RESUMO
We have examined the expression of several genes whose transcripts have increased levels in Alzheimer's disease and have found heterogeneity in these levels in different patients with this condition. The level of expression of these genes was compared to different clinical and pathological aspects of the disease. A case with markedly elevated alpha 1-antichymotrypsin mRNA levels demonstrated prominent neuronal accumulation of this protein. Many of the neurons which demonstrated alpha 1-antichymotrypsin staining did not have neurofibrillary tangles, and vice versa. This suggests that alpha 1-antichymotrypsin staining might identify a different facet of the pathology of Alzheimer's disease than does neurofibrillary tangle staining and may provide new information in the study of this condition.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Expressão Gênica , Hipocampo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Biomarcadores , Encéfalo/patologia , Feminino , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA/genética , RNA/isolamento & purificação , RNA Ribossômico 18S/biossíntese , Valores de ReferênciaAssuntos
Processamento Alternativo , Proteínas do Citoesqueleto/genética , Neoplasias Neuroepiteliomatosas/genética , Neurônios/metabolismo , Proteína da Polipose Adenomatosa do Colo , Animais , Células Cultivadas , Cerebelo/citologia , Cerebelo/metabolismo , DNA/química , DNA/genética , Análise Mutacional de DNA , Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Meduloblastoma/genética , Meduloblastoma/patologia , Mutação , Neoplasias Neuroepiteliomatosas/patologia , Neurônios/citologia , Polimorfismo Conformacional de Fita Simples , RNA/genética , RNA/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/citologia , Medula Espinal/embriologia , Medula Espinal/metabolismo , Células Tumorais CultivadasRESUMO
We have examined the expression of the major histocompatibility complex (MHC) antigens and related genes in scrapie-infected hamster brain. Both the class I and the class II MHC genes as well as the class II-associated invariant chain were found to have an increased brain expression after scrapie infection. The increased expression of the class I complex was immunohistochemically localized primarily to neurons, though some astrocytes contained much smaller amounts of the class I complex. While there is no detectable immune response to scrapie infection, the possibility that increased MHC expression affords some defense against the scrapie agent is discussed.
Assuntos
Encéfalo/imunologia , Encéfalo/microbiologia , Complexo Principal de Histocompatibilidade , Scrapie/imunologia , Animais , Cricetinae , Expressão Gênica , Genes MHC Classe I , Genes MHC da Classe II , Imuno-Histoquímica , Mesocricetus , RNA/genética , RNA/isolamento & purificação , RNA Viral/genética , RNA Viral/isolamento & purificação , Valores de ReferênciaRESUMO
Mutations in the tumor suppressor gene APC invariably lead to the development of colorectal cancer. The vast majority of these mutations are nonsense or frameshifts resulting in nonfunctional, truncated APC protein products. Eleven cyclin-dependent kinase (CDK) consensus phosphorylation sites have been identified in the frequently deleted carboxyl-terminal region of APC; loss of these phosphorylation sites by mutation could therefore compromise the ability of APC to inhibit cell growth. This report demonstrates that immunoprecipitates of full-length, but not truncated, APC protein include a mitosis-specific kinase activity in vivo. Biochemical and Western analysis of these immunoprecipitates confirms the presence of the CDK p34(cdc2). We also show that APC is a substrate for recombinant human p34(cdc2)-cyclin B1. Modification of APC by p34(cdc2) implicates phosphorylation as a mechanism for regulating APC function via a link to the cell cycle.