RESUMO
A 29-year-old woman with hepatitis C presented 2 years after an orthotopic liver transplant with several weeks of fevers, abdominal pain, nausea, and a painful ulcerated nodular eruption on her abdomen and lower extremities. The patient was evaluated, and her case is presented and the differential discussed.
Assuntos
Abdome/patologia , Cryptococcus neoformans/isolamento & purificação , Dermatomicoses/diagnóstico , Exantema/patologia , Perna (Membro)/patologia , Transplante de Fígado/efeitos adversos , Dor Abdominal , Adulto , Antígenos de Fungos/isolamento & purificação , Criptococose/diagnóstico , Criptococose/microbiologia , Criptococose/patologia , Cryptococcus neoformans/imunologia , Dermatomicoses/microbiologia , Dermatomicoses/patologia , Evolução Fatal , Feminino , Humanos , Pele/microbiologia , Pele/patologiaRESUMO
CpG islands frequently contain gene promoters or exons and are usually unmethylated in normal cells. Methylation of CpG islands is associated with delayed replication, condensed chromatin and inhibition of transcription initiation. The investigation of aberrant CpG-island methylation in human cancer has primarily taken a candidate gene approach, and has focused on less than 15 of the estimated 45,000 CpG islands in the genome. Here we report a global analysis of the methylation status of 1,184 unselected CpG islands in each of 98 primary human tumours using restriction landmark genomic scanning (RLGS). We estimate that an average of 600 CpG islands (range of 0 to 4,500) of the 45,000 in the genome were aberrantly methylated in the tumours, including early stage tumours. We identified patterns of CpG-island methylation that were shared within each tumour type, together with patterns and targets that displayed distinct tumour-type specificity. The expression of many of these genes was reactivated by experimental demethylation in cultured tumour cells. Thus, the methylation of particular subsets of CpG islands may have consequences for specific tumour types.
Assuntos
Metilação de DNA , Fosfatos de Dinucleosídeos/análise , Neoplasias/genética , Adenocarcinoma/genética , Sequência de Bases , Neoplasias Encefálicas/genética , Neoplasias da Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Lobular/genética , Neoplasias do Colo/genética , Fosfatos de Dinucleosídeos/genética , Feminino , Genoma Humano , Humanos , Masculino , Dados de Sequência Molecular , Mapeamento por RestriçãoRESUMO
G2A is an orphan G protein-coupled receptor (GPCR), expressed predominantly in T and B cells and homologous to a small group of GPCRs of unknown function expressed in lymphoid tissues. G2A is transcriptionally induced in response to diverse stimuli, and its ectopic expression suppresses transformation of B lymphoid precursors by BCR-ABL. G2A induces morphological transformation of NIH 3T3 fibroblasts. Microinjection of constructs encoding G2A into Swiss 3T3 fibroblasts induces actin reorganization into stress fibers that depends on RhoA, but not CDC42 or RAC. G2A elicits RhoA-dependent transcriptional activation of serum response factor. Direct evaluation of RhoA activity demonstrates elevated levels of RhoA-GTP in G2A-expressing cells. Microinjection of embryonic fibroblasts derived from various G alpha knockout mice establishes a requirement for G alpha 13 but not G alpha 12 or G alpha q/11 in G2A-induced actin rearrangement. In conclusion, G2A represents a family of GPCRs expressed in lymphocytes that may link diverse stimuli to cytoskeletal reorganization and transcriptional activation through a pathway involving G alpha 13 and RhoA.