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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 253 records · Page 14Linked to original sources
PubMed1996

Comparison of Xe-CT/CBF and quantitative ECD-SPECT.

We compared stable xenon enhanced X-ray computed tomography (Xe-CT) with Technetium-99m ethylsteinate dimer single-photon emission computed tomography (ECD-SPECT) in 12 patients. We evaluated the cerebral blood flow (CBF) values in the territory of the anterior, middle and posterior cerebral artery, and in the thalamus. The CBF values were higher in ECD-SPECT than in Xe-CT except for the values of the thalamus. The posterior cerebral artery territory showed a lower correlation and the thalamus had no correlation between two methods. We discussed causes of these differences.

Aged↗
PubMed1996

Surgical modulation of the natural course of collateral circulation in chronic ischemic patients.

The purpose of this study was to evaluate hemodynamic compromise in terms of baseline CBF and CRC in patients with chronic cerebral occlusive lesions and its modulation by a superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. The study subjects were 10 healthy volunteers and 49 chronic ischemic patients with stenosis or occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA). The hemodynamics were measured using stable xenon enhanced computed tomographic CBF measurement with the acetazolamide challenge. The compromised hemodynamics in patients with chronic steno-occlusive lesions did not improve during their natural course after two months. STA-MCA bypass modulated hemodynamic compromise in the ischemic patients. We recommend STA-MCA bypass for patients with reduced CRC, regardless of whether baseline CBF is reduced or normal. Hemodynamic classification using a combination of baseline CBF values and CRC values is useful for evaluating cerebral hemodynamics and for choosing the best treatment for cerebral ischemia with occlusive lesions.

Adult↗
PubMed1996

Modulation of cerebral hemodynamics by surgical revascularization in patients with moyamoya disease.

The purpose of this study was to evaluate hemodynamic compromise in the patients with moyamoya disease and surgical modulation of the hemodynamics using stable xenon enhanced computed tomographic CBF measurement with the acetazolamide challenge. The study group consisted of 15 preoperative cases and 17 postoperative cases. In the preoperative group, regional resting cerebral blood flow (rCBF) and regional cerebrovascular reserve capacity (rCRC) were reduced. The reduction was more prominent in the anterior circulation than in the posterior circulation. In the postoperative group, rCBF and rCRC were still low in the anterior circulation. Revascularization increased the resting CBF but did not change the CRC. Postoperative CBF did not increase in adults but increased in children. These findings suggest that the misery perfusion state may be present only in the child's brain. Measurement of CBF and CRC is useful to evaluate the hemodynamics of moyamoya disease.

Acetazolamide↗
PubMed1996

Effect of angiotensin converting enzyme inhibitor on chronic ischemic patients.

Most of patients with cerebrovascular disease are associated with hypertension. Hypertension induces progressive atheromatous changes in cerebral arteries, and often causes steno-occlusive lesions of cerebral arteries. Angiotensin converting enzyme (ACE) inhibitor cilazapril is one of the antihypertensive drugs. It was reported that cilazapril improved resting cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) in experimental studies. In this clinical study, the authors investigated whether long-term treatment with cilazapril could improve CBF and CRC in patients with steno-occlusive lesions of the major cerebral arterial trunk, measured by stable xenon computerized tomography (Xe-CT) with acetazolamide challenge. On the other hand, CBF and CRC in the calcium blocker-treated patients were measured in the same way. CBF did not change after long-term treatment with both cilazapril and calcium blocker. In the cilazapril-treated group, CRC was increased significantly (p < 0.05). However, CRC did not change in the calcium blocker-treated group. It was recognized that long-term treatment with cilazapril did not decrease CBF and improved CRC in patients with occlusive lesions of the major cerebral arterial trunk.

Acetazolamide↗
PubMed1996

Hemodynamics of hypertensive putaminal hemorrhage evaluated by Xenon-enhanced computed tomography and acetazolamide test.

Cerebral blood flow (CBF) is usually decreased in patients with hypertensive putaminal hemorrhage (HPH). However, there are few reports concerning cerebrovascular reserve capacity (CRC) in these cases. This study evaluated cerebral hemodynamics in patients with HPH by measuring CBF and CRC. CBF and CRC were measured by stable xenon enhanced computed tomography (Xe-CT) in 11 patients with HPH (HPH group) and 11 patients with essential hypertension without intracerebral hematoma (non-HPH group). CBFs of the hemisphere and thalamus in the HPH group were lower than those in the non-HPH group. And the CBF of the hemisphere was increased transiently after the surgical evacuation of the hematoma. Thereafter, it fell gradually. The CRCs were also lower in acute stage of the HPH group. The CRC recovered during the chronic stage. Hemodynamics in patients with HPH can be modulated by surgical removal of hematoma. However, some adjunct therapies are necessary to prevent delayed neuronal inactivity, Stable Xe-CT with acetazolamide test is useful to evaluate hemodynamics in the HPH patients.

Acetazolamide↗
PubMed1996

Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk.

The intervertebral disk is routinely subjected to compressive loads that alter with posture and muscle activity and can produce pressures > 2 MPa in human lumbar disks in vivo (A. Nachemson and G. Elfstrom. Scand. J. Rehabil. Med. 2, Suppl. 1:1-40, 1979; A. Nachemson and J. M. Morris. J. Bone Jt. Surg. Am. Vol. 46A: 1077-1092, 1964). We measured the effect of load on hydrostatic pressures in bovine caudal disks. With increase in applied load, pressure increased linearly in the nucleus and inner annulus. The resting pressure measured after slaughter (0.19 +/- 0.05 MPa) and the pressure at failure (34 MPa, estimated from the vertebrae/disk segment failure load of 7,430 +/- 590 N) define the limits that can occur in vivo. Because hydrostatic pressure influences matrix synthesis in articular cartilage, we have examined the effects of pressures in the range 1-10 MPa applied for 20 s or 2 h on proteoglycan synthesis in bovine caudal and human lumbar intervertebral disks in vitro. In the nucleus pulposus and inner annulus of bovine disks, application of hydrostatic pressure in the range of 1-7.5 MPa for only 20 s stimulated matrix synthesis over the following 2 h at atmospheric pressure. The maximum stimulation in the bovine disks was seen in the inner annulus after application of 2.5 MPa, where proteoglycan synthesis rates doubled. Exposure to 2.5 MPa also stimulated synthesis in the nucleus pulposus of human disks taken at surgery, whereas 7.5 MPa inhibited synthesis in five out of six specimens. With 2-h continuous exposure to the same levels of pressure, no stimulation was seen in the nucleus of bovine disks, and significant stimulation was only observed at 5.0 MPa in the inner annulus. Exposure to 10 MPa for either 20 s or 2 h inhibited proteoglycan synthesis in these regions of the disks. In contrast, in the outer annulus, where loading does not lead to a rise in hydrostatic pressure in vivo, there was no significant response to hydrostatic pressure over the range of 1-10 MPa in bovine or human disks.

Animals↗
PubMed1996

Comparison of the insulin and insulin-like growth factor 1 mitogenic intracellular signaling pathways.

We compared the intracellular insulin-like growth factor-1 (IGF-1) and insulin signaling pathways in Rat1 fibroblasts expressing the equivalent number of insulin receptors and endogenous IGF-1 receptors. Insulin and IGF-1 stimulated tyrosine phosphorylation of IRS-1 and Shc in a similar dose- and time-dependent manner. The time course of Shc phosphorylation by both IGF-1 and insulin was slower than that of IRS-1. Both phosphorylated IRS-1 and Shc associated with Grb2.Sos complexes, leading to p21ras activation. To compare the functional importance of p21ras for IGF-1-and insulin-induced DNA synthesis, single cell microinjection studies were performed. BrdU incorporation into newly synthesized DNA was measured by immunofluorescence microscopy to assess the functional importance of p21ras. Both IGF-1 and insulin stimulated BrdU incorporation, but the effect of IGF-1 was greater. Microinjection of anti-p21ras antibody completely inhibited both IGF-1-and insulin-induced DNA synthesis, indicating the central role of p21ras in signaling by both hormones. Signal transduction from these receptors to Grb2.Sos complexes can occur through IRS-1 and/or Shc. To assess these two possible pathways, we performed Western blots for Grb2 in anti-Shc and anti-IRS-1 immunoprecipitates and found that 5-fold more Grb2 was associated with Shc than with IRS-1 after either IGF-1 or insulin stimulation. Microinjection of anti-Shc antibody inhibited IGF-1 and insulin stimulation of DNA synthesis by 78% and 74%, respectively. By microinjecting Shc subdomains of GST fusion proteins, we found that Shc N-terminus, but not the Shc SH2, was the functionally important domain through which Shc interacts with IGF-1 and insulin receptors. Insulin stimulation caused hyperphosphorylation and decreased electrophoretic mobility of Sos, and a similar effect was seen with IGF-1, although the time course was delayed compared with insulin. Finally, IGF-1 activated mitogen-activated proten kinase activity more effectively than insulin. These data indicate that Shc, rather than IRS-1, appears to be the predominant functional link to Grb2.Sos complexes from the IGF-1 receptor, as it is from the insulin receptor. Although IGF-1 and insulin stimulate cell cycle progression with similar coupling mechanisms from the receptor to Shc, to Grb2.Sos, to p21ras, the delayed IGF-1 induced mobility shift of Sos could lead to, at least in part, more efficient coupling to mitogen-activated protein kinase. These findings might explain the greater mitogenic activity of IGF-1 compared with insulin.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Glucose-regulated translational control of proinsulin biosynthesis with that of the proinsulin endopeptidases PC2 and PC3 in the insulin-producing MIN6 cell line.

In the short term (< 2 h), proinsulin biosynthesis is predominately glucose regulated at the translational level; however, the details at the molecular level behind this mechanism are not well defined. One of the major hindrances for gaining a better understanding of the proinsulin biosynthetic mechanism has been a lack of an abundant source of beta-cells that express a phenotype of regulated proinsulin biosynthesis in the appropriate 2.8-16.7 mmol/l glucose range as defined in normal pancreatic islets. In this study, we demonstrate that in the MIN6 cell line, specific glucose-regulated translational control of proinsulin biosynthesis is present in the appropriate glucose concentration range. In addition to that of proinsulin, the biosynthesis of the two proinsulin conversion endopeptidases, PC2 and PC3, was coordinately glucose regulated in MIN6 cells, whereas that of the exopeptidase, carboxypeptidase H, was unaffected by glucose. Proinsulin, PC2 and PC3 biosynthesis was specifically stimulated over that of total MIN6 cell protein synthesis above a threshold of 4 mmol/l glucose that reached a maximum rate between 8 and 10 mmol/l glucose. Glucose-induced proinsulin, PC2, and PC3 biosynthesis was rapid (occurring after a 20-min lag period but reaching a maximum by 60 min), unaffected by the presence of actinomycin D; and in parallel experiments, stimulatory glucose concentrations did not alter MIN6 cell total preproinsulin, PC2, or PC3 mRNA levels. Thus, short-term (< 2 h) glucose stimulation of proinsulin, PC2 and PC3 biosynthesis in MIN6 cells, like that in isolated islets, was mediated at the translational level. Intracellular signals for mediating glucose-stimulated proinsulin PC2 and PC3 biosynthesis translation in MIN6 cells also appeared to be similar to those in pancreatic islets, requiring glucose metabolism and a supporting role for protein kinase A. However, protein kinase C or a Ca(2+)-dependent protein kinase did not appear to be required for glucose-regulated proinsulin biosynthesis in MIN6 cells, as in islets. MIN6 cells are the first beta-cell line that indicate glucose-regulated proinsulin biosynthesis translation essentially identical to that in differentiated islet beta-cells and will be an important experimental model to better define the mechanism of proinsulin biosynthesis in detail.

Animals↗
PubMed1996

Effect of mitochondrial and/or cytosolic glycerol 3-phosphate dehydrogenase overexpression on glucose-stimulated insulin secretion from MIN6 and HIT cells.

The glycerol phosphate shuttle consists of FAD-linked mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) and its cytosolic NAD-linked isoform (cGPDH). Impaired mGPDH activity has recently been suggested to be one of the primary causes of insulin secretory defects in beta-cells. We found that mGPDH and cGPDH activities in MIN6 cells are comparable to those of isolated islets and higher than those in HIT cells by eightfold and threefold, respectively. Therefore, we selected the MIN6 cell line as a beta-cell model with normally regulated insulin secretion and normal shuttle enzyme activities and the HIT cell line as a beta-cell model with impaired insulin secretion and lower activities of these enzymes. The role of these dehydrogenases in glucose-stimulated insulin secretion was addressed by examining the effects of overexpression of mGPDH and/or cGPDH via recombinant adenoviruses in these cells. Infection with recombinant adenovirus with a cDNA encoding the Escherichia coli beta-galactosidase gene resulted in expression of its gene in 90% of MIN6 and HIT cells. Infection with a recombinant adenovirus with mGPDH cDNA (Adex1CAmGPDH) caused 2.1-fold and 5.7-fold increases in dehydrogenase activity as compared with those of control MIN6 and HIT cells, respectively. Infection with a recombinant adenovirus with cGPDH cDNA (Adex1CAcGPDH) caused a more than 50-fold increase in activity in both cell lines. Glycerol phosphate shuttle flux, as estimated by [2-3H]glycerol conversion to [3H]H2O, was increased to 120-130% by infection with Adex1CAmGPDH, but not with Adex1CAcGPDH infection, in both MIN6 and HIT cells. No further increase in flux through the glycerol phosphate shuttle was detected when the cells were infected with Adex1CAmGPDH together with Adex1CAcGPDH. Furthermore, neither [U-14C]glucose oxidation nor the insulin secretory response to glucose was affected in either cell line. Thus, mGPDH abundance in MIN6 and HIT cells is not directly related to their insulin secretory capacity in response to glucose, and reduced expression of mGPDH is not the primary cause of abnormal insulin secretory responses in HIT cells. The present data indicate that the emerging hypothesis pointing to mGPDH deficiency as a possible cause of NIDDM needs to be carefully evaluated.

Adenoviridae↗
PubMed1996

[The effect of preoperative oral fluid intake on the volume and pH of gastric contents in elective surgical patients--a comparison of tea with apple juice].

This study aimed to investigate the effect of 150 ml of either tea or apple juice on the volume and pH of gastric contents in 40 elective surgical patients, ranging in age from 18 to 70 years. They were given diazepam 5 approximately 10 mg and roxatidine 75 mg orally 2 hours before the start of isoflurane anesthesia or modified neuroleptic anesthesia. Immediately following the induction of anesthesia with thiopental and vecuronium, a nasogastric tube was placed to aspirate the gastric content to measure its volume and pH. The volume and pH of gastric contents were 6.4 +/- 8.5 ml, 6.0 +/- 2.2 in tea group and 17.1 +/- 18.4 ml, 4.4 +/- 2.6 in apple juice group, respectively. There was a significant difference in the gastric volume between the two groups (P < 0.05), while no significant difference in gastric pH was observed. This result suggests that apple juice is not appropriate as preoperative drink because apple juice increases gastric contents, and may cause aspiration pneumonia.

Adolescent↗
PubMed1996

[Difficult tracheal intubation and abnormal response to thiopental in a patient with arthrogryposis multiplex congenita].

Anesthesia was administered for six times to a patient with arthrogryposis multiplex congenita (AMC) at the age of 10 to 17 years. In the first four occasions of anesthesia, difficult tracheal intubation was encountered due to limited neck extension, inadequate mouth opening and the short epiglottis. On the fifth anesthesia, the patient remained conscious even after intravenous injection of thiopental 6.6 mg.kg-1, and enflurane in combination with nitrous oxide was administered to induce anesthesia. During the induction of the sixth anesthesia, excessive oral secretion and severe continued nausea were observed just after intravenous administration of thiopental 5.3 mg.kg-1. These were overcome by intravenous administration of ketamine 2.0 mg.kg-1. Problems such as difficulty in tracheal intubation and abnormal response to thiopental need special attention in patients complicated with AMC, particularly during induction of anesthesia.

Abnormalities, Multiple↗
PubMed1996

Beta-cell loss and glucose induced signalling defects in diabetes mellitus caused by mitochondrial tRNALeu(UUR) gene mutation.

Japanese diabetic patients with diabetic mothers were screened, using peripheral leukocytes, for an A to G transition at nucleotide pair 3243, a tRNALeu(UUR) mutation of the mitochondrial gene. This mutation was identified in four pedigrees from among 300 unrelated patients. Diabetes mellitus cosegregated with the mutation, except in one young subject, and was maternally inherited. Long-term follow-up revealed that the underlying disorder, in affected individuals, is a progressive impairment of insulin secretion. In accordance with this finding, the mutation was found to be highly prevalent in a diabetes mellitus subset termed slowly progressive IDDM; the mutation was identified in 3 out of 27 subjects enrolled in the prospective study of islet cell antibody (ICA)-positive, initially non-insulin-dependent diabetic Japanese patients, who are at high risk of progressing to insulin dependence over several years. The histologic characteristics of slowly progressive insulin-dependent diabetes mellitus include substantial loss, though incomplete, of pancreatic beta-cells. Mitochondrial gene defects in beta-cells could therefore cause glucose-induced signalling defects as well as beta-cell loss. This would explain the wide range of diabetic phenotypes, from NIDDM to IDDM, in patients with this mitochondrial gene mutation.

Adult↗
PubMed1995

Unusual long target duplication by insertion of intracisternal A-particle element in radiation-induced acute myeloid leukemia cells in mouse.

Retrotransmission into the IL-3/GM-CSF gene locus by the retrotransposon intracisternal A-particle (IAP) had been observed in distinct tumor cell lines. We analyzed the locus in genomes from 7 different myeloid leukemia cell strains which were originally generated by whole-body X-irradiation of the inbred C3H/He mice at a dose of 3 Gy and maintained by in vivo passage. In one leukemia cell strain out of 7 such cases, RFLP of an allele of the interleukin-3 gene was found. Sequence analysis after cloning from the genomic library showed that a type I delta 2 IAP element was inserted in the region upstream of the IL-3 gene in the head-to-head orientation. This suggests that the locus in myeloid cells is sensitive for integration of IAP elements. Additionally, an unusual long target duplication of 82 bp, 14-fold larger than normal one, was found at the junction of the element. This suggests the possibility of a radiation-induced integration mechanism which is distinct from normal retrotransmission.

Animals↗
PubMed1995

Anti-platelet effects of clopidogrel in rat middle cerebral artery thrombosis model.

We have developed a model whereby the middle cerebral artery (MCA) in an experimental animal can be occluded by photochemical reaction between rose bengal and green light which causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of photochemical reaction. Using this model, we investigated the effect of clopidogrel, an analogue of ticlopidine which is a potent inhibitor of adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Oral clopidogrel (3-10mg/kg) inhibited ex-vivo platelet aggregation induced by ADP, thrombin or the thromboxane A2 mimetic, and U46619, when platelets had been primed with low concentration of phorbol myristate acetate. At these doses, clopidogrel significantly (P < 0.001) prolonged the time to produce thrombotic occlusion of the MCA and induced a significant (P < 0.001) reduction in the size of ischaemic cerebral damage examined 24 hours after photochemical reaction. The results suggest that ADP has a key role in the thrombotic occlusion of the MCA in this model. Clopidogrel may be beneficial in the prevention of arterial thrombosis.

Adenosine Diphosphate↗
PubMed1995

Specific detection of the precursor of ras p21 with a mouse monoclonal anti-C-terminal peptide antibody, SARA-K1.

In an attempt to clarify the post-translational modifications of ras oncogene product p21, we have established a mouse monoclonal antibody specific for the precursor of p21. The C-terminal peptide (156-188) of K(4A)-ras oncogene product p21 (p21K(4A), termed K(4A)-peptide, was used as the immunogen. In Western blotting, monoclonal antibodies were examined for their differential reactivity between two types of p21K(4A) expressed in Escherichia coli (esh-p21K(4A)) and mammalian cell (mam-p21K(4A)). One monoclonal antibody, designated SARA-K1, reacted selectively with esh-p21K(4A). The epitope for SARA-K1 was defined on tryptic peptide (177-184), containing Cys180, of the K(4A)-peptide. Pulse-chase experiments of mam-p21K(4A) synthesis at 24 degrees C revealed that SARA-K1 precipitated a 21 kDa protein within a 7 min chase but not after a 10 min chase, indicating that SARA-K1 recognizes the precursor of mam-p21K(4A). Furthermore, in Triton X-114 partitioning experiments using mammalian cells pre-treated with Mevalotin, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, SARA-K1 precipitated [35S]methionine-labeled, [3H]mevalonic acid-unlabeled mam-p21K(4A) in the aqueous phase, but did not precipitate [3H]mevalonic acid-labeled mam-p21K(4A) in either aqueous or detergent phase. The data presented clearly show that the SARA-K1 specifically recognizes the primary translational product pro-p21K(4A).

Amino Acid Sequence↗
PubMed1995

Inhibition of pancreatic beta-cell glucokinase by antisense RNA expression in transgenic mice: mouse strain-dependent alteration of glucose tolerance.

We have generated transgenic mice, in either C57BL/6 or C3H background, expressing antisense glucokinase mRNA in beta-cells. The glucose phosphorylating activity at 60 mM glucose in transgenic islets was significantly lower than that in controls, and the insulin secretory response to glucose was lower in transgenic islets than in those of controls in both strains. Following i.p. glucose challenge, higher blood glucose levels were observed in transgenic mice than in controls in the C57BL/6 but not the C3H background. These data suggest that a beta-cell secretory defect, in combination with other undefined genetic factors, causes impaired glucose homeostasis in mice.

Animals↗