Identification and characterization of BPTF, a novel bromodomain transcription factor.

The bromodomain is a 110-amino-acid conserved structural region associated with proteins that regulate signal-dependent, nonbasal transcription. The bromodomain can regulate histone acetyl transferase activity and interacts specifically with acetylated lysine residues. A key role for bromodomain proteins in maintaining normal proliferation is indicated by the implication of several bromodomain proteins in cancer, with four of these identified at translocation breakpoints. We searched EST databases for novel bromodomain genes. The sequence from one EST was used to initiate generation of a full-length clone from a testis cDNA library. The completed sequence encodes a predicted protein of 2781 amino acids, which, in addition to the bromodomain, harbors further motifs characteristic of a transcriptional coactivator: two PHD fingers and an extensive glutamine-rich acidic domain. There are several other regions that are conserved with the Caenorhabditis elegans putative protein F26H11, which may be functionally homologous. The novel gene, called BPTF, is expressed in all tissues examined as a 10.5-kb transcript. The protein has extensive identity with the smaller FAC1 protein, suggesting that the two either are derived from the same locus or are synonymous. BPTF has been mapped to 17q23. Functional domains found within BPTF are consistent with a role for this protein in hormonally regulated, chromatin-mediated regulation of transcription.

A novel family of bromodomain genes.

The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. Bromodomain proteins have been identified as integral components of chromatin remodeling complexes and frequently possess histone acetyltransferase activity. Their encoding genes have been identified at translocation breakpoints, and at least one, CBP, is a tumor suppressor gene. We have identified a series of novel bromodomain genes by EST database and cDNA library screening. Comparison of sequences for four clones indicated that they represent genes belonging to a novel bromodomain family. Full-length sequences for these genes, which are widely expressed, predict encoded proteins of between 1527 and 1972 amino acids. In addition to a carboxy-terminal bromodomain, an adjacent PHD finger, and a WACZ motif, at least four other conserved novel motifs are present in each protein. The genes contain regions conserved with Drosophila Acf1 and Caenorhabditis elegans ZK783.4. The novel genes, termed BAZ1A, BAZ1B, BAZ2A, and BAZ2B, localize to chromosomes 14q12-q13, 7q11-q21, 12q24.3-qter, and 2q23-q24, respectively. Conservation of multiple domains throughout these genes with Acf1 indicates that they are likely to be components of chromatin remodeling complexes.

[Herpetic esophagitis]. / Esofagitis herpética.

Herpetic esophagitis is an infrequent ulcerative infection of the esophagus caused by Herpes Virus type I. It is usually seen in immunocompromised patients though it may present in immunocompetent ones. Odynophagia and/or dysphagia associated with chest pain are the most frequent clinical symptoms. Radiology, endoscopy, biopsy and serological markers are the basis for diagnosis. We report 3 patients with herpetic esophagitis diagnosed between 1984-1989 and evaluated the clinical, endoscopic and biopsy characteristics. Certain clinical and endoscopic findings common to our patients tend to identify the disease, with biopsy and or serological markers the diagnosis may be established.

[Alcoholic liver disease in Venezuela. Clinical hepato-functional and histopathologic course]. / Hepatopatía alcohólica en Venezuela. Comportamiento clínico, funcional hepático e histopatológico.

24 patients with alcoholic intake were classified according to the amount of alcohol ingestion; clinical symptoms and signs, liver function tests (bilirubin, aminotransferases and prothrombin time) were analyzed. In all patients a percutaneous liver biopsy was performed and tissue stained by hematoxylin-eosin, wilder reticulin and Mallory trichromic. 9 Histologic criteria were analyzed. 4 groups according to the histology were identified. Group 1 (5 patients) hepatic fibrosis and/or fatty liver. Group 2 (5 patients) alcoholic hepatitis. Group 3 (10 patients) cirrhosis. Group 4 (4 patients) normal. 20% of patients with fatty liver, 80% of alcoholic hepatitis and 100% of cirrhotics referred ingestion or more than 160 g of ethanol and important correlation between liver histological damage and alcohol ingestion. Telangiectasia was the most common clinical finding and present in all hepatitis, 70% of cirrhotics and only 20% of fatty livers. Hemosiderosis was found in 60% of cirrhotics and in alcoholic hepatitis. Only 40% of patients with fatty liver and inflammatory cells while this was evident in all patients with alcoholic hepatitis and those with cirrhosis. Mallory bodies were identified in only 20% of cirrhotics and in none of the alcoholic hepatitis. The results suggest that there are significant differences from a histological and clinical point of view that distinguish alcoholic liver disease as seen in Venezuela from that reported in other countries.

[Cytology and biopsy by fine needle aspiration with ultrasound guidance in abdominal tumors]. / Citología y biopsia por aspiración con aguja fina guiadas por ultrasonido en tumores abdominales.

To determine the value of fine needle aspiration biopsy (FNAB) we selected 53 patients with liver, pancreas and other abdominal tumors, their diagnosis was made on clinical and ultrasound grounds, we performed FNAB in all these patients. The specimens were sent for cytology and histopathology. 33 out of 53 cases were reported as liver cancer: true positives: 29, false negative 2, and true negatives: 2, for sensibility; 93% specificity: 100%. 15 cases were pancreatic cancer, true positives: 11, true negatives: 3; with 1 false negative, sensibility 91%; specificity 100%. 5 cases were tumors from other abdominal cavity locations (true positives: 3, false negatives: 2; sensibility: 60% specificity: 100%. All these results were well correlated with surgery, clinical follow up and other diagnostic methods ERCP, CT, Laparoscopy. We conclude (FNAB) has a high sensibility and specificity and should be used as a routine procedure in the study of abdominal tumors. No false positive was reported.