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Biomedical subjects

K Takebe

Publications and source records attributed to K Takebe.

At least 307 records · Page 17Linked to original sources

In vivo evidence that arginine vasopressin is involved in the adrenocorticotropin response induced by interleukin-6 but not by tumor necrosis factor-alpha in the rat.

We examined whether arginine vasopressin (AVP) is involved in the adrenocorticotropin (ACTH) response induced by interleukin (IL)-6 or tumor necrosis factor (TNF)-alpha in the rat. To accomplish this, we employed immunoneutralization of brain AVP by injecting anti-AVP antiserum intracerebroventricularly (i.c.v., 3rd ventricle). For comparison, we also tested the effect of immunoneutralization of corticotropin-releasing hormone (CRH) in the brain. Anti-CRH antibody, anti-AVP antibody, or normal rabbit serum (control) was given i.c.v. 15 min before an i.c.v. administration of human recombinant IL-6 (100 ng) or TNF-alpha (100 ng). Both IL-6 and TNF-alpha significantly elevated plasma ACTH levels. The IL-6-induced ACTH response was significantly suppressed by both anti-CRH and anti-AVP antibodies. On the other hand, the TNF-alpha-induced ACTH response was not significantly affected by anti-AVP antibody, although anti-CRH antibody could suppress the response. These results suggest that the IL-6-induced ACTH response may be mediated by both CRH and AVP, whereas the ACTH response to TNF-alpha is only via CRH.

Adrenocorticotropic Hormone↗

Effects of gender and gonadectomy on ACTH response to interleukin-1beta in the rat: comparison with the modulation of ACTH response to immobilization stress.

We examined the influence of gender and gonadectomy on the plasma adrenocorticotropin (ACTH) response to intravenous administration of human recombinant interleukin (IL)-1beta (3 microg/kg) in the rat. For comparison, we also examined whether gender and gonadectomy affect ACTH secretion after immobilization stress (a 30-min period), which is a nonimmunological stressor. IL-1beta induced a significantly higher ACTH response in females than in males, and this sexual difference was abolished by gonadectomy in both sexes. By contrast, ACTH secretion after immobilization was statistically the same in males and females, but tended to be higher in gonadectomized males than in gonadectomized females. These results may suggest a dissociative regulation by gonadal steroids of IL-1beta- and immobilization-induced ACTH responses in the rat. The sexual difference in ACTH response to IL-1beta may represent another example of the sexually dimorphic immunological activity, which is known to be higher in females than in males.

Adrenocorticotropic Hormone↗

Effects of FL-386 on faecal lipid excretion in humans.

A newly synthesized inhibitor of pancreatic lipase and micelle formation, FL-386, was administered at a dose of 400 mg (in the diet, for seven consecutive days) to nine healthy adult volunteers, and changes in faecal mass, frequency of defaecation, and properties of the stools were observed. High performance liquid chromatography and gas-liquid chromatography were used to analyse the faeces for short-chain carboxylic acids, neutral sterols, bile acids, fats and hydroxyfatty acids. FL-386 had little effect on the amounts and composition of short-chain carboxylic acids, neutral sterols, and bile acids excreted, nor did it produce changes in the composition of fatty acids, or the percentages of hydroxyfatty acids in the stool. However, in those patients treated with FL-386, the faecal mass was increased, and stools were softer and contained increased amounts of fatty acids. The compound did not produce particularly fatty stools. It was concluded that FL-386 induces slight disturbance in the digestion and absorption of dietary lipids.

Adult↗

Effect of an alpha-glucosidase inhibitor on intestinal fermentation and faecal lipids in diabetic patients.

Eight non-insulin-dependent diabetes mellitus patients, in whom oral hypoglycaemic agents were not effective, were treated with an alpha-glucosidase inhibitor, AO-128 (0.9 mg/day) for 6 months. After 6 months of treatment there was a statistically significant decrease in the blood glucose level 1 and 2 h postprandially. The 2 h blood glucose level was also significantly reduced after 2 months' treatment. The insulin and HbA1c levels after 2 and 6 months' treatment were lower than those before administration. Faecal weight, the frequency of bowel movements, the ratio of hydroxy fatty acids to total fatty acids, and faecal short-chain carboxylic acid content were all increased significantly during treatment. The initially hard stools became normal or soft, although no actual diarrhoea developed. Both faecal bile-acid excretion and the ratio of primary bile acids to total bile acids were increased significantly after 2 months, but they showed some recovery towards the pretreatment levels after 6 months' treatment. There was no distinct change in neutral sterol and fatty acid excretion. Breath hydrogen excretion showed a slight increase after treatment. These results suggest that intestinal fermentation was promoted and the intestinal transit time was shortened by AO-128 administration.

Adult↗

Changes in plasma fatty acid profile in Japanese patients with chronic pancreatitis.

The serum zinc, prealbumin, retinol-binding protein and carotene concentrations and the plasma fatty acid composition were determined to assess the nutritional condition of 24 patients with chronic pancreatitis compared with that of 20 healthy controls. The daily food intake and faecal fat excretion of the two groups were also measured. In the chronic pancreatitis group, the calorie and fat intakes were significantly lower than those of the controls. Serum levels of zinc, prealbumin and carotene were also significantly lower than those of the controls. Percentages of plasma linoleic and arachidonic acids were low, while percentages of palmitoleic acid, eicosapentaenoic acid and docosahexaenoic acid were high. Fish oil intake correlated negatively with plasma linoleic acid concentration (P < 0.05). The above results indicate that the relatively high intake of fish oil and the relatively low intake of dietary fat in Japanese patients with chronic pancreatitis with a mild degree of steatorrhoea results in an abnormally low plasma level of linoleic acid.

Adult↗

Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases.

Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56,600 U/g, Fédération Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective.

Adult↗

Faecal triglycerides and fatty acids in the differential diagnosis of pancreatic insufficiency and intestinal malabsorption in patients with low fat intakes.

To investigate possible parameters for the differential diagnosis of steatorrhoea in patients with low fat intakes, faecal specimens were analysed from 15 patients with steatorrhoea due to chronic pancreatitis and seven patients with steatorrhoea due to intestinal malabsorption. The fat intakes of the patients ranged from 30.1 to 60 g, less than the average in American and European patients. The group with pancreatic steatorrhoea showed a significantly lower faecal output than the group with intestinal steatorrhoea but the two groups did not differ significantly in their total faecal fat excretion or concentration. The percentage triglycerides and the molecular ratio of triglycerides to fatty acids in the faeces were significantly higher (P < 0.01) in the group with pancreatic steatorrhoea than in those with intestinal steatorrhoea. The molecular percentage ratio of triglycerides to fatty acids was 6.8 +/- 2.2 for the chronic pancreatitis group and 2.4 +/- 1.0 for the intestinal malabsorption group; while the respective faecal hydroxy fatty acid contents were 3.1 +/- 3.6% and 10.1 +/- 3.3% (means +/- SDs). These latter two parameters appeared to be the most valuable for distinguishing the two forms of steatorrhoea.

Adult↗

Effects of iso and xeno fetal liver fragments transplantation on acute and chronic liver failure in rats.

Isogeneic (rat) and xenogeneic (swine) fetal liver fragments (FLF) transplantation into the omentum was performed for D-galactosamine (D-Gal)-induced acute and carbon tetrachloride (CCl4)-induced chronic hepatic failure in rats. The recipients that had iso or xeno FLF showed higher survival rates than the nontransplanted controls on a lethal dose (2.6 g/kg body weight) of D-Gal (survival rates: Iso 70%, Xeno 80%, and control 9.1%). On a sublethal dose (1.0 or 1.2 g/kg) of D-Gal, iso, or xeno FLF caused marked improvement of the values of GPT, GOT, and total bilirubin (T.Bil); at 72 h after D-Gal injection they went significantly lower than those of controls (Iso vs. control; p < 0.01, Xeno vs. control; p < 0.05). Histological examination of the livers revealed severe damage in controls, however, only a slight damage was found in iso or xeno FLF transplanted rats. Iso grafts were fairly well preserved in the omentum at 72 h posttransplants, however, xeno graft had almost changed into a necrotic tissue. CCl4 was administered subcutaneously for 14 wk to induce chronic hepatic failure and then iso FLF were transplanted 3 days after the last CCl4 injection. Iso FLF transplanted rats showed higher improvement of GPT and GOT values at 12 days posttransplants compared with controls (GPT p < 0.01, GOT p < 0.05), although histological improvement was not so remarkable in both group. Iso grafts formed nodules with many hepatocytes in the omentum 12 days posttransplant. The results indicate that iso or xeno FLF transplantation could be an alternative approach for incurable liver insufficiencies.

Animals↗

Immunological analysis in xenogeneic fetal porcine liver transplantation into a beagle.

BACKGROUND/AIMS: While allogeneic organ transplantation has been performed safely, a major barrier in xenogeneic transplantation is how to inhibit hyperacute rejection. METHODOLOGY: We challenged xenogeneic fetal liver transplantation from pig to dog. The graft was investigated by immunohistochemical analysis on recipient's IgG, IgM and C3. RESULTS: In 1 of 4 cases, the graft escaped hyperacute rejection for about 4 hours after transplantation, however, the recipient died next day due to hemorrhage from the torn capsule of the liver due to the arterial blood pressure of the recipient. Histologically, the parenchyma showed good countenance and no congestion nor hemorrhage was shown in the vessels. On immunohistochemical analysis, canine IgG, IgM and C3 were deposited on the sinusoidal epithelium of the fetal liver more moderately than that of adult control. Fetal porcine liver showed less expression of major histocompatability complex class I antigen than that of the adult one. CONCLUSIONS: We consider that the hyperacute rejection occurred more slowly in xenogeneic fetal liver transplantation than in the adult one due to not only less expression of major histocompatability complex class I, but also lower expression of the epitope recognized by a natural antibody of the recipient.

Animals↗

Topography of Alzheimer's neurofibrillary change distribution in myotonic dystrophy.

Histological changes that explain the mental symptoms of patients with myotonic dystrophy (MD) have not fully been demonstrated yet. Recently, the presence of Alzheimer's neurofibrillary changes (ANCs) in the brain have been reported in this disease. We studied the brain of a 61-year-old male with MD. The distribution of ANCs was investigated and mapped through careful histological examinations. The examinations disclosed that in MD, ANCs distributed along their preferential sites of the brain; a great number of ANCs were found in the parahippocampus, hippocampus, amygdaloid nucleus, fusiform gyrus, insula, and olfactory bulb, many in the nucleus basalis of Meynert, inferior temporal gyrus, hypothalamus, and brain stem, and a few in the cingulate, frontal and temporal gyri, neostriatum, and mammillary body. In the brain stem, ANCs were seen in the central gray, oculomotor nucleus, linear nucleus, substantia nigra, locus coeruleus, dorsal raphe nucleus, superior central nucleus, retriculotegmental nucleus, and reticular formation. From this result and the previous reports by others, it may be suggested that the presence of ANCs concentrated mostly in the limbic system is a regular and significant histological finding in the brain in MD. Therefore, this limbic lesion must be related to some of the mental symptoms unique to MD. In addition, diffuse and considerable neuronal atrophy and gliosis in the thalami in the absence of ANCs also may have played a causative role in some of the mental symptoms of the present case. Besides the more concentrated occurrence of ANCs within the limbic system, the minimal presence of senile plaques in the CNS may differentiate the brain in MD from that in Alzheimer-type dementia.

Adult↗

Effect of intravenous administration of EM523L on gastric emptying and plasma glucose levels after a meal in patients with diabetic gastroparesis: a pilot study.

EM523L, a newly developed erythromycin derivative, has a powerful motilin-like biologic effect and no antibacterial activity. In this pilot study, EM523L was administered to six patients with diabetic gastroparesis, and its effects on gastric emptying function and the change in plasma glucose levels after eating were examined. Gastric emptying was evaluated by the simultaneous measurement of solid and liquid food intake using 99mTc-Sn-colloid and acetaminophen, respectively. Eggs labeled with isotope and milk with added acetaminophen were used as the test meals. The change in plasma glucose level after ingestion of the test meal was also examined. A total of 2 mg of EM523L dissolved in 100 mL of physiologic saline was administered by intravenous infusion over a period of 15 minutes after ingestion of the test meal. The retention rates of the gastric isotope decreased following the administration of EM523L at 20 to 120 minutes after ingestion of the test meal. Plasma acetaminophen concentrations following EM523L administration increased at 20 and 30 minutes. The plasma glucose levels showed an increase at 30 to 60 minutes after eating--the result of improved gastric emptying function. From these results, we concluded that intravenous administration of EM523L in patients with severe diabetic gastroparesis promotes gastric emptying of a solid and liquid meal and, as a result, plasma glucose levels increase after eating.

Acetaminophen↗

Pheochromocytoma with multiple islet cell carcinoma.

We reported a rare case of a 17-year-old female with pheochromocytoma associated with multiple islet cell carcinoma. Pheochromocytoma was identified in the right adrenal gland. Multiple pancreas tumours were demonstrated unpredictably in the diagnostic imaging of the pheochromocytoma. No other endocrinological neoplasm was observed in the pituitary, thyroid and parathyroid gland. The patient underwent right adrenalectomy and total pancreatectomy. Pheochromocytoma was benign, however, pancreas tumours were non-functioning islet cell tumours and histologically malignant. This combination is assumed to represent a mixed form of multiple endocrine neoplasia (MEN) 1 and MEN 2.

Adolescent↗