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1.
Cells ; 10(2)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672296

RESUMO

Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal-dominant Parkinson's disease (PD) and contribute to sporadic PD. Common genetic variation in LRRK2 modifies susceptibility to immunological disorders including Crohn's disease and leprosy. Previous studies have reported that LRRK2 is expressed in B lymphocytes and macrophages, suggesting a role for LRRK2 in immunological functions. In this study, we characterized the LRRK2 protein expression and phosphorylation using human lymphoblasts. Lipopolysaccharide (LPS), a proinflammatory agent, induced the increase of LRRK2 expression and kinase activities in human lymphoblasts in a time-dependent manner. Moreover, LPS activated the Toll-like receptor (TLR) signaling pathway, increased TRAF6/LRRK2 interaction, and elevated the phosphorylation levels of MAPK (JNK1/2, p38, and ERK1/2) and IkBα. Treatment with LRRK2 inhibitor 68 reduced LPS-induced TRAF6/LRRK2 interaction and MAPK and IkBα phosphorylation, thereby reducing TNF-α secretion. These results indicate that LRRK2 is actively involved in proinflammatory responses in human lymphoblasts, and inhibition of GTP binding by 68 results in an anti-inflammation effect against proinflammatory stimuli. These findings not only provide novel insights into the mechanisms of LRRK2-linked immune and inflammatory responses in B-cell-like lymphoblasts, but also suggest that 68 may also have potential therapeutic value for LRRK2-linked immunological disorders.


Assuntos
Guanosina Trifosfato/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Lipopolissacarídeos/farmacologia , Linfócitos/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Ativação Enzimática/efeitos dos fármacos , Células HEK293 , Humanos , Linfócitos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/metabolismo
2.
Curr Med Chem ; 20(33): 4102-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23931282

RESUMO

In the past 50 years, thalidomide has undergone a remarkable metamorphosis from a notorious drug inducing birth defects into a highly effective therapy for treating leprosy and multiple myeloma. Today, most notably, thalidomide and its analogs have shown efficacy against a wide variety of diseases, including inflammation and cancer. The mechanism underlying its teratogenicity as well as its anticancer activities has been intensively studied. This review summarizes the biological effects and therapeutic uses of thalidomide and its analogs, and the underlying mechanisms of thalidomide's action with a focus on its suppression of tumor growth.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Talidomida/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Adesão Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Talidomida/análogos & derivados , Talidomida/farmacologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-20877039

RESUMO

Onychomycosis is caused primarily by dermatophytes, candida sp and nondermatophytic moulds. Trichosporon beigelii is an inhabitant of soil and occasionally is part of the normal flora of human skin. A 38- year- old male presented with brown discolouration of both big toes since one year. Repeated KOH preparation and culture of nail scrapings and clippings yielded Trichosporon beigelii, which was identified by standard techniques.

4.
Philadelphia; F.A. Davis Company; 2 ed; 1995. xxvi,442 p. ilus, tab, graf, 26cm.(Comtemporary perspectives in rehabilitation).
Monografia em Inglês | LILACS, HANSEN, HANSENIASE, SESSP-ILSLACERVO, SES-SP | ID: biblio-1085836
6.
Indian J Lepr ; 65(2): 243-4, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8345241
11.
Indian J Lepr ; 57(4): 872-5, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-3938988

RESUMO

Both leprosy and Recklinghausen's disease (Neurofibromatosis) are diseases affecting the Schwann cells of the peripheral nerves, though both are quite different entities. Lesions of Neurofibromatosis may be mistaken for nodules of lepromatous leprosy and vice versa, but when they occur simultaneously in the same patient, this may pose difficulty in the diagnosis of leprosy. Their coexistence is only a casual one. One such case of Multiple Neurofibromatosis (VRHD) associated with Diffuse LL is reported here.


Assuntos
Hanseníase/complicações , Neurofibromatose 1/complicações , Neoplasias Cutâneas/complicações , Humanos , Hanseníase/patologia , Masculino , Pessoa de Meia-Idade , Neurofibromatose 1/patologia , Neoplasias Cutâneas/patologia
13.
Int J Lepr Other Mycobact Dis ; 49(1): 1-8, 1981 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7195878

RESUMO

The early lepromin reaction was studied clinically and histologically in 38 leprosy patients. There was a quantitative and a qualitative difference in the character of the early inflammatory response to lepromin in the different groups of leprosy patients. In tuberculoid patients, the extent and degree of inflammation and the density of lymphocytic infiltration were maximal. In the polar lepromatous group, the inflammatory reaction was far less intense, and lymphocytes were scarce or absent. An intermediate histology was noted in the borderline and indeterminate groups of patients. In 11 patients with negative clinical reactions, the histology showed moderately dense lymphocytic infiltrations. The paucity of the clinical reaction could be due to the injection and localization of the antigen in the mid- and deep dermis. The correlation between early and late lepromin reactivity, both clinically and histologically, in the polar tuberculoid group and the polar lepromatous group was good. In the borderline and indeterminate groups, only the correlation between the early and late histological reactions to lepromin was good. The relationships between the early and late clinical reactions to lepromin showed marked variation. It is suggested that the early reaction is as good an indicator of lepromin reactivity as the late reaction in all forms of leprosy but only if it is assessed histologically.


Assuntos
Antígeno de Mitsuda , Hanseníase/patologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Hanseníase/diagnóstico , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia
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