Atsuo Jimi

Epidermoid cyst of the spleen with CA19-9 or carcinoembryonic antigen productions: report of three cases.

True splenic cyst is a relatively rare disease, and the majority of the cases are classified as epidermoid cysts. Three cases of epidermoid cysts in the spleen or accessory spleen were studied using an immunohistochemical technique and staining for mucin. In case 1, serum carcinoembryonic antigen (CEA) and CA19-9, and in cases 2 and 3, serum CA19-9, before surgery were markedly elevated, and these levels decreased postoperatively. This strongly indicates the relationship between the increase of tumor marker levels and the presence of the epidermoid cyst. In addition, stratified squamous epithelium in the resected tissues of cases 1 and 2 was positive for anti-CEA antibody and anti-CA19-9 antibody, and that of case 3 was positive for anti-CA19-9 antibody. This strongly supports CEA or CA19-9 production in the squamous epithelium.

Role of CCK-A Receptor for Pancreatic Function in Mice : A Study in CCK-A Receptor Knockout Mice

Introduction The cholecystokinin (CCK) family of peptides and receptors is present throughout the brain and gastrointestinal tract. The CCK receptors can be pharmacologically subdivided into two subtypes: CCK-A and CCK-B. CCK-A receptor is enriched in the pancreas of mice. Aims To determine pancreatic functions in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. Methodology To examine exocrine functions, amylase release from the dispersed acini in vitro was examined. In the in vivo study, the mixture of bile–pancreatic juice was collected, and amylase, bicarbonate, and bile acid outputs were determined after the administration of various stimulants. The cystic duct of the gallbladder and the pylorus were ligated to exclude the involvement of gallbladder contraction and gastric acid. Pancreatic enzyme content was measured, and histologic examinations by HE and lacZ staining were conducted. To examine endocrine functions, oral glucose tolerance test (2 g/kg) was determined. Results The body weight, pancreatic wet weight, and enzyme content in the pancreas were similar among the three genotypes. Amylase release in vivo and in vitro and bicarbonate secretion in vivo were not stimulated by CCK-8 in CCK-AR (−/−) mice, whereas the responses to other stimulants were substantial in (−/−) mice. Administration of secretin did not increase bicarbonate secretion regardless of genotype. A normal glucose tolerance was observed in (−/−) mice. Acinar cells, islets, and duct cells were stained by lacZ, and HE staining revealed no pathologic findings. Conclusion The CCK-A receptor is important for pancreatic exocrine secretion, but not essential for maintaining glucose concentration and pancreatic growth in mice.

Induction of acute pancreatitis by cerulein in human IL-6 gene transgenic mice.

Whether acute pancreatitis induced by cerulein was aggravated in human interleukin 6 (IL-6) transgenic mice and whether a specific anti-IL-6 receptor antibody improved pancreatitis were investigated. To induce acute pancreatitis, cerulein (50 &mgr;g/kg, seven injections) with or without 1 mg/kg lipopolysaccharides (LPS) was injected intraperitoneally every hour. In some mice, a monoclonal anti-IL-6 receptor antibody was administered before the first cerulein injection. The animals were killed 1 hour after the last injection. The pancreatic wet weight induced by cerulein alone was significantly higher in IL-6 transgenic mice compared with wild-type mice, but pretreatment with a specific anti-IL-6 receptor antibody did not reduce interstitial edema. When cerulein was administered with LPS, the pancreatic wet weight increased much more than when pancreatitis was induced by cerulein alone in both genotypes, and pretreatment with the anti-IL-6 receptor antibody decreased the pancreatic edema only in human IL-6 transgenic mice. These results suggest that anticytokine antibodies may be effective in improving acute pancreatitis.

High Plasma Pancreastatinlike Immunoreactivity in a Patient With Malignant Insulinoma

High levels of pancreastatinlike immunoreactivity were detected in the plasma (2.9 pmol/ml, greater than 200-fold the normal level), pancreas (2.9 nmol/g wet wt, greater than 450-fold the normal level), and liver (1.6 nmol/g wet wt) of a patient with pancreatic insulinoma with metastasis to the liver by a sensitive and specific radioimmunoassay for human pancreastatin. Antiserum was produced against the C-terminal fragment of human pancreastatin-(24-52), which was synthesized according to the sequence of human chromogranin A corresponding to that of pancreastatin. With the antiserum, intense immunocytochemical staining was detected in the tumors. Sephadex G-50 gel filtration showed that the tumors and plasma contained two molecular forms of pancreastatinlike immunoreactivity--a molecular form coeluted with synthetic human pancreastatin-52 and a larger molecular form (Mr approximately 12,000-15,000). The smaller form eluted in the same position as synthetic human pancreastatin-52 on reverse-phase high-performance liquid chromatography.

Amylase Secretion from Dispersed Human Pancreatic Acini : Neither Cholecystokinin A Nor Cholecystokinin B Receptors Mediate Amylase Secretion In Vitro

Introduction In humans, cholecystokinin (CCK) stimulates pancreatic secretion, and CCK-A receptor antagonists prevent it in vivo. However, the human pancreas has been reported to express mainly CCK-B receptors. Aim To elucidate this discrepancy. Methodology We prepared dispersed acini from human pancreas and examined whether various doses of CCK stimulated the release of amylase, in comparison with the effects of neuromedin C, carbamylcholine, and secretin. Results Human pancreatic acini did not respond to any dose of CCK or secretin. Amylase release was stimulated by carbamylcholine and neuromedin C dose-dependently and was inhibited by respective antagonists. The localizations of CCK receptors in the human duodenum were determined. High concentrations of CCK-A receptors were detected in the mucosa as well as in smooth muscle of the duodenum by microautoradiography. Conclusion In conclusion, human pancreatic acinar cells are responsible for carbamylcholine and neuromedin C but not for secretin. Neither CCK-A nor CCK-B receptor mediates amylase release from human pancreatic acini in vitro. Pancreatic secretion in humans in vivo may be regulated indirectly by CCK (via CCK-A receptors).

Overexpression of Cholecystokinin-B/ Gastrin Receptor Gene in the Stomach of Naturally Occurring Cholecystokinin-A Receptor Gene Knockout Rats

We examined the cholecystokinin (CCK)-B/gastrin receptor, H+/K+-ATPase and somatostatin gene expression, the histology and immunohistochemistry of gastrin and somatostatin of the stomach, plasma gastrin levels, and gastric acid secretion in naturally occurring CCK-A receptor gene knockout (Otsuka Long-Evans Tokushima fatty, OLETF) rats. The CCK-B/gastrin receptor, H+/K+-ATPase and somatostatin mRNAs were determined by Northern transfer analysis. The gastric acid secretion and the plasma gastrin level were measured in vivo. The levels of CCK-B/gastrin receptor mRNA in the forestomach and the glandular stomach in OLETF rats were 2-fold higher than those of control rats, although those of H+/K+-ATPase and somatostatin mRNAs were not different. Histological examination revealed thickening of the fundic mucosa, and hyperplasia and hypertrophy of parietal cells, although immunohistochemistry of gastrin and somatostatin revealed no significant difference from the control rats. Gastric acid secretion stimulated by gastrin or histamine was enhanced, whereas the fasting plasma gastrin level was not significantly different from that in control rats. The overexpression of CCK-B/gastrin receptor mRNA and the hyperfunction of parietal cells were observed in rats without CCK-A receptor gene expression.

Bioactivity of human pancreastatin and its localization in pancreas

Synthetic human pancreastatin and its C-terminal fragment were first evaluated with respect to the biological activity on the insulin secretion in the isolated rat islets. Both these pancreastatins inhibited glucose-stimulated insulin secretion at a concentration of 100 nM. The relative molar potency of human pancreastatin compared to that of porcine pancreastatin was equivalent. The pancreastatin-reactive cells were widely located in the islets of Langerhans, and not observed in exocrine acinar cells by immunocytochemistry using human pancreastatin C-terminal specific antibody. These results suggest that human pancreastatin may modulate endocrine function of the pancreas, especially insulin secretion.

Synchronous or metachronous double cancers of the pancreas and other organs: Report on 12 cases

Pancreatic carcinoma carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. This retrospective study describes the results of the treatment and prognosis for double cancers in which cancer of the pancreas was associated with malignancies in other organs in 12 patients who were diagnosed and treated at Kurume University Hospital. The patients included 4 women and 8 men, with an average age of 67 years. Of the 12 tumors, 7 were metachronous pancreatic cancers which occurred after resections of other organ malignancies. Five patients had synchronous double cancers, one of whom was diagnosed to have gastric cancer on admission. Two other patients of this group were diagnosed to have lung cancer, while the remaining 2 patients suffered from colon cancer. By the time pancreatic cancer was diagnosed, gastrectomies had been performed in 7 patients for either gastric cancer or ulcers. In addition, one patient underwent a hysterectomy for uterine carcinoma and another received a low anterior resection for rectal carcinoma. Four of 5 patients in the synchronous group had nonresectable tumors and a palliative bypass operation was performed in 2 of these patients. Six patients who had metachronous double cancers died because of pancreatic cancer recurrence or metastases. We conclude that the prognosis of double cancers, where cancer of the pancreas is associated with other organ malignancies, primarily depends on the prognosis of the pancreatic carcinoma, and the present study suggests the necessity of long-term follow-up examinations for gastrectomy patients in order to make an early diagnosis of pancreatic cancer.

Pancreatic Endocrine Dysfunction in Rats Not Expressing the Cholecystokinin-a Receptor

Summary Cholecystokinin (CCK) has been suggested to modulate insulin output. We have shown that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no expression of the CCK-A receptor gene in the pancreas. We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion. Gene expressions of CCK receptors were determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization and Northern transfer analysis using LETO rats as controls. Pancreatic endocrine function was examined in perfusion (exogenous CCK stimulation) and meal ingestion (endogenous CCK stimulation) studies. CCK-A receptor mRNA was detected in the islets of LETO rats but not OLETF rats. Expression of the CCK-B receptor gene was detected in both strains by RT-PCR. Insulin secretion was impaired in OLETF rats, but the insulin contents of OLETF and LETO rats were not different. No abnormalities were detected histologically in either strain. These results suggest that the occurrence of pancreatic endocrine dysfunction in OLETF rats may be due to a defect in expression of the CCK-A receptor gene, not to insulin deficiency.

Schwannoma of the liver: Report of two surgical cases

Two surgical cases of benign schwannoma of the liver were examined: A 64‐year‐old female who was admitted to hospital for the treatment of early gastric cancer (case 1) and a 69‐year‐old female who had pitting edema In the legs (case 2). Diagnostic imaging revealed large solid masses located In the caudate lobe through to the left lobe of the liver in case 1 and in the left lobe in case 2. Both patients showed no signs of von Recklinghausens disease. Partial hepatectomies were performed and the maximum diameter of their resected hepatic tumors was 4 cm and 15 cm, respectively. Histologically, the well‐demarcated tumors were yellowish In color, elastic‐hard In consistency and consisted predominantly of short spindle‐shaped cells proliferatlng In an interlacing fashion. The tumor lesions were separated by fibrous bands and surrounded by a lymphoid cuff. Immunohistochemically, the tumor cells were positive for S‐100 protein. The tumors were diagnosed as benign hepatic schwannoma.