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Hirschsprung disease is a heterogeneous genetic disorder, causative genes of which include the endothelin B receptor (ETB). To investigate the mutations of ETB in Hirschsprung disease, expression of the ETB gene in lymphoblastoid cells from patients and normal healthy adults was examined, and novel mutant transcripts were found. The mutant ETB gene transcripts lacked a 134-bp nucleotide sequence corresponding to exon 5, and some also contained a substitution from A to G at position 950 in exon 4, resulting in an amino acid substitution from glutamine (Q) to arginine (R). This substitution was suspected to be the result of RNA editing because it was not present in the genomic sequence. Transfection experiments using ETB minigenes containing the editing site with or without the gene for double-strand RNA deaminases (ADAR1 and ADAR2) revealed that the deaminases were involved in RNA editing. Furthermore, a c-Myc-tagged mutant ETB protein was not detected by Western blot analysis. The present results show that the mutant ETB transcripts were novel splice variants, which might not be translated, or that the products translated from splice variants might be quickly degraded, presumably because of their instability. The preferential production of this null function ETB by RNA editing/splicing could be involved in the etiology of some cases of Hirschsprung disease.

Cyclin-dependent kinase (CDK) inhibitor p27/Kip1 (p27) is a diagnostic and prognostic marker of various malignancies. Low expression of p27 reflects poor differentiation and poor prognosis, and an inverse correlation between the expression of p27 and degree of tumor malignancy has been reported. Because p27 mutation is extremely rare in human tumors, it is important to study the expression of p27 and its inactivator, p38/Jab1 (JAB1). Here we analyzed the expression of p27 and JAB1 by immunohistochemistry in embryonal rhabdomyosarcoma (E-RMS). We first confirmed the expression of p27 and JAB1 in normal human tonsillar epithelium, and observed a coordinated expression pattern depending on cell differentiation. Subsequently, specimens of eight poorly- and three well-differentiated E-RMS were examined for the expression of p27 and JAB1. The analyses revealed that four out of eight poorly-differentiated E-RMS were negative for p27, with positivity for nuclear JAB (NJAB) (- / + for p27/NJAB) in three and negativity for any JAB-1 expression ( - / -) in one. The remaining four poorly-differentiated E-RMS expressed p27 in the nuclei, together with predominant NJAB (+ / +). In three well-differentiated E-RMS, only one expressed nuclear p27 and all of these three expressed no NJAB (+ / - for p27/NJAB), but expressed predominant cytoplasmic JAB1 (CJAB). These findings suggest that JAB1 may play an important role in determining the differentiation stage of rhabdomyosarcoma cells by modulating the activity of CDK inhibitor p27.

Li-Fraumeni syndrome is a relatively rare disease entity characterized by sarcomas of the soft tissues, bone and miscellaneous tumors ofjuvenile onset and frequent occurrence of metachronous tumors (1). Germline mutation of the p53 tumor suppressor gene has been reported in approximately 70% ofthe Li-Fraumeni kindreds (2). Here we report a case of Li-Fraumeni syndrome presenting a gastric cancer in the proband and a hepatosarcoma in his son. The proband was a 38-year-old Japanese male referred to a clinic with a diagnosis of gastric carcinoma with multiple liver metastases. There was no previous history of malignant disorders, but his 1] -year-old son suffered from a liver tumor diagnosed as a hepatosarcoma and underwent surgical resection followed by systemic chemotherapy (Fig. l ). The proband received systemic chemotherapy comprising seven courses of 5FU and MTX.

The Japanese Biliary Atresia Society founded in 1980 for the aim of investigations of all aspects of biliary atresia (BA), started a nationwide registry of BA patients in 1989. A total of 626 cases were registered from 1989 to 1994. The male to female ratio was 0.58. Corrective surgery was performed in 603 patients. Regarding the type of obstruction, 63 cases were Type I, atresia of the common bile duct, 9 were Type II, atresia of the hepatic ducts, and 543 were Type III, atresia of the porta hepatis. As initial corrective procedures, original Roux-en Y, Suruga II and Roux-en Y with intestinal valve were mainly employed. Jaundice cleared in 346 patients (57%) and decreased in 131, while it persisted in 120. The 5-year-follow-up showed that 34 patients, 49% of the patients who were followed up, were alive without jaundice, while 28 (41%) are dead. Thirty five, 33% of the patients who were entered to the Registry, were lost to follow-up.

Among various anomalies related to the trachea and esophagus, atretic and stenotic lesions are the most common and challenging objects in pediatric surgery. Tracheoplasty with the costal cartilage grafts is the treatment of choice for the extensive congenital stenosis of the thoracic trachea. We treated 4 cases of tracheal stenosis with this technique. Observation for following 2 years suggests that this technique is useful for such extensive lesions as an end-to-end anastomosis is not indicated.One hundred and thirty seven cases of esophageal atresia were treated at our institute with an overall mortality rate of 38%. Primary or staged end-to-end esophageal anastomosis was performed on 94 patients with a 20% mortality rate, whereas jejunal or colonic interposition was indicated for 13 patients with a mortality rate of 30%.The cause of stenosis of the esophagus was fibromuscular hypertrophy in 20, bronchial remnants in the esophageal wall in 7 and the ectopic gastric mucosa in 2 of our series of patients. Esophagoesophageal anastomosis was a possible procedure when the length of resection of the esophagus was limited to within 2.5cm. Intestinal interposition was, however, required when the esophagus was resected 3.5cm and more.