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T Segawa

Publications and source records attributed to T Segawa.

At least 19 recordsLinked to original sources
PubMed1992

Fluorescence digital image analysis of thrombin and ADP induced rise in intracellular Ca2+ concentration of single blood platelets.

Cytoplasmic free Ca2+ concentration, [Ca2+]i, was estimated in single rabbit blood platelets by digital imaging microscopy with the use of the specific Ca(2+)-indicator dye Fura-2. Uneven distribution and low level of [Ca2+]i was found in the resting platelet even in the presence of extracellular 1 mM Ca2+. Thrombin at 1 unit/ml immediately caused a transient increase in [Ca2+]i, which was followed by a secondary and sustained increase in [Ca2+]i. The distribution of increased levels of [Ca2+]i was also shown to be uneven within the cell. The presence of 1 mM EGTA in the medium only slightly decreased the initial rise in [Ca2+]i, but completely inhibited the latter phase, a sustained rise in [Ca2+]i. This result shows that the initial rise of [Ca2+]i might not be caused by Ca2+ influx, but might be induced by mobilization of Ca2+ from intracellular Ca2+ storage sites. This speculation is further supported by the fact that the elevated [Ca2+]i induced by thrombin immediately decreased to the base line value when 3 mM EGTA was applied. Thus, thrombin induced elevation of [Ca2+]i is suggested to consist of two different processes, namely the mobilization of Ca2+ from the intracellular storage sites and the successive Ca2+ influx through the receptor activated Ca2+ channels. Stimulation with ADP also caused a rapid elevation of platelet [Ca2+]i, but this effect of ADP was different form that of thrombin. Thus, the ADP induced rise in [Ca2+]i was accompanied by oscillation and was inhibited by extracellular EGTA. Our present experiment is the first report that clearly and directly reveals the differences between the effects of thrombin and ADP on [Ca2+]i of platelets.

Adenosine Diphosphate↗
PubMed1992

Pretreatment with catalase or dimethyl sulfoxide protects alloxan-induced acute lung edema in dogs.

We tested the preventive effects of catalase, an enzymatic scavenger of hydrogen peroxide, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, on intravenous alloxan-induced lung edema in four groups of pentobarbital sodium-anesthetized, ventilated dogs for 3 h: saline (20 ml.kg-1.h-1) infusion alone (n = 5), alloxan (75 mg/kg) + saline infusion (n = 5), catalase (150,000 U/kg) + alloxan + saline infusion (n = 5), or DMSO (4 mg/kg) + alloxan + saline infusion (n = 5). Catalase or DMSO significantly prevented the increase in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha over 3 h after alloxan and the accumulation of extravascular lung water after 3 h [3.95 +/- 0.52 (SE) g/g with catalase, 3.06 +/- 0.42 g/g with DMSO] but not early pulmonary arterial pressor response. An electron microscopic study indicated that catalase or DMSO significantly reduced the endothelial cellular damages after alloxan. These findings strongly suggest that hydrogen peroxide and hydroxyl radical are major mediators responsible for intravenous alloxan-induced edematous lung injury in anesthetized ventilated dogs.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Differing actions of endothelin-1 on canine systemic resistance and capacitance vessels.

In anesthetized open-chest dogs, an intravenous bolus injection of endothelin-1 (ET-1, 400 pmol/kg) caused transient hypotension (initial hypotensive phase; phase 1), followed by a continuous elevation of blood pressure (late hypertensive phase; phase 2). The constriction and dilation of the systemic capacitance and resistance vessels were evaluated from the change in mean circulatory pressure (MCP) and in total peripheral resistance (TPR) in phases 1 and 2. To examine the modification of the action of ET-1 on the blood vessels by the baroceptor reflex or by the endothelium-derived relaxing factor (EDRF) released by ET-1 in phase 1, we performed experiments in dogs under total spinal anesthesia (TSA group), methylene blue-treated dogs (MB group) as well as in the untreated dogs (control group). ET-1 decreased the TPR significantly, and increased the MCP significantly in phase 1 in the control (n = 8) and TSA (n = 8) groups; there was no difference between the groups. ET-1 had no significant effect on TPR but increased the MCP significantly in MB group (n = 8) during phase 1. The percentage increase of MCP in the MB group significantly exceeded that of the control group. ET-1 increased both the TPR and MCP significantly in phase 2 in the control group (n = 8). This study indicated that the vasoconstrictor action of ET-1 on the systemic capacitance vessels in phase 1 did not result from a baroceptor reflex, and that the vasodilator action of ET-1 on the systemic resistance vessels may be at least in part mediated via EDRF released by ET-1. We suggest that the vasoconstrictor action of ET-1 on the systemic capacitance vessels is strong, but the vasodilator action of EDRF on the systemic capacitance vessels is weak.

Animals↗
PubMed1992

Isolation of substance P binding protein from rat brain.

Substance P (SP) binding protein of rat brain was solubilized by digitonin. The solubilized proteins were then purified by sequential gel filtration, concanavalin A lectin Sepharose, and SP-affinity chromatography. The calculated molecular weight of this purified SP binding protein was 76-74 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The rabbits were immunized with the purified protein and resulting polyclonal anti-sera were tested. The immune serum significantly inhibited [3H]SP binding to the 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate solubilized membrane fractions from rat brain, whereas pre-bleed antiserum failed to inhibit the binding. This polyclonal antibody also inhibited the activity of 45Ca influx into astroglioma cells stimulated by SP, but does not inhibit that stimulated by histamine. Furthermore, this polyclonal antibody recognized the 76-74 kDa band as assessed by Western blotting. These data strongly suggest that this polyclonal antibody could recognize a part of the natural SP receptor site.

Animals↗
PubMed1992

[Recurrent hepatocellular carcinoma after hepatic resection].

A total of 125 patients with hepatocellular carcinoma (HCC) treated by hepatic resection in our department from 1970 to 1989 were reviewed to determine recurrent factors, recurrent modes of HCC and to assess the treatment for recurrent HCC. Seventy-five of 125 patients had recurrent tumors after the first hepatic resection. The 1-, 2-, and 3-year cumulative recurrent rates after hepatic resection were 25%, 52% and 67% respectively. The size of the tumor, intrahepatic metastasis, portal vein involvement, clinical stage and DNA ploidy pattern were judged as useful predictive factors for recurrence of HCC after hepatic resection. In the patients with intrahepatic metastases, the bilateral lobes of the remnant liver were the most frequent recurrent sites. The treatment for recurrent HCC was divided into 3 groups such as re-resection, transcatheter arterial embolization (TAE) and palliative treatment. The survival curves of patients receiving re-resection and TAE were significant better than those of patients receiving palliative treatment. Patients treated by re-resection for recurrent HCC had the longest survival. The 1-, 3- and 5-year cumulative survival rates after re-resection were 84%, 60% and 48% respectively. It is concluded that the early detection of recurrent HCC is important and re-resection or TAE is effective treatment for recurrent HCC.

Adult↗
PubMed1992

[Evaluation of hepatectomy in small hepatocellular carcinoma--comparison with transcatheter arterial embolization therapy].

Therapeutic effect on 81 hepatectomized patients with hepatocellular carcinoma (HCC) less than 5cm in diameter was compared to that achieved by transcatheter arterial embolization therapy (TAE) in 61. The 5-year cumulative survival rate after hepatectomy was 38%, which was better than that of TAE (8%). Outcome after hepatectomy was better than that after TAE, according to tumor size in less than 2cm in diameter and single nodule. The 3-, and 5-year survival rates for curative hepatectomy were significantly better than those for TAE. But there was no significant difference in survival curves between relative noncurative hepatectomy and TAE. In terms of hepatic reserve with reference to Child's classification, the survival curve for TAE was better than that for relative noncurative hepatectomy in patients with Child-A, but there was no significantly difference between these two methods. Survivors more than 3 years after hepatectomy and TAE were 24 (48.0%) and 11 (23.4%) patients, respectively. Nineteen of 24 patients with hepatectomy had recurrent HCCs, of which reresection was done in 6, TAE in 11 and other treatments in 2. The advantage of hepatectomy in comparison with TAE is a possibility of long-term survival, if curative hepatectomy is performed.

Adolescent↗
PubMed1992

[Circumvention of the intrinsic multidrug-resistance in renal cell carcinoma].

Most of renal cell carcinomas (RCCs) are refractory at the start of chemotherapy. We have demonstrated that the frequently elevated expression of the multidrug resistance gene (MDR) in RCCs is associated with the intrinsic vinca alkaloids and anthracyclines resistance. The preliminary clinical trials using verapamil or amiodarone in combination with vinblastine or doxorubicin to overcome multidrug-resistant (MDR) tumors could not achieve satisfactory results owing to severe cardiovascular toxicities of such reversing agents. In the present study, we studied the sensitizing ability of bis-benzyl-isoquinoline (cepharanthine) and SDB-ethylenediamine (N-1379) in natural MDR kidney cancer cells. Cepharanthine remarkably sensitized vinblastine and doxorubicin sensitivities in those cells with high MDR RNA levels. From a clinical point of view, cepharanthine seems to be a potent and less toxic agent to treat natural MDR kidney cancers.

Alkaloids↗
PubMed1991

Histamine H2-receptor in atrium: signal transduction and response.

We have examined the signal transduction for H2-receptor mediated positive chronotropic response of guinea-pig right atrium. Our results indicate that phospholipid methylation is rapidly induced by histamine acting on H2-receptor in guinea-pig right atrium and therefore plays a predominant role in the signal transfer of H2-receptor-mediated cyclic AMP generation to exert positive chronotropic effect of atrium, as well as GTP-binding protein activation.

Adenylyl Cyclases↗
PubMed1991

Characterization of the carbohydrate chain on the substance P receptor in the rat brain cortex: effect of lectins on [3H]substance P binding.

The characteristics of the carbohydrate chain on the rat cerebral cortical substance P (SP) receptor were studied. We examined the effects of pretreatment with three lectins (concanavalin A, wheat germ agglutinin, lens culinaris agglutinin) on the [3H]SP binding activities. Each lectin can bind to the specific carbohydrate chain. Among these lectins, only concanavalin A inhibited specific [3H]SP binding by reducing the affinity of the binding sites. The inhibitory action of concanavalin A was dose-dependent and diminished by the addition of alpha-methyl-D-mannoside. The present results suggest that the rat cortical SP receptor has either a biantennary complex-type or a high mannose-type of carbohydrate chain, and that the carbohydrate chain is implicated in the SP binding activity of the SP receptor system.

Animals↗
PubMed1991

Clonidine reduces substance P binding in rat spinal cord membrane preparation.

The effects of clonidine on substance P (SP) binding was investigated using rat brain and spinal cord membrane preparations preincubated with various concentrations of clonidine. [3H]SP specific binding in the spinal cord was significantly decreased with 10(-4) M clonidine, but no effect on binding was seen in the brain. Scatchard analysis of SP binding indicated that Bmax was significantly depressed without changing the affinity. The mechanism of clonidine-induced analgesia includes a spinal neural component and action on the SP receptors.

Animals↗
PubMed1991

Substance P receptors in mammalian central nervous system.

1. Multiple distinct affinity states or sites of substance P (SP) receptors exist in freshly-prepared rat brain membranes. 2. Substance P receptors may couple with islet-activating protein (pertussis toxin) sensitive GTP-binding protein(s). 3. Substance P receptors may be regulated Mg2+ and Na+ in an opposite manner. 4. Some important factor(s), in addition to GTP-binding protein, appear to be involved in SP binding activity. 5. An apparent molecular weight of the SP binding site is approximately 46,000 Da.

Animals↗
PubMed1979

Decrease in muscarinic cholinergic response of the rat heart following treatment with 6-hydroxydopa.

Pretreatment with 6-hydroxydopa (6-OHDOPA) at birth produced a decrease in the number of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites in adult rat heart homogenates. The treatment caused hyposensitivity to acetylcholine (ACh) but did not alter the maximal negative inotropic action of ACh in isolated atria of the rat. These results suggest that 6-OHDOPA affects the negative inotropic response to ACh by modifying the receptor number or through an effect on a step between receptor activation and biological response.

Acetylcholine↗