Search

Multiseptate gallbladder is a rare congenital malformation. We present a case that emphasizes the importance of ultrasonography and magnetic resonance imaging. Ultrasound examination of the abdomen showed multiple linear internal echoes consistent with multiple septa crossing the entire gallbladder lumen, creating a honeycomb appearance. Magnetic resonance cholangiopancreatography showed a grapelike cluster of the whole gallbladder.

Intramural injection of peptidoglycan-polysaccharide polymers into the distal colon in rats induces granulomatous colitis associated with extracolonic manifestations. We sought to clarify the effects of Kupffer-cell depletion induced by the intravenous administration of gadolinium on colonic and extracolonic inflammation in this model. The effects of Kupffer-cell depletion on acute and chronic inflammation were evaluated 3 days and 3 weeks after injection of peptidoglycan-polysaccharide, respectively. We assessed the effects of gadolinium on colonic cytokine levels in vivo and the viability of elicited peritoneal macrophages and peptidoglycan-polysaccharide-induced production of nitrite, an indirect index of nitric oxide production, by these cells in vitro. A single injection of gadolinium caused a marked decrease in the number of Kupffer cells stained with antibodies within 3 days. Gadolinium treatment did not alter acute inflammation at 3 days. Repeated treatment with gadolinium dramatically attenuated grossly observed chronic inflammation, including thickening of colon wall, hepatic and splenic nodules, and swelling of foot joints; and significantly reduced the proportional areas occupied by granulomas in the colon, liver, and spleen at 3 weeks. These protective effects were reflected in significant reduction in colon and liver weights; gross scores; colonic myeloperoxidase activity, an indirect quantitative index of granulocyte infiltration; colonic interleukin-1β levels; plasma nitrite and nitrate levels; and decreased tendency toward arthritis. Although gadolinium did not cause injury in elicited peritoneal macrophages in vitro, the compound dose-dependently attenuated peptidoglycan-polysaccharide–induced production of nitrite by these cells. Chronic Kupffer-cell depletion attenuates peptidoglycan-polysaccharide–induced granulomatous inflammation in the colon, liver, and spleen and reduces the incidence of arthritis, possibly by suppressing the production of interleukin-1β and nitric oxide.

We examined taurochenodeoxycholic acid-induced hepatotoxicity with reference to Ca2+ and calpain involvement, intracellular bile acid content, and zone specificity in isolated perfused rat liver.Taurochenodeoxycholic acid or chenodeoxycholic acid was infused into the portal vein and lactate dehydrogenase release, a marker of hepatocyte injury, in the effluent and bile acid output were measured in the presence and absence of either nickel, a membranous Ca2+ channel blocker, or calpain inhibitor in isolated perfused rat liver.Taurochenodeoxycholic acid induced a significant and transient increase (first peak; 4 min) and subsequent time- and dose-dependent elevation in lactate dehydrogenase release which was proportional to accumulated bile acids in the liver. Although the first peak was significantly suppressed by pretreatment with nickel, the subsequent release was not reduced. Lactate dehydrogenase release at 15, 20, and 25 min was significantly suppressed by the calpain inhibitor. Numbers of damaged hepatocytes stained with trypan blue were significantly increased in the periportal region (zone 1) compared with the pericentral region (zone 3) and these cells were consistently stained with anti-calpain antibody.Taurochenodeoxycholic acid causes both transient damage and subsequent increasing hepatotoxicity which are respectively dependent on Ca2+ influx via membranous Ca2+ channels and calpain, with the periportal region being more susceptible.

This is a review of the characteristic findings of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) and their usefulness in the diagnosis of sclerosing cholangitis. PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD. IBD-associated with PSC (PSC-IBD) shows an increased incidence of pancolitis, mild symptoms, and colorectal malignancy. Although an increased incidence of pancolitis is a characteristic finding, some cases are endoscopically diagnosed as right-sided ulcerative colitis. Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon. The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition. The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are similar to those of PSC. The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.

We assessed T cell association with acinar cell apoptosis and a preventive effect of tacrolimus, a T cell suppressant, on the development of chronic pancreatitis in male Wistar Bonn/Kobori rats. At 15 wk, cellular infiltrates composed of F4/80-positive cells (monocytes/macrophages), CD4-positive cells, and CD8-positive cells were extensive in the interlobular connective tissue and parenchyma. In particular, CD8-positive cells invaded pancreatic lobules and formed close associations with acinar cells, some of which demonstrated features of apoptosis. At 20 wk, CD8-positive cells were still abundant in the fibrotic tissue formed with loss of acinar cells. Repeated subcutaneous injection of 0.1 mg · kg−1· day−1but not 0.025 mg · kg−1· day−1of tacrolimus for 10 wk completely prevented the occurrence of acinar cell apoptosis, infiltration of CD4- and CD8-positive cells, and development of pancreatitis at the age of 20 wk, but these maneuvers did not recover the decreased plasma corticosterone levels, which may be responsible for the development of disease. We demonstrated that T cells, possibly CD8-positive cells, are involved in inducing apoptosis of acinar cells, raising the possibility that tacrolimus might find clinical application in the treatment of autoimmune chronic pancreatitis.

We report the case of a 34-year-old woman with a solid cystic tumor (SCT) of the pancreas accompanied by ossification and possible malignancy, coexisting nonfusion of the pancreatic ducts. There was a 24 x 29 x 33-mm mass with a prominent calcified lesion in the tail of the pancreas detected by abdominal ultrasonography, computed tomography, and magnetic resonance imaging. There were no distal metastases detected. Endoscopic retrograde pancreatography revealed nonfusion of the pancreatic ducts. The resected tumor consisted of solid and cystic components. The tumor was not encapsulated and included a severely ossified lesion inside. On microscopy, the tumor cells were small, eosinophilic, and proliferated in a solid or pseudo-papillary pattern. The tumor cells infiltrated into the surrounding normal pancreas parenchyma and invaded part of the mesentery. The immunostaining was positive for alpha-1-antitrypsin, neuron-specific enolase, vimentin, and chromogranin A. In the literature, only a few cases of SCT of the pancreas described ossification. As far as we know, only three cases of SCT of the pancreas, which demonstrated nonfusion of the pancreatic ducts, have been reported. Thus, SCT of the pancreas with ossification, possible malignancy, and coexisting nonfusion of the pancreatic ducts is extremely rare.

The involvement of pancreatic acinar cell apoptosis and its relation to glucocorticoid exposure were investigated in spontaneously occurring chronic pancreatitis in male Wistar Bonn/Kobori (WBN/Kob) rats. Although most lobules were not inflamed in 10-week-old WBN/Kob, increased apoptosis of pancreatic acinar cells, confirmed by TUNEL staining was focally observed (0.10 +/- 0.10 vs. 0.05 +/- 0.10/field in 10-week Wistar rats). Localized hemorrhagic lesions and brown foci in the splenic lobes were apparent, with significant decrease in pancreas weight in 20-week WBN/Kob rats along with marked apoptosis (1.95 +/- 0.31 vs. 0.07 +/- 0.04/field in 20-week Wistar rats). Electron microscopy revealed apoptotic bodies to be present in acinar cells. Pancreatic myeloperoxidase activities, indirect indices of granulocyte infiltration, as well as histologic scores were significantly increased at 15 and 20 weeks, and endogenous corticosterone levels were significantly decreased at 10, 15, and 20 weeks as compared with values for age-matched Wistar rats. Prednisolone in the drinking water (0.01 mg/mL; calculated dose, 1.03 0.03 mg/kg/d) for 10 weeks significantly attenuated increases in numbers of apoptotic acinar cells and pancreatic myeloperoxidase activities and tended to reduce the histologic scores in 20-week WBN/Kob rats as compared with the vehicle group. In summary, (a) apoptosis of pancreatic acinar cells is involved in chronic pancreatitis, (b) endogenous corticosterone is decreased, and (c) prednisolone treatment attenuates both apoptosis of pancreatic acinar cells and chronic pancreatitis in male WBN/Kob rats. We conclude that apoptosis of acinar cells related to decreased corticosterone may be a trigger of chronic pancreatitis in this model.

Background Mixed-lineage leukemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukemia (AML), and are associated with poor prognosis. Report of the incidence and prognostic relevance of MLL-PTD in pediatric AML is limited and large differences in the frequency have been reported. In pediatric AML cases, a frequency of 10-13% for MLL-PTD was detected using mRNA RT-PCR, whereas a frequency of only 2.5% was detected using multiplex ligation-dependent probe amplification (MLPA). We studied the frequency and prognostic effect of MLL-PTD in pediatric patients with AML treated with JPLSG AML-05 trial (between 2006-2010). Methods MLL-PTD of 331 pediatric de novo AML in the AML-05 trial was analyzed from genomic DNA extracted from their diagnostic bone marrow samples using MLPA analysis. We designed a probe mix for MLPA analysis containing adjacent probes within exon 2-5 and exon 7-13 of the MLL gene for the detection of common and rare type MLL-PTD. Exon 17 of the MLL gene was used as an internal control. We also performed RT-PCR to detect MLL-PTD transcripts to allow comparison with the MLPA results. To assess whether MLL-PTD overlap with known gene abnormalities, such as FLT3, KIT, and NPM1 mutations, mutational analyses of these genes were also performed in patients in the AML-05 trial. Results MLL-PTD was detected in 9 (2.7%) of 331 patients by MLPA analysis. In 303/331 samples mRNA RT-PCR screening for MLL-PTD was performed, and MLL-PTD was detected in 38 (12.5%). In 9 cases, both MLPA and mRNA-RT-PCR were positive for MLL-PTD. The characteristics of the 9 patients with MLL-PTD using MLPA analysis were below. None of the patients harbouring an MLL-rearrangement, t(8;21) or inv(16) revealed a MLL-PTD. All MLL-PTD cases were found in patients with normal cytogenetics. FLT3-ITD was present in 4 of 9 patients with MLL-PTD, while none of KIT and NPM1 mutation was detected in MLL-PTD cases. There was a significantly higher frequency of FLT3-ITD in patients with an MLL-PTD than in those without MLL-PTD (p=0.016). Among these 9 patients, 5 patients were classified as FAB-M5a (p=0.0068), and other 4 patients were classified as FAB-M1, M2, M4 and M6a. The age of patients with MLL-PTD was higher than that of patients without MLL-PTD (median 11.8 years (range; 9-15) and 7.4 years (range; 0-17), respectively; p=0.004). Patients with MLL-PTD tend to have higher white blood cell counts (WBC) at initial diagnosis than those without MLL-PTD (median WBC 6.0×10*9/l (range; 1500-151000) versus 2.2×10*9/l (range; 617-985000a) respectively; p=0.18). All 9 patients with MLL-PTD had events. There was a significantly higher frequency of event including refractory disease, relapse and death in patients with an MLL-PTD than in those without MLL-PTD (p=0.001). Only one of 9 patients was achieved complete remission (CR) after induction therapy (p= 1.1×10-11). Six of 9 patients relapsed, and 5 patients died. Conclusion Using DNA-MLPA as a novel screenings technique, low frequency of MLL-PTD in pediatric AML was found. However, MLL-PTD is highly associated with a poor prognosis in pediatric AML. These data suggest that screening for MLL-PTD in pediatric patients with AML is critical not only for outcome prediction but also for risk-adapted therapy. Disclosures: No relevant conflicts of interest to declare.

Background Granulocyte colony-stimulating factor (G-CSF; CSF3) and its receptor (G-CSFR; CSF3R) control neutrophil production under basal circumstances and during episodes of bacterial infections. Mutations in a region of the CSF3R gene coding for the intracytoplasmic domain of the G-CSFR have been discovered in patients with severe congenital neutropenia (CN) and were initially suggested to be the cause of CN. Mutations in CSF3R gene are regarded as an early marker of malignant transformation in CN. Common genetic abnormalities like acquired clonal cytogenetic alterations or activating RAS mutations have also been observed to be associated with CN-related myelodysplastic syndrome(MDS)/leukemia. In adults, a frequency of CSF3R mutation was common (59%) in patients with chronic neutrophilic leukemia (CNL) and atypical (BCR-ABL1–negative) chronic myeloid leukemia (CML), whereas that was low (1%) in patients with de novo acute myeloid leukemia (AML). Sequence variants that were identified included membrane proximal mutations and a number of different frameshift or nonsense mutations that truncate the cytoplasmic tail of CSF3R. These mutations segregate within two distinct regions of CSF3R and lead to preferential downstream kinase signaling through SRC family-TNK2 or JAK kinases and differential sensitivity to kinase inhibitors. However, little is known about the incidence and prognostic values of CSF3R mutations in pediatric myeloid malignancies. Methods CSF3R mutations (exon14 and 17) in a total of 376 samples of pediatric de novo AML, 40 samples of juvenile myelomonocytic leukemia (JMML), and 20 samples of MDS were analyzed from gDNA or cDNA extracted from diagnostic bone marrow samples using direct sequencing. Moreover, we assessed whether CSF3R mutations overlap with known gene abnormalities, such as FLT3, c-KIT, NPM1 and SETBP-1. Mutational analyses of FLT3, c-KIT, NPM1 and SETBP-1 were also performed in AML samples. Results We identified a CSF3R mutation in 5 of 376 patients (1.3%) with AML, 2 frameshift mutations (E788X) and 3 missense mutations (L777F and T618I). The patients with 3 (L777F and E788X) of these 5 mutations had complex chromosomal abnormalities involved in chromosome 8 and 21 (t(8;21) and ins(21;8); AML1/ETO). The other 2 patients with missense mutations (T618I) had normal karyotype. They presented with a relatively high WBC counts of 100.6×10*9/l and 159.5×10*9/l. Although 2 of 5 these patients relapsed, all of them were salvaged successfully. Two of 5 had c-KIT mutations, while none of them had FLT3, NPM1, and SETBP-1 mutations. No mutations of CSF3R in JMML and MDS patients were found. Conclusions To our knowledge, this is the first report to describe the CSF3R mutation in a pediatric de novo AML patient. In our study, CSF3R mutation is detected in 1.3% in childhood de novo AML, which suggests the involvements of CSF3R mutations in the pathogenesis of pediatric de novo AML, JMML and MDS are extremely rare compared with those in SCN and adult CNL and atypical CML cases. Since CSF3R mutation is rare event, the prognostic values of CSF3R mutations in de novo AML are still unclear. Further data accumulation is necessary. Disclosures: No relevant conflicts of interest to declare.

To investigate the microdynamics and the structural architecture of the membrane phospholipid bilayer during the course of cardiomyopathy, membrane fractions were prepared from hearts of cardiomyopathic Syrian hamsters (BIO 14.6) aged 4, 18 and 31 weeks and compared with age-matched control hamsters (F1b). Membrane cholesterol, phospholipids and phospholipid fatty acids were measured by thin-layer chromatography, gas-liquid chromatography and high performance liquid chromatography. Microdynamics of the phospholipid bilayer were determined by a nanosecond fluorometer using pulsed excitation of a fluorescent probe, diphenyl-hexatriene. At the age of 4 weeks, there was no difference in lipid compositions and microdynamics between the BIO 14.6 and F1b. At the age of 18 weeks, saturated fatty acids, 18:0 and 22:0 increased and 20:0, 20:2 and 32:4 decreased in the BIO 14.6. At the age of 31 weeks, adding to the above changes in phospholipid fatty acids, unsaturated fatty acids 20:4 and 22:6 decreased, moreover membrane phospholipids, especially phosphatidylinositol and phosphatidylethanolamine significantly decreased. The viscosity and the wobbling angle of phospholipid molecules were decreased significantly. We have previously demonstrated that intracellular Ca2+ accumulation might be responsible for the pathogenesis of cardiomyopathy. Thus, we conclude that cardiomyopathic membrane may alter its structure and function with age. These alterations in cell membranes might be involved in the cardiac hypertrophy and dysfunction through impaired Ca2+ handling in cardiomyopathic hamsters.

We demonstrated that phosphatidylinositide-specific phospholipase C (PLC) activity was greater in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) then in hamster controls (F1b). Inositol trisphosphate (IP3) production was markedly greater in both of the cardiomyopathic hamsters, BIO 14.6 and BIO 53.58. We have also determined the sarcoplasmic reticulum (SR) function of heart. Calcium uptake into SR markedly increased in BIO 14.6. On the other hand, it significantly decreased in BIO 53.58 compared with F1b. It is well known that IP3 stimulates calcium release from SR. In BIO 14.6, calcium relrease from SR stimulated by IP3 increased, but its effect decreased in BIO 53.58 compared with F1b. These results suggest that PI response may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in the BIO 53.58 hamster the sarcoplasmic reticulum deteriorate in function. It was concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes. The expression of angiotensinogen mRNA was observed in the hamster heart. There was no differences in its expression level between F1b, BIO 14.6 and BIO 53.58. There was no effect of ages on its expression in these hamster hearts. We have also determined the distribution of angiotensinogen in these hamsters. At 4 weeks of age, the immunohistochemical study revealed that angiotensinogen was widely distributed in subendcardium in these hamsters. There was no difference in its distribution between F1b, BIO 14.6 and BIO 53.58. But at 20 weeks old of age its immunoreactivity decreased in BIO 53.58. There was no effect of age on its reactivity in F1b and BIO 14.6. We have detected angiotensinogen in heart, but its role is still not clear. A further study should be done to clarify its role in cardiac hypertrophy and cell damage.

The accumulation of both Inositol-(1,4,5)-trisphosphate (IP3) and Inositol-(1,3,4,5)-tetrakisphosphate (IP4) after hormonal stimulation has a physiological role, possibly in altering Ca2+ levels in cardiac tissue. However, the accumulation of inositol polyphosphate under pathophysiological conditions has not been studied. In our experiments the metabolism of phatidylinositol and IP3 in cardiac myocytes as investigated. It was shown that basal levels of cytosolic phosphatidylinositol specific phospholipase C (PI-PLC), phosphatidylinositol-(4,5)-bisphosphate specific phospholipase C (PIP2-PLC) activities markedly increased in stroke-prone spontaneously hypertensive rats (SHRSP) with age compared with age matched Wistar Kyoto rats (WKY). IP3 kinase and IP3 phosphatase activities also increased in SHRSP hearts with age. Their activities increased in WKY, but to a lesser extent than in SHRSPs. These data suggest that a PI turnover pathway such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride-protein kinase C pathway may have an important role in the development of hypertrophy in SHRSP heart.

In cardiac hypertrophy,collagen accumulation in the myocardial interstitium is associated with hypertrophy of cardiomyocytes [1]. Collagen remodeling causes impaired ventricular compliance,abnormal electrical conduction and impaired oxygenation of the cardio-myocytes [2].At present,factors that regulate cardiac collagen metabolism are not elucidated.Eghbali et al [3] found that cardiac fibroblasts are mainly responsible for the synthesis of fibrillar type I and III co11agen.Recent studies have demonstrated that angiotensin II (A II),in addition to its inotropic and chronotropic actions,may exert effects by acting as a growth factor in the car¬diovascular system and that there may be local autocrine or paracrine renin-angiotensin system in several tissues [4].There are no data concerning the effects of A II on cardiac nonmyocytes.In this study we examined the effects of A II on collagen synthesis by cardiac fibroblasts in normotensive and hypertensive rats.

Plasma membrane inositol phospholipids were breakdown by hormones and neurotransmitters through the mediation of the specific receptors (1–4). This phosphatidylinositol (PI) turnover pathway generates two second messengers, inositol-(l,4,5)-trisphosphate (IP3) and sn-1,2-diacylglycerol (DAG) (5,6). DAG stimulates membrane-bound phospholipid-dependent, Ca2+- dependent protein kinase C (7), while IP3 releases Ca2+ from stores in the sarcoplasmic reticulum (8,9). The physiological significance of this Pi–turnover pathway is not still clear in any mammalian cell system. It is controversial whether IP3 stimulates Ca2+ release from SR in cardiac myocytes.

It has been demonstrated that components of the renin-angiotensin system such as renin, angiotensinogen (ATN), angiotensin-converting enzyme (ACE) and angiotensin II receptor exist within the heart and function independently from circulating renin-angiotensin system [1–4]. The potent myotropic actions of angiotensin II, as well as its effects on positive inotropism and chronotropism, make it likely that the heart is the site of a locally active renin-angiotensin system. It is suggested that angiotensin II is one of the contributing factors to regulation of cell growth, moreover, ACE inhibitors regress left ventricular hypertrophy. The purpose of this study is to determine whether intrinsic renin-angiotensin system play a role for the development and the regression of left ventricular hypertrophy in spontaneously hypertensive rats (SHR).

Introduction Inflammatory pseudotumor is rare benign mass composed of chronic inflammatory cell infiltration and proliferating fibrous tissue. Some cases of inflammatory pseudotumor show abundant infiltrating IgG4-positive plasma cells and obliterative phlebitis, which are the pathologic hallmarks of autoimmune pancreatitis. Case presentation A 77-year-old Japanese man was admitted to our hospital because of epigastric pain. A solitary mass with delayed enhancement by dynamic computed tomography was present in the left hepatic lobe. Endoscopic retrograde cholangiography showed only segmental stenosis of the left intrahepatic bile duct. No abnormal findings were detected in the pancreas. The patient was clinically diagnosed as having intrahepatic cholangiocarcinoma and underwent surgery. Histological examination of the hepatic mass and bile duct wall showed abundant IgG4-positive plasma cell infiltration with obliterative phlebitis. The final diagnosis was IgG4-related hepatic inflammatory pseudotumor with sclerosing cholangitis. Delayed enhancement by computed tomography is a characteristic feature of IgG4-related inflammatory pseudotumor similar to that of autoimmune pancreatitis. Conclusion IgG4-related hepatic inflammatory pseudotumor unassociated with autoimmune pancreatitis should be one of the entities considered for differential diagnosis of liver tumors. Delayed enhancement on computed tomography might be useful finding for diagnosing IgG4-related hepatic inflammatory pseudotumor.

We demonstrated that the activities of phosphatidylinositide-specific phospholipase C, inositol 1,4,5-trisphosphate (IP3) kinase, and IP3 phosphatase were enhanced in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) in comparison to control hamsters (F1b). Release of both arachidonic acid and prostacyclin was markedly enhanced by norepinephrine in the cardiomyopathic hamsters. Phospholipase C in heart has high substrate specificity to phosphatidylinositol. IP3 production was markedly enhanced in the cardiomyopathic hamsters. We also determined the intracellular calcium concentration, which was higher in BIO 53.58 hamsters than in BIO 14.6 hamsters at 5-20 weeks of age. There was no significant difference in the intracellular calcium level between F1b and BIO 14.6 hamsters at 5 weeks of age. These results suggest that phosphatidylinositol turnover stimulated by norepinephrine may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in BIO 53.58 hamsters, some mechanism such as the sarcoplasmic reticulum, which controls the intracellular calcium level, may deteriorate in function. We concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes.

In this study, we examined the effects of streptokinase on arachidonic acid release and prostacyclin biosynthesis in cultured bovine pulmonary artery endothelial cells. When intact cells were incubated with streptokinase, a significant stimulatory effect on prostacyclin biosynthetic activity in cells was evident without any cellular damage at all concentrations used (1–10 000 units/ml). Streptokinase also caused a marked release of arachidonic acid. It induced rapid phospholipid hydrolysis, resulting in the release of up to 15% of incorporated [ 3 H]arachidonic acid into the medium. After the addition of streptokinase, degradation of phosphatidylcholine and phosphatidylethanolamine was observed and lysophosphatidylcholine and lysophosphatidylethanolamine were produced. We also observed a transient rise in diacyglycerol after the addition of streptokinase. To test for phospholipase C activity, the release of incorporated [ 3 H]choline, [ 3 H]inositol and [ 3 H]ethanolamine into the culture medium was determined. The level of radioactive inositol showed an increase, but the changes in choline and ethanolamine were comparatively small. An increase in inositol was detectable within 1 min after streptokinase addition and peaked after 15 min. Inositol phosphate and inositol trisphosphate were released, and these releases were suppressed by the addition of neomycin (50 μM). These results suggest that streptokinase stimulates phospholipase A 2 and C activity, and that prostacyclin biosynthesis is subsequently increased in cultured endothelial cells.

1) Captopril was orally administered in a dose of 12.5 mg to 12 patients with congestive heart failure to follow changes in its blood concentration and determine changes in clinical test values. 2) The blood concentration of captopril reached its peak in 2 h after medication, the mean value being 274 ng/ml and the half-life 3.16 h. The Tmax and T1/2 were found to be extended as compared with those of normal humans and hypertensive patients that had been reported. No significant differences were noted between Group I of mild cases and Group II of serious cases. 3) Following administration of captopril, a rise in angiotensin I and renin activity and a reduction in aldosterone were noted. These were found to be correlated or inversely correlated with the changes in the blood concentration of captopril. Greater changes were noted in Group II than in Group I. All clinical test values in each group tended to return to the control value 6h after the administration.

症例は，45歳男性大酒家．膵石，膵嚢胞の治療目的にて紹介となる．各種画像検査にて，膵管の拡張，膵管内に多数の結石像を認め，膵頭部には，膵管と交通を有する7cm大の嚢胞性病変を認めた．膵石に対するESWL治療に先立ち，膵嚢胞の縮小目的にて，経乳頭的にステントを挿入した．術後4日目に発熱を認め，高度の炎症所見および膵嚢胞の増大を認めたため，経皮的に膵嚢胞ドレナージを行った．術後経過は良好で膵嚢胞は消失し，膵石はESWL治療にて消失した．本例は，膵嚢胞を有する膵石症治療の上で，示唆に富む症例と考えられ，ここに報告した．

To the Editor:Autoimmune pancreatitis (AIP) is a recently recognized disorder and a new clinical entity associated with the irregular narrowing of the pancreatic duct and the enlargement of the entire pancreas.1 AIP is often associated with sclerosing cholangitis (SC). SC with AIP and primary sclero

Background: Acute pancreatitis is the most common complication of ERCP. Many risk factors such as direct mechanical trauma, hydrostatic forces, chemical effects of contrast agent injected under pressure, and microbial contamination for post-diagnostic ERCP pancreatitis have been reported. However, whether patency of the accessory pancreatic duct (APD) influences post-diagnostic ERCP pancreatitis is unknown. Aim: To evaluate the closure of the APD and several other risk factors for post-diagnostic ERCP pancreatitis. Patients and Methods: This study was conducted on 536 patients from 836 consecutive ERCPs over the past seven years. Serum pancreatic enzymes (amylase, lipase, elastase-1, trypsin, pancreatic secretary trypsin inhibitor {PSTI}) and neutrophil counts were evaluated at pre- , 5, 24, 48 and 72 hours after ERCP. Percent of increase compared with pre- ERCP value also estimated respectively. The severity of pancreatitis was classified into three groups (severe, moderate, or mild) according to the established criteria. By multivariate analysis, twelve factors: age, gender, cannulation frequency, bile duct cannulations, pancreatic contrast injections, closure of the APD, pre-ERCP values of serum pancreatic enzymes and neutrophil counts were evaluated. Results: Overall, 14/536 (2.6%) patients developed pancreatitis; 6 mild, 6 moderate, 2 severe. Patency of APD was significantly lower in the pancreatitis group than that in the non-pancreatitis group (pancreatitis vs. non-pancreatitis: 2/14, 14.3% vs. 173/522, 33.1%, respectively). The rate of pancreatitis was significantly higher in the closed APD group than in the patent APD group and two cases with severe pancreatitis were documented only in the closed APD group (closed vs. patent: 12/246, 4.9% vs. 2/175, 1.1% and 2 severe, 5 moderate, 5 mild vs.1 moderate, 1 mild). In the non-pancreatitis group, serum pancreatic enzyme values at pre-ERCP were similar between closed and patent APD groups, whereas the percent increases at 24 and 48 hours after the procedure in the closed group were higher than those in the patent group. By multivariate analysis, the significant risk factors were: female sex, cannulation frequency, closure of APD, bile duct cannulations, and pancreatic contrast injections. Conclusion: Closure of APD also carries a high risk of developing post-diagnostic ERCP pancreatitis. The appropriate use of this new prognostic indicator may provide a significant benefit in the early diagnosis of post-ERCP pancreatitis.

Background/Aim: Endoscopic pancreatic stenting is performed to reduce pancreatic intraductal pressure and/or to release stricture of the pancreatic duct. However, endoscopic sphincterotomy(EST) or endoscopic pancreatic sphincterotomy(EPST) as a pretreatment of stenting, may cause bleeding, perforation and pancreatitis. Furthermore, EST/EPST may cause retrograde infection of the bile and pancreatic ducts. To establish a more convenient and safer method of endoscopic pancreatic stenting, we have prospectively performed stenting without EST or EPST. Methods: From Jan. 1991 to Oct. 1999, we performed pancreatic stenting in 20 patients (aged 21-80, median=50, M:F=18:2). 15 patients consumed alcohol regularly, and 17 patients had pancreatolithiasis. We used polyethylene tubes(5Fr-10Fr) to create stents. Stenting was performed in the following cases: 1)abdominal and back pain caused by stricture of the pancreatic duct or increased intrapancreatic ductal pressure due to pancreatolithiasis (9 cases), 2)an adjuvant therapy for extracorporeal shock wave lithotripsy(ESWL) for pancreatolithiasis (6 cases), 3)obstructive acute suppurative pancreatitis due to stricture or stones (3 cases), and 4)intractable pancreatic pseudocysts that connected with the pancreatic duct (2 cases). Results: Pancreatic stenting was successful in 19 of 20 cases (95%) without EST or EPST (except 1 case, EPST had been previously performed). We placed stent through major papillae in 14 (5Fr-7Fr:2, 8Fr:8, 10Fr:4) cases, and through minor papillae in 5 (7Fr:1, 10Fr:4) cases. The periods of stenting were 10 to 780 days (median=78). Symptoms disappeared or improved in 8 of 9 cases with pain; discharge of stone fragments was hastened in 100% of ESWL cases; acute pancreatitis was improved in 100% of cases, and pseudocysts reduced in 1 out of 2 cases. Therefore, stenting effectiveness was 90%. Complications included occlusion of stents (2 cases), migration into the pancreatic duct (1 case) and transient hepatic dysfunction (1 case). Conclusions: EST or EPST is not necessary for endoscopic pancreatic stenting in most patients. Pancreatic stenting may be a useful therapy to improve symptoms associated with chronic pancreatitis.

Background/Aim: The low cost and ease of handling of biliary plastic tube stents has led to their extensive use, however clogging of stents remains a major problem. While biliary expandable metallic stents (EMS) improved patency, they are unsuitable for primary biliary stenting because of their high cost and difficulty in replacement. Recently, biliary tube stents without sideholes were also reported to prolong patency. To evaluate the clinical utility and relative advantages of three types of biliary stents, we reviewed clinical results of three types of stents, including; 1) plastic tube stents with sideholes (PWS), 2) plastic tube stents without sideholes (PWOS) and 3) EMS. Patients and methods: 128 patients (M:F=72:56,mean age 69 years, range 34-91) consisting of 52 with pancreatic cancer, 24 with gallbladder cancer, 22 with biliary cancers, 18 with metastatic lymph nodes, 4 with Vater papilla cancer, and 8 with other malignant diseases. PWS (10 Fr), PWOS (double layer stents, Olympus, 10Fr or Soehendra tannenbaum stents, Wilson Cook, 10Fr), and EMS (Boston scientific, 30Fr) were inserted in 65, 25, and 38 cases, respectively. Cumulative stent patency of each stent was analyzed with Kaplan-Meier method, supplemented by Wilcoxon's method. Medical costs of each stent insertion were compared(as $1=105yen). Results: PWS and PWOS were inserted as the primary stenting whereas EMS were inserted as the secondary in all cases.Overall cumulative stent patency rates of EMS and PWOS were significantly higher than that of PWS, and their patency rates at 50, 100, and 200 days were: EMS; 94, 81, and 66%, PWOS; 95, 87, and 39%, and PWS; 70, 41, and 31%. In middle and lower biliary tract strictures, patency of EMS and PWOS were significantly higher than that of PWS, and their patency rates were: EMS; 93, 80, and 63%, PWOS; 94, 86, and 46%, and PWS; 77, 54, and 43%. In the cases with pancreas cancer, cumulative patency rates of EMS and PWOS were significantly higher than that of PWS. These patency rates were: EMS; 94, 72, and 60%, PWOS; 90, 90, and 61%, and PWS; 63, 49, and 37%. In Japan, PWS, PWOS, and EMS cost $24, $133, and $2,286, respectively and ERCP costs $721. Then the costs divided by mean patent period of PWS, PWOS, EMS were $9.3, $7.9, and $19.6/day, respectively. Conclusion:We recommend PWOS for the primary biliary stenting in the middle and lower biliary stricture, especially those due to pancreatic cancer, based on its lower price and sufficient patency without replacement after diagnoses of inoperability.

We report a case of idiopathic portal hypertension associated with prominent polyclonal hyperimmunoglobulinemia and plasmacytosis in the bone marrow and the spleen. Microscopic examination of the liver showed chronic inflammation in the portal area and abnormal vasculature adjacent to the portal tracts. In the spleen, polyclonal plasma cell proliferation was demonstrated histochemically in addition to the presence of remarkable sinus hyperplasia and periarterial fibrosis. In the present case, a chronic inflammatory state such as connective tissue disease was strongly suspected to exist in the liver, since pancytopenia and hyperimmunoglobulinemia persisted even after splenectomy. It is suggested that the pathogenesis in the present case may have been due to this chronic inflammatory state.

The effects of various therapeutic drugs for ulcer on oxygen consumption and anaerobic glycolysis of the gastric mucosa and the ulcer tissue were investigated utilizing Warburg manometer, the oxygen consumption and the glycolysis were markedly promoted with 3 types of drugs, namely Calf Blood Ex., Gefarnate and Human Placenta Ex. Accordingly, it seems that the results mentioned above can be one of the guides for the clinical treatment of peptic ulcer.

Various autoantibodies have been reported to be detected during the progression of infectious mononucleosis. We observed a case of infectious mononucleosis due to Epstein–Barr virus primary infection for 2 months, and noticed the transiently increased titer of thyrotropin receptor autoantibodies detected at the acute phase on the 3rd day after admission. At that time, real-time quantitative PCR also revealed the mRNA expressions of an immediate early lytic gene, BZLF1, and a latent gene, EBNA2. The expression of BZLF1 mRNA means that Epstein–Barr virus infects lytically, and EBNA2 protein has an important role in antibody production as well as the establishment of Epstein–Barr virus latency. These results suggest that Epstein–Barr virus lytic infection is relevant to thyrotropin receptor autoantibody production. Thyrotropin receptor autoantibodies stimulate thyroid follicular cells to produce excessive thyroid hormones and cause Graves’ disease. Recently, we reported the thyrotropin receptor autoantibody production from thyrotropin receptor autoantibody-predisposed Epstein–Barr virus-infected B cells by the induction of Epstein–Barr virus lytic infection in vitro. This case showed in vivo findings consistent with our previous reports, and is important to consider the pathophysiology of Graves’ disease and one of the mechanisms of autoimmunity.