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1.
Cell Death Differ ; 8(4): 367-76, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11550088

RESUMO

It has been shown that oxygen deprivation results in apoptotic cell death, and that hypoxia inducible factor 1 (HIF1) and the tumor suppressor p53 play key roles in this process. However, the molecular mechanism through which hypoxia and HIF1 induce apoptosis is not clear. Here we show that the expression of pro-apoptotic gene BNIP3 is dramatically induced by hypoxia in various cell types, including primary rat neonatal cardiomyocytes. Overexpression of HIF1alpha, but not p53, induces the expression of BNIP3. Overexpression of BNIP3 leads to a rather unusual type of apoptosis, as no cytochrome c leakage from mitochondria was detected and inhibitors of caspases were unable to prevent cell death. Taken together, these data suggest that HIF1-dependent induction of BNIP3 may play a significant role during hypoxia-induced cell death.


Assuntos
Apoptose , Hipóxia Celular , Proteínas de Membrana/biossíntese , Miocárdio/citologia , Proteínas Proto-Oncogênicas , Proteínas Supressoras de Tumor , Animais , Animais Recém-Nascidos , Caspase 3 , Caspase 9 , Caspases/fisiologia , Células Cultivadas , Células HeLa , Humanos , Proteínas de Membrana/genética , Miocárdio/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/biossíntese , Ratos , Ativação Transcricional , Transfecção , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/fisiologia
2.
J Comb Chem ; 2(6): 691-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11126297

RESUMO

A new tetrafluorophenol activated resin that facilitates the use of 19F NMR to quantitate loading is presented. This new resin provides a useful tool for acylation, and a novel activated polymeric sulfonate ester to generate sulfonamides. This activated resin reacts with a wide scope of N-nucleophiles including primary and secondary amines, and anilines. This new activated resin methodology provides a powerful tool for pure single-compound library synthesis.

3.
J Med Chem ; 39(10): 2087-94, 1996 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-8642568

RESUMO

A series of prolineboronic acid (boroPro) containing dipeptides were synthesized and assayed for their ability to inhibit the serine protease dipeptidyl peptidase IV (DPPIV). Inhibitory activity, which requires the (R)-stereoisomer of boroPro in the P1 position, appears to tolerate a variety of L-amino acids in the P2 position. Substitution at the P2 position which is not tolerated include the D-amino acids, alpha,alpha-disubstituted amino acids, and glycine. Specificity against DPPII and proline specific endopeptidase is reported. A correlation between the ability to inhibit DPPIV in cell culture and in the human mixed lymphocyte reaction is demonstrated. A synthesis of prolineboronic acid is reported as well as conditions for generating the fully unprotected boronic acid dipeptides in either their cyclic or acyclic forms.


Assuntos
Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Teste de Cultura Mista de Linfócitos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estereoisomerismo , Relação Estrutura-Atividade
4.
Neurol Neurochir Pol ; 29(4): 545-52, 1995.
Artigo em Polonês | MEDLINE | ID: mdl-8544933

RESUMO

21 patients with thoracic outlet syndrome (t.o.s.) were operated on in the Department of Neurosurgery of MMA in Lódz between 1982-1991. Early and long-term results of treatment were analyzed in the group of 13 cases. In early postoperative period 5 patients were free of pain and neurologic or vascular disturbances in the upper limb. In other 6 cases pain disappeared partially and mild neurological or vascular syndromes persisted. Altogether satisfactory results of treatment were obtained in 8 patients (85%). There was some improvement in 2 patients but pain and neurological or vascular disorders were still significant after surgery. Long-term results were assessed at least 1 year after operative treatment. Recurrent pain with or without mild neurological (vascular) syndromes appeared in 6 patients (46%). Recurrent t.o.s. occurred mainly in cases of young women with low position of shoulder girdle and poorly developed musculature of this region. Only 2 patients still remained free of preoperative syndromes. Altogether only 8 patients (61%) had acceptable results of surgical treatment at long-term follow-up. The remaining 5 patients (39%) had unsatisfactory long-term results.


Assuntos
Síndrome do Desfiladeiro Torácico/cirurgia , Braço/fisiopatologia , Feminino , Seguimentos , Humanos , Dor/etiologia , Dor/fisiopatologia , Estudos Retrospectivos , Síndrome do Desfiladeiro Torácico/complicações , Síndrome do Desfiladeiro Torácico/fisiopatologia
5.
Res Dev Disabil ; 11(3): 273-88, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-1697973

RESUMO

The purpose of this study was to assess the effects of video presentations on the acquisition of both spoken and manually signed lexical items by students with mental retardation. A 10-lesson curriculum in which lexical items were introduced and reviewed by one of three pedagogical methods (therapist only, therapist plus video, or video only) was implemented over a four week period. Pretest and posttest measures of expressive and receptive vocabulary of 35 students with mental retardation revealed that all three methods resulted in significant increases in both spoken and manual sign production of the targeted lexical items compared to control items which were not taught. The therapist only and therapist plus video methods yielded significantly higher sign production scores than the video only method. Receptive vocabulary was not significantly improved by the intervention.


Assuntos
Recursos Audiovisuais , Educação de Pessoa com Deficiência Intelectual , Transtornos do Desenvolvimento da Linguagem/terapia , Comunicação Manual , Língua de Sinais , Adolescente , Adulto , Criança , Pré-Escolar , Currículo , Feminino , Humanos , Masculino , Fonoterapia , Vocabulário
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