Publications

non acid-fast fluorescent m. leprae (?) in skin smears from leprosy patients.	smears from 74 known smear negative cases of leprosy were examined after staining with auramine 'o'. 40.54% cases were positive for fluorescent bacilli. 60.52% of cases on treatment and 19.44% cases after rft had fluorescent bacilli in the skin smears. results suggest the possibility of a non acid-fast fluorescent positive variant of m. leprae.	1993	8182291
leprosy in women: characteristics and repercussions.	"health is often measured in terms of low mortality; nevertheless, merely being alive is not a measure of the quality of life" h. méndez castellanos. physiological, socioeconomic and cultural factors play important roles in the response of women to mycobacterium leprae and in the impact of leprosy on their lives. they appear to develop stronger immunological responses to m. leprae than men, as suggested by lower incidence and less severe clinical forms of disease in most areas of the world, as w ...	1993	8211257
attempts to cultivate mycobacterium leprae in fat tissue.	the behaviour of m. leprae in fat tissue was studied. preadipocyte cells were infected with m. leprae and injected intradermally (i.d.) into nude mice. adipose nodules obtained by in vivo differentiation of infected cells were maintained in vivo for 3 months and subsequently incubated in vitro for 3 months. counts of bacilli showed no increase over this 6 months period. it is concluded that undifferentiated preadipocyte and mature fat cells are not permissive for m. leprae. the morphological cha ...	1993	8213048
immunity to mycobacteria.	recent progress in the field of immunity to mycobacteria has centered on t cell subset responses and the cytokines these cells secrete. in addition, there has been steady progress in identifying and characterizing several classes of major mycobacterial proteins; included amongst these are the secreted/export proteins of mycobacterium tuberculosis, which several laboratories now believe may represent the key protective immunity-inducing antigens of the bacillus.	1993	8216924
anti-pgl1 levels in leprosy patients and their contacts.	1. we determined the anti-pgl1 levels of 402 individuals from the ribeirão preto region since the phenolic glycolipid (pgl1) is a specific mycobacterium leprae antigen. this group consisted of 47 leprosy patients (26 with the lepromatous form, 16 with the tuberculoid form and 5 with the borderline form), 12 tuberculosis patients, 19 leprosy contacts, and 324 healthy blood donors from the hemocenter of the university hospital, faculty of medicine of ribeirão preto, university of são paulo. anti-p ...	1993	8220267
human t cells recognize mycobacterial heat shock proteins in the context of multiple hla-dr molecules: studies with healthy subjects vaccinated with mycobacterium bovis bcg and mycobacterium leprae.	heat shock proteins (hsp) are considered to be important targets of the immune response to mycobacteria and, as such, relevant to subunit vaccine design. if hsp are major antigens in cell-mediated immunity, they should be recognized in the context of most of the hla-dr molecules required for presentation of mycobacterial antigens to t cells. we tested peripheral blood mononuclear cells (pbmc) and t-cell lines from mycobacterium leprae- and m. bovis bcg-vaccinated subjects for proliferation in re ...	1993	8225603
quantitative determination of pcr products by colorimetric method.		1993	8226396
construction of genomic dna library of mycobacterium leprae thai-53 strain, and detection of m. leprae specific genes in the library by polymerase chain reaction.		1993	8226397
immune regulation: learning from leprosy.	the specific anergy seen in severe, disseminated leprosy appears to represent multifaceted actions of macrophages and suppressor t lymphocytes. identification of cytokine mediation in these events helps to account for the immune system's "choice" of cellular versus humoral defenses--and points toward manipulation of cytokine switches for immunotherapy against infectious and autoimmune disease.	1993	8227249
relationship between host histones and armadillo-derived mycobacterium leprae.	a major protein previously recognized as being primarily associated with the cell walls of mycobacterium leprae, major wall protein (mwp), is now identified as histoprotein h2b based on n-terminal amino-acid sequencing, electrophoretic comparisons, and several other properties. an avid association between several host/armadillo-derived histones and m. leprae was demonstrated. since such armadillo-derived m. leprae are the basis of several ongoing vaccine trials, a simple procedure that permits t ...	1993	8228435
detection of mycobacterium leprae by the polymerase chain reaction in nasal swabs of leprosy patients and their contacts.	nose swabs from 4 paucibacillary (pb) and 8 multibacillary (mb) leprosy patients and their contacts were tested for the presence of mycobacterium leprae by two polymerase chain reactions (pcr); 30% of the samples contained inhibitors for the pcr, 1 of 52 (1.9%) swabs and 13 of 164 (7.9%) swabs were positive for m. leprae among contacts of pb and mb patients, respectively. since this difference is not significant, and some positives were found among contacts of mb patients treated and cured of th ...	1993	8228436
armadillos (dasypus novemcinctus) as a model to test antileprosy vaccines; a preliminary report.	the efficacy of two candidate leprosy vaccines, bcg and a mixture of bcg and killed mycobacterium leprae, was tested in 62 armadillos caught in the wild. the abilities of the vaccines to convert lepromin-negative armadillos to a positive reaction were compared with a group of control animals. both vaccines upgraded subsequent lepromin skin-test histopathology. the conversion results parallel the protection values obtained in some bcg vaccine trials against leprosy in humans. before conducting ex ...	1993	8228437
reconstitution of mycobacterium leprae immunity in severe combined immunodeficient mice using a t-cell line.	to test whether mycobacterium leprae-immune t cells can confer protection against infection with leprosy bacilli, severe combined immunodeficient (scid) mice were reconstituted with a balb/c-derived, m. leprae-responsive, t-cell line. flow cytometric analysis of spleen and peripheral blood cells confirmed reconstitution with t cells. in vitro lymphokine production and the proliferation of spleen cells from the reconstituted animals established that the donor cells had maintained their functional ...	1993	8228438
activity of phenazine analogs against mycobacterium leprae infections in mice.	twenty-five compounds structurally related to clofazimine were tested for their ability to inhibit the growth of mycobacterium leprae using the kinetic method of drug evaluation in the mouse foot pad model of leprosy. seven of the phenazine derivatives displayed anti-m. leprae activity comparable to that of clofazimine when administered at a concentration of 0.01% (w/w) in the diet. three of the compounds, b746, b4087, and b4101, were active when administered at 0.001% in the diet. at a dietary ...	1993	8228439
preservation of mycobacterium leprae in vitro for four years by lyophilization.	although the viability of mycobacterium leprae suspended in distilled water with or without 10% fetal calf serum was reduced approximately 10(-2) to 10(-4) from that of the starting material during the process of lyophilization, bacilli capable of multiplication in nude mouse foot pads were found in the lyophilized samples stored for 4 years at 4 degrees c. the multiplication rate of the lyophilized bacilli which were suspended in 10% serum-water was much higher than that of the bacilli suspende ...	1993	8228440
immunoreactivity of mycobacterial strain icrc and mycobacterium leprae antigens with polyclonal and monoclonal antibodies.	icrc, a cultivable mycobacterium, is undergoing clinical trials as an antileprosy vaccine in india. in the present study, we have investigated the crossreactivity between antigens of the mycobacterial strains of icrc and mycobacterium leprae using polyclonal and monoclonal antibodies in a radioimmunoprecipitation assay. it was observed that polyclonal anti-icrc and anti-m. leprae antibodies showed predominant reactivity to a 21-kda protein of the mycobacterial strain icrc and the 21- and 14-kda ...	1993	8228441
higher specificity in the serodiagnosis of leprosy by combined titration of antiphenolic glycolipid-i and antiphospholipid antibodies.		1993	8228448
evaluation of the autoimmune response in leprosy.	immunological responses to a panel of antigens were evaluated in 27 patients with lepromatous and 20 patients with tuberculoid leprosy and compared with 24 pulmonary tuberculosis patients, 25 systemic lupus erythematosus patients and 41 healthy blood donors. some autoantibody specificities were extensively studied for the first time in mycobacterial infections. striking immunoserological abnormalities were found in patients with lepromatous leprosy, particularly in those presenting with relapse. ...	1993	8231599
modulation of peripheral blood derived monocytes/macrophages from leprosy patients using 'tuftsin' for production of reactive oxygen intermediates.	phagocytic cells respond to a variety of membrane stimulants by producing reactive oxygen intermediates (roi), i.e. o2-, h2o2 and oh.metabolites. plasma membrane activation is associated with superoxide generating nadph oxidase, thereby causing the production of these toxic species. stimulation of phagocytic cells also results in activation of purine catabolism, which directs the metabolic flux through xanthine oxidase to produce the superoxide anion. we previously observed that bl/ll macrophage ...	1993	8231600
pgl-i antibody in hiv infected patients.		1993	8231609
roles of soluble fibronectin and beta 1 integrin receptors in the binding of mycobacterium leprae to nasal epithelial cells.	the mechanisms by which mycobacterium leprae invades the human host are presently unknown. we investigated the ability of m. leprae to bind to human rpmi 2650 cells, a human nasal septal epithelial cell line, using both microscopic observation and an elisa technique. the results demonstrated that m. leprae adheres to nasal cells after binding to soluble fibronectin. furthermore, it was observed that m. leprae could bind to the beta 1 chain of the integrins in the absence of serum or mucus. these ...	1993	8242899
metabolism and pharmacokinetics of [14c]-deoxyfructosylserotonin creatinine sulfate administered orally and intravenously to rats and mice.	deoxyfructosylserotonin (dfs) has been shown in in vitro tests to inhibit l-dopa-oxidase and also to suppress the multiplication of mycobacterium leprae. the possible therapeutic use of dfs makes necessary the study of its metabolic fate in animal models. labelled [14c]-dfs was synthesized by condensation of serotonin and [14c]-glucose and administered per os or intravenously to rats and mice. after oral administration, some of the radioactivity transited through the intestinal tract to be excre ...	1993	8243496
sequence and expression of the mycobacterium leprae dnaj gene.	study of mycobacterium leprae, the causative agent of leprosy, has been advanced by the isolation of genes encoding mycobacterial proteins including dnak encoding the m. leprae 70 kda heat shock protein. the sequence downstream from dnak revealed a second open reading frame coding for a protein of 389 amino acids with a calculated molecular mass of 41.2 kda. sequence analysis demonstrated significant dna homology with the dnaj gene of other organisms. high amino acid sequence identity was obtain ...	1993	8245828
investigations into the growth of mycobacterium leprae in a medium with palmitic acid under different gaseous environments.	low oxygen tension has often been considered important for the growth of mycobacterium leprae. palmitic acid has been suggested as the oxidizable substrate for the in vitro cultivation of leprosy bacilli. the combined effects of palmitic acid and various known gas mixtures on the in vitro growth of m. leprae were investigated. when palmitic acid was included in the medium an optimal growth in both liquid and solid media was obtained between 16 to 20 weeks of incubation under gas mixtures contain ...	1993	8246810
subclinical infection with mycobacterium leprae--a problem for leprosy control strategies.	tests for the serodiagnosis of leprosy, including those based on phenolic glycolipid-i (pgl-i), have shown poor specificity for leprosy in studies of endemic communities, despite initially promising results in studies of selected patients. during a 5 years follow-up study of a hyperendemic community in papua new guinea, a marked reduction in numbers of seropositive children and an increase in age of those seropositive followed introduction of multi-drug therapy. this was accompanied by a reduced ...	1993	8249066
in-vitro activity of three new fluoroquinolones and synergy with ansamycins against mycobacterium leprae.	the efficacy of three fluorinated quinolones, clinafloxacin (pd 127391), sparfloxacin (pd 131501) and pd 131628, either alone or in combination with rifampicin/rifabutin, against mycobacterium leprae was evaluated in vitro using two biochemical parameters to measure the metabolic activity of the organism. clinafloxacin was found to be most effective with an mic of 0.75 mg/l, followed by sparfloxacin (mic 1.5 mg/l) and pd131628 (mic 3.0 mg/l). when combined with rifampicin each of the three quino ...	1993	8262866
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