The pathology of early leprous neuropathy

Shetty, Vanaja; Antia, N. H.; Jacobs, Jean M.

doi:10.1016/0022-510x(88)90210-9

Cited by 65 publications

(42 citation statements)

References 16 publications

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“…Schwann cells serve as a reservoir for M. leprae after peripheral nervous system infection (7,8,10,11). To recapitulate the fate of human Schwann cells in response to long-term intracellular residence of M. leprae in vivo, we isolated adult Schwann cells from peripheral nerves from different human donors, and each isolate was purified to homogeneity by FACS sorting using mAbs against neurotrophin receptor p75 as a marker for Schwann cells (18), and further characterized (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequent to infection, M. leprae preferentially invade human nonmyelinating Schwann cells and maintain long-term intracellular bacterial survival, which eventually leads to irreversible immune-mediated peripheral nerve damage, the hallmark of leprosy (10)(11)(12)(13)(14). One key to the pathogenic potential of M. leprae survival lies in the ability of this extremely slow-growing and strictly obligate intracellular bacterium to propagate its preferred niche so that sufficient Schwann cells are available for bacterial residence, survival, and replication (7,8,13).…”

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Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli

Tapinos

Rambukkana

2005

Proc. Natl. Acad. Sci. U.S.A.

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Activation of extracellular signal-regulated kinase (Erk) 1͞2, which plays a critical role in diverse cellular processes, including cell proliferation, is known to be mediated by the canonical Rafmitogen-activated protein kinase kinase (MEK) kinase cascade. Alternative MEK-independent signaling pathways for Erk1͞2 activation in mammalian cells are not known. During our studies of human primary Schwann cell response to long-term infection of Mycobacterium leprae, the causative organism of leprosy, we identified that intracellular M. leprae activated Erk1͞2 directly by lymphoid cell kinase (p56Lck), a Src family member, by means of a PKC-dependent and MEK-independent signaling pathway. Activation of this signaling induced nuclear accumulation of cyclin D1, G 1͞S-phase progression, and continuous proliferation, but without transformation. Thus, our data reveal a previously unknown signaling mechanism of glial cell proliferation, which might play a role in dedifferentiation as well as nerve regeneration and degeneration. Our findings may also provide a potential mechanism by which an obligate intracellular bacterial pathogen like M. leprae subverts nervous system signaling to propagate its cellular niche for colonization and long-term bacterial survival.cell signaling ͉ cell cycle ͉ peripheral nerve ͉ human ͉ Mycobacterium leprae

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli

Tapinos

Rambukkana

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…However the early detection of leprous involvement of the peripheral nervous system is difficult, as even before clinical signs of leprosy are evident, there is evidence that extensive nerve damage has already taken place?, 3 As early detection of leprosy neuropathy is based on clinical sensory and motor testing, 4 , 5 a considerable amount of underlying neural damage is present at the time of diagnosis. Much of the nerve damage will be irreversible.…”

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confidence: 99%

Vasomotor reflex testing in leprosy patients, healthy contacts and controls: a cross-sectional study in Western Nepal

Wilder‐Smith

Wilder-Smith²,

Brakel³

et al. 1996

Leprosy Review

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Summary Objective: To examine test characteristics of laser Doppler vasomo tor reflex testing for leprosy and to determine the prevalence of abnormal responses in leprosy patients, healthy contacts and controls.Design and participants: Cross-sectional study including 89 leprosy patients (mean age 35 years, 74% male), 36 healthy contacts (29 years, 64% male) and 47 controls (30 years, 68% male), for a total of 172 participants.Setting: Leprosy hospital in an endemic region 200 km west of Kathmandu, Nepal.Outcome measure: Finger-tip and toe-tip vasomotor reflexes elicited by inspira tory gasp were measured using a laser-doppler flow temperature technique. Results were expressed in per cent as the maximal reduction in bloodflow from baseline.Results: For all 12 measurement sites there were highly significant (p > 0·000 1 to < 0'004) differences between the three groups tested. Leprosy patients consistently had the lowest responses and controls the highest, with healthy contacts showing intermediate values. Thresholds defined as mean bloodfiow reductions among controls minus 1·64 or minus 1·96 standard deviations provided optimal combinations of sensitivity and specificity. Using these cut-off values around 80% of leprosy patients, 50% of healthy contacts and 20% of controls had two or more abnormal reflexes (p < 0·000 1 for differences between groups).Conclusions: In endemic regions, subclinical autonomic neuropathy may be an early but detectable marker for the risk of subsequent leprosy, making early treatment and prevention of transmission possible. Prospective studies are needed to establish the predictive value of abnormal vasomotor reflexes.

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“…Even though the water temperature (45°C) is, in theory, able to stimulate warming fibers (C fibers), as well as nociceptors responsible for heat pain (Aδ and C fibers), this study revealed that the temperature range of the stimulus measured on the skin during the stimuli (34.3 to 35.8°C) is related to warming fibers (29 to 45°C) 9,13 . One can note, by relating the data collected from the present study with the temperature values recommended by the Brazilian Ministry of Health for the assessment of leprosy patients, that the test tube method can be useful in the study of thermal sensitivity, because, in skin injuries, alterations begin in the heating and cooling sensations, progressing to pain sensations (hot and cold) and then to tactile sensitivity [14][15][16][17][18][19][20][21][22][23][24][25][26] . Therefore, in endemic areas, in the investigation of injuries, the test can be useful in the disease's early diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Thermal record of the test tubes method used for small fibers assessment

Collina

Villarroel

Tierra-Criollo

2011

Arq. Neuro-Psiquiatr.

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In Brazil, the test that uses test tubes filled with cold water (25ºC) and tubes filled with water heated to a temperature of 45ºC is recommended by the Ministry of Health as a way of evaluate thermal sensitivity on the injured skin of leprosy patients. The purpose of this work was to quantify the thermal stimulation applied to the skin, as well as the temperature variation of the heated water and of the tube's outer surface during stimulation sessions. The experiment had the participation of 14 healthy volunteers (31.2±11.4 years-old), ten of which were male (33.1±13.5 years-old) and four were female (26.5±4.7 years-old). Three consecutive stimulation sessions were carried out, each of them with four stimuli. The maximum skin temperature at the end of the stimuli was measured at 35.8±0.6ºC. Such temperature values may be useful in the assessment of the loss of small fibers, which are responsible for the sensation of warmth. Key words: leprosy, thermal sensation, thermal sensory testing.Registro térmico do método dos tubos de ensaio aplicado na avaliação de fibras finas RESUMO No Brasil, o teste que utiliza tubos de ensaio preenchidos com água aquecida (45ºC) e resfriada (25ºC) é preconizado pelo Ministério da Saúde como forma de avaliar a sensibilidade térmica nas lesões de pele de pacientes com hanseníase. O objetivo deste trabalho foi quantificar o estímulo térmico na pele e a variação das temperaturas da água aquecida e da superfície externa do tubo, durante as sessões de estimulação. O experimento contou com 14 voluntários saudáveis (31,2±11,4 anos), sendo dez do gênero masculino (33,1±13,5 anos) e quatro do gênero feminino (26,5±4,7 anos). Realizaram-se três sessões seguidas de estimulação com quatro estímulos em cada sessão. A temperatura registrada na pele, ao final dos estímulos, apresentou diferenças entre as sessões, atingindo o máximo de 35,8±0,6ºC. Estes valores de temperatura podem ser úteis na avaliação da perda de fibras finas responsáveis pela sensação de aquecimento. Palavras-Chave: hanseníase, sensibilidade térmica, teste de sensibilidade térmica.

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The pathology of early leprous neuropathy

Cited by 65 publications

References 16 publications

Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli

Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK-independent and p56Lck-dependent pathway from leprosy bacilli

Vasomotor reflex testing in leprosy patients, healthy contacts and controls: a cross-sectional study in Western Nepal

Thermal record of the test tubes method used for small fibers assessment

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