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Sadao Imamura - One of the best experts on this subject based on the ideXlab platform.

  • appearance of γδ t cell receptor positive cells following αβ t cell receptor positive cells in the Lepromin reaction of human skin
    Immunology Letters, 1993
    Co-Authors: Mayumi Fujita, Y Miyachi, Koh Nakata, Sadao Imamura
    Abstract:

    To elucidate the involvement of human gamma delta T cell receptor (TcR)+ cells in mycobacterial infection, we examined the kinetics of these cells in skin lesions of human Lepromin reaction. The majority of CD3+ cells two days after induction of the Lepromin reaction were alpha beta TcR+, while gamma delta TcR+ cells accounted for only 4.4 +/- 1.4% of the CD3+ cells. On day 21, the incidence of gamma delta TcR+ cells was greater (16.0 +/- 2.1%), although alpha beta TcR+ cells remained the predominant population. These kinetics of alpha beta TcR+ cells and gamma delta TcR+ cells contradict the 'early response, self-surveillance' hypothesis for gamma delta TcR+ cells in mice. Most of the gamma delta TcR+ cells in this study of the Lepromin reaction were V delta 1- V delta 2+ V delta 9+, and some of them proliferated in the skin lesions, suggesting that gamma delta TcR+ cells in the lesions may respond to mycobacterial antigens and may play an active part in the Lepromin reaction. However, these gamma delta TcR+ cells were not correlated with granuloma formation, the size of necrotic areas, mycobacterial content, or the incidence of CD4+ cells and CD8+ cells.

  • immunohistochemical study of Lepromin reaction in healthy adults
    Journal of Dermatological Science, 1991
    Co-Authors: Mayumi Fujita, Yoshiki Miyachi, Shinzo Izumi, Hiroshi Ishida, Akiko Obara, Sadao Imamura
    Abstract:

    Lepromin reaction was studied with immunoperoxidase techniques using monoclonal antibodies. The skin reactions were induced by injecting Mitsuda antigen into healthy adults without a family history of leprosy. Both early (48 hours) and late (3 weeks and 2 months) reactions were examined. In the late reaction, focal collections of epithelioid cells had formed, and not only T- but also B-lymphocytes were observed around the granuloma. CD1a+ cells were also confirmed to have increased in the late reaction.

Isabela Maria Bernardes Goulart - One of the best experts on this subject based on the ideXlab platform.

  • risk benefit assessment of bacillus calmette guerin vaccination anti phenolic glycolipid i serology and mitsuda test response 10 year follow up of household contacts of leprosy patients
    Revista Da Sociedade Brasileira De Medicina Tropical, 2015
    Co-Authors: Sergio Eduardo Alonso Araujo, Luiz Ricardo Goulart, Diogo Carrijo Rodrigues De ,sousa, Marina Monteiro Figueiredo Rezende, Maraisa Resende Rosa, Danielle Cristina Dos Santos, Isabela Maria Bernardes Goulart
    Abstract:

    INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guerin (BCG) vaccine, Mitsuda test (Lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS : Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies.

  • interaction of taqi polymorphism at exon 9 of the vitamin d receptor gene with the negative Lepromin response may favor the occurrence of leprosy
    Fems Immunology and Medical Microbiology, 2006
    Co-Authors: Luiz Ricardo Goulart, Frederico Roga Rio Ferreira, Isabela Maria Bernardes Goulart
    Abstract:

    Controversies over the vitamin D receptor (VDR) acting as a susceptibility factor in Mycobacterium sp. infections may be the result of incorrect population stratification. The risk of leprosy occurrence conditioned by VDR polymorphism was investigated by stratifying the population of a highly endemic Brazilian region into negative and positive Mitsuda responses. Leprosy patients (102) and a group of healthy nonconsanguineous household contacts (68) were genotyped for the VDR TaqI polymorphism (T/t). TT and Tt genotypes were not considered to be risk factors as their odds ratios (OR) were not different from those presented by the negative Mitsuda response individuals. The combination of the tt genotype and the negative Mitsuda test provided an occurrence rate 13 times higher in leprosy patients than in controls with positive Mitsuda responses. This suggests that there is a higher risk of leprosy development when individuals carry this unfavorable combination, and demonstrates a possible synergistic role of these two variables in leprosy susceptibility via effects on cellular immunity.

  • susceptibility to leprosy may be conditioned by an interaction between the nramp1 promoter polymorphisms and the Lepromin response
    International Journal of Leprosy and Other Mycobacterial Diseases, 2004
    Co-Authors: Frederico Rogerio Ferreira, Luiz Ricardo Goulart, Heyder Diniz Silva, Isabela Maria Bernardes Goulart
    Abstract:

    Controversial results have been achieved by attempting to associate the NRAMP1 gene with Mycobacterium leprae susceptibility as well as with the Mitsuda reaction, which represents a specific immune response to M. leprae. This study evaluated this association as well as the interaction of the polymorphism (GT)(n) in the promoter region of the NRAMP1 gene with a specific immune response to M. leprae measured by the intradermal Mitsuda test in leprosy patients and in non-consanguineous household contacts. The study aimed to evaluate the association of this gene polymorphism with resistance or susceptibility to the disease, and/or with clinical forms of the disease, in a population in an endemic area served by the State Reference Center in Sanitary Dermatology and Leprosy, Federal University of Uberlandia, MG, Brazil. Leprosy patients (90) were diagnosed according to Ridley and Jopling criteria and they grouped into multibacillary (MB) and paucibacillary (PB) patients. The control group consisted of 61 non-consanguineous contacts. NRAMP1 promoter genotypes were obtained through amplification by the polymerase chain reaction (PCR) followed by the detection through the low ionic-strength single strand conformational polymorphism (LIS-SSCP) electrophoretic technique. There were no significant differences in the allelic and genotypic frequencies for alleles 2, 3, and 4 in relation to the Mitsuda test among patients and household contacts, nor between those with MB and PB forms. However, individuals with a negative Lepromin response associated with genotypes 22 and 23 presented a 7- and 8-fold greater chance of developing leprosy, respectively. Therefore, the NRAMP1 gene promoter polymorphism exhibited an interaction with the Lepromin response, suggesting that allele 2 of the NRAMP1 promoter is an independent genetic factor that predisposes cells to enable pathogen survival, probably due to its low efficiency in iron transport. However, establishment of the infection and disease development may be conditioned by other immunological and genetic factors.

Laurent Abel - One of the best experts on this subject based on the ideXlab platform.

  • granulomatous reaction to intradermal injection of Lepromin mitsuda reaction is linked to the human nramp1 gene in vietnamese leprosy sibships
    The Journal of Infectious Diseases, 2000
    Co-Authors: Alexandre Alcais, Fabio Sanchez, Nguyen Van Thuc, J Oberti, Philippe Lagrange, Erwin Schurr, Laurent Abel
    Abstract:

    The Mitsuda test, which measures the specific immune response against intradermally injected Lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative ( ) or as a categorical ( ) trait. Separate analyses among P ! .002 P= .001 healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction. Leprosy is a chronic infectious disease caused by Mycobacterium leprae, with an annual incidence of »500,000‐600,000 cases worldwide [1]. The expression of the disease results from the interactions between the leprosy bacillus and the immune system of the infected host [2]. Whereas most infected persons develop an effective immunity without disease, others present a wide spectrum of clinical manifestations correlated with the immunologic response of the patient. At one pole of this spectrum, patients with tuberculoid leprosy show well-developed specific cellular responses and low levels of antibody to M. leprae, whereas the opposite is observed for patients at the other end of the spectrum, with lepromatous (multibacillary) leprosy. The so-called Mitsuda skin reaction, which measures the granulomatous immune response to intradermally injected heatkilled leprosy bacilli (Lepromin), is an interesting indicator of

  • granulomatous reaction to intradermal injection of Lepromin mitsuda reaction is linked to the human nramp1 gene in vietnamese leprosy sibships
    The Journal of Infectious Diseases, 2000
    Co-Authors: Alexandre Alcais, Fabio Sanchez, J Oberti, Erwin Schurr, Nguyen Van Thuc, Vu Dinh Lap, P H Lagrange, Laurent Abel
    Abstract:

    The Mitsuda test, which measures the specific immune response against intradermally injected Lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.

Kunal Saha - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of single dose rom therapy plus low dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion
    International Journal of Leprosy and Other Mycobacterial Diseases, 2000
    Co-Authors: Vivek Majumder, S K Hajra, Bibhuti Saha, Surajit Kumar Biswas, Kunal Saha
    Abstract:

    L'etude recente sur le terrain, organisee par l'Organisation mondiale de la Sante, concernant le traitement de la lepre paucibacillaire (PB) avec lesion cutanee unique (LCU) par une dose unique de rifampicine associee a l'ofloxacine et al minocycline (ROM) a apporte de nouveaux espoirs chez ceux qui sont engages dans le programme d'eradication de la lepre en Inde. Encourages par ce rapport de l'OMS, nous avons entrepris une etude clinique basee sur en hopital et avons trouve que les patients hanseniens PB avec LCU etaient morphologiquement et histopathologiquement heterogenes. Le spectre hisologique des LCU s'etendait de lepre indeterminee a lepre tuberculoide (TT) en passant par des lepres borderline (BT), cette derniere etant la plus souvent rencontree chez les patient, souvent d'aspect tres actif. Quatre-vingt-dix-neuf Patients lepreux PB non traites avec LCU furent inclus dans cette etude qui avait pour but d'evaluer et de comparer l'efficacite du traitement ROM et du traitement ROM associe au vaccin Convit. Les enfants, les femmes enceintes et les patients presentant un epaississement des nerfs furent ecartes de l'etude. Tous les patients etaient negatifs a l'examen bacterioscopique mais positifs au test a le Lepromine. Les patients furent divises en deux groupes apres ajustement du statut morphologique et histologique de LCU: un groupe teste (a) incluant 60 patients et un groupe temoin (b) incluant 30 patients, Il fut administre au groupe teste une seule dose de ROM initialement et deux injections de vaccin Convit a faible dose, une a l'initiation du traitement et l'ature apres 3 mois. Le groupe temoin ne recut que la dose unique de ROM initiale. Les deux groupes furent suivis cliniquement toute les 2 semaines pendant 6 mois et leur status histologique, bacteriologique et au test a la Lepromine fut evalue au bout de 6 mois. Apres cela, ils furent suivis cliniquement tous les mois pendant une autre periode de 6 mois. Dans le groupe teste, les LCU ont disparu dans 33,3% des patients, ont regresse dans 48,3% et sont restees actives dans 18,3% des patients, tandis que les granulomes ont disparu dans 70% des cas. Seulement un patient a developpe une nevrite et chez un autre patient, il y eut rechute de la maladie apres 8 mois. En comparaison, les LCU du groupe temoin ont disparu, regresse et sont restees actives dans 13,3%, 63,3% et 23,3% des cas, respectivement, tandis que les granulomes on disparu dans 53,3% des cas. Chez les sept patients qui sont demeures en phase active de la maladie, cette derniere a montre un caractere progressif, deux d'entre eux ayant developpe des nevrites. L'amelioration clinique des patients traites par ROM associe au vaccin Convit a faible dose fut statistiquement plus importante que celle des patients traites seulement par administration unique de ROM.

  • why relapse occurs in pb leprosy patients after adequate mdt despite they are mitsuda reactive lessons form convit s experiment on bacteria clearing capacity of Lepromin induced granuloma
    International Journal of Leprosy and Other Mycobacterial Diseases, 1998
    Co-Authors: S Chaudhuri, A Mukherjee, S K Hajra, Bibhuti Saha, D Chattapadhya, B Mazumder, Kunal Saha
    Abstract:

    It is amazing how after years of scientific research and therapeutic progress many simple and basic questions about protective immunity against Mycobacterium leprae remain unanswered. Although the World Health Organization (WHO) has recommended short-term multidrug therapy (WHO/MDT) for the treatment of paucibacillary (PB) leprosy patients, from time to time several workers from different parts of the globe have reported inadequate clinical responses in a few tuberculoid and indeterminate leprosy patients following adequate WHO/MDT despite the fact that they are Mitsuda responsive. A few borderline tuberculoid patients harbor acid-fast bacilli (AFB) in their nerves for many years even though they become clinically inactive following MDT, a fact which has been ignored by many leprosy field workers. Keeping these patients in mind, we have attempted to investigate the cause of the persistence of AFB in PB cases and have looked into the question of why Mitsuda positivity in tuberculoid and indeterminate leprosy patients, as well as in healthy contacts, is not invariably a guarantee for protectivity against the leprosy bacilli. We have: a) analyzed the histological features of Lepromin-induced granulomas, b) studied the bacteria-clearing capacity of the macrophages within such granulomas, and c) studied the in vitro leukocyte migration inhibition factor released by the blood leukocytes of these subjects when M. leprae sonicates have been used as an elicitor. The results of these three tests in the three groups of subjects have been compared and led us to conclude that the bacteria-clearing capacity of the macrophages within Lepromin-induced granuloma (positive CCB test) may be taken as an indicator of the capability of elimination of leprosy bacilli and protective immunity against the disease. This important macrophage function is not invariably present in all tuberculoid and indeterminate leprosy patients or in all contacts even though they are Mitsuda responsive and are able to show a positive leukocyte migration inhibition (LMI) test. It is likely but not certain that this deficit of the macrophage is genetically predetermined and persists after completion of short-term WHO/MDT. Thus, after discontinuation of treatment slow-growing, persisting M. leprae multiply within macrophages leading to relapse.

  • immunotherapy of Lepromin negative borderline leprosy patients with low dose convit vaccine as an adjunct to multidrug therapy a six year follow up study in calcutta
    International Journal of Leprosy and Other Mycobacterial Diseases, 1997
    Co-Authors: S Chaudhury, S K Hajra, A Mukerjee, Bibhuti Saha, V Majumdar, D Chattapadhya, Kunal Saha
    Abstract:

    The present report, which describes management of Lepromin-negative borderline leprosy patients with low-dose Convit vaccine, is an extension of our earlier study on the treatment of lepromatous leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy (MDT). The test Group I, consisting of 50 Lepromin-negative, borderline leprosy patients, were given low-dose Convit vaccine plus MDT. The control group II consisted of 25 Lepromin-negative, borderline leprosy patients given BCG vaccination plus MDT and 25 Lepromin-negative, borderline leprosy patients given killed Mycobacterium leprae (human) vaccine plus MDT. The control group III consisted of 50 Lepromin-positive, borderline leprosy patients not given any immunostimulation but given only MDT. Depending upon the Lepromin unresponsiveness, the patients were given one to four inoculations of the various antileprosy vaccines and were followed up every 3 months for 2 years for clinical, bacteriological and immunological outcome. All patients belonging to the test and control groups showed clinical cure and bacteriological negativity within 2 years. However, immunologic potentiation, assessed by Lepromin testing and the leukocyte migration inhibition test (LMIT), was better in the test patients receiving low-dose Convit vaccine plus MDT than in the control patients receiving BCG vaccine plus MDT or killed M. leprae vaccine plus MDT or MDT alone. But the capacity of clearance bacteria (CCB) test from the Lepromin granuloma showed poor bacterial clearance in the test patients. However, there was no relapse during 6 years of follow up. Two mid-borderline (BB) patients had severe reversal reactions with lagophthalmos and wrist drop during immunotherapy despite being given low-dose Convit vaccine.

U Sengupta - One of the best experts on this subject based on the ideXlab platform.

  • induction of Lepromin reactivity in cured lepromatous leprosy patients impaired chemokine response dissociates protective immunity from delayed type hypersensitivity
    Microbes and Infection, 2009
    Co-Authors: Dipendra K Mitra, Beenu Joshi, Amit K Dinda, Ambak Kumar Rai, B K Girdhar, K Katoch, Maninder S Bindra, U Sengupta
    Abstract:

    Delayed Type Hypersensitivity (DTH) and protective immunity are thought to be tightly linked. Remarkable similarity exists between their cellular and immune mechanisms. However, their dissociation is also well known. Here we investigate the immunological mechanisms relevant for their dissociation in a group of non-relapsing cured lepromatous leprosy (CLL) patients. In these patients, using Lepromin reaction as a model system of DTH we report critical role of tissue chemokine response in synchronous manifestation of these linked phenomena. Results indicate elevation of the threshold of tissue chemokine induction thus dissociating DTH from protective immunity in Lepromin -ive CLL patients. We also show that the DTH anergy in these subjects is not an absolute one but depends on the strength of the stimulus. Our data provide insights into the intricate relationship between DTH and immunity and highlight the persistent presence of effector immune mechanisms involving these two pathways in apparently unresponsive lepromatous leprosy patients.

  • experience and lessons from the use of Lepromin and mycobacterium leprae specific serology
    Leprosy Review, 2000
    Co-Authors: U Sengupta
    Abstract:

    Skin testing with Lepromin, which produces a delayed-type hypersensitivity reaction, has been used in the classification of leprosy, and a good correlation has been found between immunological status and the reaction to Lepromin. In addition, the prognostic value of the Lepromin test has been demonstrated. More recently, skin testing with two soluble antigens of Mycobacterium leprae showed no difference of the mean size of the reaction between household contacts and non-contacts, indicating that these antigens are not useful for the diagnosis of leprosy. This and other evidence points to the need for a better skin test antigen capable of detecting infection of individuals by M. leprae. Whereas serological assays for antibodies against both PGL-1 and the 35 kDa antigen of M. leprae have been found to yield positive results in 90-100% of patients with lepromatous (BL/LL) leprosy, these assays fail to identify 40-60% of patients with tuberculoid (BT/TT) leprosy, because of the presence of only an insignificant level of antibody against components of M. leprae in these patients' serum, although, in many BT patients, antibody signal could be detected in the local lesions. These data indicate that there remains a need for a specific diagnostic test for leprosy.

  • Studies on Lepromin and soluble antigens of M.leprae: their classification standardization and use.
    Indian journal of leprosy, 1991
    Co-Authors: U Sengupta
    Abstract:

    Before the discovery of armadillo as a susceptible animal the source of M.leprae was limited and hence the use of Lepromin was not common in the field. In recent times, the soluble antigens of armadillo-derived M.leprae have been used extensively in the field. Although the results of the study show that these antigens do not differentiate always a susceptible form from the resistant form, they are able to segregate the polar forms of leprosy. In a given field situation the criteria for diagnosis is so stressed that leprosy is overdiagnosed and within one year of follow up nearly half the number of cases are noted as not leprosy. Hence, in such situations Lepromin reaction would be definitely a poor correlate with the type of leprosy. However, in hospital based studies the Lepromin reaction has always been and would remain useful in confirming the classification (Sengupta et al 1984). Lepromins and M.leprae soluble antigens have gone through extensive standardization procedures. As these antigens contain mostly common mycobacterial antigens along with the M.leprae-specific antigens, these antigens are unable to specifically diagnose M.leprae infection. After purification of M.leprae from infected armadillo tissue, it was expected that the soluble antigen of M.leprae would probably be as useful as tuberculin. However, this was not found to be true in case of Lepromin. Specificity for M.leprae has been noted in the epitopes (antigenic sites) on cross reacting molecules (12 kd, 18 kd, 28 kd, 35 kd, 36 kd) of mycobacteria (Ivanyi et al 1983; Watson 1989). These specific epitopes, if synthesized, could be of use as skin test antigens for determining M.leprae infection.(ABSTRACT TRUNCATED AT 250 WORDS)