Search PubMed⌕ Search

Biomedical subjects

M Saitoh

Publications and source records attributed to M Saitoh.

At least 343 records · Page 19Linked to original sources
PubMed1988

Electrophysiological effects of maprotiline, a tetracyclic antidepressant agent, on isolated cardiac preparations.

We studied the effects of maprotiline, a tetracyclic antidepressant agent, on transmembrane potentials recorded from papillary muscles of guinea pigs and sinoatrial nodes of rabbits, using standard microelectrode techniques. Maprotiline (10-100 microM) produced dose-dependent decreases in the maximum rate of rise (Vmax) and action potential duration in papillary muscles, while the resting potential (Em) was not significantly affected. Maprotiline also shifted the Vmax-Em relation to more negative potentials. The slow action potentials of papillary muscles elicited by high [K+]o were also depressed by the drug application. In sinoatrial node cells, maprotiline (above 10 microM) reduced heart rate, Vmax, and action potential amplitude, and increased the action potential duration at half-amplitude. The slope of the phase 4 depolarization was decelerated by the drug. These results suggest that maprotiline depresses not only the fast inward sodium current but also the slow inward calcium current, and that relatively high concentrations of maprotiline exert an inhibitory effect on the electrical activity of the fast- and slow-response fibers of the hearts.

Action Potentials↗
PubMed1988

[Female urethral carcinoma: results of irradiation in 2 patients].

Urethral carcinoma in 2 females has been treated with irradiation together with adjunct chemotherapy. In case 1, a 73-year-old female with squamous cell carcinoma was successfully treated with irradiation of 4,000 rad and peplomycin of 60 mg intravenously given. She has been free from the disease for the past 43 months. In case 2, a 61-year-old female with transitional cell carcinoma was initially treated with irradiation of 5,000 rad together with peplomycin 90 mg, which was followed by another 5,000 rad irradiation. The tumor recurred and the patient was operated on for cystourethrectomy and partial resection of the vagina. A further chemotherapy of cisplatin, peplomycin, and mitomycin C was instituted. She died of the tumor recurrence 23 months after the first visit to our clinic. Diagnosis and treatment modalities on the female urethral carcinoma are briefly discussed.

Aged↗
PubMed1988

[Character of a human cholangiocarcinoma CHGS, serially transplanted to nude mice].

With the progress in surgical technique, remarkable improvement has been noted in the treatment of bile duct carcinoma. However, in the cholangiocarcinoma at porta hepatis or in the progressive carcinoma, many cases have been reported, for which radical surgery is not achievable. In recent years, discussion has been concentrated on the necessity of multidisciplinary treatment for the bile duct carcinoma, but fundamental research has not been done enough. In the present paper, the process for obtaining CHGS strain implantable to the nude mouse derived from a human cholangiocarcinoma as achieved in our department was discussed, and its biological characteristics-above all, the sensitivity to carcinostatic agents and to radiation-were evaluated. The doubling time of CHGS strain is 6.2 days, and nude mice showed stable proliferation with 100% viability. Histologically, it was tubular adenocarcinoma similar to the primary tumor. It has high mucin producing ability, and necrosis hardly occurs. The search for DNA ploidy by flow cytometry revealed the presence of two types of cells: The cells of diploid pattern and aneuploid pattern. In the tests to determine the sensitivity of CHGS strains to carcinostatic in MMC, ADR, 5-FU and CDDP groups, and to radiation according to the Battele Columbus Laboratories Protocol, the regression of tumor was observed in MMC, ADR, CDDP groups. Particularly, in MMC group, some of the tumors had disappeared. Recurrence was also noted in this case, but the survival, was still recognized nearly four years after the operation through the postoperative auxiliary therapy. This was regarded as the case, where the sensitivity test using the nude mouse implantable tumor strain was reflected well in clinical application.

Adenoma, Bile Duct↗
PubMed1988

[A case report of carcinoid of the rectum coexisting with adenocarcinoma in a single lesion].

A 69-year-old female, chiefly complaining of diarrhea, was admitted to the Toyama Medical & Pharmaceutical University Hospital. A barium enema and an endoscopic examination revealed a villous adenocarcinoma of the rectum. Computerized tomography disclosed multiple metastatic lesions in the liver. She underwent an amptatio recti and an intra-arterial cannulation of the common hepatic artery in order to administer anticancer agents. Gross findings of the resected specimen showed villous adenocarcinoma containing a small ulcerated lesion. Histologic findings of this lesion revealed a collision neoplasm containing both an adenocarcinoma and a carcinoid with no obvious transitional region between the two lesions. The type D carcinoid, determined according to Soga's histologic classification, showed positive argyrophil granules but no argentaffin granules in the cytoplasm. The electron-microscopic findings of the carcinoid revealed small electron-dense endocrine granules measuring about 150 approximately 300 nm in diameter. The woman died 4 months after this operation.

Adenocarcinoma↗
PubMed1988

ML-9 inhibits the vascular contraction via the inhibition of myosin light chain phosphorylation.

We investigated the effects of a newly synthesized compound, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), a myosin light chain kinase (MLCK) inhibitor of superprecipitation of actomyosin, isometric tension development, and phosphorylation of the 20,000-Da myosin light chain (LC20) in vascular smooth muscle. Superprecipitation of actomyosin from bovine aorta was inhibited by the addition of ML-9 in a dose-dependent manner. In chemically skinned smooth muscles of the rabbit mesenteric artery, ML-9 inhibited the Ca2+-independent contraction provoked by application of trypsin-treated MLCK. In the intact rabbit mesenteric artery, increases in LC20 phosphorylation reached a maximal value of 0.49 mol of Pi/mol of LC20 within 10 sec from a resting value of 0.15 mol of Pi/mol of LC20 and then declined to near the basal level during the maintained isometric force developed in response to 50 mM KCl. Preincubation with 10-30 microM ML-9 for 30 min significantly inhibited both the maximal rate and extent of KCl-induced contraction and the phosphorylation of LC20, in a dose-dependent manner. There was a linear relationship between the initial rate of tension development and the extent of LC20 phosphorylation at 10 sec after stimulation. ML-9 nonspecifically antagonized the contraction induced by various contractile agonists, such as CaCl2, norepinephrine, serotonin, histamine, and angiotensin II. ML-9 dose dependently produced a shift to the right and down, in the dose-response curves, to all the agonists tested. These results suggest that ML-9 inhibits the actin-myosin interaction through the modulation of LC20 phosphorylation via the inhibition of MLCK activity. Thus, ML-9 may be a useful compound for investigating the physiologic role of myosin light chain phosphorylation by MLCK in living cells and tissues as well as in vitro.

Animals↗
PubMed1987

Different sensitivities of Ca2+, calmodulin-dependent cyclic nucleotide phosphodiesterases from rabbit aorta and brain to dihydropyridine calcium channel blockers.

The concentrations of the dihydropyridines, CD-349, nicardipine, and nimodipine, producing 50% inhibition of Ca2+, calmodulin (CaM)-dependent cyclic nucleotide phosphodiesterase (CaPDE) from rabbit aorta in the absence of Ca2+-CaM complex were approximately 7 to 13-fold higher than these of aorta CaPDE in the presence of Ca2+-CaM complex and of the trypsin treated enzyme form. On the other hand, these dihydropyridine derivatives inhibited CaPDE from rabbit brain at much the same IC50 values seen in the absence and presence of the Ca2+-CaM complex and the trypsin-treated enzyme. Kinetic analysis revealed that these dihydropyridines inhibited the activities of CaPDEs from both the aorta and brain, competitively with cyclic GMP as substrate, and the Ki values of CD-349 for CaPDE from aorta or brain in the absence or presence of Ca2+-CaM complex and trypsin-treated enzyme were 9.6, 0.75, 0.75 or 0.69, 0.70, 0.66 microM, respectively. These results suggest that CaPDE from the rabbit aorta differs from this enzyme in the brain, with regard to the relationship between the dihydropyridine binding sites on CaPDE molecules and the domains regulated by the Ca2+-CaM complex or limited proteolysis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

On the ionic mechanism of cyproheptadine-induced bradycardia in a rabbit sinoatrial node preparation.

The effects of cyproheptadine (0.1-10 microM) on the membrane potentials and currents of rabbit sinoatrial node were examined with the double-microelectrode voltage clamp technique. Cyproheptadine reduced the heart rate, maximum rate of depolarization and action potential amplitude. It also decreased the slope of phase 4 depolarization. On the current systems, cyproheptadine decreased the slow inward current (Isi), the time-dependent potassium outward current (Ik) and the hyperpolarization-activated current (Ih). The reduction of Isi was the major effect. Furthermore, Isi was progressively decreased by repetitive membrane depolarization during administration of cyproheptadine, an effect suggestive of frequency-dependent block of Isi. These electrophysiological observations indicate that cyproheptadine has a calcium antagonistic property, and additionally, decreases Ik and Ih in rabbit sinoatrial node.

Action Potentials↗
PubMed1987

Decreased phorbol ester receptor and protein kinase C in P388 murine leukemic cells resistant to etoposide.

A variant P388 murine leukemic cell resistant to 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene)-beta-D-glucopyr anoside (etoposide) (VP-16-213) was cloned. The variant P388/VP-16 cell line was 159-fold resistant to 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene)-beta-D- glucopyranoside and showed cross-resistance to vincristine (18.9-fold) and Adriamycin (522.9-fold), determined by comparing the 50% inhibitory concentrations in a 48-h growth inhibition assay. To identify the possible role of Ca2+-phospholipid-dependent protein kinase (protein kinase C) in this drug resistance, we studied the specific phorbol ester binding component and protein kinase C in the parent and drug-resistant sublines of P388 cells. The phorbol ester receptor, as expressed by the numbers of sites per cell, significantly decreased in P388/VP-16 (57.6% of control). Scatchard analysis revealed that the variant contained a single class of binding sites. However, no difference was observed in the dissociation constants (Kd), thereby suggesting much the same affinity of receptors between the two lines. Phorbol diester analogues inhibited [20-3H]phorbol-12,13-dibutyrate binding of both the variant and control cell lines, in a stereospecific manner and consistent with their binding potency. The activity of protein kinase C, which is related to the phorbol ester receptor, significantly decreased in the variant cell. The enzyme activity, particularly in the membrane fraction of P388/VP-16 cells, was remarkably decreased. These data suggest that the decrease in the specific phorbol diester receptor and protein kinase C in the variant cells might correlate with the pleiotropic drug resistance.

Animals↗
PubMed1987

Selective inhibition of catalytic activity of smooth muscle myosin light chain kinase.

Systematically synthesized derivatives of ML-9, 1-(5-chloronaphthalenesulfonyl)-1H-hexahydro-1,4-diazepine, were found to inhibit both Ca2+-calmodulin-dependent and -independent smooth muscle myosin light chain kinases with a similar concentration dependence, and their inhibitions were of the competitive type with respect to ATP. Moreover, ML-9 as well as ATP or ADP exhibited an effective protection to inactivation of smooth muscle myosin light chain kinase by the nucleotide affinity label 5'-p-fluorosulfonylbenzoyladenosine, suggesting that ML-9 binds at or near the ATP-binding site on the kinase molecule. These derivatives, which were structurally unrelated to ATP and exhibited more hydrophobic properties detected by reverse-phase high-performance liquid chromatography, exhibited more potent inhibition toward smooth muscle myosin light chain kinase, indicating that the hydrophobic properties of these derivatives positively correlated well with their potencies of inhibiting the catalytic activity for the enzyme. These findings suggest that the ATP-binding site at the active center of smooth muscle myosin light chain kinase is located in a hydrophobic environment. The potent vaso-relaxing effect of ML-9 on rabbit vascular strips and on saponin-treated skinned smooth muscle cells was discussed in relation to the in vivo inhibition by this drug of smooth muscle myosin light chain kinase.

Adenosine↗
PubMed1987

Inhibition of Ca2+ inward current in rabbit sinoatrial node by bunazosin, an alpha-adrenoceptor antagonist.

The electrophysiological effects of bunazosin, a novel alpha-adrenoceptor antagonist, were examined on isolated spontaneously beating sinoatrial node preparations of the rabbit by means of a double-microelectrode voltage clamp method. Bunazosin (above 10 microM) reduced the beating frequency, and the maximum rate of rise and the amplitude of action potentials. The slope of the diastolic depolarization (phase 4) was also decreased by the drug whereas the action potential duration at 50% repolarization was prolonged. Bunazosin decreased the slow inward current (Isi) and the time-dependent potassium outward current (IK). However, the major effect was the reduction of Isi. The results indicate that bunazosin, an alpha-adrenoceptor antagonist, depresses the action potential and automaticity of the sinoatrial node by inhibition of Ca channels.

Action Potentials↗