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1.
J Neuropathol Exp Neurol ; 60(6): 621-7, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11398838

RESUMO

In order to investigate the mechanism of Bell's palsy, we developed an animal model of facial nerve paralysis induced by the reactivation of herpes simplex virus type 1 (HSV-1). Eight weeks after recovery from facial nerve paralysis caused by inoculation with HSV-1, the mice were treated with auricular skin scratch at the site of the previous inoculation, or with intraperitoneal injection of anti-CD3 monoclonal antibody (mAb), or combination of both procedures. No mice developed facial nerve paralysis when they were treated with either auricular scratch or mAb injection alone. In contrast, 20% of mice developed facial nerve paralysis with the combined treatment. With one exception, no mouse treated with either auricular scratch or mAb injection showed HSV-I DNA in their facial nerve tissue, whereas 4 out of 6 mice receiving both treatments showed HSV-1 DNA on day 10 after treatment. Histopathological findings showed neuronal degeneration in the geniculate ganglion and demyelination of the facial motor nerve in paralyzed mice. These findings suggest that a combination of stimuli, local skin irritation, and general immunosuppression is essential for successfully inducing facial nerve paralysis in mice with latent HSV-1 infection.


Assuntos
Paralisia de Bell/virologia , Herpes Simples/virologia , Simplexvirus/fisiologia , Ativação Viral , Animais , Anticorpos Monoclonais/farmacologia , DNA Viral/análise , Modelos Animais de Doenças , Orelha Externa/lesões , Feminino , Gânglio Geniculado/patologia , Gânglio Geniculado/virologia , Herpes Simples/sangue , Herpes Simples/genética , Herpes Simples/patologia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Simplexvirus/classificação , Linfócitos T/patologia , Latência Viral
2.
Ann Neurol ; 48(2): 254-6, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10939578

RESUMO

In a retrospective study, 52 children were diagnosed with Ramsay Hunt syndrome. The facial palsy was milder and complete recovery of the function was achieved in 78.6% of patients. Associated cranial neuropathies were less common in children than in adults. The timing of vesicle appearance tended to be delayed in children. In preschool children, Ramsay Hunt syndrome was rare, although the frequency has recently increased. The syndrome is relatively common in older children. This study suggested that vaccination can prevent or reduce the occurrence of Ramsay Hunt syndrome.


Assuntos
Herpes Zoster da Orelha Externa/epidemiologia , Herpes Zoster da Orelha Externa/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Nervo Facial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos
3.
Cancer Res ; 56(8): 1817-22, 1996 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-8620498

RESUMO

Monoclonal antibody (MAb) JT-95 was produced by immunization of mice with membrane fractions of a human thyroid carcinoma. Immuno-histochemical staining has demonstrated that the antigen recognized by JT-95 is strongly expressed in 95 (95%) of 100 cases of papillary carcinomas and in 3 (75%) of 4 cases of follicular carcinomas. In benign diseases of the thyroid gland, MAb JT-95 reacted with 0 (0%) of 39 adenomas, 1 (4%) of 21 adenomatous goiters, 0 (0%) of 8 hyperthyroidism specimens, and 3 (38%) of 8 chronic thyroiditis specimens. The antigen detected by MAb JT-95 has an apparent Mr 250,000 in thyroid carcinomas. Moreover, circulating antigen in thyroid carcinoma patients was detected by MAb JT-95 in an ELISA and in Western blotting. The circulating antigen has a Mr 105,000. MAb JT-95 conjugated with (131) I was administrated to nude mice bearing a human thyroid carcinoma. JT-95 131I accumulation at the transplanted tumor was visualized by autoradiography with 2.68-14.75-fold higher levels detected at the xenograft compared to that for normal organs. Based on these data, MAb JT-95 may be useful in the diagnosis detection and therapy of thyroid carcinoma.


Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Doenças da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/patologia , Adenoma/patologia , Animais , Anticorpos Monoclonais/farmacocinética , Autorradiografia , Carcinoma Papilar/patologia , Clonagem Molecular , Ensaio de Imunoadsorção Enzimática , Bócio/patologia , Humanos , Hipertireoidismo/patologia , Imuno-Histoquímica , Radioisótopos do Iodo , Camundongos , Camundongos Endogâmicos BALB C/imunologia , Camundongos Nus , Valores de Referência , Sensibilidade e Especificidade , Distribuição Tecidual , Transplante Heterólogo
4.
Blood ; 87(5): 1990-6, 1996 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8634449

RESUMO

Treatment of human myeloid leukemia cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with induction of protein kinase activity and early-response gene expression. The present studies in ara-C-treated U-937 cells extend these findings by demonstrating activation of a protein kinase that phosphorylates myelin basic protein (MBP). Purification by sequential ion-exchange chromatography and gel filtration supports the detection of a 40-kD MBP kinase. Substrate and inhibitor studies further support a pattern similar to that of protein kinase C (PKC) isozymes. Results of N-terminal amino acid sequencing and immunoblot analysis demonstrate detection of a 40-kD catalytic fragment of PKCdelta. The results also demonstrate the activation and cleavage of PKCdelta (1) is inhibited by expression of antiapoptotic proteins, and (2) is induced by camptothecin (CAM) and mitomycin C (MMC). These findings support proteolytic activation of PKCdelta in the cellular response to ara-C and other DNA-damaging agents.


Assuntos
Citarabina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Isoenzimas/metabolismo , Leucemia Mieloide/patologia , Linfoma Difuso de Grandes Células B/patologia , Proteínas de Membrana , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteína Quinase C/metabolismo , Sequência de Aminoácidos , Apoptose/efeitos dos fármacos , Camptotecina/farmacologia , Dano ao DNA , Endopeptidases/metabolismo , Ativação Enzimática/efeitos dos fármacos , Genes jun , Humanos , Mitomicina/farmacologia , Dados de Sequência Molecular , Proteína Básica da Mielina/metabolismo , Substrato Quinase C Rico em Alanina Miristoilada , Células-Tronco Neoplásicas/enzimologia , Nucleossomos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteína Quinase C-delta , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Especificidade por Substrato , Células Tumorais Cultivadas
5.
EMBO J ; 14(24): 6148-56, 1995 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-8557034

RESUMO

These studies demonstrate that treatment of human U-937 cells with ionizing radiation (IR) is associated with activation of a cytoplasmic myelin basic protein (MBP) kinase. Characterization of the kinase by gel filtration and in-gel kinase assays support activation of a 40 kDa protein. Substrate and inhibitor studies further support the induction of protein kinase C (PKC)-like activity. The results of N-terminal amino acid sequencing of the purified protein demonstrate identity of the kinase with an internal region of PKC delta. Immunoblot analysis was used to confirm proteolytic cleavage of intact 78 kDa PKC delta in control cells to the 40 kDa C-terminal fragment after IR exposure. The finding that both IR-induced proteolytic activation of PKC delta and endonucleolytic DNA fragmentation are blocked by Bcl-2 and Bcl-xL supports an association with physiological cell death (PCD). Moreover, cleavage of PKC delta occurs adjacent to aspartic acid at a site (QDN) similar to that involved in proteolytic activation of interleukin-1 beta converting enzyme (ICE). The specific tetrapeptide ICE inhibitor (YVAD) blocked both proteolytic activation of PKC delta and internucleosomal DNA fragmentation in IR-treated cells. These findings demonstrate that PCD is associated with proteolytic activation of PKC delta by an ICE-like protease.


Assuntos
Apoptose/fisiologia , Cisteína Endopeptidases/metabolismo , Isoenzimas/metabolismo , Proteína Quinase C/metabolismo , Sequência de Aminoácidos , Apoptose/genética , Apoptose/efeitos da radiação , Sítios de Ligação , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Caspase 1 , Linhagem Celular , Cisteína Endopeptidases/genética , Dano ao DNA , Ativação Enzimática/efeitos da radiação , Quinase 3 da Glicogênio Sintase , Humanos , Isoenzimas/química , Isoenzimas/genética , Dados de Sequência Molecular , Peptídeos/química , Proteína Quinase C/química , Proteína Quinase C/genética , Proteína Quinase C-delta , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Especificidade por Substrato
6.
Mol Pharmacol ; 46(1): 67-72, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8058058

RESUMO

1-beta-D-Arabinofuranosylcytosine (ara-C) is an effective antileukemic agent that misincorporates into DNA. Recent studies have demonstrated that ara-C treatment is associated with transient induction of the c-jun early response gene. The present studies have examined the effects of ara-C on c-jun expression in a phorbol ester-resistant variant of the HL-60 myeloid leukemia cell line, designated HL-525, that is deficient in protein kinase C (PKC)-mediated signal transduction and fails to respond to 12-O-tetradecanoylphorbol-13-acetate with induction of c-jun transcripts. The results demonstrate that treatment of HL-525 cells with ara-C is associated with transcriptional activation of the c-jun gene. We also demonstrate that ara-C treatment is associated with activation of a PKC-like activity. Partial purification of this Ca(2+)-independent activity has demonstrated phosphorylation of synthetic peptides derived from (a) amino acids 4-14 of myelin basic protein and (b) the pseudosubstrate region of PKC (amino acids 19-31), with substitution of Ala25 with serine. The finding that the ara-C-induced activity is inhibited by the pseudosubstrate PKC(19-36) supports the activation of a PKC-like enzyme. Because PKC can act upstream of the mitogen-activated protein (MAP) kinases, we studied the effects of ara-C treatment on MAP kinase activity. The results demonstrate that MAP kinase is activated in ara-C-treated cells and that the kinetics of this activation are similar to those of the PKC-like activity. Because 12-O-tetradecanoylphorbol-13-acetate has little, if any, effect on the PKC-like and MAP kinase activities in HL-525 cells, these findings suggest that ara-C activates a distinct signaling cascade that may contribute to induction of the c-jun gene.


Assuntos
Citarabina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Genes jun , Leucemia Mieloide/enzimologia , Leucemia Mieloide/genética , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Resistência a Medicamentos , Ativação Enzimática , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Células Tumorais Cultivadas
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