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T Asano

Publications and source records attributed to T Asano.

At least 145 records · Page 8Linked to original sources
PubMed2000

Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells.

We investigated the antitumor effects induced by the production of interleukin-12 (IL-12) or IL-18, which influence the function of T helper type 1 cells, in murine colon carcinoma cells (Colon 26). Retrovirally transduced cells with IL-12 genes that encoded both p35 and p40 (Colon 26/IL-12) lost their tumorigenicity when inoculated subcutaneously or intraperitoneally into syngeneic immunocompetent mice. Moreover, the mice that had rejected the Colon 26/IL-12 cells generated protective immunity to wild-type (wt) cells when subsequently challenged. Colon 26 cells transduced with the IL-18 gene (Colon 26/IL-18) could not form subcutaneous tumors in immunocompetent mice, and the mice became resistant to inoculated wt cells. Immunohistochemical analysis revealed that the numbers of blood vessels in Colon 26/IL-12 or Colon 26/IL-18 tumors were markedly reduced, and that the expression of adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 increased on the endothelium in the stroma of Colon 26/IL-12 tumors. The loss of tumorigenicity of Colon 26/IL-12 or Colon 26/IL-18 cells was not observed in immunocompromised mice. However, the survival days of the immunocompromised mice inoculated with Colon 26/IL-12 but not Colon 26/IL-18 cells were significantly longer than those inoculated with wt cells. The secretion of cytokines that stimulate T helper type 1 cells from tumor cells can thereby induce an antitumor response. However, the effector cells involved in these antitumor effects could differentially migrate to the tumors, and the inhibition of angiogenesis may partially contribute to the antitumor responses observed.

Animals↗
PubMed2000

Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts.

We examined the antitumor effects caused by murine colon carcinoma cells (Colon 26) transduced with interleukin-15 (IL-15) gene. Although the in vitro proliferation rate of IL-15-secreting Colon 26 (Colon 26/IL-15) cells was not different from that of wild-type (wt) cells, small subcutaneous tumors of Colon 26/IL-15 cells that developed in syngeneic immunocompetent mice regressed spontaneously in contrast to tumors of wt cells. The mice that had eliminated tumors of Colon 26/IL-15 cells rejected wt cells when subsequently challenged. The survival of the mice that had been inoculated intraperitoneally with Colon 26/IL-15 cells was significantly prolonged compared with that of the mice injected with wt cells. However, in an experimental lung metastasis model, the survival of the mice inoculated with Colon 26/IL-15 cells remained the same as that of the mice inoculated with wt cells. The inoculation of Colon 26/IL-15 cells into immunocompromised nude or severe combined immunodeficient mice produced tumors, but the survival of the immunocompromised mice was significantly longer than that of the mice inoculated with wt cells. The nude mice inoculated with Colon 26/IL-15 cells also survived longer than the severe combined immunodeficient mice with Colon 26/IL-15 cells. Depletion of natural killer cells in nude mice with anti-asialo GM1 antibody did not influence the survival of the mice injected with Colon 26/IL-15 cells. Immunohistological examination revealed that CD31+ cells migrated into tumors of Colon 26/IL-15 cells that developed in immunocompetent and immunocompromised mice. Taken together, our results indicate that an inoculation of IL-15-producing tumor cells can produce antitumor effects that are mediated by a variety of immunocompetent cells.

Animals↗
PubMed2000

Expression of IL-8 in Kawasaki disease.

We investigated, by Northern blotting, ELISA, and a chemotaxis assay, the expression of IL-8 mRNA, the production of IL-8 protein, and the biological activity of mononuclear cells (MNC), polymorphonuclear neutrophils (PMN) and plasma, respectively, from patients with Kawasaki disease (KD) who received intravenous immunoglobulin (IVIG). IL-8 mRNA expression by MNC and PMN, the level of IL-8 protein, and the neutrophil chemoattractant activity within plasma were all increased in the acute phase of KD, and were significantly elevated following IVIG therapy. The level of chemotactic activity of neutrophils, but not that of monocytes, in response to F-met-leu-phe was decreased in patients with KD after IVIG. The increased expression of IL-8 in PMN and MNC, the increased plasma level of IL-8 and the decreased level of neutrophil chemotactic activity of the patients who received IVIG therapy might inhibit the accumulation of neutrophils at the sites of inflammation, and may thus reduce the risk of aneurysm formation.

Chemotactic Factors↗
PubMed2000

Possible role of the superoxide anion in the development of neuronal tolerance following ischaemic preconditioning in rats.

There is a large body of evidence that reactive oxygen species play a major role in the pathogenesis of ischaemic brain damage. On the other hand, it has recently been suggested that superoxide anions participate in the development of neuronal tolerance against lethal ischaemia following ischaemic preconditioning (PC). The present study aimed to examine whether or not the intravenous administration of human recombinant Cu/Zn superoxide dismutase (hr SOD) prior to PC would affect the subsequent development of neuronal tolerance. Animals were randomly assigned to the following three groups: group 1, sham PC treated with vehicle; group 2, PC treated with hr SOD and group 3, PC treated with vehicle. For PC, 10 min occlusion of the middle cerebral artery (MCA) by a modified intraluminal suture method was followed by 60 min recirculation and this procedure was successively repeated three times. The procedures were similar for sham PC except that the MCA was kept unoccluded. Just prior to PC or sham PC, a bolus of hr SOD (6 x 103 IU/2 ml/kg) was administered intravenously. Seventy-two hours thereafter, rats were subjected to lethal ischaemia, i.e. MCA occlusion for 100 min followed by recirculation for 48 h. The infarct area and volume were assessed with the 2,3,5-triphenyltetrazolium stain. A significant difference in the infarct volume was revealed between the sham PC/vehicle and the PC/vehicle groups (total and cortex P < 0.01; striatum P < 0.05), showing that PC induced a marked neuronal tolerance against lethal ischaemia. The infarct volume in the PC/SOD group was close to that in the sham PC/vehicle group, being significantly greater than that in the PC/vehicle group (total and cortex P < 0.01) and showing that the administration of hr SOD suppressed the development of neuronal tolerance induced by PC. In a parallel experiment, expression of 72-kDa heat-shock protein (hsp 72) at 72 h after PC was considerably reduced in rats treated with hr SOD compared with those treated with vehicle. These results suggest that superoxide anions intraluminally generated within cerebral microvessels participate in the development of neuronal tolerance as well as the induction of hsp 72 following PC.

Animals↗
PubMed2000

Expression of monocyte chemoattractant protein-1 in Kawasaki disease: the anti-inflammatory effect of gamma globulin therapy.

We investigated the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA, protein, and its bioactivity in plasma, mononuclear cells (MNC) and polymorphonuclear leukocytes (PML) in patients with Kawasaki disease, including those who were treated with intravenous gamma globulin. MCP-1 mRNA expression was increased in the MNC and the plasma level of MCP-1 and monocyte chemotactic activity in plasma in the acute phase as compared with healthy control levels and decreased after the gamma globulin therapy. The infused gamma globulin contained MCP-1 protein with monocyte chemotactic activity and did not show a neutralising effect against MCP-1 protein in vitro. Our results suggest that the infusion of gamma globulin may reduce the production of MCP-1 in MNC in patients with Kawasaki disease, subsequently reducing its level in plasma. The changes in MCP-1 level after gamma globulin therapy may serve to alleviate the symptoms in the acute phase in patients with Kawasaki disease.

Acute Disease↗
PubMed2000

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Journal Article↗
PubMed2000

Antinociception by epidural and systemic alpha(2)-adrenoceptor agonists and their binding affinity in rat spinal cord and brain.

UNLABELLED: This study was designed primarily to relate the antinociceptive and hemodynamic effects of clinically available alpha(2)-adrenoceptor agonists to their binding affinity for alpha(2)-adrenoceptors in the spinal cord and brain. In rats with chronic indwelling epidural catheters, the percentage maximal possible effect on tail-flick latency was measured after epidural or IM dexmedetomidine (DXM), clonidine (CL), or tizanidine (TZ) administration. To examine their binding affinities, isolated spinal cord and brain membranes with an alpha(2) agonist were incubated with (3)H-UK14304, a selective alpha(2) agonist, and the radioactivity in the reaction mixtures was measured by liquid scintillation spectrometry. Epidural DXM (0.5-10 microg), CL (10-500 microg), and TZ (5-500 microg) all produced dose-dependent antinociceptive effects; the rank order of potencies was DXM > CL > TZ, the same as for their systemic administration. The antinociceptive effects were blocked by epidural yohimbine. The receptor binding affinities expressed as the concentration that inhibits 50% for spinal cord and brain, respectively, were 0.25 and 1.3 nM (DXM), 10.8 and 12.5 nM (CL), and 48.2 and 96.8 nM (TZ). The changes in arterial blood pressure and heart rate evoked by antinociceptive doses did not correlate with the rank order of antinociceptive potencies. The relative antinociceptive potencies of epidural alpha(2) agonists may depend on their binding affinities to alpha(2)-adrenoceptors in the spinal cord, but their cardiovascular effects may result from actions both inside and outside the central nervous system. IMPLICATIONS: Spinal antinociception caused by the epidural administration of alpha(2) agonists is well correlated with their binding affinity to spinal alpha(2)-adrenoceptors.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2000

Antinociceptive action of epidural K+(ATP) channel openers via interaction with morphine and an alpha(2)- adrenergic agonist in rats.

Potassium (K(+)) channels may play some role in the analgesic actions of mu-opioid agonists and alpha(2)-adrenergic agonists (alpha(2) agonists). We examined whether the adenosine triphosphate-sensitive K(+)(K(+)(ATP)) channel openers, levcromakalim and nicorandil, (given epidurally), might have antinociceptive effects in a tail flick test in adult male Sprague-Dawley rats implanted with a lumbar epidural catheter. The interactions with morphine and an alpha(2) agonist were also examined. The epidural administration of levcromakalim (10 microg, 100 microg) or nicorandil (10 microg, 100 microg) alone did not produce antinociception, but 100 microg levcromakalim or nicorandil did potentiate the antinociceptive effect induced by epidural morphine. Epidural glibenclamide (10 microg), a K(+)(ATP) channel blocker, or naloxone (10 microg) antagonized this potentiation. Systemic administration of levcromakalim or nicorandil (at the same dose as that given into the epidural space) did not potentiate the epidural morphine-induced analgesia. A combination of epidural dexmedetomidine (1 microg) and morphine (1 microg) (each at a subantinociceptive dose) had a significant antinociceptive effect, and epidural glibenclamide (10 microg) partly antagonized this antinociception. These data suggest that levcromakalim and nicorandil potentiate the analgesic action of both morphine and dexmedetomidine, probably via an activation of K(+)(ATP) channels at the spinal cord level.

Adenosine Triphosphate↗
PubMed2000

Presence of 22-kDa protein reacting with sera in piglets experimentally infected with Brachyspira hyodysenteriae.

In order to examine the effect of spectinomycin on outbreaks of swine dysentery, experimental infection of piglets with Brachyspira hyodysenteriae was carried out. Feed with and without spectinomycin (SP) was given to each piglet ad libitum and the susceptibility of the piglets to infection with B. hyodysenteriae was compared between SP-treated and untreated piglets. The results showed that the SP-treated piglets did not display clinical signs of swine dysentery unlike the untreated piglets. The sera obtained from these piglets were examined by the microscopic agglutination test and antibodies to B. hyodysenteriae in both groups of experimentally infected piglets were detected and the reaction was serogroup-specific. The agglutination titers were very high in the untreated piglets with dysentery while the titers in the SP-treated piglets were lower than those in the untreated piglets. In addition, the immunoblotting technique was applied and the results demonstrated that 22- and 17-kDa proteins in strain ATCC 31212 (serogroup B) reacted strongly with the sera from the untreated piglets but not with the sera from the SP-treated piglets. The 22- and 17-kDa proteins also reacted with strain ATCC 27164 (serogroup A) which belongs to a different serogroup. The 22- and 17-kDa proteins were also confirmed in six other strains of B. hyodysenteriae which belong to six different serogroups. These proteins were sensitive to proteinase K. These results indicate that the 22- and 17-kDa proteins are common to eight strains of B. hyodysenteriae which differ serologically from each other.

Agglutination Tests↗
PubMed2000

Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF rats.

To determine the contribution of hyperglycemia to the insulin resistance in various insulin-sensitive tissues of Zucker diabetic fatty (ZDF) rats, T-1095, an oral sodium-dependent glucose transporter (SGLT) inhibitor, was administered by being mixed into food. Long-term treatment with T-1095 lowered both fed and fasting blood glucose levels to near normal ranges. A hyperinsulinemic euglycemic clamp study that was performed after 4 wk of T-1095 treatment demonstrated partial recovery of the reduced glucose infusion rate (GIR) in the T-1095-treated group. In the livers of T-1095-treated ZDF rats, hepatic glucose production rate (HGP) and glucose utilization rate (GUR) showed marked recovery, with almost complete normalization of reduced glucokinase/glucose-6-phosphatase (G-6-Pase) activities ratio. In adipose tissues, decreased GUR was also shown to be significantly improved with a normalization of insulin-induced GLUT-4 translocation. In contrast, in skeletal muscles, the reduced GUR was not significantly improved in response to amelioration of hyperglycemia by T-1095 treatment. These results suggest that the contribution of hyperglycemia to insulin resistance in ZDF rats is very high in the liver and considerably elevated in adipose tissues, although it is very low in skeletal muscle.

Adipocytes↗
PubMed2000

Control of membrane sealing in injured mammalian spinal cord axons.

The process of sealing of damaged axons was examined in isolated strips of white matter from guinea pig spinal cord by recording the "compound membrane potential," using a sucrose-gap technique, and by examining uptake of horseradish peroxidase (HRP). Following axonal transection, exponential recovery of membrane potential occurred with a time constant of 20 +/- 5 min, at 37 degrees C, and extracellular calcium activity ([Ca(2+)](o)) of 2 mM. Most axons excluded HRP by 30 min following transection. The rate of sealing was reduced by lowering calcium and was effectively blocked at [Ca(2+)](o) </= 0.5 mM, under which condition most axons continued to take up HRP for more than 1 h. Sealing at higher [Ca(2+)](o) was blocked by calpain inhibitors (calpeptin and calpain inhibitor-1) indicating a requirement for type II (mM) calpain in the sealing process. Following compression injury, the amplitude of the maximal compound action potential conducted through the injury site was reduced. The extent of amplitude reduction was increased when the tract was superfused with calcium-free Krebs' solution (Ca(2+) replaced by Mg(2+)). These results suggest that the fall in [Ca(2+)](o) seen following injury in vivo is sufficient to prevent membrane sealing and may paradoxically contribute to axonal dieback, retrograde cell death, and "secondary" axonal disruption.

Action Potentials↗
PubMed2000

A new model of cerebral microthrombosis in rats and the neuroprotective effect of a Rho-kinase inhibitor.

BACKGROUND AND PURPOSE: The aim of this study was to develop a new model of stroke based on endothelial damage and thrombotic occlusion in a perforating artery, leading to small cerebral infarcts and neurological deficits in rats. Moreover, the neuroprotective efficacy of fasudil, a rho-kinase inhibitor, was investigated in this model. METHODS: Fifty-six male Sprague-Dawley rats were used in the present study. Rats were anesthetized with sodium pentobarbital, and 100 microg of sodium laurate was injected into the left internal carotid artery on days 1 and 3. The thrombus induction and consequent of ischemic brain damage were examined by histopathological analyses and neurological deficit scoring in a posture reflex test. To investigate the neuroprotective effects of fasudil, 1 or 10 mg/kg was administered intraperitoneally 5 minutes after the first injection of sodium laurate and once daily thereafter on the following 2 days. RESULTS: One hour after the injection of sodium laurate, microscopic examination of phosphotungstic acid hematoxylin-stained sections (n=5) revealed that microthrombi containing fibrin strands obstructed the perforating arteries in the ipsilateral hemisphere. Under a transmission electron microscope (n=6), endothelial cells appeared exfoliated and the vascular lumen was obstructed by a thrombus composed of degranulated platelets, fibrin, leukocytes, and erythrocytes. No evidence of endothelial cell damage or thrombus could be found in the ipsilateral side of the pial artery (middle cerebral artery). Twenty-four hours after the second injection of sodium laurate (day 4), 13 of 15 rats (86.6%) showed mild to severe neurological deficits. Multiple small cerebral infarcts were observed in the hippocampus, cortex, and thalamus. Treatment with fasudil (1 and 10 mg/kg, n=15 each) resulted in a significant improvement in neurological deficits. Fasudil also significantly reduced the area of cerebral infarction. CONCLUSIONS: We present a new model of stroke in rats, in which the perforating arteries are selectively occluded by microthrombi. This model is useful to investigate the pathophysiology and treatment of small cerebral infarction, which is caused by perforating arterial occlusive diseases such as lacunar infarcts. Fasudil may be beneficial in the treatment of acute ischemic stroke.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Ventricular arrhythmias with left bundle branch block pattern and inferior axis: assessment of their mechanisms on the basis of response to ATP, nicorandil and verapamil.

The present study investigated the mechanism of ventricular arrhythmias showing left bundle branch block (LBBB) pattern with an inferior axis. The effects of 3 drugs, adenosine triphosphate (ATP), nicorandil and verapamil, were evaluated in 17 patients. ATP suppressed the arrhythmias in 14 patients and nicorandil suppressed them in 8 of those 14. Verapamil suppressed 5 of the 6 ATP-nicorandil-sensitive arrhythmias. Four patients with ATP- or nicorandil-sensitive arrhythmias were not sensitive to verapamil. On the other hand, 3 of the ATP-insensitive arrhythmias were sensitive to neither nicorandil nor verapamil. The QT intervals and QTc were shortened by nicorandil in 5 of the 6 patients who were sensitive to all 3 drugs. One mechanism of suppression by nicorandil could be related to less Ca++ entering the myocardium, which would decrease the duration of the action potential as indicated by the shortened QT intervals. The results suggest that the mechanism of some ventricular arrhythmias is related to triggered activity. Arrhythmias that are sensitive to ATP or nicorandil, but not to verapamil, may be caused by abnormal automaticity. On the other hand, arrhythmias that are insensitive to all 3 drugs might be related to reentry. The features of ventricular arrhythmias with LBBB pattern and inferior axis differ and therefore the causative mechanisms are not the same.

Adenosine Triphosphate↗
PubMed2000

Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction.

Glucocorticoids reportedly induce insulin resistance. In this study, we investigated the mechanism of glucocorticoid-induced insulin resistance using 3T3-L1 adipocytes in which treatment with dexamethasone has been shown to impair the insulin-induced increase in glucose uptake. In 3T3-L1 adipocytes treated with dexamethasone, the GLUT1 protein expression level was decreased by 30%, which possibly caused decreased basal glucose uptake. On the other hand, dexamethasone treatment did not alter the amount of GLUT4 protein in total cell lysates but decreased the insulin-stimulated GLUT4 translocation to the plasma membrane, which possibly caused decreased insulin-stimulated glucose uptake. Dexamethasone did not alter tyrosine phosphorylation of insulin receptors, and it significantly decreased protein expression and tyrosine phosphorylation of insulin receptor substrate (IRS)-1. Interestingly, however, protein expression and tyrosine phosphorylation of IRS-2 were increased. To investigate whether the reduced IRS-1 content is involved in insulin resistance, IRS-1 was overexpressed in dexamethasone-treated 3T3-L1 adipocytes using an adenovirus transfection system. Despite protein expression and phosphorylation levels of IRS-1 being normalized, insulin-induced 2-deoxy-D-[3H]glucose uptake impaired by dexamethasone showed no significant improvement. Subsequently, we examined the effect of dexamethasone on the glucose uptake increase induced by overexpression of GLUT2-tagged p110alpha, constitutively active Akt (myristoylated Akt), oxidative stress (30 mU glucose oxidase for 2 h), 2 mmol/l 5-aminoimidazole-4-carboxamide ribonucleoside for 30 min, and osmotic shock (600 mmol/l sorbitol for 30 min). Dexamethasone treatment clearly inhibited the increases in glucose uptake produced by these agents. Thus, in conclusion, the GLUT1 decrease may be involved in the dexamethasone-induced decrease in basal glucose transport activity, and the mechanism of dexamethasone-induced insulin resistance in glucose transport activity (rather than the inhibition of phosphatidylinositol 3-kinase activation resulting from a decreased IRS-1 content) is likely to underlie impaired glucose transporter regulation.

3T3 Cells↗
PubMed2000

[Hemodynamics of the lower extremities in patients with decubitus ulcers using the ultrasonic Doppler method].

Our clinical experience indicates that decubitus ulcers with tissue loss/necrosis extending beyond the subcutaneous fat in aged patients are liable to become refractory and that most of these patients experience a cold feeling/cyanosis in the lower extremities. In order to determine the relationship between the severity of the decubitus ulcers and the hemodynamics in the lower extremities, we conducted a blood flow test using the ultrasonic Doppler method on the lower extremities in patients. Sixty-eight inpatients (38 men, 30 women, with an average age of 80.5 +/- 7.6 years old) were selected. B-mode tomographs were obtained with an ultrasonic diagnostic apparatus. The power Doppler method was used to measure blood flow rate, vascular lumen diameter, and intravascular blood flow at the dorsalis pedis artery, posterior tibial artery, peroneal artery furcation, and femoral artery. The subjects were divided into three groups: patients without decubitus ulcers; patients with mild to moderate decubitus ulcers of IAET Classification grade I-III; and patients with severe decubitus ulcers (IAET Classification grade IV), and the measurements were compared among the groups. The results revealed a tendency for the vascular lumen to become narrowed and intravascular blood flow to be reduced at all sites as decubitus ulcers increased in severity and showed the hemodynamics in the lower extremities to be particularly poor in the severe group. We measured the hemodynamics in the lower extremity with the ultrasonic Doppler method from the viewpoint of decubitus ulcer prevention and found differences in blood flow in the lower extremities according to the severity of decubitus ulcers. A reduction in blood flow in the lower extremities is considered to indirectly indicate a susceptibility to decubitus ulcers and to serve as a sign of its exacerbation. We consequently considered the test to be useful and concluded that deterioration of hemodynamics due to the progress of arteriosclerosis is one of the causes of decubitus ulcer exacerbation.

Aged↗
PubMed2000

[Relation between hippocampal damage and cerebral cortical function in Alzheimer's disease].

We investigated the relation between hippocampal damage and cerebral cortical dysfunction in Alzheimer's disease (AD) using MRI and SPECT. Nineteen patients with AD and 10 control subjects were studied. Hippocampal damage (including hippocampal formation, entorhinal cortex, and parahippocampal white matter) was assessed to evaluate the severity of atrophy and the magnetization transfer ratio (MTR) and cerebral cortical dysfunction was evaluated by quantitative cerebral blood flow (CBF) measurements using SPECT with 99mTc-ECD. Compared with controls, patients with AD had significantly more atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus and parahippocampus. There were significant correlations between the severity of hippocampal damage and regional CBF in temporoparietal lobes. Mini-Mental State Examination scores significantly correlated with the severity of hippocampal damage and regional CBFs in temporoparietal lobes. These results suggest that the functional effect of hippocampal damage occurs in temporoparietal lobes in AD, probably due to neuronal disconnections between hippocampal areas (including the entorhinal cortex) and temporoparietal lobes.

Aged↗