Neuropeptide Y in guinea pig, rabbit, rat and man. Identical amino acid sequence and oxidation of methionine-17.

Neuropeptide Y (NPY) was isolated and characterised from acid-ethanol extracts of rabbit and guinea pig brain. In both instances the chromatographic purification was a two-step procedure of gel filtration followed by reverse-phase high-performance liquid chromatography. The amino acid sequence of rabbit and guinea pig NPY was found to be identical to human and rat NPY as deduced from the cDNA structures. With the exception of the porcine peptide, all mammalian NPYs characterised to date have a methionine residue in position 17. This methionine residue is readily oxidized as indicated by the high degree of spontaneous oxidation of peptides found in the rabbit and guinea pig brain extracts and in NPY extracted from a rat phaeochromocytoma cell line. It is concluded that NPY is among the most highly conserved peptides and that NPYs containing methionine in position 17 are prone to oxidation.

Interaction of NPY and VIP in regulation of myometrial blood flow and mechanical activity.

The occurrence, molecular characteristics and biological function of neuropeptide Y (NPY) has been studied in the female genital tract of non-pregnant rabbits. NPY immunoreactivity was demonstrated throughout the genital tract. Maximum concentrations were found in the salpinx (fallopian tube), 570 pmol/g (median) lower within the uterine body (1.5 pmol/g), cervix (2.8 pmol/g) and vagina (3.6 pmol/g). In vitro, NPY had a dose-dependent stimulatory effect on non-vascular smooth muscle (ED50 10(-9) mol/l) as studied by myometrial tension recordings. In vivo, NPY (50 pmol/min.kg) induced a dose-related, non-adrenergic and non-cholinergic decrease in myometrial blood flow. Small C-terminal (NPY31-36) or N-terminal (NPY1-16) fragments of NPY had no effect on myometrial blood flow. NPY was found to interact with the smooth muscle effect of VIP; the presence of VIP (10(-8) mol/l) counteracted the contraction elicited by NPY (10(-8) mol/l) returning the response to control value. VIP and NPY displayed a similar physiological antagonism on myometrial blood flow. There was a clear difference in the response to VIP and NPY as the effect of NPY on myometrial blood flow first appeared after a lag period of 2 minutes whereas the effect of VIP was almost instantaneous. It is concluded that NPY and VIP may interact in the local nervous control of genital functions.

Factors influencing insulin secretion after pancreatoduodenectomy.

Preoperative patients with periampullary cancer had a higher mean sigma IRI value than that of normal controls, and also had a delayed pattern of insulin response and a lower insulinogenic index during oral-GTT. sigma IRI levels after pancreatoduodenectomy were similar to those of normal controls when the pancreatic remnants were histologically intact at the time of surgery. Postoperative sigma IRI levels could not be predicted based on the extent of histological fibrosis of the distal pancreas at the time of surgery. Patency of pancreatojejunostomy was obtained with the modified Warren's method in 39 out of 40 patients, and sigma IRI levels were maintained up to 5 years postoperatively. No significant difference was found in sigma IRI levels between pancreatoduodenectomised patients with the conventional Roux-en-Y procedure and those with the inverted Roux-en-Y with jejunal interposition. The mean insulin peak value and sigma IRI level were higher in pancreatoduodenectomised patients than in normal controls, and higher in gastrectomised patients than in pancreatoduodenectomised patients. Pancreatoduodenectomy with superior mesenteric arterial dissection resulted in remarkably low sigma IRI levels.

Clinicopathological study on cystadenocarcinoma of the pancreas.

Although rare, mucinous cystadenocarcinoma of the pancreas is an established pathological entity. However, its characteristic features on diagnostic imaging have not yet been defined. Based upon clinicopathological studies on 5 cases, two subgroups of mucinous cystadenocarcinoma of the pancreas are proposed: the endophytic and the exophytic types. The former consist of large well-demarcated cystic tumors with numerous inward-growing cauliflower-like excrescences in mucinous material, which were characteristically demonstrated either by CT or ultrasonography. Tumors of this subtype were visualized as hypervascular masses in the capillary phase of angiography. Areas of malignant tissue were well-demarcated without capsular invasion, and tumors were free from lymph node or distant metastasis. Though cystic, the exophytic subtype had negligible inward-growing papillary projections. Corresponding to their macroscopic features, these tumors were demonstrated as cystic lesions lacking papillary projections on ultrasonography or CT. No tumor stains could be demonstrated by angiography. Despite of their smaller size than the former subtype, cancerous growth penetrated through the cyst wall and metastasized to lymph nodes, causing poorer prognosis than in the former.

Endocrine and exocrine pancreatic functions following partial pancreatectomy + partial hepatectomy.

Comparative studies were performed on changes in endocrine and exocrine responses of the pancreas after partial hepatectomy, partial pancreatectomy or combination of these procedures in rats, in order to clarify the effect of the combined operation on the remnant pancreatic parenchyma. Three days after partial (60%) pancreatectomy with partial (70%) hepatectomy, endocrine function was better preserved than after partial pancreatectomy alone, suggesting that hypersecretion of insulin initiated by partial hepatectomy may ameliorate the defective glucose-induced insulin secretion following partial pancreatectomy. Further, exocrine function in terms of amylase output was relatively well maintained 3 days after partial pancreatectomy + partial hepatectomy as compared with partial pan after partial pancreatectomy + partial hepatectomy as compared with partial pancreatectomy alone.

Effect of obstructive jaundice on amylase secretion in rat pancreatic acini.

The effect of obstructive jaundice on pancreatic amylase secretion was studied in isolated pancreatic acini prepared from bile duct ligated rats (7 days postoperatively), sham operated rats being used as control. Obstructive jaundice caused increase in pancreatic wet weight, pancreatic protein content and pancreatic amylase content by 27.9%, 40.1% and 33.2%, respectively. In acini prepared from obstructive jaundice group, compared with acini from sham operation group, responsiveness to cholecystokinin (CCK) and carbachol was decreased when amylase release was expressed as the percentage of total amylase activity initially present in acini. However, sensitivity to both secretagogues was unchanged when expressed as the percentage of maximally stimulated amylase release. The dose-response curves to Ca2+ ionophore for amylase release were similarly shaped in both groups. These results suggested that a pancreatico-trophic effect, compared with altered responsiveness of pancreatic acini, should play a major role in hypersecretion in obstructive jaundice.

[Clinical study on glucose intolerance and insulin response in obstructive jaundice].

Insulin responses to oral glucose loads were studied in patients with obstructive jaundice and compared with those of other liver diseases (fatty liver, chronic hepatitis and liver cirrhosis), pancreatic diseases, and definite diabetes mellitus. Compared with their corresponding glucose intolerance, high insulin responses were characteristic in fatty liver, chronic hepatitis and liver cirrhosis, and insulin responses and insulinogenic index decreased in chronic hepatitis and liver cirrhosis as glucose intolerance progressed. In obstructive jaundice with the pancreatic ducts stenotic or obstructed, insulin responses were suppressed in comparison with their corresponding glucose intolerance, and also insulinogenic index were below 0.5 in most of the cases. However, in obstructive jaundice with the pancreatic ducts intact, high insulin responses were observed in almost half of the cases with insulinogenic index above 0.5, and insulin response and insulinogenic index decreased as glucose intolerance progressed. While most cases of fatty liver, chronic hepatitis and liver cirrhosis with insulinogenic index above 0.5 were distributed in non-diabetes zone in sigma BS-sigma IRI plane (Kosaka's), those with insulinogenic index below 0.5 were distributed in intermediate zone. Most cases with obstructive jaundice with pancreatic ducts stenotic or obstructed, had insulinogenic index below 0.5 and were distributed in diabetes zone. However, half of cases with obstructive jaundice with pancreatic ducts intact, had insulinogenic index above 0.5 and their distribution in non-diabetes zone, while the other half had insulinogenic index below 0.5 and their distribution in diabetes zone. Therefore, it may be concluded that insulin responses increase at the early stage of obstructive jaundice mainly under influence of liver dysfunction itself, but that insulin response is suppressed at later stage of obstructive jaundice as pancreatic islets are affected.

[Islet cell tumor:insulinoma].

UNLABELLED: Twenty-eight patients with insulinoma treated at our institutions during the years 1935-1983 were available for this study. These patients included 15 males and 13 females ranging 20 to 77 years of age and averaging 48 years. DIAGNOSIS: Inappropriate elevations of plasma insulin (IRI/BS greater than 0.3) in the fasting state were demonstrated in all 18 patients. Accurate tumor localization was defined by arteriography in 61% of 18 patients. Decision of localization by transhepatic portal catheterization and insulin assay was successful in all of 4 patients in whom it was performed. Pathology: Twenty-five patients had a single tumor and 3 had multiple tumors. The tumor was located in the head in 8, in the body in 12 and in the tail in 14. Thirty of 34 tumors were benign and 4 were malignant. SURGICAL TREATMENT: Enucleation was performed in 6 patients, 19 patients underwent distal pancreatectomy and one patient had pancreatoduodenectomy, One patient with occult tumor in the head had 80% resection of the pancreas. One patient with two tiny occult tumors close to the duodenum underwent distal left to right pancreatectomy finally resulting in total pancreatectomy. RESULT: There was no operative death and no recurrence of symptoms in all patients after operation.

[Experimental studies on the selective profound hypothermia of the abdominal viscera by descending aorta and inferior caval vein occlusion].

In the present study, an effort was made to establish the procedure for 60 minutes selective profound hypothermia below 20 degrees C of the abdominal viscera. In 6 mongrel dogs, hemodynamic changes were investigated during 60 minutes normothermic vascular exclusion of the abdominal viscera by occluding the aorta and inferior caval vein just above the diaphragm. Hemodynamic state just after the combined occlusion of these vessels was stable, but 60 minutes occlusion was followed by hypoperfusion of the cranial half of the body. In 15 mongrel dogs, the 60 minutes selective profound hypothermia below 20 degrees C of the abdominal viscera was performed after occluding these vessels with an aid of extracorporeal circuit. Pooled blood in the splanchnic region during hypothermia was warmed and drained to jugular vein to maintain the hemodynamic state in the cranial half of the body. Twelve of 15 dogs survived 2 weeks after the procedure with minimal hepatic damage. In 7 mongrel dogs, blood coagulation system was investigated. Decrease of platelet, fibrinogen, plasminogen, anti-thrombin III, prothrombin and cold insoluble globulin concentration, elongation of prothrombin time and partial thromboplastin time, and elevation of FDP occurred during and after the selective profound hypothermia. But these changes were self limiting and recovered soon after heparin neutralization. In 9 mongrel dogs, extended pancreatectomy with splenectomy and combined resection of portal vein using selective profound hypothermia was performed. Bleeding and splanchnic congestion during extended pancreatectomy was minimum. Five of 9 dogs survived 2 weeks with slight hepatic and renal damage.

Retroperitoneal hemangiopericytoma associated with hypoglycemia: report of a case.

A 34-year-old woman had episodes of hypoglycemic attack 8 years after a surgical resection of a retroperitoneal hemangiopericytoma. In spite of normal levels of serum IRI, insulin radioreceptor assay demonstrated high level of plasma ILA (insulin like activity). The patient underwent resection of a recurrent retroperitoneal tumor with metastatic lesions of the liver. Postoperatively, ILA level in plasma by insulin radioreceptor assay decreased, and hypoglycemic attacks disappeared. Therefore, this associated hypoglycemia was presumed to be not caused by excess glucose consumption by the tumor, not by excess secretion of IRI by the tumor, but caused by the presence of high level of ILA related to the tumor.