Masatake Iida

Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.

Wilson’s disease, an autosomal recessive disorder, is characterized by the excessive accumulation of copper in the liver. WND (ATP7B) gene, which encodes a putative copper transporting P-type ATPase, is defective in the patients. To investigate the in vivo function of WND protein as well as its intracellular localization, WNDcDNA was introduced to the Long-Evans Cinnamon rat, known as a rodent model for Wilson’s disease, by recombinant adenovirus-mediated gene delivery. An immunofluorescent study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the Long-Evans Cinnamon rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of WND protein with respect to the copper transport. Consequently, the appearance of holoceruloplasmin in plasma was confirmed by Western blot analysis and plasma measurements for the oxidase activity and the copper content. These findings indicate that introduced WND protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for WND protein to manifest its function.

Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces cerevisiae

Wilson disease is a genetic disorder of copper metabolism characterized by the toxic accumulation of copper in the liver. The ATP7B gene, which encodes a copper transporting P‐type ATPase, is defective in patients with Wilson disease. To investigate the function of ATP7B, wild type or mutated ATP7B cDNA was introduced into a yeast strain lacking the CCC2 gene (Δccc2), the yeast homologue of ATP7B. Wild type and the H1069Q mutant could rescue Δccc2, however, the N1270S mutant could not, reflecting phenotypic variability of Wilson disease. In addition, the mutant containing only the sixth copper binding domain could rescue Δccc2, indicating its functional importance.

Biliary excretion of copper in LEC rat after introduction of copper transporting P‐type ATPase, ATP7B

Wilsons disease, an autosomal recessive disorder, is characterized by the excessive accumulation of hepatic copper that results from reduced biliary copper excretion and disturbed incorporation of copper into ceruloplasmin. The ATP7B gene, responsible for the disease, encodes a copper transporting P‐type ATPase. We previously demonstrated the involvement of ATP7B in hepatic copper secretion into plasma after the introduction of ATP7B into the Long‐Evans Cinnamon (LEC) rat, a rodent model of Wilsons disease. In this study we found the increased copper contents of the hepatic lysosomal fractions and bile in the LEC rats after ATP7B introduction, indicating the participation of ATP7B in the biliary excretory pathway for copper.

Increased expression of co-chaperone HOP with HSP90 and HSC70 and complex formation in human colonic carcinoma

Co-chaperone HOP (also called stress-inducible protein 1) is a co-chaperone that interacts with the cytosolic 70-kDa heat shock protein (HSP70) and 90-kDa heat shock protein (HSP90) families using different tetratricopeptide repeat domains. HOP plays crucial roles in the productive folding of substrate proteins by controlling the chaperone activities of HSP70 and HSP90. Here, we examined the levels of HOP, HSC70 (cognate of HSP70, also called HSP73), and HSP90 in the tumor tissues from colon cancer patients, in comparison with the non-tumor tissues from the same patients. Expression level of HOP was significantly increased in the tumor tissues (68% of patients, n = 19). Levels of HSC70 and HSP90 were also increased in the tumor tissues (95% and 74% of patients, respectively), and the HOP level was highly correlated with those of HSP90 (r = 0.77, p < 0.001) and HSC70 (r = 0.68, p < 0.01). Immunoprecipitation experiments indicated that HOP complexes with HSC70 or HSP90 in the tumor tissues. These data are consistent with increased formation of co-chaperone complexes in colon tumor specimens compared to adjacent normal tissue and could reflect a role for HOP in this process.

Adenocarcinoma at the site of ileoanal anastomosis in Crohn's disease

PURPOSE: Proctocolectomy with ileoanal anastomosis has gained acceptance for the treatment of patients with ulcerative colitis. However, there are some patients with Crohns disease who received ileoanal anastomosis, because some Crohns colitis is difficult to differentiate from ulcerative colitis. The risk of cancer development at the site of ileoanal anastomosis has not been emphasized in Crohns disease. METHODS: A 12-year-old patient with Crohns disease was treated by proctocolectomy with straight ileoanal anastomosis. Twenty-five years after the operation, the patient noticed the tumor that developed at the site of ileoanal anastomosis. RESULTS: This article presents a patient with Crohns disease who developed invasive adenocarcinoma at the site of ileoanal anastomosis 25 years after proctocolectomy with ileoanal anastomosis. CONCLUSIONS: An ileoanal anastomosis does not eliminate the risk of cancer development, and surveillance after this operation seems advisable.

Acute Emphysematous Cholecystitis Preceded by Symptoms of Ileus: Report of a Case

Abstract We herein describe a case of acute emphysematous cholecystitis in which the patient presented with symptoms of ileus. The patient was a 72-year-old man with no history of diabetes mellitus. He presented with epigastric pain, vomiting, and low-grade fever. Plain abdominal radiography showed some intestinal gas and niveau, and he was admitted to our hospital with a diagnosis of ileus. The next day, the abdominal pain increased and was accompanied by muscular defense. Plain radiography and computed tomography of the abdomen were carried out, and an emergency laparotomy was performed under a diagnosis of panperitonitis due to a perforation of the gallbladder caused by acute emphysematous cholecystitis. The patient made favorable progress after the operation and was discharged on postoperative day 14. Percutaneous transhepatic gallbladder drainage has been increasingly performed for the treatment of acute emphysematous cholecystitis, but when a perforation of the gallbladder is suspected, a laparotomy first should be considered.

The Transformation of a Nonfunctioning Islet Cell Tumor of the Pancreas into a Proinsulinoma under Conditions of Lung Metastasis

We herein report the first case of a nonfunctioning islet cell tumor that transformed into a proinsulinoma during the process of metastasis to the lungs. This phenomenon was confirmed in a 69-year-old woman with an advanced pancreatic islet cell tumor and multiple liver metastases who later developed multiple lung metastases. She underwent pancreatic resection followed by the administration of chemotherapy and survived for seven years. Although the patient initially had hyperglycemia due to diabetes mellitus, she conversely began to manifest hypoglycemic attacks 63 months postoperatively with the concomitant development of multiple lung metastases. An autopsy revealed that only the tumor in the lungs produced proinsulin; no other hormones were detected.

Usefulness of Oblique Multiplanar Images on Multi-Detector Computed Tomography for Diagnosing Intersigmoid Hernia

Background: Intersigmoid hernia is a hernia of the small intestine into the intersigmoid fossa. Because the cavity of the intersigmoid fossa is so small, the preoperative detection of incarcerated intestine and/or mesenteric convergence is very difficult. We report a case of intersigmoid hernia in which the incarcerated bowel and mesenteric convergence could be visualized by oblique multiplanar reconstruction (MPR) images on multi-detector computed tomography (MDCT). Case Report: An 82-year-old man with small bowel obstruction was treated conservatively with a long intestinal tube. Axial plane images of MDCT detected only a thickening of the small bowel wall and a narrowing of the lumen in the pelvis. Since a fourteen-day waiting period did not improve the condition at all, he underwent surgery. The small bowel was herniated into the intersigmoid fossa. After surgery, we studied the preoperative images of MDCT once again. However, neither converged mesentery nor hernia orifice had been depicted. We attempted to make oblique coronal/sagittal MPR images using SYNAPSE VINCENT® and succeeded in visualizing not only the incarcerated bowels but also the hernia orifice and mesenteric convergence. Conclusion: Creating oblique MPR images from the MDCT volume data would help in making a preoperative diagnosis of sigmoid mesocolon hernias such as intersigmoid hernia with increasing confidence.

18FDG-PET at 1-Month Intervals Is a Better Predictive Marker for GISTs That Are Difficult to Be Diagnosed Histopathologically: A Case Report

Imatinib mesylate is a tyrosine kinase inhibitor of c-KIT and PDGFRA. Imatinib mesylate is an effective drug that can be used as a first-choice agent for treatment of GISTs. Prior to treatment, molecular diagnosis of c-KIT or PDGFRA is necessary; however, in some types of GISTs, it is impossible to obtain a sufficient amount of specimen for diagnosis. An inoperable or marginally resectable GIST in a 79-year-old female was difficult to be diagnosed at a molecular pathological level, and hence, exploratory treatment was initiated using imatinib combined with 18FDG-PET evaluation at 1-month intervals. PET imaging indicated a positive response, and so we continued imatinib treatment in an NAC setting for 4 months. As a result, curative resection of the entire tumor was successfully performed with organ preservation and minimally invasive surgery. 18FDG-PET evaluation at 1-month intervals is beneficial for GISTs that are difficult to be diagnosed histopathologically.

Efficacy for Preoperative Screening of Liver Metastasis using Computed Tomography and Ultrasonography in Patients with Colon Cancer.

効率的な大腸癌肝転移の術前検査の確立を目的に, 進行大腸癌症例354例 (内, 肝転移例63例) を対象にして, CTとUSの感度や正診率, 肝転移発見の効率や費用を検討した. 肝転移の判定は術後5年の観察で判明したもので行った. 肝転移検出のsensitivity, specificity, accuracyは, CTで65%, 94%, 89%, USで57%, 97%, 91%と, 両者に有意差はなかった. また, CTとUSが共に施行された例では65%, 93%, 88%と, 単独検査に比べて双方を行うことによる診断能の有意な向上はなかった.肝転移例における肝内進展状況の診断能は十分ではなかった. 肝転移例1例発見に要した費用は単純CTで6,298点, 造影CTで20,169点, USで5,773点と, USが安価だった. 大腸癌肝転移の診断能は, CTとUSでほぼ同等であり相補する点も少ないことから双方の検査を行う必要性はなく, cost-benefitの点からUSを選択すべきである.