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the source of infection: an unsolved issue. 200011008657
prospects for chemotherapy of leprosy. 200011008659
thioredoxin reductase as a pathophysiological factor and drug target.human cytosolic thioredoxin reductase (trxr), a homodimeric protein containing 1 selenocysteine and 1 fad per subunit of 55 kda, catalyses the nadph-dependent reduction of thioredoxin disulfide and of numerous other oxidized cell constituents. as a general reducing enzyme with little substrate specificity, it also contributes to redox homeostasis and is involved in prevention, intervention and repair of damage caused by h2o2-based oxidative stress. being a selenite-reducing enzyme as well as a s ...200011012663
the rubino test for leprosy is a beta2-glycoprotein 1-dependent antiphospholipid reaction.we describe the isolation and identification of three components required for the rubino reaction (rr), which is the rapid sedimentation of formalinized sheep red-blood cells (srbc) initiated by serum from leprosy patients with defective mycobacterium leprae-specific cell immunity. the rubino reaction factor (rrf) required for this phenomenon, previously identified as an immunoglobulin m (igm), was purified from leprosy patient serum by adsorption to formalinized srbc. purified rrf igm, when add ...200011012766
t cell-monocyte contact enhances tumor necrosis factor-alpha production in response to mycobacterium leprae.tumor necrosis factor (tnf)-alpha has been implicated as a key factor in inflammatory processes occurring in erythema nodosum leprosum (enl). in the present study, the roles of soluble factors and contact-mediated interaction in the induction of enhanced tnf-alpha secretion in leprosy have been investigated. in vitro studies have demonstrated that mycobacterium leprae per se is a poor stimulus for tnf-alpha production by purified monocytes obtained from normal subjects, although this could be en ...200011023469
high prevalence of antiphospholipid antibodies in leprosy: evaluation of antigen reactivity.antiphospholipid antibodies (apl) have been reported not only in autoimmune disorders but also in various infectious diseases. accumulating evidence indicates that beta2 glycoprotein i (beta2gpi) and prothrombin are the main proteins to which autoimmune apl bind. the aim of this study was to evaluate the prevalence of different apl in patients with leprosy. we included 51 outpatients (42 lepromatous and 9 borderline leprosy) without any clinical feature of the antiphospholipid syndrome (aps). 35 ...200011035434
mycobacterium leprae typing by genomic diversity and global distribution of genotypes.the genetic diversity and related global distribution of 51 mycobacterium leprae isolates were studied. isolates were obtained from leprosy patients from 12 geographically distinct regions of the world and two were obtained from nonhuman sources. polymerase chain reaction (pcr) followed by dna sequencing was performed targeting the rpot gene of m. leprae. isolates were classified into two groups based on the number of tandem repeats composed of 6 base pairs in the rpot gene. isolates from japan ...200011036491
distinct patterns of microvasculature in the cutaneous lesions of leprosy.this work is an investigation on the microvasculature of the cutaneous infiltrates of leprosy with the immunohistochemical staining of endothelial cells in cutaneous biopsies. anti-factor viii-related antigen antibody (anti-fviii-ra) and ulex europaeus-1 lectin (uea-1) binding were utilized as endothelial cell markers. thirty-nine patients grouped according to the ridley-jopling classification (14 borderline tuberculoid, 18 borderline lepromatous, 6 lepromatous, and 1 indeterminate leprosy) were ...200011036494
experimental mycobacterium leprae infection in balb/c mice: effect of bcg administration on tnf-alpha production and granuloma development.in the present study, the experimental model of mycobacterium leprae infection in the foot pads of balb/c mice was used to investigate the effects of bcg administration on tumor necrosis factor-alpha (tnf-alpha) production and granuloma development. it was observed that mice intravenously infected with bcg 7 months after m. leprae inoculation into the foot pads presented a more effective mycobacteria clearance, revealed by a significant reduction of bcg-colony forming units in the spleen and by ...200011036496
comparative genomics of the mycobacteria.the genus mycobacteria includes two important human pathogens mycobacterium tuberculosis and mycobacterium lepra. the former is reputed to have the highest annual global mortality of all pathogens. their slow growth, virulence for humans and particular physiology makes these organisms extremely difficult to work with. however the rapid development of mycobacterial genomics following the completion of the mycobacterium tuberculosis genome sequence provides the basis for a powerful new approach fo ...200011045919
solitary tuberculoid hansen lesion of the ulnar nerve. 200011059678
comparison of the udp-n-acetylmuramate:l-alanine ligase enzymes from mycobacterium tuberculosis and mycobacterium leprae.in the peptidoglycan of mycobacterium leprae, l-alanine of the side chain is replaced by glycine. when expressed in escherichia coli, murc (udp-n-acetyl-muramate:l-alanine ligase) of m. leprae showed k(m) and v(max) for l-alanine and glycine similar to those of mycobacterium tuberculosis murc, suggesting that another explanation should be sought for the presence of glycine.200011073931
clinico-histopathological concordance in leprosy.histopathological examination of biopsies from 111 patients with clinically diagnosed leprosy was carried out in order to observe the clinico-histopathological correlation. clinical diagnosis was based on ridley and jopling (r-j) classification and world health organization (who) classification. the concordance rate between the two clinical classifications was 73.8%. sections were stained with haematoxylin and eosin (h&e) and ziehl-neelsen's (z-n) stains. the histological classification was as p ...200011075660
[the comparative cultural-biochemical and immunochemical identification of laboratory strains of cultured mycobacteria from leprous patient lesions and from soil].the paper presents the results of studied of cultural biochemical and immunochemical properties of the cultured mycobacteria isolated from patients with leprous lesions of (m.01, m.011) and the soil (m. lufu) in compared to other well-known mycobacteria and between them. m.01, m.011, and m. lufu differ from other representatives of the genus mycobacterium, but they are close to each other in their cultural biochemical and immunochemical properties, antigenic composition, and protein spectra. the ...200011077855
role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of mycobacterium leprae.the cell wall of pathogenic mycobacteria is abundant with complex glycolipids whose roles in disease pathogenesis are mostly unknown. here, we provide evidence for the involvement of the specific trisaccharide unit of the phenolic glycolipid-1 (pgl-1) of mycobacterium leprae in determining the bacterial predilection to the peripheral nerve. pgl-1 binds specifically to the native laminin-2 in the basal lamina of schwann cell-axon units. this binding is mediated by the alpha(2lg1, alpha2lg4, and a ...200011081637
interactions between mycobacterium leprae and simian immunodeficiency virus (siv) in rhesus monkeys.groups of rhesus monkeys were inoculated with: 1) simian immunodeficiency virus (siv)b670 alone; 2) mycobacterium leprae alone; 3) siv plus m. leprae on the same day; and 4) m. leprae 2 weeks after siv. animals were monitored at intervals for virus loads, antibody responses to m. leprae glycolipid antigens and to siv gp120, t-cell cd4+ and cd4+ cd29+ subset percentages, leprosy and acquired immunodeficiency syndrome (aids) clinical symptoms. five out of six animals developed leprosy in each co-i ...200011085588
bacterial and host-derived cationic proteins bind alpha2-laminins and enhance mycobacterium leprae attachment to human schwann cells.it has recently been demonstrated that laminin alpha2 chains present on the surface of schwann cells are involved in the process of attachment of mycobacterium leprae to these cells. in this study, a protein in the m. leprae cell wall that was found to be capable of binding alpha2-containing laminins (merosin) was isolated and characterized. the m. leprae laminin-binding protein was identified as a 21-kda histone-like protein (hlp), a highly conserved cationic protein present in other species of ...200011099926
variable numbers of ttc repeats in mycobacterium leprae dna from leprosy patients and use in strain differentiation.strain differentiation of mycobacterium leprae would be of great value for epidemiological investigation to identify the infectious sources of leprosy, to understand transmission patterns, and to distinguish between relapse and reinfection. from the m. leprae genome sequence database, ttc dna repeats were identified. primer sets designed to amplify the region flanking ttc repeats revealed pcr products of different sizes, indicating that the number of repeats at each locus may be variable among m ...200011101592
current understanding of leprosy as a peripheral nerve disorder: significance of involvement of peripheral nerve in leprosy. 200011105275
recent advances in the microbiology of leprosy. 200011105277
the pattern of decline in bacillary index after 2 years of who recommended multiple drug therapy: the amfes cohort.with effective antibiotic treatment, the bacillary index (bi) in multibacillary leprosy patients declines over a number of years. this can be quantified as a rate of decline in log-units per year or as the time until smear negativity is reached. in the amfes cohort 220 cases had data on the changes in their bi over time, while 170 cases are documented until smear negativity. the average bi at the start was 3.3 (sd 1.5; range 0.3-5.5) and the mean rate of decline was 0.85 units per year (median 0 ...200011105492
production of transforming growth factor-beta 1 (tgf-beta1) by blood monocytes from patients with different clinical forms of leprosy.in the present study, the concentration of tgf-beta1 secreted by adherent cells isolated from human peripheral blood mononuclear cells (pbmc) and either stimulated with pgl-1 or lipopolysaccharide (lps) or left unstimulated was determined by elisa. the cells were isolated from untreated patients with different clinical forms of leprosy and healthy individuals. the adherent cells exhibited spontaneous release of tgf-beta1 in all clinical forms of leprosy and in healthy individuals; however, lepro ...200011122237
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
comparison of polymerase chain reaction, immunohistochemistry and conventional histopathology in the diagnosis of early leprosy in sichuan province of china.46 formalin-fixed, paraffin-embedded skin biopsy specimens, which were clinically suspected or diagnosed as early leprosy, were retrieved from the files of sichuan, china from 1997 to 1999. all of them were examined by polymerase chain reaction (pcr) using the primers amplifying the 130 base-pair fragment of the gene from the 16s ribosomal rna of mycobacterium leprae, hematoxylin and eosin (h&e) staining, modified fite-faraco technique for m. leprae and immunostaining with the antiserum against ...200011187722
evidence for symmetric chromosomal inversions around the replication origin in bacteria.whole-genome comparisons can provide great insight into many aspects of biology. until recently, however, comparisons were mainly possible only between distantly related species. complete genome sequences are now becoming available from multiple sets of closely related strains or species.200011178265
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
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
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
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
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
genomes 2000. intimate portraits of bacterial nemeses. 200010809648
protection against virulent mycobacterium avium infection following dna vaccination with the 35-kilodalton antigen is accompanied by induction of gamma interferon-secreting cd4(+) t cells.mycobacterium avium is an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency of m. avium infection is also increasing in the immunocompetent population. the antigen repertoire of m. avium varies from that of mycobacterium tuberculosis, with the immunodominant 35-kda protein being present in m. avium and mycobacterium leprae but not in members of the m. tuberculosis complex. here we show that a dna vector encoding this m. avium 35-kda antigen (dna- ...200010816448
genomic arrangement of a putative operon involved in maltose transport in the mycobacterium tuberculosis complex and mycobacterium leprae.a mycobacterium bovis gene coding for a putative male maltose binding protein was cloned and its full-length sequence determined. database searches revealed 99.9% identity with ipqy, encoding a putative sugar uptake protein from mycobacterium tuberculosis strain h37rv. the deduced protein product showed high sequence similarity to male-like proteins from a variety of bacterial species, including mycobacterium leprae. analysis of flanking database sequences from m. tuberculosis and m. leprae reve ...200010817516
dihydropteroate synthase of mycobacterium leprae and dapsone resistance.two mycobacterium leprae genes, folp1 and folp2, encoding putative dihydropteroate synthases (dhps), were studied for enzymatic activity and for the presence of mutations associated with dapsone resistance. each gene was cloned and expressed in a folp knockout mutant of escherichia coli (c600deltafolp::km(r)). expression of m. leprae folp1 in c600deltafolp::km(r) conferred growth on a folate-deficient medium, and bacterial lysates exhibited dhps activity. this recombinant displayed a 256-fold-gr ...200010817704
a 6 week quadruple drug regimen for the treatment of multibacillary leprosy. 200010820986
light and electron microscopic study of peripheral nerve damage in patients with lepromatous leprosy (ll) and borderline lepromatous leprosy (bl).cutaneous branches of radial nerves in patients with lepromatous leprosy (ll) and borderline lepromatous (bl) were studied by light and electron microscopy. foamy macrophages were found more or less in the nerve fibers of all leprosy patients and distributed in the epineurial, perineurial and endoneurial areas. in the endoneurium, the foamy macrophages were mainly located in the subperineurial and perivascular spaces. vacuolated schwann cells were also found in the nerve fasciculus. in electron ...200010824461
large unilamellar vesicles as trehalose-stabilised vehicles for vaccines: storage time and in vivo studies.liposomes, as a pharmaceutical formulation must display a long shelf life. the recombinant heat-shock protein from mycobacterium leprae (18-kda hsp) or its n-acylated derivative, when entrapped within or externally associated with large unilamellar vesicles, acts as a t-epitope source. freeze-fracture electron microscopy shows unequivocally that trehalose avoids aggregation and fusion of these vesicles. formulations containing trehalose retained up to 98% of the entrapped protein. the highest an ...200010825571
association of mycobacterium leprae with human endothelial cells in vitro.endothelial cell infection by mycobacterium leprae has long been described histologically in all types of leprosy and in some of the acute reactions occurring in this disease. recent evidence from experimental lepromatous neuritis indicates that m. leprae colonizes endothelial cells of epineural blood vessels even in sites of minimal infection, suggesting that interaction between these cells and m. leprae may play an important role in the selective localization of this organism to peripheral ner ...200010830776
inhibition of metabolism and growth of mycobacterium leprae by gamma irradiation.mycobacterium leprae is uncultivable on artificial medium, but viability can be maintained without multiplication for a limited time in vitro. in this study, we evaluated gamma-irradiation (gamma-irr) as a means to kill this slowly growing organism. freshly harvested, viable, athymic, nu/nu mouse-derived m. leprae were exposed to varying doses of gamma-irr from a 60co source. two indicators of bacterial viability were determined: metabolism, measured by oxidation of 14c-palmitic acid to 14co2 in ...200010834063
the effect of ultraviolet light radiation on mycobacterium leprae.ultraviolet (uv) light is recognized as a potent sterilizing aid, but its relative effectiveness against mycobacterium leprae has not been shown. we examined the influence of uv on the growth and metabolic activity of m. leprae harvested fresh from foot pads of nude mice. temporary static suspensions were exposed to timed intervals of uv radiation generated from a fixed source to constitute dosages ranging from 0-12.64 x 10(4) erg/cm2. the metabolic activity of the bacilli was indexed by the oxi ...200010834064
comparative study of mitsuda reaction to nude mouse and armadillo lepromin preparations using nine-banded armadillos.in 14 nine-banded armadillos the mitsuda response to nude mouse-derived lepromin (lepromin-nu/nu) was compared to that of armadillo-derived lepromin (lepromin-a) by injecting the reagents intradermally into either side of the abdomen of the animal and examining the biopsies from the sites after 12 days. the histopathologic responses to both antigens were found to be similar, whether the animal was mitsuda-negative (lepromatous) or mitsuda-positive (tuberculoid). it is pointed out that armadillos ...200010834065
pathology of a lepromatous eye.histopathological examination of an enucleated eye from a lepromatous leprosy patient showed the cornea, ciliary body, and part of the choroid to be infiltrated by macrophages filled with mycobacterium leprae. the walls of blood vessels in the sclera, ciliary body and the anterior choroid demonstrated the presence of m. leprae, giving credence to the blood-borne entry of m. leprae into the eye. unlike the eyes of experimental animals infected with m. leprae, histopathological study of this eye f ...200010834066
antileprosy protective vaccination of rhesus monkeys with bcg or bcg plus heat-killed mycobacterium leprae: immunologic observations.groups of rhesus monkeys were vaccinated and boosted with mycobacterium bovis bacillus calmette guerin (bcg) or bcg plus low-dose (ld) or high-dose (hd) heat-killed m. leprae (hkml), or were unvaccinated. prior to and following vaccination-boosting and subsequent m. leprae (ml) challenge, these and unvaccinated, unchallenged control monkeys were observed longitudinally for approximately 3 years. vaccination with bcg plus hkml initially stimulated significant in vitro blood mononuclear cell blast ...200010834067
interferon-gamma responses to candidate leprosy skin-test reagents detect exposure to leprosy in an endemic population.new tools for the detection of leprosy exposure in a community will be necessary for the eradication of leprosy. candidate leprosy skin-test antigens derived from the fractionation of the leprosy bacillus into cytoplasmic and cell-wall proteins free of immuno-inhibitory mycobacterial lipoglycans and carbohydrates were used in an overnight blood test to determine whether exposure to leprosy can be detected by the production of the cytokine interferon gamma (ifn-gamma). strong ifn-gamma responses ...200010834068
human leukocyte antigens in forms of leprosy among japanese patients.human leukocyte antigens (hla) class ii alleles were analyzed among japanese leprosy patients to ascertain whether immunogenetic differences exist among the leprosy classification forms of ridley and jopling. ninety-three unrelated japanese leprosy patients (21 lepromatous, 24 borderline lepromatous, 17 mid-borderline, 26 borderline tuberculoid, 5 tuberculoid) and 114 healthy control subjects were investigated. the frequencies of hla-drb1*1501, -drb5*0101, -dqa1*0102 and dqb1*0602 were significa ...200010834069
epidemiology of leprosy in taiwan; its pattern in children.to study the epidemiology of leprosy in children in taiwan.200010834070
clarification to rada-schlaefli, et al. 200010834071
phagocytic myeloperoxidase in leprosy pathogenesis. 200010834075
cellular immune response to klebsiella pneumoniae antigens in patients with hla-b27+ ankylosing spondylitis.to study the reactivity of peripheral blood mononuclear cells (pbmc) of patients with ankylosing spondylitis (as) and rheumatoid arthritis (ra) and healthy controls to klebsiella pneumoniae antigens and to the groel-like proteins from k. pneumoniae (hsp60kp) and mycobacterium leprae recombinant heat shock protein 65 (rhsp65ml).200010852270
in vivo splicing and functional characterization of mycobacterium leprae reca.the reca proteins from mycobacterium tuberculosis and mycobacterium leprae contain inteins. in contrast to the m. tuberculosis reca, the m. leprae reca is not spliced in escherichia coli. we demonstrate here that m. leprae reca is functionally spliced in mycobacterium smegmatis and produces resistance toward dna-damaging agents and homologous recombination.200010852894
comparative genomics of the leprosy and tubercle bacilli.to achieve the quantum leap in understanding required to overcome two major human diseases, leprosy and tuberculosis, systematic and comparative genome analysis has been undertaken. new insight into the biology of their causative agents has been obtained and the principle findings are reported here.200010865959
[dissertations about leprosy in the seville at the end of the enlightenment age].introduction: leprosy is a well-known disease from ancient history. society reacts violently due to the fear of infection, and the fact that it causes appalling physical mutilation. it is produced by mycobacterium leprae, which only affects the nervous system of human beings. development: the norms and examinations that for many years were practiced upon those suspected of being infected by the leprosy organism are based almost always in a series of requirements that were in keeping with cases o ...200010870206
leprosy.leprosy is a unique infectious disease with a prolonged incubation period and a predilection for skin and nerves. the involvement of nerves by the primary infection as well as the immunologically mediated reversal reactions result in impairment of nerve function and severe disabilities. the introduction of the world health organization multi drug therapy over the last two decades has produced dramatic changes in the management and control programmes of leprosy. a recent important contribution to ...200010871258
a role for cd40-cd40 ligand interactions in the generation of type 1 cytokine responses in human leprosy.the interaction of cd40 ligand (cd40l) expressed by activated t cells with cd40 on macrophages has been shown to be a potent stimulus for the production of il-12, an obligate signal for generation of th1 cytokine responses. the expression and interaction of cd40 and cd40l were investigated in human infectious disease using leprosy as a model. cd40 and cd40l mrna and surface protein expression were predominant in skin lesions of resistant tuberculoid patients compared with the highly susceptible ...200010903757
leprosy--a new look at an old disease. 200010906079
progression of eye disease in "cured" leprosy patients: implications for understanding the pathophysiology of ocular disease and for addressing eyecare needs.ocular damage in leprosy is due either to nerve damage or infiltration by mycobacteria. there is currently little information about the magnitude and nature of incident ocular pathology in cured leprosy patients. this information would increase our understanding of the pathophysiology of ocular involvement in leprosy and help in developing programmes to address the eyecare needs of leprosy patients who have been released from treatment. the cumulative incidence of leprosy related ocular patholog ...200010906083
characterization of derivatives of the high-molecular-mass penicillin-binding protein (pbp) 1 of mycobacterium leprae.mycobacterium leprae has two high-molecular-mass multimodular penicillin-binding proteins (pbps) of class a, termed pbp1 and pbp1* [lepage, dubois, ghosh, joris, mahapatra, kundu, basu, chakrabarti, cole, nguyen-disteche and ghuysen (1997) j. bacteriol. 179, 4627-4630]. pbp1-xaa-beta-lactamase fusions generated periplasmic beta-lactamase activity when xaa (the amino acid of pbp1 at the fusion junction) was residue 314, 363, 407, 450 or 480. truncation of the n-terminal part of the protein up to ...200010926828
mycobacterium leprae--millennium resistant! leprosy control on the threshold of a new era.over the past decades, the conditions of leprosy control implementation have changed dramatically. introduction of multidrug therapy, together with the global effort of the world health organization to eliminate leprosy as a public health problem, had a tremendous impact on leprosy control, particularly by decreasing the registered prevalence of the disease. at the beginning of the new millennium, leprosy control programmes face several new challenges. these relate not only to changes in the pre ...200010929137
search for newer antileprosy drugs.in 1991 world health organization proclaimed the goal of global elimination of leprosy as a public health problem by year 2000 by implementing multidrug therapy (mdt). since then the prevalence rate has declined by 85%. however, during the same period the incidence rate of leprosy has remained constant or even has been increasing. this suggests that it will take a long time for the eradication of leprosy and that without in-vitro cultivation of m. leprae, eradication of leprosy is not likely to ...200010935183
immunotherapy and immunoprophylaxis of leprosy. 200010935184
systemic involvement in leprosy and its significance. 200010935191
developments in experimental leprosy. 200010935192
novel mechanisms in the immunopathogenesis of leprosy nerve damage: the role of schwann cells, t cells and mycobacterium leprae.the major complication of reversal (or type 1) reactions in leprosy is peripheral nerve damage. the pathogenesis of nerve damage remains largely unresolved. in situ analyses suggest an important role for type 1 t cells. mycobacterium leprae is known to have a remarkable tropism for schwann cells that surround peripheral axons. reversal reactions in leprosy are often accompanied by severe and irreversible nerve destruction and are associated with increased cellular immune reactivity against m. le ...200010947859
role of inducible nitric oxide synthase in resistance to mycobacterium leprae in mice.the manifestation of leprosy in humans is largely determined by host immunity to mycobacterium leprae and is a model for immunoregulation in a human disease. however, animal models available for exploration of the leprosy spectrum are inadequate. this study explored m. leprae infection in mice deficient in inducible nitric oxide synthase, and this report describes elements resembling borderline tuberculoid leprosy in humans.200010948185
antiphospholipid antibodies in leprotic patients: a correlation with disease manifestations.previous studies showed that antiphospholipid antibodies (apl) are frequent in the sera of leprosy patients and are most probably directed against body tissue cardiolipins. some groups have demonstrated differences between the binding specificity of "autoimmune-apl" and "non-autoimmune-apl". it is widely accepted that a plasma protein, beta 2-glycoprotein i (beta 2-gpi), is required for the binding of autoimmune anticardiolipin antibodies (acl) to cardiolipin. however, some reports suggested het ...200010949725
how does mycobacterium leprae target the peripheral nervous system?mycobacterium leprae has the capacity to invade the peripheral nervous system and cause neuropathy. the molecular mechanisms responsible have remained unknown until recently. identification of the endoneurial laminin-2 isoform and its receptor alpha-dystroglycan as neural targets of m. leprae has not only opened up a new area of scientific inquiry into the pathogenesis of neurological damage in leprosy, but has also revealed unexpected biological properties of these important host molecules.200010637640
gene expression, amino acid conservation, and hydrophobicity are the main factors shaping codon preferences in mycobacterium tuberculosis and mycobacterium leprae.mycobacterium tuberculosis and mycobacterium leprae are the ethiological agents of tuberculosis and leprosy, respectively. after performing extensive comparisons between genes from these two gc-rich bacterial species, we were able to construct a set of 275 homologous genes. since these two bacterial species also have a very low growth rate, translational selection could not be so determinant in their codon preferences as it is in other fast-growing bacteria. indeed, principal-components analysis ...200010654259
three pathways for trehalose biosynthesis in mycobacteria.trehalose is present as a free disaccharide in the cytoplasm of mycobacteria and as a component of cell-wall glycolipids implicated in tissue damage associated with mycobacterial infection. to obtain an overview of trehalose metabolism, we analysed data from the mycobacterium tuberculosis genome project and identified orfs with homology to genes encoding enzymes from three trehalose biosynthesis pathways previously characterized in other bacteria. functional assays using mycobacterial extracts a ...200010658666
detection of disease related immune complexes in the serum of leprosy patients. a novel single step method.mycobacterium leprae antigen and antibody complexes could be detected in the serum of leprosy patients using monoclonal antibody ml34 and anti-bcg antibodies by enzyme-linked immunosorbent assay. this simplified system detects disease related complexes without the need for isolating and purifying them from the serum. immune complexes captured using monoclonal antibody ml34 revealed positivity in seven out of eight neuritic, two out of nine tuberculoid (tt), five out of ten borderline tuberculoid ...200010713365
hla-restricted immune response to mycobacterial antigens: relevance to vaccine design.identification of mycobacterial antigens that are recognized by cd4+ th1 cells in hla-nonrestricted manner or in association with multiple allelic products is required to develop universally effective vaccines against mycobacterial diseases. our studies in this direction have shown that several recombinant mycobacterial antigens of cytosolic and culture filtrate origin are recognized by cd4+ th1 cells. mapping of t cell epitopes with overlapping synthetic peptides covering the entire sequence of ...200010717810
interaction of mycobacterium avium complex with human respiratory epithelial cells.adherence of mycobacterium avium complex (mac) to human respiratory epithelial cells (hep-2) induced 2 distinct modes of internalization. in the first, mac induced ruffling of hep-2 cell membrane and formation of surface projections securing the bacilli on the surface, and concurrent membrane depressions, beneath the sites of attachment of bacilli, resulted in internalization of the organisms. the second mode involved formation of membrane folds wrapping around the bacilli, followed by internali ...200010720553
role of a bacillus calmette-guérin fibronectin attachment protein in bcg-induced antitumor activity.intravesical mycobacterium bovis bacillus calmette-gu*erin (bcg) is the treatment of choice for superficial bladder cancer. previous studies showed that attachment of bcg to fibronectin within the bladder was necessary for mediation of the antitumor response. further studies identified a bacterial receptor, fibronectin attachment protein (fap), as an important mediator of bcg attachment to fibronectin. in vitro studies showed that a stable bcg/fibronectin interaction was dependent on fap binding ...200010728599
interleukin-12 amplifies the m. leprae hsp65-cytotoxic response in the presence of tumour necrosis factor-alpha and interferon-gamma generating cd56+ effector cells: interleukin-4 downregulates this effect.interleukin-12 (il-12) is a major immunomodulatory cytokine that represents a functional bridge between the early resistance and the subsequent antigen specific adaptive immunity. tnf-alpha and ifn-gamma have an important role in the generation of hsp65 specific cytotoxic t lymphocytes (ctl) that lyse hsp65-pulsed autologous macrophages (hsp65 ctl). since a positive feedback mechanism between tnf-alpha, ifn-gamma and il-12 has been described, we undertook to evaluate the role of il-12 on the hsp ...200010736095
immunological cytokine correlates of protective immunity and pathogenesis in leprosy.the in vitro production of interferon (ifn)-gamma, interleukin (il)-5, tumour necrosis factor (tnf)-alpha and il-10 by blood mononuclear cells in response to whole mycobacterium leprae and polyclonal stimulii of 23 individuals, representing a variety of conditions in relation to exposure/susceptibility to m. leprae, was assayed. in most cases, healthy household contacts of newly diagnosed multibacillary leprosy patients, designated exposed household contacts (ec), showed low-to-undetectable in v ...200010736116
atp content of mycobacterium tuberculosis grown in vivo and in vitro.in order to determine the reason for the slow growth of mycobacterium leprae either in a host or in vitro, the growth characteristics of mycobacterium tuberculosis were studied. the atp content of in vitro-grown m. tuberculosis was about 520 pg/10(6) viable organisms. the atp levels from in vivo-derived organisms obtained from liver and spleen of mice was about 130 pg (in cases of chronic infection) and about 270 pg (in cases of acute infection). when the in vivo-derived organisms were inoculate ...200010738981
mycobacterium leprae and neuropathies. 200010754571
leprosy in the new millennium. 200010755622
regulation by protein kinase of phagocytosis of mycobacterium leprae by macrophages.mycobacterium leprae multiplies within host macrophages. the mechanism of internalisation of the bacteria by the phagocytic cells is unknown. in this study, m. leprae was purified from the foot pads of experimentally infected nu/nu mice. peritoneal macrophages were harvested from balb/c mice or c57 beige (bg/bg) mice. the effect of protein kinase inhibitors (erbstatin, genistein or staurosporine for balb/c and bg/bg mice, plus herbimycin for bg/bg mice) on phagocytosis of the mycobacteria by the ...200010755627
cross-reactive epitopes and hla-restriction elements in human t cell recognition of the mycobacterium leprae 18-kd heat shock protein.we have previously demonstrated that the mycobacterium leprae 18-kd heat shock protein (hsp18) is represented among the antigenic targets of human t cell responses induced by m. leprae immunization and that the peptide 38-50 serves as an immunodominant epitope recognized by cd4+ t cell clones. by using peripheral blood mononuclear cells and t cell lines from the same donor group, we have in this study shown that the m. leprae hsp18 and peptide 38-50 were recognized by memory t cells 8 years afte ...200010759768
evidence for human cd4+ t cells in the cd1-restricted repertoire: derivation of mycobacteria-reactive t cells from leprosy lesions.both the cd4-cd8- (double negative) and cd4-cd8+ t cell lineages have been shown to contain t cells which recognize microbial lipid and glycolipid ags in the context of human cd1 molecules. to determine whether t cells expressing the cd4 coreceptor could recognize ag in the context of cd1, we derived cd4+ t cell lines from the lesions of leprosy patients. we identified three cd4+ mycobacterium leprae-reactive, cd1-restricted t cell lines: two cd1b restricted and one cd1c restricted. these t cell ...200010779786
generalized annular borderline tuberculoid leprosy and update in management of hansen's disease.we describe a patient with widespread borderline tuberculoid leprosy and significant peripheral nerve involvement. despite the presence of widespread lesions, fite stains and polymerase chain reaction studies were initially negative. we discuss the diagnosis and treatment of leprosy including recent changes in treatment regimens and duration.200010795079
the crystal structure and active site location of isocitrate lyase from the fungus aspergillus nidulans.isocitrate lyase catalyses the first committed step of the carbon-conserving glyoxylate bypass, the mg(2+)-dependent reversible cleavage of isocitrate into succinate and glyoxylate. this metabolic pathway is an inviting target for the control of a number of diseases, because the enzymes involved in this cycle have been identified in many pathogens including mycobacterium leprae and leishmania.200010801489
extensive sequence homology between the mycobacterium leprae lsr (12 kda) antigen and its mycobacterium tuberculosis counterpart.the mycobacterium leprae lsr (12 kda) protein antigen has been reported to mimic whole cell m. leprae in t cell responses across the leprosy spectrum. in addition, b cell responses to specific sequences within the lsr antigen have been shown to be associated with immunopathological responses in leprosy patients with erythema nodosum leprosum. we have in the present study applied the m. leprae lsr dna sequence as query to search for the presence of homologous genes within the recently completed m ...200010617795
inhibition of multiplication of mycobacterium leprae in mouse foot pads by recombinant bacillus catmette-guérin (bcg).immunization of mice with recombinant mycobacterium bovis bacillus calmette-guérin (rbcg) which over-produces a putative protective antigen candidate, the a component of antigen 85 complex (ag85a), reduced the multiplication of mycobacterium leprae in the foot pads of mice. the inhibition by this rbcg (rbcg/85a) was more evident than that with parental bcg. repeated rbcg/85a immunization significantly could reduce m. leplae multiplication in mice. this is first report of rbcg to control mycobact ...200010618524
the gene encoding mycobacterial dna-binding protein i (mdpi) transformed rapidly growing bacteria to slowly growing bacteria.pathogenic species of mycobacterium are slowly growing intracellular bacteria. slow growth is important for the parasitism of these organisms and chronicity of the disease, but its precise mechanism has not been elucidated. recently, we found that a novel dna-binding protein (mdpi) was expressed (7-10% in total protein) in mycobacteria, such as mycobacterium bovis bacillus calmette-guérin, mycobacterium tuberculosis, and mycobacterium leprae. in this study, we observed that mdpi interfered with ...200010620682
identification of mycobacterium avium dna sequences that encode exported proteins by using phoa gene fusions.mycobacterium avium is the major cause of disseminated infection in patients with late stage aids.objective: in order to identify m. avium genes that may be involved in bacterial uptake and intracellular survival, a phoa -based reporter system was used to identify genes that encoded surface-expressed or exported proteins.200010970760
dendritic epidermal gamma/delta t cells (detc) activated in vivo proliferate in vitro in response to mycobacterium leprae antigens.gamma/delta t-cell receptor (tcr)+ dendritic epidermal t cells (detc) are part of a primitive defense system in the skin; they are capable of responding only to a limited number of antigens. the aim of the present study was to test whether detc can proliferate in vitro in response to antigens of mycobacterium leprae.200010971729
effect of peroxidase on the development of experimental leprosy in mice after intraplantar infection.lyophilized horseradish peroxidase (activity 100 u/mg) administered per os in a dose of 100-200 mg/kg fodder enhanced bactericidal activity of phagocytes in mice experimentally infected with mycobacterium leprae, which manifested in suppression of m. leprae growth in comparison with untreated controls.200010977959
[study on recombinant bcg to prevent infections of intracellular pathogens].studies on recombinant bcg (rbcg) which my group carried out so far were reviewed. recombinant bcg which secreted alpha antigen-fused foreign antigen was constructed and tested for its ability to induce protective immunity. thus, rbcg secreting merozoite surface protein 1 (msp1) of plasmodium yoelii efficiently protected the infection more than recombinant msp 1 mixed with artificial adjuvant ras or ifa did. rbcg which secreted excess amounts of antigen 85 complex a inhibited the multiplication ...200010979272
effect of treatment on pcr positivity in multibacillary leprosy patients treated with conventional and newer drugs ofloxacin and minocycline.in order to develop objective criteria to monitor trends of therapeutic responses positivity of pcr signals and atp assay methods has been compared in multibacillary (mb) leprosy patients. biopsies from lesions of 95 bl/ll patients before and after one year of treatment with a new drug regimen comprising of conventional and newer drugs ofloxacin and minocycline have been studied. these biopsies were processed for bacillary atp assay and pcr positivity for a 36 kda gene target by earlier publishe ...199910987049
in vitro activities of phenothiazine-type calmodulin antagonists against mycobacterium leprae.calmodulin-like protein has been established as the primary receptor for calcium in eukaryotic as well as prokaryotic cells. the calmodulin-calcium complex regulates a variety of enzymes including nucleotide phosphodiesterase. recently, the presence of this protein in mycobacterium leprae has been demonstrated and the effects of phenothiazine-type calmodulin antagonists on in vitro growth of m. leprae in a cell-free culture system were investigated. two biochemical parameters were used to measur ...199910624009
[mycobacterium leprae]. 199910635795
drug resistance in leprosy: lessons from past and future perspective.some recent studies indicate that the problem of drug resistance in leprosy is very much there but the exact picture is not clear. in the emerging scenario with increasing number of new cases with low bacterial load, the conventional in-vivo and most of current in-vitro methods for determination of drug resistance may not help. it is pointed out that newer molecular approaches may be more useful and that it will be important to undertake studies to develop such tools.199910804973
community participation in case detection of leprosy in nagpur district of maharashtra.involving special community groups for new case detection is of great importance for achieving the target of elimination of leprosy. during 1998-99, thirty village level mahila mandals (women's groups), 6950 teachers and students and 34,548 heads of families were co-opted to participate in case detection. they examined 56,113 persons including 378,959 school students and 184,940 family members. of the examined population, 275 were suspected to be cases of leprosy by mahila mandals, 411 by teache ...199910804974
"outside project area" leprosy cases in 'a' ward of mumbai.analysis of newly registered smear-positive cases in a ward of the metropolitan city of mumbai, which has a railway terminus during 1990-97 revealed that 72% of the patients came from outside the project area, most of them arising from the states of uttar pradesh, bihar and orissa. they had unstable and temporary residences in the area and were employed in low income hard labour jobs. nevertheless, it was found that their treatment completion rate was high. using different approaches, e.g. throu ...199910804975
comparative leprosy vaccine trial in south india. 199910804976
survey of labour in "usana" rice factory, in bhandara district (maharashtra) 199910804977
shedding of soluble receptor for tumor necrosis factor alpha induced by m. leprae or lps from human mononuclear cells.cell surface expression and release of the tumor necrosis factor receptor (tnfr type i) was analyzed after stimulation of peripheral blood mononuclear cells (pbmc) with mycobacterium leprae (m. leprae) or lipopolysaccharide (lps). a transient spontaneous expression of tnfr type i on the surface of pbmc was observed. two hr after activation with lps, a significant reduction of tnfr type i expression was detected: release of tnfr type i by m. leprae or lps-stimulated pbmc was evaluated with an enz ...199910659614
isolation, characterization, molecular cloning and amplification of a species-specific m. leprae antigen.a polyclonal serum sample from a lepromatous leprosy (ll) patient, which presented a specific recognition pattern for leprosin, was used to screen a mycobacterium leprae genomic library constructed with dna isolated from human lepromas. one clone, designated ml4-1, which expressed a specific antigenic determinant of m. leprae as part of a beta-galactosidase fusion protein, was isolated. the 1.932 bp m. leprae-derived genomic fragment was sequenced, and it had an incomplete open-reading frame sho ...199910700913
histopathological activity in paucibacillary leprosy patients after rom therapy.histopathological activity was assessed in the skin tissue of 13 skin-smear negative, borderline tuberculoid leprosy patients after administration of a single dose of rom (rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg) therapy. biopsies taken just before therapy showed mycobacterium leprae to be present in eight cases. after 6 months, only three showed granulomatous lesions and others showed only resolving or inactive lesions. acid-fast bacilli (afb) persisted in the nerves of three c ...199910700915
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