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Isolated sphenoid sinusitis is rare and difficult to diagnose. The difficulty arises because it is located in the deepest part of the nasal sinuses and the associated inflammation does not lead to typical symptoms of sinusitis. There are many important structures in the vicinity of the sphenoid sinus: the internal carotid artery, cavernous sinus and cranial nerves. Therefore, sphenoid sinusitis causes severe complications. From January 2003 to December 2007, we encountered 15 patients with isolated sphenoid sinusitis. Its incidence in all sinus diseases is 2.2%. Many patients complain of headaches, and they often visit neurologists or neurosurgeons. The pathological spectrum included 10 cases of bacterial sinusitis (5 acute sinusitis, 3 chronic sinusitis and 2 asymptomatic sinusitis), 3 fungal sinusitis, 1 mucocele and 1 retention cyst. When we diagnose isolated sphenoid sinusitis, CT and endoscopy are essential. CT becomes a more useful tool for performing a differential diagnosis when we independently change the window height and width. The endoscopic findings regarding draining from the sphenoethmoidal recess may indicate the severity of inflammation. A detailed observation with CT and endoscopy is the most important to accurately diagnose the pathology of isolated sphenoid sinusitis.

A region in the vicinity of D17Mit119 on mouse chromosome 17 harbors a susceptibility gene, designated as Ahl3, to age-related hearing loss (AHL). We produced congenic lines of C57BL/6 background that substituted regions around D17Mit119 with MSM-derived ones, and examined auditory brainstem response (ABR) thresholds for their hearing capacity at 6 and 12months of age. Three congenic lines carrying the approximately 14-Mb region between D17Mit274 and D17Mit183 retained normal hearing at 12months of age whereas two congenic lines not carrying this region tended to lose hearing at that age. We also investigated noise-induced hearing loss (NIHL) in congenic lines at 1, 7 and 14days after exposure to the noise of 100dB for 1h. Most congenic mice carrying the 14-Mb region did not exhibit permanent threshold shift (PTS) whereas mice not carrying this region exhibited a strong tendency of PTS, indicating the role of Ahl3 in susceptibility to NIHL. These results indicate that Ahl3 exists within the 14-Mb region and affects not only AHL but also NIHL.

Objectives: The prevalence of Helicobacter pylori (Hp) infection and the development of gastric cancer are both believed to increase with age in Japan. However, no studies have investigated people older than 65 years in detail. In this study, we investigated the prevalence of Hp infection and gastric cancer in the elderly, and analyzed the influence of both factors on longevity. Methods: All patients investigated were 65 years old and over. A total of 1877 autopsy cases were used to investigate the prevalence of gastric cancer and colonic cancer. Serum samples were obtained from 644 patients with dyspepsia and analyzed for Hp-IgG antibodies. Of these 644 patients, 63 underwent upper gastrointestinal endoscopies. Five biopsies were obtained and evaluated for the following morphological variables: neutrophils, mononuclear cell, atrophy, and intestinal metaplasia. Hp infection was evaluated histologically and with the 13C-urea breath test. Results: The prevalence of gastric cancer was significantly lower in subjects older than 85 years. The positive rate of serum Hp-IgG, and Hp infection as detected histologically and by the 13C-urea breath test, also decreased with age. In Hp(+) patients, the neutrophil score significantly decreased with age. In Hp(–) patients, however, the intestinal metaplasia score significantly increased with age. Conclusions: The non-infection of Hp itself is not related to longevity in Japanese elderly, because even Hp(–) patients appear to have been infected previously with Hp. The lower prevalence of gastric cancer in the elderly may be due to the disappearance of Hp colonization, which may contribute to longevity in Japanese elderly. © 2005 Blackwell Publishing Asia Pty Ltd

A prognostic estimation formula of acute liver damage was evaluated by using clinical data and technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) scintigraphy in order to determine operability for orthotopic liver transplantation (OLT). Forty-six patients hospitalized for acute liver damage were divided into survival (n = 35) and non-survival (n = 11) groups. Univariate and multivariate analyses were used to identify significant factors that affected prognosis. Logistic regression analysis was performed to predict prognosis with effective factors. Ten independent factors with significant differences were identified and further analyzed for significance by logistic regression analysis. Among the 10 factors, age and LHL15/HH15 were identified as having meaningful differences for predicting convalescence. The following formula was developed: R = − 0.159 × age + 14.622 × LHL 15 HH 15 − 3.500 A negative value for R indicates non-survivals, and a positive value indicates survivals. The mortality rate was calculated as = 1/(1 + eR). The sensitivity was 0.909, specificity was 1.000, and accuracy was 0.978. The reliability of this formula was as good as that of another formula presented previously by the Intractable Liver Diseases Study Group of Japan. The use of 99mTc-GSA for estimating the prognosis of acute liver damage is useful, especially before the onset of hepatic encephalopathy.

We recently demonstrated that both lisinopril and candesartan, an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, respectively, attenuate pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori (WBN/Kob) rats. The purpose of the present study was to assess whether combination therapy with low doses of both, ineffective when given alone, might synergistically exert protective effects. Lisinopril, candesartan, or a combination of both in drinking water was administered to 10-week-old male WBN/Kob rats for 10 weeks. Parameters of inflammation and fibrosis, positive immunostaining for alpha-smooth muscle actin, and gene expression of cytokine and growth factors were assessed, as well as circulating renin-angiotensin system components. Dose-dependent effects of combination therapy were also investigated. Only combination therapy attenuated gross alterations in the pancreas, as quantitatively confirmed by increases in pancreatic weights and decreases in myeloperoxidase activity, hydroxyproline content, histologic scores, relative fibrosis area, and relative area of alpha-smooth muscle actin-positive cells. Combination therapy suppressed up-regulation of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA in the pancreas. Dose dependence of combination therapy was recognized with reference to improvement in these parameters. The conclusions are that combination therapy synergistically alleviated pancreatic inflammation and fibrosis in male WBN/Kob rats. This effect may be related to suppression of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA. Compared with the either therapy alone, combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker may be more beneficial for treating chronic pancreatitis.

Background Sclerosing cholangitis with autoimmune pancreatitis has a cholangiographic appearance that is similar to that of primary sclerosing cholangitis, but only the former responds well to corticosteroid therapy. It, therefore, is necessary to distinguish between these two diseases. Cholangiography is the reference standard for the diagnosis of primary sclerosing cholangitis. The present study compared the characteristic findings for these two types of sclerosing cholangitis. Methods Cholangiograms from patients with primary sclerosing cholangitis (n=29) and sclerosing cholangitis with autoimmune pancreatitis (n=26) were studied with regard to length and region of stricture formation, and other characteristic findings. Results Band-like stricture, beaded or pruned-tree appearance, and diverticulum-like formation were significantly more frequent in primary sclerosing cholangitis. In contrast, segmental stricture, long stricture with prestenotic dilatation and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with autoimmune pancreatitis. Discriminant analysis based on these findings correctly identified 27 of 28 patients with primary sclerosing cholangitis and 25 of 26 patients with sclerosing cholangitis with autoimmune pancreatitis. It also identified a patient with an incorrect diagnosis of primary sclerosing cholangitis who proved, on review of a surgical specimen, to have findings consistent with lymphoplasmacytic sclerosing cholangitis. Conclusions Characteristic cholangiographic features allow discrimination of sclerosing cholangitis with autoimmune pancreatitis and lymphoplasmacytic sclerosing cholangitis without pancreatitis from primary sclerosing cholangitis.

Genetic variation in humans probably plays a role in determining the range of individual susceptibility to age-related hearing loss (AHL), but no contributing loci have been identified because of the difficulties of dissecting complex traits in humans. This paper reports mapping of an AHL locus using a panel of consomic mice between C57BL/6J (B6) and MSM strains, which covered more than a half of chromosome sets. B6 strain exhibited AHL beginning at 10 months of age whereas MSM strain, derived from Japanese wild mice, had normal hearing throughout life. Individuals in the panel were examined with auditory brainstem response (ABR) at various months of age, revealing that one particular strain (B6-Chr17(MSM)) substituting the chromosome 17 with the MSM-derived one showed a prominent resistance, having still good hearing at 18 months of age. Subsequent mapping using 89 individuals in the cross between B6-Chr17(MSM) and B6 was performed, which showed a significant association of ABR thresholds with loci in the vicinity of D17Mit119. These results show a novel AHL-resistant locus, designated as Ahl3, on the chromosome 17.

Background: The effect of Helicobacter pylori infection on systemic disorders is not well understood. Aim: The purpose of this study was to elucidate the systemic effects of H. pylori infection by comparing differential counts of leukocytes and platelets in peripheral blood before and after eradication of H. pylori. Methods: A total of 164 H. pylori-positive patients underwent eradication therapy, and populations of peripheral blood leukocytes and platelets before and 0 (just after therapy), 1, 3 and 12 months after eradication were retrospectively analysed. Results: In the eradicated group (n = 138), blood leukocytes, neutrophils and monocytes decreased significantly after eradication, but there was no significant change in eosinophils, basophils, lymphocytes or platelets. In the non-eradicated group (n = 26), there was no significant change in any studied parameter. With regard to smoking status, although leukocytes and neutrophils did not decrease after eradication in the smoking group, they significantly decreased after eradication in the nonsmoking group. Conclusions: These findings suggest that: (1) H. pylori infection increases neutrophil and monocyte counts in the peripheral blood, which indicates a significant role of H. pylori infection in systemic disorders; and (2) Smoking may mask the effect of H. pylori eradication on peripheral leukocytes, which would explain the controversy in previous reports concerning H. pylori infection and peripheral leukocytes.

We report an autoimmune pancreatitis case with diverse manifestation of biliary stricture, lung fibrosis and immune thrombocytopenic purpura. The patient was a 70-year-old man who presented with jaundice. Abdominal ultrasonography and computed tomography revealed enlargement of the entire pancreas and endoscopic retrograde pancreatography showed diffuse irregular narrowing of the main pancreatic duct. Endoscopic retrograde cholangiography revealed a band-like stricture of the bile duct in the hilar hepatic region with intrahepatic duct dilation. Chest X-rays and computed tomography revealed interstitial fibrosis of the bilateral lower lungs. Thrombocytopenia and purpura appeared. Antinuclear antibody, anti-Ro (SS-A) and anti-La (SS-B) antibodies and rheumatoid factor were positive. All manifestations responded well to steroid therapy. From the present case it would appear that a multitude of manifestations are linked within one syndrome. If we encounter patients with autoimmune pancreatitis, we should not focus on a disease but rather on the possibility of a syndrome complex.

ATBF1 was first discovered as a suppressor of AFP expression in hepatocytes. It is present in brain, adult liver, lung, and gastro-intestinal tract. Recently, it has been reported that ATBF1 regulates myoblastic differentiation and interacts with v-Myb in regulation of its transactivation. Using the yeast two-hybrid system, we searched for protein-protein interactions to uncover new functions for ATBF1. We present here experimental evidence that ATBF1 is a new regulatory factor for STAT3-mediated signal transduction through its interaction with PIAS3. PIAS3 was thus identified as an ATBF1-binding protein. In co-transfection experiments, the full-length ATBF1 was found to form complexes with PIAS3 in Hep G2 cells. In the luciferase assay, ATBF1 was found to have no influence on STAT3 signaling induced by IL-6 stimulation, but it did synergistically enhance PIAS3 inhibition of activated STAT3. In conclusion, ATBF1 can suppress the IL-6-mediated cellular response by acting together with PIAS3.

A 34-year-old woman with liver insufficiency due to glycogen storage disease III underwent a living spousal liver transplantation. Soon after the successful operation, moderate hypercalcemia along with hyperbilirubinemia emerged without clarified reasons. The hypercalcemia persisted for over a month despite calcitonin treatment and the serum calcium level surged to 13.2 mg/dl with albumin correction. Renal dysfunction was indicated by an acute increase in serum creatinine (approximately 0.8 to approximately 2.8 mg/ml), which was assumed to be hypercalcemia-induced and was effectively treated with bisphosphonate, pamidronate (30 mg, i.v.). Recent topics related to transplantation-associated hypercalcemia are discussed.

The three-dimensional cytoarchitecture of the normal rat olfactory epithelium was examined by scanning electron microscopy (SEM) of KOH digested tissues as well as by light and transmission electron microscopy of plastic sections. Observations specimens from the lateral side of the olfactory epithelium allowed identification of four cell types by their surface structure: olfactory neurons, supporting cells, basal cells, and duct cells of the Bowman's gland. The olfactory neurons were characterized by the presence of a thick apical process (i.e., dendrite) and a thin basal process (i.e., axon). These olfactory neurons tended to be aligned along the vertical axis of the epithelium. Immature olfactory neurons were present at the basal part of the epithelium and had a pear-shaped cell body with a thin and long axon and a short dendrite which failed to reach the epithelial surface. Supporting cells were roughly columnar in shape and occupied the full length of the epithelium. They became thinner in the basal two thirds of their length but had branched foot processes spreading on the basal surface of the epithelium. Basal cells located in the basal epithelial region were oval, round or cuboidal and present among the foot processes of the supporting cells. The ducts of the Bowman's gland entered the epithelium from the lamina propria and took straight, perpendicular courses within the epithelium. These intraepithelial ducts were composed of several slender cells. The acinar cells are sometimes present in the epithelium and appeared as a globular bulge of the duct at the basal part of the epithelium. SEM observation of the basal surface of the olfactory epithelium also clearly showed that axon bundles were surrounded by the sheet-like processes of Schwann cells, the investment being found at the base of the epithelium just before axon bundles leave the epithelium.

A 59-year-old man with bloody stools, and previously diagnosed with sigmoid colon carcinoma, visited our hospital. Preoperative abdominal ultrasonography (US) showed another tumor, with an uneven irregular surface, measuring about 9 x 5 cm, below the left hypochondrium. The tumor consisted of several cysts. Abdominal computed tomography (CT) showed a multicystic tumor attached to the stomach, and its septum and marginal region were intensely stained on contrast imaging. On magnetic resonance imaging (MRI), low and markedly high signals were revealed in the tumor on T1-weighted and T2-weighted sequences, respectively. Contrast imaging of the upper digestive tract showed extramural compression of the greater curvature of the antral stomach by the tumor. The tumor was partially imaged by endoscopic ultrasonography (EUS), but continuity to the stomach was not confirmed. On abdominal angiography, the tumor was slightly stained via the gastroepiploic arteries. Surgical treatment was performed to excise both the gastric tumor and the sigmoid colon carcinoma. The gastric tumor was removed with gastric wall tissue where the tumor was attached to a 2-cm pedicle. It was multicystic, contained watery fluid, and had a smooth outer surface. Histologically, the tumor consisted of multiple irregular cysts without epithelial lining, and solid epitheloid cell nests in between. The tumor cells had clear or eosinophilic cytoplasm and round nuclei. No mitotic figures were seen. The tumor cells in the pedicle were connected with the muscularis propriae of the stomach. Immunohistochemistry showed c-kit-positive, CD34-positive smooth muscle actin (SMA)-negative, and S-100-negative staining of tumor cells. The final diagnosis was gastrointestinal stromal tumor (GIST).

Background: Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back-diffusion into the mucosal layer. Our previous study indicated that trans-epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin. Aim: Evaluate the effects of a mucoprotective agent, rebamipide, on the nonsteroidal anti-inflammatory drug (NSAID)-induced increase of gastric epithelial permeability. Methods: Rat gastric epithelial cells were plated on tissue culture inserts. Cells were exposed to a NSAID (indometacin, 10 -7 M). Trans-epithelial permeability was measured by TER and diffusion rate of 14 C-mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E 2 (PGE 2 ) production in culture medium was also measured. Results: Indometacin gradually and significantly decreased TER and increased 14 C-manitol permeability. Rebamipide reversed the indometacin-induced changes in epithelial permeability and induced PGE 2 synthesis. This induction was blocked by either indometacin or a Cyclooxygenase (COX)-2 specific inhibitor. Conclusions: COX inhibitors such as indometacin inhibit regulation of epithelial permeability by reducing PGE 2 . COX-1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin-induced increase in gastric epithelial permeability by increasing PGE 2 levels in a COX-2 dependent manner.

Background & Aims: Pancreatic stellate cells have some similarities to hepatic stellate cells and an intrinsic renin-angiotensin system is present in the pancreas and is enhanced in acute pancreatitis and chronic pancreatic hypoxia. We assessed the effects of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, on spontaneously occurring chronic pancreatitis. Methods: Lisinopril in drinking water (20, 50, or 200 mg/L) was administered to 10-week-old male Wistar Bonn/Kobori (WBN/Kob) rats for 10 weeks and then the inflammatory parameters, fibrosis, serum and pancreatic ACE activity, and expression of transforming growth factor-β1 (TGF-β1) messenger RNA (mRNA) as well as positive immunostaining for α-smooth muscle actin (α-SMA) were assessed. Results: Lisinopril attenuated gross alterations in the pancreas. This protective effect was confirmed quantitatively by significant increases in pancreatic weights and decreases in pancreatic myeloperoxidase (MPO) activity (an index of granulocyte infiltration), pancreatic hydroxyproline content (an index of collagen deposition), ratio of fibrous tissue, and histologic scores. Lisinopril significantly reduced serum ACE activity but it did not affect pancreatic activity. High doses of lisinopril suppressed the overexpression of TGF-β1 mRNA measured by reverse-transcription polymerase chain reaction (RT-PCR) and decreased the number of α-SMA-positive cells (activated pancreatic stellate cells) in the pancreas. Conclusions: Lisinopril alleviated chronic pancreatitis and fibrosis in male WBN/Kob rats. It suppressed the expression of TGF-β1 mRNA, resulting in the prevention of pancreatic stellate cell activation, which may be involved in the observed protection. We propose that an ACE inhibitor may be useful for treating chronic pancreatitis.

AIMS: To quantitatively determine the influence of estradiol on acinar cell apoptosis and chronic pancreatitis; assess its effects on infiltration of CD4 and CD8 T cells in the pancreas; investigate the role of testosterone on chronic pancreatitis in 20-week-old male WBN/Kob rats; and determine the impact of estradiol on proliferation of splenocytes derived from these animals in vitro. METHODOLOGY AND FINDINGS: Treatment with high (0.4 mg x kg x week) but not low (0.1 mg x kg x week) doses of estradiol for 10 weeks significantly decreased the number of apoptotic acinar cells stained with an anti-single strand DNA antibody, histologic scores, and pancreatic myeloperoxidase activity in 20-week-old WBN/Kob rats, in comparison with control values. The high doses also significantly attenuated the increase in pancreatic hydroxyproline content, an indicator of collagen deposition, at 20 weeks. They caused significant decreases in the numbers of CD4 and CD8 T cells infiltrating the pancreas. Both doses suppressed levels of testosterone but without any influence on the serum corticosterone concentrations. Androgen receptors could not be immunohistochemically identified in the pancreas at 20 weeks, and dietary treatment with flutamide, an androgen receptor antagonist, did not influence the chronic pancreatitis. Estradiol significantly reduced 1% phytohemagglutinin-induced incorporation of bromodeoxyuridine into the splenocytes in vitro. CONCLUSIONS: We conclude that estradiol dose-dependently attenuates acinar cell apoptosis and development of chronic pancreatitis, independent of any change in endogenous corticosterone and testosterone, by suppressing infiltration and function of T cells.

Simple liver cysts are rarely complicated by intracystic hemorrhage. We encountered a case of simple liver cyst that was morphologically similar to biliary cystadenocarcinoma, which was complicated by asymptomatic intracystic hemorrhage and successfully treated by right lobectomy. A large cystic lesion of the liver was detected in a 57-year-old woman during a mass screening health check. Abdominal ultrasonography (US) revealed that the cystic lesion, containing many hyperechoic papillary structures, occupied almost the entire region of the right hepatic lobe. In addition, a round mural nodule, measuring approximately 5 cm in diameter, was detected in the cystic wall. Abdominal computed tomography (CT) revealed that the inner part of the cystic lesion showed homogeneous low density, but CT did not show the round nodule detected by US. On T1-weighted sequence of magnetic resonance imaging (MRI), the lesion showed homogeneous high signals, together with a low-signal tumorous lesion in the cystic wall. T2-weighted sequence of MRI showed unhomogeneous high signals, together with high signals in the tumorous part. These findings did not exclude the possibility of a malignant cystic tumor, such as biliary cystadenocarcinoma. Therefore, right lobectomy was performed. Histological examinations of resected tissue specimens revealed that the lesion was a liver cyst containing a large amount of blood clot, and that the tumorous lesion detected by US and MRI was a large mass of blood clot which was partly liquefied. This case indicates the diagnostic importance of the morphological discordance between CT and US or MRI findings for liver cyst containing a large amount of blood clot.

We previously reported that the intracutaneous injection of DNA vaccines encoding Helicobacter pylori heat shock proteins elicited specific immune responses, and led to reduced infection in mice. In this study, we constructed DNA vaccine encoding H. pylori-catalase (pcDNA3.1-kat) and investigated the immune responses to intranasal and intracutaneous administration of pcDNA3.1-kat. C57/BL6 mice were immunized intracutaneously with 10 microg of pcDNA3.1-kat or intranasally with 50 microg of pcDNA3.1-kat. Catalase-specific IgG antibody was detected in the sera of intranasal and intracutaneous immunized mice. Both intranasal and intracutaneous immunized mice were significantly protected from colonization by H. pylori and had significantly reduced degrees of gastritis. These results demonstrate that DNA vaccine encoding H. pylori-catalase can induce an immune response against H. pylori, and that intranasal immunization works as well as intracutaneous immunization.

This case report describes a ruptured pancreaticoduodenal artery aneurysm (PDAA) causing pancreatic pseudotumour and duodenal obstruction. A 59-year-old man was referred to our hospital with a chief complaint of frequent vomiting without abdominal pain. Because a mass lesion 10 cm in diameter was palpated in the right para-umbilical region and found in the head of the pancreas on computerized tomography (CT) and ultrasonography, malignant tumour of the pancreas or tumour-forming pancreatitis was strongly suspected, and further examination was performed.Magnetic resonance imaging (MRI) results suggested subacute haematoma inside the mass. On angiography, an aneurysm 8 mm in diameter was found in the posterior superior pancreaticoduodenal artery (PSPD). Since an ultrasound-guided percutaneous needle biopsy from the solid part of the mass indicated no malignancy, the lesion was considered an inflammatory pseudotumour in the head of pancreas due to ruptured aneurysm. Bypass surgery was planned, but the tumour shrank significantly with conservative treatment. Obstruction disappeared completely without surgery 4 weeks after the first symptom.

Background and Aims: The purpose of this study was to clarify the value and limitation of imaging modalities for diagnosing small hepatocellular carcinoma (HCC). Methods: Nodules (n = 207) with diameters of 20 mm or less detected by periodic ultrasonography and computed tomography in 139 patients with chronic liver disease were investigated with digital subtraction angiography (DSA) and magnetic resonance imaging (MRI). These findings were compared with histological findings. Results: Histological diagnoses were adenomatous hyperplasia (AH, n = 27), well-differentiated HCC (n = 99), moderately differentiated HCC (n = 79) and poorly differentiated HCC (n = 2). We compared two groups: group A (n = 62), nodules of 10 mm diameters or less; and group B (n = 145), nodules 11–20 mm. Adenomatous hyperplasia accounted for approximately 30% of group A, but was difficult to diagnose with imaging modalities alone. We diagnosed those nodules showing hypervascular staining on DSA or hyperintensity on MRI T2-weighted images as HCC. Imaging alone was sufficient to diagnose HCC in 58% of the well-differentiated nodules and 87% of the moderately and poorly differentiated nodules (P < 0.01). It was possible to diagnose HCC by imaging alone in 60% of all nodules or 45% of group A and 68% of group B (A vs B, P < 0.005). Conclusions: With decreasing differentiation and increasing diameter of nodules, the use of imaging modalities to diagnose HCC improved. Tumour biopsy was required to diagnose 55% of the cases in group A and 32% of the cases in group B. © 1999 Blackwell Science Asia Pty Ltd

Background Although biliary expandable metallic stents (EMS) improve patency, they are unsuitable for primary biliary stenting. Although plastic tube stents without side holes (PWOS) are also reported to prolong patency, their efficacy remains controversial. Goals To evaluate clinical utility and relative advantages, we reviewed clinical results of three types of stents: plastic tube stents with side holes (PS), PWOS, and EMS. Study The 130 patients comprised 56 with pancreatic cancers, 26 with gallbladder cancers, 21 with bile duct cancers, and 27 with other malignant diseases. Plastic tube stents with side holes (10 French [Fr]), PWOS (10 Fr), and EMS (30 Fr) were inserted in 64, 28, and 38 cases, respectively. Results Overall cumulative stent patency rates for EMS and PWOS groups were significantly higher than that of PS. This was also the case with middle and lower biliary tract strictures and with pancreas cancers. In Japan, medical costs with endoscopic retrograde cholangiopancreatography ($631.00) divided by the mean patent period with PS, PWOS, and EMS were $8.80/d, $4.60/d, and $20.40/d, respectively. Conclusion We recommend PWOS for primary biliary stenting of middle and lower biliary strictures, especially those caused by pancreatic cancer, based on its lower price and sufficient patency without replacement after diagnosis of inoperability.

Decay-accelerating factor (DAF, CD55), one of the membrane-binding regulators of complement activation, prevents host cells from the autologous complement-mediated attack. However, specific localization of DAF in the different layers of the digestive tract has not been defined. Using a crypt isolation procedure, we separated epithelium from the remnant stromal tissue and assessed the expression of DAF isoforms in the two layers in the guinea pig digestive tract. Both Northern hybridization and immunohistochemistry revealed DAF was preferentially expressed in the small intestinal epithelium compared to the stomach and colon. Reverse-transcriptase PCR demonstrated that the glycosyl-phosphatidylinositol (GPI)-anchored isoforms are predominant over the transmembrane (TM) isoforms in all digestive epithelium. However, there was no difference between GPI-anchored type and TM type in the stromal tissue. In conclusion, DAF was found to be primarily expressed in the small intestinal epithelium with isoforms differing between the epithelium and stromal tissue, suggesting differential roles in the guinea pig digestive tract.

Five patients with non-resectable pancreatic head carcinoma complicated by duodenal and biliary obstructions were successfully treated by double stenting with covered self-expandable metallic stents (EMS). Diamond (Boston Scientific, Natick City, MA, USA) stents covered with a polyurethane membrane were used to treat biliary obstructions, whereas covered Ultraflex (Boston Scientific) stents for esophageal stenting were used to treat duodenal obstructions. That is, Diamond stents were initially placed in the biliary tract percutaneously in one patient and endoscopically in the remaining four patients. Subsequently, covered Ultraflex stents were placed in the duodenum. Double stenting with EMS was successfully performed in all five patients without inducing early technical complications. All patients were able to take a liquid diet orally at a mean 1.6 days after the double stenting procedure and were able to eat solid foods thereafter. Sludge-induced biliary obstructions were detected in two patients 3 and 6 months after the placement of EMS. However, recurrent biliary obstruction was not noted in the remaining three patients. The EMS left in the duodenum were not obstructed during the observation period. The survival period of the patients ranged from 86 to 363 days (mean 172 days). There have not been any reports evaluating the usefulness of double stenting using covered EMS for duodenal and biliary obstructions. Because favorable results were obtained by double stenting in our patients, stenting for duodenal and biliary obstructions caused by non-resectable pancreatic head carcinoma may become a useful treatment modality substituting for bypass surgery.

An imbalance in helper T-cell type 1 (Th1) and type 2 (Th2) cytokines is suggested to play an important role in the pathogenesis of chronic viral infections, but this issue is not resolved in patients with hepatitis C virus (HCV) infection. The aim of this study was to clarify the relationship between the balance of Th1 and Th2 cytokines and liver damage. Methods. We investigated cytokine levels in the peripheral blood and liver tissue of patients with chronic HCV infection (n = 59) by three different methods; we used flow cytometry to detect intracellular cytokines, and we measured cytokine titers in sera and in the supernatants of lymphocyte cultures with enzyme-linked immunosorbent assays (ELISAs). Results. In both CD4+ and CD8+ cells, interferon (IFN) γ-producing cell populations increased, while there was no difference in interleukin (IL)-10 production, indicating a shift to a Th1 cytokine profile with the progression of liver disease. With respect to the ratio of IFN-γ to IL-10, a correlation was found in CD4+ cells between peripheral blood and liver tissue (r = 0.98; P = 0.0011). Th1 cytokine was predominant in intrahepatic CD4+ cells, while it was predominant in peripheral blood CD8+ cells. Conclusions. These findings indicate a correlation between dominant Th1 response and disease activity and progression. In addition, we suggest that intrahepatic CD4+ T cells play a pathogenetic role in the hepatic injury of HCV infection.

We present a case of 2 brothers with idiopathic chronic pancreatitis associated with pancreatic duct stones which could be successfully disintegrated by extracorporeal shock wave lithotripsy (ESWL). An obvious etiology for the pancreatolithiasis, like alcohol or biliary disease, was lacking and point mutations of the cationic trypsinogen gene exons 2 and 3 were not detected in the long arm of the 7th chromosome. However, a hereditary etiology could not be precluded since pancreatolithiasis occurred in the siblings. There has been no recurrence of pancreatic stones during 42 months of follow-up periods, for both. ESWL, the least invasive therapy, appeared applicable and effective for pancreatolithiasis in the present cases.

We investigated the effect of DNA vaccines encoding H. pylori -heat shock protein A and B (pcDNA3.1- hspA and - hspB ) on inducing immune responses against H. pylori in mice. C57BL/six mice aged 5 weeks were immunized by single injection of 10 μg of pcDNA3.1- hspA and pcDNA3.1- hspB into intracutaneous tissue. Plasmid DNA lacking the inserted hsp were injected as a control. Three months after vaccination, significant specific antibodies against H. pylori were detected by ELISA in the sera of vaccinated mice. Antibody isotypes were predominantly IgG2a (Th1-like) with pcDNA3.1- hspA and mixed IgG1/IgG2a (Th0-like) with pcDNA3.1- hspB. DNA vaccination dramatically suppressed colonies of bacteria in stomach of vaccinated mice (28,400 ± 21,600/mm 2 for pcDNA3.1- hspA and 6800 ± 3470/mm 2 for pcDNA3.1- hspB ) compared to control mice (128,000 ± 42,200/mm 2 ). Histological analysis of the gastric mucosa demonstrated that the degree of gastritis was significantly lower in the vaccinated mice than in control mice. These results demonstrated that DNA vaccines encoding H. pylori -Hsp induce significant immune response against H. pylori to decrease gastric mucosal inflammation, indicating that a DNA vaccine can be a new approach against H. pylori in humans.

We have reported successful implantation of self-expandable metallic stents for palliative treatment in a case of an 87-year-old female patient with carcinoma of the papilla of Vater. She suffered from both duodenal and biliary stenoses, but refused surgical treatment. For the duodenal stenting, a self-expandable knitted nitinol metallic stent, for esophageal use, was inserted endoscopically. For the biliary stenting, a self-expandable metallic stent, partially polyurethane-covered on the proximal part to prevent tumor ingrowth and overgrowth, was inserted via the percutaneous transhepatic biliary drainage route. No major complications occured during these procedures. After the two stents were inserted in an end-to-side fashion, she was able to eat a normal diet adequately and suffered from no abdominal symptoms and jaundice during the follow-up period of 13 months. These stenting procedures might be less invasive and more useful than surgical treatment and provide long patency of biliary stenting and a good quality of life.

A 50-year-old male received conservative medical treatment for acute exacerbation of chronic pancreatitis. High fever, abdominal pain, as well as enhancement of inflammatory response and pancreatic enzymes in serum, persisted after treatment for 1 month. Purulent pancreatic fluid was drained by endoscopically placing an 8F plastic stent in the main pancreatic duct, resulting in marked improvement of clinical symptoms. This case appears to provide useful information in considering indications for pancreatic stents.

Evidence is accumulating that gap junctional intercellular communication (GJIC) plays an important role in the gastric mucosal defense system. This study was conducted to determine whether GJIC mediates a restitution process in gastric mucosa. Male Sprague-Dawley rats were fasted and anesthetized. Gastric injury was induced by luminal perfusion with 0.2N HCl for 10 minutes. Mucosal integrity was continuously monitored by measuring the clearance of chromium 51–labeled ethylenediaminetetraacetic acid, which was used for analysis of recovery from the injury. Perfusion with 0.25% octanol (OCT; inhibitor of GJIC) was started after acid injury to assess its effect on restitution. The effect of irsogladine (IG; activator of GJIC) was also tested. Gastric mucosal GJIC was immunohistochemically evaluated with monoclonal antibody gap junction protein (connexin 32). Recovery from acid-induced mucosal injury occurred rapidly when acid perfusion was discontinued (within about 60 minutes). OCT, which didn't cause any injury to normal gastric mucosa, significantly inhibited the restitution. IG reversed this inhibition in a dose-dependent manner. In an immunohistochemical study, OCT-induced damage of gap junction was demonstrated, but not after IG pre-treatment. These findings suggest that GJIC may play a critical role in restitution in rat gastric mucosa and that gap junction function may be one of the important factors for the mucosal defense system. (J Lab Clin Med 2000;136:93-9)

Ruptures of nonamebic (pyogenic) liver abscesses into the thorax and peritoneum are very uncommon; but, hepatoduodenal and hepatocolonic fistulas are ever more rare. We report a case where ascending cholangitis was associated with pyogenic liver abscess formation and a gastric fistula. Drainage into the stomach was demonstrated by gastroduodenal endoscopy for gastric bleeding. After fistula formation, we could successfully treat the inflammation caused by infection of Citrobacter freundii and Candida albicans with intravenous infusion of both antibiotic and antifungal agents.

Background : Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer. Although several cytotoxins related to H. pylori have been reported, their effects on gastroduodenal mucosa have not been well evaluated in vivo. Aim : To investigate the effects of the combination of acid and toxic substances derived from H. pylori on gastroduodenal mucosa, and to observe the effect of sucralfate on such factors in the rat. Methods : Male Sprague–Dawley rats were fasted overnight and anaesthetized. The pylorus was ligated, and a double-lumen cannula was inserted into the forestomach for gastric luminal perfusion. In other animals, a cannula was inserted to perfuse the proximal duodenum. 51Cr-EDTA was administered intravenously and mucosal integrity was monitored by measuring the blood-to-lumen 51Cr-EDTA clearance. After 72 h of culture of H. pylori (NCTC11637 and Sydney strain 1), Brucella broth containing 3% FBS was filtered to remove the bacteria (supernate of H. pylori culture fluid; HPsup). HPsup was acidified (pH=2.0) with HCl, and tested for its injurious action on gastric or duodenal mucosa by luminal perfusion. HPsup was incubated with sucralfate for 30 min. The supernate was collected by centrifugation and the pH was readjusted to 2.0. This sucralfate-treated HPsup was used to test the effect of sucralfate against H. pylori-related mucosal injurious factors. Results : Non-acidified and acidified HPsup did not cause any detectable injury to the gastric mucosa. Non-acidified HPsup did not cause injury in the duodenal mucosa. However, acidified HPsup induced a significantly greater increase in 51Cr-EDTA clearance and greater histological damage than in controls. Sucralfate completely reversed this. Conclusion : These results suggest that an H. pylori-related toxic substance may aggravate duodenal acid injury by acting on luminal surfaces, and that the detoxification of this substance by sucralfate may contribute to its anti-ulcer action.

There are two types of carboxypeptidases present in human blood, carboxypeptidase N (CPN) and arginine carboxypeptidase (CPR). CPR is generated during coagulation from a precursor (proCPR) which can be converted to the active form by trypsin in vitro. Since it is difficult to distinguish the two types of carboxypeptidases in human blood by the measurement of enzyme activity, we established a quantitative sandwich ELISA by which CPR can be quantitated. The amount of CPR in plasma, fresh serum and heated serum were essentially the same. Therefore the ELISA assay does not distinguish proCPR, activated CPR and inactivated CPR. With the ELISA method, CPR was quantitated in plasma from fifty patients with rheumatoid arthritis and eleven patients with severe hepatitis as well as healthy individuals. The amount of CPR in plasma obtained from patients with rheumatoid arthritis was not found to be lower than that of normal subjects. Furthermore, the patients who suffered severe hepatitis and had very low levels of CPR-total were fatal. This suggests that a decrease of CPR level might be a good indication of a patient's prognosis to death by hepatitis.

症例は21歳, 男性. 1995年5月, 感冒様症状が出現し, 近医を受診. 肝機能障害を指摘され治療を受けるも軽快せず, 当院を紹介された. 入院時血液生化学検査ではGOT 3, 569U/l, GPT 3, 262U/l, 総ビリルビン値3.5mg/dl, プロトロンビン時間活性 (PT) 37.2%と著明な肝機能障害を認め, また白血球数は500/mm3と著明な低下を示した. 骨髄像では細胞数は減少していたが, 腫瘍細胞は認めなかった. ステロイドパルス療法などの治療により, 自・他覚症状ともに改善し退院したが, 同年10月, 再び肝機能障害が出現し再入院した. 第2回入院時に行った肝生検組織像, および骨髄像で腫瘍細胞を認め, 骨髄染色および表面マーカーから急性リンパ性白血病 (ALL) と診断した. ALLに重症肝障害をきたした報告は, 現在までに本症例を含め4例みられるが, 他の3症例では重症肝障害発症早期に死亡しており, 長期間にわたり経過を観察し得たのは本例のみであった.

In order to estimate the maximum amylograph viscosity of wheat, an automatic method for the measurement of α-amylase activity was developed using a commercial blocked ρ-nitrophenyl maltoheptaoside as a suitable substrate. A Type AAIIauto-analyzer (Bran + Luebbe) partially modified can rapidly and conveniently analyze α-amylase activity at almost 50 samples per hour, and can save the cost of reagents as compared to manual analysis. There was no significant difference between α-amylase activity measured by hand and the auto-analyzer. The α-amylase activity in flour correlated well with the maximum amylograph viscosity (r=-0.922). The correlation coefficient between α-amylase activity and maximum amylograph viscosity was slightly lower in ground wheat (r=-0.906). With regard to fresh wheat, there was no apparent relationship in wheat sampled before maturity, but a high correlation (r=-0.884) was exhibited after maturity. To monitor the levels of maximum amylograph viscosity in cargo samples and classify grades, we made tentative criterion for α-amylase activity in fresh wheat. Group 1: most of the wheat with α-amylase activity below 300 mU/g showed a high amylograph viscosity (mean=755B.U.). Group 2: wheat with α-amylase activity between 300 to 500 mU/g widely ranged from low to high viscosity (mean=502B.U.). Group 3: most of the wheat with α-amylase activity over 500 mU/g showed unacceptably levels of amylograph viscosity (mean=109B.U.). Therefore, the auto-analyzer can be utilized to rank wheat quality at receival points, and can also be adapted as a selection method for the development of low α-amylase varieties in wheat breeding.

Recently geoelectrical monitoring by subsurface visualization has become to contribute to the earth environmental resources problems such as groundwater resource cycling delineation, earth and water contamination, detection of rock fractures in active geothermal energy extraction system, mining with faults and groundwater effects, nuclear waste disposal, and environment/ground improvement by In-Situ Virtrification (ISV) technology. In this paper, a simple model study on resistivity monitoring for the effective utilization of earth resources and environmental system design has been investigated by the subsurface visualization pseudo-effects which are sometimes very useful as same as the high accuracy inverted resistivity solutions by the finite element 2D-3D algorithm.Key words: Subsurface visualized information, Inhomogeneous monitoring, Earth resources and Environmental system design, Enviromental geophysical engineering, Pseudo-effects.

Objectives Sclerosing cholangitis (SC) with autoimmune pancreatitis (AIP) is similar to primary sclerosing cholangitis (PSC) with regard to cholangiographic findings, but only the former responds well to steroid therapy. This report concentrates on the clinical differences between these diseases. Methods The presenting complaint or abnormality, associated disease, cholangiographic findings, pancreatic changes, treatment, and clinical course were studied for several cases of PSC (n = 27) and SC with AIP (n = 20). Results SC with AIP as a diagnosis occurs abruptly with obstructive jaundice compared with PSC where diagnosis is often based on findings of asymptomatic liver test abnormalities. In addition, inflammatory bowel disease is only associated with PSC. The most prominent features of cholangiograms for the SC with AIP cases were stenosis of the lower common bile duct. However, sclerosing changes in the intra- and extrahepatic bile ducts or hilar hepatic region were observed for half of the cases. Only PSC showed stage III or IV liver biopsy findings. IgG4 was significantly higher in SC with AIP. Conclusions SC with AIP and PSC are different clinical entities.

Phospholipase C (PLC)-mediated signal transduction processes in rat hepatocytes are subject to modulation by protein phosphatases (PPases) and protein kinases, including protein kinase A (PKA) and protein kinase C. Ethanol (EtOH) stimulates PLC activity in liver cells in the absence of hormones, and EtOH pretreatment inhibits the subsequent stimulation of PLC by hormonal stimuli. There is evidence that protein kinase activities are involved in these actions of EtOH. We investigated the effects of okadaic acid (OKA), a PPase inhibitor, and 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt-cAMP), a cell permeant cAMP analog that activates PKA, on EtOH-induced PLC activation. In addition, we studied the combined effects of cpt-cAMP and EtOH/OKA on vasopressin-induced PLC activation. PLC activation (cytosolic Ca 2+ mobilization and inositol trisphosphate accumulation) induced by EtOH and vasopressin was inhibited by treatment with OKA, and was potentiated by cpt-cAMP. OKA treatment prevented the effect of cpt-cAMP. Pretreatment with EtOH caused inhibition of vasopressin-induced PLC activation. EtOH also decreased the enhancing effect of cpt-cAMP on the responses to vasopressin. The susceptibility to enhancement by cpt-cAMP plotted as a function of the initial rate of vasopressin-induced Ca 2+ mobilization in EtOH-treated cells was similar to the pattern observed in OKA-treated cells. These data suggest that interactions of OKA and PKA on EtOH-induced PLC activation occurred at the level of G-protein, and indicate that EtOH may act as an inhibitory agent of PPase.

The effect of oxidized and reduced glutathione on inositol 1,4,5-trisphosphate (InsP3)-induced Ca 2+ release from endoplasmic reticular Ca 2+ stores was studied in digitonin-permeabilized hepatocytes from chronically ethanol-fed rats and pair-fed control animals. The fractional Ca 2+ release induced by a subsaturating concentration of InsP3 was significantly enhanced in cells from ethanol-fed rats in the absence of a change in maximal InsP3-releasable Ca 2+ pool size, and this difference was not affected by preincubation with reduced glutathione. Incubation with oxidized glutathione (1 mM) increased the efficacy of Ca 2+ release by subsaturating concentrations of InsP3 in both control preparations and in cells from ethanol-fed rats. The shift in the InsP3 dose-response curve was not significantly different between the two preparations. These findings suggest that the enhanced efficacy of InsP3-induced Ca 2+ release in hepatocytes from ethanol-fed rats is not caused by the oxidation of protein-bound thiol groups on the InsP3 receptor.

Hepatocyte growth factor (HGF) is the most potent mitogen identified for hepatocytes and is thought to be an important growth factor in the regulation of liver regeneration. Its effects are mediated through a tyrosine kinase receptor, the product of c-met proto-oncogene. One of the downstream signaling processes activated by HGF is phospholipase C-y. HGF stimulation of liver cells causes formation of inositol 1,4,5-triphosphate, which releases Ca 2+ from intracellular Ca 2+ ([Ca 2+ ]i) stores, and causes elevation of cytosolic Ca 2+ levels. It is known that liver regeneration is inhibited by both acute and chronic ethanol (EtOH) treatment. We Investigated the effect of EtOH on HGF-induced DNA synthesis and mobilization of [Ca 2+ ] I , in rat hepatocytes in primary culture. DNA synthesis was monitored by [3H]thymidine incorporation in primary cultures of hepatocytes 42 hr after stimulation with HGF. HGF concentration required for maximum DNA synthesis was 0.3 to 1 ng/ml, and DNA synthesis was inhibited by 100 mM EtOH at HGF concentrations in the range of 0.1 to 5 ng/ml. This inhibition was strongest (45 to 47% inhibition) at a low concentration of HGF (0.1 to 0.3 ng/ml) and decreased at an HGF concentration >1 ng/ml. HGF-induced changes in [Ca 2+ ] i were measured in single fura 2-loaded hepatocytes by fluorescence imaging techniques. The Ca 2+ response induced by HGF (0.3 to 5 ng/ml) was inhibited by EtOH, with an EC 50 of 50 mM. Analysis of Ca 2+ response pattems in individual cells indicated that EtOH suppressed the number of responsive cells and made Ca 2+ responses more transient, but did not affect peak [Ca 2+ ] i elevation; thus suggesting an inhibition at the level of phospholipase C-γ-activation. These data indicate that inhibition by EtOH of the response of liver cells to HGF may contribute to the inhibitory effect of EtOH on liver regeneration.

ラット分離肝細胞においてエタノール(EtOH)によるフォスフォリパーゼC(PLC)活性化に対するプロテインフォスファターゼ阻害剤のokadaic acid (OKA)の効果とvasopressinによるPLC活性化に対するEtOHとOKAの相互作用について検討した.EtOH (300mM)刺激によりイノシトールリン脂質(PtdInsP, PtdInsP2)は上昇し,OKA前処置(1μM, 5分間)により,さらに上昇した.EtOH (30-300mM)による細胞内Ca2+([Ca2+]C)の上昇,イノシトール三リン酸(InsP3)の産生はOKA前処置により有意に抑制された.EtOH, OKAはそれぞれvasopressinによるPtdInsP2の分解,InsP3の産生,[Ca2+]C上昇を抑制し,受容体-G蛋白-PLC複合体に作用すると考えられたが,両者併用により相乗・相加効果がみられた.また,この併用効果は飽和濃度のEtOHにおいても認められ,OKAとEtOHは作用部位が異なることが示唆された.

Shunsuke Nojiri,1 Atsunori Kusakabe,1 Kei Fujiwara,1 Noboru Shinkai,1 Kentaro Matsuura,1 Etsuko Iio,1 Tomokatsu Miyaki,1 Tomoyuki Nomura,2 Satoshi Sobue,3 Hitoshi Sano,4 Izumi Hasegawa,5 Tomoyoshi Ohno,5 Yoshitsugu Takahashi,6 Etsuro Orito,7 Takashi Joh11Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, 2Inabe General Hospital, Inabe, 3Kasugai Municipal Hospital, Kasugai, 4Tajimi Prefectural Hospital, Tajimi, 5Social Chukyo Insurance Hospital, Nagoya, 6Chita Kousei Hospital, Aichi-ken, 7Nagoya Daini Red Cross Hospital, Showa-ku, JapanBackground: Sorafenib has been approved in the indication of unresectable hepatocellular carcinoma, but there are many cases in which administration of the drug is discontinued due to severe side effects. In this study, we compared the characteristics of patients who continued and discontinued sorafenib.Methods: Ninety-six patients (75 men and 21 women) were initiated on sorafenib from July 2009 through September 2011. The patient characteristics of interest included gender, age, etiology, Child-Pugh classification, treatment history and frequency, and levels of α-fetoprotein, des-gamma-carboxy prothrombin, aspartate amino acid transferase, and alanine aminotransferase. Duration of administration of sorafenib and reasons for its discontinuation were compared.Results: Median overall survival was 11.8 months. Discontinuation of sorafenib within 90 days was identified as an independent prognostic factor for overall survival on multivariate analysis (P < 0.0001). Transarterial chemoembolization performed six times or more (P = 0.013) was also identified as an independent factor contributing to discontinuation of sorafenib within 90 days in multivariate analysis. Patients who received sorafenib for ≥90 days had significantly longer overall survival than those who discontinued it (P < 0.0001).Conclusion: Prolonged treatment with sorafenib is an important factor in achieving extended overall survival. We recommend starting sorafenib before latent liver damage has occurred as a result of too many transarterial chemoembolization procedures.Keywords: sorafenib, hepatocellular continuation, discontinuation, efficacy