The REV1 protein is a member of the growing family of translesion DNA polymerases. A cDNA of the human REV1 gene that we had originally isolated encoded 1250 amino acids residues, which was one amino acid shorter than previously reported ones. The shorter form of REV1 was named REV1S. All individuals examined expressed equivalent amounts of REV1S and REV1 mRNA, suggesting that the REV1S mRNA is a splicing variant. We show that the REV1S protein also possesses deoxycytidyl transferase activity that inserts a dCMP opposite a DNA template apurinic/apyrimidinic site. Deletion and point mutation analysis of the REV1S protein revealed that the domain required for deoxycytidyl transferase and DNA binding activities of the REV1S protein are located in a conserved domain of translesion DNA polymerases. This result indicates that the structure of the catalytic site of the deoxycytidyl transferase closely resembles that of the translesion DNA polymerases. Therefore, the molecular mechanism of the dCMP transfer reaction of the REV1S protein and maybe also the REV1 protein might be the same as that of the dNTP transfer reaction of the translesion DNA polymerases.In yeast Saccharomyces cerevisiae, almost all induced mutations arise during translesion replication, a process that promotes elongation past sites of unrepaired lesions (1). The mutagenesis pathway (rev) mutants were initially isolated by their reduced mutations after UV treatment (2). The REV1, REV3, and REV7 genes are required for the major pathway for translesion replication in yeast (3-6). The REV1 gene encodes a deoxycytidyl transferase that incorporates dCMP opposite apurinic/apyrimidinic (AP) 1 sites in the template (7). The REV3 and REV7 genes encode a translesion DNA polymerase, pol (8, 9), which works together with the REV1 protein for translesion replication (7). Recently, the human orthologues of REV1 (10, 11), REV3 (12, 13), and REV7 (14) have been identified. It has been shown that the human REV1 protein possesses a deoxycytidyl transferase activity (10) and that the human REV1 and REV3 genes are required for mutagenesis induced by UV light in humans (11,12).The REV1 gene is a member of a growing family including umuC (15) (18,(23)(24)(25)(26)(27)(28)(29). However, the REV1 protein does not possess such polymerase activity although it contains the conserved domain in translesion polymerases.In this work, we made various mutants of the human REV1S protein. Biochemical analysis of those mutant proteins showed that the domain required for deoxycytidyl transferase activity and DNA binding is located in a conserved domain of translesion DNA polymerases. EXPERIMENTAL PROCEDURES Isolation of Human REV1 cDNAWe found a partial sequence of a candidate of the human REV1 cDNA in a data base (accession number AJ131720). Based on the sequence, a portion of the cDNA fragment of the human REV1 was amplified by RT-PCR from human breast cancer using primers 5Ј-AA-TCTAGCTGGAGCTGTTGA-3Ј and 5Ј-GTAAAACCACCTGGACATTG-3Ј, and it was used as a probe for screening a human testi...
Most cases of intramural haematoma are acute aortic dissections with an intimal tear without re-entry. Intramural haematoma should be referred to as thrombosed-type acute aortic dissection. Thrombosed type can be easily diagnosed on contrast-enhanced computed tomography and has features distinct from those of classic dissection. Our classification may be useful for the diagnosis of these types of aortic dissection.
Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.
Background and study aims Few studies have evaluated detection of pancreatic carcinoma in situ (PCIS). We evaluated findings of endoscopic ultrasound (EUS) and pathological features of PCIS. Patients and methods We histopathologically studied 16 patients with PCIS following EUS. Diagnostic features evaluated retrospectively included stricture of the main pancreatic duct (MPD) on EUS, presence or absence of hypoechoic areas surrounding the MPD stricture on EUS, the noncancerous part (pancreas of background) on EUS and histopathology, and histological findings adjacent to the area of PCIS. Results On EUS, stricture of the MPD was found in 15 patients (93.8 %). Hypoechoic areas surrounding the MPD stricture were observed in 9 patients (56.3 %), including three (18.8 %) with a 10- to 11-mm hypoechoic mass. EUS findings of the noncancerous part indicated chronic pancreatitis in six patients (37.5 %), pancreatic fatty infiltration in seven (43.8 %), early chronic pancreatitis in two (12.5 %), and normal pancreas in one (6.3 %). Histological findings of the noncancerous part (proximal to the MPD stricture) indicated chronic pancreatitis in 13 patients (81.3 %) and pancreatic fatty infiltration in five patients (31.3 %). Histopathologically, subepithelial inflammatory cell infiltration and fibrosis were present in all 16 patients with PCIS. Conclusions PCIS frequently causes localized changes in inflammation and fibrosis around the pancreatic duct. PCIS often accompanies chronic pancreatitis and pancreatic fatty infiltration in the background of the pancreas. EUS offers sufficient resolution to demonstrate pancreatic changes of PCIS.
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