Kiyoyuki Takahashi

Usefulness of selective arterial secretin injection test for localization of gastrinoma in the Zollinger-Ellison syndrome.

Secretin was injected into a feeding or nonfeeding artery of a gastrinoma and blood samples were taken from the hepatic vein (HV) or a peripheral artery (PA) to measure the changes of serum immunoreactive gastrin concentration (IRG). The IRG in the HV rose within 40 seconds and in the PA rose within 60 seconds after the injection of secretin into a feeding artery, but not after secretin was injected into a nonfeeder. These results indicated that secretin directly stimulates a gastrinoma to release gastrin in vivo. The selective arterial secretin injection test (SASI test) was applied in three patients in whom gastrinomas could not be located by computed tomography, ultrasonography, or arteriography, and functioning gastrinomas were located in all three patients. In one patient, malignant gastrinomas in the head of the pancreas and in the duodenum could be resected radically with the help of this test.

Curative resection of multiple gastrinomas aided by selective arterial secretin injection test and intraoperative secretin test

Recently a number of surgeons have recommended radical resection of gastrinomas in Zollinger-Ellison syndrome (ZES). We have developed a useful technique for preoperative localization of gastrinomas--the selective arterial secretin injection test (SASI)--and we recommend an intraoperative secretin test (IOS) for deciding the radicality of resection of gastrinomas. Here the results of SASI and IOS tests in 11 patients with ZES are examined and compared with the results of other techniques. The SASI test localized gastrinomas in all of the patients, while the sensitivity of ultrasonography, computed tomography, arteriography, or portal venous blood samplings was between 1/11 and 5/11. On the basis of the results of the SASI test, radical resection of gastrinoma was performed in four patients (three pancreatoduodenectomies and one extirpation). After pancreatoduodenectomy, immunohistologic study of the specimen revealed multiple microgastrinomas and lymph node metastases in two patients and the coexistence of a microgastrinoma and a gastinoma in one patient. The IOS test was useful in the estimation of the advisability of radicality, and in two patients total gastrectomy was not performed because of the results of the IOS test. These four patients are well and have returned to work, and their serum gastrin levels are below 35 pg/mL. Thus we believe SASI and IOS tests are helpful for planning curative resection of gastrinomas.

Effects of mechanical stress on the volume phase transition of poly(N-isopropylacrylamide) based polymer gels

The effects of mechanical stress on the volume phase transition of a poly(N-isopropylacrylamide) (PNIPA) gel as well as a copolymer gel composed of N-isopropylacrylamide (NIPA) and sodium acrylate (SA) were investigated in the relatively low stress region. The PNIPA gel without elongational stress showed the behavior close to the second order phase transition. The character of the first order transition became clear under tension, and the transition temperature increased with increasing applied stress. Similar behavior was observed for the NIPA-SA copolymer gel, but the copolymer gel showed the first order transition in the whole stress range investigated. The thermodynamical linear region, where the transition temperature varies linearly with applied stress, was narrower than the mechanical linear region determined by the stress–strain relation of the gels. The change in the transition behavior by the application of the mechanical stress originated chiefly from the volume change in the gels by the applie...

AN AUTOPSY CASE

A diagnosis of the heritable disorder Sipples syndrome was made in a Japanese male aged 28 years. The coexistence of bilateral pheochromocytomas, bilateral medullary thyroid carcinomas and secondary hyperplasia of parathyroid was confirmed at the time of autopsy. Pancreatic islets were hyperplastic with marked proliferation of A and D cells. Transition of the ductal cell to the islet, i.e. ‘nesidioblatosis’ was observed. There was no proliferation of B cells, but a retention of B cell granules, a manifestation of suppressed secretion of insulin attributed to the overproduction of catecholamines was evident. In the stomach, numerous petechial hemorrhages and proliferation of gastrin cells were found. The pathogenesis of changes in the pancreatic islets and stomach is discussed from the viewpoint of hormonal disorders induced by pheochromocytoma and medullary thyroid carcinoma such as are found in Sipples syndrome. ACTA PATH. JAP. 27: 739˜748,1977.

Change in Young’s modulus of poly(N-isopropylacrylamide) gels by volume phase transition

Abstract Mechanical properties of poly( N -isopropylacrylamide) (PNIPA) gels were examined both in swollen and collapsed state. Stress–strain curve of the gel in the swollen state was linear and the collapsed gel also showed almost linear stress–strain behavior. The initial Young’s modulus ( E 0 ) in the collapsed state was much higher than that in the swollen state. The number of cross-links increased largely by the introduction of the physical cross-links due to collapse of the gels.

Gastrin release from gastrinoma cells stimulated with secretin

SummaryThe secretin injection test has been proved to be useful in the diagnosis of gastrinomain vivo. Fresh gastrinoma cells were cultured for a short timein vitro and then stimulated with secretin. A rise in the gastrin concentration in the culture medium was observed within 10 min after the addition of secretin. This fact may be evidence that gastrinoma cells have receptors which bind with secretin resulting in the release of gastrin.

Induction of follicular gastritis following postthymectomy autoimmune gastritis in Helicobacter pylori-infected BALB/c mice

ABSTRACT Helicobacter pylori is the major causative agent of chronic antral gastritis and is thought to be involved in the pathogenesis of mucosa-associated lymphoid tissue lymphoma (MALToma) developing in the human stomach. The aim of this study was to clarify whether corporal autoimmune gastritis (AIG), which is known to decrease acidity due to destruction of parietal cells, predisposes mice toH. pylori infection, thereby leading to MALToma-like pathology. BALB/c mice in which AIG had been induced by thymectomy 3 days after birth (AIG mice) were used. The AIG mice were orally administered mouse-adapted H. pylori at the age of 6 weeks and were examined histologically and serologically after 2 to 12 months. The results were compared with those obtained from uninfected AIG mice and infected normal mice. Germinal centers were induced in the corpus in 57% of the H. pylori-infected AIG mice, which elicited anti-H. pylori antibody responses in association with upregulation of interleukin-4 (IL-4) mRNA. In these mice, parietal cells remained in the corpus mucosa. These findings were in contrast to those with the uninfected AIG mice: fundic gland atrophy due to disappearance of parietal cells associated with upregulation of gamma interferon, but not IL-4, mRNA and no germinal center formation in the corpus. These observations suggest that AIG alters the infectivity ofH. pylori, leading to MALToma-like follicular gastritis, at an early stage after H. pylori infection.

A functional study of a case of glucagonoma exhibiting typical glucagonoma syndrome.

A 46‐year‐old man had a 7‐year history of severe rash, which was then diagnosed as necrolytic migratory erythema. He had a weight loss of 6 kg, abnormal glucose tolerance test findings, anemia, glossitis, hair loss, and hypoproteinemia. Plasma amino acids levels were significantly decreased, and the fasting plasma glucagon (IRG) level was high at 5000 to 8000 pg/ml. Circulating IRG significantly increased after oral glucose loading, meal ingestion, and arginine infusion, and decreased with somatostatin infusion and insulin‐induced hypoglycemia. No other gut or pancreatic hormone levels in plasma were elevated. Plasma IRG was eluted by gel‐filtration, mainly in the position of true glucagon (MW 3500) by antiserum 30K. The rash was markedly improved after infusion of amino acids. Computerized tomography (CT) scan and celiac angiography revealed a large pancreatic tumor with multiple liver and lymph node metastases. The pancreatic tumor was totally resected, and was identified as glucagonoma by immunohistochemical technique. Since the plasma IRG levels remained high after surgery, the patient received dimethyltriazenoimidazole carboxamide therapy. After several courses of this treatment, plasma IRG levels decreased to 1000 to 2000 pg/ml, and the hepatic metastases were remarkably diminished in size.

Localization of pancreatic enzyme secretion-stimulating activity and trypsin inhibitory activity in zymogen granule of the rat pancreas

The intracellular localization of pancreatic enzyme secretion-stimulating activity in rat pancreas was investigated. We found and purified a pancreatic enzyme secretion-stimulating peptide from rat bile/pancreatic juice. The peptide is trypsin-sensitive (showing temporary trypsin inhibitory activity), and it is hypothesized that it acts as a trypsin-sensitive mediator in the feedback regulation of diet-induced pancreatic enzyme secretion. The zymogen granule fraction was purified 5-fold by ultracentrifugation by the Percoll density gradient method. The purity of the zymogen granule fraction was determined from the specific amylase activity and electron microscopic morphology. The specific enzyme activities of amylase and trypsin and the trypsin inhibitory activity increased in parallel during the purification, and the pancreatic enzyme secretion-stimulating activity was also localized in the zymogen granule fraction. These results suggest that the pancreatic enzyme secretion-stimulating peptide originates from the acinar cells, and that it is secreted through exocytosis of zymogen granules into the small intestine, its ratio to trypsin thus remaining constant. This idea supports our hypothesis that the stimulating peptide acts as a mediator for the feedback regulation of pancreatic enzyme secretion by trypsin.

Islet amyloid polypeptide (IAPP) and pancreatic islet amyloid deposition in diabetic and non-diabetic patients

Twenty pancreata of non-diabetic patients and 17 pancreata of diabetic patients, including two patients with insulin-dependent diabetes mellitus, were immunohistochemically studied using antiserum against human islet amyloid polypeptide (IAPP). The islet beta cells in non-diabetic patients were immunoreactive for both IAPP and insulin. Amyloid deposition immunoreactive for IAPP was detected in six of 20 pancreata of non-diabetic patients. The plasma glucose level of three of these six patients was elevated to more than 200 mg/dl, and that of the other three ranged from 143 to 162 mg/dl; all six were receiving intravenous hyper-alimentation and had no history of diabetes prior to treatment. Amyloid deposition was present in all patients with non-insulin-dependent diabetes mellitus (NIDDM). The deposition was absent in the pancreata of two secondary diabetic patients, one of whom had received steroid hormone for bronchial asthma and the other of whom had liver cirrhosis with hepatocellular carcinoma; deposition was also absent in the pancreas of a patient with impaired glucose tolerance diagnosed on a 75-g oral glucose load. Heterogeneous expression of immunoreactivities of beta cells for insulin and for IAPP was present, suggesting independently regulated production and secretion of the peptides. Immunoreactivity of beta cells was more sensitively decreased for IAPP than for insulin in the islets of NIDDM patients. The decreased immunoreactivity for IAPP suggested an initial stage of disturbed beta-cell function, even if the immunoreactivity for insulin was apparently intact or the amyloid deposition in the islets was insignificant. The degree of amyloid deposition immunoreactivity for IAPP did not necessarily reflect the severity of diabetes mellitus. Amyloid deposits were seen at the narrow spaces beneath the insular capsule of connective tissues and the perivascular region or, in some cases, occupying the whole of the islet. The diabetogenic role of IAPP is unclear, but the deposition might be an accelerating factor which disturbs beta-cell function.