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Biomedical subjects

N Matsuki

Publications and source records attributed to N Matsuki.

At least 145 records · Page 8Linked to original sources
PubMed1990

[Multivariate analysis of gastric cancer patients with liver metastases].

In 93 cases of stomach cancer with liver metastasis, the influence of surgery and chemotherapy on the patients' prognosis was examined. Chemotherapy comprised systemic administration of mitomycin C (MMC) (39 cases), intra-hepatoarterial administration of MMC (19 cases) and intra-hepatoarterial infusion of cisplatin (CDDP) + MMC (PM intra-arterial chemotherapy) (24 cases) in the first 1-2 postoperative weeks. MMC and CDDP were given by 1-4 courses every 1-3 weeks. Examination of the prognosis factors by generalized Wilcoxon test revealed significant differences in the extent of lymph node metastasis (N0-2 vs N3,4), possible resection of primary lesion, and chemotherapeutic regimen (PM intra-arterial chemotherapy and other chemotherapeutic regimens). The response rate was 4.3% (1/23), 29.4% (5/17) and 73.8% (17/23) for MMC systemic administration, MMC intra-arterial chemotherapy and PM intra-arterial chemotherapy, respectively, with a significantly high response rate for the latter. Also for the 50% survival period, the latter showed 11.8 months compared with 2.7 months for other chemotherapeutic treatments, indicating its good prognosis regardless of possible resection of the primary lesion. Cox proportional hazard model revealed the latter alone to be a significant independent factor. The above results suggest that the PM intra-arterial chemotherapy is an effective approach to stomach cancer with liver metastasis.

Adult↗
PubMed1989

Potentiation by treatment with reserpine of alpha 2-adrenoceptor-mediated contractions of rat tail artery.

The effects of a treatment with reserpine on alpha-adrenoceptor-mediated contractile responses of rat tail arteries were investigated in vitro. The potency of norepinephrine was slightly increased in arteries obtained from rats treated with reserpine. There was no significant change in the sensitivity of the arteries to serotonin, KCl and selective alpha 1-adrenoceptor agonists (methoxamine and phenylephrine). However, the potency of clonidine and UK-14,304, both selective alpha 2-adrenoceptor agonists, was greatly increased. UK-14,304-induced contractions of the arteries from rats treated with reserpine were inhibited strongly by rauwolscine, a selective alpha 2-adrenoceptor antagonist, but only slightly by corynanthine, a selective alpha 1-adrenoceptor antagonist. The contractions caused by re-introduction of Ca2+ during exposure to UK-14,304 but not to methoxamine in a Ca2(+)-free medium were potentiated by treatment with reserpine. Bay K 8644, an agonist of Ca2+ channels, produced a concentration-dependent contraction only in the arteries from rats treated with reserpine. These results suggest that treatment with reserpine potentiates alpha 2- but not alpha 1-adrenoceptor-mediated responses in rat tail arteries and that the potentiation could be related to changes in mechanisms linked to Ca2+ influx.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle.

Endothelin is a potent endothelium-derived vasoconstrictor peptide recently characterized from porcine and human vascular endothelial cells. Here we provide evidence that endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in porcine coronary artery smooth muscle. The vasoconstrictor action of endothelin is efficiently antagonized by low doses of the dihydropyridine Ca2+-channel blocker nicardipine. Endothelin augments the Ca2+-induced contraction in a high-K+ depolarizing solution, markedly enhances high-threshold Ca2+-channel current on the whole-cell patch clamp recording, and causes a sustained increase in the intracellular Ca2+ that is largely dependent on extracellular Ca2+. These findings suggest that endothelin exerts its vasoconstrictor effect by either directly or indirectly activating the voltage-dependent Ca2+ channel.

Animals↗
PubMed1989

[Effect of PMU hepatic arterial chemotherapy for liver metastases of gastric cancer. Hokuriku Cisplatin Round-table Conference].

We performed PMU hepatic arterial chemotherapy (a combination therapy consisting of intra-hepatic arterial infusion of CDDP and MMC, oral administration of UFT) in 20 patients with gastric cancer and liver metastases. In this method, 1-6 courses of one infusion of CDDP at 70-100 mg/body and MMC of 10 mg/body into the proper hepatic artery were administered at intervals of 3-4 weeks. UFT of 300-400 mg/day was orally administered with the infusion. The primary response for hepatic metastatic lesions was observed in one case of CR, 14 cases of PR, 4 cases of NC, and one case of PD. The efficacy for CR and PR was high at 75%. The median disease-free interval was 56 weeks in responders. The 50% survival period was 11.1 months; one-year survival rate, 42.1%; two-year survival rate, 12.3%; the longest survival period was 108 weeks. Mild and transient side effects were recognized in 17 cases (85%): gastrointestinal symptoms, sense of general malaise, fever, leukocytopenia, and elevated BUN. Thus, the results indicated that this combination chemotherapy was effective for liver metastases of gastric cancer.

Administration, Oral↗
PubMed1988

Fast and slowly inactivating components of Ca-channel current and their sensitivities to nicardipine in isolated smooth muscle cells from rat vas deferens.

(1) Fast and slowly inactivating components of Ca-channel current were compared to clarify whether more than one type of Ca-channel exists in smooth muscle cells from rat vas deferens using the whole cell variant of the patch clamp technique. The pipette was filled with 150 mM Cs solution to eliminate outward current and Ba was used as the charge carrier for Ca-channel current. (2) When activated by a 5 s test pulse to O mV from a holding potential of -60 mV, the inactivation process of Ba-current was well fitted by the sum of two exponentials. The time constant of the faster inactivating component was 100-300 s and that of the slower inactivating component was 1.5-3 s. Steady-state inactivation curves of the fast- and slow-components were very similar. (3) The inward current activated at O mV from -80 mV was inactivated faster than that from -30 mV. The voltage-dependencies of the peak current from holding potentials of -30 mV and -80 mV were similar. Both had voltage threshold at -30 mV and were maximal at +10 mV. (4) Low concentrations of nicardipine (10(-9) to 10(-7) M) preferentially inhibited the slow component while higher concentration (10(-6) to 10(-5) M) were required to block the fast component. The current activated from a holding potential of -30 mV was almost fully suppressed by 10(-7) M nicardipine whereas that from -80 mV was blocked only slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Suncus murinus as a new experimental model for motion sickness.

Characteristics of motion sickness and effects of possible prophylactic drugs were studied using Suncus murinus (house musk shrew) for its potential use as an experimental model in motion sickness. Mild reciprocal shaking (amplitude: 10-40 mm; frequency: 0.5-3.0 Hz) induced vomiting in most of Suncus murinus within 2 min. Adaptation was observed when the motion stimulus was repeated with an interval of 2 to 3 days. During the repetitive motion training, both the ratio of sensitive animals and the number of vomiting episodes decreased, and the time from the start of shaking to the first vomiting was extended. Subcutaneous injection of scopolamine (100 mg/kg), chlorpromazine (8 mg/kg), promethazine (50 mg/kg), diphenhydramine (20 mg/kg), chlorphenylamine (20 mg/kg) and methamphetamine (2 mg/kg) decreased the emetic effect of motion sickness, but pyrilamine (20 mg/kg), meclizine (20 mg/kg) and dimenhydrinate (32 mg/kg) were not effective or very weak. These results indicate that the Suncus murinus is sensitive to the motion stimulus and antiemetic drugs are effective as prophylaxis. The Suncus murinus is useful as a new experimental animal model for motion sickness.

Acceleration↗
PubMed1988

Characteristics of [3H]nimodipine binding to sarcolemmal membranes from rat vas deferens and its regulation by guanine nucleotide.

The binding properties of a 1,4-dihydropyridine (DHP) calcium entry blocker, [3H]nimodipine, to a microsomal fraction from rat vas deferens was characterized. The specific binding was saturable, rapid and reversible. Scatchard analysis of the binding revealed a single binding site, and the dissociation constant and the maximum number of binding sites were 0.31 +/- 0.02 nM and 97.0 +/- 7.19 fmol/mg protein, respectively. Both the Kd value obtained from the kinetic study and the IC50 value from relaxation of the K+-depolarized organ were approximately 0.4 nM, indicating that the binding site is closely related to the functional Ca2+ channel. The specific [3H]nimodipine binding was displaced by DHP derivatives at low concentration and by verapamil at high concentration, but diltiazem had no effect on the binding. Calcium chelating agents decreased the [3H]nimodipine binding which was restored by adding Ca2+. 5'-Guanylylimidodiphosphate caused a rightward shift of the displacement curve for Bay K 8644 but not for nimodipine, suggesting the involvement of guanine nucleotide binding protein in the signal transduction between the DHP binding site and the Ca2+ channel.

Animals↗
PubMed1988

Emesis induced by cancer chemotherapeutic agents in the Suncus murinus: a new experimental model.

Acute emetic responses to seven cancer chemotherapeutic agents (adriamycin, bleomycin, cisplatin, cyclophosphamide, 5-fluorouracil, methotrexate, mitomycin C) were studied in the Suncus murinus. Intravenous injection of the drugs caused vomiting with various latency. Cisplatin-induced emesis was prevented by the pretreatment with metoclopramide or chlorpromazine but not with domperidone. These results indicate that the Suncus murinus is a useful animal for testing emetic activities of cancer chemotherapeutics and antiemetic activities of prophylactic drugs.

Animals↗
PubMed1988

[Effect of PMU therapy (CDDP, MMC and UFT) against terminal gastric carcinoma. Hokuriku Cisplatin Round-table Conference].

PMU therapy with 75 mg/m2 of CDDP, 10 mg/body of MMC and 400 mg/day of UFT was performed on 57 patients with terminal gastric carcinoma. The treatment resulted in CR in 2, PR in 9, MR in 1, NC in 16 and PD in 9 of 37 patients with evaluable cases, with a response rate of 30% (11/37 patients). In the 11 responders, the mean disease-free interval was 6.6 months with a median interval of 5 months, and the mean survival period was 9.2 months with a median survival period of 6 months, while in the 46 non-responders, the mean survival period was 6.7 months with a median survival period of 5 months. In all patients, the mean survival period was 7.1 months with a median survival period of 6 months. Adverse reactions to the treatment included gastrointestinal disturbance observed in 77%, nephrotoxicity in 14%, and myelotoxicity in 26% of the patients, but all reactions became normalized during the course of observation. These results have led to the conclusion that PMU therapy may be an effective treatment for terminal gastric carcinoma.

Adult↗
PubMed1987

Suncus murinus: a new experimental model in emesis research.

Effects of various emetic and antiemetic drugs were studied using Suncus murinus for its potential use as an experimental model in emetic research. Subcutaneous injection of nicotine bitartrate (10-15 mg/kg), veratrine sulfate (0.5-1.0 mg/kg), emetine dihydrochloride (40-80 mg/kg) and oral administration of copper sulfate (20-100 mg/kg) caused dose-dependent emesis in suncus. The ED50 of nicotine, veratrine, emetine and copper sulfate were 7.9, 0.4, 47.6 and 21.4 mg/kg, respectively. However, subcutaneously injected apomorphine hydrochloride (0.1-100 mg/kg), digitoxin (0.5-1.0 mg/kg) and orally administered emetine dihydrochloride (10-80 mg/kg) did not induce the vomiting. Chlorpromazine and promethazine decreased the emetic effect of nicotine, veratrine and copper sulfate, but scopolamine hydrobromide was not effective. These results indicate that the Suncus murinus is sensitive to various emetic and antiemetic drugs and can be used as a new experimental animal model for the emesis. Emetic behavior of suncus was discussed in comparison with other animals.

Animals↗
PubMed1987

Contractile response and electrophysiological properties in enzymatically dispersed smooth muscle cells of rat vas deferens.

Electrophysiological studies were performed on single smooth muscle cells isolated from the vas deferens of the rat. The tissue was preincubated in Ca-free modified Tyrode's solution for 1 h and then transferred to a high-K solution for 1 h. It was next minced and treated with the enzyme solution composed of 600-800 unit/ml collagenase and 40 unit/ml elastase. The procedure yielded about 50% spindle shaped Ca-tolerant cells (100-250 microns in length and about 10 microns in diameter). These cells could contract during the superfusion with the solutions containing 10(-8) to 10(-3) M norepinephrine (NE) or adenosine triphosphate (ATP). The cells isolated from the epididymal portion were more sensitive to norepinephrine than were those from the prostatic part. Their basic electrical properties were studied using tight-seal suction electrode technique. The cells had resting potentials around -40 mV and their input resistance was about 0.8 G omega. Action potentials could be evoked by application of depolarizing current. During whole cell voltage clamp, an inward current followed by an outward current was recorded when 800 ms pulses from a holding potential of -60 mV to test potentials positive than -40 mV were applied. The transient outward current generally recorded in other smooth muscle cells was not seen in these cells. The amplitude of the inward current was Ca dependent and sensitive to a Ca antagonist, nicardipine, indicating that Ca ion is the main carrier of this component of the current. When the pipette was filled with Cs-containing solution, the outward current was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Adenosine triphosphate-activated inward current in isolated smooth muscle cells from rat vas deferens.

The electrophysiological effect of adenosine triphosphate (ATP) on the enzymatically dispersed smooth muscle cells from rat vas deferens was investigated. ATP always induced depolarization accompanied with a reduction in membrane resistance. In a whole cell voltage clamp experiment, an inward current was recorded when the cell was exposed to ATP-containing solution. The ATP-induced current disappeared within 2 min even in the continuous presence of ATP, which may indicate that the cells were desensitized to this compound. The ATP-induced current was also recorded in the cells superfused with 10(-5) M nicardipine or in the Cs-loaded cells, eliminating the possible involvement of voltage-gated Ca and K current. During cell-attached patch clamp, an elementary current having a mean conductance of 20 pS was observed when the intrapipette solution was changed to ATP-containing solution. The estimated zero current potentials of the ATP-activated macroscopic current and elementary current were about 0 mV. These results suggest that ATP exerts its transmitter-like action by activating ion channels in smooth muscles.

Adenosine Triphosphate↗
PubMed1987

Involvement of calcium in calcium-current inactivation in smooth muscle cells from rat vas deferens.

Ca-channel currents were recorded in Cs-loaded single smooth muscle cells from rat vas deferens to define the dependence of the inactivation time course on Ca concentration. The decay of Ca-channel current obtained in a Ba2+- or Sr2+-containing external solution during long voltage-clamp pulses was much slower than that in a Ca-containing solution. The difference was not due to a change in the surface potential of the membrane as judged from the steady-state activation and inactivation curves. When Ca was the charge carrier, increasing external Ca concentration slightly accelerated the rate of inactivation. In addition, the rate of inactivation of Ca-channel current in 10.8 mM Ba was also accelerated by adding Ca to the external solution in a concentration-dependent manner. The time course of Ca-current inactivation was slowed when the cells were dialyzed with a high concentration of citrate, a Ca-chelating agent. From these results, we concluded that a mechanism regulated by intracellular Ca activity plays a role in the inactivation of Ca channels in smooth muscle. The Ca-dependent process may protect against Ca overload by regulating Ca entry in smooth muscle cells.

Animals↗
PubMed1987

Pharmacological and electrophysiological discrimination of contractile responses to selective alpha 1- and alpha 2-adrenoceptor agonists in rat tail artery.

Pharmacological and electrophysiological properties of postsynaptic alpha-adrenoceptor subtypes in rat tail artery were compared using selective alpha 1- and alpha 2-adrenoceptor agonists. Five alpha-adrenoceptor agonists contracted the tail artery with the following order of maximal effects: norepinephrine (alpha 1 and alpha 2) greater than methoxamine (alpha 1) = phenylephrine (alpha 1) much greater than clonidine (alpha 2) greater than UK-14,304 (alpha 2). Phenoxybenzamine greatly diminished contractions induced by methoxamine and phenylephrine, but had little effect on responses to UK-14,304. Idazoxan antagonized more potently against UK-14,304 than against methoxamine. These results suggest the heterogeneity of postsynaptic alpha-adrenoceptors in the rat tail artery. Furthermore, responses to methoxamine and phenylephrine 1) had faster onsets and 2) were more resistant to Ca2+ entry blockers, nicardipine and diltiazem, and a promotor, Bay K 8644, or decreasing of extracellular Ca2+ and 3) were more sensitive to a calmodulin antagonist, W-7, than the responses to UK-14,304 and clonidine. Both methoxamine and UK-14,304 depolarized the membrane but methoxamine produced stronger depolarization than UK-14,304. Therefore, the high sensitivity of alpha 2-adrenoceptor agonists-induced responses to Ca2+ entry blockers and promotors cannot be accounted for solely by membrane depolarization. These results may indicate the differences in the Ca2+ movement for the contractions produced by alpha 1- and alpha 2-adrenoceptor agonists.

Adrenergic alpha-Agonists↗
PubMed1986

Attenuation of the development of hypertension in spontaneously hypertensive rats by chronic oral administration of eicosapentaenoic acid.

Chronic effects of highly purified eicosapentaenoic acid (EPA) on systolic blood pressure in spontaneously hypertensive rats (SHR) and normotensive rats were studied. Daily oral administration of 30 to 300 mg/kg EPA for eight weeks significantly decreased the development of hypertension in SHR dose-dependently. Eight weeks treatment of 30, 100, and 300 mg/kg EPA reduced mean systolic blood pressure by 23, 29, and 32 mmHg, respectively, compared to untreated rats. Hypotensive effect of EPA progressed slowly and was reversible after the termination of the treatment. However, daily administration of EPA to normotensive rats did not affect the systolic blood pressure. EPA may be useful as a hypotensive agent for treatment of hypertension.

Animals↗
PubMed1986

[PMU therapy of recurrent gastric cancer. A case report].

A 56-year-old woman with recurrent gastric cancer treated with PMU therapy, combined CDDP 75 mg/m2 i.v. MMC 10 mg/body i.v. and UFT 400mg/body/2 alpha/day p.o., was reported. She was admitted because of cervical lymph node swelling and abdominal tumor (para-aorta lymph node swelling). She was treated two times with this therapy and induced into complete remission. The serum CEA level, more than 500 ng/ml before the treatment, was reduced to 6.7 ng/ml after treatment. She has currently been free of disease for more than four weeks. We conclude that this PMU therapy is extremely effective for indurable gastric cancer.

Adenocarcinoma, Scirrhous↗
PubMed1984

Characterization of the block of sodium channels by phenytoin in mouse neuroblastoma cells.

The interaction of phenytoin (DPH) with membrane ionic channels of cultured N1E-115 neuroblastoma cells was studied. The single suction pipette technique was used for voltage clamp and intracellular perfusion. When the cells were held at -80 mV for periods of 1 min or more, DPH (20-100 microM) inhibited inward sodium current in a dose-dependent manner (resting block); resting block was relieved by hyperpolarizing cells to -100 mV for 1 min. A hyperpolarizing shift of the slow inactivation curve for the Na current was induced by DPH and can explain the effect of holding potential on the resting block. The fast Na inactivation curve, however, was not affected. During repetitive pulsing the DPH-induced inhibition of Na current was enhanced (conditioned block). Conditioned block was both voltage- and frequency-dependent. Conditioning pulses to potentials which do not appreciably open Na channels also produced conditioned block; prolongation of conditioning pulses even to durations longer than the time for maximal steady-state inactivation of the Na current progressively increased the extent of conditioned block, suggesting that DPH can interact with inactivated and closed Na channels. The time course of recovery from voltage-dependent inactivation of sodium current during conditioned block was both slowed and exhibited voltage dependence. Recovery occurred faster when membrane potential during the recovery period was more negative. We conclude that DPH blocks Na channels both by increasing the fraction of channels in an inactivated state and by delaying the transition from inactivated to closed but available channels. This effect is enhanced by depolarizing membrane potential and increasing the frequency of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗