Increased abundance of frost mRNA during recovery from cold stress is not essential for cold tolerance in adult Drosophila melanogaster.

Frost (Fst) is a candidate gene associated with the response to cold in Drosophila melanogaster because Fst mRNA accumulation increases during recovery from low temperature exposure. We investigated the contribution of Fst expression to chill-coma recovery time, acute cold tolerance and rapid cold hardening (RCH) in adult D. melanogaster by knocking down Fst mRNA expression using GAL4/UAS-mediated RNA interference. In this experiment, four UAS-Fst and one tubulin-GAL4 lines were used. We predicted that if Fst is essential for cold tolerance phenotypes, flies with low Fst mRNA levels should be less cold tolerant than flies with normal levels of cold-induced Fst mRNA. Cold-induced Fst abundance and recovery time from chill-coma were not negatively correlated in male or female flies. Survival of 2 h exposures to sub-zero temperatures in Fst knockdown lines was not lower than that in a control line. Moreover, a low temperature pretreatment increased survival of severe cold exposure in flies regardless of Fst abundance level during recovery from cold stress, suggesting that Fst expression is not essential for RCH. Thus, cold-induced Fst accumulation is not essential for cold tolerance measured as chill-coma recovery time, survival to acute cold stress and RCH response in adult D. melanogaster.

Undifferentiated sarcoma of the liver.

We report a case of undifferentiated (embryonal) sarcoma (USL) of the liver arising in a 5-year-old girl. She had abdominal pain and distension after a blow to her abdomen. Exploratory laparotomy disclosed a large tumor arising from left lobe of the liver, which showed a typical gross and microscopic appearance of USL. Immunohistochemically, the tumor cells reacted with antibodies against vimentin, cytokeratin, alpha-smooth muscle actin and muscle actin (HHF35). These immunohistochemical variety of the tumor cells may indicate unregulated gene expression of anaplastic tumor cells rather than divergent differentiation of immature cells as in hepatoblastoma.

Relation of patient age to premalignant alterations in choledochal cyst epithelium: histochemical and immunohistochemical studies.

Forty patients with choledochal cysts, 17 children and 23 adults, were treated by cyst excision in this institution (1972 to 1982). Histochemical and immunohistochemical studies were performed on tissue from the walls of these 40 cysts. The type and degree of histologic changes observed were found to correlate with patient age at time of cyst excision. Specimens from four patients less than two years of age at time of excision revealed epithelial desquamation, fibrosis, and minimal evidence of inflammation. Among specimens from 13 patients, 4 to 15 years of age, only two had an intact epithelial lining. Marked inflammation and intramural glandular structures were observed. Specimens from 23 patients, more than 15 years of age at the time of cyst excision, showed marked acute or chronic inflammation and destruction of the epithelial lining. In this age group, intramural glandular structures with goblet and argyrophil cells were regularly observed within the cyst walls, and gastrin and somatostatin-like immunoreactivity was detected in cells of these metaplastic glands. In association with these changes, in five of the 23 patients in the oldest age group, adenocarcinomas were observed in the cyst walls. These studies establish the increasing rate of epithelial metaplasia in the walls of choledochal cysts with advancing age, and suggest that these changes are a continuing process with malignancy one of the end results.

[Morbidity and treatment in the anomalous arrangement of the pancreaticobiliary ductal system].

A nationwide survey of cases of congenital dilatation of the biliary duct was conducted to obtain the data on cases of congenital dilation of the biliary duct in Japan between 1972 and 1982. A total of 645 cases were surveyed. An anomalous arrangement of the pancreaticobiliary ductal system (AAPABIDS) was associated with congenital dilatation of the biliary duct in 90.2% of the cases examined extensively. These cases and 62 cases that were collected in our hospital during the period from 1963 to 1984 were chosen as the subject of this study. The results may be summarized as follows: Various factors which affect the sphincter of Oddi are needed for the clinical manifestations of AAPABIDS. The incidence of biliary carcinoma increases with age, in parallel with that of intestinal metaplasia in cases of congenital dilatation of the biliary duct. These findings suggest that intestinal metaplasia may be one of the important factors in the development of biliary carcinoma. From the view points of timing and indication of surgery, it is necessary to cut off reflux of pancreatic juice into the biliary duct and remove the portion in which bile is stagnant prior to the development of serious complications.

Histochemical and immunohistochemical studies on development of biliary carcinoma in forty-seven patients with choledochal cyst--special reference to intestinal metaplasia in the biliary duct.

Histochemical and immunohistochemical studies on 47 consecutive specimens excised for choledochal cyst were performed to clarify possible metaplastic changes of the biliary duct in relation to carcinogenesis. An anomalous arrangement of the pancreaticobiliary ductal system was observed in all 39 cases examined. Among the 47 patients, 5 (10.6 per cent) had biliary carcinoma. 27.3 per cent mucous gland, 13.0 per cent goblet cell and 9.5 per cent argyrophil cell in 23 children. On the other hand, 81.8 per cent exhibited mucous gland, 41.7 per cent goblet cell and 27.3 per cent argyrophil cell in 24 adults. These metaplastic changes seemed to be an intestinal metaplasia and increased with age. Immunoreactive-gastrin or -somatostatin were evident immunohistochemically in 4 adults. These findings confirmed that intestinal metaplasia may develop in the biliary duct in cases of choledochal cyst. Although direct evidence between intestinal metaplasia and the development of biliary carcinoma was not found, reflux and stasis of pancreatic enzymes in the biliary duct may relate to the development of intestinal metaplasia and be an important factor related to the carcinogenesis of choledochal cyst.

Nationwide survey of cases of choledochal cyst. Analysis of coexistent anomalies, complications and surgical treatment in 645 cases.

A nationwide survey of cases of choledochal cyst was conducted to obtain the data on cases of choledochal cyst in Japan between 1972 and 1982. A total of 645 cases in 73 institutions, including 52 cases from this hospital, were surveyed. Choledochal cyst was associated with an anomalous arrangement of the pancreaticobiliary ductal system in 90.2% of the cases which were examined extensively. The serum amylase level was elevated in 26.6% of the cases. Calculus disease of the biliary duct was recognized in 28.5% of the cases. Biliary carcinoma developed in 54 (8.4%) of 645 cases. The incidences of biliary carcinoma were 0.3% (1/306) in cases in children and 15.6% (53/339) in adult cases; carcinoma was found in the wall of the choledochus in 30, and in the gallbladder in 16 of these 54 cases. The nationwide survey showed that an anomalous arrangement of the pancreaticobiliary ductal system was closely associated with choledochal cyst and that cases of biliary carcinoma developed with the advance of age. Therefore, early resection of the cyst wall and reconstruction of the biliary duct is proposed as suitable surgical treatment for stopping reflux of pancreatic juice into the biliary duct.

Congenital dilatation of the biliary tract; new classification and study with particular reference to anomalous arrangement of the pancreaticobiliary ducts.

Yotsuyanagi's theory is often quoted in the discussion of the etiology of congenital dilatation of the biliary duct (CDBD), but there has been no established etiology as yet. With particular reference to the relationship between anomalous arrangement of the pancreaticobiliary ducts and CDBD, Babbit collected 19 cases of CDBD. The authors also observed the anomalous arrangement in 10 of 24 cases of CDBD (42 percent). Analysis of 570 CDBD cases collected in Japan disclosed that the anomalous arrangement was present in 183 of them (33 percent), dilation of the intraheptic bile ducts in 236 (42 percent), and narrowing and malformation of the bile duct in the hepatic hilum in 58 (10 percent). The authors have proposed a new classification, including these morphologic anomalies of the whole pancreaticobiliary ductal system. This classification provides useful indices in selecting the surgical procedures. The effect of the anomalous arrangement was pathophysiologically studied on dogs. The static internal pressure of the dog pancreatic duct was 14.6 + or - 5.5 cm H2O, and that of the dog bile duct, 8.9 + or - 3.4 cm H2O. Puppies were then operated on by shunting the pancreaticobiliary ducts. As the result, the biliary tract was devastated by pancreatic juice, giving rise to similar pathologic changes to those clinically observed.