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Biomedical subjects

M Kusunoki

Publications and source records attributed to M Kusunoki.

At least 127 records · Page 7Linked to original sources
PubMed1993

Syndromes of insulin resistance in the rat. Inducement by diet and amelioration with benfluorex.

Insulin resistance, mainly in skeletal muscle, is linked to a cluster of prevalent diseases including NIDDM, dyslipidemias, hypertension, and cardiovascular disease. To determine if an oversupply of lipid is associated with the development of skeletal muscle insulin resistance, we examined the effect of the hypolipidemic agent benfluorex in dietary models of insulin resistance. Adult, male Wistar rats were divided into six groups and maintained for 4 wk on diets high in complex carbohydrate, fructose or fat, with or without 50 mg.kg-1.day-1 of benfluorex, given orally. Insulin action was assessed using a hyperinsulinemic (approximately 100 mU/L) euglycemic clamp, with 2-deoxyglucose tracer for individual tissue evaluation, in chronically cannulated conscious animals. Compared with starch feeding, fructose and fat feeding significantly impaired insulin action at the whole-body level (-46% and -41%, respectively, both P < 0.001), as well as in individual skeletal muscles. Fructose feeding increased circulating TGs (by 80%, P < 0.01) but not skeletal muscle TGs; whereas, fat feeding increased skeletal muscle TGs (by 59%, P < 0.01) but not circulating TGs. With benfluorex, however, diet had no effect on circulating and storage TGs; and development of skeletal muscle insulin resistance in the two diet groups was prevented. Feeding fructose but not fat significantly increased mean arterial BP (by 13%, P < 0.05), an effect prevented by benfluorex. These effects support the hypothesis that the development of muscle insulin resistance in these models is linked to local or systemic oversupply of lipid. These diet models--and the parallel effect of benfluorex on insulin resistance, lipids, and hypertension--may prove useful in the search for the mechanisms that underlie the human disorders associated with insulin resistance.

Analysis of Variance↗
PubMed1993

Protein tyrosine kinase in colorectal adenoma.

To determine whether protein tyrosine kinase (PTK) could be utilized as a biological indicator of colonic tumorigenesis, we examined the PTK activity in the cytosolic and particulate fractions of homogenates from 25 adenomas (polyps) and from adjacent normal mucosa. The particulate fraction PTK activity in the colorectal adenomas was significantly higher than in the normal mucosa. The adenomas were then analyzed according to size, histological type (tubular and tubulovillous), and degree of dysplasia (mild, moderate and severe). The average particulate fraction PTK activity ratio (adenoma/normal mucosa) of tubulovillous adenomas or adenomas with moderate to severe dysplasia was significantly elevated in comparison with that of tubular adenomas or adenomas with mild dysplasia. The particulate PTK activity ratio increased significantly with increasing adenoma size, while the cytosolic ratio did not. The cytosolic PTK activity ratio in tubulovillous adenomas or adenomas with severe dysplasia decreased significantly with increasing size. These findings suggest that colonic carcinogenesis might be associated with alterations in the cellular level of PTK activity and that the PTK activity ratio (adenoma/normal mucosa) in the particulate and/or cytosolic fractions may possibly correlate with the risk of malignant transformation.

Adenoma↗
PubMed1993

Effects of sodium valproate on various intestinal motor functions after ileal J pouch-anal anastomosis.

BACKGROUND: We investigate the effects of sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, on the clinico-physiologic state after ileoanal anastomosis. METHODS: Twelve patients (five with ulcerative colitis and seven with familial adenomatous polyposis coli) were studied in a placebo-controlled trial. RESULTS: Placebo had no effect, but valproate increased the resting anal pressure by 22.4% and the maximum tolerable pouch volume by 20.7%. It also prolonged pouch emptying by 47.3%, with an associated improvement in stool frequency and incontinence. These results suggested that valproate improved both reservoir continence and sphincter continence. CONCLUSIONS: Only minimal side effects were noted, so the administration of sodium valproate appears to be a safe and useful adjunct for patients with ileoanal anastomosis in the early postoperative period.

4-Aminobutyrate Transaminase↗
PubMed1992

Protein kinase C activity in human thyroid carcinoma and adenoma.

Protein kinase C (PKC) activity was examined in the cytosolic and particulate fractions of homogenates obtained from 12 papillary thyroid carcinomas, 12 follicular thyroid adenomas, and the adjacent normal thyroid tissue. Particulate PKC activity was elevated significantly in thyroid carcinomas compared with normal thyroid tissue (P < 0.01) and adenomas (P < 0.05). By contrast, cytosolic PKC activity of carcinomas and adenomas was lower significantly than that of normal thyroid tissue (P < 0.01). The percentage of particulate PKC activity in carcinoma and adenoma was higher than in normal thyroid tissue (carcinoma, P < 0.001; adenoma, P < 0.01). The average particulate PKC activity of carcinomas more than 3 cm in diameter was significantly lower than that of carcinomas less than or equal to 3 cm in diameter (P < 0.05). The average cytosolic PKC activity of carcinomas more than 3 cm also was lower significantly than that of smaller carcinomas (P < 0.05). These results suggest that alterations in PKC activity may be important in the development of papillary thyroid cancer.

Adenoma↗
PubMed1992

Protein kinase C activity in human colonic adenoma and colorectal carcinoma.

To additionally understand the molecular mechanisms and biologic indicators of colonic tumorigenesis through the adenoma-carcinoma sequence, protein kinase C (PKC) activity was examined in the cytosol and particulate fraction of specimen homogenates from 18 human colonic carcinomas and seven coexisting colonic adenomas and was compared with the adjacent normal mucosal tissues. This study showed that PKC activity could be detected precisely using mini DEAE-Sephacel column purification and histone III-S as a substrate. The PKC activity in both colonic adenoma and carcinoma progressively was reduced in the particulate fraction compared with that of the adjacent normal mucosa from each patient (74.9 +/- 11.3 and 42.4 +/- 9.37 versus 112 +/- 16.8 pmol/min/mg, P less than 0.001), although PKC activity in the cytosolic fraction was not significantly different (62.6 +/- 17.7 and 63.1 +/- 8.08 versus 56.4 +/- 7.32 pmol/min/mg) with respect to protein concentration. Both colonic adenomas and carcinomas showed a significant progressive decrease in total particulate PKC activity compared with the adjacent normal mucosa of each patient (13.5 +/- 2.18 and 7.64 +/- 1.35 versus 19.8 +/- 2.74 pmol/min/g tissue, P less than 0.001) and no difference in total cytosolic PKC activity (15.2 +/- 3.80 and 16.5 +/- 2.02 versus 14.6 +/- 1.81 pmol/min/g tissue). Among PKC activities in carcinomas, there was no difference related to histologic type, Dukes' staging, or carcinoembryonic antigen values. Among PKC activities in colonic adenomas, a significant decrease in particulate PKC correlated with size. The specific PKC activity in the particulate fraction decreased with advancing adenoma size (P less than 0.05). This study showed that colonic carcinogenesis might be associated with alterations in cellular levels of PKC activity and that the decrease in particulate PKC activity in the adenoma had a possible correlation with adenoma size.

Adenocarcinoma↗
PubMed1992

The application of a thread holding ring for ileoanal and coloanal anastomosis.

A thread holding ring, originally developed for valve replacement surgery and now commercially available, was successfully employed when performing ileoanal or coloanal anastomosis in 34 patients. The use of this instrument for ileoanal or coloanal anastomosis shortened the operation time and resulted in a decreased rate of complications related to the anastomosis.

Anastomosis, Surgical↗
PubMed1992

Reduction of the effluent volume in high-output ileostomy patients by a somatostatin analogue, SMS 201-995.

Twelve ileostomy patients were given subcutaneous SMS 201-995 therapy (100 micrograms t.d.s. for 5 days) in a randomized placebo-controlled trial. All patients had ileostomies constructed 60 cm proximal to the terminal ileum (proximal ileostomy) following restorative proctocolectomy. SMS 201-995 reduced the daily ileostomy output from 997 +/- 52 g to 736 +/- 28 g, P < 0.05, along with a decrease in daily sodium and chloride excretion (sodium: 92.60 +/- 8.51 to 75.22 +/- 8.64 mEq, chloride: 143.46 +/- 8.54 to 113.60 +/- 15.84 mEq; both P < 0.05). There were no significant changes in the plasma levels of glucagon, C peptide, insulin, renin or aldosterone with SMS 201-995 therapy. Patients developed no severe side effects and reported easier management of the ileostomy and a reduction in thirst. Our results suggest a possible clinical role for SMS 201-995 in the management of proximal ileostomy.

Adolescent↗
PubMed1992

Transitory elevation of serum amylase levels after restorative proctocolectomy.

The incidence of postoperative hyperamylasaemia was evaluated in 70 patients who underwent staged restorative proctocolectomy. On the 14th postoperative day, 27 of 70 patients after total colectomy showed hyperamylasaemia, and the serum amylase returned to normal on the 30th postoperative day. Three out of 37 after ileoanal anastomosis and 8 out of 70 after stoma closure showed elevation of serum amylase postoperatively. Total colectomy might have a possible role in the postoperative increase of serum amylase. None of these patients had any obvious clinical evidence of postoperative pancreatitis. In 7 patients showing significant elevation of serum amylase levels (over 1000 IU), this was due predominantly to the pancreatic isoenzyme. This transitory elevation of serum amylase did not seem to be altered by the administration of therapeutic agents for pancreatitis. These observations suggest that postoperative hyperamylasaemia without clinical evidence of pancreatitis is very common after total colectomy, and that postoperative hyperamylasaemia itself does not necessarily require treatment.

Adenomatous Polyposis Coli↗
PubMed1992

Insulin action and determinants of glycaemia in a rat model of type 2 (non-insulin-dependent) diabetes mellitus.

We aimed to assess prandial responses, basal glucose turnover and insulin action (euglycaemic clamp) in a very low-dose neonatal streptozotocin model of Type 2 (non-insulin-dependent) diabetes mellitus. Male Wistar rats were injected at 2 days of age with 45 mg/kg streptozotocin or vehicle (control). At 8 weeks, the groups were subdivided and fed either a high-fat or high-starch diet for 3 weeks. Both the fat diet and streptozotocin treatments had independent hyperglycaemic effects (streptozotocin/fat 9.3 +/- 0.3 mmol/l; streptozotocin/starch 7.5 +/- 0.3 mmol/l; control/fat 7.4 +/- 0.1 mmol/l; all p less than 0.01 vs control/starch 6.4 +/- 0.1 mmol/l). The fat diet effect was associated with both a reduction in basal glucose clearance (p less than 0.001) and in basal hepatic glucose output (p less than 0.05). Streptozotocin increased basal hepatic glucose output. Significantly higher prandial glycaemia in the streptozotocin/starch group occurred despite similar insulin levels and appeared to be related to an impaired early insulin response. Whole-body and tissue-specific insulin sensitivity were significantly depressed in fat-fed animals compared to starch-fed animals, however there were no significant effects of streptozotocin treatment. We conclude that fasting hyperglycaemia associated with abnormalities in both glucose production and clearance can exist in the presence of a basal hepatic glucose output which is reduced compared to control animals. Furthermore, dietary-fat-induced insulin resistance is not exacerbated by the relative insulin deficiency and/or mild hyperglycaemia observed when dietary fat and neonatal streptozotocin-treatments are combined.

Adipose Tissue↗
PubMed1992

Malignant histiocytosis of the intestine simulating Crohn's disease. Report of a case.

We report a case of malignant histiocytosis of the intestine (MHI) in which clinical and small bowel barium examination led to an initial diagnosis of Crohn's disease. The patient's symptoms and radiologic features improved dramatically with steroid therapy, and the patient remained free of severe symptoms for five years; at this stage, massive rectal bleeding occurred and segmental ileal resection was performed. Pathology findings of the resected specimen revealed nonspecific ulceration of the ileum. The correct diagnosis, MHI, became apparent six months after surgical intervention, on the appearance of multiple lymphadenopathy.

Adult↗
PubMed1992

Quality of life after total proctocolectomy and ileal J-pouch-anal anastomosis.

We investigated the daily life and opinions of patients after total proctocolectomy and ileal J-pouch-anal anastomosis. Eighty patients answered a questionnaire, completed Cattell's anxiety scale, and recorded bowel function for one month. Both colitis and polyposis patients defecated five times daily, had 1.6 episodes of nocturnal motions weekly, and soiled twice weekly. However, colitis patients were more satisfied with their bowel function and surgical outcome than were polyposis patients. This difference had a close relationship to the personality factors of ego strength and frustration. All patients with either disease who defecated less than three times daily, had no nocturnal motions, and had no soiling showed normal ego strength and frustration and were completely satisfied with their bowel status and operation. In contrast, patients defecating more than seven times daily or more than once per week nocturnally and soiling more than four times weekly had high frustration and were dissatisfied. Thus, satisfaction with surgery correlated not only with the objective outcome but also with personality and lifestyle.

Adenomatous Polyposis Coli↗
PubMed1992

Steroid complications in patients with ulcerative colitis.

Physicians treating patients with ulcerative colitis are confronted with the difficult task of deciding whether medical or surgical treatment is best for their patients. There are no definitive criteria to indicate when medical therapy should be exchanged for definitive surgery. Even in patients who respond well to glucocorticoid treatment, the side effects of these drugs may necessitate surgery. We reviewed the steroid complications of our operative cases retrospectively. Although ulcerative colitis was usually in remission, severe steroid complications were no longer tolerable and definitive surgery was required. We also reviewed the literature regarding the adverse effects of steroid. Because of advances in sphincter-preserving surgery, re-evaluation of the treatment of ulcerative colitis is necessary. Although conservative treatment remains the first choice, tolerance of irreversible side effects (especially in children) no longer seems to be justified. In such patients, early definitive surgery may offer more than it appears to sacrifice.

Adult↗
PubMed1992

Influence of sympatho-adrenal system on insulin sensitivity using the euglycemic clamp technique.

The aim of the present study was to further investigate the role of the adrenergic system on insulin action using the euglycemic clamp technique. Whole-body glucose metabolism (GM) was calculated as the glucose infusion rate for maintaining euglycemia under insulin infusion and used as an indicator of insulin sensitivity. Euglycemic clamps were performed in adrenodemedullated, epinephrine-treated, phentolamine-treated (alpha-blockade), propranolol-treated (beta-blockade), and epinephrine plus phentolamine and/or propranolol-treated rats. The following results were obtained at an insulin level of approximately 80 mU/l. GM in adrenodemedullated rats (13.97 +/- 0.98 mg/kg/min) was significantly higher than that of the control rats (10.26 +/- 0.50 mg/kg/min, P less than 0.01). GM in epinephrine-treated rats (1.7 mg/kg body weight/h) was 2.12 +/- 0.49 mg/kg/min (P less than 0.001 vs. control). Dose-response curves for phentolamine and propranolol established maximally effective doses (3.0 mg and 12 mg/kg body weight/h, respectively). Using these doses, GM in epinephrine plus phentolamine-treated rats (4.90 +/- 0.39 mg/kg/min) was significantly higher than that of epinephrine alone and GM in epinephrine and propranolol-treated rats (4.49 +/- 0.47 mg/kg/min) was also significantly higher than that of the epinephrine alone. GM in the epinephrine plus both propranolol and phentolamine (5.94 +/- 0.45 mg/kg/min) was significantly higher than that of the epinephrine alone, but not different from either treatment alone and was not additive. Neither phentolamine alone (9.48 +/- 1.45 mg/kg/min), propranolol alone (10.36 +/- 0.55 mg/kg/min) or the combination of blockades (11.14 +/- 0.65 mg/kg/min) had any effect on GM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1992

Lipocortin-present perforating and lipocortin-absent nonperforating Crohn's disease.

To investigate whether Crohn's disease has two different clinical forms, a relatively aggressive perforating type and a more indolent nonperforating type, we compared the concentrations of lipocortin and prostaglandin E2 (PGE2) in the inflamed mucosa of 12 patients with strictly controlled Crohn's disease with those found in histologically normal mucosa of control subjects. The inflamed mucosa obtained from eight patients with nonperforating Crohn's disease did not react with antilipocortin antibody on immune blot analysis. In contrast, the inflamed mucosa from four patients with perforating Crohn's disease, as well as that obtained from histologically normal controls, contained lipocortins. In addition, higher concentrations of intramucosal ileal and colonic PGE2 were found in patients with nonperforating Crohn's disease (902 +/- 454 pg/wet weight [WW] mg and 1,268 +/- 567 pg/WW mg, respectively) compared with normal controls (90.2 +/- 43.1 pg/WW mg and 173 +/- 76.5 pg/WW mg, respectively) (p less than 0.01). The difference in intramucosal ileal and colonic PGE2 levels between patients with perforating Crohn's disease (109.6 +/- 16.7 pg/WW mg and 252 +/- 34.4 pg/WW mg, respectively) and normal controls was not significant. These findings indicate that there may be two distinct patterns of Crohn's disease that differ in the amount of lipocortin present in the intestinal mucosa.

Adult↗
PubMed1992

Correlation between protein kinase C activity and histopathological criteria in human colorectal adenoma.

We examined protein kinase C (PKC) activity in the cytosolic and particulate fractions of homogenates obtained from 25 colorectal adenomas and adjacent normal mucosa in patients with colorectal carcinoma. The total PKC activity of colorectal adenomas was significantly reduced compared with that of normal mucosa in all cases (122 +/- 45.8 vs 174 +/- 50.5 pmol min-1 mg-1) (means +/- s.d.) (P less than 0.001). The particulate fraction PKC activity of adenomas was also significantly lower than in normal mucosa (71.4 +/- 31.3 vs 115 +/- 39.6 pmol min-1 mg-1) (P less than 0.001). Adenomas were classified by size, histological type and degree of dysplasia. The average particulate PKC activity ratio (adenoma/normal mucosa) of tubulovillous adenomas or those with severe dysplasia was significantly reduced compared with that of tubular adenomas or tumours with mild and moderate dysplasia (both P less than 0.001), while there were no significant differences in the cytosolic PKC activity ratio. The particulate PKC activity ratio decreased significantly with increasing adenoma size (P less than 0.001), while the cytosolic ratio again showed no difference. These findings suggested that the particulate PKC activity ratio had a possible correlation with the malignant potential of colorectal adenomas and that this ratio may be a useful biological indicator of colorectal carcinogenesis.

Adenocarcinoma↗
PubMed1992

Capillary filling analysis by digital subtraction angiography for vertebro-basilar insufficiency.

Vertebro-basilar insufficiency (VBI) is a vague clinical entity including several symptoms such as faintness, dizziness, vertigo. Millikan and Siekert reported a 'syndrome of intermittent insufficiency of basilar arterial system'. But vascular abnormalities responsible for such symptoms are often hardly diagnosed by conventional angiography, because vertebro-basilar artery systems have many kinds of anomalous congenital origins. Conventional angiography gives us arterial informations such as stenosis, occlusion and malformations, but it often fails to reveal capillary perfusions because of its relatively poor density resolution. Digital subtraction angiography (DSA) is considered to have improved density resolution, and it may enable us to detect vascular perfusions more sensitively in the capillary phase. In this study, we evaluated the usefulness of the capillary filling analysis in digital subtraction angiography for diagnosis of VBI.

Capillaries↗