Search PubMed⌕ Search

Biomedical subjects

T Asano

Publications and source records attributed to T Asano.

At least 649 records · Page 36Linked to original sources
PubMed1989

A novel CD3-J11d+ subset of CD4+CD8- cells repopulating thymus in radiation bone marrow chimeras.

Sequential appearance of T cell subpopulations occurs in the thymus of irradiated AKR (H-2k, Thy-1.1) mice at an early stage after transplantation with bone marrow cells of C3H/HeN (H-2k, Thy-1.2) mice. The donor-derived thymocytes were first detected on day 8 after bone marrow reconstitution. Although most of the thymocytes were CD4-CD8- cells, an appreciable level of CD4+CD8- cells was detected in the thymus at this stage. The early appearing CD4+CD8- cells were a novel subset of thymocytes that were J11d+CD3-. From day 10 to day 21 the proportion of CD4+CD8-CD3-J11d+ cells decreased while the proportion of CD4+CD8+ cells and CD4+CD8-CD3+J11d- cells increased. The CD4+CD8-CD3- cells seem to diversify to form CD4+CD8+ thymocytes after short-term culture in vitro. These results suggested the existence of a differential pathway from CD4-CD8- cells to CD4+CD8+ cells via CD4+CD8- cells in thymus.

Animals↗
PubMed1989

Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs.

The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 alpha (PGF2 alpha). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1-29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2 alpha-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.

Animals↗
PubMed1989

Elevated levels of the alpha subunit of GTP-binding protein Go in cerebrospinal fluid of patients with neurological disorders.

By employing a highly sensitive immunoassay method, concentration of the alpha subunit of GTP-binding protein, Go (Go alpha), recently shown to be localized mainly in nervous tissues and neuroendocrine cells, was determined in cerebrospinal fluids (CSF) of 192 patients with various neurological disorders and 50 control subjects. The results were compared with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in the same samples. Normal levels of Go alpha were 51.9 +/- 21.7 pg/ml. The levels of Go alpha, as well as NSE and S-100b, in CSF were enhanced in some patients with acute conditions, e.g., meningitis (48%), encephalitis (100%), and cerebral infarct (56%). In these disorders, cases with enhanced Go alpha levels were more frequent than those with enhanced NSE or S-100b. Three patients with encephalitis whose Go alpha levels were more than 1000 pg/ml all died; the remaining two patients with encephalitis and slightly elevated Go alpha levels had a good prognosis. Concentration of Go alpha in CSF correlated well with that of NSE but poorly with that of S-100b. However, cervical spondylosis and demyelinating diseases, CSF levels of Go alpha were generally lower than those of NSE or S-100b. These results suggest that Go alpha in CSF is a useful marker for monitoring patients with acute neuronal damage. Since these three proteins are distributed differently in the central nervous system, simultaneous determination of Go alpha, NSE, and S-100b levels in CSF might provide valuable information about the pathophysiology of neurological disorders.

Biomarkers↗
PubMed1989

The role of free radicals and eicosanoids in the pathogenetic mechanism underlying ischemic brain edema.

Results of our consecutive study on the pathogenic mechanism underlying ischemic brain edema are summarized in this paper. Pertinent findings are as follows: (1) there is a close correlation between the influxes of water and sodium following ischemia; (2) the edema fluid can be regarded as the ultrafiltrate of serum; (3) there is a significant increase in the brain content of HETEs following ischemia; (4) the lipoxygenase activity of brain microvessels is increased following ischemia; (5) the lipoxygenase activity as well as the Na+, K+-ATPase activity of brain microvessels are enhanced by a hydroperoxide, 15-HPETE; (6) inhibition of Na+, K+-ATPase of brain microvessels by intraarterial infusion of ouabain resulted in a significant decrease in edema formation; and (7) not the cyclooxygenase, but the lipoxygenase pathway seems to be involved in the enhancement of microvessel Na+, K+-ATPase. Lipoxygenase(s) and Na+-K+-ATPase of brain microvessels, the activities of which are enhanced by an increased level of free radicals and/or hydroperoxides, may play a significant role in the occurrence of ischemic brain edema.

Animals↗
PubMed1989

Escherichia coli-derived human interferon-gamma with Cys-Tyr-Cys at the N-terminus is partially N alpha-acylated.

Purified preparations of recombinant human interferon-gamma (rIFN-gamma) with Cys-Tyr-Cys at the N-terminus ([ Cys-Tyr-Cys]IFN-gamma) derived from Escherichia coli gave two closely migrating bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and two peaks on reversed-phase high-performance liquid chromatography (rpHPLC). In contrast, rIFN-gamma without Cys-Tyr-Cys and rIFN-gamma in which both Cys-1 and Cys-3 were substituted with serine behaved as a single species on both SDS-PAGE and rpHPLC. These results suggest that the N-terminal portion of rIFN-gamma is heterogeneous. To elucidate the structure of the N-terminal portion, the N-terminal peptide preparation was obtained by binding rIFN-gamma to thiopropyl-Sepharose 6B gel with disulfide linkage followed by trypsin digestion and elution with 2-mercaptoethanol. The preparation gave four peaks (NT-1, NT-2, NT-3, and NT-4, in order of elution) on rpHPLC; all four were found to be Cys-1-Lys-9 by amino acid analysis after acid hydrolysis. Various analyses indicate that NT-1 is the intact nonapeptide, that NT-3 and NT-4 are N alpha-formyl and N alpha-acetyl forms of NT-1, respectively, and that NT-2 may be S-blocked at Cys-1. It is concluded that E. coli-derived [Cys-Tyr-Cys]IFN-gamma is partially N alpha-acylated. The data also suggest that N alpha-acylation does not affect the biological activity of [Cys-Tyr-Cys]IFN-gamma.

Amino Acid Sequence↗
PubMed1989

5-Isoquinolinesulfonamide derivatives. 1. Synthesis and vasodilatory activity of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide derivatives.

Two novel series of N-(2-guanidinoalkyl)-5-isoquinolinesulfonamides, 2 and 3, were prepared. Many of the compounds possessed vasodilatory activity when injected locally into the femoral artery of dogs. The most potent compound, 1-amidino-4-(5-isoquinolylsulfonyl)-1,4-perhydrodiazepine, 33, was comparable to diltiazem, which is used clinically as a vasodilator.

Animals↗
PubMed1989

5-Isoquinolinesulfonamide derivatives. 2. Synthesis and vasodilatory activity of N-(2-aminoethyl)-5-isoquinolinesulfonamide derivatives.

A new series of aromatic sulfonamides, the N-(2-aminoethyl)-5-isoquinolinesulfonamide derivatives, 3, was synthesized from 5-isoquinolinesulfonic acid and shown to possess vasodilatory action. Vasodilatory activity was evaluated in vivo in terms of increases in arterial blood flow in dogs after local injection in the femoral and/or vertebral arteries. When the alkylene group between the two nonaromatic nitrogen atoms was ethylene, the most potent activity was obtained. Alkylations of either of the two nonaromatic nitrogens yielded more active compounds, although bulky or excessively long alkyl groups reduced the potency. Among these derivatives, 27 and 47 were equipotent to diltiazem, which is used clinically as a cardiovascular drug. These two compounds also had antihypertensive and vasodilatory activities when administered intravenously, although the activities were less than that of diltiazem when given by this route.

Animals↗
PubMed1989

Effects of neuropeptide Y and calcitonin gene-related peptide on local cerebral blood flow in rat striatum.

The effects of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) on local cerebral blood flow (LCBF) were studied in vivo in rat striatum. Administration of 1 and 5 nmol NPY as a bolus into the internal carotid artery caused a dose-dependent decrease in the ipsilateral striatal LCBF. This decrease developed slowly and persisted for at least 2 h, without affecting mean blood pressure. In contrast, CGRP, at a concentration of 10 pmol, increased striatal LCBF by about 30%, and the duration of the increase was about 1 h. However, at higher doses of CGRP no increase in LCBF was observed. These results suggest that NPY and CGRP released from nerve fibers innervating blood vessels can function as long-acting modulators of CBF.

Animals↗
PubMed1989

Clinical study of OKY-046, a thromboxane synthetase inhibitor, in prevention of cerebral vasospasms and delayed cerebral ischaemic symptoms after subarachnoid haemorrhage due to aneurysmal rupture: a randomized double-blind study.

A double-blind study was conducted at 48 neurosurgical services in Japan to investigate the usefulness of OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, on cerebral vasospasm and cerebral ischaemic symptoms in patients with ruptured cerebral aneurysms. OKY-046 was administered in two daily doses of 80 mg (L group) and 400 mg (H group), and compared with a group given a placebo (P group). The following results were obtained: the occurrence of cerebral vasospasm was significantly lower in the L group than in the P group; the development of low density area (LD) in CTs was significantly lower in both the L and H groups than in the P group; motor paralysis in the L group improved significantly sooner, and that in the H group tended to improve sooner than that in the P group; in subjects with severe vasospasm, the incidence of LD was significantly lower, with better functional prognosis, in the L group than in the P group; in subjects with severe grades on the Glasgow Coma Scale (GCS), Japan Coma Scale (JCS) or High Density (HD) Score the functional prognosis at 1 month after the aneurysmal rupture was significantly better in the L group than in the P group, though no significant differences were seen in the overall investigation; there were no significant differences among the three groups in the development of either laboratory-determined abnormality or of adverse reactions. It is thus concluded that OKY-046 is clinically useful at a dose of 80 mg/d for cerebral vasospasm and cerebral ischaemic symptoms after subarachnoid haemorrhage (SAH) caused by aneurysmal rupture.

Acrylates↗
PubMed1989

Optimal serum trough levels of FK506 in renal allotransplantation of the beagle dog.

The present study was performed to estimate the optimal serum trough levels of FK506 (FK) for prophylactic use and for the treatment of acute rejection in renal allotransplantation of the beagle dog. The serum trough levels of an immunosuppressive dose of FK 1.0 mg/kg p.o. ranged from 0.1 to 0.4 ng/ml. The data indicate that the effective serum trough level is about 100 times lower than that of cyclosporine, as was already observed in previous in vitro studies. Combining treatment with a nonimmunosuppressive dose of cyclosporine of 2.5 mg/kg could lower the effective trough levels of FK. By the combining treatment, 2 out of 5 renal recipient dogs survived with well-functioning grafts as long as 60 days with the trough levels between 0.04 and 0.07 ng/ml. High-dose 5-day i.m. FK treatment of 0.5 or 1.0 mg/kg was effective in the reversal of acute rejection, with peak serum trough levels during successful rejection therapy ranging between 0.28 and 3.7 ng/ml. Two dogs died of malaise or pneumonia with peak trough levels of 2.25 and 2.78 ng/ml. Among the wide range of the effective trough levels for successful acute rejection therapy, those above 2.0 ng/ml seem to be toxic in some renal-transplanted dogs.

Administration, Oral↗
PubMed1989

Effects of combination treatment with FK506 and cyclosporine on survival time and vascular changes in renal-allograft-recipient dogs.

In our previous experiments studying the effects of FK506 on renal allografting in the dog, we encountered two major problems. One problem was anorexia and the other problem was vascular changes mainly in the recipient heart. Anorexia was generally dose dependent, but the vascular changes were seen to be more prominent at lower doses rather than at higher immunosuppressive doses. The present study was undertaken to study these two problems. A nonanorexic, vascular change-related, nonimmunosuppressive dose of FK506 was combined with a low dose of cyclosporine or prednisolone in beagle dogs after renal allografting. Treatment with either FK506 alone at a dose of 0.32 mg/kg or cyclosporine alone at 2.5 mg/kg was not effective in prolonging renal recipient survival. The recipient dogs died of rejection, and a variety of vascular changes were observed in the hearts of both groups. Combined treatment with FK506 and cyclosporine at these same doses resulted in statistically significant prolongation of the survival time of the renal recipient (P less than 0.01), and histologic studies showed that the frequency and severity of the vascular changes were suppressed in the recipient receiving the combined treatment. The combination of FK506 and prednisolone at 0.5 mg/kg was not effective in prolonging survival. Furthermore, the extent of vascular changes was similar to those found in recipients receiving FK506 alone. The data suggest that combined treatment with low doses of both FK506 and cyclosporine acted synergistically in prolonging canine renal allografts and that the vascular changes frequently seen at low doses of FK506 were reduced by additional immunosuppression with a low dose of cyclosporine.

Animals↗
PubMed1989

Cerebral infarction due to disseminated intravascular coagulation with thromboexclusion for dissecting aortic aneurysma.

Cerebral infarction due to chronic disseminated intravascular coagulation (DIC) after thromboexclusion for thoracic dissecting aortic aneurysma is described. Chronic DIC may be caused by the delay of thrombus formation at the site of thromboexclusion, and local DIC occurred at that site. It is difficult to find chronic DIC. This case shows that DIC after thromboexclusion for dissecting aortic aneurysma may be one of the causes of recurrent cerebral infarction.

Aortic Dissection↗
PubMed1989

The GTP-binding proteins, Go and Gi2, of neural cloned cells and their changes during differentiation.

The levels of the alpha-subunits of two GTP-binding proteins, Go and Gi2, were determined in neural and nonneural cloned cells by immunoassays. Go alpha was detected in all neural cells and some of nonneural cells, but not in HL-60 leukemic cells and PYS-2 teratocarcinoma-derived cells. The level of Go alpha was highest in the PC12 pheochromocytoma cells. Gi2 alpha was present in all types of cells tested, and its level was highest in the HL-60 cells and relatively high in glioma cells. Treatment of PC12 cells and neuroblastoma x glioma hybrid NG108-15 cells with nerve growth factor and forskolin, respectively, caused the extension of neuronal-like processes and increase in the level of Go alpha by 60-80%, but small changes in the levels of Gi2 alpha.

Adrenal Gland Neoplasms↗
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

Beneficial effects of cervical spinal cord stimulation (cSCS) on patients with impaired consciousness: a preliminary report.

Electrical stimulation of the spinal cord can be used for treatment of intractable pain and spasticity. Based on our experimental findings cervical spinal cord stimulation (cSCS) was performed on eight patients with severe brain dysfunction due to traffic accidents, pronounced vasospasm caused by subarachnoid hemorrhage or surgery of huge cerebral tumors (chordoma). After a 1 to 2 month period of stimulation, two patients became conscious and began to speak. It remains unclear whether cSCS induced the restoration of consciousness and improved neurological deficits. Although the successful results might be due to chance, cSCS might have stimulated brain function. This preliminary report shows such excellent results that further studies are warranted.

Adult↗
PubMed1989

Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats.

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.

Animals↗
PubMed1989

Prostaglandin profiles in relation to local circulatory changes following focal cerebral ischemia in cats.

We explored the temporal and topographic relations between local cerebral blood flow and regional brain prostaglandin profile following prolonged or transient occlusion of the middle cerebral artery in cats. Each experimental group was subjected to a sham operation, prolonged ischemia, or recirculation. Local cerebral blood flow was measured by the hydrogen clearance method. Following in situ freezing, cortical samples were obtained from each gyrus for determination of prostaglandin (PG) F2 alpha, PGE2, 6-keto-PGF1 alpha, and thromboxane (TX) B2 concentrations by radioimmunoassay. During prolonged ischemia, the concentrations of PGF2 alpha and PGE2 within the middle cerebral artery territory were significantly increased. Immediately after recirculation, there was a prominent but transient increase in PGF2 alpha and PGE2 in gyri that had been exposed to moderate ischemia (perifocal area). By contrast, the increases in these prostaglandins were slow and less prominent in gyri that had been exposed to severe ischemia (the focal area). The concentration of 6-keto-PGF1 alpha did not change during prolonged ischemia but transiently increased following recirculation in both the focal and perifocal areas. The TXB2 concentration did not change in any experimental group. Our study revealed a homogeneous increase in the regional brain content of PGE2 or PGF2 alpha in spite of the heterogeneous reduction of local cerebral blood flow during prolonged ischemia. Following recirculation, the focal and perifocal areas exhibited different patterns of prostanoid content. No correlation was found between local cerebral blood flow and the regional concentration of any prostaglandin examined.

6-Ketoprostaglandin F1 alpha↗