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Biomedical subjects

Keiko Shiratori

Publications and source records attributed to Keiko Shiratori.

At least 19 recordsLinked to original sources

Prevalence of pancreatic and biliary tract tumors in pancreas divisum.

BACKGROUND: The present study was undertaken to evaluate the prevalence of pancreatic and biliary tract tumors in pancreas divisum (PD). METHODS: A retrospective single-center study was performed, and a total of 118 cases of complete PD and 7850 cases of fused pancreas were identified among the 8537 consecutive new endoscopic retrograde cholangiopancreatography (ERCP) examinations performed between 1980 and 2002. The prevalence of pancreatic cancer (PCA), intraductal papillary mucinous neoplasms (IPMNs), other pancreatic tumors, and biliary tract cancer in the patients with PD and the patients with a fused pancreas were compared. RESULTS: The prevalence of the pancreatic tumors in the PD patients was: PCA, 10%; IPMN, 5.1%; other pancreatic tumors, 2.5%. The prevalence of pancreatic tumors in the patients with a fused pancreas was: PCA, 4.8%; IPMN, 2.6%; and other pancreatic tumors, 1.1%. The prevalence of PCA was significantly higher in the patients with PD than in those with a fused pancreas (P = 0.008; OR, 2.24). The percentages of PD patients with PCA who had pancreatic-type pain and a serum pancreatic enzyme elevation were significantly higher than among the PD patients without PCA. The prevalence of biliary tract cancer was 0.8% in the PD group and 5.3% in the fused pancreas group, and it was significantly lower in PD than in fused pancreas (P = 0.031). CONCLUSIONS: The results of this study showed a significantly higher prevalence of PCA in PD than in fused pancreas. We concluded that patients with PD, especially patients presenting with pancreatic-type pain and pancreatic enzyme elevation, should be carefully followed up because of the risk of developing PCA.

Adolescent↗

[Gastrinoma].

Explore the source record for details and available documents.

Diagnosis, Differential↗

Long-term outcome of autoimmune pancreatitis after oral prednisolone therapy.

OBJECTIVE: We investigated the long-term outcome of autoimmune pancreatitis (AIP) including morphological changes in the pancreas, pancreatic duct, biliary tract, pancreatic function, and changes in the clinical manifestations after oral prednisolone (PSL) therapy. PATIENTS AND METHODS: We prospectively followed 12 patients for a period of over 12 months (median follow-up period: 41 months; range: from 13 to 133 months). All twelve patients were treated with PSL. The morphological findings consisted of pancreatic enlargement (n=12), an irregularly narrowed main pancreatic duct (n=12), and bile duct stricture (n=10), and salivary gland swelling was observed in six patients. The initial dose of PSL was 30-40 mg/day, and it was subsequently tapered. RESULTS: All 12 patients responded to PSL therapy. The enlargement of the pancreas and the irregularly narrowed main pancreatic duct improved to almost normal. Pancreatic atrophy developed in four of them (4/12, 33%), but no pancreatic calcification was observed in any of the patients. The bile duct stricture improved to various degrees in all 10 patients , but it persisted in the lower part of the bile duct in four of them (4/10, 40%). The salivary gland swelling also improved after PSL therapy. There was no recurrence of enlargement of the pancreas or irregularly narrowed main pancreatic duct after PSL therapy, but the bile duct stricture recurred in one case, and in three cases there was a relapse of salivary gland swelling that required a temporary increase in PSL dose during tapering. No deterioration of pancreatic exocrine function was detected in any of the patients. A malignant tumor was diagnosed in two patients during PSL therapy: early gastric cancer in one and rectal cancer in the other. All patients are alive. CONCLUSIONS: AIP treated with PSL has a favorable long-term outcome based on the morphological findings and assessments of pancreatic function. However, since two of the twelve patients developed a malignancy during PSL therapy, strict follow up should be part of the management of AIP.

Administration, Oral↗

Lipoteichoic acid may affect the pathogenesis of bile duct damage in primary biliary cirrhosis.

AIM: Intrahepatic bile ducts are the targets for inflammation in primary biliary cirrhosis (PBC), but their pathogenesis is not known. Gram-positive bacterial DNA was detected recently in gallbladder bile of PBC patients. In the present study, we assessed the possible pathological role of lipoteichoic acid (LTA), the gram-positive bacterial cell wall component, in PBC. METHODS: Liver samples, obtained from 20 patients with PBC (stage 1-2 with CNSDC: stage 3-4 with loss of bile ducts = 10:10) and from 13 patients with chronic hepatitis due to hepatitis C virus (CH-C) with lymphocytic cholangitis, were subjected to immunohistochemical staining with polyclonal rabbit anti-LTA as the primary antibody. Serum reactivities to LTA were studied by ELISA. After 1 microg of purified LTA was placed in a 96-well microplate as an antigen, an antibody capture assay was carried out using serum samples from PBC (n = 20), CH-C (n = 13) and healthy subjects (n = 11). RESULTS: LTA was localized around the sites of chronic non-suppurative destructive cholangitis (CNSDC) in the portal area in stage 1-2 PBC but was not detected in the portal area in CH-C. In stage 3-4 PBC, LTA was localized around sites of ductular proliferation at the periphery of portal tracts. IgM class anti-LTA serum titers were significantly higher in PBC than in CH-C. IgA class anti-LTA serum titers were significantly higher in PBC than in healthy subjects. CONCLUSIONS: In the PBC livers, the profile of immunoreactivity to LTA changed markedly as the disease progressed. Sera from PBC showed higher levels of anti-LTA titers than CH-C (IgM) or from healthy subjects (IgA). The LTA-mediated immune system might affect the initiation and/or progression of PBC.

Adult↗

Clinicopathologic features of patients with intrahepatic cholangiocarcinoma who are seropositive for alpha-fetoprotein-L3 and those with combined hepatocellular and cholangiocarcinoma.

BACKGROUND: Some patients who are seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) have intrahepatic cholangiocarcinoma (ICC). There have been no studies regarding the features of ICC patients seropositive for AFP-L3. Thus, the purpose of the present paper was to compare the features of ICC patients from the viewpoint of two different tumor markers, AFP-L3 and carbohydrate antigen (CA) 19-9. METHODS: The ICC patients who underwent hepatectomy (n = 51) were divided into three groups, and their clinicopathologic features were compared: (i) group A, seropositive for AFP-L3 >or= 15%; (ii) group B, seropositive for CA 19-9 >or= 37 U/mL; and (iii) group C, seronegative for both AFP-L3 and CA 19-9. The features of combined hepatocellular and cholangiocarcinoma (n = 11) were also studied. RESULTS: Group A had a higher positivity rate for hepatitis viruses than group B (60%vs 20%, P < 0.05). More patients in group A were misdiagnosed as having hepatocellular carcinoma (HCC) at surgery (70%vs 5.7%, P < 0.001) who also had chronic liver disease (80%vs 25.7%, P < 0.01) than in group B. Seven, 10 and 11 of the 11 patients with combined hepatocellular and cholangiocarcinoma were seropositive for AFP-L3, CA 19-9 and hepatitis viruses, respectively. Ten were diagnosed as having HCC at surgery and nine had chronic liver disease. CONCLUSIONS: Patients with ICC seropositive for AFP-L3 and those with combined hepatocellular and cholangiocarcinoma have features close to HCC. The present study has, for the first time, identified a subgroup of ICC patients, seropositive for AFP-L3, having features close to HCC that are very different from those of the classical ICC patients seropositive for CA 19-9.

Adult↗

Hyaluronic acid levels can predict severe fibrosis and platelet counts can predict cirrhosis in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver disease from simple steatosis to cirrhosis. Therefore, markers for predicting NAFLD with advanced fibrosis are needed. The aim of this study was to establish non-invasive predictive markers of liver fibrosis in NAFLD. METHODS: One hundred and forty-eight patients were diagnosed as having biopsy-proven NAFLD. In order to separately identify severe fibrosis (bridging fibrosis plus cirrhosis) and cirrhosis, the patients were analyzed twice: first, as mild fibrosis versus severe fibrosis; and second, as non-cirrhosis versus cirrhosis. Univariate and multivariate analyses were conducted. The diagnostic ability to detect severe fibrosis and cirrhosis was assessed by the area under the receiver operating characteristic curve. The cut-off values of serum markers to detect severe fibrosis and cirrhosis were determined. RESULTS: Hyaluronic acid was selected as a predictive marker for severe fibrosis. A cut-off value of 42 ng/mL of hyaluronic acid had a 100% predictive value for patients free of severe fibrosis and was associated with an optimal combination of sensitivity (100%, 95% confidence interval [CI] 90-100%) and specificity (89%, 95%CI 80-94%). The platelet count was found to be an independent predictor of cirrhosis. A cut-off value of 16 x 10(4)/microL for the platelet count was associated with an optimal combination of sensitivity (100%, 95%CI 82-100%) and specificity (95%, 95%CI 90-98%). CONCLUSIONS: Hyaluronic acid levels can accurately identify NAFLD patients with severe fibrosis, and the platelet count can identify NAFLD patients with cirrhosis. Thus, these markers offer a good guideline for the assessment of hepatic fibrosis in the many patients with NAFLD.

Adolescent↗

[The effect of previous HBV infection on hepatocellular carcinoma with alcoholic liver disease].

In this study, it was investigated whether previous hepatitis B virus (HBV) infection might be associated with carcinogenesis of hepatocellular carcinoma (HCC) with alcoholic liver disease (ALD). (Method) We compared two HCC groups with ALD, one with previous HBV infection and the other without. In addition, ALD with HCC and without were compared. (Results) The two HCC groups did not differ in terms of age, sex, liver function and liver histology. About 90% of both HCC groups had septal fibrosis or liver cirrhosis. Regarding the comparison of ALD with and without HCC, age and cumulative alcohol were significantly higher in ALD with HCC. The frequency of HBc antibody tended to be higher in ALD with HCC, but the difference was not significant. (Conclusion) There was no difference in HCC with ALD between with and without previous HBV infection. In ALD with severe fibrosis, old age and heavy cumulative alcohol intake, it was important to be on the lookout for the occurrence of HCC.

Adult↗

[Early diagnosis and staging of pancreatic cancer].

Case of pancreatic cancer have increased in number, and the number of deaths from that disease has reached 20,000 in recent years in Japan. Only a few patients with pancreatic cancer can be cured. However, the prognosis in small pancreatic cancer such as TS1 less than 2 cm is relatively good if radical surgical resection is performed. Therefore early diagnosis of pancreatic cancer is important to improve the dismal prognosis. Although clinical symptoms are not reliable for the diagnosis of pancreatic cancer, 30% of TS1 patients have abdominal or back pain. Recent epidemiologic studies have shown that familial history of pancreatic cancer, chronic pancreatitis, diabetes, obesity, and smoking are possible high-risk factors for pancreatic cancer. Serum pancreatic enzyme and tumor markers in terms of CA19-9 and CEA are measured first. Ultrasonography (US) should be performed as soon as possible. Not only tumors but also slightly dilated main pancreatic ducts and/or small simple cysts that may represent indirect changes due to pancreatic cancer can be detected with US. Enhanced computed tomography, magnetic resonance cholangiopancreatography and endoscopic US are also useful. Endoscopic retrograde cholangiopancreatography yields more detailed images of branch ducts, and the cytology of pancreatic juice can be determined following examination. Unfortunately, position-emission tomography is not a reliable method for the diagnosis of small tumors in the pancreas. Finally, TNM staging of pancreatic cancer is performed based on the results of these imaging examinations.

Amylases↗

[A case of Turner syndrome complicated with Crohn's disease, erythema nodosum and Hashimoto disease].

A 26-year-old woman, who had had Turner syndrome from age 10 years old, had diarrhea, fever, joint pain, and erythema in the lower left leg. She was given a diagnosis of Crohn's disease, erythema nodosum, and Hashimoto disease. Systemic steroid therapy was very effective for both intestinal and skin lesions. It has been reported that half of inflammatory bowel disease patients with Turner syndrome have 46XiX (q) type chromosome abnormality, and this case also has this type of abnormality.

Adult↗

Intrahepatic biliary epithelial cell damage and inflammation in portal tract in association with chronic colitis-harboring TCRalpha(-/-) mice.

BACKGROUND: Intrahepatic bile ducts are the target for inflammation in both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The mechanisms of biliary epithelial cell damage in both diseases are not clearly understood. Ulcerative colitis (UC) is one of the known complications in PSC. In this study, we assessed the possible influence of apoptosis inhibitor expressed by macrophages (AIM) on intrahepatic bile ducts in the chronic colitis-harboring condition by generating T cell receptor alpha-deficient (TCRalpha(-/-))xAIM-deficient (AIM(-/-)) double-knockout mice. METHODS: TCRalpha(-/-)xAIM(-/-) mice were generated by crossbreeding TCRalpha(-/-) mice with AIM(-/-) mice. At 24 weeks of age, mice were sacrificed to obtain liver tissues for pathological examinations, and blood was collected to study the serum levels of IgG, IgM and IgA. RESULTS: In female TCRalpha(-/-)xAIM(-/-) mouse livers, mixed cellular infiltration in the portal area and epithelial cell damage in bile ducts were observed, when compared with female TCRalpha(-/-)xAIM(+/-) and male TCRalpha(-/-)xAIM(-/-) mice. Inflammation in hepatic parenchyma was mild to none in all mice. In the female mouse group, the serum IgA level was relatively increased in TCRalpha(-/-)xAIM(-/-) mice compared to TCRalpha(-/-)xAIM(+/-) mice. CONCLUSION: The defect of AIM might be involved not only in colonic mucosal inflammation but also in portal inflammation, as well as in biliary epithelial cell damage in the livers of female TCRalpha(-/-)xAIM(-/-) mice.

Journal Article↗

The characteristics and natural history of Japanese patients with nonalcoholic fatty liver disease.

AIMS: The aim of our study was to elucidate the characteristics and natural history of Japanese nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: Two hundred and forty-seven patients were diagnosed as having biopsy-proven NAFLD at Tokyo Women's Medical University or an affiliated hospital from 1990 to June 2004. Biopsies were scored for the severity of steatosis, necro-inflammation, and fibrosis according to modified Brunt criteria. We assessed the clinicopathological features and natural history of NAFLD in patients stratified by the stage of their fibrosis. Univariate and multivariate logistic analyses were performed, and the diagnostic ability was assessed by the area under the receiver operating characteristic curve. RESULTS: Clinicopathological features: The median age of the patients was 53 years, with a range from 10 to 89 years. There were 130 males and 117 females. Histologically, 46 patients were classified as F3 (bridging fibrosis), and 43 patients had F4 (cirrhosis). Females and older patients were more common in the F3-4 patients. Most of the F3-4 patients showed mild elevation of transaminases with significant deterioration of liver function tests compared with F0-2 patients. Ten patients were simultaneously diagnosed as having cirrhotic NASH and hepatocellular carcinoma (HCC). Natural history: During follow-up (median 44 months) of the F3-4 patients, 10 patients developed liver-related morbidity and five patients developed HCC. In the F3-4 patients, the 5-year cumulative incidence of HCC was 20%. Eight patients died (two of liver failure, four of HCC and two of other carcinomas). Serum markers for detecting F3-4: Serum hyaluronic acid levels can accurately evaluate NAFLD patients with F3-4. CONCLUSIONS: The most important consequence of NAFLD patients with advanced fibrosis was HCC. Regular screening for this complication is extremely important.

Journal Article↗

A murine model of acute liver injury induced by human monoclonal autoantibody.

We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.

Animals↗

Pediatric nonalcoholic steatohepatitis associated with hypopituitarism.

We experienced two cases of pediatric nonalcoholic steatohepatitis (NASH) associated with hypopituitarism. The first patient was diagnosed with a craniopharyngioma at 5 years of age. After an operation to treat the condition, the patient gradually became obese, and an elevation of transaminases was observed. At 16 years of age, the patient was diagnosed as having NASH with liver cirrhosis. He was started on hormone replacement therapy; however, his insulin resistance and liver fibrosis, as evaluated by hyaluronic acid and platelet count, progressed. In addition, his hyperleptinemia continued. The second patient was diagnosed, at 10 years of age, as having pituitary dysfunction due to fetal asphyxia, and he was started on hormone replacement therapy. This patient was noted to have been obese throughout his life. He was diagnosed as having NASH with advanced fibrosis at 18 years of age. It is important for both hepatologists and endocrinologists to be aware of the association between pituitary dysfunction and NASH.

Adiponectin↗

Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful?

BACKGROUND: There are no surrogate serum markers for autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). An AIH scoring system was reported by the International Autoimmune Hepatitis Group; however, the criteria did not focus on making the distinction between AIH and NAFLD. We examined the effectiveness of using the AIH score for diagnosing AIH in NAFLD patients. We also identified the prevalence of autoimmune phenomena, in terms of various auto-antibodies, including antinuclear antibodies (ANA), to determine whether these markers had any clinicopathological significance, and whether they were related to the patients' clinical courses. METHODS: We studied 212 patients (103 males and 109 females) with biopsy-proven NAFLD. The AIH score of each patient was calculated without including the liver biopsy results. The patients were divided into three groups based on their clinicopathological features: the overlap group (those with clinical and histological features of both NAFLD and AIH), the systemic group (those with systemic autoimmune disease other than AIH), and the "other" group (patients with no autoimmune disease). To evaluate the clinicopathological significance of ANA in NAFLD patients, those without autoimmune diseases (the "others" group) were classified according to their ANA positivity and ANA titer. RESULTS: Seventy patients (33.0%) were positive for ANA. Among the female patients, 106 patients (97.2%) had an AIH score of 10 or more. Of the 103 male patients, 21 (20.4%) had an AIH score of 10 or more. However, after liver biopsy, only 1 patient (0.5%) could be classified as "definite AIH." In the NAFLD patients without autoimmune diseases ("other" group), multivariate logistic regression analysis found that female sex was an independent predictor of the presence of ANA (P = 0.029). In contrast, multivariate logistic regression analysis found that severe obesity (body mass index [BMI], >or=30 kg/m2) was the only independent predictor of the presence of an ANA titer of 1 : 80 or more (P = 0.026). CONCLUSIONS: The AIH score without liver biopsy findings was not useful for diagnosing AIH in NAFLD patients. In patients with elevated ANA titers and risk factors for NAFLD, it is very important to perform a liver biopsy to make a definitive diagnosis before treatment.

Antibodies, Antinuclear↗

Cytokines and peroxisome proliferator-activated receptor gamma ligand regulate phagocytosis by pancreatic stellate cells.

BACKGROUND & AIMS: Pancreatic stellate cells have been characterized as the major source of extracellular matrix and cytokine production in the pancreas. This study showed that pancreatic stellate cells have a phagocytic function. METHODS: The morphological features of periacinar phagocytic cells were investigated by immunohistochemically staining serial sections of the pancreas from male WBN/Kob rats and an animal model of acute pancreatitis for glial fibrillary acidic protein and alpha-smooth muscle actin. Pancreatic stellate cells were assayed for phagocytic activity by incubating them with senescent polymorphonuclear neutrophils or fluorescence-labeled latex beads in the presence or absence of cytokines, growth factors, and peroxisome proliferator-activated receptor gamma ligand. The role of CD36 and peroxisome proliferator-activated receptor gamma in phagocytosis was investigated by blocking endogenous CD36 and peroxisome proliferator-activated receptor gamma activity with anti-CD36 antibody and peroxisome proliferator-activated receptor gamma small interfering RNAs, respectively. RESULTS: Phagocytic cells were observed in areas of inflammation, and they were identical to the glial fibrillary acidic protein-positive and alpha-smooth muscle actin-positive cells, thus suggesting that they were pancreatic stellate cells. Aged polymorphonuclear neutrophils were ingested into the cytoplasm of the pancreatic stellate cells. Transforming growth factor beta, tumor necrosis factor alpha, and interleukin 1beta decreased the phagocytic activity of pancreatic stellate cells, whereas troglitazone induced a dose-dependent increase in both phagocytic activity and expression of CD36. Blockade of CD36 reduced troglitazone-induced phagocytosis. Silencing of the peroxisome proliferator-activated receptor gamma gene decreased phagocytosis and expression of CD36. CONCLUSIONS: Pancreatic stellate cells act as resident phagocytic cells, and CD36 promotes troglitazone-induced phagocytic activity via peroxisome proliferator-activated receptor gamma transactivation. Because phagocytosis is essential to limit the extent of inflammation, enhancement of phagocytic activity may provide an important approach to the treatment of pancreatic diseases.

Animals↗

Clinical significance of soluble TNF receptor in Japanese patients with non-alcoholic steatohepatitis.

BACKGROUND: Soluble tumor necrosis factor receptor (sTNFR) is reported to be a good indicator of TNF production and severity in inflammatory diseases. To investigate the clinical significance of sTNFR in non-alcoholic steatohepatitis (NASH), we measured the serum levels of soluble TNF receptor-1 and -2. PATIENTS AND METHODS: We analyzed 82 NASH patients and 15 healthy subjects (control). The grades of fibrosis, inflammation and fatty deposit were evaluated on liver biopsy. The serum levels of sTNFR-1 and -2 were measured by ELISA. RESULTS: There was significant correlation between platelet count and sTNFRs. The titers of sTNFR-2 in NASH patients with diabetes mellitus (DM) were higher than in those without DM. The serum levels of sTNFRs in NASH patients with advanced fibrosis were increased compared with those of control and NASH patients with low-grade fibrosis. Soluble TNFRs in patients with moderate inflammation were increased compared to those of control and patients with mild inflammation. There was no significant association between fatty deposit grade and sTNFRs. CONCLUSION: Soluble TNFRs have a significant correlation with fibrosis in NASH.

Adolescent↗