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mycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid.the systems participating in detoxification of reactive oxygen intermediates in mycobacterium tuberculosis are believed to play a dual role in the biology of this highly adapted human pathogen: (i) they may contribute to the survival of this bacterium in the host; and (ii) alterations in the gene encoding catalase/peroxidase have been linked to this organism's resistance to the front-line antituberculosis drug isoniazid. these relationships prompted us to extend investigations of the oxidative-s ...19958596438
green fluorescent protein as a marker for gene expression and cell biology of mycobacterial interactions with macrophages.the green fluorescent protein (gfp) of the jellyfish aequorea victoria offers certain advantages over other bioluminescence systems because no exogenously added substrate or co-factors are necessary, and fluorescence can be elicited by irradiation with blue light without exposing the cells producing gfp to invasive treatments. a mycobacterial shuttle-plasmid vector carrying gfp cdna was constructed and used to generate transcriptional fusions with promoters of interest and to examine their expre ...19958596439
the hamster cheek pouch: an immunologically privileged site suitable to the study of granulomatous infections.the hamster cheek pouch is an invagination of oral mucosa, characterized histologically as skin-like. in this paper we describe anatomical, histological and embriological features of the pouch and comment on the pouch as an immunologically privileged site since it lacks lymphatic drainage and has few langerhans cells. we present the review from literature and our observations after inoculation in the pouch of mycobacteriae (bcg, mycobacterium tuberculosis and mycobacterium leprae) and a fungus ( ...19958599058
analysis of the immunological humoral response to mycobacterium tuberculosis glycolipid antigens (dat, pgltb1) for diagnosis of tuberculosis in hiv-seropositive and -seronegative patients.using an enzyme immunoassay (eia) test, the concentrations of igg antibodies against 2,3 diacyl trehalose (dat) and phenolic glycolipid tb1 (pgltb1) were measured in the sera of 153 patients with active tuberculosis, 50 of whom were coinfected with hiv, and in the sera of 152 healthy blood donors, 149 asymptomatic hiv-seropositive patients, 12 hiv-seronegative patients with conditions simulating tuberculosis, 23 hiv-seropositive patients with disseminated infection caused by mycobacteria other t ...19958605902
humoral immunity in hansen's disease.for many years immune response in leprosy has been studied. since 1960 several reports dealing with humoral immunity have been described in the literature. different autoantibody rates occur in leprosy. there is an increase in the prevalence of autoantibodies in elderly patients with long standing disease, in lepromatous leprosy and in those with reactional states. the differences in rates among various studies are attributed to different methods and variations among patient samples concerning a ...19958729870
immunohistochemical study of cutaneous neuritis in positive lepromin reactions.sixty skin biopsies taken from positive tuberculoid and borderline-tuberculoid late lepromin reaction were studied using histological techniques. the distribution of mycobacterial antigen and nerves was demonstrated using immunochemical methods. a total of 557 nerve bundles was observed in 51 biopsies; 9 were devoid of nerves in the sections examined; 475 nerve bundles showed some relationship to the inflammatory infiltrate (85%); perineuritis being seen in 144 (30%) and endoneuritis in 5 (0.9%) ...19958637381
extended studies on the viability of mycobacterium leprae outside the human body.very little is known in leprosy regarding the transmission of the infection from the source to the susceptible host. one of the important factors which governs the transmission of the disease is the viability of mycobacterium leprae outside the human body. in this study m. leprae obtained from untreated patients have been subjected to several adverse conditions. their viability was verified by their multiplication in the footpads of normal mice. after drying in the shade the organisms were viabl ...19958637382
detection of iga anti-pgl-i specific antigen to mycobacterium leprae in mangabey monkeys inoculated with m. leprae.using sera from 4 pairs of mangabey monkeys inoculated with titrated doses of mycobacterium leprae we demonstrated that iga antibodies against m. leprae specific pgl-i antigen were present in 75% of inoculated monkey's sera. high iga antibody was detected in 50% (3/6) of infected animals and all three developed lepromatous leprosy (ll). antibody titers correlated with pgl-i antigen in serum. the highest iga peak appeared late and corresponded to the beginning of treatment, and in two of them app ...19958637383
cd4+ t-cell responses to recombinant hsp65 and hsp18 of m. leprae and their trypsin-digested fragments in leprosy: diversity in hla-dr restriction.mycobacterium leprae heat-shock proteins hsp65 and hsp18 have received immense attention as major t-cell target antigens in leprosy. both of these hsps and their tryptic fragments were characterized for their ability to stimulate cd4+ t cells derived from polar leprosy cases and healthy contacts. the optimal digestion of hsps with trypsin yielded four fragments of hsp65--tdb65-1 (24 kda), tdb65-2 (18 kda), tdb65-3 (17 kda), tdb65-4 (14 kda)-- and three of hsp18--tdb18-1 (10 kda), tdb18-2 (5 kda) ...19958642214
study on the roles of cd4+ and cd8+ t cells in the expression of host resistance to mycobacterium leprae infection induced in athymic nude mice.the contribution of cd4+ or cd8+ t cells in the host resistance to mycobacterium leprae was investigated. athymic balb/c nude mice were infected subcutaneously with m. leprae into the foot pads 1 or 3 weeks after adoptive transfer with whole, cd4 t cell-depleted, or cd8 t cell-depleted lymphocyte fractions prepared from spleen cells (spcs) of euthymic balb/c mice. spcs from all of the recipient mice showed nearly the same levels of proliferative responses to phytohemagglutinin (pha) and lipopoly ...19958642217
immune response of armadillos (dasypus novemcinctus). i. use of lectins to identify lymphocyte subpopulations and to evaluate cell proliferation.lectins have been used to study populations and discrete differentiation stages of lymphocytes. likewise, lectins have been of practical importance in promoting mitogenic stimulation of lymphocytes in numerous species. in this research project, we took advantage of these tools in an attempt to identify specific subsets of peripheral blood lymphocytes obtained from healthy nine-banded armadillos (dasypus novemcinctus). the same cell source served to evaluate mitogenic stimulation. twelve fitc-lab ...19958642218
antileprosy vaccine; an apprehension. 19958642223
regarding analysis of vaccines. 19958642226
development of a mucosal challenge test for leprosy using leprosin a.there is little information about the mucosal immune response in leprosy. we have developed a nasal provocation test with leprosin a which will be used to investigate mucosal immunity to mycobacterium leprae. initial studies were performed with increasing doses of leprosin a (1.0 pg/ml-10 micrograms/ml) to determine the optimal safe dose of leprosin a. anti-m. leprae iga antibody and normal iga concentrations were measured in the saliva of leprosy contacts and controls before and after instillat ...19958551052
[immunohistochemical study on temporal bone of autopsy cases with mycobacterium leprae infection].three temporal bones were obtained en bloc from autopsy cases with lepromatous leprosy from the middle cranial fossa side after removing the brain. after fixation with 10% formalin followed by sufficient decalcification, the specimens were embedded in paraffin en bloc and cut serially to stain every 10th section with hematoxylin and eosin (h&e) for anatomical orientation. an immunohistochemical study with anti-neurofilament, anti-mbp (myelin basic protein), anti-bcg (bacillus calmette-gue'rin) a ...19958551377
new vaccines against tuberculosis.it has proved difficult to vaccinate effectively against tuberculosis with mycobacterial components or even with whole dead mycobacteria; protection was always inferior to that obtained with the live attenuated vaccine known as bacillus calmette-guérin (bcg). we have found that this may no longer be the case. expression of the gene for a single mycobacterial antigen (mycobacterium leprae hsp65) in adult balb/c mice resulted in substantial cell-mediated protection against challenge with m. tuberc ...19958555985
protection against tuberculosis by bone marrow cells expressing mycobacterial hsp65.although mice acquire only a slight degree of protection against tuberculosis by immunization with mycobacterium leprae (m. leprae) hsp65 in incomplete freund's adjuvant, protection is substantial following immunization by injection with j774 macrophage-like tumour cells that express the protein from the mycobacterial gene via a retroviral vector. we here took the same vector, used it to transfect the gene into normal murine bone marrow cells in vitro, and then used the transfected cells to reco ...19958567015
nucleotide sequence analysis and seroreactivities of the 65k heat shock protein from mycobacterium paratuberculosis.mycobacterium paratuberculosis is the causative agent of johne's disease, a chronic enteritis in ruminants. it has also been implicated as a possible cause of crohn's disease, an inflammatory bowel disease of unknown etiology. the mycobacterial 65k heat shock proteins (hsp-65k) are among the most extensively studied mycobacterial proteins, and their immunogenic characteristics have been suggested to be the basis for autoimmunization in chronic inflammatory diseases. in this context, we isolated ...19958574825
study on nude mice inoculated with mycobacterium leprae by multiple routes.immune-deficient nude mice were inoculated with nude mouse derived mycobacterium leprae by multiple routes (intravenously, subcutaneously at the foot pads and ears). the results showed that these inoculated animals were capable of producing a great number of mycobacterium leprae to a level 10 per gram of tissue and were detected histopathologically to have heavy lepromatous lesions. the dissemination of the infection was found particularly in sites with lower body temperature. the organisms have ...19958580487
[infection and cytokine]. 19958582875
[leprosy and vaccine]. 19958582876
[heat shock protein and immunity]. 19958582878
[present and future in leprosy research]. 19958582879
[uveitis in leprosy patients].we examined 24 dermatologically cured leprosy patients with ongoing uveitis (uv+) and 22 age and type matched controls (uv-) to study the late phase leprous uv. all patients have been skin smear negative for more than 10 years. the history of chemotherapy, 5 years before and after a accomplishing bacterial negativity, was evaluated and represented by "score". it was found that anti-pgl-i and anti-lam-b antibodies were significantly higher in uv+ group compared to the controls. the mean score of ...19958582882
[intraepidermal mass of m. leprae in a case of seborrheic keratosis due to hansen's disease (lls)].a 67-year-old patient has had exanthema in the lower right limb since 51 years ago (16 years old at onset), which underwent repeated remission and recurrence. at present, he has bilateral symmetrical widespread infiltrating exanthema and asymmetrical marked neuralhypertrophy, and has been diagnosed typical lls (his father had the same disease). the exanthema recurred several years ago, and the patient is being treated for hansen's disease. he had a dark brown flat elevation with a rough surface ...19958582883
cloning and expression of the mycobacterium fortuitum superoxide dismutase gene.in this paper we report the cloning, sequencing and expression of the superoxide dismutase (sod) gene from mycobacterium fortuitum. a single gene was found to code for superoxide dismutase activity with its identity being confirmed by expression in m. aurum. the amino acid sequence was found to be similar to that of superoxide dismutases of several other origins. a region downstream of the sod gene also showed similarities to the corresponding sequences of the two main mycobacterial pathogens: m ...19958586279
the contribution of slippage-like processes to genome evolution.simple sequences present in long (> 30 kb) sequences representative of the single-copy genome of five species (homo sapiens, caenorhabditis elegans, saccharomyces cerevisiae, e. coli, and mycobacterium leprae) have been analyzed. a close relationship was observed between genome size and the overall level of sequence repetition. this suggested that the incorporation of simple sequences had accompanied increases of genome size during evolution. densities of simple sequence motifs were higher in no ...19958587102
[the problem of resistance in the treatment of mycobacterium infections: new experimental results and combinations for the treatment of tuberculosis and leprosy]. 19958592712
in vitro activity of levofloxacin, singly and in combination with rifamycin analogs, against mycobacterium leprae.the in vitro susceptibility of mycobacterium leprae to levofloxacin was studied by using two biochemical parameters to measure the metabolic activity of the organism. levofloxacin consistently exhibited twofold greater bactericidal activity than ofloxacin, with the mic being 0.75 microgram/ml. when combined with one of the three rifamycin analogs, synergism was obtained with krm-1648 and rifabutin but not with rifampin.19958540726
leprosy. 19958521365
leprosy in five human immunodeficiency virus-infected patients.we present five cases of leprosy in five human immunodeficiency virus-positive individuals. the patients were five men between the ages of 18 and 45 years. the five patients presented with skin lesions; three patients with hypopigmented skin lesions, one with skin macules and a history of leprosy, and one with papular lesions. in one patient, there was bilateral "claw hands." histologically, two cases were categorized as lepromatous leprosy, two as borderline tuberculoid, and one as borderline l ...19958532702
arylsulphatase from alteromonas carrageenovora.arylsulphatase activity was identified in cultures of the marine bacterium alteromonas carrageenovora, using methylumbelliferyl sulphate as substrate. in contrast with most other microbial arylsulphatases, arylsulphatase production in a. carrageenovora was not repressed by sulphate. the structural gene of arylsulphatase (atsa) was cloned and sequenced. an orf of 984 bp was found, specifying a primary translation product of 328 amino acids with a molecular mass of 35797 da. arylsulphatase was par ...19958535517
evaluation of the mycobacterium leprae particle agglutination (mlpa) test as a tool in the epidemiology of leprosy in high prevalence village in south sulawesi, indonesia.this study reports on the usefulness of an igm phenolic glycolipid-1 (pgl-1) mycobacterium leprae particle agglutination (mlpa) test for serodiagnosis of leprosy in a prospective longitudinal community survey in a high prevalence village in south sulawesi, indonesia, igm pgl-1 mlpa has simple and limited value as a screening method for detection of transmission of leprosy in the community. many normal persons in the community in a high prevalence area had increased igm anti pgl-1 antibodies, pre ...19959139365
il12 and the human immune response to mycobacteria. 19958839157
effect of t-cell depletion on bacterial multiplication and pattern of nerve damage in m. leprae-infected mice.various mechanisms for nerve damage in tuberculoid leprosy have been proposed. a common feature amongst them is the crucial role played by t-cells. therefore, the present study was designed to determine the role of t-cells in the induction of nerve damage in leprosy using two different protocols for obtaining graded levels of t-cell depletion: (i) cyclosporine a, for depletion of t-helper cells and (ii) anti thy 1.2, for total depletion of t-cells. the findings indicate that the early changes se ...19958849913
in vivo activities of novel benzoxazinorifamycins against mycobacterium leprae.among the four newly synthesized benzoxazinorifamycin derivatives, krm-1648 and krm-2312 completely inhibited the multiplication of rifampicin-sensitive as well as rifampicin-resistant strains of m. leprae in the foot-pads of mice. both were found to be more potent than rifampicin and were bactericidal. in combination with ofloxacin, another potent bactericidal drug against m. leprae, both krm-1648 and krm-2312 exhibited synergism. thus, combination of one of these benzoxazinorifamycin derivativ ...19958849914
viability of mycobacterium leprae in lepromatous patients after five years of dapsone monotherapy supplemented with two years of multidrug therapy.eleven lepromatous leprosy (ll) patients with a bacterial index (bi) of three and above who had undergone two years of multidrug therapy (mdt) and yet had positive skin smears at the end of treatment were chosen for this study. biopsies from the skin and lymphnodes were histopathologically evaluated for the presence of granulomas and m. leprae. m. leprae isolated from the skin and lymphnodes were inoculated into the foot-pads of normal mice to test their viability. on histopathological examinati ...19958849919
staining of m.leprae by carbol-fuchsin prepared in different solvents. 19958849925
clonal dominance and selection for similar complementarity determining region 3 motifs among t lymphocytes responding to the hla-dr3-associated mycobacterium leprae heat shock protein 65-kd peptide 3-13.in order to establish whether specific mhc class ii-peptide complexes are capable of selecting tcr v regions, we investigated in detail the tcr beta chain used in the recognition of hla-dr3 restricted hsp65 peptide 3-13 in a tuberculoid leprosy patient. using rt-pcr, a clear dominance of the tcrbv5 gene family was observed in a hsp65 peptide 3-13-specific t-cell line; however, not in fresh, unstimulated pbmcs, pha-stimulated pbmcs, or a t-cell line specific for tetanus toxoid. dna sequence analy ...19958770635
cd26 expression in leprosy and other granulomatous diseases correlates with the production of interferon-gamma.leprosy represents a spectrum of clinical manifestations that reflect the immune response to antigens of mycobacterium leprae. the tuberculoid form of leprosy, which is characterized by an organized development of granulomas, has recently been correlated with a th1-like immune response. the lepromatous form of leprosy, with a characteristic lack of cellular immunity, has been correlated with a th2-like immune response to mycobacterial antigens. dipeptidylpeptidase iv (cd26) is an ectopeptidase t ...19957474942
characterization of the gene encoding the immunodominant 35 kda protein of mycobacterium leprae.analysis of the interaction between the host immune system and the intracellular parasite mycobacterium leprae has identified a 35 kda protein as a dominant antigen. the native 35 kda protein was purified from the membrane fraction of m. leprae and termed mmpi (major membrane protein i). as the purified protein was not amenable to n-terminal sequencing, partial proteolysis was used to establish the sequences of 21 peptides. a fragment of the 35 kda protein-encoding gene was amplified by the poly ...19957476185
the mycobacterium leprae genome: systematic sequence analysis identifies key catabolic enzymes, atp-dependent transport systems and a novel pola locus associated with genomic variability.in the framework of the mycobacterial genome sequencing project, a continuous 37,049 bp sequence from the mycobacterium leprae chromosome has been determined. computer analysis revealed 10 complete open reading frames, and nine of their products show similarity to known proteins. seven of these were identified as the enzyme isocitrate lyase, two p-type atpase cation transporters, two amp-binding proteins, the ribosomal protein s1, and dna polymerase i. interestingly, the pola gene, encoding dna ...19957476188
unique gene organization of thioredoxin and thioredoxin reductase in mycobacterium leprae.the thioredoxin system comprising thioredoxin (trx), thioredoxin reductase (tr) and nadph operates via redox-active disulphides and provides electrons for a wide variety of different metabolic processes in prokaryotic and eukaryotic cells. thioredoxin is also a general protein disulphide reductase involved in redox regulation. in bacteria, the trx and tr proteins previously identified were encoded by separate genes (trxa and trxb). in this study, we report a novel genomic organization of tr and ...19957476189
[assessment of the mitsuda reaction in lepromatous patients inactive before and after immunotherapy].in this study the immunopotentiator levamisole as well as a mixture of bcg/mycobacterium leprae were investigated in inactive lepromatous leprosy patients by using the mitsuda reaction as a parameter. twenty lepromatous patients ten years ago classified as histologically negative for mitsuda's test were divided into three groups: five patients that were only retested with mitsuda antigen; eight patients that received oral levamisol and seven patients that received a mixture of alive bcg plus aut ...19957480918
cross-recognition by t cells of an epitope shared by two unrelated mycobacterial antigens.the molecular mimicry represented by cross-recognition of determinants shared by unrelated antigens by antibodies or t cells is of broad immunological interest. in this study, we analyzed the cross-recognition by cd4+ t cells of a peptide epitope shared by two mycobacterial proteins of diverse sequence, represented by the 19-kda antigen of mycobacterium tuberculosis and the 28-kda antigen of mycobacterium leprae. this epitope was immunodominant with respect to the 19-kda antigen, but cryptic in ...19957489760
genomic organization of the mycobacterial sigma gene cluster.we have previously described sigma a and sigma b and their structural genes, mysa and mysb, respectively, in mycobacterium smegmatis. we have now sequenced the corresponding regions in the m. tuberculosis and m. leprae chromosomes, and have found the two homologous genes. the chromosomal linkage and the deduced amino acid (aa) sequences of the two genes show very high similarity in the three species of mycobacteria. we also report the finding of two other open reading frames (orf) in these clust ...19957489918
the 65 kda protein of mycobacterium habana and its putative role in immunity against experimental tuberculosis.mycobacteria including mycobacterium tuberculosis and mycobacterium leprae possess multiple antigens some of which inhibit other anti-mycobacterial immune responses. whole cell vaccines are not free from these suppressive molecules and may adversely affect the immunogenic response(s). purified protein components having only immunogenic properties should prove to be superior vaccine(s). mycobacterium habana, a candidate vaccine for mycobacterial infections has been dissected for analysing its ant ...19957493776
characterization of the mycobacterium tuberculosis erp gene encoding a potential cell surface protein with repetitive structures.using the phoa gene fusion methodology adapted to mycobacteria, several mycobacterium tuberculosis dna fragments encoding exported proteins were recently identified. in this paper, the molecular cloning, genomic positioning, nucleotide sequence determination and transcriptional start site mapping of a new m. tuberculosis gene, identified by this methodology, are reported. this gene was called erp (for exported repetitive protein) and has a sequence similar to that of the mycobacterium leprae 28 ...19957496523
naturally processed peptides from rheumatoid arthritis associated and non-associated hla-dr alleles.naturally processed peptides from immunoaffinity-purified hla-drb1*0401, -drb1*0404 (rheumatoid arthritis (ra)-associated), and -drb1*0402 (non-ra-associated) molecules were analyzed by capillary liquid chromatography and mass spectrometry. the molecular weights observed for more than 60 eluted peptides from each hla-dr protein ranged from 788 to 3535 atomic mass units, corresponding to peptides 7 to 32 amino acids in length. sequencing of more than 60 of the abundant peptides revealed nested se ...19957499850
role of reactive oxygen species in renal damage in experimental leprosy.renal involvement is known to occur in leprosy. in the present study the possible role of reactive oxygen species (ros) in causation of renal damage in mice infected with mycobacterium leprae has been investigated. at least six animals from each group (control and infected) were killed at 0 day, 3, 6 and 9 months postinfection. the results showed a significant increase in the chemiluminescence (cl) response of peritoneal macrophages which was maximum between 3 and 6 months. no significant increa ...19957500814
relapse with multibacillary leprosy caused by rifampicin sensitive organisms following paucibacillary multidrug therapy.many leprosy patients treated with multidrug therapy (mdt) had previously received dapsone (dds) monotherapy for many years. we report here 2 such patients treated with modified paucibacillary mdt composed of rifampicin and dds who subsequently relapsed with multibacillary leprosy 5 and 6 years after release from treatment. isolates of mycobacterium leprae from both patients were resistant to dds but sensitive to rifampicin, suggesting that the relapses were caused by rifampicin sensitive 'persi ...19957500815
sustained t-cell reactivity to mycobacterium tuberculosis specific antigens in 'split-anergic' leprosy.split anergy represented by delayed-type hypersensitivity skin reaction to tuberculin, but not to leprosin, is known to occur in a distinct proportion of leprosy patients. the mechanism was originally attributed to mycobacterium leprae-specific suppression of t cells toward common mycobacterial antigens. this study ascertained an alternative explanation, attributing the phenomenon to selective responsiveness to m. tuberculosis-specific epitopes. indeed, the results of blood t-cell proliferative ...19957537350
recognition of mycobacterium leprae recombinant 18,000 mw epitopes by igg subclasses in leprosy.igg subclasses are known to be differentially regulated by cytokines (elaborated by activated t cells), which act as growth factors and immunoglobulin switch factors on b cells. in leprosy, we have previously shown that igg subclass antibodies to a purified recombinant antigen of mycobacterium leprae (18,000 mw) are restricted to igg1 and igg3 across the disease spectrum. the only significant difference observed was that lepromatous patients with low to undetectable t-cell responses showed a str ...19957538491
[biological properties of m. leprae passaged in laboratory animals]. 19957539910
cd1-restricted t cell recognition of microbial lipoglycan antigens.it has long been the paradigm that t cells recognize peptide antigens presented by major histocompatibility complex (mhc) molecules. however, nonpeptide antigens can be presented to t cells by human cd1b molecules, which are not encoded by the mhc. a major class of microbial antigens associated with pathogenicity are lipoglycans. it is shown here that human cd1b presents the defined mycobacterial lipoglycan lipoarabinomannan (lam) to alpha beta t cell receptor-bearing lymphocytes. presentation o ...19957542404
detection of antibodies against phenolic glycolipid-1 (pgl-1), 35-kda and 30-40-kda components of mycobacterium leprae in the cerebrospinal fluid of of leprosy patients.the involvement of the central nervous system (cns) in lepromatous leprosy (ll) patients was investigated; 33 patients were examined clinically in detail and upper motor neuron involvement was observed in eight and lower motor neuron in three of these patients. anti-mycobacterium leprae antibodies could be detected in the csf by pgl-1 enzyme-linked immunosorbent assay (elisa) and monoclonal antibody (mab) based competitive assays against defined epitopes on the 35-kda protein and 30-40-kda polys ...19957543155
a putative fad-binding domain in a distinct group of oxidases including a protein involved in plant development.using methods for database screening with individual protein sequences and alignment blocks, a conserved domain is delineated in a group of proteins including several fad-dependent oxidases. two motifs within this domain resemble phosphate-binding loops and may be directly involved in fad binding. these motifs can be readily distinguished from previously described nucleotide-binding sites using a method for database screening with position-dependent weight matrices derived from alignment blocks. ...19957549889
activity of mycobacterial promoters during intracellular and extracellular growth.pus933, a bifunctional mycobacterium-escherichia coli translational fusion vector containing an amino-terminally truncated e. coli lacz reporter gene, was constructed. derivatives of pus933, containing the promoter, rbs and start codon of the mycobacterium bovis bcg hsp60 gene, the mycobacterium leprae 28 kda gene and the m. leprae 18 kda gene were constructed and introduced into e. coli, mycobacterium smegmatis and m. bovis bcg. beta-galactosidase activity was measured for mycobacteria grown in ...19957551043
a 46 kda integral membrane protein from mycobacterium leprae resembles a number of bacterial and mammalian membrane transport proteins.in this paper we describe the nucleotide sequence of a 3.4 kbp region of the mycobacterium leprae genome. this region contains an open reading frame of 1290 bp with a coding capacity for a protein of 46,179 da, designated the 38l protein. using antibodies against part of the 38l protein, we were able to demonstrate that the 38l protein is present in the membrane protein fraction of m. leprae. the 38l protein showed significant matches with a number of integral membrane proteins involved in the t ...19957551058
t cell clones from a non-leprosy exposed subject recognize the mycobacterium leprae 18-kd protein.although mycobacterium leprae shares many protein antigens with other mycobacterial species, there is a degree of specificity in the t cell response to the organism. this is evident in the failure of cross-protection between mycobacterial species and the specific unresponsiveness to m. leprae in lepromatous leprosy patients. the antigenic basis of this specificity is unresolved, but the m. leprae 18-kd protein is one candidate because of its restricted distribution and the isolation of m. leprae ...19957554400
distribution and persistence of mycobacterium leprae nasal carriage among a population in which leprosy is endemic in indonesia.in order to understand better the relationship among mycobacterium leprae, its transmission and the human host or the chain of infection which may lead to the development of leprosy, we performed a population survey in which nasal carriage of m. leprae was determined by a specific polymerase chain reaction (pcr), 2 years after an earlier survey in the same population. 1923 persons were registered, 1171 were clinically examined for signs of leprosy, and 418 were tested by pcr. the detection rate ...19957570870
immunoaffinity chromatographic isolation of a high molecular weight seroreactive protein from mycobacterium leprae cell sonicate.the purpose of this study was to isolate mycobacterium leprae antigen(s) by immunoaffinity chromatography using immunoglobulins from leprosy patients and from rabbit anti-m. leprae hyperimmune serum coupled to cnbr-sepharose 4b. a high molecular weight (m(r)) m. leprae protein (mlp) with a subunit m(r) of 22,000 was isolated. mlp was recognized by monoclonal antibody mmpii1g4 which is known to react with mmpii, a 22 kda protein of m. leprae. the n-terminal sequence of the 22 kda subunit (met-gln ...19957581267
local comparison of the genomes of mycobacterium tuberculosis and mycobacterium leprae using the polymerase chain reaction.to facilitate comparison of the genome maps of mycobacterium tuberculosis and m. leprae, sequence data from the m. leprae sequencing project were used to design primers suitable for the amplification of short segments from conserved genes by the polymerase chain reaction. in most cases, both organisms yielded products of identical size that were then used as probes for a comparative genomic walk. the hybridization data often, but not always, revealed a similar organization of various regions of ...19957590183
cloning and sequence analysis of the gene encoding the dna polymerase i from mycobacterium tuberculosis.the pola gene (encoding dna polymerase i) from mycobacterium tuberculosis was cloned using an internal gene segment probe generated by pcr amplification of genomic dna [mizrahi et al., gene 136 (1993) 287-290]. the gene encodes a polypeptide 904 amino acids (aa) in length that shares 89% identity with a 911-aa homologue from mycobacterium leprae. the polypeptide has all of the primary structural elements necessary for dna polymerase and 5'-3' exonuclease activity, but lacks the motifs required f ...19957590302
glycoside-bearing liposomal delivery systems against macrophage-associated disorders involving mycobacterium leprae and mycobacterium tuberculosis.asiaticoside, a plant glycoside with rhamnose as end sugar and having microbicidal properties was tested against mycobacterium leprae and mycobacterium tuberculosis both in vivo and in vitro. as rhamnose is reported to have no tissue specificity, corchorusin d having glucose as end sugar was used for targeting with an equimolar proportion of asiaticoside in liposomal form for testing the drug value. results showed that liposomal asiaticoside had better microbicidal property against m. leprae and ...19957590855
cytokine profile of circulating t cells of leprosy patients reflects both indiscriminate and polarized t-helper subsets: t-helper phenotype is stable and uninfluenced by related antigens of mycobacterium leprae.cytokine profiles of circulating mononuclear cells were studied with the aim of delineating t-cell subsets in leprosy patients with active disease. using reverse transcriptase-polymerase chain reaction (rt-pcr) for cytokine mrna and enzyme-linked immunoassay (elisa) for the secreted products, interferon-gamma (ifn-gamma), interleukin-4 (il-4), il-6 and granulocyte-macrophage colony-stimulating factor (gm-csf) were studied. three antigens, native mycobacterium leprae, a recombinant antigen lsr/a1 ...19957590888
molecular characterization and t-cell-stimulatory capacity of mycobacterium leprae antigen t5.a mycobacterium leprae lambda gt11 clone designated t5 has previously been selected with sera from tuberculoid leprosy patients. sequence analysis of this clone revealed the presence of two overlapping open reading frames (orfs) present on the two cdna strands. the first orf codes for the serologically recognized antigen, which was fused with the lacz gene in the lambda gt11 clone. the second orf, present on the complementary strand, displays strong sequence homology with the aspartyl-trna synth ...19957591123
identification and functional characterization of thioredoxin of mycobacterium tuberculosis.we have previously described a mycobacterium tuberculosis protein designated mpt46 that was present in culture filtrates. here we report that the mpt46 protein is thioredoxin of m. tuberculosis. mpt46 is recognized by antibodies to thioredoxin (trx) of escherichia coli, and antibodies of mpt46 recognize mycobacterium leprae trx. moreover, mpt46 was shown to have enzymatic activity identical to that of trx of other species, such as its ability to reduce insulin. these findings identify mpt46 as a ...19957591163
[new technique: pcr method for diagnosis of patients with leprosy]. 19957592157
[inoculum sizes necessary for maintaining the activity of mycobacterium leprae in cell-free liquid media].evidence was presented in the previous paper that the activity of cells of mycobacterium leprae was maintained in the phosphate buffer(ph 7) containing fetal calf serum (10%) with/without glycerin (2%) for approximately 4 weeks during incubation of cells at 30 degrees c, when the inoculum having more than 3,000 pg atp was used. in the present paper, it is confirmed that the definite inoculum sizes are essential for obtaining the reproducible results that are described above, by using the inocula ...19957592160
[recent development in immunology of leprosy: roles of immunoregulatory cytokines in the establishment of immuno-unresponsiveness to m. leprae in leprosy patients]. 19957592164
cytokine responses in leprosy lesions.the clinical spectrum of leprosy reflects the diverse nature of human immune responses to mycobacterium leprae. the clinical presentations correlate with the level of cell-mediated immunity against m. leprae. cell-mediated immunity, as assessed by the mitsuda reaction, is positive in tuberculoid patients and negative in lepromatous patients. in contrast, humoral immunity, as assessed by anti-m. leprae antibodies is greatest in lepromatous patients. the inverse correlation between cell-mediated i ...19957592165
purification and functional analysis of the mycobacterium leprae thioredoxin/thioredoxin reductase hybrid protein.in mycobacterium leprae, thioredoxin and thioredoxin reductase are expressed from a single gene. this results in the expression of a hybrid protein with subunits attached to each other by a hydrophilic peptide linker. in all other organisms studied so far, thioredoxin (trx) and thioredoxin reductase (tr) are expressed as two separate proteins. this raises the question of whether the hybrid protein is enzymatically active and, if so, whether tr reduces its own trx partner or alternatively a heter ...19957592733
the biosynthesis of cyclopropanated mycolic acids in mycobacterium tuberculosis. identification and functional analysis of cmas-2.the major mycolic acid produced by mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. the gene whose product cyclopropanates the proximal double bond was cloned by homology to a putative cyclopropane synthase identified from the mycobacterium leprae genome sequencing project. this gene, named cma2, was sequenced and found to be 52% identical to cma1 (which cyclopropanates the distal double bond) and 73% identical to the gene from m. leprae. both cma genes were f ...19957592990
analysis of t-cell and b-cell responses to recombinant m. leprae antigens in leprosy patients and in healthy contacts: significant t-cell responses to antigens in m. leprae nonresponders.the recognition of a panel of recombinant mycobacterium leprae antigens by t cells and b cells from 29 borderline tuberculoid/tuberculoid (bt/tt) and 18 lepromatous leprosy (ll) patients and from 21 healthy controls (hc) in leprosy-endemic regions of ethiopia was examined. all 11 antigenic molecules tested (including m. leprae hsp 10, hsp18, hsp65 and several novel m. leprae antigens) were shown to be recognized by t cells, but clear quantitative differences existed between reactivities induced ...19957594920
immunogenic properties of the m. leprae recombinant 18-kda antigen purified from saccharomyces cerevisiae; enhancement of delayed-type hypersensitivity after gamma-irradiation.in this paper we report the purification and study of the immunogenic properties of the mycobacterium leprae 18-kda protein antigen produced and secreted by the yeast saccharomyces cerevisiae, using an expression system we recently described [biotech. lett. 16 (1994) 1241-1246]. the 18-kda protein was purified from the yeast culture media by precipitation, ion exchange chromatography (monoq) and exclusion size chromatography (sephacryl s-100). the biological properties of the recombinant protein ...19957594921
relapses during long-term follow up with drug-susceptible m. leprae among multibacillary leprosy patients treated with multidrug therapy regimens; case reports.a controlled clinical trial in highly bacilliferous multibacillary leprosy patients was initiated in 1977. we report here two cases of relapse during long-term follow up of patients 15 years after the start of treatment. the patients reported here were treated with rifampin, isoniazid, clofazimine and dapsone for the first 3 months followed by clofazimine and dapsone until 84 months in one case; the other case received the same treatment but had received dapsone alone for 60-80 months. the relap ...19957594922
electrophysiological correlates of hanseniasis.sensory nerve action potentials (snaps) and compound nerve action potentials (cnaps) were recorded from 25 normal subjects and 21 hanseniasis patients following electrical stimulation of the median nerve at the wrist. the various nerve conduction parameters from the affected nerves of the patients were compared with those from the clinically normal nerves of patients as well as data from healthy individuals. analysis of the data and clinical correlation studies indicate the suitability of amplit ...19957594923
the immunology of leprosy; unravelling an enigma. 19957594927
ultrastructural changes in m. leprae passed to laboratory animals. 19957594933
clinical and histological discrepancies in diagnosis of enl reactions classified by assessment of acute phase proteins saa and crp.sixteen out of 45 (36%) leprosy patients with clinical features of acute erythema nodosum leprosum (enl) did not show the characteristic presence of neutrophils (polymorphs) in histology of the enl lesion. the acute-phase reactants, serum amyloid a (saa) and c-reactive protein (crp) which are systemic markers of inflammation, and igm and igg antibody to mycobacterium leprae were determined in these patients in order to understand the differences in histological diagnosis. both saa and crp were e ...19957602217
identification of igm as the leprosy patient serum factor responsible for rapid sedimentation of formolized sheep erythrocytes.the serum of some leprosy patients with impaired specific cellular immunity for mycobacterium leprae causes rapid sedimentation of formolized sheep erythrocytes, a phenomenon known as the rubino reaction. the rubino factor was precipitated from positive sera by 5% (w/v) polyethylene glycol (peg), bound to a concanavalin a (cona)-sepharose column and eluted with d-mannose, and was also eluted from a mono q column, ph 8.0, with 0.4 m nacl. the rubino factor was eluted in a volume which coincided w ...19957602218
biometals in skin and sera of leprosy patients and their correlation to trace element contents of m. leprae and histological types of the disease; a comparative study with cutaneous tuberculosis.the present study has provided information on the biometal contents of killed and dried mycobacterium leprae as well as dermal granulomas induced by the invading mycobacteria in various histological types of leprosy patients. for comparison, the biometal contents of the contralateral leprosy-unaffected skin of the same patients also were measured. the study also reports changes of serum levels of the biometals in these patients which were compared with those in healthy control subjects and patie ...19957602220
activity of combinations of dapsone, rifampin, minocycline, clarithromycin, and sparfloxacin against m. leprae-infected mice.in these studies we evaluated the activity of low levels of five antimicrobials against mycobacterium leprae-infected mice when administered singly and in all possible two- and three-drug combinations. antibiotics studied were: dapsone (d) 0.0001% in the diet, rifampin (r) 20 mg/kg by gavage once monthly, minocycline (m) 0.004% in the diet, clarithromycin (c) 0.001% in the diet, and sparfloxacin (s) 5 mg/kg by gavage five times weekly. singly each agent was found bacteriostatic (d + r) or partia ...19957602221
beige mice infected with mycobacterium leprae. 19957602228
identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in mycobacterium tuberculosis.mycolic acids represent a major constituent of the mycobacterial cell wall complex, which provides the first line of defense against potentially lethal environmental conditions. slow-growing pathogenic mycobacteria such as mycobacterium tuberculosis modify their mycolic acids by cyclopropanation, whereas fast-growing saprophytic species such as mycobacterium smegmatis do not, suggesting that this modification may be associated with an increase in oxidative stress experienced by the slow-growing ...19957604045
ultraviolet radiation decreases the granulomatous response to lepromin in humans.ultraviolet radiation (uvr) modulates cellular immunity in humans and experimental animals and can interfere with immune responses against infectious agents in animal models. we used the lepromin reaction, a cell-mediated immune response to antigens of mycobacterium leprae, to determine whether uvr affects the cellular immune response to an infectious agent in humans. we selected 29 healthy, lepromin-positive contacts of leprosy patients and determined their minimal erythema dose (med) of uvr. i ...19957615981
[a microtitration variant of the latex agglutination reaction in the diagnosis of leprosy].the authors describe the preparation of antigenic diagnostic agent based on stained polyacrolein latex particles conjugated with beta-(3-aminopropyl) 3, 6-dimethylglucopiranoside (dmg), a synthetic analog of psl = 1 from m. leprae (l-pmg), and its use in the microtitration variant of latex agglutination for the serological diagnosis of lepra. the test was performed in polystyrene plates. a total of 45 blood sera of patients with lepra, 34 sera of subjects who had contacts with leper patients, an ...19957620770
immunological aspects of relapse in leprosy. 19957622933
microbiological aspects of relapse in leprosy. 19957622934
the in-vitro activities of novel benzoxazinorifamycins against mycobacterium leprae.the activities of four newly synthesized benzoxazinorifamycin derivatives, either alone or in combination with ofloxacin, against strains of mycobacterium leprae were determined by assessing their effects on two biochemical parameters of metabolic activity which served as surrogate markers for growth in vitro. krm-1648 and krm-2312 were the most active agents tested against both a rifampicin-susceptible isolate (mics of 0.05 and 0.1 mg/l respectively) and a rifampicin-resistant isolate (mics of ...19957628981
structural requirements of peptide and mhc for dr(alpha, beta 1*0401)-restricted t cell antigen recognition.we identified functionally important regions of the dr(alpha, beta 1*0401) peptide binding site and present a model of bound peptide. dr(alpha, beta 1*0401)-restricted t cell recognition and peptide binding of mycobacterium leprae (ml) peptide 38-50 and overlapping peptides from the 18-kda heat-shock protein were analyzed. ml38-50 is unusual in its restricted binding pattern, binding to only one of five dr4 subtypes and no other dr molecules tested. amino acid substitutions were introduced into ...19957636246
experimental leprosy in monkeys. ii. longitudinal serological observations in sooty mangabey monkeys.in this study, 11 smm were grouped and inoculated with differing doses of smm-origin mycobacterium leprae (ml) between 4.5 x 10(8) and 1 x 10(9) by either combined iv/ic routes or by iv or ic route alone. the combined route was the most effective in eliciting progressive, disseminated ll leprosy. in all, 6 of 7 smm inoculated by the combined routes developed leprosy requiring treatment at some point. only 1 of 4 inoculated by a single route developed persisting leprosy requiring chemotherapy. ei ...19957637522
concomitant occurrence of leprosy and tuberculosis: leprosy vaccine, a myth or reality? 19957637529
inoculation of the mycobacterium leprae into the hamster cheek pouch. 19957637530
experimental leprosy in monkeys. i. sooty mangabey monkeys: transmission, susceptibility, clinical and pathological findings.a total of 31 sooty mangabey monkeys (smm) (cercocebus torquatus atys) inoculated by various routes with differing numbers of smm-origin mycobacterium leprae (ml) and 4 smm inoculated with human-origin ml were observed for 4-12 years. smm-origin ml was more pathogenic in smm than human-origin ml. the spectrum of disease ranged from indeterminate to borderline and lepromatous in different animals. some animals developed pure neural leprosy. erythema nodosum leprosum (snl) was also observed. combi ...19957637533
evaluation of pcr mediated dna amplification in non-invasive biological specimens for subclinical detection of mycobacterium leprae.dna from mycobacterium leprae, present in non-invasive clinical samples from leprosy patients, such as nasal secretion and hair bulbs, was submitted to amplification by the polymerase chain reaction using a m. leprae-specific repetitive sequence as a target. after optimization of sample processing and of the pcr conditions, we were able to detect dna from m. leprae in both types of clinical samples, even from paucibacillary leprosy patients. the use of hair bulbs and nasal secretion as clinical ...19957640671
the potent bone-resorbing mediator of actinobacillus actinomycetemcomitans is homologous to the molecular chaperone groel.actinobacillus actinomycetemcomitans is a gram-negative bacterium implicated in the pathology of localized juvenile periodontitis, a condition involving rapid destruction of alveolar bone. we have established that gentle extraction of this bacterium in saline releases a proteinaceous fraction (which we have termed surface-associated material [sam] which has potent osteolytic activity in the murine calvarial bone resorption assay. fractionation of the sam has now revealed that activity is associa ...19957657790
t and b cell responses to mycobacterial 65-kda heat-shock protein in sheep infected with maedi visna virus.sheep infected with maedi visna virus were tested for immune reactivity to recombinant hsp65 and tuberculin ppd from mycobacteria. the results showed that both naturally and experimentally infected animals had elevated igm but not igg or iga antibodies to hsp65 from mycobacterium leprae or m. bovis. in experimentally infected animals, the elevated igm antibodies appeared in blood from about 3 to 4 weeks postinfection. increased t cell proliferative responses to hsp65 and ppd were also found in b ...19957532120
differing antibody igg isotypes in the polar forms of leprosy and cutaneous leishmaniasis characterized by antigen-specific t cell anergy.leprosy and american cutaneous leishmaniasis are tropical diseases which present a spectrum of clinical and immunological manifestations. lepromatous leprosy and diffuse cutaneous leishmaniasis are the severe, progressive polar forms of disease characterized by persistent t cell anergy. relative concentrations of antibodies belonging to the four igg isotypes have been determined in these forms of disease as well as active visceral leishmaniasis, which presents transitory t cell anergy. leishmani ...19957697923
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