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simultaneous detection of mycobacterium leprae and its susceptibility to dapsone using dna heteroduplex analysis.currently recommended control measures for treating leprosy with multidrug therapy should control the spread of drug-resistant strains; however, dapsone (dds) resistance continues to be reported. comprehensive estimates of drug-resistant leprosy are difficult to obtain due to the cumbersome nature of the conventional drug susceptibility testing method using mouse footpad inoculation, which requires at least 6 months to obtain results. recently, it has been determined that dds-resistant strains c ...200111376039
genomics: leprosy - a degenerative disease of the genome.analysis of the genome of the leprosy bacillus uncovers evidence of extensive deletion and inactivation of genes. secluded in a specialised niche, it has discarded much of its genetic heritage, though retaining just enough to be a major human pathogen.200111378400
unique expression of a highly conserved mycobacterial gene in is901(+) mycobacterium avium.expression of a gene encoding a novel protein antigen of 40 kda (p40) was detected in is901(+) strains of mycobacterium avium, but not in any other species or subspecies of mycobacterium tested, including is901(-) m. avium and the other members of the m. avium complex. although southern hybridization revealed that the p40 gene is widely distributed within the genus, expression of the antigen could not be detected on western blots of mycobacterial cell lysates. nucleotide sequence analysis of the ...200111390686
resuscitation of dormant mycobacterium tuberculosis by phospholipids or specific peptides.the presence of dormant tubercle bacilli presents a major problem for tuberculosis treatment. the culture supernatant of mycobacterium tuberculosis was previously shown to resuscitate dormant bacilli in vitro. here we report identification of active components as phospholipids and a tuberculosis protein rv1174c. remarkably, dormant bacilli from a one year old culture which failed to form any colonies could be resuscitated with peptides derived from rv1174c and formed 10(5-7) colonies/ml. this fi ...200111394916
leprosy and the genome--not yet a burnt-out case. 200111425365
intracellular signals triggered during association of mycobacterium leprae and mycobacterium bovis bcg with human monocytes.to gain a better understanding of mycobacteria-host cell interaction, the present study compared the signal transduction events triggered during the interaction of mycobacterium leprae (the causative agent of leprosy) and of mycobacterium bovis bcg (an attenuated strain used as a vaccine against leprosy and tuberculosis) with human monocytes. the assays consisted of pre-treating or not thp-1 cells (a human monocytic cell line) with different kinase inhibitors, followed by incubation with fluores ...200111427035
serological expression cloning and immunological evaluation of mtb48, a novel mycobacterium tuberculosis antigen.improved diagnostics are needed for the detection of mycobacterium tuberculosis, especially for patients with smear-negative disease. to address this problem, we have screened m. tuberculosis (h37rv and erdman strains) genomic expression libraries with pooled sera from patients with extrapulmonary disease and with sera from patients with elevated reactivity with m. tuberculosis lysate. both serum pools were reactive with clones expressing a recombinant protein referred to here as mtb48. the geno ...200111427558
a role for il-12 receptor expression and signal transduction in host defense in leprosy.the generation of cell-mediated immunity against intracellular infection involves the production of il-12, a critical cytokine required for the development of th1 responses. the biologic activities of il-12 are mediated through a specific, high affinity il-12r composed of an il-12rbeta1/il-12rbeta2 heterodimer, with the il-12rbeta2 chain involved in signaling via stat4. we investigated il-12r expression and function in human infectious disease, using the clinical/immunologic spectrum of leprosy ...200111441083
driving a stake into resurgent tb. 200111452108
the prevalence of folp1 mutations associated with clinical resistance to dapsone, in mycobacterium leprae isolates from south korea. 200111454253
modulation of p53 dependent gene expression and cell death through thioredoxin-thioredoxin reductase by the interferon-retinoid combination.we have shown earlier that the ifn-beta and all-trans retinoic acid (ra) combination, but not the single agents, induces death in several tumor cell lines. employing a genetic technique we have identified several genes associated with retinoid-ifn induced mortality (grim). one of the grims was human thioredoxin reductase (tr), a redox enzyme. since the overexpressed tr augments ifn/ra stimulated cell death, we explored the mechanisms of tr-mediated death. here we show that tr augments cell death ...200111464290
identification and mutagenesis by allelic exchange of choe, encoding a cholesterol oxidase from the intracellular pathogen rhodococcus equi.the virulence mechanisms of the facultative intracellular parasite rhodococcus equi remain largely unknown. among the candidate virulence factors of this pathogenic actinomycete is a secreted cholesterol oxidase, a putative membrane-damaging toxin. we identified and characterized the gene encoding this enzyme, the choe monocistron. its protein product, choe, is homologous to other secreted cholesterol oxidases identified in brevibacterium sterolicum and streptomyces spp. choe also exhibits signi ...200111466283
detection of toll-like receptor 2 (tlr2) mutation in the lepromatous leprosy patients.toll-like receptor 2 (tlr2) is critical in the immune response to mycobacterial infections and the mutations in the tlr2 have been shown to confer the susceptibility to severe infection with mycobacteria. to define this, we screened the intracellular domain of tlr2 in 131 subjects. groups of 45 lepromatous and 41 tuberculoid leprosy (tt) patients and 45 controls were investigated. ten subjects among the lepromatous leprosy (ll) patients had a band variant detected by single-stranded conformation ...200111476982
identification of catalase-like activity from mycobacterium leprae and the relationship between catalase and isonicotinic acid hydrazide (inh).as mycobacterium leprae proliferate inside macrophages, it has been speculated that catalase encoded by katg may protect the bacilli from deleterious effects of peroxide generated from the macrophage and may also play a crucial role in the survival of m. leprae in vivo. however, unlike that of m. tuberculosis, the katg of m. leprae has been reported to be a pseudogene, implicating that isoniazid, which is activated to a potent tuberculocidal agent by catalase, is unlikely to be of therapeutic be ...200111478670
viable m. leprae as a research reagent.mycobacterium leprae remain a rare research resource. they cannot be cultivated on artificial media, and the only established means to quantify viability of m. leprae has been by its relative growth in the foot pads of conventional mice (mfp). the mfp method is technically difficult and requires several months to yield results. more effective methods are needed. we examined the association between m. leprae's ability to oxidize 14c-palmitate in axenic culture and the mfp growth results of a larg ...200111480310
limited atp generation in cells of mycobacterium leprae thai-53 strain in enriched kirchner liquid medium containing adenosine.the atp generation in cells of mycobacterium leprae thai-53 strain takes place in vitro when the cells are cultivated in kirchner liquid medium, ph 7.0, enriched with egg-yolk solution, pyruvate, transferrin, and adenosine at 30 degrees c. among the supplements, adenosine was key and critical for the atp generation. the optimal concentration of adenosine was 50 micrograms/ml of the medium. atp generation, however, was limited; the rates of increase in atp content extracted from the cells were ap ...200111480311
pcr-restriction fragment length polymorphism analysis (pra) of mycobacterium leprae from human lepromas and from a natural case of an armadillo of corrientes, argentina.polymerase chain reaction (pcr)-restriction fragment length polymorphism analysis (pra) which relies on the amplification of a 439-bp portion of the hsp65 gene present in all mycobacteria, followed by two distinct digestions (with bsteii and haeiii) of the pcr product, offers a rapid and easy alternative that allows identification of the species without the need for specialized equipment. wild leprosy in the nine-banded armadillo (dasypus novemcinctus) is characterized by the presence of multipl ...200111480312
factors influencing the development of leprosy: an overview.the clinical manifestations of leprosy vary, seemingly depending on the host's immune response. mode and route of infection, such as skin versus nasal mucosa, insect bites, sexual and gastroenteral transmission, together with genetic factors that may contribute to the outcome of the infection, including hla, lewis factor, nramp1 and more subtle inherited alterations, are discussed. it is theorized that a balance between host responses elicited by different routes of infection and size and spacin ...200111480313
comparative characteristics of antigenic profile of m. leprae and m. lufu. 200111480317
effects of vaccination with several mycobacterial proteins and lipoproteins on mycobacterium leprae infection of the mouse. 200111480318
a study on the reproducibility of two serological assays for detection of mycobacterium leprae infection. 200111480319
peroxidase in therapy of experimentally induced leprosy. 200111480320
histological resolution and bacterial clearance with pulse rom therapy in borderline lepromatous leprosy. 200111480321
does dapsone resistance really matter in the mdt era? 200111480322
response of mycobacterium habana vaccine in patients with lepromatous leprosy and their household contacts. a pilot clinical study.single dose vaccination was carried out with mycobacterium habana vaccine, 31 lepromatous leprosy cases receiving 1.5 mg (1.5 mg = 6.27 x 10(8) bacilli) and 36 household contacts randomly receiving 1.5, 2.0, 2.5 mg vaccine intradermally. duration of study was 18 weeks. vaccination induced lepromin conversion in 100% of lepromatous leprosy cases and lepromin negative household contacts and augmentation of lepromin reactivity in 100% of lepromin positive household contacts, which was stable for th ...200111495449
erp, an extracellular protein family specific to mycobacteria.erp (exported repeated protein) was originally characterized as a virulence factor in mycobacterium tuberculosis and was thought to be present only in mycobacterium leprae and members of the tb complex. here it is shown that erp is a ubiquitous extracellular protein found in all of the mycobacterial species tested. erp proteins have a modular organization and contain three domains: a highly conserved amino-terminal domain which includes a signal sequence, a central variable region containing rep ...200111496008
[late diagnosis of lepromatous leprosy in a geriatric patient]. 200111503588
size matters? 200111514197
update on leprosy.leprosy, a result of infection by mycobacterium leprae, is a leading cause of peripheral neuropathy. the world health organization aimed to eliminate leprosy as a public health problem by 2000, but this has not been attained. patients with leprosy continue to present in the uk. the diagnosis of leprosy is frequently not considered, with resultant pathological and psychological problems for patients.200111530584
the genome of mycobacterium leprae: a minimal mycobacterial gene set.comparison of the recently sequenced genome of the leprosy-causing pathogen mycobacterium leprae with other mycobacterial genomes reveals a drastic gene reduction and decay in m. leprae affecting many metabolic areas, exemplified by the retention of a minimal set of genes required for cell-wall biosynthesis.200111532219
molecular and functional analyses of the gene (esha) encoding the 52-kilodalton protein of streptomyces coelicolor a3(2) required for antibiotic production.analysis of proteins recovered in the s100 precipitate fraction of streptomyces griseus after ultracentrifugation led to the identification of a 52-kda protein which is produced during the late growth phase. the gene (esha) which codes for this protein was cloned from s. griseus, and then its homologue was cloned from streptomyces coelicolor a3(2). the protein was deduced to be 471 amino acids in length. the protein esha is characterized by a central region that shows homology to the eukaryotic- ...200111567001
il-12 and il-18 synergistically induce the bactericidal activity of murine peritoneal cells against m. leprae.we examined the effect of il-12 and il-18 on bactericidal activities of mouse peritoneal cell (pc) against mycobacterium leprae (m. leprae). we demonstrated that il-12 and il-18 synergistically induced the no-dependent bactericidal activity of pc by stimulating natural killer (nk) cells and t-cells through ifn-gamma production. il-12 and il-18 induced host cell death through nk-cells and t-cells. therefore. il-12 and il-18 play an important role on direct killing of intracellular m. leprae and o ...200111579508
[reasons why mycobacterium leprae cells do not multiply under the cell-free condition].our previous paper reported that the intracellular atp content in cells of m. leprae consistently increased in the medium containing adenosine after 4-6 weeks of cultivation and decreased thereafter. the reason why atp generation ceased 4-6 weeks after cultivation is not clear, but it was determined that the termination in atp generation was not a result of deterioration in the culture medium during cultivation because a renewal trial of the old culture medium by freshly prepared culture medium ...200111579510
[genome features of mycobacterium leprae].recent studies have revealed that the mycobacterium leprae genome contains many pseudogenes. this short review summarizes the structural features of the m. leprae genome and genes.200111579511
[a morphological study of nerve biopsies in leprous neuropathy].peripheral nerve biopsies from 10 leprosy patients(6 tuberculoid patients and 4 lepromatous patients) were studied morphological aspect. light microscopical examination showed that the perineurium was markedly thickened by infiltrated cell in tuberculoid type and mycobacterium leprae in lepromatous type. schwann cell markedly decreased in number, and nerve fiber disappeared without regeneration in severe cases. in mild cases, subperineurial edema was present. the nerve fiber density was normal o ...200111579512
borderline tuberculoid leprosy with darier's disease. 200111579654
the esat-6 gene cluster of mycobacterium tuberculosis and other high g+c gram-positive bacteria.the genome of mycobacterium tuberculosis h37rv has five copies of a cluster of genes known as the esat-6 loci. these clusters contain members of the cfp-10 (lhp) and esat-6 (esat-6) gene families (encoding secreted t-cell antigens that lack detectable secretion signals) as well as genes encoding secreted, cell-wall-associated subtilisin-like serine proteases, putative abc transporters, atp-binding proteins and other membrane-associated proteins. these membrane-associated and energy-providing pro ...200111597336
control of skin infections by a combined action of ultraviolet a (from sun or uva lamp) and hydrogen peroxide (huva therapy), with special emphasis on leprosy.despite its abundance and certain therapeutic value, the importance of sunlight in the treatment of infectious skin diseases has not been fully exploited. one reason is that a sufficient amount of the damaging components of sunlight (uvc and most uvb) cannot reach us and the band of uv that can reach (uva) is a poor inactivator of living cells. uva, however, can be deleterious to cells in the presence of sensitizers and a number of biological and chemical sensitizers have been identified which c ...200111601875
leprosy. 200111641922
t cell responses to major membrane protein ii (mmp ii) of mycobacterium leprae are restricted by hla-dr molecules in patients with leprosy.major membrane protein ii (mmp ii) of mycobacterium leprae (m. leprae) is a 22kda protein inducing humoral immune response in leprosy patients. mmp ii-specific bulk t cell lines were established from leprosy patients to determine major t cell epitopes in mmp ii and to evaluate lymphokine production induced by mmp ii. these bulk t cell lines reacted to one or more peptides in the locus of amino acid residues from 23 to 109 of mmp ii. the proliferative responses of all t cell lines were mainly inh ...200111672912
mycobacterium bovis bcg but not mycobacterium leprae induces tnf-alpha secretion in human monocytic thp-1 cells.in this study, we compared the level of tnf-alpha secretion induced in monocytic thp-1 cells after phagocytosis of mycobacterium leprae, the causative agent of leprosy, and m. bovis bcg, an attenuated strain used as a vaccine against leprosy and tuberculosis. the presence of m. leprae and bcg was observed in more than 80% of the cells after 24 h of exposure. however, bcg but not m. leprae was able to induce tnf-alpha secretion in these cells. moreover, thp-1 cells treated simultaneously with bcg ...200111685264
identification of the first eubacterial endonuclease coded by an intein allele in the pps1 gene of mycobacteria.a survey of a vast range of mycobacterial strains led us to discover a new pps1 intein allele in mycobacterium gastri which differs from those of mycobacterium tuberculosis and mycobacterium leprae in both its sequence and insertion site. while little is known about pps1, except that it belongs to the yc24 family of abc transporters, we show that, unlike the other inteins described so far from eubacteria, the mgapps1 intein possesses a specific endonuclease activity. the intein is the first euba ...200111691918
signaling lymphocytic activation molecule expression and regulation in human intracellular infection correlate with th1 cytokine patterns.induction of th1 cytokines, those associated with cell-mediated immunity, is critical for host defense against infection by intracellular pathogens, including mycobacteria. signaling lymphocytic activation molecule (slam, cd150) is a transmembrane protein expressed on lymphocytes that promotes t cell proliferation and ifn-gamma production. the expression and role of slam in human infectious disease were investigated using leprosy as a model. we found that slam mrna and protein were more strongly ...200111698444
leprosy in israel: an imported disease--the support of histopathological examination for its detection.leprosy is rare and non-endemic in israel. cases of leprosy are invariably imported by immigrants or foreign workers arriving from endemic areas. in view of the relative rarity of the disease, clinicians and pathologists are not always alert to the possibility of the disease or recognize potential symptoms. a case history is presented of a 31-year-old immigrant presenting symptoms of skin lesions and nodules on the hands and facial region, especially the ear lobe. confirmation of the infection w ...200111700948
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
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
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
distinguishing between relapse and late reversal reaction in multidrug (mdt)-treated bt leprosy. 200111715270
a high incidence of viable mycobacterium leprae in post-mdt recurrent lesions in tuberculoid leprosy patients. 200111715280
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
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
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
a plea to revive skin smear examination. 200111757169
leprosy with peripheral t-cell lymphoma: a rare association. 200111757170
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
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
south india immunoprophylaxis trial against leprosy: relevance of findings in the context of leprosy trends. 200111757173
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
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
immunopathology of leprosy; a state of the art. 200111757177
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
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
[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
leprosy. oldest and most feared disease. 200111784588
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
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
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
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
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
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
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
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
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
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
mycobacterium leprae genome sequence; a landmark achievement. 200111826474
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
the microbial physiologist's guide to the leprosy genome. 200111826476
dna metabolism in mycobacterium leprae. 200111826477
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
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
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
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
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
leproma: a mycobacterium leprae genome browser. 200111826483
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
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
persisting m. leprae in a nerve in the pampiniform plexus of a lepromatous patient: an unusual finding. 200111840600
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
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
[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
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
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
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
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
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
acceptance of who/mdt over the last 20 years. 200111875769
tumor necrosis factor (tnf) production in leprosy patients. 200111875771
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
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
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
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