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Biomedical subjects

K Shima

Publications and source records attributed to K Shima.

At least 217 records · Page 12Linked to original sources
PubMed1993

Is exercise training effective in preventing diabetes mellitus in the Otsuka-Long-Evans-Tokushima fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus?

We determined whether exercise training is effective in preventing the development of diabetes mellitus in a model rat (Otsuka-Long-Evans-Tokushima Fatty [OLETF]) with non-insulin-dependent diabetes mellitus (NIDDM). Thirty male OLETF rats aged 5 weeks were assigned to one of the following three groups: trained rats placed individually in an exercise wheel (EW) cage, EW-control rats housed in the same cages equipped with a fixed rotatory wheel, and sedentary rats maintained two or three to a conventional cage. Eight male diabetes-resistant Long-Evans rats were used as nondiabetic controls. At 24 weeks of age, the trained, EW-control, sedentary, and nondiabetic control rats weighed an average of 445, 559, 621 and 513 g and had abdominal fat deposits of 16, 55, 67, and 23 g, respectively. The mean amount of exercise of trained rats was 5,243 m/d. At 24 weeks of age, the cumulative incidences of diabetes mellitus in sedentary and EW-control rats were 78% and 50%, respectively, while neither trained nor nondiabetic control rats became diabetic. Fasting and 120-minute plasma immunoreactive insulin (IRI) levels after oral glucose administration were significantly lower in the trained group than in the other groups. In vivo insulin-stimulated glucose uptake as measured with a euglycemic clamp was reduced 37% in sedentary rats and increased 35% in trained rats compared with that in nondiabetic control rats. Morphological studies on the pancreas of sedentary and EW-control rats showed enlarged multilobulated fibrotic islets, whereas sections of islets from trained rats appeared normal but slightly enlarged.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Cyclophosphamide-induced diabetes in Long-Evans Tokushima Lean rats: influence of ovariectomy on the development of diabetes.

We studied the effect of treatment with cyclophosphamide (CY) on the incidence of diabetes in Long-Evans Tokushima Lean (LETL) rats, a newly established strain of spontaneously type I diabetic rats. The overall incidence of diabetes among 356 LETL rats treated with CY was 25.6%, which was significantly higher than the 10.5% among 857 untreated LETL rats at 27 weeks of age, and there was no significant sex difference. The incidence of CY-induced diabetes in adult (> 16 weeks of age) female LETL rats was 7.7% (10/130), which was significantly lower than that in other CY-treated groups of LETL rats. No diabetes mellitus was induced by administration of CY to 23 diabetes-resistant LETO rats. There were no significant differences in the degrees of hyperglycemia or hyperketonemia in spontaneously and CY-induced diabetic LETL rats, but the plasma glycated albumin level of CY-induced diabetic rats (10.3% +/- 2.1%) was significantly higher than that of spontaneously diabetic rats (8.2% +/- 1.3%), suggesting that plasma glucose levels increased more rapidly in the latter. More than half of the diabetic rats showed type C or D morphological changes of the islets, ie, atrophic change with little mononuclear cell infiltration or almost complete loss of the islets. However, distributions of various types of morphological changes in the islets were not significantly different in the two groups. Ovariectomy (OVX) significantly increased the incidence of CY-induced diabetes in adult female rats from 7.7% to 20.8%. The number of CD8+ cells was significantly increased in noncastrated adult female LETL rats and decreased to the level of other groups after OVX.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Radioimmunoreactive plasma bradykinin levels and histological changes during the course of cerulein-induced pancreatitis in rats.

The plasma bradykinin (BK) and serum amylase levels and histological changes in rats during the course of acute pancreatitis induced by a large dose of cerulein were examined. Animals were given four intraperitoneal injections of 20 micrograms/kg body wt of cerulein at hourly intervals. The plasma concentration of BK-like immunoreactivity (BK-LI), measured by a highly sensitive and specific radioimmunoassay established in this study, was found to reach a peak 6 h after the first injection of cerulein and then to remain elevated. On the other hand, the serum amylase and the histological alterations (i.e., interstitial edema, vacuolization, and inflammatory infiltration) were maximal 9 h after the first injection and returned to nearly normal after 24 h. These observations suggest that the BK generation is indicative of the participation of the kallikrein-kinin system in the pathophysiological change and that the plasma BK-LI level is a good marker of cellular damage and inflammation within the pancreas during the course of acute pancreatitis.

Acute Disease↗
PubMed1993

Glucagon and ALS.

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Amyotrophic Lateral Sclerosis↗
PubMed1993

Plasma glucagon responses to insulin-induced hypoglycemia and arginine in spontaneous non-insulin-dependent diabetes mellitus (NIDDM) rats, Otsuka Long Evans Tokushima Fatty (OLETF) strain.

Pancreatic A-cell function in the newly developed Otsuka Long Evans Tokushima Fatty (OLETF) strain of non-insulin-dependent diabetes mellitus (NIDDM) rats was examined in relation to the morphological changes in their islets and the plasma glucagon responses to insulin-induced hypoglycemia and an arginine test by chronological studies in seven male OLETF and seven male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats each at 10, 16 and 24 weeks of age and eight male OLETF rats that were placed in a cage with a wheel for exercising from 5 to 24 weeks of age. The hormonal contents and morphological features of the pancreas of these rats were examined. After iv injection of insulin, the plasma glucagon level rose significantly from the basal level in OLETF rats at 10 weeks old, but little if at all in those of 16 and 24 weeks old. The pancreatic A cells of LETO rats of all age groups responded equally well to glucopenia. The areas under the response curves of plasma glucagon (sigma delta IRG) during the 90 min of insulin-induced hypoglycemia were 14496 +/- 7860 vs 9588 +/- 3930, 2257 +/- 3018 vs 9235 +/- 5447 (p < 0.05) and 826 +/- 985 vs 9707 +/- 2510 (p < 0.01) ng.min-1.l-1 in OLETF rats vs LETO rats of 10, 16 and 24 weeks old, respectively. The plasma glucagon responses during the arginine test were higher in OLETF rats than in LETO rats at 10 and 16 weeks but not at 24 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Local cerebral blood flow and glucose metabolism in hydrostatic brain edema.

This study investigated the effect of hydrostatic pressure gradient on the cerebrovascular dynamics and metabolism during the development of brain edema. Hydrostatic brain edema was induced by bolus injection of autologous blood through the common carotid artery in Sprague-Dawley rats. Rats were divided into two groups, with craniectomy (Cr+ group) and without (Cr- group). Animals were sacrificed 0, 24, and 48 hours after hypertensive insult. Brain water content was determined by the gravimetric method. Regional cerebral blood flow and local cerebral glucose utilization were measured by the quantitative autoradiographic method using [14C]iodoantipyrine and [14C]deoxyglucose, respectively. Hypertensive insult produced multifocal lesions stained by Evans blue. Brains from the Cr- group showed a transient increase in water content and no significant change in cerebrovascular dynamics and metabolism. Brains from the Cr+ group showed a pronounced increase in water content which persisted 48 hours later. Misery perfusion was also observed 24 hours after the insult and the cerebrovascular dynamics and metabolism were significantly decreased after 48 hours. These results indicate that an increased hydrostatic pressure gradient enhances tissue damage and causes reopening of the blood-brain barrier.

Animals↗
PubMed1993

Vascular dysfunction detected by a simplified venous occlusion test in NIDDM patients.

OBJECTIVE: To elucidate the relationship between angiopathies and vascular function evaluated by a simplified venous occlusion test in patients with NIDDM. RESEARCH DESIGN AND METHODS: The serum concentration of FDP was measured before and 5 min after venous occlusion in 23 NIDDM patients, 11 patients with cerebrovascular accident, and 10 age-matched healthy control subjects. RESULTS: The increment of serum FDP level after venous occlusion was significantly less in patients with NIDDM (60.6 +/- 33.5 to 81.5 +/- 49.6 ng/ml) and in those with cerebrovascular accident (101.4 +/- 51.5 to 116.2 +/- 47.2 ng/ml) than in control subjects (79.9 +/- 41.0 to 148.8 +/- 65.4 ng/ml). The increment of serum FDP after venous occlusion in NIDDM patients with macroangiopathy was significantly lower than that in those without macroangiopathy. CONCLUSION: The responsiveness of fibrinolytic activity to venous occlusion was significantly less in NIDDM patients with macroangiopathy, as in patients with cerebrovascular accident, compared with that in healthy control subjects.

Adult↗
PubMed1993

Immunohistochemical localization of pituitary gonadotropins and estrogen in human postmenopausal ovaries.

Immunohistochemical localization of pituitary gonadotropins (FSH, LH) and estrogen was investigated in 17 ovaries from ten postmenopausal women. Positive immunostaining for 17 beta-estradiol was demonstrated in the cortical stroma of 14 postmenopausal ovaries. Positive immunostaining for FSH was localized in the cortical stroma of 12 postmenopausal ovaries, and positive immunostaining for LH was also localized in 12 ovaries. Immunohistochemical localization for pituitary gonadotropins (FSH and/or LH) and 17 beta-estradiol was identified in the same hypertrophic cortical stroma of 13 postmenopausal ovaries. The ultrastructural study suggested steroidogenic activity in the cortical stromal cells of the postmenopausal ovary. In addition, peripheral and ovarian venous concentrations of 17 beta-estradiol were measured in 13 postmenopausal subjects, and significant concentration gradient for serum 17 beta-estradiol was noted. The ovarian/peripheral concentration gradient for 17 beta-estradiol had a tendency to be higher in the subjects with positive immunostaining for 17 beta-estradiol compared with that in the subjects with negative immunostaining. The present results suggest that the human ovary secretes estrogen in response to pituitary gonadotropins even after the menopause.

Aged↗
PubMed1993

Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 3rd communication: antihypertensive effects of S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3-b] pyridine-5-carboxylate in hypertensive rats and dogs.

Hypotensive and antihypertensive effects of S-312-d (S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate, CAS 120056-57-7) in Wistar Kyoto rat (WKY), spontaneously hypertensive rat (SHR), stroke-prone SHR (SHRSP), and DOCA-salt hypertensive rat (DOCA-HR) were compared with those of other representative calcium antagonists. The minimal effective hypotensive dose of S-312-d in WKY was 3 mg/kg p.o. and those in SHR, SHRSP, and DOCA-HR were 1 mg/kg p.o. in gum arabic suspension. The minimal antihypertensive dose of S-312-d in polyethylene glycol solution was 0.3 mg/kg p.o. in SHRSP. The antihypertensive effects of S-312-d was the most potent and long-lasting compared with the calcium antagonists, nifedipine, nicardipine, nimodipine, nilvadipine, and flunarizine. In conscious two-kidney Goldblatt-type hypertensive dogs, a significant antihypertensive effect and concomitant increases of heart rate with S-312-d at 1 mg/kg lasted for 4 to 6 h after oral administration. Determination of the plasma concentration of S-312-d by HPLC showed that more than 4.3 ng/ml of S-312-d is required for a significant antihypertensive effect. Subcutaneous administration of atenolol at 20 mg/kg 30 min before S-312-d significantly inhibited the tachycardia with S-312-d at 1 mg/kg p.o. but not its antihypertensive effect. S-312-d is considered useful for the treatment of essential hypertension and related organ disorders.

Animals↗
PubMed1993

The effect of VA-045 on disturbance in consciousness in experimental animal models.

The effect of VA-045, a novel apovincaminic acid derivative, on disturbance in consciousness was investigated in mice and rats. VA-045 and thyrotropin-releasing hormone (TRH) shortened the duration of pentobarbital-induced sleeping in rats. VA-045 and TRH improved head impact-induced disturbed behavior in mice. The duration of action of the improving effect of VA-045 was longer than that of TRH. VA-045 and TRH also ameliorated the global cerebral ischemia-induced neurological deficits. Global cerebral ischemia was produced by a 10 min occlusion of both common carotid arteries 24 hr after the permanent electrocauterization of bilateral vertebral arteries. VA-045, but not TRH, attenuated the global cerebral ischemia-induced decreased step through latency (STL) in a passive avoidance task in rats. TRH enhanced spontaneous locomotor activity in mice, whereas VA-045 had no effect on it. The pharmacological effects of VA-045 on disturbance in consciousness will be discussed.

Animals↗
PubMed1993

[Spinocerebellar ataxia 1--clinical study of 17 patients in a large pedigree].

We studied a large pedigree with dominant spinocerebellar ataxia, genetically and clinically. At now, 27 members over 5 generations have been affected. Linkage study for the disease locus to D6S89 in a total of 44 individuals showed maximum lod scores of 3.99 at theta = 0.000. This result indicates that the disease locus of this pedigree locates near D6S89 on chromosome 6p (SCA 1). We studied 17 patients clinically. Mean age at onset was 37.7 +/- 8.6, and mean duration after onset was 11.3 +/- 6.8 years. Their clinical features were characterized by progressive ataxia, pyramidal involvement with hyperreflexia or spasticity, and mild posterior column involvement. Mild gaze nystagmus at early stage became unclear with the progress of illness. The frequent signs in the advanced stage were diffuse amyotropy, twitching of face or tongue, bulbar palsy, slow saccade, external ophthalmoparesis, mydriasis, coarse postural tremor, and dementia with emotional disturbance. There are so much clinical similarities between our pedigree and other SCA 1 pedigrees in the literature. Generally, SCA 1 shows hyperreflexia, spasticity, and terminal slow saccade. On the other hand, non-SCA 1 type OPCA is characterized by progressive hyporeflexia, slow eye movement from early stage, and frequent choreoathetosis. Gaze nystagmus, external ophthalmoparesis, amyotrophy, and spasticity are common in both SCA 1 and Machado-Joseph disease (MJD). However, they are more frequent in MJD than SCA 1. Moreover, extrapyramidal signs, such as dystonia, are rare is SCA 1. Based on these difference, SCA 1 could be clinically differentiated from other similar hereditary ataxias.

Adult↗
PubMed1992

High-performance affinity chromatography system for the rapid, efficient assay of glycated albumin.

A high-performance affinity chromatographic system was constructed and shown to permit highly reproducible, rapid, automatic assays of serum glycated albumin (GA) by separation of albumin (Alb) on an anion-exchange column (Asahipak ES-502N) packed with a vinyl alcohol copolymer bearing diethylamino groups and consecutive separation of GA on a column packed with a vinyl alcohol copolymer bearing boronate groups. The first column selectively retained Alb free of other serum proteins and permitted at least a 95% recovery of sample Alb. The purity of the Alb peak was confirmed by two-dimensional electrophoresis. Chromatographic analyses of human serum Alb incubated with glucose on the second column showed that the peak area for GA increased in accordance with the incubation time and suggested selective adsorption of GA on the second column. Optimization of the conditions for the two-column system reduced the analysis time to 10 min. Analyses of human sera with the present system showed GA to be 16.1 +/- 1.1% (mean +/- S.D.) of total Alb in non-diabetic children and 39.9 +/- 9.1% (mean +/- S.D.) in diabetic children (0-17 years old).

Adolescent↗
PubMed1992

Correlation between residual beta-cell function and age at onset of spontaneous diabetes in Long Evans Tokushima lean rats.

We studied the natural course of disease in spontaneously diabetic rats, Long Evans Tokushima Lean (LETL) rats, to determine whether it showed similar pathogenetic heterogeneity to that of patients with insulin-dependent diabetes mellitus (IDDM) with regard to the relationships between age at onset, rapidity of disease progress, and degree of beta-cell function at the time of its manifestation. Type 1 diabetes developed in 35 rats (6.3%) between 40 and 140 days of age. Eight rats that became diabetic at age 69 days or less were more severely ketotic at the time of first detection of glycosuria and showed more rapid deterioration than seven rats that became diabetic later after birth (mean plasma 3-hydroxybutyrate levels, 4,707 +/- 1,215 pmol/L v 1,390 +/- 859 pmol/L; mean +/- SEM, P < .01). The mean plasma levels and pancreatic content of immunoreactive insulin (IRI) of the early onset rats, 47 +/- 13 pmol/L and 19 +/- 12 pmol/g tissue weight, were significantly lower (P < .01) than the corresponding values of the late-onset rats, 262 +/- 52 pmol/L and 348 +/- 87 pmol/g tissue weight, respectively. Both values were markedly lower than the mean values of 25 nondiabetic LETL rats, 976 +/- 122 pmol/L and 3,488 +/- 628 pmol/g tissue weight. Plasma immunoreactive glucagon (IRG) levels were significantly increased in the diabetic groups (early onset, 57 +/- 13 pmol/L; late-onset, 51 +/- 12 pmol/L; nondiabetic, 18 +/- 1 pmol/L; P < .01). These changes in pancreatic hormone levels of the early onset and late-onset rats were compatible with the histological features of their pancreatic islets.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Decrease in plasma GLP-1 immunoreactivity in starved rats.

To determine whether starvation affects the metabolism of glucagon-like peptide-1 (GLP-1), we measured the plasma levels of proglucagon-derived peptides and the biosynthesis and posttranslational processing of proglucagon in groups of six rats starved for 1, 3 and 5 days. The plasma levels of GLP-1 immunoreactivity (GLP-1 IR) and glucagon-like immunoreactivity (GLI) decreased during starvation reaching 79 and 56% of the respective control values by day 5 (P less than 0.05 and less than 0.01 vs control). The same is true of the plasma IRI level. The ileal contents of GLP-1 IR and GLI were 50.8 +/- 3.8 pmol/g wet weight and 161.8 +/- 13.2 pmol/g wet weight, respectively, on day 5 of starvation, which were significantly lower (P less than 0.01) than the respective values of 94.8 +/- 16.6 pmol/g wet weight and 262.7 +/- 28.1 pmol/g wet weight in control rats. However, the pancreatic contents of proglucagon-derived peptides tended to increase during starvation, although their increases were not statistically significant. No significant change in the posttranslational processing of proglucagon was detected during starvation. The decrease in the ileal proglucagon-derived peptides content was not associated with a decrease in intestinal proglucagon mRNA transcripts. These results suggested that decreased synthesis of proglucagon-derived peptides by the intestine was largely responsible for the reductions in their circulating levels in starved rats.

Analysis of Variance↗
PubMed1992

The response of glycated albumin to blood glucose change in the circulation in streptozotocin-diabetic rats--comparison of theoretical values with experimental data.

The contribution of the preceding blood glucose level to glycated protein was theoretically analyzed using a linear kinetic model and was compared with experiments using streptozotocin-diabetic rats. We assumed that the glycation process can be described by one irreversible step and that the fraction of glycated protein is small. A formula based on these two assumptions showed that the level of glycated protein was proportional to the weighted mean blood glucose concentration in the preceding period and that the weight function was determined by the metabolic characteristics of each protein. For assessing the usefulness of the present formula, the value calculated for the response of glycated albumin (GA) to acute blood glucose change in streptozotocin-diabetic rats was compared with the data obtained under three experimental conditions. The calculated responses of GA showed a little more retardation than the observed data, but showed enough agreement with them.

Animals↗
PubMed1992

Epidermal growth factor binding sites in porcine granulosa cells and their regulation by follicle-stimulating hormone.

Epidermal growth factor (EGF) modulates ovarian function, including folliculogenesis and steroidogenesis. We investigated the localization of EGF binding sites in the porcine ovary, and the effect of FSH on EGF binding to cultured granulosa cells. Autoradiographic study demonstrated that the binding sites for 125I-labeled mouse EGF in the porcine ovary were present in the granulosa and luteal cells, but not in the thecal cells. Porcine granulosa cells were collected by the needle aspiration method from small (1-2 mm) and medium-sized (3-5 mm) follicles. Scatchard analysis showed that a single class of the specific binding sites for EGF was present in the granulosa cells. The number of binding sites and the apparent dissociation constant were 5,540 binding sites/cell and 0.23 nM (medium-sized follicle), respectively. No significant difference was observed between small and medium-sized follicles. Granulosa cells were cultured for 48 h at 37 degrees C in medium alone or with increasing doses of ovine FSH (1-100 ng/ml). FSH treatment significantly increased EGF binding in a dose-dependent manner. In conclusion, it is suggested that the specific high affinity, low capacity binding sites for EGF are present in porcine granulosa cells, and that they are up-regulated by FSH.

Animals↗