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Biomedical subjects

M Shibuya

Publications and source records attributed to M Shibuya.

At least 361 records · Page 20Linked to original sources
PubMed1989

The use of continuous spinal anesthesia in severe tetanus with autonomic disturbance.

Eight patients with severe tetanus experienced episodes of marked cardiovascular instability. During these unstable periods, cardiac output and vascular resistance varied independently. Beta blocking and low doses of ganglionic blocking agents failed to control cardiovascular instability even when combined. High doses of ganglionic blockers stabilized hemodynamics for a short period, but caused the elevation of transaminases. After unsuccessful treatment with cardiovascular drugs, continuous spinal anesthesia (CSA) was applied to five patients. For 5 to 23 days circulation was regulated artificially under complete blockade of the autonomic nervous system by infusing isotonic 0.5% bupivacaine intrathecally. Catecholamine was added intravenously to maintain adequate blood pressure. Before the introduction of CSA, three patients died of circulatory failure. In contrast, CSA dramatically suppressed the cardiovascular instabilities, and all five treated patients survived. This suggests that both sympathetic and parasympathetic nervous systems need to be blocked to stabilize hemodynamics in severe tetanus.

Adult↗
PubMed1989

Co-amplification of c-myc and c-erbB-2 oncogenes in a poorly differentiated human gastric cancer.

c-erbB-2 oncogene has been reported to be frequently amplified in differentiated, tubular type of gastric cancer. Here we report a human gastric cancer which bore co-amplified c-myc and c-erbB-2 oncogenes: a portion of the amplified c-erbB-2 oncogene was found to be rearranged. Furthermore, c-myc and c-erbB-2 oncogenes were over-expressed in the tumor cells. In contrast to the previous reports, this gastric adenocarcinoma was classified as a poorly differentiated type, and was highly tumorigenic in nude mice. These results might suggest that activated c-myc and c-erbB-2 oncogenes co-operate and influence the malignant state of some gastric carcinomas.

Adenocarcinoma↗
PubMed1989

Vasodilator actions of HA1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase.

The in vitro and in vivo vasorelaxant effects of HA1077, 1-(5-isoquinolinesulphonyl)-homopiperazine HCl, a novel vasodilator were examined. The inhibitory effects of HA1077 on contractile responses to various agonists were examined on strips of rabbit aorta. The concentration-response curves to 5-hydroxytryptamine, prostaglandin F2alpha, histamine, angiotensin II, noradrenaline and dopamine were concentration-dependently shifted to the right in the presence of HA1077 (0.3-3.0 microM). The in vivo vasodilator effects of HA1077 were examined in the constant-pressure autoperfused coronary vascular bed of dogs. Intra-coronary administration of HA1077 (3-30 micrograms per dog) dose-dependently increased coronary blood flow (CBF), with no effect on mean blood pressure (MBP) or heart rate (HR). Intra-coronary infusion of atropine, propranolol or diphenhydramine did not modify the in vivo coronary vasodilator response to HA1077. To determine the flow profile for HA1077 in dogs, blood flow in four vascular beds was measured, by use of noncannulating electromagnetic flow probes. HA1077 (0.01-0.3 mg kg-1, i.v.) dose-dependently decreased MBP and increased vertebral blood flow (VBF), CBF, renal blood flow (RBF) and femoral blood flow (FBF). A haemodynamic analysis showed that continuous i.v. infusion of HA1077 (0.01 and 0.033 mg kg-1min-1) dose-dependently decreased peripheral vascular resistance and increased cardiac output. There were no significant changes in right atrial pressure, dP/dt or ventricular minute work. The effects of HA1077 on various enzymes considered to be related to the regulation of smooth muscle contraction were examined. HA1077 had little effect on cyclic nucleotide phosphodiesterases, yet it potently inhibited protein kinases such as cyclic nucleotide dependent protein kinases and Ca2+/calmodulin dependent myosin light chain kinase. The present study demonstrates that HA1077 is a novel type of arterial vasodilator.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Changes in striatal dopamine metabolism measured by in vivo voltammetry during transient brain ischemia in rats.

In vivo voltammetry was used in rats with brain ischemia induced by four-vessel occlusion to measure changes in dopamine metabolism via measurement of peak 2 (dopamine compounds) in the striatum. Changes in regional cerebral blood flow in the striatum were also assessed by means of a temperature-controlled thermoelectrical device. Peak 2 increased by 600-900% during 30 minutes of four-vessel occlusion, which may have reflected an ischemia-provoked increase in the release of dopamine and a disturbance in the outward transport of its metabolites. Following reperfusion by discontinuation of carotid occlusion, peak 2 rapidly decreased to below control values and then gradually increased, exceeding control values at 180-210 minutes after reperfusion. REgional cerebral blood flow in the striatum decreased to almost 0 ml/100 g/min during the ischemic period, transiently increased to greater than control values after reperfusion, then gradually decreased during the next 240 minutes. Since dopamine is known to have various effects on cerebral metabolism and blood flow, alterations in its behavior may contribute to changes in cerebral blood flow and to postischemic brain damage. In vivo voltammetry may be useful in the investigation of the pathophysiology of brain ischemia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Isolation and characterization of new mammalian kinase genes by cross hybridization with a tyrosine kinase probe.

We isolated two novel mammalian kinase genes by weak cross-hybridization with v-ros oncogene. (1) A cDNA of about 7.7 kb obtained from a human placenta cDNA library carried a 4.2 kb open reading frame, and the predicted amino acid sequence of 1338 residues contained extracellular, transmembrane and tyrosine kinase domains. The overall structure including cysteine motifs in its extracellular domain and a long peptide insertion in its tyrosine kinase domain indicates that this new gene is closely related to the fms family. Consequently, the gene was designated as flt(fms-like tyrosine kinase) gene. The expression of the flt gene was examined in normal and transformed cells, and it was mapped to human chromosome 13q12-13. (2) Another new gene was found to be expressed almost exclusively in testis. The cDNA sequence analysis revealed that the predicted product carried protein kinase consensus motifs in its amino-terminal region. Comparison of the deduced amino acid sequence of this gene in the kinase domain with those of other protein kinase genes will be discussed.

Amino Acid Sequence↗
PubMed1988

Neosynthesis of neolacto- and novel ganglio-series gangliosides in a rat fibroblastic cell line brought about by transfection with the v-fes oncogene-containing Gardner-Arnstein strain feline sarcoma virus-DNA.

Transfection of retrovirus DNA from Gardner-Arnstein strain feline sarcoma virus containing v-fes oncogene into a rat fibroblastic cell line 3Y1 caused not only cell transformation but also a remarkable change in ganglioside expression. The ganglioside phenotype of the 3Y1 cells was characterized by the exclusive expression of GM3, along with a trace amount of "A" pathway-related gangliosides (GM2-GM1a-GD1a), whereas in the transfected transformant, 3Y1-GA, sialosylparagloboside containing N-acetyl neuraminic acid (NeuAc) and novel ganglio-series gangliosides (presumably GM1b and GD1 alpha) were expressed in addition to GM3. Thus, the Gardner-Arnstein strain feline sarcoma virus DNA transfection open two new ganglioside metabolic pathways, one leading to the synthesis of neolacto-series and the other to that of ganglio-series gangliosides. These results were in striking contrast to the cases of transfection with so-called "intranuclearly expressed" transforming genes, adenovirus E1, SV40-T, and myc, with which the same 3Y1 cells newly expressed GD3 with a concomitant decrease in precursor ganglioside GM3. The difference in underlying mechanisms of ganglioside metabolism shown by these two different types of oncogenes might reflect differences in the modes of action of the oncogenes and their biological activities.

Animals↗
PubMed1988

Effects of neuropeptide Y on canine cerebral circulation.

The effects of neuropeptide Y (NPY) on the vascular tone of isolated cerebral arteries and vertebral blood flow (VBF) were studied in dogs. NPY elicited a dose-dependent contraction of arteries derived from the brain with ED50 values of 2 nM for the middle cerebral and basilar arteries. Arteries from the neck did not respond to NPY. Intra-arterial administration of NPY as a bolus reduced the VBF dose dependently, with no significant alteration of mean arterial blood pressure and heart rate. The decrease in VBF developed slowly and had a long duration, which was consistent with the observations made in vitro. NPY suppressed the contractile effect of noradrenaline (NA) on isolated cerebral arteries and pretreatment with NPY suppressed the effect of NA on VBF, indicating that NPY contributes to the inhibitory modulation of postsynaptic adrenergic mechanisms. These findings suggest that NPY could have a role in the regulation of cerebral circulation.

Animals↗
PubMed1988

Glucocorticoids increase insulin binding and the amount of insulin-receptor mRNA in human cultured lymphocytes.

The effect of steroid hormones on insulin binding and the amount of insulin-receptor mRNA was examined in IM-9 lymphocytes. Cortisol and cortexolone, but not oestrogen, increased both the binding of insulin and the amount of insulin-receptor mRNA in a time- and dose-dependent manner. Cortisol was most potent, and induced a 2-fold increase in insulin binding and a 4-fold increase in mRNA. The elevation in binding was due to an increased number of insulin receptors at the cell surface. The increase in mRNA involved all four of the insulin-receptor mRNAs and could not be inhibited by cycloheximide. The cortisol-induced increase in mRNA was associated with a 3-4-fold increase in the synthesis of pro-receptor. The relative potency of the three steroids indicated that these effects were mediated by an interaction with the glucocorticoid receptor. The results of this study suggest that cortisol can increase the number of insulin receptors at the cell surface by increasing the amounts of insulin-receptor mRNA and the synthesis de novo of insulin receptors.

17-Hydroxycorticosteroids↗
PubMed1988

Analysis of cellular expression of gangliosides by gene transfection. II: Rat 3Y1 cells transformed with several DNAs containing oncogenes (fes, fps, ras & src) invariably express sialosylparagloboside.

The transfection of several DNAs, containing oncogenes ras, src, fes or fps, into rat 3Y1 cells invariably induced the neosynthesis of sialosylparagloboside (SPG; IV3 alpha NeuAc nLcOse4Cer), with a concomitant decrease in GM3. All these oncogenes are 'extranuclear' type oncogenes, of which the products are expressed in the cytoplasm or on the cell surface membrane. These results are in striking contrast to those on the transfection of 'intranuclear' type oncogenes (ex., adeno E1) into the same 3Y1 cells, where GD3 neosynthesis was specifically brought about by the transfection.

Animals↗
PubMed1988

Undetectable bcr-abl rearrangements in some CML patients are due to a deletion mutation in the bcr gene.

Most patients with chronic myelogenous leukemia (CML) have Philadelphia (Ph) chromosome. Breakpoints on chromosome 22 in CML occur in a small region designated as the breakpoint cluster region (bcr). More than 90 percent of CML patients have breakpoints in the bcr; the remaining patients had no detectable rearrangement. In our study, a commercially available 1.2 kb HindIII-BglII (1.2 HBg) bcr probe was used to locate breakpoints in the bcr, which were found in 22 of 24 patients. Furthermore, using a probe upstream from the 1.2 HBg probe, rearranged bands were clearly detected in the two patients in whom no extra bands had been found with the 1.2 HBg probe. These results strongly suggest that these two patients carry a deletion at the acr-abl recombination point encompassing the area of the 1.2 HBg probe. Therefore, in our series, all CML patients eventually had breakpoints in the bcr, and the involvement of rearrangement was demonstrated to be highly specific for CML. Our data indicate that hybridization of CML cellular DNA with several bcr probes is important in examining accurately the frequency of bcr-abl rearrangements in CML, as some cases contain a deletion within the region.

Chromosome Aberrations↗
PubMed1988

The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs.

The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nifedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10(-6) M HA 1077 for the "intracranial" basilar and middle cerebral arteries, while a 10(-5) M was needed to obtain the same effect for the "extracranial" common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the "two haemorrhage" model of Varsos et al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5-3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20-30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

The interaction of calcitonin gene-related peptide with angiotensin II on blood pressure and renin release.

Calcitonin gene-related peptide (CGRP) has been shown to be a potent vasorelaxant. We tested the interaction of CGRP with angiotensin II (Ang II) in conscious, unrestrained Wistar rats. Rat CGRP (rCGRP, 0.1 and 1.0 nmol/kg per min) dose-dependently lowered mean arterial blood pressure and increased the heart rate. The effects continued throughout the infusion period of 30 min. Moreover, rCGRP significantly attenuated the pressor responses to Ang II (100 ng/kg per min). High-dose rCGRP (1.0 nmol/kg per min) almost abolished the pressor action of Ang II, and a much higher dose of Ang II (1000 ng/kg per min) was needed to restore the pre-infusion pressure. Plasma renin activity was dose-dependently increased by rCGRP, but was attenuated by simultaneous Ang II infusion. Rat CGRP also increased the plasma aldosterone concentration, as did Ang II. These results suggest that CGRP may have a neuromodulatory role in cardiovascular regulation.

Aldosterone↗
PubMed1988

Early diagnosis of invasive candidiasis and rapid evaluation of antifungal therapy by combined use of conventional chromogenic limulus test and a newly developed endotoxin specific assay.

Since beta-1,3-glucan is a common component of fungal cell wall, its detection might be useful in diagnosing invasive candidiasis. Not only endotoxin but beta-1,3-glucan activates proclotting enzyme contained in a conventional chromogenic limulus test (CCLT). Endotoxin activates this enzyme through factor C, while the beta-1,3-glucan activates through factor G. Since endotoxin specific test (EST) contains factor C, endotoxin would be quantified. By subtracting EST value from CCLT value, beta-1,3-glucan would be quantified. We named this value Fungal Index (FI), and examined if it actually reflects the candidal infection. Ninety-two patients were tested for CCLT and EST prospectively. FI increased significantly in candidal infection (p less than 0.05) but remained low in GNR infection. Moreover, FI increased proportionally to the severity of candidal infection. Elevated FI decreased when antifungal therapy was successful. Thus FI was a useful index not only in the diagnosis of invasive candidiasis but also in the evaluation of antifungal therapy.

Antifungal Agents↗
PubMed1988

Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors.

By using Southern blot analysis, we found that in two cases of human glioblastoma multiforme, cells carried amplified c-erbB genes which bore short deletion mutations within the ligand-binding domain of the epidermal growth factor (EGF) receptor. The products of these mutated c-erbB genes were about 30 kilodalton (kDa) smaller than the normal 170-kDa EGF receptor, and the tumor cell membrane fractions containing the 140-kDa abnormal EGF receptor showed a significant elevation of tyrosine kinase activity without its ligand. In view of the similarity to the activated viral and cellular erbB genes in the avian system, these mutated and overexpressed EGF receptors might play a role in the onset or development of human glioblastoma cells.

Animals↗
PubMed1988

Protein kinase activity in canine basilar arteries after subarachnoid hemorrhage.

To investigate the intracellular physiology of cerebral arterial vasospasm after subarachnoid hemorrhage (SAH), we measured the activity of three protein kinases related to vascular smooth muscle function. Myosin light chain kinase (MLCK), cyclic adenosine monophosphate (cAMP)-dependent protein kinase and cyclic guanosine monophosphate (cGMP)-dependent protein kinase activity was determined in canine basilar arteries using the SAH model created by two intracisternal injections of autologous blood. Moderate chronic cerebral vasospasm was confirmed angiographically 7 days after the first injection of blood, with a mean decrease in the diameter of the basilar artery to 61.2 +/- 2.3% (SE) of preinjection controls. Enzymatic analysis of basilar arteries excised from control dogs and from SAH model dogs 2 to 10 days after an intracisternal injection of blood demonstrated detectable MLCK and cyclic nucleotide-dependent protein kinase activity. The MLCK activity was approximately 3 times higher than the cyclic nucleotide-dependent protein kinase activity. There was no significant difference in basilar artery protein kinase activity between control animals and SAH model animals at any time for up to 10 days after the intracisternal injection of blood. As MLCK is involved with smooth muscle contraction and cAMP- and cGMP-dependent protein kinases are involved in smooth muscle relaxation, our results suggest that the metabolic machinery of vascular smooth muscle in the cerebral arterial wall is intact after SAH and that prolonged vasospasm represents an appropriate physiological response by the vascular smooth muscle to external stimuli. If this is correct, the successful pharmacological manipulation of vasospasm after SAH is more likely than if profound disruption had occurred, and further investigative efforts in this area should be encouraged.

Animals↗