No abstract

Inflammatory bowel diseases (IBDs), i.e., Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, impairing quality of life. [1][2][3][4][5] Although the etiology of IBDs still remains unclear, nationwide epidemiologic studies have clarified that the geographic incidence varies substantially, with higher rates in Northern and Western Europe, and Northern America than in Central and Southern Europe and many developing countries.2-5) Epidemiologic and linkage studies strongly suggested the importance of a genetic factor for susceptibility to IBDs, but a genome-wide screening has identified a number of candidate loci, indicating the complexity of IBDs.6) Among candidates, recent attention has focused on the gene MDR1/ABCB1 and its product, multidrug resistant transporter MDR1/P-glycoprotein, which is a glycosylated membrane protein of 170 kDa, belonging to the ATP-binding cassette superfamily of membrane transporters, [7][8][9][10][11][12] as a consequence of several non-clinical and clinical investigations as summarized below. In 1998, Panwala et al. reported that mdr1a-/-knock-out mice were susceptible to a spontaneous UC-like intestinal inflammation under specific pathogen-free conditions. 13) Since mdr1a-/-knock-out mice are immunologically normal, the development of spontaneous colitis is presumably due to a defect in the barrier function of the intestinal epithelium. They also indicated that infection with Helicobacter bilis induced diarrhea, weight loss, and IBDs in mdr1a-/-knockout mice.14-16) Macroscopic, microscopic and biochemical examinations have confirmed that the colitis which develops in this model is similar to that of human IBDs, [14][15][16][17] and very recently, it has been confirmed that MDR1 mRNA expression in colonic tissues is down-regulated in patients with UC, but not with CD.18) Next, MDR1 is located on chromosome 7 at q21.1, 19) which was one of the loci of susceptibility toIBDs identified by a genome-wide analysis in an UK cohort, 6) and the linkage in this region has recently been confirmed by genome scan meta-analysis. 20) Finally, in 2003Finally, in -2005, independent groups in Germany and Scotland indicated that a silent genetic polymorphism in exon 26, C3435T, is associated with susceptibility to UC, but not to CD, 21,22) though the results are disputed. [23][24][25][26] In the present study, the MDR1 polymorphisms of T-129C in the promoter region, a silent C1236T in exon 12, G2677A, T in exon 21, resulting in Ala893Thr and Ala893Ser, respectively, and C3435T were examined in 66 Japanese UC patients and 173 healthy subjects, and their value for predicting UC was analyzed independently. The effects of the G2677T/C3435T haplotype proposed by Johne et al. were also evaluated,27) as well as those of the haplotype assigned by 4 polymorphisms. Here, the patients were stratified into 2 subpopulations based on age at onset; early onset patients and later onset patients, since epidemiologic investigatio...

We describe a case of malignant endocrine tumor of the pancreas associated with von Recklinghausen's disease. A 66-year-old woman with familial von Recklinghausen's disease was admitted to our hospital with weight loss and lower abdominal pain. Endoscopy revealed a submucosal tumor in the second part of the duodenum. Contrast-enhanced computed tomography showed a heterogeneous low-density tumor, measuring 20 x 15 mm, in the head of the pancreas, and metastatic lymphadenopathy. Angiography showed faint tumor staining without encasement or apparent increase in vascularity. Pancreatoduodenectomy was performed. Macroscopically, there was a solid tumor, measuring 20 x 18 mm, in the head of the pancreas. Histologically, a malignant endocrine tumor was shown, with direct invasion to the duodenum, and lymph node metastases. This is the thirteenth case of pancreatic malignant tumor and the fourth case of pancreatic endocrine tumor associated with von Recklinghausen's disease reported in the world literature.

We describe a highly sensitive and accurate automated continuous-flow method for determining bile acids in serum. The bile acids are first liberated from serum protein by dialysis at alkaline pH and then measured fluorometrically after the following enzymic reaction. Bile acids are converted to 3-oxo bile acids with 3alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) with concomitant reduction of NAD+ to NADH. The hydrogen in the generated NADH is transferred by diaphorase (EC 1.6.4.3) to resazurin to yield resorfin, the fluorophore. Only 100 microliter of serum is required and 40 determinations can be done per hour. The CV for 20 replicate determinations in serum with a mean bile acid concentration of 9.8 mumol/liter was 2.6%. The CV for day-to-day variation for another serum on 27 successive days was 3.0% (mean concentration, 10.0 mumol/liter). We applied this method to 826 sera from various diseases; 29% exceeded the upper limit of normal, 10 mumol/liter, and abnormally high values (greater than 20 mumol/liter) were almost exclusively limited to sera from hepatobiliary and enteric disorders.

Endoscopic balloon dilation (EBD) is an established therapy for esophageal stenosis. To assess its usefulness in children, we reviewed 11 years of pediatric cases of EBD in our hospital. Over the last 11 years, EBD was performed on 14 pediatric patients (10 boys and four girls; 7 months-11 years) at our hospital. All EBD sessions were performed under general anesthesia and fluoroscopic monitoring. The sessions were repeated every week or alternate weeks until resolution of dysphagia or development of smooth endoscope passage. Stenosis was resolved in 14 of 14 patients (100%). None of the patients (0%) showed recurrence of stenosis. As for postoperative complications, mediastinitis occurred only in one patient (7.1%). The median number of session repeats for an individual patient was three (range 1-10). EBD is a safe and effective therapeutic modality for esophageal stenosis in children.