RESUMO
Three cDNA clones encoding a DQ beta and two DR beta polypeptides have been isolated and sequenced from an American black individual expressing a DR2,DQw1 haplotype. The sequences of the cDNA clones are identical to previously described DR and DQ sequences from a DR2,Dw2 cell. The differences between DQw1-associated beta chains from DR2 and DR1 haplotypes is substantial, although a DQw1-specific sequence can be identified. The identical DQ and DR beta sequences found in unrelated individuals from different racial backgrounds suggests that class II structural polymorphism within the human population will be limited.
Assuntos
DNA/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Sequência de Aminoácidos , Sequência de Bases , Genes MHC da Classe II , Antígeno HLA-DR2 , Haplótipos , Humanos , Dados de Sequência Molecular , Polimorfismo GenéticoRESUMO
While endocrine steroid hormones have been known for many years to regulate normal and malignant mammary epithelium, recent studies have led to an appreciation of polypeptide growth factors as locally-acting autocrine and paracrine effectors. In the current article we summarize what is known about growth factor regulation and action in the normal mammary gland and about perturbations of the steroid-growth factor interplay as cancer progresses. A major theme is that oncogenic activation modulates both regulation of production and function of growth factors in the mammary gland.
Assuntos
Neoplasias da Mama/etiologia , Transformação Celular Neoplásica , Substâncias de Crescimento/fisiologia , Animais , Neoplasias da Mama/genética , Divisão Celular/genética , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos , OncogenesAssuntos
Neoplasias da Mama/fisiopatologia , Aberrações Cromossômicas , Estrogênios/fisiologia , Substâncias de Crescimento/fisiologia , Neoplasias Hormônio-Dependentes/fisiopatologia , Mama/crescimento & desenvolvimento , Neoplasias da Mama/genética , Divisão Celular , Fator de Crescimento Epidérmico/fisiologia , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Neoplasias Hormônio-Dependentes/genética , Progesterona/fisiologia , Proto-Oncogenes , Fatores de Crescimento Transformadores/fisiologiaRESUMO
BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is a complex procedure, which requires appropriate sedation. The aim of this prospective, randomized, double-blind study was to compare the quality and characteristics of sedation with midazolam or propofol in patients undergoing ERCP. PATIENTS AND METHODS: A total of 32 patients undergoing ERCP were randomly allocated for sedation with propofol (n = 15) or midazolam (n = 17). Blood pressure, heart rate, and O2 saturation were monitored. Sedation was maintained at near constant levels by use of the spectral edge frequency (SEF) technique, an EEG-based method for measuring the depth of sedation. Clinical variables, patient cooperation, time to recovery, and amnesia served as outcome variables. RESULTS: There was no significant difference between the two study groups in patient characteristics. The "target SEF" was 13.6 +/- 0.7 Hz for the propofol group and 14.8 +/- 1.1 Hz for the midazolam group (n.s.). The only clinical parameter with a significant difference between the groups was the percent of time in which the heart rate deviated more than 20% from baseline for at least 2 minutes, i.e. 14.6 +/- 2.0 % for propofol and 48.2 +/- 38.0% for midazolam (P<0.01). Patient cooperation was better in the propofol group than in the midazolam group (full cooperation, 13/15 vs. 1/17, respectively; P<0.001). Patient recovery was significantly quicker in the propofol group (P<0.001). The degree of amnesia was similar in both groups; no patient in either group remembered details of the procedure. CONCLUSIONS: ERCP is better tolerated by patients sedated with propofol compared with midazolam, with a shorter recovery time and lesser hemodynamic side effects. Propofol should be considered to be the sedative drug of choice for ERCP.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Sedação Consciente/métodos , Eletroencefalografia , Hipnóticos e Sedativos , Midazolam , Propofol , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Mixed lymphocyte typing provides an exquisitely sensitive means of detecting the polymorphism of HLA class II molecules. By using this technique, the differences between divergent human populations become apparent. This study describes a DR1 haplotype commonly present in the American black population. Unlike the Northern European population in which almost all DR1 individuals are DQw1 and type as Dw1 by using mixed lymphocyte typing, approximately 50% of DR1, DQw1 positive American blacks express an undefined Dw specificity. The DR beta polypeptide encoded by a DR1,Dw-cell differs from a previously described DR1,Dw1 beta sequence by two amino acid replacements at positions 85 and 86 in the first domain. One silent nucleotide substitution has also been identified. DQ alpha and beta first domain cDNA sequences from this haplotype are identical with previously described DQ sequences from a DR1,Dw1 cell. This relatively minor change in amino acid sequence of the DR molecule appears to produce the undefined HLA-D specificity in this haplotype. The variant DR1 sequence is shared with a DR beta-chain from the DR2,DwMN2 haplotype suggesting that a gene conversion-like mechanism has generated this difference.