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leprosy in israel: an imported disease--the support of histopathological examination for its detection.leprosy is rare and non-endemic in israel. cases of leprosy are invariably imported by immigrants or foreign workers arriving from endemic areas. in view of the relative rarity of the disease, clinicians and pathologists are not always alert to the possibility of the disease or recognize potential symptoms. a case history is presented of a 31-year-old immigrant presenting symptoms of skin lesions and nodules on the hands and facial region, especially the ear lobe. confirmation of the infection w ...200111700948
signaling lymphocytic activation molecule expression and regulation in human intracellular infection correlate with th1 cytokine patterns.induction of th1 cytokines, those associated with cell-mediated immunity, is critical for host defense against infection by intracellular pathogens, including mycobacteria. signaling lymphocytic activation molecule (slam, cd150) is a transmembrane protein expressed on lymphocytes that promotes t cell proliferation and ifn-gamma production. the expression and role of slam in human infectious disease were investigated using leprosy as a model. we found that slam mrna and protein were more strongly ...200111698444
identification of the first eubacterial endonuclease coded by an intein allele in the pps1 gene of mycobacteria.a survey of a vast range of mycobacterial strains led us to discover a new pps1 intein allele in mycobacterium gastri which differs from those of mycobacterium tuberculosis and mycobacterium leprae in both its sequence and insertion site. while little is known about pps1, except that it belongs to the yc24 family of abc transporters, we show that, unlike the other inteins described so far from eubacteria, the mgapps1 intein possesses a specific endonuclease activity. the intein is the first euba ...200111691918
mycobacterium bovis bcg but not mycobacterium leprae induces tnf-alpha secretion in human monocytic thp-1 cells.in this study, we compared the level of tnf-alpha secretion induced in monocytic thp-1 cells after phagocytosis of mycobacterium leprae, the causative agent of leprosy, and m. bovis bcg, an attenuated strain used as a vaccine against leprosy and tuberculosis. the presence of m. leprae and bcg was observed in more than 80% of the cells after 24 h of exposure. however, bcg but not m. leprae was able to induce tnf-alpha secretion in these cells. moreover, thp-1 cells treated simultaneously with bcg ...200111685264
t cell responses to major membrane protein ii (mmp ii) of mycobacterium leprae are restricted by hla-dr molecules in patients with leprosy.major membrane protein ii (mmp ii) of mycobacterium leprae (m. leprae) is a 22kda protein inducing humoral immune response in leprosy patients. mmp ii-specific bulk t cell lines were established from leprosy patients to determine major t cell epitopes in mmp ii and to evaluate lymphokine production induced by mmp ii. these bulk t cell lines reacted to one or more peptides in the locus of amino acid residues from 23 to 109 of mmp ii. the proliferative responses of all t cell lines were mainly inh ...200111672912
leprosy. 200111641922
control of skin infections by a combined action of ultraviolet a (from sun or uva lamp) and hydrogen peroxide (huva therapy), with special emphasis on leprosy.despite its abundance and certain therapeutic value, the importance of sunlight in the treatment of infectious skin diseases has not been fully exploited. one reason is that a sufficient amount of the damaging components of sunlight (uvc and most uvb) cannot reach us and the band of uv that can reach (uva) is a poor inactivator of living cells. uva, however, can be deleterious to cells in the presence of sensitizers and a number of biological and chemical sensitizers have been identified which c ...200111601875
the esat-6 gene cluster of mycobacterium tuberculosis and other high g+c gram-positive bacteria.the genome of mycobacterium tuberculosis h37rv has five copies of a cluster of genes known as the esat-6 loci. these clusters contain members of the cfp-10 (lhp) and esat-6 (esat-6) gene families (encoding secreted t-cell antigens that lack detectable secretion signals) as well as genes encoding secreted, cell-wall-associated subtilisin-like serine proteases, putative abc transporters, atp-binding proteins and other membrane-associated proteins. these membrane-associated and energy-providing pro ...200111597336
borderline tuberculoid leprosy with darier's disease. 200111579654
[a morphological study of nerve biopsies in leprous neuropathy].peripheral nerve biopsies from 10 leprosy patients(6 tuberculoid patients and 4 lepromatous patients) were studied morphological aspect. light microscopical examination showed that the perineurium was markedly thickened by infiltrated cell in tuberculoid type and mycobacterium leprae in lepromatous type. schwann cell markedly decreased in number, and nerve fiber disappeared without regeneration in severe cases. in mild cases, subperineurial edema was present. the nerve fiber density was normal o ...200111579512
[genome features of mycobacterium leprae].recent studies have revealed that the mycobacterium leprae genome contains many pseudogenes. this short review summarizes the structural features of the m. leprae genome and genes.200111579511
[reasons why mycobacterium leprae cells do not multiply under the cell-free condition].our previous paper reported that the intracellular atp content in cells of m. leprae consistently increased in the medium containing adenosine after 4-6 weeks of cultivation and decreased thereafter. the reason why atp generation ceased 4-6 weeks after cultivation is not clear, but it was determined that the termination in atp generation was not a result of deterioration in the culture medium during cultivation because a renewal trial of the old culture medium by freshly prepared culture medium ...200111579510
il-12 and il-18 synergistically induce the bactericidal activity of murine peritoneal cells against m. leprae.we examined the effect of il-12 and il-18 on bactericidal activities of mouse peritoneal cell (pc) against mycobacterium leprae (m. leprae). we demonstrated that il-12 and il-18 synergistically induced the no-dependent bactericidal activity of pc by stimulating natural killer (nk) cells and t-cells through ifn-gamma production. il-12 and il-18 induced host cell death through nk-cells and t-cells. therefore. il-12 and il-18 play an important role on direct killing of intracellular m. leprae and o ...200111579508
molecular and functional analyses of the gene (esha) encoding the 52-kilodalton protein of streptomyces coelicolor a3(2) required for antibiotic production.analysis of proteins recovered in the s100 precipitate fraction of streptomyces griseus after ultracentrifugation led to the identification of a 52-kda protein which is produced during the late growth phase. the gene (esha) which codes for this protein was cloned from s. griseus, and then its homologue was cloned from streptomyces coelicolor a3(2). the protein was deduced to be 471 amino acids in length. the protein esha is characterized by a central region that shows homology to the eukaryotic- ...200111567001
the genome of mycobacterium leprae: a minimal mycobacterial gene set.comparison of the recently sequenced genome of the leprosy-causing pathogen mycobacterium leprae with other mycobacterial genomes reveals a drastic gene reduction and decay in m. leprae affecting many metabolic areas, exemplified by the retention of a minimal set of genes required for cell-wall biosynthesis.200111532219
update on leprosy.leprosy, a result of infection by mycobacterium leprae, is a leading cause of peripheral neuropathy. the world health organization aimed to eliminate leprosy as a public health problem by 2000, but this has not been attained. patients with leprosy continue to present in the uk. the diagnosis of leprosy is frequently not considered, with resultant pathological and psychological problems for patients.200111530584
size matters? 200111514197
[late diagnosis of lepromatous leprosy in a geriatric patient]. 200111503588
erp, an extracellular protein family specific to mycobacteria.erp (exported repeated protein) was originally characterized as a virulence factor in mycobacterium tuberculosis and was thought to be present only in mycobacterium leprae and members of the tb complex. here it is shown that erp is a ubiquitous extracellular protein found in all of the mycobacterial species tested. erp proteins have a modular organization and contain three domains: a highly conserved amino-terminal domain which includes a signal sequence, a central variable region containing rep ...200111496008
response of mycobacterium habana vaccine in patients with lepromatous leprosy and their household contacts. a pilot clinical study.single dose vaccination was carried out with mycobacterium habana vaccine, 31 lepromatous leprosy cases receiving 1.5 mg (1.5 mg = 6.27 x 10(8) bacilli) and 36 household contacts randomly receiving 1.5, 2.0, 2.5 mg vaccine intradermally. duration of study was 18 weeks. vaccination induced lepromin conversion in 100% of lepromatous leprosy cases and lepromin negative household contacts and augmentation of lepromin reactivity in 100% of lepromin positive household contacts, which was stable for th ...200111495449
does dapsone resistance really matter in the mdt era? 200111480322
histological resolution and bacterial clearance with pulse rom therapy in borderline lepromatous leprosy. 200111480321
peroxidase in therapy of experimentally induced leprosy. 200111480320
a study on the reproducibility of two serological assays for detection of mycobacterium leprae infection. 200111480319
effects of vaccination with several mycobacterial proteins and lipoproteins on mycobacterium leprae infection of the mouse. 200111480318
comparative characteristics of antigenic profile of m. leprae and m. lufu. 200111480317
factors influencing the development of leprosy: an overview.the clinical manifestations of leprosy vary, seemingly depending on the host's immune response. mode and route of infection, such as skin versus nasal mucosa, insect bites, sexual and gastroenteral transmission, together with genetic factors that may contribute to the outcome of the infection, including hla, lewis factor, nramp1 and more subtle inherited alterations, are discussed. it is theorized that a balance between host responses elicited by different routes of infection and size and spacin ...200111480313
pcr-restriction fragment length polymorphism analysis (pra) of mycobacterium leprae from human lepromas and from a natural case of an armadillo of corrientes, argentina.polymerase chain reaction (pcr)-restriction fragment length polymorphism analysis (pra) which relies on the amplification of a 439-bp portion of the hsp65 gene present in all mycobacteria, followed by two distinct digestions (with bsteii and haeiii) of the pcr product, offers a rapid and easy alternative that allows identification of the species without the need for specialized equipment. wild leprosy in the nine-banded armadillo (dasypus novemcinctus) is characterized by the presence of multipl ...200111480312
limited atp generation in cells of mycobacterium leprae thai-53 strain in enriched kirchner liquid medium containing adenosine.the atp generation in cells of mycobacterium leprae thai-53 strain takes place in vitro when the cells are cultivated in kirchner liquid medium, ph 7.0, enriched with egg-yolk solution, pyruvate, transferrin, and adenosine at 30 degrees c. among the supplements, adenosine was key and critical for the atp generation. the optimal concentration of adenosine was 50 micrograms/ml of the medium. atp generation, however, was limited; the rates of increase in atp content extracted from the cells were ap ...200111480311
viable m. leprae as a research reagent.mycobacterium leprae remain a rare research resource. they cannot be cultivated on artificial media, and the only established means to quantify viability of m. leprae has been by its relative growth in the foot pads of conventional mice (mfp). the mfp method is technically difficult and requires several months to yield results. more effective methods are needed. we examined the association between m. leprae's ability to oxidize 14c-palmitate in axenic culture and the mfp growth results of a larg ...200111480310
identification of catalase-like activity from mycobacterium leprae and the relationship between catalase and isonicotinic acid hydrazide (inh).as mycobacterium leprae proliferate inside macrophages, it has been speculated that catalase encoded by katg may protect the bacilli from deleterious effects of peroxide generated from the macrophage and may also play a crucial role in the survival of m. leprae in vivo. however, unlike that of m. tuberculosis, the katg of m. leprae has been reported to be a pseudogene, implicating that isoniazid, which is activated to a potent tuberculocidal agent by catalase, is unlikely to be of therapeutic be ...200111478670
detection of toll-like receptor 2 (tlr2) mutation in the lepromatous leprosy patients.toll-like receptor 2 (tlr2) is critical in the immune response to mycobacterial infections and the mutations in the tlr2 have been shown to confer the susceptibility to severe infection with mycobacteria. to define this, we screened the intracellular domain of tlr2 in 131 subjects. groups of 45 lepromatous and 41 tuberculoid leprosy (tt) patients and 45 controls were investigated. ten subjects among the lepromatous leprosy (ll) patients had a band variant detected by single-stranded conformation ...200111476982
identification and mutagenesis by allelic exchange of choe, encoding a cholesterol oxidase from the intracellular pathogen rhodococcus equi.the virulence mechanisms of the facultative intracellular parasite rhodococcus equi remain largely unknown. among the candidate virulence factors of this pathogenic actinomycete is a secreted cholesterol oxidase, a putative membrane-damaging toxin. we identified and characterized the gene encoding this enzyme, the choe monocistron. its protein product, choe, is homologous to other secreted cholesterol oxidases identified in brevibacterium sterolicum and streptomyces spp. choe also exhibits signi ...200111466283
modulation of p53 dependent gene expression and cell death through thioredoxin-thioredoxin reductase by the interferon-retinoid combination.we have shown earlier that the ifn-beta and all-trans retinoic acid (ra) combination, but not the single agents, induces death in several tumor cell lines. employing a genetic technique we have identified several genes associated with retinoid-ifn induced mortality (grim). one of the grims was human thioredoxin reductase (tr), a redox enzyme. since the overexpressed tr augments ifn/ra stimulated cell death, we explored the mechanisms of tr-mediated death. here we show that tr augments cell death ...200111464290
the prevalence of folp1 mutations associated with clinical resistance to dapsone, in mycobacterium leprae isolates from south korea. 200111454253
driving a stake into resurgent tb. 200111452108
a role for il-12 receptor expression and signal transduction in host defense in leprosy.the generation of cell-mediated immunity against intracellular infection involves the production of il-12, a critical cytokine required for the development of th1 responses. the biologic activities of il-12 are mediated through a specific, high affinity il-12r composed of an il-12rbeta1/il-12rbeta2 heterodimer, with the il-12rbeta2 chain involved in signaling via stat4. we investigated il-12r expression and function in human infectious disease, using the clinical/immunologic spectrum of leprosy ...200111441083
serological expression cloning and immunological evaluation of mtb48, a novel mycobacterium tuberculosis antigen.improved diagnostics are needed for the detection of mycobacterium tuberculosis, especially for patients with smear-negative disease. to address this problem, we have screened m. tuberculosis (h37rv and erdman strains) genomic expression libraries with pooled sera from patients with extrapulmonary disease and with sera from patients with elevated reactivity with m. tuberculosis lysate. both serum pools were reactive with clones expressing a recombinant protein referred to here as mtb48. the geno ...200111427558
intracellular signals triggered during association of mycobacterium leprae and mycobacterium bovis bcg with human monocytes.to gain a better understanding of mycobacteria-host cell interaction, the present study compared the signal transduction events triggered during the interaction of mycobacterium leprae (the causative agent of leprosy) and of mycobacterium bovis bcg (an attenuated strain used as a vaccine against leprosy and tuberculosis) with human monocytes. the assays consisted of pre-treating or not thp-1 cells (a human monocytic cell line) with different kinase inhibitors, followed by incubation with fluores ...200111427035
leprosy and the genome--not yet a burnt-out case. 200111425365
resuscitation of dormant mycobacterium tuberculosis by phospholipids or specific peptides.the presence of dormant tubercle bacilli presents a major problem for tuberculosis treatment. the culture supernatant of mycobacterium tuberculosis was previously shown to resuscitate dormant bacilli in vitro. here we report identification of active components as phospholipids and a tuberculosis protein rv1174c. remarkably, dormant bacilli from a one year old culture which failed to form any colonies could be resuscitated with peptides derived from rv1174c and formed 10(5-7) colonies/ml. this fi ...200111394916
unique expression of a highly conserved mycobacterial gene in is901(+) mycobacterium avium.expression of a gene encoding a novel protein antigen of 40 kda (p40) was detected in is901(+) strains of mycobacterium avium, but not in any other species or subspecies of mycobacterium tested, including is901(-) m. avium and the other members of the m. avium complex. although southern hybridization revealed that the p40 gene is widely distributed within the genus, expression of the antigen could not be detected on western blots of mycobacterial cell lysates. nucleotide sequence analysis of the ...200111390686
genomics: leprosy - a degenerative disease of the genome.analysis of the genome of the leprosy bacillus uncovers evidence of extensive deletion and inactivation of genes. secluded in a specialised niche, it has discarded much of its genetic heritage, though retaining just enough to be a major human pathogen.200111378400
simultaneous detection of mycobacterium leprae and its susceptibility to dapsone using dna heteroduplex analysis.currently recommended control measures for treating leprosy with multidrug therapy should control the spread of drug-resistant strains; however, dapsone (dds) resistance continues to be reported. comprehensive estimates of drug-resistant leprosy are difficult to obtain due to the cumbersome nature of the conventional drug susceptibility testing method using mouse footpad inoculation, which requires at least 6 months to obtain results. recently, it has been determined that dds-resistant strains c ...200111376039
leprosy research in the post-genome era. 200111355523
effect of unique mycobacterium leprae phenolic glycolipid-i (pgl-i) on tumour necrosis factor production by human mononuclear cells.mycobacterium leprae cell wall-associated components are found in large amounts in the tissues of leprosy patients, particularly those at the lepromatous pole. among these molecules, the phenolic glycolipid-i (pgl-i), unique to m. leprae, has been involved in the selective anergy observed in the lepromatous patients. armadillo-derived m. leprae retains only a small proportion of the total pgl-i found in infected tissues. therefore, the addition of pgl-i to m. leprae in vitro is important for a b ...200111355520
a critique on commentary 'how mycobacterium leprae infects peripheral nerves' by freedman et al. 200111355512
dipstick assay to identify leprosy patients who have an increased risk of relapse.classification of leprosy patients into paucibacillary (pb) and multibacillary (mb) determines the duration of treatment; misclassification increases the risk of relapse because of insufficient treatment if an mb patient is classified as pb. we explored the possibility of using a simple dipstick assay based on the detection of antibodies to the mycobacterium leprae-specific phenolic glycolipid-i (pgl-i) as a tool for classification of patients into pb and mb for treatment purposes. the sensitivi ...200111348523
leukocyte antimicrobial function in patients with leprosy.patients with lepromatous leprosy are unresponsive to lepromin skin-test material and possess defective lymphocyte function in vitro, including impaired mitogenesis in response to antigens of mycobacterium leprae. it has been claimed that their macrophages cannot digest m. leprae in vitro; such a defect could explain both lepromin nonreactivity and impaired lymphocyte function on the basis of failure of the afferent limb of the immune response (i.e., defective macrophage "processing" of m. lepra ...197411344550
isolation of pdx2, a second novel gene in the pyridoxine biosynthesis pathway of eukaryotes, archaebacteria, and a subset of eubacteria.in this paper we describe the isolation of a second gene in the newly identified pyridoxine biosynthesis pathway of archaebacteria, some eubacteria, fungi, and plants. although pyridoxine biosynthesis has been thoroughly examined in escherichia coli, recent characterization of the cercospora nicotianae biosynthesis gene pdx1 led to the discovery that most organisms contain a pyridoxine synthesis gene not found in e. coli. pdx2 was isolated by a degenerate primer strategy based on conserved seque ...200111344146
mycobacterium leprae-specific, hla class ii-restricted killing of human schwann cells by cd4+ th1 cells: a novel immunopathogenic mechanism of nerve damage in leprosy.peripheral nerve damage is a major complication of reversal (or type-1) reactions in leprosy. the pathogenesis of nerve damage remains largely unresolved, but detailed in situ analyses suggest that type-1 t cells play an important role. mycobacterium leprae is known to have a remarkable tropism for schwann cells of the peripheral nerve. reversal reactions in leprosy are often accompanied by severe and irreversible nerve destruction and are associated with increased cellular immune reactivity aga ...200111342602
lucio's phenomenon: clinical and therapeutic aspects.we report four cases of necrotizing reactions of the lucio's phenomenon type, an entity rarely observed in brazil despite the high prevalence of leprosy. clinical, histopathological and therapeutic aspects are described and compared to those reported in the literature for cases classified as diffuse, non-nodular lepromatous leprosy with lucio's phenomenon.200011336069
utility of fine-needle aspiration cytology in the classification of leprosy.the role of fine-needle aspiration cytology (fnac) in the diagnosis of benign skin lesions has been restricted primarily to the evaluation of bacteriologic and morphologic indices in leprosy. this study was undertaken to evaluate the efficacy of fnac in the diagnosis and classification of lepromatous lesions. aspirates of 94 newly diagnosed cases of leprosy were studied, and the bacterial load was determined by modified ziehl-neelsen (zn) stain. a skin biopsy was taken from the same site at the ...200111335960
use of ml dipstick as a tool to classify leprosy patients.leprosy control services face the problem of leprosy patients being misclassified by the lack of or the poor quality of skinsmear examination services. misclassification increases the risk of relapse due to insufficient treatment if a multibacillary (mb) patient is classified as paucibacillary (pb), thereby also prolonging the time that the patient is infectious. the world health organization (who) recommends at present an alternative classification based on the number of skin lesions. its relia ...200011332289
a mycobacterium leprae isolate resistant to dapsone, rifampin, ofloxacin and sparfloxacin.mycobacterium leprae were isolated from a japanese patient, and susceptibility to antileprosy drugs was examined by the mouse foot pad method. the isolate was susceptible to clofazimine and clarithromycin, and resistant to dapsone, rifampin, ofloxacin and sparfloxacin. mutations were identified in the genes associated with resistance to these drugs. the risk of the emergence of leprosy with multidrug resistance is emphasized.200011332288
antileprosy protective vaccination of sooty mangabey monkeys with bcg or bcg plus heat-killed mycobacterium leprae: immunologic observations.groups of sooty mangabey monkeys (smm) were vaccinated and boosted with mycobacterium bovis bacillus calmette-guerin (bcg), or bcg + 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 immunologically observed longitudinally for approximately 3 years. smm [multibacillary (mb) leprosy-prone as a species] were not protected c ...200011332286
immuno-histopathology in the diagnosis of early leprosy.the present study of 45 early leprosy cases in an endemic area in china indicates: a) sensitivity of acid-fast bacilli (afb) detection can be significantly improved by examining approximately 30 serial sections. afb and/or phenolic glycolipid-i (pgl-i) were mostly detected in the infiltrates in the subepidermal zone, intraneurium, perineurium and around blood vessels. b) pgl-i antigen was positive in 10 clinically suspected, single lesion leprosy cases and afb positive in 7 patients, afb and/or ...200011332285
presence of human t-cell responses to the mycobacterium leprae 45-kilodalton antigen reflects infection with or exposure to m. leprae.the ability of the 45-kda serine-rich mycobacterium leprae antigen to stimulate peripheral blood mononuclear cell (pbmc) proliferation and gamma interferon (ifn-gamma) production was measured in leprosy patients, household contacts, and healthy controls from areas of endemicity in mexico. almost all the tuberculoid leprosy patients gave strong pbmc proliferation responses to the m. leprae 45-kda antigen (92.8%; n = 14). responses were lower in lepromatous leprosy patients (60.6%; n = 34), but so ...200111329466
polyunsaturated fatty acids levels in edible oils: a nutritional factor contributing to the growth of mycobacterium leprae. 200111326602
relapses in leprosy patients treated with rifampicin plus dapsone after varying periods of dapsone monotherapy.leprosy patients treated formerly with dapsone monotherapy followed by combined therapy with rifampicin plus dapsone were surveyed for relapse and rifampicin resistance. the relapse rate was significantly low for the 482 multibacillary (mb) patients receiving > 12 months combined therapy compared with the 49 mb cases receiving < 12 months of combined therapy. the relapse rate was related to the duration of dapsone monotherapy prior to combined therapy. the difference in relapse rate in 247 pauci ...200111326592
characterization and expression of seca in mycobacterium avium.mycobacterium avium is both a pathogen that infects several hosts such as humans, pigs, and birds, as well as a microorganism that is encountered in environmental sources (soil and water). protein secretion by the bacterium is likely to influence its ability to overcome adverse and competitive conditions both within or outside the host. using a combination of cloning and information available in the databank, we characterized the seca gene from m. avium, encoding for a major preprotein transloca ...200111313128
connectivity patterns in tuberculosis and leprosy patients are indistinguishable from that of healthy donors.connectivity, the self-defined interactions between antigen-recognising molecules in a network system can in part be assessed by measuring the reactivity of a given serum against an ordered set of immunoglobulin (ig)g f(ab')2 fractions, separated by means of isoelectric focusing so that, the serum reactivity against the whole set of fractions defines a characteristic pattern of connectivity. deviations from the normal condition (healthy donors) have so far been documented for two autoimmune dise ...200111309162
drug targeting mycobacterium tuberculosis cell wall synthesis: genetics of dtdp-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dtdp-glucose to dtdp-rhamnose.an l-rhamnosyl residue plays an essential structural role in the cell wall of mycobacterium tuberculosis. therefore, the four enzymes (rmla to rmld) that form dtdp-rhamnose from dttp and glucose-1-phosphate are important targets for the development of new tuberculosis therapeutics. m. tuberculosis genes encoding rmla, rmlc, and rmld have been identified and expressed in escherichia coli. it is shown here that genes for only one isotype each of rmla to rmld are present in the m. tuberculosis geno ...200111302803
multiple mutations in the rpob gene of mycobacterium leprae strains from leprosy patients in thailand.a new finding is reported of multiple mutations in the rpob gene of 9 mycobacterium leprae strains from leprosy patients in thailand, who did not respond to therapy even when rifampicin, the main drug in multi-drug therapy was used. by means of sequence analysis of 9 thai m. leprae strains, various mutations in 289 bps of the rpob gene revealed forms of mutation never before described, such as multiple mutations (ie, mutation at two, three, six, seven, eight and nine positions in the rpob gene), ...200011289008
epidemiology of selected mycobacteria that infect humans and other animals.this paper provides a summary of salient clinical and epidemiological features of selected mycobacterial diseases that are common to humans and other animals. clinical and diagnostic issues are discussed and related to estimates of the incidence and prevalence of these diseases among humans. source of infection, route of transmission and control measures are also presented. the mycobacteria discussed in this paper are mycobacterium bovis, m. ulcerans, m. leprae and m. avium complex, although thi ...200111288519
mycobacterium leprae and mycobacterium lepraemurium infections in domestic and wild animals.mycobacterium leprae, the aetiological agent of leprosy in humans, gives rise to a chronic granulomatous disease that affects primarily the skin and peripheral nerves, and secondarily some internal organs such as the testis and the eye; viscera are seldom involved. depending on host resistance, leprosy may present as a benign disease (tuberculoid leprosy) or as a malignant disease (lepromatous leprosy), with a spectrum of intermediate stages appearing between the two. immunity against leprosy de ...200111288514
m. leprae genome sequence. 200111286866
further biochemical characterization of mycobacterium leprae laminin-binding proteins.it has been demonstrated that the alpha2 chain of laminin-2 present on the surface of schwann cells is involved in the process of attachment of mycobacterium leprae to these cells. searching for m. leprae laminin-binding molecules, in a previous study we isolated and characterized the cationic proteins histone-like protein (hlp) and ribosomal proteins s4 and s5 as potential adhesins involved in m. leprae-schwann cell interaction. hlp was shown to bind alpha2-laminins and to greatly enhance the a ...200111285456
hansen's disease in a native-born, united states resident, after a brief stay in an endemic area abroad. 200111285160
a major susceptibility locus for leprosy in india maps to chromosome 10p13.leprosy, a chronic infectious disease caused by mycobacterium leprae, is prevalent in india, where about half of the world's estimated 800,000 cases occur. a role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (hla) association studies. we report here a genetic linkage scan of the genomes of 224 families from south india, containing 245 independent affected sibpai ...200111279529
[late reversal leprous reaction appearing 18 months after the termination of treatment]. 200111268894
identification and characterization of a gene encoding a 35-kda protein from mycobacterium avium subspecies paratuberculosis.mycobacterium avium subspecies paratuberculosis is the causative agent of johne's disease, a chronic enteritis in ruminants. a gene homologous to that of 35-kda antigen of mycobacterium leprae was cloned and sequenced from mycobacterium paratuberculosis. the database searches revealed 82.79% and 95.67% similarities of its nucleotide sequence, with those of immunodominant 35-kda protein of m. leprae and m. avium, respectively.200111267779
[pcr in leprosy].detection of m. leprae dna using pcr is very sensitive enough to detect very few number of bacilli which are not recognized by acid-fast staining method. because the detection of m. leprae is crucial for the diagnosis of leprosy, pcr method has been expected to make a diagnosis easy and precise. a new pair of pcr primers for m. lepare was selected in the department of dermatology, yokohama city university school of medicine, and many samples obtained from many institutes have been examined in th ...200111244785
evaluation of b7-1 (cd80) and b7-2 (cd86) costimulatory molecules and dendritic cells on the immune response in leprosy.the cell activation depends on t cell antigen receptor binding to antigen plus mhc and costimulation. the binding of cd28, expressed on the t cell surface to b7 (b7-1 or cd80/b7-2 or cd86) present on the antigen--presenting cells (apcs), determines, in several t cell function models, if activation or anergy follows antigenic stimulation. in leprosy, the role of cd80 and cd86 as costimulatory signal in m. leprae-specific cellular immunity has not yet been defined. we investigated the role of b7-c ...200111244783
massive gene decay in the leprosy bacillus.leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen mycobacterium leprae, a close relative of the tubercle bacillus. mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. comparing the 3.27-megabase (mb) genome sequence of an armadillo-derived indian isolate of the leprosy bacillus with that of mycobacterium tuberculosis (4.41 mb) provides clear explanations f ...200111234002
development of a species-specific pcr assay for detection of leishmania donovani in clinical samples from patients with kala-azar and post-kala-azar dermal leishmaniasis.we have developed a pcr assay that is capable of amplifying kinetoplast dna (kdna) of leishmania donovani in a species-specific manner among old world leishmanias. with indian strains and isolates of l. donovani the assay was sensitive enough to detect kdna in an amount equivalent to a single parasite or less. the extreme sensitivity of the assay was reflected in its ability to detect parasite dna from small volumes of peripheral blood of patients with kala-azar (ka) and from skin lesions from p ...200111230394
immunoresititution disease in relation to infection with mycobacterium avium complex and to leprosy. 200111229860
protective responses against experimental mycobacterium leprae infection in mice induced by recombinant bacillus calmette-guérin over-producing three putative protective antigen candidates.the components of ag85 (ag85a, ag85b, and ag85c) are putative protective antigen candidates against mycobacterial infection. a recombinant mycobacterium bovis bacillus calmette-guérin (rbcg) over-producing ag85a, ag85b, and mpb51 (rbcg/ba51) was constructed. rbcg/ba51 could secrete these antigens at levels more than five times higher than parental bcg. immunization of c57bl/6 and balb/c mice with this rbcg reduced the multiplication of mycobacterium leprae in the foot pads of both strains of mic ...200111228360
lysis of autologous macrophages pulsed with hsp10 from mycobacterium leprae is associated to the absence of bacilli in leprosy.peripheral blood mononuclear cells from leprosy patients and normal individuals were analysed for their ability to lyse autologous macrophages pulsed with the mycobacterium leprae 10 kda heat shock protein (hsp10), an antigen considered to have an important role in the protective responses in leprosy. strong cytotoxic responses, with an involvement of gammadelta t and class-i and class-ii restricted alphabeta t cells and/or cd16+56+ cells, were observed in normal individuals, paucibacillary (pb) ...200111222914
tumor necrosis factor promoter polymorphism (tnf2) seems to protect against development of severe forms of leprosy in a pilot study in brazilian patients. 200011221098
dapsone drug resistance in the mdt era. 200011221097
development of tt leprosy in a bcg-vaccinated individual: immunological response during disease and after spontaneous healing. 200011221096
leprosy at a turning point? 200011221095
hansen's disease in a patient with a history of sarcoidosis.we report a rare case of concomitant hansen's disease (hd) and sarcoidosis. reticulin staining may be a helpful diagnostic tool in establishing the diagnosis of sarcoidosis in skin lesions. the diagnosis of hd can be established despite negative polymerase chain reaction results for the detection of mycobacterium leprae dna. finally, a well-established diagnosis of sarcoidosis does not preclude the development of another granulomatous disorder. hence, when new lesions developed in a patient with ...200011221094
efficacy of single-dose rom therapy plus low-dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion.the recent world health organization multicentric field study on the treatment of paucibacillary (pb) leprosy patients with single skin lesion (ssl) and a single dose of rifampin-ofloxacin-minocycline (rom) brought new hope to those who are engaged in the eradication of leprosy from india. being encouraged by the who report, we undertook the present hospital-based study and found that pb leprosy patients with ssl were morphologically and histopathologically heterogeneous. the histological spectr ...200011221091
relapse as histoid leprosy after receiving multidrug therapy (mdt); a report of three cases.the histoid type of leprosy has been described as occurring in lepromatous leprosy patients who relapse after many years of apparently successful dapsone monotherapy. three patients who had received the world health organization-recommended regimens of multidrug therapy (who/mdt) relapsed as histoid leprosy 12-15 years after completion of treatment. in one patient, through mouse foot pad studies, the bacilli were found to be sensitive to rifampin and clofazimine and resistant to dapsone. in the ...200011221089
single lesion paucibacillary leprosy: baseline profile of the brazilian multicenter cohort study.in brazil, there is little information about the clinical and epidemiological characteristics of paucibacillary, single skin lesion leprosy patients (ssl-pb). only recently has the official notification system distinguished leprosy patients with a single lesion as a clinical entity, for whom the single-dose rom (rifampin, ofloxacin and minocycline) regimen has been recommended. in this paper, we describe the baseline clinical features and the immunological background of a multicenter cohort of s ...200011221086
histoid leprosy--an unusual presentation. 200011212483
multidrug therapy--the pathway for global leprosy elimination.introduction of dapsone therapy paved the way for better and more humanitarian way of dealing with the leprosy victims who, prior to 1943, were simply rejected and segregated from society. emergence of dapsone-resistant m. leprae and mycobacterial persistence provoked our quest for another solution. more drugs were discovered for treatment of leprosy. but the real breakthrough was the recommendation of regimens of multidrug therapy (mdt) for the treatment of leprosy by the who study group on che ...200011212482
intranasal administration of fusidic acid cream in leprosy.the effect of local treatment of nostrils with fusidic acid cream was investigated in 30 previously untreated lepromatous leprosy patients. the cream was applied in the nostrils after flushing the nostrils with normal saline, twice a day for a period of four weeks. it was found that 20 mg/gm of sodium fusidate was effective in reducing the morphological index of the nose-blow smear to zero in two weeks in majority of the patients. no untoward side effect was seen in any of the patients. such nas ...200011212479
assessment of viability by normal mouse foot-pad and bacillary atp bioluminescence assay in multibacillary cases treated with an mdt regimen using conventional as well as newer drugs like minocycline and ofloxacin.the therapeutic effect of a drug regimen of conventional drugs as well as newer drugs like ofloxacin and minocycline in smear-positive multibacillary (mb) leprosy cases was assessed by mouse foot-pad and atp bioluminiscence methods. biopsies were taken before starting treatment and after one year of treatment. they were processed for viability assessment by normal mouse foot-pad inoculation and bacillary atp assay techniques. the test regimen was quite effective in its anti-bacterial effect as i ...200011212477
pcr primers that can detect low levels of mycobacterium leprae dna.there are several specific pcr-based methods to detect mycobacterium leprae dna, but the amplicons are quite large. for example, primers that target the 36-kda antigen gene and are in common diagnostic use yield a 530-bp product. this may be a disadvantage when examining samples in which the dna is likely to be damaged and fragmented. therefore, two sets of m. leprae-specific nested primers were designed, based on existing primer pairs which have been shown to be specific for m. leprae. primers ...200111211226
rapid detection of resistance to rifampicin in mycobacterium leprae. 200011201897
dapsone resistance in mycobacterium leprae.the folp1 gene of mycobacterium leprae, which encodes dihydropteroate synthase (dhps), was studied for the presence of mutations associated with resistance to dapsone (dds). when the folp1 of several dds-resistant clinical isolates of m. leprae were sequenced, two missense mutations were identified. one mutation occurred at codon 53, substituting isoleucine for threonine in dhps-1, and a second mutation occurred in codon 55, substituting arginine for proline. dna sequencing of strains of m. lepr ...200011201896
combination of rifapentine-moxifloxacin-minocycline (pmm) for the treatment of leprosy.to further the development of a multidrug regimen for treatment of leprosy that is suitable for monthly administration and fully supervisable, the bactericidal activities against mycobacterium leprae of hmr 3647 (hmr), moxifloxacin (mxfx) and rifapentine (rpt) were measured by the proportional bactericide technique in the mouse footpad system, and compared with those of the established antileprosy drugs clarithromycin (clari), ofloxacin (oflo) and rifampicin (rmp). administered in five daily dos ...200011201894
a rapid, microplate-based assay for evaluating the activity of drugs against mycobacterium leprae, employing the reduction of alamar blue. 200011201892
use of a mycobacterium leprae dipstick to classify patients with leprosy. 200011201891
experience and lessons from the use of lepromin and mycobacterium leprae-specific serology.skin testing with lepromin, which produces a delayed-type hypersensitivity reaction, has been used in the classification of leprosy, and a good correlation has been found between immunological status and the reaction to lepromin. in addition, the prognostic value of the lepromin test has been demonstrated. more recently, skin testing with two soluble antigens of mycobacterium leprae showed no difference of the mean size of the reaction between household contacts and non-contacts, indicating that ...200011201890
whole blood assays for interferon-gamma: practicalities and potential for use as diagnostic tests in the field.recent years have seen the introduction of a number of whole-blood assays, in which unseparated heparinized blood is stimulated with antigen either overnight or for as long as 6 days, and cytokine production is measured in the plasma or supernatant. these assays have potential for use in the field as immunodiagnostic assays, as they require only a small blood sample and basic laboratory facilities. use of these assays in a large study of the immunological effects of bcg vaccination in malawi has ...200011201889
diagnostic assays for leprosy based on t-cell epitopes.to date, only a limited number of antigens have been described as specific for mycobacterium leprae, and in many cases, homologues have subsequently been shown to exist in mycobacteria such as m. avium and m. intracellulare. a leprosy synthetic peptide skin test initiative was established by the steering committee on the immunology of mycobacteria of the undp/world bank/who special programme for research and training in tropical diseases, to investigate the potential of synthetic peptides that e ...200011201888
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