The Liver Cancer Study Group of Japan registered 11,379 patients with hepatocellular carcinoma (HCC) diagnosed from January 1, 1990 to December 31, 1991 in 536 hospitals throughout the country. This nationwide survey revealed the current status of HCC in Japan regarding the epidemiology, clinical characteristics, histopathological features, diagnosis, surgical and conservative treatments, and the outcome. The survival rates of the HCC patients who received hepatic resection, transarterial embolization (TAE), and percutaneous ethanol injection (PEI) were also calculated based on follow-up from January 1, 1987 to December 31, 1991. Three-year and 5-year survival rates of the patients who underwent hepatic resection were 57.5% and 40.8%, respectively, and those of TAE were 19.5% and 8.0%, respectively. Three-year survival rate of the patients with PEI was 53.2%. Cox's multivariate analysis showed that significant prognostic variables after partial hepatectomy were serum alpha-fetoprotein level, tumor size, number of tumors, associated liver cirrhosis, age, surgical curability, and portal involvement.

Adolescent↗

PubMedDate not supplied

Immunologic observations on 9 sets of twins either concordant or discordant for SLE.

The influence of genetic and nongenetic factors on abnormalities of the immune response in systemic lupus erythematosus (SLE) was studied in 9 sets of twins in which one or both twins had SLE. Particular emphasis was placed on contrasting the results between the sibs of 3 monozygotic pairs discordant for clinical SLE. Depression of cell-mediated immunity, determined by lymphocyte blastogenic response to mitogens, was associated with the clinical expression of illness. In contrast, autoreactive antilymphocyte antibodies and lymphocyte tubuloreticular structures were found in both clinically affected and unaffected subjects and were more prominently associated with the presence of other serologic abnormalities. No evidence of antigens or cell surfaces determinants unique to affected sibs was encountered.

Adult↗

PubMedDate not supplied

Use of selective arterial secretin injection test to guide surgery in patients with Zollinger-Ellison syndrome.

It is often difficult to localize gastrinomas in patients with Zollinger-Ellison syndrome (ZES). We have developed a new useful method, the selective arterial secretin injection test (SASI test), for localizing gastrinomas in patients with ZES. The SASI test first determines the arteries feeding the gastrinomas and then locates the gastrinomas. In 12 patients with ZES, the SASI test clearly localized the gastrinomas, while results obtained with computed tomography or portal venous blood sampling had a positive predictability of less than 10%. Following localization with the SASI test, curative resection of gastrinomas was successfully performed on 7 patients who consented to the operation. Each of 3 patients had one duodenal submucosal microgastrinoma and one or more metastatic lymph node; the other 4 patients had 2 to 10 microgastrinomas or large gastrinomas in the duodenum or the pancreas. All 7 patients, who exhibited negative responses with a postoperative secretin test, have been completely cured from 3 months to 4 years postoperatively. The usefulness of the SASI test for preoperative evaluation is demonstrated by the fact that it gives a 100% positive predictability rate as well as a 100% negative predictability rate. Hence the SASI test precisely locates functioning gastrinomas.

Adult↗

PubMedDate not supplied

Sequential immunotherapy using interleukin-1 followed by interleukin-2 of ascitic MOPC104E-bearing mice.

This study shows that intraperitoneal injection of interleukin-1 (IL-1), followed by interleukin-2 (IL-2), can effectively eradicate murine ascitic tumor cells. This antitumor effect of IL-1 and IL-2 was abolished when administration of IL-2 preceded that of IL-1. Solid tumors inoculated subcutaneously (s.c.) into the back of mice were also sensitive to this combined i.p. therapy, indicating a systemically-operating antitumor mechanism. Splenocytes from tumor-bearing mice treated with IL-1 followed by IL-2 showed a strong tumor-neutralizing activity. The population responsible proved to be Lyt2.2 (CD8)-positive cells.

Animals↗

PubMedDate not supplied

Clinicopathological characteristics of duodenal microgastrinomas.

Duodenal gastrinomas do not seem to behave as malignantly as sporadic pancreatic gastrinomas. Statistical analysis of 49 patients with sporadic pancreatic gastrinoma and 21 patients with sporadic duodenal gastrinoma reported since 1980 in Japan revealed that the incidence of hepatic metastasis was 57% in patients with sporadic pancreatic gastrinoma and only 9% in patients with sporadic duodenal gastrinoma (p less than 0.01). These findings suggest that there is an essential biological differences between duodenal and pancreatic gastrinoma. Five patients with sporadic duodenal microgastrinoma (tumor diameter less than 5mm) in our hospital had no hepatic metastases; however, 4 patients had lymph node metastases. Immunohistochemical study of 5 sporadic duodenal microgastrinomas and 6 sporadic pancreatic gastrinomas revealed that the sporadic duodenal gastrinomas contained significantly fewer insulin-producing or glucagon-producing cells than sporadic pancreatic gastrinomas. The cellular composition of the metastatic lymph nodes from duodenal microgastrinomas was similar to that of the primary tumor. This difference in cellular composition between the duodenal microgastrinomas and the pancreatic gastrinomas suggests that the process of development and differentiation of gastrinoma cells is different.

Adult↗

PubMedDate not supplied

A newly developed three-layer agarose microcapsule for a promising biohybrid artificial pancreas: rat to mouse xenotransplantation.

We examined the effectiveness of an improved version of a three-layer agarose microcapsule in islet xenotransplantation. The microcapsule is composed of a mixture of 5% agarose and 5% polystyrene sulfonic acid. The other two outer layers are polybrene and carboxymethyl cellulose. The agarose/polystyrene sulfonic acid membrane is for the purpose of immunoisolation, suppression of complement activity and reinforcement of the microcapsule. The polybrene layer suppresses the polystyrene sulfonic acid leakage by forming a polyionic complex at the surface of the agarose/polystyrene sulfonic acid membrane. The outermost layer, a carboxymethyl cellulose coating, improves the biocompatibility of the microcapsule. In vitro static incubation study showed that the insulin secretion from rat islets in microcapsules in response to 16.7 mM glucose stimulation was more than four times higher than that on 3.3 mM glucose stimulation (n = 8). In an in vivo study, 500 rat islets in microcapsules were xenogenically implanted in the abdominal cavity of mice with streptozotocin-induced diabetes. The graft survival times ranged from 2 to 5 mo, the average being 75 days (n = 5). Our results demonstrate that the improved version of the three-layer agarose microcapsule can effectively prolong the xenograft survival time without employing immunosuppressants, suggesting that this microcapsule could provide a promising biohybrid artificial pancreas for future clinical applications.

Animals↗

PubMedDate not supplied

Application of a novel B cell line MIN6 to a mesh-reinforced polyvinyl alcohol hydrogel tube and three-layer agarose microcapsules: an in vitro study.

This study examines the function of a novel B cell line (MIN6) enclosed in hybrid bioartificial pancreas with mesh-reinforced polyvinyl alcohol hydrogel tube (MRPT) or with improved, three-layer agarose microcapsules. MIN6 was established from insulinomas obtained by targeted expression of the simian virus 40 T-antigen gene in transgenic mice. MIN6 retains the ability to secrete insulin in response to physiological glucose concentrations. The MRPT and the three-layer agarose microcapsules, which were developed to act as an artificial pancreas, were readily permeated by insulin, glucose, and other nutrients. Both can immunoisolate enclosed MIN6 cells from the recipient's humoral and cellular immunosystems, which causes a xenogeneic rejection response. MIN6 cells (5.0 x 10(6) or 1.5 x 10(6)) were enclosed in MRPT or in a hundred three-layer microcapsules and subjected to an in vitro perifusion study or a static incubation study to observe the insulin release from each bioartificial pancreas in response to glucose stimulation. In vitro study revealed that the insulin secretion in response to 16.7 mM glucose stimulation was twice that with 3.3 mM glucose stimulation with both MRPT and the three-layer agarose microcapsules. The present study demonstrates that MIN6 effectively functions as a bioreactor for the hybrid bioartificial pancreas. The application of MIN6 cells to the hybrid bioartificial pancreas may offer a solution to the current serious dearth of organs.

Animals↗

PubMedDate not supplied

Ovulation stimulating substances in Drosophila biarmipes males: their origin, genetic variation in the response of females, and molecular characterization.

Ovulation responses of Drosophila biarmipes females to an injection of methanolic extract from conspecific males vary with the strains of females. This strain difference seems to be controlled by a small number of autosomal genes, with low responsiveness being recessive. Strangely, all D. biarmipes strains show a high level of ovulation after mating. We pursued the reason for this discrepancy and found that D. biarmipes males produce two different substances with ovulation-inducing activity. One of them is derived from the accessory glands and effective in females of all strains. Another originates in the ejaculatory duct and is inactive in some strains. In an active HPLC fraction of the ejaculatory duct extract, we found a peptide consisting of 32 amino acids. Its C-terminal region has a striking similarity to the sex-peptide of D. melanogaster, but the N-terminal region was entirely different. Evolutionary implications of these findings are discussed.

Amino Acid Sequence↗

PubMedDate not supplied

Novel control system for blood glucose using a model predictive method.

We developed a novel blood glucose control system, using a model predictive method, to achieve optimal control of the blood glucose level in severely diabetic or pancreatectomized patients. This system is designed to predict glucose level changes in advance, considering delayed response time and the administered doses of insulin. This method is also designed to calculate the most appropriate insulin infusion rate by considering differences in individual response to insulin. In this study, we compared our system with a conventional proportional and differential controller (PD controller) to determine whether the new system could regulate the glucose level efficiently in pancreatectomized dogs. The model predictive control method resulted in a significant reduction of mean insulin infusion rate compared with the conventional PD controller (0.71 mU/kg per min vs. 1.81 mU/kg per min, p = 0.0005), when the glucose level in both methods reached the planned target level (100 mg/dl). The new system also tended to have a reduced mean glucose infusion rate for compensating for overshooting of the glucose level compared with the PD controller (0.7 mg/kg per min vs. 1.1 mg/kg per min, p = 0.16). These results indicate that the new system should be a useful tool for regulating the glucose level in severely diabetic patients.

Animals↗

PubMedDate not supplied

Effects of local inhibition of the cardiac renin-angiotensin system with CV-11974 in a canine ischaemia-reperfusion model.

1. To determine whether total interruption of the local cardiac renin-angiotensin system by angiotensin II (AngII) receptor antagonist limits myocardial ischaemia, intracoronary (i.c.) or intravenous (i.v.) infusion of AngII receptor antagonists was compared in ischaemic dogs. 2. Dogs subjected to 90 min coronary artery occlusion and 270 min reperfusion assigned to saline (n = 10) or i.c. low dose (LD, n = 10), i.v. low dose (n = 10) or i.v. high dose (HD, n = 10) of AngII AT1-receptor antagonist, CV-11974. The CV-11974 was infused from 15 min pre-occlusion for 180 min. Cardiac and regional function, area at risk and infarct size were measured. 3. Although i.c. CV-11974 did not cause systemic haemodynamic changes, it abolished reduction in coronary blood flow induced by i.c. AngII injection. Elevation in LV end-diastolic pressure during ischaemia was smaller in both i.c. and i.v.-HD CV-11974 dogs than in i.v.-LD and control dogs. Regional wall thickening was not different among the four groups. With comparable area at risk, i.c. CV-11974 reduced infarct size to the same extent as i.v.-HD CV-11974 (18 vs 21%), which was smaller than i.v.-LD CV or the controls (38 and 42%). 4. The results indicate that AngII receptor antagonist can reduce ischaemia-reperfusion injury in experimental ischaemia. These cardioprotective effects might be mediated through direct inhibition of local angiotensin action in the heart. Local cardiac AngII formation may play a crucial role in cardiac injury during ischaemia and reperfusion.

Angiotensin II↗

PubMedDate not supplied

Expression of insulin-like growth factor-2 can predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival.

Expression of insulin-like growth factor-2 (IGF-2) has been reported in tissue specimens and cell lines of human colorectal cancers. However, the effects of IGF-2 in colorectal cancer patients are not well known. In this study, IGF-2 staining was performed on tissue samples from 92 patients with colorectal cancer, and the relationship of IGF-2 staining to clinicopathological variables, proliferating cell nuclear antigen (PCNA) staining and patient survival was analyzed. IGF-2 staining was correlated with tumor progression, PCNA staining and patient survival. Our results suggest that IGF-2 plays an important role in tumor progression and that IGF-2 staining is useful as a prognostic factor in colorectal cancer patients.

Adult↗

PubMedDate not supplied

Pathogenesis of experimental aural cholesteatoma in the chinchilla.

Histopathological observation of celloidin serial sections of the chinchilla middle ear after treatment with propylene glycol disclosed the development of severe inflammation of the middle ear mucosa and tympanic membrane, papillary proliferation of the epidermis of the tympanic membrane and external auditory meatus, and retraction and adhesion of the tympanic membrane. The findings for the tympanic membrane, impedance testing and histopathological examination suggested that there were two types of acquired cholesteatoma formation, probably with a difference in the pathogenesis. In one type, the proliferated epidermal layer of the tympanic membrane penetrated into the middle ear cavity making tympanic perforations. In the other type, there was progressive retraction of the tympanic membrane forming a retraction pocket. We discuss the two different patterns of cholesteatoma development.

Animals↗