RESUMO
The immune mechanisms regulating epithelial cell repair after injury remain poorly defined. We demonstrate here that lymphotoxin beta receptor (LTßR) signaling in intestinal epithelial cells promotes self-repair after mucosal damage. Using a conditional gene-targeted approach, we demonstrate that LTßR signaling in intestinal epithelial cells is essential for epithelial interleukin-23 (IL-23) production and protection against epithelial injury. We further show that epithelial-derived IL-23 promotes mucosal wound healing by inducing the IL-22-mediated proliferation and survival of epithelial cells and mucus production. Additionally, we identified CD4(-)CCR6(+)T-bet(-) RAR-related orphan receptor gamma t (RORγt)(+) lymphoid tissue inducer cells as the main producers of protective IL-22 after epithelial damage. Thus, our results reveal a novel role for LTßR signaling in epithelial cells in the regulation of intestinal epithelial cell homeostasis to limit mucosal damage.
Assuntos
Interleucina-23/biossíntese , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Receptor beta de Linfotoxina/metabolismo , Transdução de Sinais , Animais , Colite/genética , Colite/imunologia , Colite/metabolismo , Colite/patologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Expressão Gênica , Homeostase , Interleucinas/genética , Interleucinas/metabolismo , Mucosa Intestinal/patologia , Receptor beta de Linfotoxina/deficiência , Receptor beta de Linfotoxina/genética , Camundongos , Camundongos Knockout , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Cicatrização , Interleucina 22RESUMO
The article deals with materials on radiation hygienic evaluation of radiologic diagnostic departments in various medical institutions of Moscow. The studies covered work of medical staffers in X-ray examination and in contact with short-lived isotope generators. The authors outlined the examination types and stages with maximal radiation danger. Disimetric information obtained during the study helped to calculate values of equivalent, effective doses of radiation for medical personnel and maximal potential doses.
Assuntos
Pessoal de Saúde , Serviço Hospitalar de Medicina Nuclear , Exposição Ocupacional/análise , Monitoramento de Radiação/normas , Proteção Radiológica/normas , Serviço Hospitalar de Radiologia , Humanos , Moscou , Serviço Hospitalar de Medicina Nuclear/normas , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/normas , Doses de Radiação , Serviço Hospitalar de Radiologia/normasRESUMO
The article covers results and prospects of research in special industrial medicine on improving methodology of complex evaluation of work conditions in major economy branches including medical sphere workers. On the basis of ecologic epidemiologic research, remote effects of occupational and non-industrial hazards in workers and general population were studied, new technologic processes and equipment were assessed, principles for unifying methods to control chemicals in workplace air were defined, regulation methodical documents concordant with WHO, ILO and EC are specified.
Assuntos
Monitoramento Ambiental/métodos , Doenças Profissionais , Exposição Ocupacional , Ocupações/classificação , Local de Trabalho , Projetos de Pesquisa Epidemiológica , Pessoal de Saúde , Humanos , Exposição por Inalação/efeitos adversos , Exposição por Inalação/prevenção & controle , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Saúde Ocupacional , Medicina do Trabalho/métodos , Avaliação da Tecnologia Biomédica/métodos , Avaliação da Tecnologia Biomédica/normas , Local de Trabalho/classificação , Local de Trabalho/normasRESUMO
The article deals with results of epidemiologic study on evaluating the health state of workers engaged into graphite ware production, through three various parameters based on data about chronic non-occupational diseases. The authors evaluate carcinogenic risk for the population residing on various distances from the enterprise.
Assuntos
Medicina Baseada em Evidências/métodos , Grafite/efeitos adversos , Indústrias , Neoplasias/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Adulto , Carcinógenos , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Neoplasias/induzido quimicamente , Doenças Profissionais/etiologia , Fatores de Risco , Federação Russa/epidemiologiaRESUMO
The spectrum of human antigens allows a monitoring of various pathological processes such as autoimmune disorders and tumorigenesis. Serological analysis of cDNA expression libraries (SEREX) is now used to search for new cancer-associated antigens, which are potential diagnostic markers or targets for immunotherapy of cancer. The results obtained for several solid tumors are reviewed. Groups of antigens detectable by SEREX, causes of immunogenicity of autoantigens, and prospective implication of antigens in diagnostics and monitoring of cancer are discussed.
Assuntos
Antígenos de Neoplasias/sangue , Autoantígenos/sangue , Humanos , Monitorização Fisiológica , Neoplasias/diagnóstico , Neoplasias/imunologiaRESUMO
The authors compared nonspecific anti-infectious resistance among medical staffers varying in speciality. Skin microflora parameters and salivary lysozyme content appeared to be considerably lower in obstetric staffers and in State sanitary and epidemiologic supervision officers than in general population.
Assuntos
Pessoal de Saúde , Imunidade Inata , Infecções/imunologia , Muramidase/análise , Saliva/enzimologia , Pele/microbiologia , Adulto , Humanos , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Selective proteolysis is one of the mechanisms for the maintenance of cell homeostasis via rapid degradation of defective polypeptides and certain short-lived regulatory proteins. In prokaryotic cells, high-molecular-mass oligomeric ATP-dependent proteases are responsible for selective protein degradation. In eukaryotes, most polypeptides are attacked by the multicatalytic 26S proteasome, and the degradation of the majority of substrates involves their preliminary modification with the protein ubiquitin. The proteins undergoing the selective proteolysis often contain specific degradation signals necessary for their recognition by the corresponding proteases.
Assuntos
Homeostase , Proteínas/metabolismo , Animais , Cisteína Endopeptidases/metabolismo , Endopeptidases/metabolismo , Humanos , Complexos Multienzimáticos/metabolismo , Complexo de Endopeptidases do Proteassoma , Proteínas/químicaRESUMO
Conserved residues of the proteolytic domain of Escherichia coli protease Lon, putative members of the classic catalytic triad (H665, H667, D676, and D743) were identified by comparison of amino acid sequences of Lon proteases. Mutant enzymes containing substitutions D676N, D743N, H665Y, and H667Y were obtained by site-directed mutagenesis. The mutant D743N retained the adenosine triphosphate (ATP)-dependent proteolytic activity, thereby indicating that D743 does not belong to the catalytic site. Simultaneously, the mutants D676N, H665Y, and H667Y lost the capacity for hydrolysis of protein substrates. The ATPase activity of these three mutants was decreased by more than an order of magnitude, which suggests a close spatial location of the ATPase and proteolytic active sites and their tight interaction in the process of protein degradation.