[Histochemical changes of islet cells of Langerhans after hepatectomy and effect of glucagon and insulin].

It has been made by a number of studies that after hepatic resection, portal factors such as insulin and glucagon play an important role in liver regeneration. We have reported hypertrophy of Langerhans islands of dogs after partial hepatectomy. In the present study we attempted to clarify the mechanism of this hypertrophy. In a control group, a forty-percent hepatectomy was carried out. One and four weeks after surgery, 0.5g/kg of glucose was administered intravenously followed by a blood sampling from the portal vein to measure the changes of glucose, insulin and glucagon respectively. In addition area changes of the islets of Langerhans after the operation were measured with PAP technique. In a GI group, the same experiment as in the control group was done and 1mg of glucagon and 2IU/kg of insulin were administered every morning after the operation. The following results were obtained. In the GI group, there were no decrease in portal plasma insulin level and no enlargement of the sizes of the islets four weeks after surgery.

Spontaneous rupture of hepatocellular carcinoma: a review of 172 Japanese cases.

The spontaneous rupture of a primary hepatocellular carcinoma (HCC) accounts for 10% mortality of HCC patients in Japan. Because this problem occurs much less frequently in western countries, it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a HCC. In an effort to advance the general knowledge of this disease and clarify a selection for its treatment, we review 172 cases of spontaneous rupture of a HCC reported in the Japanese literature. The chief complaint of the patients was sudden epigastralgia or right hypochondriac pain. Abdominal paracentesis was positive in 86% of the patients. Liver failure was the cause of death in 42% of the patients. Therefore, it is important to evaluate liver reserve quickly. In addition, emergency hemostatic procedures must be implemented to avoid hemorrhagic shock. Although two-stage hepatectomy was performed in only 12% of the cases, these had the highest survival rates. Consequently, this is the procedure of choice for the treatment of spontaneous rupture of a HCC.

[Effect of glucagon on bile acid after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis].

Hepatic function frequently becomes worse, after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis. We usually use insulin and glucagon to treat patients with poor hepatic function, so we examined hepatic function in these patients in relation to bile acid metabolism. 1) Total serum bile acid levels were increased in patients with cirrhosis, and serum GCDCA, TCDCA values were especially high. After surgery, they rose even higher. 2) Glucagon was shown to stimulate C-AMP and decreased total serum bile acid, and especially serum GCDCA and TCDCA values.

[A case of prolonged jaundice after surgical treatment of obstructive jaundice caused by a carcinoma of the head of the pancreas relieved with dibutyryl cyclic AMP].

Recently, we experienced a case of obstructive jaundice caused by a carcinoma of the head of the pancreas which could not be relieved by reduction surgery. The operation performed was a cholecystectomy and supraduodenal choledochotomy with T-tube insertion. Glucagon and insulin were, therefore, administered with the aim towards the recovery of the liver function to be induced by the enhancement of the liver regeneration. The treatment, however, was not effective. Then, dibutyryl cyclic AMP was administered to the case by intravenous drip infusions at the rate of 5 micrograms/kg/min. Thereafter, the value of serum total bilirubin was reduced remarkably. A prolonged and intense obstructive jaundice is generally accompanied by damage to the liver function, and the condition carries a high risk of postoperative complication. In this paper, the effectiveness of dibutyryl cyclic AMP on liver cell damage caused by prolonged obstructive jaundice are reported.

Assessment of antimicrobial penetration into the pancreatic juice in dogs.

The pancreatic ductal penetration of piperacillin, cefuzonam, fosfomycin and netilmicin, injected intravenously, was studied in four dogs with chronic pancreatic fistula. Serum and pancreatic juice were collected simultaneously, frozen, and later assayed for antibiotic concentration. Each antibiotic achieved its therapeutic serum level. The pancreatic ductal levels of piperacillin and cefuzonam were therapeutic, in contrast, the fosfomycin and netilmicin levels were subtherapeutic. These results are considered to be of interest in prevention and treatment of pancreatic infections.

[Clinical studies on hypercreatine phosphokinasemia in emergency diseases].

Unexplained serum creatine phosphokinase (CPK) elevation is not a rare clinical problem, especially in emergency diseases. We studied hypercreatine phosphokinasemia (hyper-CPK-emia) in 161 cases of emergency diseases. Correlations between CPK and various laboratory data, various conditions were investigated. The hyper-CPK-emia was found to obtain no correlations with GPT, GOT, LDH, creatinine and body temperature. For this reason, we could not discover the unknown factors of which contributed to elevate the serum CPK. The sources of the serum CPK in these diseases were concluded to be the skeletal muscle. This is based on the facts that CPK MM (muscle type) is specifically increased among the CPK isozymes. The elevation of serum CPK activity in emergency diseases was considered to result from muscle hypoxia due to severe stress and general circulatory failure.

Effect of glucagon on bile acid metabolism after resection of liver cancer in patients with cirrhosis.

After hepatectomy patients with cirrhosis and liver cancer may develop progressive hepatic dysfunction and eventually hepatic failure. Insulin and glucagon are often used to treat certain kinds of hepatic dysfunction and hepatic insufficiency. We investigated the effect of glucagon on bile acid metabolism and pancreatic endocrine function. In 7 patients with severe cirrhosis and cancer of the liver, 1 mg of glucagon was injected intravenously pre- and post-operatively, and total bile acids, C-AMP, and bile acid fractions were determined. In the pre-operative glucagon tolerance test, the C-AMP level rose from a baseline of 14 +/- 0.8 PMol/ml to 362 +/- 94 PMol/ml 30 min after the injection of glucagon (p less than 0.01); and the level of total bile acids decreased from a baseline of 28 +/- 9 microMol/ml to 11 +/- 3 microMol/ml 60 min after the injection of glucagon. The post-operative C-AMP level increased from a baseline of 13 +/- 1 PMol/ml to 192 +/- 58 PMol/ml level of 30 min after the injection of glucagon (p less than 0.01), and the post-operative level of total bile acids decreased from a baseline of 64 +/- 20 microMol/ml to 26 +/- 7 microMol/ml 60 min after the injection of glucagon. There was a significant correlation between the 5-min increment ratio of C-AMP and the decrement ratio of total bile acids (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenously administered fat emulsion on liver function in totally depancreatized dogs.

Total Pancreatectomy was performed under nembutal anesthesia in 16 adult mongrel dogs after a 24-hour fast, and the depancreatized dogs were given parenteral nutrition containing fat emulsion. Serum lipids, intravenous fat tolerance and post-heparin lipolytic activity were determined and liver biopsy was done to demonstrate the presence or absence of fatty liver. The animals were divided into three groups: group A (n = 6) received fat emulsion 1 g/kg/day; group B (n = 5), fat emulsion 2 g/kg/day; and group C (n = 5), no fat emulsion. Blood levels of cholesterol and phospholipid were increased in group B, while only a mild elevation of the blood triglyceride (TG) level was noted in group A. In group C, cholesterol and phospholipid levels were decreased, and hypoglycemia was liable to occur. The rate of disappearance of blood fat (K2) was decreased two weeks after surgery in group B, but there were no significant change in the other two groups. These findings suggest that if insulin is present, the administration of fat emulsion will not cause fatty liver.

A case of concomitant association of duodenal carcinoma and jejunal carcinoma with cerebral metastasis.

A case of concomitant association of primary suprapapillary and jejunal carcinomas with cerebral metastasis is reported. A 42-year-old woman was admitted to our hospital complaining of melena. Preoperative endoscopy and abdominal angiography showed primary suprapapillary carcinoma, and brain CT showed a high density mass in the right parietal lobe causing involuntary movement of the left upper extremity. During surgery another tumor was revealed in the jejunum about 80 cm from the Treitz' ligament. These were removed surgically and examined histologically.

[Study of in vitro OK432-induced IFN-gamma production in patients with gastric and esophageal cancers: comparison with in vitro skin tests].

In the present study, we measured in vitro production of IFN-gamma induced by OK432 in peripheral mononuclear cells (PMC) and investigated the relationship between the skin reaction to Su-Ps, an extract of Streptococcus Pyogenes, and purified protein derivative (PPD) and the productibility of IFN-gamma in patients with gastric and esophageal cancers. PMC isolated with the Ficoll-conray centrifugation technique were adjusted to 10(6) cells/ml in RPMI-1640 medium supplemented with 10% fetal calf serum and incubated over 7 days at 37 degrees C in the presence of OK432 at 0.17 KE/ml in microculture plates. IFN-gamma secreted in the supernatants was measured consecutively during the observation period with radioimmunoassay. The results are summarized as follows. 1. The production of IFN-gamma in PMC from patients with negative skin reaction to Su-Ps and PPD was significantly decreased as compared with the value obtained from patients who were positive in these skin tests (p less than 0.001). 2. In vitro production of IFN-gamma induced by OK432 was significantly correlated with the degree of skin tests to Su-Ps and PPD as well (r = 0.48, r = 0.41, p less than 0.01, respectively). Thus, it is concluded that the assay of IFN-gamma produced in PMC cultures is useful to evaluate the immunological status of patients with cancer.

[OK 432-induced production of IFN-gamma in peripheral mononuclear cells from healthy subjects and patients with cancer].

OK 432, a well-established immunopotentiator, has been recently noticed as one of biological response modifiers (BRM). IFN-gamma, also called immune interferon, is regarded as an important immunoregulator secreted by T-lymphocytes. In the present study, we measured the in vitro production of IFN-gamma in human peripheral mononuclear cells (PMC) induced by OK 432. PMC were isolated from the peripheral blood with the Ficoll-Conray centrifugation technique. The number of cells for culture was adjusted to 1 x 10(6) cells/ml in RPMI-1640 medium supplemented with 10% fetal calf serum. Incubation was performed over 7 days at 37 degrees C in the presence of OK 432 at 0.17KE/ml in microculture plates. IFN-gamma secreted in the supernatants was measured consecutively during the observation period with radioimmunoassay. IFN-gamma production in PMC from healthy subjects was already detectable at 24 hours of culture and elevated gradually with incubation, reaching as much as 94.3 +/- 44.6 u/ml (mean +/- SD) after 7 days of culture. In contrast, the production of IFN-gamma in patients with cancer was severely suppressed as 21.9 +/- 25.4 u/ml after 7 days of culture (p less than 0.01). Furthermore, both surgical and radiation treatments inhibited the production of IFN-gamma in PMC from patients with cancer.

Expression of interleukin-2 receptor (IL-2R) in feline peripheral blood lymphocytes.

A monoclonal anti-interleukin-2 receptor (IL-2R) antibody has been identified as a putative antibody against the human IL-2R. In the present study, anti-Tac antibody CD-25 was used to determine cell expressing IL-2 receptor in feline peripheral blood lymphocytes by means of direct immunofluorescence tests and complement-mediated lymphocytotoxicity tests. With complement-mediated lymphocytotoxicity, approximately 18% of feline peripheral blood lymphocytes expressed the receptors. By the direct immunofluorescence test, we found approximately 22% of IL-2R positive cells in lymphocytes of feline peripheral-blood.

Cross-reactivity between human and canine helper and suppressor T cell antigens using monoclonal antibodies RPA-T4 and HuLy-m8.

The murine monoclonal antibodies RPA-T4 and HuLy-m8, specific for a framework determinant of human helper/inducer and suppressor/cytotoxic T cell antigens, cross-reacted with canine cell membrane molecules recognizing a biomolecular complex (50,000 to 55,000 daltons) similar to that described in humans. We investigated the distribution of these helper and suppressor T cell-like antigens on canine peripheral blood lymphocytes. With complement-mediated lymphocytotoxicity, 34% and 35% of the canine lymphocytes expressed the helper T cell-like antigens and the suppressor-like T cell antigens, respectively. When the lymphocytes were treated with RPA-T4 and HuLy-m8, the respective helper and suppressor function was significantly inhibited.

[Effects of glucagon and insulin on poly(ADP-ribose) polymerase activity and blood ketone body ratio after partial hepatectomy in rats].

The effects of glucagon and insulin on liver nuclear poly(ADP-ribose) polymerase activity and blood ketone body ratio after rat partial (68%) hepatectomy were examined. Liver weight regeneration rate was enhanced by glucagon and insulin after 5th posthepatectomy day. The maximal value of poly(ADP-ribose) polymerase activity without glucagon and insulin was revealed as 368 +/- 64 pmole/mg/min on 5 days after the hepatectomy. In contrast, the enzyme activity with glucagon and insulin reached to the peak value as 253 +/- 42 pmole/mg/min on 2 days after the hepatectomy. The amounts of DNA per nuclear protein showed similar changes with the changes of poly (ADP-ribose) polymerase activity after the hepatectomy. Blood ketone body ratio showed almost similar changes in both groups, except transitional decrease in the group without glucagon and insulin on 5th postoperative day. It is suggested that, to promote remnant liver regeneration, the combined therapy of glucagon and insulin may act directly to nucleic acid metabolism through the changes of poly(ADP-ribose) polymerase activity and preserve energy charge level by the suppression of NAD consumption by massive poly(ADP-ribose) formation.

Hepatocellular carcinoma with extrahepatic growth: a case report and review of the Japanese literature.

A case of extrahepatically growing hepatocellular carcinoma is reported, and the Japanese literature is reviewed. A 42-year-old man was admitted to our hospital on December 27, 1985 complaining of epigastralgia and nausea. Ultrasonography and computerized tomography showed a large tumor in the right hepatic lobe. This Was removed surgically and examined histologically.