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molecular analysis of ancient microbial infections.the detection of ancient microbial dna offers a new approach for the study of infectious diseases, their occurrence, frequency and host-pathogen interaction in historic times and populations. moreover, data obtained from skeletal and mummified tissue may represent an important completion of contemporary phylogenetic analyses of pathogens. in the last few years, a variety of bacterial, protozoal and viral infections have been detected in ancient tissue samples by amplification and characterizatio ...200212167530
the detection of mycobacterium leprae protein and carbohydrate antigens in skin and nerve from leprosy patients with type 1 (reversal) reactions.type 1 (reversal) reactions are the most common immunological complications of leprosy. these episodes of delayed hypersensitivity produce severe local immunopathology and ultimately nerve damage. to date, the mycobacterium leprae antigens associated with type 1 reactions have not been identified. using monoclonal antibodies to defined protein and carbohydrate m. leprae epitopes (65, 35 and 28 kd and lipoarabinomannan [lam]) in a two-step immunoperoxidase staining technique, m. leprae antigens w ...200212164297
the multiple faces of the immune response to mycobacterium tuberculosis. 200212160631
role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the mycobacterium tuberculosis complex. evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene.diesters of phthiocerol and phenolphthiocerol are important virulence factors of mycobacterium tuberculosis and mycobacterium leprae, the two main mycobacterial pathogens in humans. they are both long-chain beta-diols, and their biosynthetic pathway is beginning to be elucidated. although the two classes of molecules share a common lipid core, phthiocerol diesters have been found in all the strains of the m. tuberculosis complex examined although phenolphthiocerol diesters are produced by only a ...200212138124
is soil an alternative source of leprosy infection?leprosy is believed to be transmitted only through human contacts. however, many anomalous observations had gradually accumulated which had weakened such beliefs. these are: only 1/3 rd cases of leprosy give a definite history of being transmitted from other known cases; life-long spouses, in whom only one has leprosy, seldom lead to leprosy to others; while mdt applied intensively in most leprosy endemic countries, could successfully reduce incidence of leprosy, however, simultaneously new case ...200112136740
a comparative and combinatorial study on two serological assays for detection of mycobacterium leprae infection.the performances of two mycobacterium leprae specific serological assays namely: phenolicglycolipid-l-based enzyme-linked immunosorbent assay (pgl-elisa) and a monoclonal antibody-based inhibition test (mait) were studied for there efficiency to detect m. leprae infection. as usual, both the tests were more sensitive to detect lepromatous leprosy patients than tuberculoid type of leprosy patients. considering the efficiency to detect leprosy patients, the mait was slightly more sensitive and spe ...200112136738
[what shall we make of the arrival of "generalized" antibiotics to anti-hansen's therapy?]. 200112136737
local nerve damage in leprosy does not lead to an impaired cellular immune response or decreased wound healing in the skin.this study investigated whether peripheral nerve damage in patients with leprosy impairs local cellular immune responses, thereby reducing wound healing and leading to chronic skin ulceration. anesthetic and contralateral sensitive skin sites in 42 patients with leprosy were compared for delayed-type hypersensitivity responses to purified protein derivative (ppd) of tuberculin. leukocyte recruitment, epidermal activation, keratinocyte proliferation, and rates of wound healing after skin biopsy w ...200212134264
detection of mycobacterium leprae dna by pcr in blood sample from nine-banded armadillo: preliminary results. 200212120038
light and ultrastructural study of sciatic nerve lesions induced using intraneural injection of viable mycobacterium leprae in normal and immunosuppressed swiss white mice.freshly harvested m. leprae were microinjected into the sciatic nerves of nonimmunosuppressed (non-tr) and immunosuppressed (tr) mice using the technique described by wisniewski and bloom. the lesions thus induced, on bypassing the blood-nerve barrier, were biopsied at regular intervals beginning 24 hr and followed up to one year. the fate of m. leprae and the ensuing inflammation and nerve damage were studied using light and electron microscopy. the lesions in both non-tr and tr mice at 24 hr s ...200212120037
a study on a possibility of predicting early relapse in leprosy using a nd-o-bsa based elisa.serological methods have been used for detecting infection with mycobacterium leprae. we have applied a serological test to explore the possibility it could detect a bacterial relapse among patients who have been cured with chemotherapy. more specifically we used an indirect enzyme-linked immunosorbant assay (elisa) using the natural disaccharide (nd) of the phenolic glycolipid antigen of m. leprae linked to bovine serum albumin as antigen. antibody levels were measured in sera from normal contr ...200212120035
novel 33-kilodalton lipoprotein from mycobacterium leprae.a novel mycobacterium leprae lipoprotein lpk (accession no. ml0603) was identified from the genomic database. the 1,116-bp open reading frame encodes a 371-amino-acid precursor protein with an n-terminal signal sequence and a consensus motif for lipid conjugation. expression of the protein, lpk, in escherichia coli revealed a 33-kda protein, and metabolic labeling experiments and globomycin treatment proved that the protein was lipidated. fractionation of m. leprae demonstrated that this lipopro ...200212117918
[raoul against basil]. 200212108197
association of a missense mutation of the laminin alpha2 gene with tuberculoid type of leprosy in indonesian patients.leprosy, an infection caused by mycobacterium leprae, has a specific tropism for the myelinating schwann cells of peripheral nerves. recently, the g domain of laminin alpha2 has been shown to be a mediator for m. leprae to bind to alpha-dystroglycan in schwann cells. in order to analyse the association of leprosy with the mediator, three genetic polymorphisms encoding the g domain of the laminin alpha2 chain were analysed by direct sequencing in 53 leprosy patients and 58 healthy contact individ ...200212100448
studying genomes through the aeons: protein families, pseudogenes and proteome evolution.protein families can be used to understand many aspects of genomes, both their "live" and their "dead" parts (i.e. genes and pseudogenes). surveys of genomes have revealed that, in every organism, there are always a few large families and many small ones, with the overall distribution following a power-law. this commonality is equally true for both genes and pseudogenes, and exists despite the fact that the specific families that are enlarged differ greatly between organisms. furthermore, becaus ...200212083509
overexpression, purification, and site-directed spin labeling of the nramp metal transporter from mycobacterium leprae.it has long been recognized that the pathogenicity of a broad range of intracellular parasites depends on the availability of transition metal ions, especially iron. nramp1 (natural resistance-associated macrophage protein 1), a proton-coupled divalent metal ion transporter, has been identified as a controlling factor in the resistance or susceptibility to infection with a diverse range of intracellular pathogens such as toxoplasma, salmonella, mycobacterium, and leishmania. the role of divalent ...200212077319
the truncated hemoglobin from mycobacterium leprae.truncated hemoglobins (trhb's) form a family of low molecular weight o2 binding hemoproteins distributed in eubacteria, protozoa, and plants. trhb's branch in a distinct clade within the hemoglobin (hb) superfamily. a unique globin gene has recently been identified from the complete genome sequence of mycobacterium leprae that is predicted to encode a trhb (m. leprae trhbo). sequence comparison and modelling considerations indicate that monomeric m. leprae trhbo has structural features typical o ...200212074585
[developing and using a pcr test to detect subclinical mycobacterium leprae infection].while the prevalence of leprosy has declined around the world, there has not been a corresponding decrease in its incidence, thus indicating that it has not been possible to prevent transmission of the disease. despite the small number of patients with lepromatous leprosy, the majority of the inhabitants of endemic areas show signs of exposure to mycobacterium leprae, which could be explained by the presence of subclinical bacilliferous infections in the community. the objective of this study wa ...200212049031
the use of protein structure/activity relationships in the rational design of stable particulate delivery systems.the recombinant heat shock protein (18 kda-hsp) from mycobacterium leprae was studied as a t-epitope model for vaccine development. we present a structural analysis of the stability of recombinant 18 kda-hsp during different processing steps. circular dichroism and elisa were used to monitor protein structure after thermal stress, lyophilization and chemical modification. we observed that the 18 kda-hsp is extremely resistant to a wide range of temperatures (60% of activity is retained at 80 deg ...200212045839
the mycobacterium leprae hsp65 displays proteolytic activity. mutagenesis studies indicate that the m. leprae hsp65 proteolytic activity is catalytically related to the hslvu protease.the present study reports, for the first time, that the recombinant hsp65 from mycobacterium leprae (chaperonin 2) displays a proteolytic activity toward oligopeptides. the m. leprae hsp65 proteolytic activity revealed a trypsin-like specificity toward quenched fluorescence peptides derived from dynorphins. when other peptide substrates were used (beta-endorphin, neurotensin, and angiotensin i), the predominant peptide bond cleavages also involved basic amino acids in p(1), although, to a minor ...200212044173
biochemical aspects of mycobacterium leprae binding proteins: a review of their role in pathogenesis. 200112035295
analysis of quantitative relationship between viability determination in leprosy by mfp, atp bioluminescence and gene amplification assay.two hundred twenty-one untreated, borderline lepromatous/lepromatous (bl/ll) leprosy patients have been investigated for viability by the mouse foot pad method (mfp), adenosine triphosphate (atp) and polymerase chain reaction (pcr). the biopsies were collected at the beginning of and 12/24 months after treatment. the patient group was treated with a) immunotherapy (bcg/mw) + mdt; b) mdt + pyrazinamide; c) control mdt; d) mdt + minocycline 100 mg once a month supervised + ofloxacin 400 mg once a ...200112035294
simplified pcr detection method for nasal mycobacterium leprae.we report here a simplified method for the detection of nasal carriage of mycobacterium leprae. dna extracted from nasal swabs was analyzed by pcr, and m. leprae specific amplicons detected by means of a novel peptide-nucleic-acid-elisa (pna-elisa) method. parameters for the method were established using swabs taken from untreated lepromatous leprosy patients. we have developed this method to study nasal carriage in endemic populations. however, due to the sensitivity of pcr based techniques, we ...200112035291
[genomic evolution of pathogenic bacteria and horizontal gene transfer]. 200212013818
[speech of sakurane award recipient: pcr in leprosy]. 200212013817
ddt inhibits the functional activation of murine macrophages and decreases resistance to infection by mycobacterium microti.ddt is still widely used in several parts of the world to control malaria, typhoid and dengue vectors, even though its use was banned in many countries based on toxicity data in wild life species. ddt has been shown to have immunotoxic effects in mice and to increase susceptibility to intracellular pathogens such as mycobacterium leprae. however, little is known about the mechanisms underlying this effect. activated macrophages play an important defensive role against intracellular pathogens, th ...200212007859
[the discovery of the leprosy bacillus].gerhard henrik armauer hansen (1841-1912) worked on leprosy throughout his career. following his discovery of the leprosy bacillus in 1873, he proposed legislation that, when enacted in 1877 and 1885, established preventive measures aimed at isolating infectious patients. around 1920, leprosy was more or less eradicated in norway after a period of decline starting in 1850. over this period, more than 8,000 cases were registered. armauer hansen's unique research achievement was based on a scienti ...200211998735
dna-pcr and rt-pcr for the 18-kda gene of mycobacterium leprae to assess the efficacy of multi-drug therapy for leprosy.dna-pcr and reverse transcription (rt)-pcr for the 18-kda protein of mycobacterium leprae were used to examine the efficacy of multi-drug therapy (mdt) in leprosy. mdt was administered for 0-24 months. fourteen (63.6%) of 22 patients showed positive pcr results after treatment for 12 months and the positive results decreased to 30% after 24 months of mdt. these results did not correlate with the bacterial index (bi) or the igm antibody titre for the phenolic glycolipid (pgl)-1. one-dimensional d ...200211990494
contact-dependent demyelination by mycobacterium leprae in the absence of immune cells.demyelination results in severe disability in many neurodegenerative diseases and nervous system infections, and it is typically mediated by inflammatory responses. mycobacterium leprae, the causative organism of leprosy, induced rapid demyelination by a contact-dependent mechanism in the absence of immune cells in an in vitro nerve tissue culture model and in rag1-knockout (rag1-/-) mice, which lack mature b and t lymphocytes. myelinated schwann cells were resistant to m. leprae invasion but un ...200211988579
microbiology. subversion of schwann cells and the leper's bell. 200211988561
human t cell responses to peptides of the mycobacterium leprae 45-kd serine-rich antigen.in order to identify t cell epitopes within the mycobacterium leprae 45-kd serine-rich antigen, we analysed responses to overlapping 17-mer peptides encompassing the whole antigen in non-exposed uk controls, pakistani leprosy patients and tuberculosis patients in both the united kingdom and pakistan. this antigen has been described as m. leprae-specific, although it has a hypothetical homologue in m. tuberculosis. human peripheral blood mononuclear cells were stimulated with peptide for 5 days a ...200211982601
[susceptibility to mycobacterium leprae of congenic hypertensive nude rat (shr/ncrj-rnu) and production of cytokine from the resident peritoneal macrophages].we have established a congenic hypertensive nude rat strain, shr/ncrj-rnu, carrying nude (rnu) and hypertension genes which was produced using females of the shr/ncrj rat and males of the f344/njcl nude rat by cross-intercross system for 12 generations. we demonstrated the susceptibility to m. leprae infection of shr/ncrj-rnu rats as compared with f344/njcl-rnu rats. shr/ncrj-rnu rats were highly susceptible to m. leprae, and the shr/ncrj-rnu rats of both sexes showed massive swelling of legs du ...200211979757
prevention of diabetes in non-obese diabetic mice by a single immunization with mycobacterium leprae.the incidence of overt diabetes was completely prevented by a single intradermal inoculation of mycobacterium leprae (m. leprae) into non-obese diabetic (nod) mice as young as 6-7 weeks. partial prevention was also observed in cases when 65 kd heat-shock protein (hsp65) with freund's incomplete adjuvant (fia) was injected, and no prevention was observed by 38 kd with fia immunization. histological examination of pancreata demonstrated that control and m. leprae-immunized mice at 24 weeks of age ...200211979756
[leprosy reactions].in leprosy, the causative bacteria, mycobacterium leprae, will not threaten the lives of the hosts directly because they proliferate only slowly in the schwann cells of the peripheral nerves. it is the "reactions" which give the patients irreversible morbidity through the inflammatory damages to the peripheral nerves. physicians should be aware of the possibility of the state of the "reaction" when they examine leprosy patients. they also should be aware of the possibility of leprosy and the sta ...200211979755
spoilt for choice: protein target selection in a time of plenty.experiences in the application of boolean logic to the clusters of orthologous groups of proteins (cogs) database for target selection in the mycobacterium tuberculosis genome are described.200211976509
ifn-gamma and no in mycobacterial disease: new jobs for old hands.granulomatous disease following exposure to mycobacterium tuberculosis, mycobacterium leprae or mycobacterium avium is correlated with strong inflammatory and protective responses. the mouse model of mycobacterial infection provides an excellent tool with which to examine the inter-relationship between protective cell-mediated immunity and tissue-damaging hypersensitivity. it is well established that t cells and interferon (ifn)-gamma are necessary components of anti-bacterial protection. we pro ...200211973155
reactive nitrogen and oxygen intermediates and bacterial defenses: unusual adaptations in mycobacterium tuberculosis.the production of reactive oxygen and reactive nitrogen intermediates is an important host defense mechanism mediated in response to infection by bacterial pathogens. not surprisingly, intracellular pathogens have evolved numerous defense strategies to protect themselves against the damaging effects of these agents. in enteric bacteria, exposure to oxidative or nitrosative stress induces expression of numerous pathways that allow the bacterium to resist the toxic effects of these compounds durin ...200211970850
progress towards development of immunoassays for detection of mycobacterium leprae infection, employing 35kda antigen: an update.the 35 kda antigen of mycobacterium leprae is a membrane component that contains both b and t-cell stimulating epitopes. monoclonal antibodies, primarily specific to m. leprae, have been developed against this antigen. moreover, this antigen has been genetically engineered. using recombinant 35 kda antigen and/or a monoclonal antibody against an epitope on 35 kda, a variety of antibody/antigen detecting tests have been described for detection of m. leprae infection. 35 kda protein also stimulate ...200211969136
bacterial index of granuloma and its relevance compared to bi of skin smears. 200211969131
typing of clinical isolates of mycobacterium leprae and their distribution in korea.although there is no genetic diversity in isolates of mycobacterium leprae, the variance of tandem repeats in the rpot gene was recently demonstrated. we have typed clinical isolates of m. leprae in korea using difference of the tandem repeats in the rpot gene. among 69 patients, 65 korean isolates (94.2%) demonstrated four copies of the 6 bp tandem repeat (gacatc) in the rpot gene, and incidences of three copies were found in only two koreans and two foreigners (2.9%, respectively).200211969125
rifampicin resistant leprosy: a review and a research proposal of a pilot study. 200211969122
identification and characterization of the esat-6 homologue of mycobacterium leprae and t-cell cross-reactivity with mycobacterium tuberculosis.in this paper we describe identification and characterization of mycobacterium leprae esat-6 (l-esat-6), the homologue of m. tuberculosis esat-6 (t-esat-6). t-esat-6 is expressed by all pathogenic strains belonging to the m. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (tb). therefore, we analyzed whether l-esat-6 is a similarly powerful tool for the study of leprosy by examining t-cell respon ...200211953394
royal society of tropical medicine and hygiene meeting at manson house, london, 18th january 2001. pathogen genomes and human health. mycobacterial genomics.the small size of their genomes made bacterial ideal model organisms for the emerging field of genomics. elucidating the genome sequences of mycobacteria was particularly attractive owing to the difficulties inherent in their manipulation. the slow growth rate, clumping, and requirement for category iii containment make manipulation of mycobacterium tuberculosis-complex strains laborious. m. leprae presents even greater problems as it has resisted all attempts at axenic culture. availability of ...200211925980
management of erythema nodosum leprosum by thalidomide: thalidomide analogues inhibit m. leprae-induced tnfalpha production in vitro.thalidomide is being successfully used for the treatment of erythema nodosum leprosum (enl), among other disorders with inflammatory and immunological bases. although the active molecules responsible for the diverse therapeutic activities of the drug and the sequence of reactions triggered inside the cells remain unclear, it was demonstrated that thalidomide (thal) inhibits tnfalpha mrna expression and protein production by stimulated monocytes and activated t lymphocytes. patients treated with ...200211905505
increased expression of fas ligand in human tuberculosis and leprosy lesions: a potential novel mechanism of immune evasion in mycobacterial infection.to study the location and mechanism of apoptosis within the human tuberculosis (tb) and leprosy lesions, parallel sections were analyzed for mycobacterial antigens (m.ag), fas ligand (fasl), fas, cd68 and mac387 by immunohistochemistry, and apoptotic cells by the terminal deoxynucleotidyl-transferase-mediated dutp-digoxigenin nick end labelling method. cutaneous leishmaniasis and foreign body granulomas were analyzed for comparison. the heavily infected macrophages in multibacillary tb and lepro ...200111902340
correlation of clinical, histological and immunological features across the leprosy spectrum.the ridley-jopling system of classification of the variegated clinical pattern of leprosy is based on the specific cell-mediated immunity observed in the histopathology of skin lesions conforming to a spectrum from tt at one end to ll at the other. in this study a fairly large sample of 90 patients was classified on clinical grounds; the histopathology of the skin lesions was studied blind. there was an overall concordance of 90% between the clinical and histological classifications. in addition ...200111898465
leprosy bacillus--possibly the first chemoautotrophic human pathogen cultivated in vitro and characterised.leprosy bacillus (lb) and leprosy derived in vitro culture forms, the chemoautotrophic nocardioform (can) bacteria, showed an extremely close homology and identity with each other as regards a chemoautotrophic nutritional pattern, a nocardioform morphology, a weak acid-fastness coupled with gram and gomori's stain positivity, an exclusive mycolate and lipid profile, a phenolic glycolipid (pgl-i) and a highly sequestrated dna characteristic, namely, a unique small size, a low g+c % mole, an excep ...200111883520
tumor necrosis factor (tnf) production in leprosy patients. 200111875771
acceptance of who/mdt over the last 20 years. 200111875769
pentoxifylline downregulates nitric oxide and tumor necrosis factor-alpha induced by mycobacterial lipoarabinomannan in a macrophage cell line.pentoxifylline (ptx), a phosphodiesterase inhibitor, is known to downregulate tumor necrosis factor-alpha (tnf-alpha) secretion induced by lipopolysacchride (lps) and gamma interferon (ifn-gamma). we have had limited success in treating leprosy reactions, including erythema nodosum leprosum (enl), in which tnf-alpha has been identified as a major proinflammatory cytokine. ptx inhibited production of no (ic50 approximately equal to 1.0 mg/ml) and tnf-alpha (ic50 approximately equal to 0.05 mg/ml) ...200111875767
cytokine profiles in paraffin-embedded biopsy samples of lepromatous leprosy patients: semi-quantitative measure of cytokine mrna using rt-pcr.a reproducible technique for fixation of tissue, rna extraction and reverse transcription polymerase chain reaction (rt-pcr) analysis from paraffin-embedded leprosy biopsies, has been developed and used to study the mrna profiles. this approach is valuable in retrospective analysis of gene expression, and the handling of infectious biopsy material is also minimized. among the methods of rna extraction compared, the most efficient method was found to be incubation of the tissue sections in digest ...200111875764
immunological profile of treated lepromatous leprosy patients.the immune responses of 19 treated lepromatous patients who had remained smear negative for a long period were assessed for specific cell-mediated immunity (cmi), anti-mycobacterium leprae antibodies and cytokine release in response to challenge with m. leprae soluble antigen (mlsa). all of these patients remained anergic to mitsuda lepromin. lymphoproliferation in response to m. leprae antigen was noted in only two patients. significant reduction in the phenolic glycolipid i (pgl-i) antibody re ...200111875763
impact of combined mycobacterium w vaccine and 1 year of mdt on multibacillary leprosy patients.a total of 20 bacteriologically positive multibacillary (mb) leprosy patients older than 18 years of age with a bacterial index (bi) of 2+ or greater were given standard world health organization multiple drug therapy (mdt-mb) for 12 consecutive months plus four intradermal doses of mycobacterium w vaccine at 3 monthly intervals (study group). twenty age-matched mb patients were given who/mdt alone (control group). the patients of both groups were followed up for 1 year. improvements in the pati ...200111875762
distinct histopathological patterns in single lesion leprosy patients treated with single dose therapy (rom) in the brazilian multicentric study.this paper aims to describe the histomorphologic features of skin biopsies of single lesion leprosy patients recruited at outpatient clinics in four brazilian states in the northeast (amazonas and rondonia), southeast (rio de janeiro) and center-west (goiás) between october 1997 and december 1998. patients clinically diagnosed as single skin lesion paucibacillary (ssl-pb) leprosy had a standard 4-mm punch biopsy taken from the lesion before rifampin, ofloxacin, minocycline (rom) therapy. the fea ...200111875761
[electron microscopy of mycobacterium leprae passed in laboratory animals].the ultrastructure of m. leprae was studied in the process of its intraplantar passage from man to mice (passages 1-8). changes in the morphology of m. leprae, observed in the course of 3 passages, were established. from the phase of dormant forms (passage 1) the bacteria became adapted to the new host by passage 3, which was confirmed by the absence of differences in the ultrastructure of cells by passages 3-8. the possibilities of the phenotypic variability of m. leprae in the process of in vi ...200111871293
the study of mycobacterium leprae infection in interferon-gamma gene--disrupted mice as a model to explore the immunopathologic spectrum of leprosy.mycobacterium leprae infection was evaluated in interferon-gamma knockout (gko) mice. at 4 months, growth of the bacilli in the footpads of gko mice plateaued a log(10) higher than that in control mice. control mice exhibited mild lymphocytic and histiocytic infiltrates, whereas gko mice developed large, unorganized infiltrates of epithelioid macrophages and scattered cd4 and cd8 t cells. flow cytometric analysis of popliteal lymph node cells demonstrated similar profiles of t cells; however, gk ...200211865434
selective t-cell recognition of the n-terminal peptide of groes in tuberculosis.peptides derived from the whole sequence of mycobacterial groes heat shock proteins were tested for the ability to induce the proliferation of blood mononuclear cells from tuberculosis patients and sensitized healthy subjects. the response to the n-terminal peptide (residues 1 to 16) was found to be more frequent and stronger in tuberculosis patients. this finding is exceptional, considering that recognition of all other groes peptides by patients was either diminished or not different from that ...200211854259
persisting m. leprae in a nerve in the pampiniform plexus of a lepromatous patient: an unusual finding. 200111840600
poor correlation of systemic immunological parameters with clinical features in macular leprosy.on the basis of clinical features and bacteriological status, macular skin lesions of nine cases of leprosy were classified as falling within a spectrum between the tuberculoid at one end and the lepromatous at the other. while histologic correlation was seen in 60% of cases, humoral and cellular systemic immunologic features were found to be uncharacteristic. it is suggested that macular lesions form an early stage in the development of leprosy where the systemic immunological response is yet t ...200111840596
comparative study of anti-pgl-1, anti-35 kda and anti-lipoarabinomannan assays for serodiagnosis of leprosy.three antibody assays (anti-pgl-1, anti-35 kda and anti-lam) were used to determine the levels of antibodies in the sera of untreated leprosy patients. all the three assays showed higher levels of antibodies in bl/ll patients as compared to i and tt/bt patients, as well as healthy controls. bl/ll patients showed positivity of 100%, 84.2% and 78.9% by anti-pgl-1, anti-35 kda and anti-lam assays respectively. all the three assays were negative for leprosy in healthy controls. anti-pgl-1 assay was ...200111840595
leproma: a mycobacterium leprae genome browser. 200111826483
the integrated genome map of mycobacterium leprae.the integrated map of the mycobacterium leprae genome unveiled for the first time the genomic organization of this obligate intracellular parasite. selected cosmid clones, isolated from a genomic library created in the cosmid vector lorist6, were identified as representing nearly the complete genome and were subsequently used in the m. leprae genome sequencing project. now a new version of the integrated map of m. leprae can be presented, combining the mapping results from the lorist6 cosmids wi ...200111826482
repetitive sequences in mycobacterium leprae and their impact on genome plasticity.about 2% of the genome of mycobacterium leprae is composed of repetitive dna. there are more than 26 extinct is elements together with four families of dispersed repeats, present in five copies or more, rlep (37 copies), replep (15 copies), leprep (eight copies), and leprpt (five copies). although there is no sequence similarity to known transposable elements, rlep occurs predominantly at the 3'-end of genes and, in several cases, within pseudogenes, suggesting that it was capable of disseminati ...200111826481
a method for rapid detection of rifampicin-resistant isolates of mycobacterium leprae.a genotypic method for predicting rifampicin resistance in mycobacterium leprae has been developed and rigorously tested on mouse footpad-derived and clinical specimens. a series of immobilized oligonucleotide capture probes can discriminate between wild type and mutant rpob alleles, and positive controls are available for the most frequent mutation affecting ser425. two different non-radioactive detection formats have been tested with comparable success in both an industrialized and a developin ...200111826480
genomics and the chemotherapy of leprosy.the information deduced from the genome sequence of mycobacterium leprae is of immense value for the chemotherapy of leprosy. knowing the complete set of genes, enzymes and proteins allows us to understand why some drugs are without effect whereas others are fully active. it may also enable better use to be made of existing drugs, such as beta-lactams, and opens new avenues for the development of novel compounds. m. leprae is relatively susceptible to a wide range of drugs, unlike the highly rel ...200111826479
genomic evidence for the retention of the essential mycobacterial cell wall in the otherwise defective mycobacterium leprae.the obligate intracellularism of mycobacterium leprae may be attributable to the effects of mutations in major metabolic areas due to a genome capable of encoding only about 1600 proteins. yet cell wall biosynthesis capability remains relatively intact and comparisons with the genome of mycobacterium tuberculosis provide insights into the genetic basis of a minimal mycobacterial cell wall.200111826478
dna metabolism in mycobacterium leprae. 200111826477
the microbial physiologist's guide to the leprosy genome. 200111826476
the decaying genome of mycobacterium leprae.everything that we need to know about mycobacterium leprae, a close relative of the tubercle bacillus, is encrypted in its genome. inspection of the 3.27 mb genome sequence of an armadillo-derived indian isolate of the leprosy bacillus identified 1,605 genes encoding proteins and 50 genes for stable rna species. comparison with the genome sequence of mycobacterium tuberculosis revealed an extreme case of reductive evolution, since less than half of the genome contains functional genes while inac ...200111826475
mycobacterium leprae genome sequence; a landmark achievement. 200111826474
where are the pseudogenes in bacterial genomes?most bacterial genomes have very few pseudogenes; notable exceptions include the genomes of the intracellular parasites rickettsia prowazekii and mycobacterium leprae. as dna can be introduced into microbial genomes in many ways, the compact nature of these genomes suggests that the rate of dna influx is balanced by the rate of dna deletion. we propose that the influx of dangerous genetic elements such as transposons and bacteriophages selects for the maintenance of relatively high deletion rate ...200111825713
cloning of the o-acetylserine lyase gene from the ruminal bacterium selenomonas ruminantium hd4.the gene coding for o-acetylserine lyase (oasl) was cloned from a selenomonas ruminantium hd4 lambda zap ii genomic library by degenerative probe hybridization and complementation. sequence analysis revealed a 933 bp orf with a g + c content of 53%. the orf had significant homology with enzymes involved in cysteine biosynthesis. a curablastn homology search showed that the orf shared 59% nucleotide identity with the cysk of bacillus subtilis. the deduced amino acid sequence exhibited high (>70%) ...200211821922
enhanced antibody activity in serum depleted of antigen.presence of antigen and antibodies in a sample may interfere with the antibody, as well as with antigen detection assays. in such a situation, avidity of the probing antigen or antibody plays the key role in the assay. in the present study, using monoclonal antibodies against a mycobacterial antigen, lipoarabinomannan, patient serum is depleted of mycobacterial antigen by capture immunoradiometric assay and this antigen-depleted serum is tested for anti-lipoarabinomannan antibodies by inhibition ...200111816807
in vivo activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with dapsone, against mycobacterium leprae.the antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, either singly or in combination with dapsone against mycobacterium leprae, were evaluated in vivo using a mouse footpad model. when fed to mice at concentration of 0.05% in diet, epiroprim completely inhibited the growth of both dapsone-sensitive and dapsone-resistant strains of m. leprae in the footpads of mice and the effects were bactericidal. to achieve similar effects, the concentration of dapsone in the diet h ...200211814771
structure of mycobacterium tuberculosis chaperonin-10 at 3.5 a resolution.chaperonin-60 (cpn60) and chaperonin-10 (cpn10) are essential proteins involved in atp-dependent folding of several intracellular proteins in the bacterial cell. folding of the nascent substrate polypeptide takes place in the large central cavity formed by each ring of the tetradecameric cpn60. this large cavity is closed upon capping by the heptameric cpn10. cpn10s interact with cpn60s primarily through a 17-residue mobile loop and regulate the release and binding of the substrate polypeptide f ...200211807250
learning from leprosy: insights into contemporary immunology from an ancient disease.leprosy provides an ideal model to study immune responses in humans and in skin. learning from leprosy, we have gained insight into mechanisms of host resistance and susceptibility to infection. new paradigms include the role of th1/th2 cytokines, the ability of cd1 to present nonpeptide antigens to t cells, the ability of microbial lipoproteins to stimulate antimicrobial activity in monocytes and the demonstration that t cells can mediate a direct antimicrobial activity through release of granu ...200211803252
antigenic specificity of the mycobacterium leprae homologue of esat-6.the sequence of the mycobacterium leprae homologue of esat-6 shows only 36% amino acid correspondence to that from mycobacterium tuberculosis. anti-m. leprae esat-6 polyclonal and monoclonal antibodies and t-cell hybridomas reacted only with the homologous protein and allowed identification of the b- and t-cell epitopes. the protein is expressed in m. leprae and appears in the cell wall fraction. thus, m. leprae esat-6 shows promise as a specific diagnostic agent for leprosy.200211796642
short report: do intestinal nematodes increase the risk for multibacillary leprosy?intestinal helminths are known to subvert the host's immune response towards a th2 response, which in turn may lead to both eosinophilia and high immunoglobulin e titers often associated with these parasites. mycobacterium leprae infection may lead to different clinical and pathological forms. multibacillary forms are associated with th2 cytokines, whereas paucibacillary forms are associated with th1 cytokines. we report a significantly higher frequency of intestinal helminthic infections in pat ...200111791986
mycobacterium leprae and leprosy: a compendium.leprosy is a chronic infectious disease caused by mycobacterium leprae, which was discovered by g.h.a. hansen in 1873. m. leprae is an exceptional bacterium because of its long generation time and no growth in artificial media. entire sequencing of the bacterial genome revealed numerous pseudogenes (inactive reading frames with functional counterparts in m. tuberculosis) which might be responsible for the very limited metabolic activity of m. leprae. the clinical demonstration of the disease is ...200111791665
detection of mycobacterium leprae dna by polymerase chain reaction in the blood of individuals, eight years after completion of anti-leprosy therapy.thirty eight patients with indeterminate leprosy (hi), at least 4 to 6 years after discharge from multibacillary (mb) or paucibacillary (pb) schemes of anti leprosy multidrug therapy (mdt), were submitted to traditional diagnostic procedures for leprosy and to polymerase chain reaction (pcr) analysis of different clinical samples for detection of mycobacterium leprae dna. no significant difference was observed for any of the parameters analyzed between pb or mb schemes of treatment and no indica ...200111784934
leprosy. oldest and most feared disease. 200111784588
[comparative characterization of the antigenic composition of m. leprae and m. lufu].the antigenic structure of m. leprae and m. lufu was comparatively studied for the first time. m. lufu was found to have m. leprae-specific protein with a molecular weight of 36 kda. m. leprae and m. lufu were similar in their fractional composition of proteins and an antibody response to determinants with equal molecular weights in patients with different forms of leprosy and its varying severity. the findings may improve a diagnostic system in leprosy by using m. lufu antigens as an alternativ ...200111767394
the heat shock response of fusobacterium nucleatum.the heat-shock response of the oral gram-negative bacterium fusobacterium nucleatum was examined. different strains of f. nucleatum were grown at 37 c. 42 degrees c and 48 c in the presence of [35s]methionine. cellular proteins synthesised after shifts to higher temperatures were analysed by sds-page and autoradiography. strains atcc 10953, f1, f3 and fev1 exhibited heat-shock response, and major proteins were observed at 60, 70 and 90 kda. but increased protein synthesis was also observed for o ...200111767277
detection of mycobacterium leprae by polymerase chain reaction.the improved procedure based on polymerase chain reaction (pcr) for detection of m. leprae has been developed. the sensitivity and specificity of this method were tested using different concentration of genomic dna of m. leprae thai 53 and genomic dnas from mycobacterial species and related microorganisms respectively. application of this method to biopsy samples obtained from bangladesh was conducted and detected m. leprae dna in 7 of the 10 clinical specimens. acid fast bacilli were not detect ...200011766004
immunopathology of leprosy; a state of the art. 200111757177
pathology and pathogenesis of leprous neuritis; a preventable and treatable complication.in conclusion, it may be said that many advances have been made in the diagnosis, treatment and prevention of nerve damage. it is now a well accepted fact that the affinity of m. leprae for schwann cells and the property of m. leprae to grow in cooler sites of the body have made certain segments of nerve trunks vulnerable. trauma that supervenes the inflammation and swelling severely aggravates the nerve damage. the reactive phase in all forms of leprosy, the etiology of which is not clearly und ...200111757175
newer drugs in leprosy.during the last 15 years, new drugs active against mycobacterium leprae have been identified. all of them belong to the fluoroquinolone, cycline and macrolide drug families. in the mouse model and in humans, minocycline, ofloxacin, and clarithromycin have demonstrated, individually or in combination, antileprosy activities much superior to those of the standard drugs dapsone and clofazimine. in humans, a single dose of the combination ofloxacin 400 mg + minocycline 100 mg was able to kill 68% to ...200111757174
south india immunoprophylaxis trial against leprosy: relevance of findings in the context of leprosy trends. 200111757173
no evidence of linkage between mitsuda reaction and the nramp1 locus.thirty sib-pairs were ascertained through unrelated lepromatous probands. they consisted of 22 healthy individuals and 8 leprosy patients. the mitsuda reactions of all sibs were evaluated both macroscopically and histologically, and high molecular weight genomic dna was extracted from the white blood cells of all sib-pairs. three dna polymorphisms identified by polymerase chain reaction (274c/t, d543n, 1729 + 55del4) were used as chromosome markers at the nramp1 locus. sib-pair comparisons did n ...200111757172
vaccination with dna of the mycobacterium tuberculosis 85b antigen protects mouse foot pad against infection with m. leprae.a dna vaccine composed of the gene for the common mycobacterial secreted protein antigen 85b was demonstrated to protect the mouse foot pad against infection with mycobacterium leprae. the protective effect was demonstrated by a 61%-88% reduction in the bacterial number, a protective effect less than that of bcg. the same dna vaccine has been shown to protect mice against m. tuberculosis infection, and the importance of testing other candidate tuberculosis vaccines for their potential to protect ...200111757171
leprosy with peripheral t-cell lymphoma: a rare association. 200111757170
a plea to revive skin smear examination. 200111757169
comparative protective effects of recombinant dna and mycobacterium bovis bacille calmette-guérin vaccines against m. avium infection.a range of strategies are being explored to develop more effective vaccines against mycobacterial infection, including immunization with dna plasmids encoding single mycobacterial bacterial genes and the use of recombinant live vectors based on the current vaccine, mycobacterium bovis bacille calmette-guérin (bcg). we have compared these two approaches using a model of virulent m. avium infection, and the gene for the immunodominant 35 kda protein which is shared by m. avium and m. leprae, but a ...200111737066
expression of inducible nitric oxide synthase and nitrotyrosine in borderline leprosy lesions.in the response to t-helper cell (th1)-type cytokines and interactions with pathogens, high levels of nitric oxide (no) are produced by activated macrophages expressing the inducible no synthase (inos). the role and importance of reactive nitrogen intermediates (rnis) such as no and peroxynitrite in the host response to diseases caused by intracellular pathogens such as mycobacterium leprae and m. tuberculosis is unclear.200111736907
molecular detection of rifampin and ofloxacin resistance for patients who experience relapse of multibacillary leprosy.molecular detection of rifampin resistance (rpob analysis) in mycobacterium leprae was determined for 49 patients who experienced relapse of multibacillary leprosy and for 34 untreated patients. molecular detection of ofloxacin resistance (gyra analysis) was determined for the 12 patients who experienced relapse and who had received ofloxacin. results of molecular tests were compared with the reference susceptibility test in the mouse footpad. overall, the efficiency of molecular detection--that ...200211731943
a high incidence of viable mycobacterium leprae in post-mdt recurrent lesions in tuberculoid leprosy patients. 200111715280
distinguishing between relapse and late reversal reaction in multidrug (mdt)-treated bt leprosy. 200111715270
multidrug resistant mycobacterium leprae from patients with leprosy.sequences of the folp1, rpob, and gyra genes were analyzed for 88 isolates of mycobacterium leprae from leprosy patients in japan, haiti, indonesia, pakistan, and the philippines. thirteen isolates (14.8%) showed representative mutations in more than two genes, suggesting the emergence of multidrug-resistant m. leprae.200111709358
distribution of gyra intein in non-tuberculous mycobacteria and genomic heterogeneity of mycobacterium gastri.to gain further insights into the understanding of the intein invasion process in mycobacteria, intein sequences in the gyra gene of 42 mycobacterial strains were searched and a new gyra intein was found in mycobacterium gastri (mga). this 1260 bp intein, named mgagyra, inserted at the gyra-a site, is highly homologous to the members of the mycobacterium leprae gyra allelic family. as the reca intein, mgagyra was detected in only one out of six mga strains examined, while the pps1 intein was a c ...200111707281
leprosy. recognition and treatment.leprosy is a slowly progressive, chronic infectious disease caused by the bacillus mycobacterium leprae. it is a very serious, multilating and stigmatizing disease in many parts of the world and early diagnosis and therapy is the most important strategy for its control. the skin and peripheral nerves are the most affected organs. it is highly infective, but has low pathogenicity and low virulence with a long incubation period. the geographical distribution of leprosy has varied greatly with time ...200111705247
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