifampin resistance which emerged in nine patients with lepromatous leprosy, who had received rifampin monotherapy, stemmed from mutations in the rpob gene, which encodes the beta subunit of rna polymerase of mycobacterium leprae. in eight cases missense mutations were found to affect a serine residue, ser-425, while in the remaining mutant a small insertion was found close to this site. these findings ...	1993	8460911
evaluation of polymerase chain reaction amplification of mycobacterium leprae-specific repetitive sequence in biopsy specimens from leprosy patients.	biopsy specimens were obtained from 102 leprosy patients before chemotherapy and examined by polymerase chain reaction (pcr) using the primers amplifying the 372-bp dna of a repetitive sequence of mycobacterium leprae. the pcr results were then compared with bacterial indices (bi) of slit-skin smears and biopsy specimens. the intensities of dna bands were in general correlated with the numbers of acid-fast bacilli, and even a sample with only one organism gave a pcr positive result. ten 5-micron ...	1993	8463401
mycobacterium leprae soluble antigen (rees) skin test responses in an endemic population in india.	the response to intradermal administration of rees soluble skin test antigen was studied in 12,142 randomly selected individuals living in a highly endemic area in south india. taking a cut-off point of 12 mm induration as the criterion for 'positivity', 73% of pb cases, 45% of mb cases and 63% of noncase population (67% in contacts and 63% in non-contacts) were found to be positive. age-specific positivity rates were higher in males than in females and in adults than in children. the difference ...	1993	8463724
detection of antibodies to phenolic glycolipid by elisa in leprosy patients.	antibody (igm) response to pgl-1, a surface glycolipid unique to mycobacterium leprae has been studied in 25 cases each of lepromatous and tuberculoid leprosy and in 25 healthy controls. the absorbance value at 488 nm was expressed as antibody titre. serum antibody titre was found to be significantly higher in patients than controls. results confirm that antibody response in leprosy patients depend upon bacterial load.	1993	8463728
a case report: dual mycobacterial infections in a paraguayan patient due to mycobacterium leprae and mycobacterium fortuitum.		1993	8464321
a new approach to the chemical synthesis of the trisaccharide, and the terminal di- and mono-saccharide units of the major, serologically active glycolipid from mycobacterium leprae.	the key intermediates for the synthesis of p-trifluoroacetamidophenyl o-(3,6-di-o-methyl-beta-d-glucopyranosyl)-(1-->4)-o-(2,3-di-o-methyl-alp ha-l- rhamnopyranosyl)-(1-->2)-3-o-methyl-alpha-l-rhamnopyranoside (15), as well as p-trifluoroacetamidophenyl o-(3,6-di-o-methyl-beta-d- glucopyranosyl)-(1-->4)-2,3-di-o-methyl-alpha-l-rhamnopyranoside (29), were the methyl and ethyl o-(2-o-benzyl-4,6-o-benzylidene-3-o-methyl-beta- d-glucopyranosyl)-(1-->4)-2,3-o-diphenylmethylene-1-thio-alpha-l- rhamnop ...	1993	8472263
suppression of adcc by immune complexes formed in vitro in mycobacterium leprae-infected mice.	antibody-dependent cellular cytotoxicity (adcc) was assessed in mice infected experimentally with mycobacterium leprae and injected simultaneously with in vitro-formed immune complexes (ic). significant decrease in the adcc function was observed in animals given ic at zero day (0dic) and 3 months (3mic) post inoculation with m. leprae, when adcc activity was assessed at 3, 6 and 9 months period. from the data obtained we believe that adcc is suppressed by ic formed in vitro.	1993	8474357
sequence and immunological characterization of a serine-rich antigen from mycobacterium leprae.	sera from lepromatous leprosy patients were used to screen a mycobacterium leprae lambda gt11 library. three positive plaques were picked, and lysogens were constructed. immunoblot analysis showed that all of the lysogens expressed an apparently identical beta-galactosidase fusion protein which reacted strongly with the sera. the 1.7-kbp insert from one clone was subcloned into the lacz gene in pur290; sequence analysis of the end fused to lacz revealed an open reading frame with no significant ...	1993	8478104
evaluation of phenolic glycolipid-i (pgl-i) antibody as a multidrug therapy (mdt) monitor.	since phenolic glycolipid-i (pgl-i) is an unequivocal marker for mycobacterium leprae, this antigen has been a good candidate for the serodiagnosis and monitoring of the effectiveness of leprosy chemotherapy. the present study, a continuation of an earlier report, was undertaken to estimate pgl-i antibody titers in 40 leprosy patients 3 and 6 months after starting mdt. all the leprosy groups showed significant declines in anti pgl-i reactivity after 6 months. there was a good correlation between ...	1993	8482747
analysis of cytokine production by mycobacterium-reactive t cells. failure to explain mycobacterium leprae-specific nonresponsiveness of peripheral blood t cells from lepromatous leprosy patients.	recent analyses of antimycobacterial t cells clones from a small number of individuals indicate that mycobacteria preferentially induce th cells that produce high levels of ifn-gamma and no or little il-4 in mycobacterium leprae-resistant tuberculoid leprosy (tt) patients and healthy subjects, whereas in one study m. leprae-induced ts clones from polar lepromatous leprosy (ll) patients showed a reciprocal cytokine secretion profile and mediated their suppressive activity via the release of high ...	1993	8482851
synovial fluid antigen-presenting cell function in rheumatoid arthritis.	we have previously demonstrated enhanced synovial fluid (sf) antigen-presenting cell (apc) function in inflammatory arthritis patients selected on the basis of marked sf mononuclear cell (mnc) responsiveness to reactive arthritis-associated bacteria (clin exp immunol 1990; 79:189-94). in this study we have assessed whether similarly enhanced synovial apc function is present in other inflammatory arthritis patients by using two assay systems to study 18 rheumatoid arthritis patients whose mnc res ...	1993	8485910
association of c4b deficiency (c4b*q0) with erythema nodosum in leprosy.	a considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the mhc. in this investigation, the association between the mhc class iii complement proteins c2, bf, c4a and c4b and leprosy in a patient population of southern brazil was studied. a total of 109 non-related leprosy patients was investigated; 73 presented with lepromatous leprosy (ll), 46 of them had the immunopathological reaction of erythema ...	1993	8485914
antigenic similarity of a cultivable acid fast bacterium to mycobacterium leprae.	a cultivable acid fast stainable bacterium obtained from leprosy nodule showed similarity to m. leprae in antigenicity to serum antibodies of lepromatous leprosy patients. the antigenic similarity has been seen more clearly in the delipidified cell components of both these bacteria. an antigen of 35-38 kda has been seen as a common antigen between m. leprae and the cultivable bacilli with binding ability to sera from leprosy patients. this cultivable bacterial component could be used for serodia ...	1993	8486404
the major secreted antigen complex (ag 85) from mycobacterium bovis bacille calmette-guérin is associated with protective t cells in leprosy: a follow-up study of 45 household contacts.	t cell proliferation and interferon (ifn)-gamma secretion were analyzed in 45 leprosy contacts stimulated with antigen 85 (ag85), the major culture filtrate antigen from mycobacterium bovis bacille calmette-guérin. all 14 mitsuda reaction-positive contacts reacted to mycobacterium leprae and ag85. three mitsuda reaction-negative contacts reacted weakly to m. leprae and ag85. the other 28 mitsuda reaction-negative contacts did not react to m. leprae, but 9 reacted to ag85. thirty-four contacts we ...	1993	8486949
a morphological study of nerve biopsies from cases of multibacillary leprosy given multidrug therapy.	nerve biopsies were examined from 17 cases of lepromatous leprosy given who-recommended multidrug therapy (mdt) for 2 years. the pathological changes were assessed qualitatively and quantitatively to judge the effectiveness of mtd. the nerves varied very considerably in the severity of their lesions. some regenerating fibres were seen in most of the nerves. in a few cases, the nerves were almost entirely populated by regenerated fibres, confirming that mtd was effective in halting the disease pr ...	1993	8493861
in vitro tumor necrosis factor production by mononuclear cells from lepromatous leprosy patients and from patients with erythema nodosum leprosum.	the production of tumor necrosis factor (tnf) by mycobacterium leprae-stimulated phagocyte cells, isolated from lepromatous leprosy patients (ll) and normal individuals, was evaluated, using the highly tnf-sensitive mouse fibrosarcoma cell line wehi164cl13. mononuclear cells, isolated from all individuals studied, showed a low level of spontaneous tnf production, except for patients undergoing erythema nodosum leprosum (enl), in which we found significantly higher levels of tnf. addition of m. l ...	1993	8500267
comparative assessment of the leprosy antibody absorption test, mycobacterium leprae extract enzyme-linked immunosorbent assay, and gelatin particle agglutination test for serodiagnosis of lepromatous leprosy.	a comparative assessment of three serological methods for leprosy diagnosis (the fluorescent leprosy antibody absorption [fla-abs] test, the mycobacterium leprae soluble-extract enzyme-linked immunosorbent assay [elisa], and the m. leprae particle agglutination [mlpa] test) was carried out. the objective was to identify their performance in clinical and epidemiological diagnosis of leprosy. the study group included 45 lepromatous leprosy patients under treatment. specificity was > 95% for all th ...	1993	8501238
immunosuppressive roles for il-10 and il-4 in human infection. in vitro modulation of t cell responses in leprosy.	il-10 and il-4 have been shown to exert an inhibitory effect on cell-mediated immune responses. our previous studies of leprosy demonstrated that il-10 and il-4 mrna were preferentially expressed in lesions from lepromatous patients, those immunologically unresponsive individuals that manifest widespread infection. to define more precisely the regulatory roles of these two cytokines in the immune response to infection, we studied in vitro responses to mycobacterium leprae. m. leprae triggered il ...	1993	8515073
leprosy.		1995	8521365
leprosy in five human immunodeficiency virus-infected patients.	we present five cases of leprosy in five human immunodeficiency virus-positive individuals. the patients were five men between the ages of 18 and 45 years. the five patients presented with skin lesions; three patients with hypopigmented skin lesions, one with skin macules and a history of leprosy, and one with papular lesions. in one patient, there was bilateral "claw hands." histologically, two cases were categorized as lepromatous leprosy, two as borderline tuberculoid, and one as borderline l ...	1995	8532702
arylsulphatase from alteromonas carrageenovora.	arylsulphatase activity was identified in cultures of the marine bacterium alteromonas carrageenovora, using methylumbelliferyl sulphate as substrate. in contrast with most other microbial arylsulphatases, arylsulphatase production in a. carrageenovora was not repressed by sulphate. the structural gene of arylsulphatase (atsa) was cloned and sequenced. an orf of 984 bp was found, specifying a primary translation product of 328 amino acids with a molecular mass of 35797 da. arylsulphatase was par ...	1995	8535517
lord of the rings: groes structure.		1996	8539614
structure of the heat shock protein chaperonin-10 of mycobacterium leprae.	members of the chaperonin-10 (cpn10) protein family, also called heat shock protein 10 and in escherichia coli groes, play an important role in ensuring the proper folding of many proteins. the crystal structure of the mycobacterium leprae cpn10 (ml-cpn10) oligomer has been elucidated at a resolution of 3.5 angstroms. the architecture of the ml-cpn10 heptamer resembles a dome with an oculus in its roof. the inner surface of the dome is hydrophilic and highly charged. a flexible region, known to ...	1996	8539620
in vitro activity of levofloxacin, singly and in combination with rifamycin analogs, against mycobacterium leprae.	the in vitro susceptibility of mycobacterium leprae to levofloxacin was studied by using two biochemical parameters to measure the metabolic activity of the organism. levofloxacin consistently exhibited twofold greater bactericidal activity than ofloxacin, with the mic being 0.75 microgram/ml. when combined with one of the three rifamycin analogs, synergism was obtained with krm-1648 and rifabutin but not with rifampin.	1995	8540726
immune response to heat-shock protein correlates with induction of insulitis in i-e alpha d transgenic nod mice.	to evaluate the correlation between heat-shock protein (hsp) and insulitis, we compared lymphocyte proliferative response to mycobacterium leprae hsp65 of nod mice with that of i-e alpha d transgenic nod (i-e+nod) mice, which show no insulitis. we found that splenocytes from 15-week-old nod mice showed a more marked proliferative response to hsp than did those from age-matched i-e+nod mice (p < 0.05). we then transferred splenocytes from 12-week-old nod mice into i-e+nod mice to induce insulitis ...	1996	8549860
development of a mucosal challenge test for leprosy using leprosin a.	there is little information about the mucosal immune response in leprosy. we have developed a nasal provocation test with leprosin a which will be used to investigate mucosal immunity to mycobacterium leprae. initial studies were performed with increasing doses of leprosin a (1.0 pg/ml-10 micrograms/ml) to determine the optimal safe dose of leprosin a. anti-m. leprae iga antibody and normal iga concentrations were measured in the saliva of leprosy contacts and controls before and after instillat ...	1995	8551052
[immunohistochemical study on temporal bone of autopsy cases with mycobacterium leprae infection].	three temporal bones were obtained en bloc from autopsy cases with lepromatous leprosy from the middle cranial fossa side after removing the brain. after fixation with 10% formalin followed by sufficient decalcification, the specimens were embedded in paraffin en bloc and cut serially to stain every 10th section with hematoxylin and eosin (h&e) for anatomical orientation. an immunohistochemical study with anti-neurofilament, anti-mbp (myelin basic protein), anti-bcg (bacillus calmette-gue'rin) a ...	1995	8551377
new vaccines against tuberculosis.	it has proved difficult to vaccinate effectively against tuberculosis with mycobacterial components or even with whole dead mycobacteria; protection was always inferior to that obtained with the live attenuated vaccine known as bacillus calmette-guérin (bcg). we have found that this may no longer be the case. expression of the gene for a single mycobacterial antigen (mycobacterium leprae hsp65) in adult balb/c mice resulted in substantial cell-mediated protection against challenge with m. tuberc ...	1995	8555985