Three urocortins in medaka: identification and spatial expression in the central nervous system.

The urocortin (UCN) group of neuropeptides includes urocortin 1/sauvagine/urotensin 1 (UTS1), urocortin 2 (UCN2) and urocortin 3 (UCN3). In recent years, evidence has accumulated showing that UCNs play pivotal roles in mediating stress response and anxiety in mammals. Evidence has also emerged regarding the evolutionary conservation of UCNs in vertebrates, but very little information is available about UCNs in non-mammalian vertebrates. Indeed, at present, there are no reports of the empirical identification of ucn2 in non-mammalian vertebrates or of the distribution of ucn2 and ucn3 expression in the adult central nervous system (CNS) of these animals. To gain insight into the evolutionary nature of UCNs in vertebrates, we cloned uts1, ucn2 and ucn3 in a teleost fish, medaka and examined the spatial expression of these genes in the adult brain and spinal cord. Although all known UCN2 genes except those in rodents have been reported to likely lack the necessary structural features to produce a functional pre-pro-protein, all three UCN genes in medaka, including ucn2, displayed all of these features, suggesting their functionality. The three UCN genes exhibited distinct spatial expression patterns in the medaka brain: uts1 was primarily expressed in broad regions of the dorsal telencephalon, ucn2 was expressed in restricted regions of the thalamus and brainstem and ucn3 was expressed in discrete nuclei throughout many regions of the brain. We also found that these genes were all expressed throughout the medaka spinal cord, each with a distinct spatial pattern. Given that many of these regions have been implicated in stress responses and anxiety, the three UCNs may serve distinct physiological roles in the medaka CNS, including those involved in stress and anxiety, as shown in the mammalian CNS.

Development of Collaterals to the Spinal Cord after Endovascular Stent Graft Repair of Thoracic Aneurysms.

OBJECTIVES: In thoracic and thoraco-abdominal aortic aneurysm repair, spinal cord injury (SCI) is devastating. Detection of the Adamkiewicz artery might be important for preventing SCI. Although thoracic endovascular stent grafts often occlude the segmental artery, the incidence of SCI in thoracic endovascular aortic repair is thought to be low compared with open repair. This study aimed to evaluate how the Adamkiewicz artery is supplied after segmental arteries are occluded by stent grafts. METHODS: From March 2007 to August 2015, 32 patients were enrolled whose segmental arteries that were connected to the Adamkiewicz arteries were occluded by stent grafts. Segmental arteries, Adamkiewicz arteries, collateral circulation into the Adamkiewicz arteries, and anterior spinal arteries were pre- and post-operatively evaluated by computed tomography angiography. RESULTS: Post-operatively, Adamkiewicz arteries were detected in 24 (75%) patients, except for two patients with paraplegia and six without paraplegia. Post-operative Adamkiewicz arteries were the same as pre-operative Adamkiewicz arteries, except for one Adamkiewicz artery that was located at two vertebral levels below the pre-operative level. SCI occurred in two (6.3%) patients. The distribution of feeding arteries into the Adamkiewicz artery post-operatively was divided into three patterns as follows: a segmental artery below the distal landing zone of the stent graft (53%), branches of the left subclavian artery (33%), and a branch of the left external iliac artery (13%). CONCLUSIONS: The length of the stent graft should be as short as possible. Blood supply to the left subclavian artery should be maintained because segmental arteries below the segmental artery occluded by the stent graft and branches of the left subclavian artery can become collaterals post-operatively.

Decision analysis of prophylactic treatment for patients with high-risk esophageal varices.

BACKGROUND: Clinical decision analyses were conducted to quantify the uncertainty and to identify important factors in selection of prophylactic therapy for patients with esophageal varices. METHODS: A Markov model compared variceal ligation, beta-blockers, and "watchful waiting" strategies in terms of bleeding-free life years. Transition probabilities were obtained from meta-analyses of published data. A hypothetical 50-year-old white man with high-risk esophageal varices and cirrhosis served as the prototypical baseline case. Traditional n-way sensitivity analyses were applied to clarify the influence of each factor, and Monte Carlo probabilistic sensitivity analyses were used to investigate clinical uncertainty. RESULTS: Probabilistic sensitivity analyses demonstrated that 77.0% of hypothetical cases had more bleeding-free life years after variceal ligation, whereas 23% had more when treated with beta-blockers. On the basis of one-way sensitivity analyses, only 2 factors (variceal bleeding rates after ligation and treatment with beta-blockers) influenced the strategy choice. CONCLUSIONS: Variceal ligation is an effective prophylactic therapy in many cases, but nearly one quarter of patients with high-risk esophageal varices and cirrhosis may benefit more from prophylactic treatment with beta-blockers. Additional clinical studies identifying key variceal bleeding risk factors may lead to more effective clinical decision making for these patients.

In situ atomic force microscopic observation of albumin adsorption onto phase-separated organosilane monolayer surface.

A mixed (n-octadecyltrichlorosilane (OTS)/[2-(perfluorooctyl)ethyl]trichlorosilane (FOETS)) monolayer was prepared on the water subphase and was subsequently immobilized onto the silicon wafer surface by chemical bonds. Atomic force microscopic (AFM) observation of the mixed (OTS/FOETS) monolayer revealed the formation of a phase-separated structure. In situ AFM observation of the adsorption behavior of bovine serum albumin (BSA) onto the mixed (OTS/FOETS) monolayers, successfully showed the adsorption behavior of BSA onto the phase-separated surface. It also revealed that in the case of pH 7.5, BSA was preferentially adsorbed onto the lower surface free energy FOETS phase of the mixed (OTS/FOETS) monolayer. On the other hand, BSA was adsorbed homogeneously onto the OTS and FOETS phases at the isoelectric point of BSA (pI 4.7). These results indicate that the preferential adsorption of BSA onto the FOETS phase in the mixed (OTS/FOETS) monolayer system may be due to: (1) the minimization of interfacial free energy between a monolayer surface and an aqueous solution; and (2) the electrostatic repulsion among BSA molecules bearing negative charges.

Bovine serum albumin adsorption onto immobilized organotrichlorosilane surface: influence of the phase separation on protein adsorption patterns.

Octadecyltrichlorosilane (OTS) and [2-(perfluorooctyl)ethyl]trichlorosilane (FOETS) monolayers and their mixed monolayer were polymerized on a water subphase and subsequently immobilized onto a silicon wafer surface by covalent bonding. Atomic force microscopic (AFM) observation of the mixed (OTS/FOETS) monolayer revealed the formation of a phase-separated structure. Protein-adsorption behavior onto the monolayers was investigated in situ on the basis of an attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopic flow cell method and the morphology of the monolayer surface-adsorbed bovine serum albumin (BSA) was observed by AFM. Protein adsorption behavior observed by ATR-FT-IR flow cell method revealed that the amount of BSA adsorption onto the OTS and FOETS monolayers increased remarkably at an initial experimental stage and attained a steady state within a few minutes at pH 7.5. The amount of steady state adsorption was c. 0.18-0.2 microgcm(-2). AFM observation of the monolayer after exposure to BSA solution suggested that BSA adsorbed in the end-on adsorption state on OTS monolayer and side-on one in the FOETS monolayer, respectively. However, in the case of the mixed (OTS/FOETS) monolayer, ATR-FT-IR flow cell experiment revealed that the amount of steady state adsorption of BSA was suppressed. Also, AFM observation revealed that at pH 7.5, BSA preferentially adsorbed onto the FOETS phase of the mixed (OTS/FOETS) monolayer, which had a higher interfacial free energy against water. On the other hand, BSA adsorbed homogeneously onto the OTS and FOETS phases at the isoelectric point of BSA (pH 4.7). These results indicate that the preferential adsorption of BSA onto the FOETS phase in the mixed (OTS/FOETS) monolayer system is due to: (1) the minimization of the interfacial free energy between a monolayer surface and an aqueous solution; and (2) the electrostatic repulsion between BSA molecules bearing negative charges.

Clinical trial of prophylactic endoscopic variceal ligation for esophageal varices.

Endoscopic variceal ligation is an effective therapy for variceal bleeding, and use of the method has recently been increasing. We evaluated the clinical usefulness of prophylactic endoscopic variceal ligation. Twenty-two patients with enlarged, tortuous varices and "red color signs" were selected. These patients were treated with ligation therapy alone and the varices were eradicated, i.e., reduced to small, straight varices without red color signs. Ligation therapy was withdrawn if the general condition of the patient worsened or if the varices could not be removed by suction. Follow-up endoscopy was performed every 4 months, and another ligation was performed if there were recurrent varices or variceal bleeding. The total reduction rate was 86.4%, and eradication required two sessions of therapy and 30 days of hospitalization on average. Complications included esophageal injury in 1 patient and treatment-induced bleeding in 1 patient; both complications were easily controlled. No variceal bleeding occurred after the eradication. There was no mortality due to gastrointestinal bleeding during the median follow-up period of 346 days. Prophylactic endoscopic variceal ligation made it possible to prevent fatal variceal bleeding with a minimum risk of complications, suggesting that this could be an alternative method for the prevention of first-time variceal bleeding.

Endoscopic resection of rectal carcinoid tumors using aspiration lumpectomy.

BACKGROUND AND STUDY AIMS: Although carcinoid tumors have malignant potential, complete resection can be curative if the lesion is located within the submucosal layer. In this study, we evaluated the effectiveness of endoscopic aspiration lumpectomy for the treatment of small rectal carcinoid tumors. PATIENTS AND METHODS: Eight patients with rectal carcinoid tumors less than 10 mm in diameter and located within the submucosa were treated by aspiration lumpectomy. It was confirmed that none of the patients had any metastatic lesions before treatment. The procedure was carried out using an endoscope with a cylinder attached to the tip and a Teflon tube along its outer axis. The lesion was aspirated into the cylinder, grasped by a snare passed through the tube, and then resected. RESULTS: All lesions were excised completely, without any complications. The resected specimens were circular, with the lesions located in the center of the surrounding mucosa. The diameter of the specimens (mean +/- SD) was 18.3 +/- 6.2 mm. All tumors were histologically typical, and the lateral and bottom margins of the specimens were free of tumor cells. No recurrences or distant metastases were found in any of the patients during the mean observation period of 13.3 months. CONCLUSIONS: We conclude that aspiration lumpectomy is a useful and safe technique for the treatment of small rectal carcinoid tumors contained within the submucosa.

Endosonographic characterization of duodenal elevated lesions.

BACKGROUND: Endoscopic diagnosis of duodenal elevated lesions is problematic for two reasons. Endoscopic biopsy often fails to confirm a histologic diagnosis of submucosal lesions. Moreover, a biopsy specimen is often insufficient to verify a differential diagnosis of mucosal lesions. In this study, we evaluated the usefulness of endosonography in the resolution of these problems. METHODS: The endoscopic and endosonographic features of 15 duodenal elevated lesions that had been confirmed histologically in our hospital were reviewed retrospectively. RESULTS: Of the 15 cases, 8 were submucosal lesions (lipoma, Brunner's gland hyperplasia, lymphangioma, carcinoid tumors, leiomyoma, and malignant lymphoma); the rest were mucosal lesions. A correct histologic diagnosis based on endoscopic biopsies was obtained in only 6 cases (three submucosal lesions and three mucosal lesions). On the other hand, ultrasonography was useful in the characterization of all submucosal lesions based on their echo level, layer of origin, and tissue homogeneity. As for mucosal lesions, the depth of infiltration was correctly estimated with endosonography. Either endoscopic resection or surgery was selected on the basis of endosonographic information. CONCLUSIONS: We conclude that endosonography is useful in the differential diagnosis of submucosal lesions and in determining suitable treatment methods for duodenal mucosal and submucosal lesions.

Endoscopic resection of gastrointestinal submucosal lesions: a comparison between strip biopsy and aspiration lumpectomy.

BACKGROUND: Endoscopic diagnosis and treatment of gastrointestinal submucosal lesions is still not established. We evaluated the clinical usefulness of two resection methods for submucosal lesions, using a "nonrandomized surgeon" design. METHODS: The strip biopsy method was evaluated at Tenri Hospital and the aspiration lumpectomy method was used at Kyoto University Hospital. The inclusion criteria for selecting patients were endosonographic findings indicating a tumor location within the submucosa. RESULTS: Seventy-seven patients were treated. The size of the specimens (mean +/- SEM) was 20.7 +/- 0.9 mm for the aspiration lumpectomy group and 14.0 +/- 0.8 mm for the strip biopsy group (p < 0.01). Aspiration lumpectomy was adequate for a definitive histologic diagnosis in 95% of the cases (36 of 38) as compared with 77% (30 to 39) of the cases treated by strip biopsy (p = 0.047). The eradication rate was 87% for the aspiration lumpectomy group, and 74% for the strip biopsy group (p = 0.274). The complication rate resulting from these procedures (hemorrhage, mean 5%) was acceptable. Repeated endoscopic examinations revealed no recurrence except for one lymphangioma. CONCLUSIONS: Endoscopic resection, especially aspiration lumpectomy, provides a significant benefit for accurate final diagnosis and eradication of submucosal lesions.

Malignant lymphoma arising in the duodenum combined with gastric lymphoma and early gastric cancer: a case report.

We report here a 65-year old man with primary duodenal malignant lymphoma combined with gastric lymphoma and early gastric cancer. Malignant lymphoma in the bulbus of the duodenum was suspected of by endoscopic biopsy during follow up of duodenal ulcer. Preoperative examination revealed an extension of malignant lymphoma from the bulbus to the stomach in combination with early gastric cancer. We performed a pancreaticoduodenectomy because the tumor invaded to the second portion of the duodenum. The postoperative course was uneventful and he received adjuvant chemotherapy following surgery. To our knowledge, this case is the first report of primary duodenal malignant lymphoma combined with gastric lymphoma and early gastric cancer.

Evaluation of pancreatic tumors with positron emission tomography and F-18 fluorodeoxyglucose: comparison with CT and US.

PURPOSE: To assess the clinical value of positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) for identification of pancreatic carcinoma. MATERIALS AND METHODS: Forty-six patients suspected of having a pancreatic neoplasm and who were to undergo surgery prospectively underwent FDG PET, computed tomography (CT), and transabdominal ultrasound (US). Endoscopic US was performed in 40 patients. Images were independently interpreted and compared with the histopathologic findings at surgery (41 patients) or with clinical follow-up findings (five patients). RESULTS: In 33 of 35 patients, foci of pancreatic carcinomas (10-100 mm in diameter) were identified as an increase in FDG uptake, whereas CT, transabdominal US, and endoscopic US depicted the foci in 31, 31, and 28, cases, respectively. Among 11 benign lesions, nine showed no increased FDG uptake (specificity = 82%). Specificities of the other modalities were lower. False-positive findings were obtained in a case of chronic active pancreatitis and in a serous cystadenoma. CONCLUSION: FDG PET, which provides "biochemical" information, is accurate in identifying pancreatic carcinoma and may be a method of choice when imaging equivocal masses detected with other "anatomic" imaging studies.