Human skin fibroblasts were cultured in the presence of 0.5 mM 4-methylumbelliferone for 12 h, and cell-free synthesis of hyaluronic acid was performed using membrane-rich fraction from the cells. The preincubation of the cells with 4-methylumbelliferone reduced hyaluronic acid synthesis to 15% of that of non-preincubated cells, although its chain length was not changed. On the other hand, without preincubation of the cells with 4-methylumbelliferone, hyaluronic acid synthesis was not changed even when 4-methylumbelliferone was added directly to the reaction mixture. These results suggest that 4-methylumbelliferone represses the expression of hyaluronic acid synthase on the cell surface.
N ‐Acetylchondrosine was incubated at pH 4.0 with a rabbit‐liver crude enzyme extract. Gel filtration of the reaction products on Sephadex G‐15 revealed the presence of monosaccharide liberated from the disaccharide. The monosaccharide fraction was analyzed by gas‐liquid chromatography, and identified as a mixture of glucuronic acid and N ‐acetylgalactosamine. These results indicate the presence of β‐glucuronidase, which degrades N ‐acetylchondrosine, in rabbit liver. The discovery of the presence of this enzyme may help to establish the complete degradation process of chondroitin sulfates.
Pancreatic fibrosis in patients with alcoholic dependence syndrome was studied histopathologically. In 30 of 41 autopsied patients with alcoholic dependence syndrome, fibrosis was observed despite the absence of clinical pancreatitis. The fibrosis was categorized into three types, according to Martin's classification: intralobular sclerosis in 15 cases, perilobular sclerosis in seven cases, and a mixed intralobular and perilobular sclerosis in the remaining eight cases. The type of the fibrosis was not related to the duration of alcohol abuse. Alcoholic liver cirrhosis was coexistent in 23 of the 30 cases of pancreatic fibrosis. These cases were also divided into categories according to the three types, as follows: intralobular sclerosis in 12 (80%) of 15 cases, perilobular sclerosis in four (57%) of seven cases, and mixed sclerosis in seven (88%) of eight cases. That is, intralobular and mixed sclerosis were frequently coexistent with alcoholic liver cirrhosis. When the pancreases from the 19 subjects with intralobular sclerosis and mixed sclerosis coexistent with liver cirrhosis in alcoholic dependence syndrome were compared with 20 pancreases from patients with nonalcoholic liver cirrhosis, periacinar (or intralobular) fibrosis was found in all cases of the former, but in none of the latter. Hence, it was concluded that periacinar fibrosis occurred as a result of alcohol abuse. Pancreatic fibrosis in patients with alcoholic dependence syndrome was distributed mainly in the intralobular areas and was frequently coexistent with alcoholic liver cirrhosis.
