Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While conducting a study to observe bone marrow cytomorphological changes in multibacillary leprosy, lipid laden macrophages as seen in sphingolipidoses were noted. The present study was planned to observe the occurrence and morphological characterization of these macrophages in various types of leprosy. Bone marrow records from 48 cases of paucibacillary and 72 cases of multibacillary leprosy were analysed. The macrophages accounting at the most for 3.5% of marrow cells were observed in 5 cases of paucibacillary and 43 cases of multibacillary leprosy with a maximum incidence being observed in patients with ENL (16/17). The lipid present in the cytoplasm of these cells could be derived from the lipid of the cell wall of Mycobacterium leprae. To the best of our knowledge, these cells have not been reported in leprosy so far.
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PMID:Lipid-laden macrophages in bone marrow of leprosy patients. 178 52

Circulating antibody levels to the phenolic glycolipid from Mycobacterium leprae and soluble M. leprae antigens were monitored before, during and following ENL episodes in 12 patients. It was observed that during ENL reaction, there was a fall in circulating antibody levels to the phenolic glycolipid but not to the soluble antigens from M. leprae. When the patients had recovered from their ENL reactions, the anti-glycolipid antibody levels usually increased again to levels similar to those observed before the ENL reaction.
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PMID:Changes in circulating antibody levels to the major phenolic glycolipid during erythema nodosum leprosum in leprosy patients. 389 38

The disintegration of Mycobacterium leprae is revealed by a study of its acid-fast component, its non-acid-fast cell walls using methenamine silver, and its BCG-positive cytoplasmic component. Solid bacilli stain by the three stain techniques used to identify these products, but the BCG component is demonstrated only with difficulty and appears granular. Degradation of M. leprae is fairly rapid in BT, BB, and BL, and clearance of bacillary products occurs almost simultaneously because of the destruction of the cell walls. However, clearance is slower in nerves and BCG-positive material persists. The breakdown of cell walls is slow in LL and their clearance is delayed, but BCG-positive material is cleared as fast as it leaks out. ENL appears to coincide with a more rapid breakdown and release of disintegration products from degenerate macrophages. The Mitsuda reaction appears as an epithelioid cell granuloma after complete degradation of M. leprae with residual BCG positive material at 30 days.
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PMID:The degradation of Mycobacterium leprae by a comparison of its staining properties. 619 26

Type 2 reactions (erythema nodosum leprosum [ENL]) are episodic, reactional states causing significant morbidity in lepromatous leprosy patients. With a view to defining the immunological differences between the stable and reactional forms of lepromatous leprosy, we determined antibody responses to LSR, a recombinant protein of Mycobacterium leprae previously described by us (S. Laal, Y.D. Sharma, H.K. Prasad, A. Murtaza, S. Singh, S. Tangri, R. S. Mishra, and I. Nath, Proc. Natl. Acad. Sci. USA 88:1054-1058, 1991), as well as to 10- to 15-mer overlapping peptides synthesized on the basis of the LSR amino acid sequence. We report here the selective recognition of B cell epitopes by sera from patients with ENL as compared with a control group with nonreactional lepromatous leprosy. Peptides 2 and 3, with the sequences GVTYEIDLTNKNAA and IDLTNKNAAKLRGD, respectively, were recognized by > 95% of sera from patients with active ENL. Peptide 3 in addition showed reactivity with sera taken from 91.6% of lepromatous leprosy patients who were apparently stable but who were recorded to have had ENL several weeks before or after the sample collection. The core sequence IDLTNKNAA common to both these peptides may be a major target of humoral responses in ENL. In addition, the RGD motif at the C terminus appeared to influence the antigenicity of peptide 3 in enzyme-linked immunosorbent assay. It would appear that humoral responses during ENL are directed to selective antigenic determinants of the leprosy bacillus. The use of such serological markers to identify lepromatous leprosy patients with a high risk for developing ENL would be of clinical and predictive value.
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PMID:Sera of leprosy patients with type 2 reactions recognize selective sequences in Mycobacterium leprae recombinant LSR protein. 750 63

The serum concentrations of lactoferrin were determined by competitive enzyme immunoassay in the sera of 38 lepromatous leprosy patients and 16 healthy volunteers. Of the 38 lepromatous patients, 25 were without any sign of reactions while 13 were suffering from ENL type of reactions. The lactoferrin levels, in both types of patients, were observed to be significantly higher (P < 0.01 and < 0.001, respectively) than in that of healthy volunteers. The rise in lactoferrin level in reactive patients was also higher (P < 0.05) when compared to those without reactions. The serum lactoferrin levels were also found to be associated with bacterial load (r = 0.414; P < 0.01) indicating that in lepromatous leprosy patients, lactoferrin may not be very effective in preventing the growth of Mycobacterium leprae. Further studies to improve the understanding of the role of elevated levels of lactoferrin in pathogenesis of lepromatous leprosy patients and in establishing its possible use in predicting the occurrence of ENL type of reactions would be worthwhile pursuing.
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PMID:Serum lactoferrin in lepromatous leprosy patients. 812 15

Although local reactions, including erythema, induration and ulcers, appeared in every patient after the injection of the combined HKML+BCG vaccine, they were accepted by the patients. There was no tendency for the local reaction to become aggravated after repeated vaccination. However, systemic reactions, mainly iridocyclitis and complaint of numbness of the fingers and toes, became quite common after the 5th vaccination and therefore significantly reduced the acceptability of vaccine by injection. It seems that repeated vaccination might activate the iridocyclitis, but the relationship between the complaint of numbness and vaccination has not been well established. Neither typical ENL nor reversal reaction had been observed throughout the trial. A significant proportion of patients converted to SMLA positivity after repeated vaccination. However, it seems the positive status was not stable as many of them reverted to negative after the following vaccination. After the 7th vaccination, the positive conversion rate to SMLA-I was 45% and to SMLA-II was 35%. After the 8th vaccination, 66.7% of patients converted to Mitsuda reaction positive, which has been confirmed by histopathological examination. Nevertheless, further follow-up is required in order to determine whether or not such conversion will be of a long duration. The reactions to SMLA-I and SMLA-II were associated but only correlated at a moderate level. Overall, the positive conversion rate to SMLA-I was significantly higher than that to SMLA-II after repeated vaccination. Neither the early reaction nor the late (Mitsuda) reaction of the lepromin test were correlated to either SMLA reaction. The repeated vaccination of HKML+BCG vaccine did not affect the weakly-positive anti-PGL-1 Mycobacterium leprae antibody level seen in the skin-smear negative lepromatous patients participating in this study.
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PMID:Pilot study to determine acceptability and ability of heat-killed Mycobacterium leprae plus BCG (HKML+BCG) vaccine to induce skin test conversion. 834 Nov 14

Immunotherapy with Mycobacterium w (M.w) vaccine was given to 45 patients with multibacillary (MB) leprosy; 41 similarly classified patients served as controls. All patients received standard multidrug therapy (MDT). Incidence, severity and frequency of type 2 (ENL) reactional episodes were monitored in both groups in a follow-up extending up to 4 years. Reactions were seen in fewer vaccinated (10/37) BL and LL patients than in the control group (12/34). A total of 20 episodes were recorded in the vaccine group as against 29 in the controls, 75% of reactions were mild in vaccinated and 51.72% were mild in the control group patients, and 3 patients in the control group had more than 3 reactional episodes. None of the vaccinated patients showed this. No additional incidence of neuritis were seen among vaccinated individuals during reactional episodes.
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PMID:Immunotherapy with Mycobacterium w vaccine decreases the incidence and severity of type 2 (ENL) reactions. 846 20

A considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the MHC. In this investigation, the association between the MHC class III complement proteins C2, BF, C4A and C4B and leprosy in a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented with lepromatous leprosy (LL), 46 of them had the immunopathological reaction of erythema nodosum (ENL), the remaining 36 were tuberculoid, borderline and indeterminate leprosy (TIBL) patients. The control group included 172 healthy individuals matched with the patients according to their ethnic and geographical origin. C2, BF, C4A and C4B allotypes were determined by standard technologies including Western blots for C2 and C4 variant alleles with monoclonal and polyclonal antibodies. Non-expressed ('silent') C4 alleles in hemizygously deficient individuals were estimated semiquantitatively on the basis of the C4A and C4B isotype ratio and by the MASC ('minimal chi-square') method. The results showed a significantly elevated presence of the non-expressed C4B allele (C4B*Q0) in the LL and ENL patient groups in comparison with the controls. The most significant difference was observed in the ENL group when compared with the controls. In addition, all patients who were homozygously C4B-deficient had ENL, and most of them had the BF*F1 allele. The comparison between LL patients with and without ENL also showed a statistically significant difference in the presence of C4B*Q0, indicating that C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4B*Q0 allele suffering from ENL was 5.3 compared with LL patients without C4B*Q0. Since immune complexes (IC) are considered to be the pathogenic cause of ENL, our findings indicate that C4B deficiency may play an important role in the abnormal immune response against Mycobacterium leprae and in the lack of IC clearance, leading to ENL reactions. Individuals with this allele seem to be at a higher risk of developing pathological immune reactivity in lepromatous leprosy.
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PMID:Association of C4B deficiency (C4B*Q0) with erythema nodosum in leprosy. 848 14

During the period 1977-1983, clinical trials of five multidrug regimens were conducted among 215 patients with previously untreated multibacillary leprosy at the Institut Marchoux, Bamako, Mali, and the Central Leprosy Teaching and Research Institute, Chingleput, South India. The trials were designed primarily to permit measurement of the proportions of persisting Mycobacterium leprae in the patients' skin lesions. In addition, the combination of the large number of patients studied, the large volume of carefully standardized data, and the employment of multidrug regimens provided a unique opportunity to measure the clinical response of patients to treatment by these regimens. Persisting M. leprae were detected in 7.8% of all specimens; the frequency did not vary with centre, regimen, or duration of treatment. The bacterial index (BI) decreased by a mean annual rate of 75%, the logarithmic biopsy index by a mean annual rate of 87%, and the logarithm10 number of acid-fast bacilli per g tissue by a mean annual rate of 69%. The rate of decrease of these measures of the numbers of M. leprae was related to the 'strength' of the regimen. Although no difference of clinical status as a function of regimen was demonstrated, a difference was observed between the two centres, probably the result of different clinical criteria employed by the responsible physicians. A change of histopathological classification in the course of the trials was recorded for 12% of the patients, most representing upgrading from LLs to BL, without relation to regimen or treatment centre. ENL was less severe for the patients treated by the maximal regimen in Chingleput, which included daily clofazimine; as expected, the majority of patients treated by this regimen were found to have maximal pigmentation. Prednisolone was evidently preferred for treatment of ENL in Chingleput, whereas thalidomide was preferred in Bamako. Fourteen cases of jaundice were observed, primarily among the patients treated by the maximal regimens, that included daily administration of rifampicin for the entire two years of the trials. Measurements of weight and blood pressure, and studies of the blood and of hepatic and urinary tract function revealed only negligible differences among regimens and between centres. In many cases, those differences that were observed were associated with ENL.
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PMID:Response to treatment by multidrug regimens in the THELEP controlled clinical drug trials. Subcommittee on Clinical Trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. 903 97

Increasing evidence has implicated TNF-alpha as a pivotal molecule involved in the systemic inflammatory manifestations of ENL, an acute inflammatory complication that may occur in the chronic course of leprosy. In the present study, the mechanism of action of pentoxifylline (PTX) as an alternative therapy for management of leprosy reactions has been evaluated. The effect of PTX on TNF-alpha production was examined in leprosy patients at the protein level and at the transcriptional level as well. Treatment of ENL patients with PTX (1200 mg daily) ameliorated the systemic symptoms and favoured the evolution of reactional leprosy lesions. Serum TNF-alpha was assayed before and during treatment with PTX in 15 patients. The increased TNF-alpha levels seen in the circulation during the reaction were dramatically reduced within 3-7 days of therapy. No significant effect on serum IL-6 was noted. In vitro TNF-alpha production was assayed upon culture stimulation with Mycobacterium leprae. A reduction of inducible TNF-alpha in peripheral blood mononuclear cells (PBMC) was seen after 1-2 weeks of in vivo administration of PTX. Furthermore, no effect of the drug on IL-10 secretion was detected in these cultures. A kinetic analysis of the expression of TNF-alpha and IL-6 mRNA at the site of leprosy lesion was performed in six reactional patients by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The amount of TNF-alpha mRNA was increased in the tissue during ENL compared with before the reaction, and decreased thereafter following treatment for reaction (either PTX or thalidomide). These data suggest that PTX inhibits TNF-alpha production in ENL patients both in vivo and in vitro, and it may be useful in the treatment of leprosy patients undergoing ENL.
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PMID:Pentoxifylline decreases in vivo and in vitro tumour necrosis factor-alpha (TNF-alpha) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL). 948 96


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