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incidence of acute nerve function impairment and reactions in leprosy: a prospective cohort analysis after 5 years of follow-up.nerve function impairment (nfi) is the key outcome of the pathological processes of infection with mycobacterium leprae, which can continue after completion of multidrug therapy (mdt) and lead to disability after leprosy patients are released from treatment. the objective of this study was to assess the need for and duration of surveillance of nfi.200415082636
production and characterization of peptide mimotopes of phenolic glycolipid-i of mycobacterium leprae.phenolic glycolipid-i (pgl-i), a mycobacterium leprae-specific antigen, has been widely used for the serodiagnosis of leprosy and has been implicated in the pathogenesis of leprosy. in an effort to produce an alternate antigen of pgl-i, the mimotope peptides of pgl-i, w(t/r)lgpy(v/m), were obtained using a monoclonal antibody, iii603.8, specific to pgl-i by a phage library. the biotin-labeled predominant mimotope peptide of pglp1, wtlgpyv, bound to iii603.8 in a dose-dependent manner in an immun ...200415094167
leprosy and aids: two cases of increasing inflammatory reactions at the start of highly active antiretroviral therapy.reported here are the cases of two hiv-positive patients with skin lesions suggestive of leprosy, based on clinical and pathological analysis, which worsened during the few weeks following initiation of highly active antiretroviral therapy. the lesions improved after a few weeks of multidrug therapy for leprosy. mycobacterium leprae was confirmed by polymerase chain reaction analysis of blood in case 1 and of a biopsy sample in case 2. neither mycobacterium avium complex nucleic acid, which is u ...200415112073
[the estimation of protective efficacy of the fusion gene vaccine encoding tubercle antigen 85b and mpt64 in mice challenged with mycobacterium tuberculosis].to evaluate the protective efficacy of the fusion dna vaccine (am) encoding tubercle ag85b and mpt64 in mice infected with mycobacterium tuberculosis.200415130316
lepra vaccine. 200415133399
comparative analysis of b- and t-cell epitopes of mycobacterium leprae and mycobacterium tuberculosis culture filtrate protein 10.culture filtrate protein 10 (cfp-10) from mycobacterium tuberculosis is a well-characterized immunodominant 10-kda protein antigen known to elicit a very potent early gamma interferon response in t cells from m. tuberculosis-infected mice and humans. the sequence of the mycobacterium leprae homologue of cfp-10 shows only 40% identity (60% homology) at the protein level with m. tuberculosis cfp-10 and thus has the potential for development as a t- or b-cell reactive antigen for specific diagnosis ...200415155617
pitfalls in the cytological classification of borderline leprosy in the ridley-jopling scale.this is a blinded, retrospective, correlative study of classification of leprosy by cytomorphology, clinical examination, and bacterial density. one hundred consecutive adequate aspirates from skin lesions of leprosy were studied. the ridley-jopling (r-j) five-group classification system was used. may-gruenwald-giemsa (mgg) and ziehl-neelsen (z-n) stains were employed. complete clinical, cytological, and bacteriological concordance was found in 88 patients. one-step mismatch in classification wa ...200415176024
genotypic variation and stability of four variable-number tandem repeats and their suitability for discriminating strains of mycobacterium leprae.it has not been possible to distinguish different strains of mycobacterium leprae according to their genetic sequence. however, the genome contains several variable-number tandem repeats (vntr), which have been used effectively in strain typing of other bacteria. to determine their suitability for differentiating m. leprae, we developed pcr systems to amplify 5 different vntr loci and examined a battery of 12 m. leprae strains derived from patients in different regions of the united states, braz ...200415184434
an in vitro model for the lepromatous leprosy granuloma: fate of mycobacterium leprae from target macrophages after interaction with normal and activated effector macrophages.the lepromatous leprosy granuloma is a dynamic entity requiring a steady influx of macrophages (mphi) for its maintenance. we have developed an in vitro model to study the fate of mycobacterium leprae in a ll lesion, with and without immunotherapeutic intervention. target cells, consisting of granuloma mphi harvested from the footpads of m. leprae-infected athymic nu/nu mice, were cocultured with normal or ifn-gamma-activated (act) effector mphi. the bacilli were recovered and assessed for viabi ...200415187161
tunel and limited immunophenotypic analyses of apoptosis in paucibacillary and multibacillary leprosy lesions.some mycobacterial infections, such as tuberculosis, are characterized by apoptosis of infected or by-stander mononuclear immune cells. for localized (paucibacillary, pb) and disseminated (multibacillary, mb) leprosy, characterized by polarized th1-like vs. th2-like immune responses, respectively, little is known about lesional apoptosis. we analyzed sections of paraffin-embedded, untreated leprosy lesions from 21 patients by an indirect immunofluorescent terminal deoxynucleotide-transferase-med ...200415196577
tissue-specific down-regulation of ripk 2 in mycobacterium leprae-infected nu/nu mice.ripk 2 is adapter molecule in the signal pathway involved in toll-like receptors. however, there has been no reported association between receptor-interacting serine/threonine kinase 2 (ripk 2) expression and the infectious diseases involving mycobacterial infection. this study found that its expression was down-regulated in the footpads and skin but was up-regulated in the liver of mycobacterium leprae-infected nu/nu mice compared with those of the m. leprae non-infected nu/nu mice. it was obse ...200415203566
lepromatous leprosy with extensive unusual ulcerations and cachexia. is it the first case of lucio's phenomenon from iran?we report a 33-year-old iranian woman with widespread ulcerative lesions in the setting of lepromatous leprosy. we think that the sudden appearance of the characteristic necrotic lesions in the absence of fever and other systemic manifestation, and in accordance with epidermal necrosis and the presence of large numbers of afb in the endothelium are all in favor of the diagnosis of lucio's phenomenon for this patient. to our knowledge this is the first patient who may have had this phenomenon rep ...200415217312
active surveillance of leprosy contacts in country with low prevalence rate.for advanced control of leprosy in pakistan where the world health organization leprosy elimination goal was achieved in 1996, we conducted surveillance of mycobacterium leprae-seropositive patients and their contacts and drug resistant strains of m. leprae. we measured anti-pgl-i antibody level in sera from leprosy patients and their contacts for early detection of m. leprae infection. out of 34 leprosy patients undergoing treatment, 4 lepromatous leprosy patients were antibody positive, and 6. ...200415217314
leprosy patients with lepromatous disease have an up-regulated il-8 response that is unlinked to tnf-alpha responses.tumor necrosis factor (tnf-alpha) in conjunction with interferon-gamma (ifn-gamma) plays an important role in lymphocyte recruitment and granuloma formation in mycobacterial diseases. lepromatous leprosy infections are typically associated with low to absent t cell responses and the absence of inf-gamma secretion. chemokines such as il-8, mcp-1, and mip-1beta, have also been shown to recruit neutrophils and lymphocytes to the site of mycobacterial infections. we have studied il-8 expression in r ...200415217317
il-10 treatment of macrophages bolsters intracellular survival of mycobacterium leprae.in these studies, metabolically active mycobacterium leprae were maintained for as long as 8 weeks in monolayer cultures of mouse peritoneal macrophages (mphi). supplemental il-10, but not tgf-beta, bolstered, directly or indirectly, m. leprae metabolism in mouse mphi. in the cell culture system temperature setting is extremely important and 31 to 33 degrees c incubation temperature was more permissive than 37 degrees c. acid fast staining and transmission electron microscopy (tem) of intracellu ...200415217319
design of the leprosy component of the brazilian bcg revaccination trial for assessing bcg effectiveness against leprosy in school children.background: bcg vaccination confers protection against leprosy, and vaccination among household contacts has been recommended in brazil. nevertheless, vaccination of the entire community against leprosy is not advocated as leprosy has low incidence in most populations. despite that, in brazil, bcg vaccination is recommended among school children to prevent tuberculosis and this large scale vaccination may also affect the occurrence of leprosy, which led to investigations of its impact on leprosy ...200415217320
relapses in multibacillary patients treated with multi-drug therapy until smear negativity: findings after twenty years.the schieffelin leprosy research and training center at karigiri, india participated in several of the world health organization (who) trials. the first trial on combined therapy in multi-bacillary leprosy was initiated in 1981. the main objectives of this field trial were to evaluate the efficacy of who recommended regimens in preventing relapses, especially drug resistance relapses. this paper reports on the relapses twenty years after patients were inducted into the who field trial. between 1 ...200415217321
detection and quantification of mycobacterium leprae in tissue samples by real-time pcr.real-time pcr technology has improved molecular diagnostics of many pathogens, but no such test is available for mycobacterium leprae. in this report we describe the establishment and the pre-clinical evaluation of such an assay. the test achieved a theoretical analytical sensitivity limit of 194 m. leprae cells per skin biopsy specimen and facilitated quantification of mycobacteria in tissue over a range of 54-54,000,000 cells per sample. in punch skin biopsies from 39 untreated ugandan patient ...200412884037
leprosy. 200415865707
current epidemiology of leprosy.every year around 4,00,000 new cases of leprosy occur in india and india contributes about 80% of the global leprosy case load. the prevalence of leprosy (case load per 1,00,000 population) has come down from 52 per 10,000 in 1981 to 2.4 per 10,000 in july 2004. there is no primary prevention for leprosy. multidrug therapy is the only intervention available against the disease. as of july 2004 there were about 2,40,000 leprosy cases on record in india. there are thirteen states and union territo ...200415871348
clinical manifestations, diagnosis and classification of leprosy.mycobacterium leprae, the causative organism of leprosy is slow-growing and the reason is its long incubation period of 2-4 years. males are predominantly affected and deformity is produced in less than 2% of people affected with the disease. the disease manifests in the skin as macules, papules, nodules, plaques or infiltration. hypopigmented or erythematous skin patches with definite sensory deficit is one of the clinical cardinal signs by which one can make a definite diagnosis. demonstration ...200415871350
biological implications of mycobacterium leprae gene expression during infection.the genome of mycobacterium leprae, the etiologic agent of leprosy, has been sequenced and annotated revealing a genome in apparent disarray and in stark contrast to the genome of the related human pathogen, m. tuberculosis. with less than 50% coding capacity of a 3.3-mb genome and 1,116 pseudogenes, the remaining genes help define the minimal gene set necessary for in vivo survival of this mycobacterial pathogen as well as genes potentially required for infection and pathogenesis seen in lepros ...200415741741
are viable mycobacterium leprae present in lepromatous patients after completion of 12 months' and 24 months' multi-drug therapy?a study was carried out to determine whether or not viable bacilli persist in mb patients treated with 12-month and 24-month multidrug therapy (mdt). in the first group, 60 untreated lepromatous patients who had an initial average bacterial index (bi) of 3+ or more were enrolled. at the completion of 12 months of mdt, skin biopsies were obtained and m. leprae concentrate was inoculated into the footpads of five thymectomized and irradiated (t900r) mice. rees technique was used for the mouse foot ...200415835604
susceptibility to leprosy may be conditioned by an interaction between the nramp1 promoter polymorphisms and the lepromin response.controversial results have been achieved by attempting to associate the nramp1 gene with mycobacterium leprae susceptibility as well as with the mitsuda reaction, which represents a specific immune response to m. leprae. this study evaluated this association as well as the interaction of the polymorphism (gt)(n) in the promoter region of the nramp1 gene with a specific immune response to m. leprae measured by the intradermal mitsuda test in leprosy patients and in non-consanguineous household co ...200415755200
a mutation at codon 516 in the rpob gene of mycobacterium leprae confers resistance to rifampin.a missense mutation at codon 516 in the rpob gene of mycobacterium leprae conferring rifampin resistance was confirmed by the correlation between sequencing results and mouse footpad assay. the isolate was obtained from a relapsed lepromatous leprosy patient. this is the first report on the complete concordance between the mutation located at codon 516 in the rpob gene and the corresponding resistance to rifampin in leprosy. the novel profile of mutation in the rpob gene will contribute to the c ...200415755201
epidemiology of leprosy. 200415755207
the relapse rate in mb leprosy patients treated with 2-years of who-mdt is not low.a group of multibacillary patients is clearly at high risk for relapse following 2-yr who-mdt. relapse is largely confined to bl or ll patients with a high bi initially, and occurs long after the discontinuation of therapy. this important group of patients at risk for treatment failure presents several important issues: the need to identify those at risk and the operational requirements needed for their long term follow-up. also, this group of patients might well benefit from an alternative anti ...200415755209
the 6th who tag report: validation and "non-existent patients". 200415755210
high resolution shadowing of mycobacterium leprae.metal shadow casting techniques for transmission electron microscopic examination was used to determine the morphological characteristics of mycobacterium leprae in untreated and treated patients. this technique is used to visualize bacterial surface structures by thermal evaporation of platinum alloys under moderate vacuum. this method gives a high contrast image at relatively low resolution and is useful for correlating micro-morphology quantitatively to early therapeutic effects of anti-lepro ...200415764287
spatial analysis of the distribution of leprosy in the state of ceará, northeast brazil.the aim of this study was to describe spatial patterns of the distribution of leprosy and to investigate spatial clustering of incidence rates in the state of ceará, northeast brazil. the average incidence rate of leprosy for the period of 1991 to 1999 was calculated for each municipality of ceará. maps were used to describe the spatial distribution of the disease, and spatial statistics were applied to explore large- and small-scale variations of incidence rates. three regions were identified i ...200415654421
differential interferon- gamma production characterizes the cytokine responses to leishmania and mycobacterium leprae antigens in concomitant mucocutaneous leishmaniasis and lepromatous leprosy.tegumentary leishmaniasis and leprosy display similar spectra of disease phenotypes, which are dependent on cell-mediated immunity to specific antigens. diffuse cutaneous leishmaniasis and lepromatous leprosy represent the anergic end of the spectrum, whereas mucocutaneous leishmaniasis and tuberculoid leprosy are associated with marked antigen-specific cellular immune response.200415655736
the upstream sequence of mycobacterium leprae 18-kda gene confers transcription repression activity in orientation-independent manner.in order to understand the role of the upstream region of the mycobacterium leprae 18-kda gene on the gene regulation, the region was divided into two at the -50 position from the first start codon of the gene and their effect on transcription was examined by using a lacz transcriptional reporter gene assay. the presence of each of these two regions conferred transcription repression not only on its cognate m. lepraerae 18-kda gene promoter, but also on a heterologous promoter such as the mycoba ...200415665583
a study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients: design, methodology and recruitment findings of colep.in this article, we describe the design, methodology and recruitment findings of the colep study. the objectives of this study were to determine the effectiveness of chemoprophylaxis with a single dose of rifampicin in the prevention of leprosy among close contacts of leprosy patients, and to find characteristics of contact groups most at risk to develop clinical leprosy. these characteristics should be usable by routine leprosy control programmes. colep consists of a cluster randomized, double- ...200415682975
a clinical trial of pefloxacin and ofloxacin in lepromatous leprosy.a 2-month clinical trial of pefloxacin and ofloxacin in previously untreated multibacillary patients was conducted at the leonard wood memorial leprosy research center, cebu, the philippines. treatment with either pefloxacin or ofloxacin resulted in rapid clinical improvement, in this regard pefloxacin appearing somewhat superior. reactions and side effects were minimal. single doses of either agent did not result in significant killing of mycobacterium leprae, but significant bactericidal activ ...200415685736
leprosy: a case series and review.hansen disease, historically known as leprosy, is caused by mycobacterium leprae. the disease is rare in the united states but remains endemic among certain immigrant populations, and may manifest years after infection. the us military has a number of active duty troops originally from endemic countries. recently, three us soldiers with hansen disease were evaluated at walter reed army medical center. the mean time to diagnosis was 8 months (range, 2 to 18 months). all three patients were initia ...200415646765
comparison between c57bl/6 and c57bl/10 mycobacterial mouse pleurisy with respect to cellular migration and nitric oxide production.mycobacterium bovis-bcg (bcg) and mycobacterium leprae (ml) have opposite inflammatory properties. mycobacteria-induced pleurisy in c57bl/6 and c57bl/10 mice was evaluated to establish if their innate responses could be comparable, verifying cellular migration and nitrite production. kinetic responses after ml or bcg intrathoracic injection were compared in those mice, sharing the h-2(b) mhc haplotype. bcg led to acute eosinophilia and late neutrophilia in both mice. in c57bl/6 late pleurisy, mo ...200415901414
comparison of multidrug therapy treatment results between multibacillary leprosy patients in hyperendemic and hypoendemic areas in gowa regency, south sulawesi, indonesia.we studied 88 multibacillary (mb) leprosy patients, who received multidrug therapy (mdt) treatment in hyperendemic (44 persons) and hypoendemic (44 persons) areas in gowa regency, south sulawesi, indonesia. bacteriological examinations were carried out (bacteria index and morphology index), immunological examinations (mlpa and tnf-alpha) and genetic variation in blood and ear lobe slit skin smears of mb leprosy patients, which had been treated by mdt, were performed. the collected data were anal ...200415691133
leprosy and peripheral neuropathy.leprosy, although rare in the united states, continues to be a leading cause of peripheral neuropathy and blindness worldwide. we describe the pathogenic agent mycobacterium leprae and discuss the epidemiology of this disease. the different classification schemes are compared and the clinical and laboratory features are presented. finally, the immunology, pathology, and the treatment are discussed.200419078734
subcutaneous nodules and joint deformity in leprosy: case report and review.leprosy (hansen's disease), known to be caused by mycobacterium leprae, is a well-known illness with multiple rheumatologic manifestations. this chronic granulomatous infection has clinical features that are variable, depending on the immune response of the host. manifestations consist mainly of involvement of the peripheral nerves, skin, upper respiratory system, eyes, and testes, as well as joints. musculoskeletal manifestations include arthralgias, arthritis, charcot arthropathy, and positive ...200317041455
leprosy in a mexican immigrant.a new diagnosis of borderline lepromatous leprosy was established in a man who had immigrated to kentucky from mexico. he was placed on a world health organization treatment regimen consisting of dapsone, clofazimine, and rifampin. the biology of leprosy, its diagnosis, treatment, and worldwide impact are reviewed. because of the potential for highly mobile populations to export endemic diseases, kentucky physicians must expand their lists of differential diagnoses.200312886712
t-cell recognition of peptides from the mycobacterium leprae 35 kda protein in thai leprosy patients, healthy contacts, and non-contacts.the objective of the study was to identify mycobacterium leprae-specific immunogenic peptides for the development of a skin test reagent. such a reagent is required for the detection of m. leprae infection and possibly for the diagnosis of patients with active leprosy. for this purpose, we analyzed the in vitro responses of human peripheral blood mononuclear cell (pbmcs) to peptides from the 35 kda protein of m. leprae. this protein is of interest since it has no homologue within the mycobacteri ...200312853165
gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy, non-mycobacterium bovis bcg-vaccinated malawian young adults.we have previously shown that young adults living in a rural area of northern malawi showed greater gamma interferon (ifn-gamma) responses to purified protein derivatives (ppd) prepared from environmental mycobacteria than to ppd from mycobacterium tuberculosis. in order to define the mycobacterial species to which individuals living in a rural african population have been exposed and sensitized, we tested t-cell recognition of recombinant and purified antigens from m. tuberculosis (38 kda, mpt6 ...200312853392
identification of strong promoter elements of mycobacterium smegmatis and their utility for foreign gene expression in mycobacteria.the isolation of elements driving high-level expression of foreign genes in mycobacteria would significantly aid characterization of mycobacterial antigens and recombinant vaccine development. mycobacterium smegmatis is a widely employed host for recombinant mycobacterial gene expression. this report describes the identification of strong promoter elements of m. smegmatis. fluorescence-activated cell sorting was employed to isolate dna fragments permitting high-level expression of the aequorea v ...200312855181
estimating the relative recurrence risk ratio for leprosy in karonga district, malawi.leprosy is a chronic disease caused by infection with mycobacterium leprae. susceptibility to leprosy is influenced by both genetic and non-genetic factors and the disease is known to cluster in families. one measure of genetic effect is the relative recurrence risk ratio, lambdar. estimates of this parameter can be inflated if environmental risk factors which also cluster in families, such as household contact, are not properly accounted for. we present the results of fitting a cross ratio mode ...200312862254
criteria for diagnosis of pure neural leprosy.the clinical diagnosis of pure neural leprosy (pnl) remains a public health care problem mainly because skin lesions-the cardinal features of leprosy-are always absent.moreover, the identification of the leprosy bacillus is not easily achieved even when a nerve biopsy can be performed. in an attempt to reach a reliable pnl diagnosis in patients referred to our leprosy outpatient clinic, this study employed a variety of criteria. the nerve biopsies performed on the 67 individuals whose clinical, ...200312883921
geographically specific infections and arthritis, including rheumatic syndromes associated with certain fungi and parasites, brucella species and mycobacterium leprae.this overview is designed to introduce the reader to the broad spectrum of rheumatic syndromes associated with certain fungal and parasitic diseases, brucellosis and leprosy. musculoskeletal disorders caused by fungi are uncommon and difficult to diagnose, particularly in the early stages. deep fungal infections involve-in order of frequency-bone, soft tissues and joints. rare but well-defined rheumatic syndromes occur in a variety of parasitic diseases. brucellosis remains a major challenge to ...200312787526
systemic dissemination in tuberculosis and leprosy: do mycobacterial adhesins play a role?more than one century after the discovery of their etiological agents, tuberculosis and leprosy remain as major health threats for humans, and the molecular mechanisms that lead to the development of both diseases are poorly understood. the elucidation of these mechanisms, and especially those allowing for the mycobacteria to systemically disseminate, should facilitate the development of new prophylactic and/or therapeutic strategies. this review is focused on the routes that mycobacterium tuber ...200312787744
the complete genome sequence of mycobacterium bovis.mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. the human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. m. bovis was also the progenitor for the m. bovis bacillus calmette-guérin vaccine strain, the most widely used human vaccine. here we describe the 4,345,492-bp genome sequence of m. bovis af2122/97 and its comparison with the genomes of mycobact ...200312788972
fine needle aspiration cytology of leprous neuritis.to document the cytomorphologic features of leprous neuritis and their correlation with bacterial density.200312789916
histoid leprosy: diagnosis by fine needle aspiration cytology. 200312789951
assessment of cell mediated immunogenicity of mycobacterium leprae-derived antigens.the antigenicity of mycobacterium leprae (m. leprae)-derived cell membrane fraction was examined using human dendritic cells (dcs). immature dcs internalized and processed the cell membrane components, and expressed m. leprae-derived antigens (ags) on their surface. the expression of mhc class ii, cd86, and cd83 ags on dcs and cd40 ligand (l)-associated il-12 p70 production from dcs were up-regulated by the membrane ags. moreover these stimulated dcs induced significantly higher level of interfe ...200312798309
comparative studies of the cell structures of mycobacterium leprae and m. tuberculosis using the electron microscopy freeze-substitution technique.the cell envelope and cytoplasmic architecture of the mycobacterium leprae thai-53 strain were examined using the freeze-substitution technique of electron microscopy and compared with those of the m. tuberculosis h37rv strain. both strains had similarly multilayered envelope architectures composed of an electron-translucent layer, a peptidoglycan layer and the plasma membrane, from outside to inside. a comparison of the structures of these two mycobacteria revealed that the m. leprae cell was s ...200312801063
comparison of two different pcr amplification products (the 18-kda protein gene vs. rlep repetitive sequence) in the diagnosis of mycobacterium leprae.to determine the best molecular method for diagnosing leprosy, two sets of mycobacterium leprae-specific primers were compared. fresh biopsies and slit skin smear samples were obtained from 67 leprosy patients and examined by touchdown (td) pcr using primers amplifying either a 129-bp fragment of the rlep repetitive sequence or a 360-bp fragment of the 18-kda protein gene of m. leprae. seventeen of 30 (56.7%) biopsy specimens and four of 37 (10.8%) slit skin smear specimens were positive using t ...200312823306
prospects for molecular epidemiology of leprosy. 200312669928
comparison of pcr mediated amplification of dna and the classical methods for detection of mycobacterium leprae in different types of clinical samples in leprosy patients and contacts.traditional staining and microscopic examination techniques for the detection of mycobacterium leprae, dna amplification by polymerase chain reaction (pcr) of a 531-bp fragment of the m. leprae specific gene encoding the 36-kda antigen, and serodiagnosis with m. leprae specific antigens (pgl-1 and d-bsa) were compared on different clinical specimens (serum samples, slit-skin smears, biopsies and swabs) from 60 leprosy patients attending the sanatorium of fontilles. patients were divided into gro ...200312669929
in-vitro activity of sitafloxacin (du-6859a), either singly or in combination with rifampin analogs, against mycobacterium leprae.the in-vitro antibacterial activity of sitafloxacin (du-6859a) against mycobacterium leprae was evaluated and compared with those of ofloxacin, levofloxacin, and ciprofloxacin. two biochemical indicators (intracellular atp and uptake of [(3)h]-thymidine) were used to measure the in-vitro growth of m. leprae in dhople-hanks (dh) medium. sitafloxacin was found to be more potent than the other three commonly used fluoroquinolones, with the minimum inhibitory concentration (mic) against m. leprae be ...200312673400
fontilles faces the future of leprosy. 200312679256
activation and regulation of toll-like receptors 2 and 1 in human leprosy.the expression and activation of toll-like receptors (tlrs) was investigated in leprosy, a spectral disease in which clinical manifestations correlate with the type of immune response mounted toward mycobacterium leprae. tlr2-tlr1 heterodimers mediated cell activation by killed m. leprae, indicating the presence of triacylated lipoproteins. a genome-wide scan of m. leprae detected 31 putative lipoproteins. synthetic lipopeptides representing the 19-kd and 33-kd lipoproteins activated both monocy ...200312692544
induction of apoptosis in monocytes by mycobacterium leprae in vitro: a possible role for tumour necrosis factor-alpha.a diverse range of infectious organisms, including mycobacteria, have been reported to induce cell death in vivo and in vitro. although morphological features of apoptosis have been identified in leprosy lesions, it has not yet been determined whether mycobacterium leprae modulates programmed cell death. for that purpose, peripheral blood mononuclear cells obtained from leprosy patients were stimulated with different concentrations of this pathogen. following analysis by flow cytometry on 7aad/c ...200312709029
role of fluorescent microscopy in detecting mycobacterium leprae in tissue sections.we compared the sensitivity of the fluorescent method with that of he modified fite-faraco method in the detection of mycobacterium leprae in tissue sections. fifty-six skin biopsies were obtained from patients having leprosy, particularly the paucibacillary type. minor alterations were made in the deparaffinization and staining technique, as compared with kuper and may's method, to obtain optimum fluorescence. of 56 biopsies studied, 39 showed organisms by the fluorescent method and only 25 sho ...200312715331
[comparative genomics of mycobacterium tuberculosis and m. leprae]. 200312718060
[leprosy]. 200312722275
detection of gene mutations related with drug resistance in mycobacterium leprae from leprosy patients using touch-down (td) pcr.the lack of methods to identify mycobacterium leprae with the resistance against multi-drugs quickly and specifically has hindered effective chemotherapy against m. leprae infection. to screen m. leprae with resistance against multi-drugs, the touch-down (td)-pcr has been used in this study. sequences of the folp, rpoa, b, and gyra, b genes were analyzed for isolates of m. leprae from leprosy patients in korea. we amplified designated region of several genes in m. leprae involved in drug resista ...200312727362
simple and fast lateral flow test for classification of leprosy patients and identification of contacts with high risk of developing leprosy.the interruption of leprosy transmission is one of the main challenges for leprosy control programs since no consistent evidence exists that transmission has been reduced after the introduction of multidrug therapy. sources of infection are primarily people with high loads of bacteria with or without clinical signs of leprosy. the availability of a simple test system for the detection of antibodies to phenolic glycolipid-i (pgl-i) of mycobacterium leprae to identify these individuals may be impo ...200312734239
atomic force microscopy as a tool for biomedical and biotechnological studies.this work presents different applications in progress with the aid of the atomic force microscopy (afm) technique for biomedical and biotechnological applications, comprising both the acquisition of three-dimensional images and spectroscopic force measurements, in the following systems: first, low-density lipoprotein (ldl)-glycosaminoglycans; second, lectins-polysaccharides; third, mycobacterium leprae cellular wall and vesicular stomatites virus (vsv) with fibronectin laminin, and lipidic membr ...200312752206
the combination of plasmid interleukin-12 with a single dna vaccine is more effective than mycobacterium bovis (bacille calmette-guèrin) in protecting against systemic mycobacterim avium infection.sub-unit vaccines utilizing purified mycobacterial proteins or dna vaccines induce partial protection against mycobacterial infections. for example, immunization with dna vaccines expressing the gene for the immunodominant 35000 mw protein, common to mycobacterium avium and mycobacterium leprae but absent from the mycobacterium tuberculosis complex, conferred significant protection against infection with either virulent m. avium or m. leprae in mice. however, the level of protection was equivale ...200312757627
the allele encoding the mycobacterial erp protein affects lung disease in mice.erp (exported repetitive protein), also known as p36, pirg and rv3810, is a member of a mycobacteria-specific family of extracellular proteins. these proteins consist of three domains, the n- and c-terminal domains are similar in all mycobacterial species, however, the central domain contains a repeated pglts module and differs considerably between species. the erp knockout mutant of mycobacterium tuberculosis displays very low levels of multiplication both in macrophage cell lines and in vivo i ...200312542471
crystal structure of the catalytic domain of the pknb serine/threonine kinase from mycobacterium tuberculosis.with the advent of the sequencing programs of prokaryotic genomes, many examples of the presence of serine/threonine protein kinases in these organisms have been identified. moreover, these kinases could be classified as homologues of those belonging to the well characterized superfamily of the eukaryotic serine/threonine and tyrosine kinases. eleven such kinases were recognized in the genome of mycobacterium tuberculosis. here we report the crystal structure of an active form of pknb, one of th ...200312551895
chromosome 6q25 is linked to susceptibility to leprosy in a vietnamese population.leprosy, a chronic infectious disease caused by mycobacterium leprae, affects an estimated 700,000 persons each year. clinically, leprosy can be categorized as paucibacillary or multibacillary disease. these clinical forms develop in persons that are intrinsically susceptible to leprosy per se, that is, leprosy independent of its specific clinical manifestation. we report here on a genome-wide search for loci controlling susceptibility to leprosy per se in a panel of 86 families including 205 si ...200312577057
expression of toll-like receptor 2 on human schwann cells: a mechanism of nerve damage in leprosy.nerve damage is a clinical hallmark of leprosy and a major source of patient morbidity. we investigated the possibility that human schwann cells are susceptible to cell death through the activation of toll-like receptor 2 (tlr2), a pattern recognition receptor of the innate immune system. tlr2 was detected on the surface of human schwann cell line st88-14 and on cultured primary human schwann cells. activation of the human schwann cell line and primary human schwann cell cultures with a tlr2 ago ...200312595460
effect of vaccination with refined components of the organism on infection of mice with mycobacterium leprae.only native products of mycobacterium leprae, whether cell wall, cytosol, or membrane derived, can confer protective immunity against challenge in the mouse footpad. previously, recombinant proteins were shown to be ineffective. the cell wall skeleton-the mycolyl-arabinogalactan-peptidoglycan complex-devoid of proteins is not protective.200312595485
did the loss of sigma factors initiate pseudogene accumulation in m. leprae?pseudogenes are non-functional regions in the genome that have arisen as a consequence of accumulating mutations that either result in the premature termination of proteins during protein synthesis or the disruption of transcription. there have been various discussions of the origins of pseudogenes and the models for their formation, but there has been little input on how pseudogenes could have accumulated in an organism. in this brief communication, i propose a two-step model for the accretion ...200312598124
in vivo susceptibility of mycobacterium leprae to sitafloxacin (du-6859a), either singly or in combination with rifampicin analogues.the antimicrobial effects of sitafloxacin (du-6859a) against mycobacterium leprae, either singly or in combination with either rifampicin, rifabutin or krm-1648, were studied using a mouse footpad assay technique and the results were compared with those obtained with ofloxacin. when used singly, the minimum concentrations of sitafloxacin and ofloxacin needed to inhibit completely the growth of m. leprae were 25 and 100 mg per kg body weight per day, respectively, and the effects were bactericida ...200312636987
recent advances in the treatment of leprosy.leprosy, a chronic infectious disease caused by mycobacterium leprae, was identified by g. h. a. hansen in 1873. the different clinical presentations of the disease are determined by the quality of the host immune response. the bacteria have affinity for the peripheral nerves and are likely the cause of neuropathy, a cardinal manifestation of the disease. who recommends a protocol of multidrug therapy (mdt), which effectively controls the disease, hence contributing to the global elimination pro ...200312639458
expression of transforming growth factor-beta isoforms and their receptors in lepromatous and tuberculoid leprosy.leprosy is an infectious disease with two polar forms, tuberculoid leprosy (tt) and lepromatous leprosy (ll), that are characterized by strong cell-mediated immunity (cmi) and cmi anergy, respectively. transforming growth factor-beta (tgf-beta) belongs to a family of pleiotropic cytokines (tgf-beta1, tgf-beta2 and tgf-beta3) that participate in the control of cell differentiation and proliferation, as well as tissue repair. this cytokine family is unique because it suppresses cmi. in this study, ...200312641657
reinvestigation on the causes of genomic gc variation between the orthologous genes of mycobacterium tuberculosis and mycobacterium leprae.genomic gc (overall g+c content of the coding sequences) variations were reinvestigated between the orthologous genes of mycobacterium tuberculosis and mycobacterium leprae species. it was observed that overall genomic gc variation between the species mainly originates from the combined effects gc(1) and gc(2) variations. but codons having identical amino acids with different codons (ia) (between the orthologous codon pairs) are responsible for the genomic gc(3) variation between the organisms, ...200312646167
cutting edge: a toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling.toll-like receptors (tlrs) are key mediators of the innate immune response to microbial pathogens. we investigated the role of tlrs in the recognition of mycobacterium leprae and the significance of tlr2arg(677)trp, a recently discovered human polymorphism that is associated with lepromatous leprosy. in mice, tnf-alpha production in response to m. leprae was essentially absent in tlr2-deficient macrophages. similarly, human tlr2 mediated m. leprae-dependent activation of nf-kappab in transfected ...200312646604
pulmonary necrosis resulting from dna vaccination against tuberculosis.the use of dna constructs encoding mycobacterial proteins is a promising new approach to vaccination against tuberculosis. a dna vaccine encoding the hsp60 molecule of mycobacterium leprae has previously been shown to protect against intravenous infection of mice with mycobacterium tuberculosis in both the prophylactic and immunotherapeutic modes. it is shown here, however, that this vaccine was not effective in a more realistic aerosol infection model or in a model of latent tuberculosis in the ...200312654841
genes required for mycobacterial growth defined by high density mutagenesis.despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. here, we describe the use of transposon site hybridization (trash) to comprehensively identify the genes required by the causative agent, mycobacterium tuberculosis, for optimal growth. these genes i ...200312657046
oxidative stress and anti-oxidant status in leprosy patients.severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. the purpose of this study was to investigate the serum lipid peroxidation products, serum ldh and important free radical scavenging enzymes, i.e. superoxide dismutase (sod), and catalase and anti-oxidant glutathione levels and total anti-oxidant status, in different types of leprosy patients. the subjects for this study were normal human volunteers (nhvs, n=14), paucibacillary leprosy patient ...200315242269
leprosy situation in endemic states of india and prospects of elimination of the disease.in india there is a dramatic fall in the prevalence rate (pr) of leprosy, but the new case-detection rate (ncdr) has not been reduced concomitantly. it is the operational efficiency of the national leprosy eradication programme (nlep) that has led to a significant reduction in the ncdr in andhra pradesh and tamil nadu. the ratio of pr to ncdr has been declining in these two states and it reveals that elimination could be reached even with the high ncdr level of 3 to 4 per 10000 population, parti ...200315242272
impact of integration of nlep into phc system in madurai district, tamil nadu, and status of integration of leprosy patients into the community.based on the encouraging results of the integration in tamil nadu, the government of india introduced integration in the entire country. in this study on integration, madurai district was taken as the study area. the impact of integration on essential indicators of leprosy elimination was analyzed and the results are discussed so that they will be useful to other states that are still considering integration.200315242273
leprosy in hiv infection: a study of three cases.the course of leprosy in patients with hiv infection has been a controversial issue for a long time. it is still a matter of debate whether the hiv status of an individual has any impact on the natural history of leprosy and response to anti-leprosy treatment. we report here three hiv-positive leprosy cases (two bt and one bb) along with their cd4 counts and hiv staging with anti-leprosy therapeutic response. both bt cases responded well to conventional who mdt (pb) for 6 months, whereas the bb ...200315242274
the genetics of nontuberculous mycobacterial infection.the molecular aetiology of familial susceptibility to disseminated mycobacterial disease, usually involving weakly pathogenic strains of mycobacteria, has now been elucidated in more than 30 families. mutations have been identified in five genes in the interleukin-12-dependent interferon-gamma pathway, highlighting the importance of this pathway in human mycobacterial immunity. knowledge derived from the study of these rare patients contributes to our understanding of the immune response to comm ...200314987409
mechanisms involved in peripheral nerve damage in leprosy with special reference to insights obtained from in vitro studies and the experimental mouse model.the histopathological observations of khanolkar and iyer, that m. leprae has a predeliction for nerves, first highlighted the central role of peripheral nerves in the pathology of leprosy. it is now well recognized that nerve damage in leprosy will still continue to be an important problem in control and rehabilitation despite the presence of more efficient therapy. the multiplicity of mechanisms postulated, identified, and demonstrated in the last three decades has received little recognition f ...200314763884
long-term efficacy of 2 year who multiple drug therapy (mdt) in multibacillary (mb) leprosy patients.relapse rate estimates after 2 year who multiple drug therapy (mdt) in multi-bacillary (mb) leprosy vary. between 1987 and 1994, 500 mb leprosy patients completing 2 year mdt were enrolled in a prospective relapse study. the majority of patients (n = 316) were treated and followed at the physician-staffed cebu skin clinic (csc), whereas others (n = 184) received therapy from government clinics and were followed by csc technicians in the field. relapse definition was an increased bacteriologic in ...200314763888
[neurological manifestations of leprosy].leprosy, also known as hansen's disease, is a chronic, infectious disease caused by mycobacterium leprae. bacilli localize preferentially in the skin and peripheral nerves and have a propensity to cause nerve damage. the resulting disability has caused great suffering for victims in many countries. despite recent advances in the immunopathogenesis, epidemiology and prognostic factors of leprosy nerve damage, many aspects of the disease have remained enigmatic. the spectrum of clinical and pathol ...200314710019
under-explored experimental topics related to integral mycobacterial vaccines for leprosy.many leprosy vaccine studies have utilized live or killed whole mycobacteria, such as bacille calmette-guérin, indian cancer research center (icrc) bacilli and mycobacterium w either alone or in combination with killed mycobacterium leprae. for bacille calmette-guérin, the vaccine dose is generally that which gives the largest delayed-type hypersensitivity response with minimal side effects. the doses of other integral mycobacterial vaccines appear to be arbitrarily chosen. hypotheses governing ...200314711362
[serodiagnostic monitoring of leprosy]. 200314689796
anti-mycobacterial immunity induced by a single injection of m. leprae hsp65-encoding plasmid dna in biodegradable microparticles.a single sub-cutaneous injection of a plasmid dna encoding a mycobacterial heat shock protein 65 (hsp65) entrapped in biodegradable poly(lactic-co-glycolic acid) microspheres produced high titers of antibodies, measured 5 months after the injection in balb/c mice. splenocytes secreted ifn-gamma and exerted an anti-bacterial effect on macrophages infected in vitro with mycobacterium tuberculosis. the results are encouraging with regard to obtaining good compliance and vaccination coverage with ca ...200314687708
leprosy: current diagnostic and treatment approaches.leprosy remains an important problem globally and leprosy patients may present to physicians outside leprosy endemic areas. we review the recent biological and clinical advances in leprosy.200314501994
in situ type 1 cytokine gene expression and mechanisms associated with early leprosy progression.we explored the prognostic value of in situ cytokine patterns in 39 patients with single-skin-lesion paucibacillary leprosy before single-dose therapy, with 3 years of follow-up. interferon (ifn)-gamma, interleukin (il)-12, il-10, il-4, tumor necrosis factor (tnf)-alpha, and macrophage inflammatory protein (mip)-1alpha mrna was quantified in skin biopsy samples at diagnosis, and mycobacterium leprae dna was detected in 51.4% of cases. type 1 immunity predominance with measurable ifn-gamma and un ...200314513423
purification of mycobacterium leprae rna for gene expression analysis from leprosy biopsy specimens.gene expression analysis in mycobacterium leprae, an obligate intracellular pathogen and the etiologic agent of leprosy, has been hampered by the lack of an efficient method to purify rna from leprosy lesions. therefore to date, transcripts for only a few genes have been identified. we report the use of a single-tube homogenization/rna extraction method that produces enough rna to study the expression of 30 genes from a single skin biopsy specimen of a multibacillary leprosy patient and demonstr ...200314513559
the secret lives of the pathogenic mycobacteria.pathogenic mycobacteria, including the causative agents of tuberculosis and leprosy, are responsible for considerable morbidity and mortality worldwide. a hallmark of these pathogens is their tendency to establish chronic infections that produce similar pathologies in a variety of hosts. during infection, mycobacteria reside in macrophages and induce the formation of granulomas, organized immune complexes of differentiated macrophages, lymphocytes, and other cells. this review summarizes our und ...200314527294
dna sequences of mycobacterium leprae recovered from ancient bones. 200314553941
reversal of t cell anergy in leprosy patients: in vitro presentation with mycobacterium leprae antigens using murabutide and trat peptide in liposomal delivery.mycobacterium leprae, the causative agent of leprosy resides and multiplies within the host monocytes and macrophages, thereby evading host immune system. cell-mediated immune response (cmi) plays a vital role as evidenced from the high cmi in bt/tt (borderline and tuberculoid) patients and conversely low in bl/ll (borderline and lepromatous) patients. in the present study, an attempt was made to immunomodulate the anergized t cells of lepromatous leprosy patients by presenting the mycobacterial ...200314555284
a tetramer-octamer equilibrium in mycobacterium leprae and escherichia coli ruva by analytical ultracentrifugation.in the context of the bacterial ruvabc system, ruva protein binds to and is involved in the subsequent processing of a four-way dna structure called holliday junction that is formed during homologous recombination. four crystal structures of ruva from escherichia coli (ecoruva) showed that it was tetrameric, while neutron scattering and two other crystal structures for ruva from mycobacterium leprae (mleruva) and ecoruva showed that it was an octamer. to clarify this discrepancy, sedimentation e ...200314568529
serology: recent developments, strengths, limitations and prospects: a state of the art overview.specific antibodies can be used as a surrogate marker for bacterial load in leprosy. tests to detect antibodies can be used for (i) the classification of patients for treatment purposes [most multibacillary (mb) patients are seropositive, most paucibacillary (pb) patients are not], (ii) the prediction of an increased risk of relapse and (iii) the identification of contacts having an increased risk of developing leprosy. with the advent of fast, robust and easy to perform serological tests such a ...200314577464
thalidomide does not modify the ability of cells in leprosy patients to incorporate [3h]-thymidine when incubated with m. leprae antigens.the immune response in reversal reaction, (rr) and in erythema nodosum leprosum (enl) is characterized in vitro by an enhancement in lymphocyte blast transformation against m. leprae. as thalidomide is an effective treatment for enl, this study assessed the effect of this drug on these phenomena. mononuclear cells from patients attending the clinic at alert and from healthy staff were cultured for 5 days with integral m. leprae (iml), or a modified dharmendra antigen (dhar), or ppd from m. tuber ...200314577465
comparison between anti-pgl-i serology and mitsuda reaction: clinical reading, microscopic findings and immunohistochemical analysis.the lepromin test, serum igm antibodies against mycobacterium leprae and in situ observations of t cell subsets in biopsies of mitsuda reaction using monoclonal antibodies were performed on 44 untreated leprosy patients belonging to various classifications of the disease. the mitsuda reaction was accessed clinically and histologically after 28 days. clinical reading and histological analysis of mitsuda reaction showed good agreement. the high positivity in clinical reading correlated with compac ...200314577472
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