Publications

addiction of anti-cd28 antibodies restores pbmc proliferation and ifn-gamma production in lepromatous leprosy patients.	during antigen recognition, t lymphocytes are primed by a physical interaction with antigen-presenting cells (apc). at least two signals are needed to activate t cells. one is provided by t cell receptor (tcr)/cd3 in the context of the mayor histocompatibility complex (mhc), and another signal is mediated by antigen-independent molecules, that is t cell membrane-bound cd28 and its specific ligand b7-1 (cd80) present in apc. both signals trigger a series of metabolic events initiating right at th ...	1999	10574615
simlep: a simulation model for leprosy transmission and control.	simlep is a computer program for modeling the transmission and control of leprosy which can be used to project epidemiologic trends over time, producing output on indicators such as prevalence, incidence and case-detection rates of leprosy. in simlep, health states have been defined that represent immunologic conditions and stages of leprosy infection and disease. three types of interventions are incorporated: vaccination, case detection and chemotherapy treatment. uncertainties about leprosy ha ...	1999	10575401
comparison of two methods of leprosy case finding in the circle of kita in mali.	kita is a health district of mali, a leprosy-endemic country in west africa. we conducted a comparative study of passive and active case finding of leprosy in this district in 1997. in may and june, a mobile team realized active case finding by visiting 32 villages of more than 1000 inhabitants. for 12 months, peripheral health center nurses did passive detection after information and education sessions about the signs of leprosy in the other 37 main villages of kita. the active detection rate ( ...	1999	10575402
seroprevalence rates of antibodies to phenolic glycolipid-i among school children as an indicator of leprosy endemicity.	in order to study whether the seroprevalence of antibodies to phenolic glycolipid-i (pgl-i) among school children is a useful indicator of the leprosy problem in certain areas, school surveys were carried out. these surveys have the advantage of targeting an easily accessible, stable and standardized population. antibodies to the species-specific pgl-i of mycobacterium leprae were detected in a simple gelatin particle agglutination test. we have determined the seroprevalence rates in 2835 school ...	1999	10575403
disabilities in multibacillary leprosy following multidrug therapy with and without immunotherapy with mycobacterium w antileprosy vaccine.	a vaccine based on autoclaved mycobacterium w was administered, in addition to standard multidrug therapy (mdt), to 157 bacteriologically positive, lepromin-negative, multibacillary leprosy patients supported by a well-matched control group of 147 patients with similar type of disease who received a placebo injection in addition to mdt. the mdt was given for a minimum period of 2 years and continued until skin-smear negativity, while the vaccine/placebo was given at 3-month intervals up to a max ...	1999	10575404
induction of lepromin positivity following immuno-chemotherapy with mycobacterium w vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: report on a hospital-based clinical trial with the candidate antileprosy vaccine.	a vaccine based on autoclaved mycobacterium w was administered, in addition to standard multidrug therapy (mdt), to 157 bacteriologically positive, lepromin-negative, multibacillary (ll, bl and bb) leprosy patients. the vaccinees were supported by a well-matched control group of 147 patients with similar type of disease who received a placebo injection in addition to mdt. the mdt was given for a minimum period of 2 years and continued until skin-smear negativity, while the vaccine was given at 3 ...	1999	10575405
risk factors for erythema nodosum leprosum.	a retrospective study of new borderline lepromatous and lepromatous patients reporting for multidrug therapy (mdt) for leprosy at the anandaban leprosy hospital, kathmandu, nepal, over an 8-year period was conducted to determine the prevalence of erythema nodosum leprosum (enl), the time and frequency of reactions, and clinical and laboratory parameters associated with enl. an overall prevalence of enl in this cohort of 19% was found. one third of these reactions occurred in patients before mdt ...	1999	10575406
rapid method for diagnosis of leprosy by measurements of antibodies to the m. leprae 35-kda protein: comparison with pgl-i antibodies detected by elisa and "dipstick" methods.	a new rapid immuno-chromatographic test card for the detection of antibodies to the mycobacterium leprae 35-kd protein is described. the new assay is compared in the same group of subjects with a direct enzyme elisa method for 35-kd antibodies and with assays for anti-phenolic glycolipid-i (pgl-i) antibodies using a standard elisa as well as the recently described "dipstick" method. good concordance was found between the rapid methods and the corresponding elisa methods. the detection of untreat ...	1999	10575407
nasal mucosa and skin of smear-positive leprosy patients after 24 months of fixed duration mdt: histopathological and microbiological study.	the skin and nasal mucosa of 10 lepromatous leprosy patients who had completed 24 doses of fixed duration multidrug therapy (mdt) but who continued to be skin-smear positive for acid-fast bacilli (afb) were examined histopathologically. the nasal mucosa showed granuloma fractions that exceeded those seen in the skin specimens, signifying that activity in this region subsides much more gradually than the activity in the skin. mouse foot pad studies done using t900r mice with an inoculum from the ...	1999	10575409
a study on the methods for early serological diagnosis of leprosy and their potential use.	this is a serial study. in this series we have established 12 methods for the early serological diagnosis of leprosy, including the fla-abs test, elisas with artificial products (nd-o-, nd-p-, nt-o-, nt-p-bsa; pgl-i, whole m. leprae and m. smegmatis), monoclonal antibody specific binding assay (mcab/sba), latex agglutination test (lat), and mlpa. these methods were compared with each other on a large scale in leprosy patients and in the field. the results indicate that 1) excellent results were ...	1999	10575411
vaccination of mice against the leprosy bacillus with skin-test antigens.		1999	10575412
single-dose treatment for paucibacillary leprosy; feasibility of long-term follow up.		1999	10575413
single-dose treatment for paucibacillary leprosy; clinical problems and management.		1999	10575414
single-dose treatment for paucibacillary leprosy; field implications.		1999	10575415
the antigen 85 complex vaccine against experimental mycobacterium leprae infection in mice.	the proteins in culture filtrate derived from bacillus calmette-guérin (bcg) were examined for protection against infection by mycobacterium leprae. immunization with the major secreted proteins, antigen 85 complex (ag 85) a, b and c, induced effective protective immunity against multiplication of m. leprae in the foot pads of mice. the most effective protection was observed when mice were immunized with ag 85a. a single immunization with ag 85 could induce antigen-specific interferon gamma (ifn ...	1999	10580191
characterization of a mycobacterium smegmatis mutant lacking penicillin binding protein 1.	the pona gene of mycobacterium smegmatis encodes a 95-kda penicillin binding protein, pbp1, that is similar to pbp1s of mycobacterium tuberculosis and mycobacterium leprae. transposon disruption of pona in m. smegmatis resulted in a pbp1-deficient mutant that was sensitive to beta-lactam antibiotics, was more permeable to glycine, and grew slowly in liquid culture.	1999	10582900
bactericidal action of ampicillin/sulbactam against intracellular mycobacteria.	the resistance of mycobacteria to beta-lactam antibiotics is attributed to their ability to synthesize beta-lactamase. in our previous studies, beta-lactam/beta-lactamase-inhibitor combinations suppressed the growth of several mycobacteria in axenic cultures and ampicillin/sulbactam was bactericidal to mycobacterium tuberculosis h37rv in vitro, and to mycobacterium leprae multiplying in mouse foot-pads. since both these organisms multiply in phagocytic cells in the host, it is important to know ...	1999	10595573
recognition of phenolic glycolipid-i (mycobacterium leprae) and sulfolipid-i (m. tuberculosis) by serum from mexican patients with leprosy or tuberculosis.	differential diagnosis of leprosy and tuberculosis in regions where both illnesses are endemic is a prerequisite for proper identification and treatment.	1999	10599015
south indian leprosy vaccine trial: important lessons for mycobacterial immunology.		1999	10603712
the us-japan joint leprosy research program meeting, san francisco, june 28-30, 1999.		1999	10603713
antibody-based enzyme-linked immunosorbent assay for determination of anti-pgl-i specific circulating immune complex in leprosy patients.	a serological study was performed in 122 individuals: 75 leprosy patients and 47 healthy controls. the elisa test was performed for igg and igm using the glycolipid pgl-i antigen from mycobacterium leprae. circulating immune complexes (cic) were isolated by peg 6000 precipitation method and after dissociation with an acid solution, the igg and igm specific against pgl-i were tested with the elisa test. the multibacillary patients had high levels of antibodies, compared with paucibacillary patien ...	1999	10603715
immunohistochemical detection of pgl-1, lam, 30 kd and 65 kd antigens in leprosy infected paraffin preserved skin and nerve sections.	a panel of lipid, carbohydrate and protein antibodies were optimized for use in detecting m. leprae antigens in paraffin embedded material. skin and nerve biopsies from 13 patients across the leprosy spectrum were studied. all antibodies detected antigen in tissues with a bi > 1. phenolic-glycolipid was not detected in bacteriologically negative tissue but lipoarabinomanan (lam) and protein antigens were detected. staining with lam was strongest and gave least background. the transfer of this im ...	1999	10603716
presence of m. leprae in tissues in slit skin smear negative multibacillary (mb) patients after who-mbr.	this study looked for m. leprae in the lymph node, nerve and skin of multibacillary (mb) leprosy patients who become slit skin smear negative after the completion of who-mbr. twenty-five who-mbr-treated multibacillary leprosy patients were studied; borderline lepromatous (bl) leprosy (n = 11) and lepromatous (ll) leprosy (n = 14)). fifteen patients had reaction (erythema nodosum leprosum 11, upgrading reaction 4) either at presentation or during therapy. all patients attained slit skin smear neg ...	1999	10603717
ribosomal protein l7 included in tuberculin purified protein derivative (ppd) is a major heat-resistant protein inducing strong delayed-type hypersensitivity.	the tuberculin purified protein derivative (ppd) is a widely used diagnostic antigen for tuberculosis. it consists of more than 100 denatured proteins in a culture filtrate of a heated culture of mycobacterium tuberculosis. in two-dimensional electrophoretic analysis of ppds from m. tuberculosis and m. bovis bcg, most proteins were diffusely separated and could not be seen as spots because of denaturation, whereas a few proteins showed relatively clear spots, indicating heat resistance. two such ...	1999	10607306
an immunotherapeutic vaccine for multibacillary leprosy.	on january 30, 1998, a vaccine for leprosy based on mycobacterium w (the code word under which this species hitherto unspecified was investigated) was launched for public use for therapeutic purposes. the vaccine has completed phase iii immunotherapeutic trials as an adjunct to chemotherapy in urban and rural leprosy control centres and has received the authorization from the drugs controller of india for industrial manufacture. it will be made available by m/s cadila pharmaceuticals, ahmedabad. ...	1999	10614726
hla-class ii-associated control of antigen recognition by t cells in leprosy: a prominent role for the 30/31-kda antigens.	the recognition of 16 mycobacterial ags by a panel of t cell lines from leprosy patients and healthy exposed individuals from an endemic population was examined within the context of expressed hla-dr molecules. although overall no significant differences were found between the frequencies of ag recognition in the different subject groups, when ag-specific t cell responses were examined within the context of hla-dr, a highly significant difference was found in the recognition of the 30/31-kda ag. ...	1999	10352313
immunohistological analysis of in situ expression of mycobacterial antigens in skin lesions of leprosy patients across the histopathological spectrum. association of mycobacterial lipoarabinomannan (lam) and mycobacterium leprae phenolic glycolipid-i (pgl-i) with leprosy reactions.	the presence of mycobacterial antigens in leprosy skin lesions was studied by immunohistological methods using monoclonal antibodies (mabs) to mycobacterium leprae-specific phenolic glycolipid i (pgl-i) and to cross-reactive mycobacterial antigens of 36 kd, 65 kd, and lipoarabinomannan (lam). the staining patterns with mab to 36 kd and 65 kd were heterogeneous and were also seen in the lesions of other skin diseases. the in situ staining of pgl-i and lam was seen only in leprosy. both antigens w ...	1999	10362804
human t cell recognition of the mycobacterium leprae lsr antigen: epitopes and hla restriction.	we have in this work mapped epitopes and hla molecules used in human t cell recognition of the mycobacterium leprae lsr protein antigen. hla typed healthy subjects immunized with heat killed m. leprae were used as donors to establish antigen reactive cd4+ t cell lines which were screened for proliferative responses against overlapping synthetic peptides covering the c-terminal part of the antigen sequence. by using this approach we were able to identify two epitope regions represented by peptide ...	1999	10378414
chaperonin function depends on structure and disorder in co-chaperonin mobile loops.	co-chaperonins from diverse organisms exhibit mobile loops which fold into a beta hairpin conformation upon binding to the chaperonin. groes, gp31, and human hsp10 mobile loops exhibit a preference for the beta hairpin conformation in the free co-chaperonins, and the conformational dynamics of the human hsp10 mobile loop appear to be restricted by nascent hairpin formation. backbone conformational entropy must weigh against binding of co-chaperonins to chaperonins, and thus the conformational pr ...	1999	10380224
antimycobacterial activities of riminophenazines.	riminophenazines were specifically developed as drugs active against mycobacterium tuberculosis but extensive research over several decades has shown that these compounds are also active against many other mycobacterial infections, particularly those caused by mycobacterium leprae and the mycobacterium avium complex (mac). clofazimine, the lead compound in this series, is included in the regimens that are approved by the who for the treatment of leprosy and has contributed significantly to the c ...	1999	10382882
molecular mechanism of nerve infection in leprosy.		1999	10383223
inferring the direction of evolutionary changes of genomic base composition.		1999	10390623
the groes antigens of mycobacterium avium and mycobacterium paratuberculosis.	the groes antigen provokes a strong immune response in human beings with tuberculosis or leprosy. we cloned and sequenced the mycobacterium avium and mycobacterium paratuberculosis groes genes. m. avium and m. paratuberculosis have identical groes sequences which differ from other mycobacterial species. this supports the current formal designation of m. paratuberculosis as m. avium subsp. paratuberculosis. immunodominant epitopes from mycobacterium tuberculosis groes are conserved in m. avium, b ...	1999	10392775
viability and drug sensitivity of m. leprae isolated from long-term who/mdt treated multibacillary leprosy patients.		1999	10405543
an assessment of the value of midfinger smears in multibacillary leprosy patients.	in view of the different opinions on fingers as sites for persisting bacilli in multibacillary leprosy patients, it was decided to examine the midfingers for the presence of acid-fast bacilli (afb) and establish its usefulness. sixty-nine multibacillary leprosy patients, [lepromatous (ll) and borderline lepromatous (bl)] treated with multidrug therapy for fixed duration (2 years) were analysed. the bacillary load in the midfinger sites was lower when compared to that in the 'compulsory' (both ea ...	1999	10405544
causative organism and host response. international leprosy congress, beijing, 7-12 september 1998. workshop report.	whether or not the leprosy elimination target is met in all endemic countries by the year 2000, the mdt programme will have greatly reduced worldwide prevalence. however, our workshop chairmen were asked to ignore the prevalence-based leprosy 'elimination' programme and focus on recommendations for a long term, incidence-based eradication target where transmission is blocked. they were asked to be concerned with basic leprosy research goals in the post 2000 era. the members of our workshops are ...	1999	10405553
role of s-100 staining in differentiating leprosy from other granulomatous diseases of the skin.	since mycobacterium leprae are rarely demonstrable in the tuberculoid spectrum of leprosy, a confirmatory diagnosis of leprosy can be made on the basis of finding active destruction of cutaneous nerves by granulomatous inflammation in a skin biopsy. immunoperoxidase staining for s-100 protein, which is a marker for schwann cells, was used to delineate nerves in lesional skin biopsies of 25 patients with tuberculoid and borderline tuberculoid leprosy as well as 15 controls with nonleprous granulo ...	1999	10407622
serum markers of treatment success in leprosy.	intercellular adhesion molecule-1 (icam-1) and e-selectin and other variables were evaluated as possible markers of the success of multidrug therapy (mdt) in leprosy. multibacillary (mb, n = 45) and paucibacillary (pb, n = 29) leprosy patients were examined during mdt, which typically lasted 12 months for mb and 6 months for pb patients. serum values for total protein, albumin, immunoglobulin gamma (igg), icam-1, and e-selectin (selectin) were recorded, as were lesion type, number, and distribut ...	1999	10407625
dermal extracellular matrix in cutaneous leprosy lesions.	thirty-eight biopsies of cutaneous lesions from leprosy patients [borderline tuberculoid (bt) 14, borderline lepromatous (bl) 18, lepromatous (ll) 6] were processed for staining of some extracellular matrix (ecm) components (collagen, proteoglycans, elastic fibers and fibronectin). specific histological staining and the indirect immunofluorescence method with antibodies to collagen and fibronectin were utilized. the ecm of the normal dermis was strikingly modified in the inflammatory infiltrate. ...	1999	10407626
roles of tumor necrosis factor-alpha and transforming growth factor-beta in regulating intercellular adhesion molecule-1 expression on murine peritoneal macrophages infected with m. leprae.	profiles of intercellular adhesion molecule-1 (icam-1) expression on murine peritoneal macrophages (m phi s) infected with mycobacterium leprae during cultivation were examined with special reference to the regulatory effects of tumor necrosis factor-alpha (tnf-alpha) and transforming growth factor-beta (tgf-beta). when m phi s were infected with m. leprae or stimulated with heat-killed m. leprae at day 0, their icam-1 expression, measured in terms of the ratio of m phi s positively stained with ...	1999	10407627
a lost talisman: catastrophic decline in yields of leprosy bacilli from armadillos used for vaccine production.		1999	10407632
effect of prophylactic corticosteroids on the incidence of reactions in newly diagnosed multibacillary leprosy patients.		1999	10407634
therapy of tuberculosis in mice by dna vaccination.	mycobacterium tuberculosis continues to kill about 3 million people every year, more than any other single infectious agent. this is attributed primarily to an inadequate immune response towards infecting bacteria, which suffer growth inhibition rather than death and subsequently multiply catastrophically. although the bacillus calmette-guerin (bcg) vaccine is widely used, it has major limitations as a preventative measure. in addition, effective treatment requires that patients take large doses ...	1999	10421369
no effect of anti-leprosy drugs in the prevention of alzheimer's disease and beta-amyloid neurotoxicity.	there is continuing controversy as to whether or not anti-leprosy drugs prevent alzheimer's disease (ad). therefore, we examined the effect of anti-leprosy drugs on the prevalence of ad in leprosy patients, and also investigated the effect of anti-leprosy drugs on amyloid beta-protein (abeta)-induced neurotoxicity in vitro. the present study suggests that anti-leprosy treatments do not prevent the onset of ad. none of our data found anti-leprosy drugs (dapsone, rifampicin, clofazimine, minomycin ...	1999	10426143
identification of fur, aconitase, and other proteins expressed by mycobacterium tuberculosis under conditions of low and high concentrations of iron by combined two-dimensional gel electrophoresis and mass spectrometry.	iron plays a critical role in the pathophysiology of mycobacterium tuberculosis. to gain a better understanding of iron regulation by this organism, we have used two-dimensional (2-d) gel electrophoresis, mass spectrometry, and database searching to study protein expression in m. tuberculosis under conditions of high and low iron concentration. proteins in cellular extracts from m. tuberculosis erdman strain grown under low-iron (1 microm) and high-iron (70 microm) conditions were separated by 2 ...	1999	9864233
opposite cellular accumulation and nitric oxide production in vivo after pleural immunization with m. leprae or m. bovis bcg.	mycobacteria as intracellular pathogens have evolved mechanisms to survive within macrophages. our previous data showed that m. leprae (ml), unlike m. bovis bcg, did not induce an inflammatory response in the mice subcutaneous tissue. further, ml inhibited bcg-induced foot pad oedema and seemed to transform macrophages in epithelioid cells. since these mycobacteria share common antigens, here we seeked to compare the acute and chronic cellular response evoked by ml and bcg in pleurisy of a mycob ...	1999	9864388
cd1 expression by dendritic cells in human leprosy lesions: correlation with effective host immunity.	a potential role for the cd1 family of lipid ag-presenting molecules in antimicrobial immunity in vivo was investigated in human leprosy skin lesions. strong induction of three cd1 proteins (cd1a, -b, and -c) was observed in dermal granulomas in biopsy samples of involved skin from patients with the tuberculoid form of leprosy or with reversal reactions, which represent clinical patterns of disease associated with active cellular immunity to mycobacterium leprae. in contrast, lesions from patien ...	1999	9973451
specificity and function of immunogenic peptides from the 35-kilodalton protein of mycobacterium leprae.	we identified a t-cell determinant of the 35-kda antigen of mycobacterium leprae which is discriminatory against cross-sensitization by its closely related homologue in mycobacterium avium. from synthetic peptides covering the entire sequence, those with the highest affinity and permissive binding to purified hla-dr molecules were evaluated for the stimulation of proliferation of peripheral blood mononuclear cells (pbmcs) from leprosy patients and healthy sensitized controls. responses to the pe ...	1999	10024600
the clpb atpase of streptomyces albus g belongs to the hspr heat shock regulon.	the clpb gene of streptomyces albus was cloned by polymerase chain reaction (pcr) using degenerate oligonucleotides. transcriptional analysis showed that the clpb gene was heat induced. primer extension identified a transcription start site preceded by typical vegetative -10 and -35 hexamer sequences. the streptomyces hspr repressor is known to bind to three inverted repeat motifs (ir1, ir2, ir3) upstream from the s. coelicolor dnak operon. we identified an inverted repeat motif identical to ir3 ...	1999	10027969
therapeutic hyperbaric oxygenation as an adjunct to multidrug therapy in hansen's disease.	hansen's disease is a chronic infection caused by mycobacterium leprae. current therapy for this disease is with the who recommended multi drug therapy (mdt) with dds, rifampicin and clofazimine. hyper baric oxygen therapy (hbot) has been used to treat many medical conditions including infections with a great deal of success. it's efficacy on various species of mycobacteria and other bacteria have been studied in vitro and in vivo and it is found to be an effective antimicrobial agent under spec ...	1999	28775595
[early diagnosis of leprosy].		1999	19785194
[the study of the genome of mycobacterium leprae].		1999	19785195
[potential applications of molecular biology to leprosy research].		1999	19785196
[vaccine trials against leprosy].		1999	19785197
[pathogenic agent and host response].		1999	19785198
extensive sequence homology between the mycobacterium leprae lsr (12 kda) antigen and its mycobacterium tuberculosis counterpart.	the mycobacterium leprae lsr (12 kda) protein antigen has been reported to mimic whole cell m. leprae in t cell responses across the leprosy spectrum. in addition, b cell responses to specific sequences within the lsr antigen have been shown to be associated with immunopathological responses in leprosy patients with erythema nodosum leprosum. we have in the present study applied the m. leprae lsr dna sequence as query to search for the presence of homologous genes within the recently completed m ...	2000	10617795
inhibition of multiplication of mycobacterium leprae in mouse foot pads by recombinant bacillus catmette-guérin (bcg).	immunization of mice with recombinant mycobacterium bovis bacillus calmette-guérin (rbcg) which over-produces a putative protective antigen candidate, the a component of antigen 85 complex (ag85a), reduced the multiplication of mycobacterium leprae in the foot pads of mice. the inhibition by this rbcg (rbcg/85a) was more evident than that with parental bcg. repeated rbcg/85a immunization significantly could reduce m. leplae multiplication in mice. this is first report of rbcg to control mycobact ...	2000	10618524
the gene encoding mycobacterial dna-binding protein i (mdpi) transformed rapidly growing bacteria to slowly growing bacteria.	pathogenic species of mycobacterium are slowly growing intracellular bacteria. slow growth is important for the parasitism of these organisms and chronicity of the disease, but its precise mechanism has not been elucidated. recently, we found that a novel dna-binding protein (mdpi) was expressed (7-10% in total protein) in mycobacteria, such as mycobacterium bovis bacillus calmette-guérin, mycobacterium tuberculosis, and mycobacterium leprae. in this study, we observed that mdpi interfered with ...	2000	10620682
genomes 2000. intimate portraits of bacterial nemeses.		2000	10809648
protection against virulent mycobacterium avium infection following dna vaccination with the 35-kilodalton antigen is accompanied by induction of gamma interferon-secreting cd4(+) t cells.	mycobacterium avium is an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency of m. avium infection is also increasing in the immunocompetent population. the antigen repertoire of m. avium varies from that of mycobacterium tuberculosis, with the immunodominant 35-kda protein being present in m. avium and mycobacterium leprae but not in members of the m. tuberculosis complex. here we show that a dna vector encoding this m. avium 35-kda antigen (dna- ...	2000	10816448
genomic arrangement of a putative operon involved in maltose transport in the mycobacterium tuberculosis complex and mycobacterium leprae.	a mycobacterium bovis gene coding for a putative male maltose binding protein was cloned and its full-length sequence determined. database searches revealed 99.9% identity with ipqy, encoding a putative sugar uptake protein from mycobacterium tuberculosis strain h37rv. the deduced protein product showed high sequence similarity to male-like proteins from a variety of bacterial species, including mycobacterium leprae. analysis of flanking database sequences from m. tuberculosis and m. leprae reve ...	2000	10817516
dihydropteroate synthase of mycobacterium leprae and dapsone resistance.	two mycobacterium leprae genes, folp1 and folp2, encoding putative dihydropteroate synthases (dhps), were studied for enzymatic activity and for the presence of mutations associated with dapsone resistance. each gene was cloned and expressed in a folp knockout mutant of escherichia coli (c600deltafolp::km(r)). expression of m. leprae folp1 in c600deltafolp::km(r) conferred growth on a folate-deficient medium, and bacterial lysates exhibited dhps activity. this recombinant displayed a 256-fold-gr ...	2000	10817704
a 6 week quadruple drug regimen for the treatment of multibacillary leprosy.		2000	10820986
light and electron microscopic study of peripheral nerve damage in patients with lepromatous leprosy (ll) and borderline lepromatous leprosy (bl).	cutaneous branches of radial nerves in patients with lepromatous leprosy (ll) and borderline lepromatous (bl) were studied by light and electron microscopy. foamy macrophages were found more or less in the nerve fibers of all leprosy patients and distributed in the epineurial, perineurial and endoneurial areas. in the endoneurium, the foamy macrophages were mainly located in the subperineurial and perivascular spaces. vacuolated schwann cells were also found in the nerve fasciculus. in electron ...	2000	10824461
large unilamellar vesicles as trehalose-stabilised vehicles for vaccines: storage time and in vivo studies.	liposomes, as a pharmaceutical formulation must display a long shelf life. the recombinant heat-shock protein from mycobacterium leprae (18-kda hsp) or its n-acylated derivative, when entrapped within or externally associated with large unilamellar vesicles, acts as a t-epitope source. freeze-fracture electron microscopy shows unequivocally that trehalose avoids aggregation and fusion of these vesicles. formulations containing trehalose retained up to 98% of the entrapped protein. the highest an ...	2000	10825571
association of mycobacterium leprae with human endothelial cells in vitro.	endothelial cell infection by mycobacterium leprae has long been described histologically in all types of leprosy and in some of the acute reactions occurring in this disease. recent evidence from experimental lepromatous neuritis indicates that m. leprae colonizes endothelial cells of epineural blood vessels even in sites of minimal infection, suggesting that interaction between these cells and m. leprae may play an important role in the selective localization of this organism to peripheral ner ...	2000	10830776
inhibition of metabolism and growth of mycobacterium leprae by gamma irradiation.	mycobacterium leprae is uncultivable on artificial medium, but viability can be maintained without multiplication for a limited time in vitro. in this study, we evaluated gamma-irradiation (gamma-irr) as a means to kill this slowly growing organism. freshly harvested, viable, athymic, nu/nu mouse-derived m. leprae were exposed to varying doses of gamma-irr from a 60co source. two indicators of bacterial viability were determined: metabolism, measured by oxidation of 14c-palmitic acid to 14co2 in ...	2000	10834063
the effect of ultraviolet light radiation on mycobacterium leprae.	ultraviolet (uv) light is recognized as a potent sterilizing aid, but its relative effectiveness against mycobacterium leprae has not been shown. we examined the influence of uv on the growth and metabolic activity of m. leprae harvested fresh from foot pads of nude mice. temporary static suspensions were exposed to timed intervals of uv radiation generated from a fixed source to constitute dosages ranging from 0-12.64 x 10(4) erg/cm2. the metabolic activity of the bacilli was indexed by the oxi ...	2000	10834064
comparative study of mitsuda reaction to nude mouse and armadillo lepromin preparations using nine-banded armadillos.	in 14 nine-banded armadillos the mitsuda response to nude mouse-derived lepromin (lepromin-nu/nu) was compared to that of armadillo-derived lepromin (lepromin-a) by injecting the reagents intradermally into either side of the abdomen of the animal and examining the biopsies from the sites after 12 days. the histopathologic responses to both antigens were found to be similar, whether the animal was mitsuda-negative (lepromatous) or mitsuda-positive (tuberculoid). it is pointed out that armadillos ...	2000	10834065
pathology of a lepromatous eye.	histopathological examination of an enucleated eye from a lepromatous leprosy patient showed the cornea, ciliary body, and part of the choroid to be infiltrated by macrophages filled with mycobacterium leprae. the walls of blood vessels in the sclera, ciliary body and the anterior choroid demonstrated the presence of m. leprae, giving credence to the blood-borne entry of m. leprae into the eye. unlike the eyes of experimental animals infected with m. leprae, histopathological study of this eye f ...	2000	10834066
antileprosy protective vaccination of rhesus monkeys with bcg or bcg plus heat-killed mycobacterium leprae: immunologic observations.	groups of rhesus monkeys were vaccinated and boosted with mycobacterium bovis bacillus calmette guerin (bcg) or bcg plus low-dose (ld) or high-dose (hd) heat-killed m. leprae (hkml), or were unvaccinated. prior to and following vaccination-boosting and subsequent m. leprae (ml) challenge, these and unvaccinated, unchallenged control monkeys were observed longitudinally for approximately 3 years. vaccination with bcg plus hkml initially stimulated significant in vitro blood mononuclear cell blast ...	2000	10834067
interferon-gamma responses to candidate leprosy skin-test reagents detect exposure to leprosy in an endemic population.	new tools for the detection of leprosy exposure in a community will be necessary for the eradication of leprosy. candidate leprosy skin-test antigens derived from the fractionation of the leprosy bacillus into cytoplasmic and cell-wall proteins free of immuno-inhibitory mycobacterial lipoglycans and carbohydrates were used in an overnight blood test to determine whether exposure to leprosy can be detected by the production of the cytokine interferon gamma (ifn-gamma). strong ifn-gamma responses ...	2000	10834068
human leukocyte antigens in forms of leprosy among japanese patients.	human leukocyte antigens (hla) class ii alleles were analyzed among japanese leprosy patients to ascertain whether immunogenetic differences exist among the leprosy classification forms of ridley and jopling. ninety-three unrelated japanese leprosy patients (21 lepromatous, 24 borderline lepromatous, 17 mid-borderline, 26 borderline tuberculoid, 5 tuberculoid) and 114 healthy control subjects were investigated. the frequencies of hla-drb11501, -drb50101, -dqa10102 and dqb10602 were significa ...	2000	10834069
epidemiology of leprosy in taiwan; its pattern in children.	to study the epidemiology of leprosy in children in taiwan.	2000	10834070
clarification to rada-schlaefli, et al.		2000	10834071
phagocytic myeloperoxidase in leprosy pathogenesis.		2000	10834075
cellular immune response to klebsiella pneumoniae antigens in patients with hla-b27+ ankylosing spondylitis.	to study the reactivity of peripheral blood mononuclear cells (pbmc) of patients with ankylosing spondylitis (as) and rheumatoid arthritis (ra) and healthy controls to klebsiella pneumoniae antigens and to the groel-like proteins from k. pneumoniae (hsp60kp) and mycobacterium leprae recombinant heat shock protein 65 (rhsp65ml).	2000	10852270
in vivo splicing and functional characterization of mycobacterium leprae reca.	the reca proteins from mycobacterium tuberculosis and mycobacterium leprae contain inteins. in contrast to the m. tuberculosis reca, the m. leprae reca is not spliced in escherichia coli. we demonstrate here that m. leprae reca is functionally spliced in mycobacterium smegmatis and produces resistance toward dna-damaging agents and homologous recombination.	2000	10852894
comparative genomics of the leprosy and tubercle bacilli.	to achieve the quantum leap in understanding required to overcome two major human diseases, leprosy and tuberculosis, systematic and comparative genome analysis has been undertaken. new insight into the biology of their causative agents has been obtained and the principle findings are reported here.	2000	10865959
[dissertations about leprosy in the seville at the end of the enlightenment age].	introduction: leprosy is a well-known disease from ancient history. society reacts violently due to the fear of infection, and the fact that it causes appalling physical mutilation. it is produced by mycobacterium leprae, which only affects the nervous system of human beings. development: the norms and examinations that for many years were practiced upon those suspected of being infected by the leprosy organism are based almost always in a series of requirements that were in keeping with cases o ...	2000	10870206
leprosy.	leprosy is a unique infectious disease with a prolonged incubation period and a predilection for skin and nerves. the involvement of nerves by the primary infection as well as the immunologically mediated reversal reactions result in impairment of nerve function and severe disabilities. the introduction of the world health organization multi drug therapy over the last two decades has produced dramatic changes in the management and control programmes of leprosy. a recent important contribution to ...	2000	10871258
a role for cd40-cd40 ligand interactions in the generation of type 1 cytokine responses in human leprosy.	the interaction of cd40 ligand (cd40l) expressed by activated t cells with cd40 on macrophages has been shown to be a potent stimulus for the production of il-12, an obligate signal for generation of th1 cytokine responses. the expression and interaction of cd40 and cd40l were investigated in human infectious disease using leprosy as a model. cd40 and cd40l mrna and surface protein expression were predominant in skin lesions of resistant tuberculoid patients compared with the highly susceptible ...	2000	10903757
leprosy--a new look at an old disease.		2000	10906079
progression of eye disease in "cured" leprosy patients: implications for understanding the pathophysiology of ocular disease and for addressing eyecare needs.	ocular damage in leprosy is due either to nerve damage or infiltration by mycobacteria. there is currently little information about the magnitude and nature of incident ocular pathology in cured leprosy patients. this information would increase our understanding of the pathophysiology of ocular involvement in leprosy and help in developing programmes to address the eyecare needs of leprosy patients who have been released from treatment. the cumulative incidence of leprosy related ocular patholog ...	2000	10906083
characterization of derivatives of the high-molecular-mass penicillin-binding protein (pbp) 1 of mycobacterium leprae.	mycobacterium leprae has two high-molecular-mass multimodular penicillin-binding proteins (pbps) of class a, termed pbp1 and pbp1* [lepage, dubois, ghosh, joris, mahapatra, kundu, basu, chakrabarti, cole, nguyen-disteche and ghuysen (1997) j. bacteriol. 179, 4627-4630]. pbp1-xaa-beta-lactamase fusions generated periplasmic beta-lactamase activity when xaa (the amino acid of pbp1 at the fusion junction) was residue 314, 363, 407, 450 or 480. truncation of the n-terminal part of the protein up to ...	2000	10926828
mycobacterium leprae--millennium resistant! leprosy control on the threshold of a new era.	over the past decades, the conditions of leprosy control implementation have changed dramatically. introduction of multidrug therapy, together with the global effort of the world health organization to eliminate leprosy as a public health problem, had a tremendous impact on leprosy control, particularly by decreasing the registered prevalence of the disease. at the beginning of the new millennium, leprosy control programmes face several new challenges. these relate not only to changes in the pre ...	2000	10929137
search for newer antileprosy drugs.	in 1991 world health organization proclaimed the goal of global elimination of leprosy as a public health problem by year 2000 by implementing multidrug therapy (mdt). since then the prevalence rate has declined by 85%. however, during the same period the incidence rate of leprosy has remained constant or even has been increasing. this suggests that it will take a long time for the eradication of leprosy and that without in-vitro cultivation of m. leprae, eradication of leprosy is not likely to ...	2000	10935183
immunotherapy and immunoprophylaxis of leprosy.		2000	10935184
systemic involvement in leprosy and its significance.		2000	10935191
developments in experimental leprosy.		2000	10935192
novel mechanisms in the immunopathogenesis of leprosy nerve damage: the role of schwann cells, t cells and mycobacterium leprae.	the major complication of reversal (or type 1) reactions in leprosy is peripheral nerve damage. the pathogenesis of nerve damage remains largely unresolved. in situ analyses suggest an important role for type 1 t cells. mycobacterium leprae is known to have a remarkable tropism for schwann cells that surround peripheral axons. reversal reactions in leprosy are often accompanied by severe and irreversible nerve destruction and are associated with increased cellular immune reactivity against m. le ...	2000	10947859
role of inducible nitric oxide synthase in resistance to mycobacterium leprae in mice.	the manifestation of leprosy in humans is largely determined by host immunity to mycobacterium leprae and is a model for immunoregulation in a human disease. however, animal models available for exploration of the leprosy spectrum are inadequate. this study explored m. leprae infection in mice deficient in inducible nitric oxide synthase, and this report describes elements resembling borderline tuberculoid leprosy in humans.	2000	10948185
antiphospholipid antibodies in leprotic patients: a correlation with disease manifestations.	previous studies showed that antiphospholipid antibodies (apl) are frequent in the sera of leprosy patients and are most probably directed against body tissue cardiolipins. some groups have demonstrated differences between the binding specificity of "autoimmune-apl" and "non-autoimmune-apl". it is widely accepted that a plasma protein, beta 2-glycoprotein i (beta 2-gpi), is required for the binding of autoimmune anticardiolipin antibodies (acl) to cardiolipin. however, some reports suggested het ...	2000	10949725
detection of disease related immune complexes in the serum of leprosy patients. a novel single step method.	mycobacterium leprae antigen and antibody complexes could be detected in the serum of leprosy patients using monoclonal antibody ml34 and anti-bcg antibodies by enzyme-linked immunosorbent assay. this simplified system detects disease related complexes without the need for isolating and purifying them from the serum. immune complexes captured using monoclonal antibody ml34 revealed positivity in seven out of eight neuritic, two out of nine tuberculoid (tt), five out of ten borderline tuberculoid ...	2000	10713365
hla-restricted immune response to mycobacterial antigens: relevance to vaccine design.	identification of mycobacterial antigens that are recognized by cd4+ th1 cells in hla-nonrestricted manner or in association with multiple allelic products is required to develop universally effective vaccines against mycobacterial diseases. our studies in this direction have shown that several recombinant mycobacterial antigens of cytosolic and culture filtrate origin are recognized by cd4+ th1 cells. mapping of t cell epitopes with overlapping synthetic peptides covering the entire sequence of ...	2000	10717810
interaction of mycobacterium avium complex with human respiratory epithelial cells.	adherence of mycobacterium avium complex (mac) to human respiratory epithelial cells (hep-2) induced 2 distinct modes of internalization. in the first, mac induced ruffling of hep-2 cell membrane and formation of surface projections securing the bacilli on the surface, and concurrent membrane depressions, beneath the sites of attachment of bacilli, resulted in internalization of the organisms. the second mode involved formation of membrane folds wrapping around the bacilli, followed by internali ...	2000	10720553
role of a bacillus calmette-guérin fibronectin attachment protein in bcg-induced antitumor activity.	intravesical mycobacterium bovis bacillus calmette-gu*erin (bcg) is the treatment of choice for superficial bladder cancer. previous studies showed that attachment of bcg to fibronectin within the bladder was necessary for mediation of the antitumor response. further studies identified a bacterial receptor, fibronectin attachment protein (fap), as an important mediator of bcg attachment to fibronectin. in vitro studies showed that a stable bcg/fibronectin interaction was dependent on fap binding ...	2000	10728599
interleukin-12 amplifies the m. leprae hsp65-cytotoxic response in the presence of tumour necrosis factor-alpha and interferon-gamma generating cd56+ effector cells: interleukin-4 downregulates this effect.	interleukin-12 (il-12) is a major immunomodulatory cytokine that represents a functional bridge between the early resistance and the subsequent antigen specific adaptive immunity. tnf-alpha and ifn-gamma have an important role in the generation of hsp65 specific cytotoxic t lymphocytes (ctl) that lyse hsp65-pulsed autologous macrophages (hsp65 ctl). since a positive feedback mechanism between tnf-alpha, ifn-gamma and il-12 has been described, we undertook to evaluate the role of il-12 on the hsp ...	2000	10736095
immunological cytokine correlates of protective immunity and pathogenesis in leprosy.	the in vitro production of interferon (ifn)-gamma, interleukin (il)-5, tumour necrosis factor (tnf)-alpha and il-10 by blood mononuclear cells in response to whole mycobacterium leprae and polyclonal stimulii of 23 individuals, representing a variety of conditions in relation to exposure/susceptibility to m. leprae, was assayed. in most cases, healthy household contacts of newly diagnosed multibacillary leprosy patients, designated exposed household contacts (ec), showed low-to-undetectable in v ...	2000	10736116
atp content of mycobacterium tuberculosis grown in vivo and in vitro.	in order to determine the reason for the slow growth of mycobacterium leprae either in a host or in vitro, the growth characteristics of mycobacterium tuberculosis were studied. the atp content of in vitro-grown m. tuberculosis was about 520 pg/10(6) viable organisms. the atp levels from in vivo-derived organisms obtained from liver and spleen of mice was about 130 pg (in cases of chronic infection) and about 270 pg (in cases of acute infection). when the in vivo-derived organisms were inoculate ...	2000	10738981