A 70-year-old man was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia. Twenty-six days after admission, he experienced hematemesis despite improvement in his respiratory symptoms. Contrast-enhanced computed tomography revealed edematous stomach wall thickening with neither ischemic findings in the gastric wall nor obstruction of the gastric artery. Emergent esophagogastroduodenoscopy showed diffuse dark-red mucosa accompanied by multiple easy-bleeding, irregularly shaped ulcers throughout almost the whole stomach without active bleeding or visible vessels. The clinical course, including the endoscopic findings, progressed favorably with conservative treatment. COVID-19 pneumonia can present with acute gastric mucosal lesion, which may be induced by microvascular thrombosis due to COVID-19-related coagulopathy.
Proteoglycans (PGs), a family of glycosaminoglycan (GAG)-protein glycoconjugates, contribute to animal physiology through interactions between their glycan chains and growth factors, chemokines and adhesion molecules. However, it remains unclear how GAG structures are changed during the aging process. Here, we found that polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin. In cultured cell lines, the EXT1 and EXT2 enzymes, initiating HS biosynthesis, were stimulated at the translational level by polyamines. Interestingly, the initiation codon recognition by 43S preinitiation complex during EXT2 translation is suppressed by let-7b, a member of the let-7 microRNA family, through binding at the N-terminal amino acid coding sequence in EXT2 mRNA. Let-7b-mediated suppression of initiation codon depends on the length of 5′-UTR of EXT2 mRNA and its suppression is inhibited in the presence of polyamines. These findings provide new insights into the HS biosynthesis related to miRNA and polyamines.
Glycosaminoglycans (GAGs), a group of structurally related acidic polysaccharides, are primarily found as glycan moieties of proteoglycans (PGs). Among these, chondroitin sulfate (CS) and dermatan sulfate, side chains of PGs, are widely distributed in animal kingdom and show structural variations, such as sulfation patterns and degree of epimerization, which are responsible for their physiological functions through interactions with growth factors, chemokines and adhesion molecules. However, structural changes in CS, particularly the ratio of 4-O-sulfation to 6-O-sulfation (4S/6S) and CS chain length that occur during the aging process, are not fully understood. We found that 4S/6S ratio and molecular weight of CS were decreased in polyamine-depleted cells. In addition, decreased levels of chondroitin synthase 1 (CHSY1) and chondroitin 4-O-sulfotransferase 2 proteins were also observed on polyamine depletion. Interestingly, the translation initiation of CHSY1 was suppressed by a highly structured sequence (positions −202 to −117 relative to the initiation codon) containing RNA G-quadruplex (G4) structures in 5′-untranslated region. The formation of the G4s was influenced by the neighboring sequences to the G4s and polyamine stimulation of CHSY1 synthesis disappeared when the formation of the G4s was inhibited by site-directed mutagenesis. These results suggest that the destabilization of G4 structures by polyamines stimulates CHSY1 synthesis and, at least in part, contribute to the maturation of CS chains.
Background The usefulness of prophylactic biliary stenting for patients with common bile duct stones (CBDS) and gallstones (GS) to prevent recurrent biliary events after endoscopic sphincterotomy (EST) and CBDS extraction before elective cholecystectomy remains controversial. The aim of this study was to evaluate the risk of recurrent CBDS around the perioperative period and clarify its risk factors. Methods The clinical data of all patients who received prophylactic biliary stenting after EST for CBDS and later underwent cholecystectomy for GS followed by stent extraction in our institution were retrospectively reviewed. The numbers of residual CBDS at the end first and second endoscopic retrograde cholangiography (ERC) studies were compared. Univariate and multivariate analyses were performed using a logistic regression model to determine risk factors for recurrent CBDS in the perioperative period. Results Forty-two consecutive patients received prophylactic biliary stenting and subsequent cholecystectomy for GS. Three of these patients were excluded from this study because the number of residual stones was not confirmed. The median maximum CBDS diameter at second ERC was 0 mm (range, 0 - 10 mm); six patients had multiple CBDS (≥ 5). The number of CBDS at second ERC was increased in comparison to that at the first ERC in 15 patients (38.4%), and was unchanged or decreased in 24 patients. The median minimum cystic duct diameter was 4 mm (range, 1 - 8 mm). The median interval between first ERC and operation was 26 days (range, 2 - 131 days). The median interval between operation and second ERC was 41 days (range, 26 - 96 days). Laparoscopic cholecystectomy (LC) was performed in 38 patients, one of whom was converted from LC to open cholecystectomy. Postoperative complications (transient bacteremia) occurred in one patient. The cystic duct diameter was an independent risk factor for an increased number of CBDS at second ERC in the multivariate analysis (odds ratio 0.611 (95% confidence interval (0.398 - 0.939)), P = 0.03). Conclusion Recurrent CBDS around the perioperative period of cholecystectomy is not a rare complication after EST and the removal of CBDS with concomitant GS. Prophylactic biliary stenting is considered useful for preventing CBDS-associated complications, especially for patients in whom the cystic duct diameter is larger (≥ 5 mm).
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