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Biomedical subjects

K Shima

Publications and source records attributed to K Shima.

At least 181 records · Page 10Linked to original sources
PubMed1995

Effect of timely insulin administration on pancreatic B-cells of Otsuka-Long-Evans-Tokushima-Fatty (OLETF) strain rats. An animal model of non-insulin dependent diabetes mellitus (NIDDM).

Morphological changes of the pancreas and impairment of pancreatic B-cell function in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) with non-insulin dependent diabetes mellitus might be the result of over-activity of B-cells to compensate for insulin insensitivity. To test this possibility, we studied whether the histological and functional alterations in the pancreas of male OLETF rats were improved by treatment with insulin for a certain period, which might reduce the burden to B-cells. Groups of 6 male OLETF rats and 5 or 4 male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats received injections of insulin (Ultralente MC; 10 U/kg/day to OLETF rats, 5 U/kg/day to LETO rats) or saline subcutaneously, once a day for 3 weeks from 24 weeks of age. Then their insulin responses to glucose (200 mg/dl) and arginine (10 mmol/l) were examined by perfusion of the pancreas. The morphological features of their pancreata were also examined. The insulin response to glucose in OLETF rats treated with insulin was significantly higher than that of OLETF rats treated with saline (sigma IRI 142.5 +/- 27.0 vs. 37.4 +/- 6.3 ng/ml.20 min, p < 0.05) and unlike in the latter showed the normal two phases. The morphological changes of the pancreas in the insulin-treated OLETF rats were remarkably ameliorated, animals showing no enlargement and only slight fibrosis of islets. Thus treatment with insulin was effective for preventing B-cell dysfunction and morphological changes of the pancreas in NIDDM model rats.

Animals↗
PubMed1995

Immediate cerebrovascular responses to closed head injury in the rat.

Changes in cerebrovascular dynamics were investigated immediately after closed head injury in the rat using a newly developed closed head injury model developed by Marmarou et al. Intracranial pressure (ICP) and mean arterial blood pressure (MABP) were monitored before and after trauma. Regional cerebral blood flow (rCBF), regional cerebral plasma volume (rCPV), and blood-brain barrier (BBB) permeability were measured autoradiographically with iodo[14C]antipyrine [14C]sucrose, and [alpha-14C]aminoisobutyric acid, respectively. rCBF responses to induced hypertension after trauma were measured by laser-Doppler flowmetry to investigate the status of autoregulation. Before injury, baseline ICP values ranged from 6 to 10 mm Hg in all animals. Immediately after trauma, ICP increased synchronously with MABP to > 100 mm Hg and then rapidly returned to baseline values: MABP increased rapidly by 20% after trauma and returned to baseline values within 30 sec. At 30 sec after injury, a significant increase in rCBF was observed in five subcortical regions (p < 0.05), and a significant increase in rCPV was observed in the frontal cortex, parietal cortex, thalamus, and hypothalamus (p < 0.05). At 10 min after injury, BBB permeability (the transfer constant for [alpha 14C]aminoisobutyric acid) was < 0.1 mL/kg/min for all regions except those with a relatively permeable BBB, for example, median eminence, choroidal plexus, pineal body, and pituitary gland. Induced hypertension resulted in a prolonged increase in rCBF after trauma. Thus, in this closed head injury model, which is not associated with marked hypertension or prolonged BBB disruption, widespread increases in rCBF and impaired cerebral autoregulation were apparent immediately after injury.

Animals↗
PubMed1995

In vivo studies of extracellular metabolites in the striatum after distal middle cerebral artery occlusion in stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We demonstrated in a previous study that 45Ca accumulation in the lateral part of the striatum was detected 3 days after distal middle cerebral artery (MCA) occlusion using a 45Ca autoradiographic technique in stroke-prone spontaneously hypertensive rats. However, the mechanism of delayed neuronal damage that occurred in the lateral part of the striatum is unknown. We examined changes in amino acids and monoamines in the striatums of rat brains after MCA occlusion in stroke-prone spontaneously hypertensive rats using an in vivo brain microdialysis technique. METHODS: Microdialysis probes were inserted into the lateral or medial part of the striatum 24 hours before the experiment. The dialysis probe was perfused continuously at 2 microL/min with Ringer's solution, and the dialysate samples were collected every 20 minutes. After a 3-hour period for baseline stabilization, the right MCA was occluded. The dialysate count of monoamines and amino acids was determined by high-performance liquid chromatography. RESULTS: After MCA occlusion, a threefold transient increase in glutamate was observed in the lateral part of the striatum. The level returned to its baseline value 60 minutes after MCA occlusion. Dopamine in the lateral part increased twofold to its peak value. This release persisted for 2 hours after MCA occlusion. There were no significant changes in these components in the extracellular fluid of the medial part of the striatum. CONCLUSIONS: Our study demonstrated that changes of neurotransmitters in the lateral part of the striatum after MCA occlusion differed from those in the medial part. These results suggest that excessive release of glutamate and dopamine is related to delayed neuronal damage that occurs in the lateral part of the striatum in this model.

Animals↗
PubMed1995

Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level.

OBJECTIVE: To examine the kinetics of HbA1c, glycated albumin (GA), and fructosamine (FA) levels in response to plasma glucose change and their relationship with the preceding plasma glucose level. RESEARCH DESIGN AND METHODS: The time courses of HbA1c, GA, and FA after acute glycemic normalization were observed in nine patients with newly diagnosed non-insulin-dependent diabetes mellitus and compared with theoretical ones. Their weight functions against preceding plasma glucose level were analyzed assuming a stepwise plasma glucose change and compared with the theoretical prediction. RESULTS: The fasting plasma glucose level was acutely normalized after admission with a half-time of 6.3 +/- 2.4 days (mean +/- SD). The HbA1c level decreased linearly during the initial 2 months with a half-time of 34.6 +/- 10.1 days, followed by a gradual decrease thereafter. GA and FA levels decreased very rapidly during the initial 2-3 weeks with half-times of 17.1 +/- 2.8 and 12.2 +/- 4.8 days, respectively, followed by a gradual decrease thereafter. The time courses of HbA1c, GA, and FA agreed well with theoretically estimated decay curves. Experimental values of weight functions against the preceding plasma glucose level agreed well with the theoretical prediction. The weight functions for glycated proteins had maximum values on the days just before the measurement of glycated proteins and gradually decreased with an increasing time interval. The lengths of the periods over which the weight functions for HbA1c, GA, and FA extend back were estimated to be roughly 100, 40, and 30 days, respectively. CONCLUSIONS: The levels of HbA1c, GA, and FA do not reflect the simple mean but reflect the weighted mean of the preceding plasma glucose level over a considerably longer period than was previously speculated.

Adult↗
PubMed1995

[Diabetogenes; which cause type II diabetes mellitus].

Glucose homeostasis depends upon a balance between glucose production by the liver and glucose utilization by insulin-dependent tissues, such as muscle and fat. Insulin, secreted by the pancreatic B cell, inhibits hepatic glucose output and facilitates glucose utilization in the muscle and fat tissues. In the diabetic patients, there are three types of pathological defects; (1) inability of the B cell to secrete normal insulin in an accurate fashion, (2) increase in the hepatic glucose output, and (3) decrease in glucose metabolism at the muscle and fat tissues. Candidate genes which cause the first defect are the insulin gene, the glucokinase gene and the mitochondrial tRNA gene. The glucokinase gene causes the second defect, too. Those which cause the third defect are the insulin receptor gene and glycogen synthase gene. However, these genes in total account for 3% or less of type II diabetes. Further analyses of systems of both insulin secretion and insulin receptor-signaling at a molecular level will help elucidate the other diabetes candidate genes.

Animals↗
PubMed1995

[A penetrating injury of the extracranial vertebral artery: a case report].

Penetrating injury to the vertebral artery is a very rare accident and no case except ours has been reported to date in Japan. We reported a case of successful treatment of a penetrating injury by a nail to the left vertebral artery with the use of interventional radiologic procedure. A 27-year-old man was admitted to our hospital with a complaint of penetrating injury in his neck. Left vertebral angiography revealed that a nail had penetrated into the vertebral artery at the C6 level. Considering the possibility of thrombus formation around the metallic foreign body and the risk of uncontrollable bleeding, we performed embolization of the injured vertebral artery with Interlocking Detachable Coil.

Adult↗
PubMed1995

[Calvarial metastasis of cervical carcinoma showing the dural tail sign on magnetic resonance imaging].

A 42-year-old female was admitted to our department on 3 August, 1993 with a 3-month history of steadily enlarging subgaleal mass (3.2 x 3.0 cm) in the parietal region. She had been doing well following radiotherapy for cervical carcinoma of the uterus one year previously. Neurological examination on admission was negative. Axial T1-weighted MR images showed a low-intensity mass with marked homogeneous enhancement in the area of bone destruction, and a dural tail adjacent to the tumor (flare sign) after Gd-DTPA administration. The tumor was totally resected, and was pathologically diagnosed as a calvarial metastasis of the cervical carcinoma. However, 5 months later the tumor recurred anterior to the site of the resection. Since the dura mater adjacent to the tumor exhibited collagen fiber proliferation, the dural tail sign was appeared to represent a reaction to the tumor. Other calvarial metastatic lesions appeared adjacent to the initial lesion 5 months after the initial lesion was resected, however, suggesting that tumor cell nests were present in the dura mater which exhibited the dural tail sign. Extensive pathological examination of the dura mater appears necessary whenever a dural tail sign is detected by magnetic resonance imaging.

Adult↗
PubMed1995

[An interlaboratory standardization of HbA1c determination in Japan].

A survey of the actual state of interlaboratory differences in HbA1c values revealed a great variation of the values among 107 laboratories throughout Japan; the coefficient of variation (CV) for measurements of fresh blood samples was as high as 10.5%. On the basis of this results, it became apparent that this large interlaboratory variation was mainly due to differences in evaluation of a labile HbA1c component and in values measured with an instrument of one manufacture with another. To verify this assumption, we asked the laboratories to measure only a stable component using common calibrations. These procedures resulted in a marked reduction of the interlaboratory difference in HbA1c values; the CV decreased to 2.82%. The reference intervals of HbA1c calculated from the HbA1c results of 725 healthy subjects measured using the standardized procedure was from 4.3% to 5.8%.

Adult↗
PubMed1995

Selective vulnerability of hippocampal CA3 neurons to hypoxia after mild concussion in the rat.

Immunohistochemical staining for microtubule-associated protein 2 (MAP2) and synaptophysin was used to investigate the effect of hypoxia on hippocampal neurons after mild concussion in the rat. Male Sprague-Dawley rats were divided into four groups: Group 1 (n = 3) was subjected to a mild impact-acceleration closed head injury, group 2 (n = 3) was subjected to 30 min of moderate hypoxia, group 3 (n = 5) was subjected to head trauma followed by 30 min of moderate hypoxia, and group 4 (n = 3) comprised sham-operated controls. All rats were fixed by transcardial perfusion 24 h after insult. No damage was observed in CA1 or CA2 neurons in any of the rats. However, rats in group 3 showed selective damage of hippocampal CA3 neurons manifested by a pycnosis and a marked decrease in MAP2 immunoreactivity. Presynaptic terminals visualized by synaptophysin immunostaining showed no differences among groups. The loss of immunoreactivity for the post-synaptic somal and dendritic protein marker MAP2 from the CA3 subfield 24 h after combined insults indicates an increased vulnerability of pyramidal cells in this brain area.

Animals↗
PubMed1994

Immunohistochemical evidence for amyloid beta in rat soleus muscle in chloroquine-induced myopathy.

Deposition of amyloid beta (A beta) is one of the pathological hallmarks of brains affected with Alzheimer's disease (AD). The accumulation of A beta have been observed in human myopathies with rimmed vacuoles (RVs) which might involve lysosomal function. Chloroquine, a potent lysosomotropic agent, induces muscle pathology in experimental animals similar to myopathy with RV. In this study, we demonstrate, for the first time, immunohistochemical evidence that A beta and cathepsin D, a lysosomal enzyme, accumulate in vacuolated rat soleus muscle due to chloroquine-induced myopathy. These data indicate that lysosomes are important in the metabolism of amyloid precursor protein to generate A beta. This experimental system seems to be useful not only to study basic mechanisms underlying RV myopathy but also to understand processing of amyloid precursor protein to A beta in AD.

Amyloid beta-Peptides↗
PubMed1994

Role for supplementary motor area cells in planning several movements ahead.

To achieve a volitional goal, we need to execute multiple movements in a specific temporal order. After repetitive performance of a particular sequence of movements, we are able to memorize and execute the whole sequence without external guidance. Where and how in the brain do we store information necessary for the orderly performance of multiple movements? We have found a group of cells in the cerebral cortex of monkeys whose activity is exclusively related to a sequence of multiple movements performed in a particular order. Such cellular activity exists in the supplementary motor area, but not in the primary motor cortex. We propose that these cells contribute a signal about the order of forthcoming multiple movements, and are useful for planning and coding of several movements ahead.

Animals↗
PubMed1994

Expression of the gene encoding the tyrosine kinase-deficient human insulin receptor in transgenic mice.

Defects in the insulin receptor (IR) in diabetic patients have been given much attention. To address the role of such defects, we generated a transgenic (TG) mouse carrying the cDNA encoding a tyrosine-kinase (TK)-deficient human IR (hIR), under the control of the native promoter. The TG mouse expressed the transgene (TG) mRNA in the liver, as identified in Northern blots. Analyses of various tissues by reverse transcription-polymerase chain reaction revealed that expressions of the TG mRNA in brain, heart, kidney, lung, stomach, skeletal muscle and adipose tissue were higher than those seen with the endogenous mouse IR (mIR), but expression in small intestine, colon, spleen, testis and ovary were approximately half those seen with the endogenous mIR. In the liver, the expression of the TG was about one tenth that of the endogenous mIR. In analyses of insulin binding and IR autophosphorylation, using a human-specific anti-IR antibody, the TK-deficient hIR was synthesized in the tissues of the TG mice. Despite the expression of TK-deficient hIRs in various tissues, including the major insulin-target tissues, muscle and adipose tissues, of the TG mice, no glucose intolerance was observed as assessed by the intraperitoneal glucose tolerance test, before and after sucrose feeding for 55 weeks. Our results suggest that a higher expression of the mutated IR, especially in the liver which is another major insulin-target tissue, or additional pathogenic factors, environmental or genetic, might be required for glucose intolerance.

Animals↗
PubMed1994

Glyburide enhances insulin gene expression and glucose-induced insulin release in isolated rat islets.

Long-term glyburide therapy has been reported to improve glucose-induced insulin secretion in patients with NIDDM. We examined the effects of glyburide on the synthesis and release of insulin and insulin gene expression in isolated islets in vitro. Incubation with glyburide (500 ng/ml) significantly increased insulin release without affecting the insulin content. The PPI mRNA level was not increased after incubation for 1 h but was increased after incubation for 20 h. Incubation with 5 ng/ml of glyburide for 1 h or 20 h had no effect on the content or release of insulin, but incubation with 5 ng/ml of glyburide for 20 h significantly increased the PPI mRNA level and enhanced insulin release induced by 11 mM glucose. These results suggest that a high concentration of glyburide stimulates insulin release directly, while a low concentration of glyburide increases the PPI mRNA level and may thereby enhance glucose-induced insulin release.

Animals↗
PubMed1994

Resolution of peritumoral brain edema following excision of meningioma.

We studied the resolution of peritumoral brain edema after meningioma excision. In twenty-nine patients with meningioma, the total volume of tumor and the peritumoral edema were measured planimetrically by serial CT scans and MRI with or without contrast enhancement. Four different patterns of postoperative resolution of hypodense volume on CT were observed: Group A: a large hypodensity rapidly decreased and disappeared, which may be related to the clearance of the real peritumoral edema in meningioma. Group B: a small hypodensity gradually disappeared. Group C: the hypodensity remained unchanged, which may result from the damaged brain tissue. Group D: the hypodensity progressively decreased but persisted, which may represent both the peritumoral edema and damaged brain tissue. We have calculated the resolution rate of edema fluid using the clearance curve of Groups A and D. The average resolution rate of edema fluid during the passage through 1 cm3 of the peritumoral white matter was 0.0493 ml/day. We speculate that 50% of edematous white matter, which presented as hypodensity on a CT scan, may be resolved in 4 days after total removal, and that 90% may be resolved in 14 days.

Blood-Brain Barrier↗
PubMed1994

Blood-brain barrier, cerebral blood flow, and cerebral plasma volume immediately after head injury in the rat.

The purpose of the present study was to determine blood-brain barrier (BBB) permeability, regional cerebral blood flow (rCBF) and regional cerebral plasma volume (rCPV) in the period immediately after head injury, and thereby to evaluate the effects of vascular factors in the pathophysiology of traumatic brain injury. Male Sprague-Dawley rats (350-450 g) anesthetized with 1.0-1.5% halothane were subjected to an impact acceleration closed head injury at the moderate level. BBB permeability (n = 5), rCBF (n = 8) and rCPV (n = 9) were measured by quantitative autoradiographic techniques using 14C-alpha-aminoisobutyric acid (AIB), 14C-iodoantipyrine and 14C-sucrose, respectively. Intravenous administration of each radiotracer was simultaneous with the traumatic impact. At 10 min after injury, BBB permeability, the transfer constant for AIB, was less than 0.1 ml/kg/min for all regions except for those with a relatively leaky BBB. At 30 s after injury, a significant and heterogeneous increase in rCBF was observed at 9 subcortical regions (p < 0.05). RCPV increased significantly in the frontal cortex, parietal cortex, thalamus, and hypothalamus (p < 0.05). In our closed head injury model without severe hypertension, BBB disruption did not occur immediately after trauma. Vascular responses in the period immediately after trauma may result from the derangement of cerebral autoregulation.

Animals↗
PubMed1994

Blood-brain barrier, cerebral blood flow, and brain edema in spontaneously hypertensive rats with chronic focal ischemia.

This study was conducted to explore the participation of blood-brain barrier (BBB) permeability and cerebral blood flow (CBF) on the development of ischemic brain edema in rats with chronic arterial hypertension. Young spontaneously hypertensive rats were used, and focal ischemia was produced by occluding the distal middle cerebral artery (MCA). On day 7 after MCA occlusion, BBB permeability and CBF were measured by autoradiographic methods using 14C-alpha-amino-isobutyric acid (AIB) and 14C-iodoantipyrine. BBB permeability (transfer constant for AIB) was significantly higher in the ischemic center and periphery. The CBF of the ischemic cortex showed a graded reduction from the ischemic center to the surrounding area. The ischemic brain regions showed significantly decreased specific gravity. We conclude that SHRSP may be more vulnerable to BBB disruption after ischemia.

Animals↗
PubMed1994

Effects of an apovincaminic acid derivative VA-045 on neuronal activity in rat brain stem reticular formation.

Extracellular single unit and spontaneous cortical electroencephalographic (ECoG) recordings were made in the brain stem reticular formation (RF) and the frontal cortex, respectively, of urethane-anesthetized rats. VA-045, an apovincaminic acid derivative had no significant effects on the spontaneous firing rate of the RF neurons and ECoG. Closed head injury (CHI) was induced by dropping a 400 g weight through a tube from 70 cm on a steel helmet placed on the vertex. CHI led to a reduction in the firing rate of RF neurons and ECoG synchronization. VA-045 dose-dependently reversed the CHI-induced decrease in the firing rate of RF and led to ECoG desyncronization. Clonidine, an alpha 2 adrenoceptor agonist, and scopolamine, a muscarinic receptor antagonist, also reduced the firing rate of RF neurons and led to ECoG synchronization. VA-045 dose-dependently antagonized the effects of clonidine, but not the effects of scopolamine on RF neuronal activity and ECoG. Thus, VA-045 has an ameliorating effect on the CHI-induced depression of neuronal activity in the RF. A central alpha 2 adrenoceptor antagonistic action may be involved.

Animals↗