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Biomedical subjects

R Inoue

Publications and source records attributed to R Inoue.

At least 253 records · Page 14Linked to original sources
PubMed1985

Two Ca-dependent K-channels classified by the application of tetraethylammonium distribute to smooth muscle membranes of the rabbit portal vein.

Dispersed single smooth muscle cells of rabbit portal vein were prepared by treatment with collagenase and trypsin. The muscle cells were 100-300 micron in length, 5-10 micron in maximum width and cylindrical in shape. In inside-out membrane patches, two different amplitudes of ionic currents were recorded, and these single channel conductances were 273 pS (KL-channel) and 92 pS (KS-channel), when both sides of the membrane were exposed to 142 mM K+ solution. The channel conductances depended on concentrations of K+ on both sides of the membrane. When K+ were replaced with Na+ or Tris+, these single-channel currents were abolished. When the concentration of Ca2+ inside the membrane was greater than 10(-7) M, the channel activity was enhanced but there was enhancement when Ca2+ was applied to the extracellular membrane surface, in concentrations ranging between 10(-9) and 10(-3) M. During application of tetraethylammonium (TEA+; 1-10 mM) to the intracellular membrane surface, amplitudes of the single-channel current of both types of the K-channel were not modified. By contrast application of TEA+ (0.1-1 mM) to the extracellular membrane surface, reduced the amplitudes of the current and increased noise levels during the open-state of the KL-channels, but did not have such an effect on the KS-channel. We conclude that there are at least two different Ca-dependent K-channels distributed on the smooth muscle membrane of the rabbit portal vein. TEA+ applied to the extracellular membrane surface blocks activation of the KL-channel, but not that of the KS-channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of calcium antagonists on smooth muscle membranes of the canine stomach.

In circular muscles of the canine stomach, diltiazem (greater than 3 X 10(-6)M) depolarized and nicardipine (greater than 10(-6)M) hyperpolarized the membrane. Diltiazem (greater than 5 X 10(-6)M) or nicardipine (greater than 3 X 10(-7M) inhibited the plateau potential of spontaneously generated or electrically evoked action potential. In Na-deficient solution (between 137 and 30 mM Na), diltiazem and nicardipine selectively inhibited the plateau potential. In Na- (15 mM Na) or Ca-deficient (0.25 mM Ca) solution, spontaneously generated action potential ceased, and only graded responses were evoked by electrical stimulation. These graded responses were inhibited by diltiazem (greater than 5 X 10(-6)M) or nicardipine (greater than 3 X 10(-7)M). The ionic contribution for generation of action potential in this muscle cell was discussed in relation to actions of Ca antagonists.

Action Potentials↗
PubMed1985

Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia.

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Multiple primary malignancies in childhood cancer.

A total of 2,609 cases of childhood cancer (9,012 person-years), among which there were nine cases of second primary malignant neoplasms, were collected from six institutions. The expected number of second primary cancers was 0.88, and the observed/expected (O/E) ratio was 10.22. The estimated incidence of multiple primary cancers in children with primary cancers was 99.9 per 100,000. The tumor registry of Kanagawa Prefecture had 1,317 cases of childhood cancer with 3,326.4 person-years, among which six multiple primary cancer cases were reported. The O/E ratio was 18.4 with 180.3/100,000 person-years at risk in this series. A total of 51 cases of multiple primary cancer, including 20 synchronous cases, were reported by four major registries of childhood cancers. Frequent association with nervous tissue tumors was noted. In 17 cases the second tumor followed retinoblastoma, and most second tumors were related to radiation therapy. In the remaining 14 cases the second tumors varied; hematopoietic neoplasms in seven, thyroid carcinoma in three, and bone and connective tissue tumors in four.

Adolescent↗
PubMed1984

Bradykinin-induced rapid breakdown of phosphatidylinositol 4,5-bisphosphate in neuroblastoma X glioma hybrid NG108-15 cells.

External application of bradykinin to neuroblastoma X glioma hybrid NG108-15 cells produced a sustained depolarization preceded by a transient hyperpolarization. Bradykinin also increased the frequency of miniature end-plate potentials recorded from cultured striated muscle cells which had been innervated by NG108-15 cells. Parallelism between facilitative phases of miniature end-plate potentials and depolarization indicates that bradykinin caused an enhanced synaptic transmission from NG108-15 cells due to depolarization. Effects of bradykinin on phospholipid metabolism in the hybrid cells were then examined to shed light upon the mechanism by which bradykinin-receptor interaction leads to facilitation of synaptic transmission. Bradykinin induced specific incorporation of 32Pi into phosphatidic acid and phosphatidylinositol without affecting [3H]glycerol incorporation into these phospholipids by 10 min after its addition. The addition of bradykinin to hybrid cells prelabeled with 32Pi caused a transient decrease (maximal effect seen at 10-30 s) in the radioactivity from phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2) which was followed by the accumulation of radioactivity in phosphatidic acid and phosphatidylinositol. A Ca2+ ionophore, A23187, failed to induce the initial degradation of PI-4,5-P2. The data show that the magnitudes of bradykinin-induced PI-4,5-P2 degradation and membrane potential changes in NG108-15 cells are both dependent on the concentration of bradykinin and that the degradation of PI-4,5-P2 precedes the electrophysiological responses. Taken together with the finding that bradykinin induced a transient increase in Ca2+ influx (at 10-20 s), it appears that a rapid and transient degradation of PI-4,5-P2 might be related to the initiation of the NG108-15 cell activities through mobilization of extracellular Ca2+ into the cells.

Animals↗
PubMed1983

A case of T-cell chronic lymphocytic leukemia (T-CLL) expressing a peculiar phenotype (E+, OKM1+, Leu 1+, OKT3- and IgG EA-).

A case of chronic leukemia is reported. Malignant cells had the morphology of lymphocytes and an affinity for skin. Cytochemically, they were peroxidase negative, and NaF-resistant alpha-naphthyl esterase positive. The peripheral mononuclear cells formed E-rosettes and reacted with Leu 1 and OKM1. They were unreactive with OKT3, OKT4, OKT6, OKT8, and OKIa1. The cells did not possess surface IG, C3b receptors, or IgG Fc receptors (EAIgG). They responded weakly to phytohemagglutinin, and did not respond to concanavalin A. The cells did not adhere to Petri dishes or phagocytose latex beads. It is concluded that it was a case of OKT3-, OKM1+, EAIgG- T-cell chronic lymphocytic leukemia. This suggests that OKT3 does not recognize all peripheral T-cells, and that OKM1 is not specific for the monocyte-myeloid lineage. These cells may be useful in the characterization of E+, OKM1+ subset of peripheral mononuclear cells.

Adult↗
PubMed1983

A multicentre double-blind comparative trial of zimeldine and imipramine in primary major depressive disorders.

Zimeldine, a new antidepressant with a selective inhibition of 5-HT reuptake, was compared with imipramine in a double-blind comparative study. The trial was conducted on 95 patients with primary major depressive disorder, of endogenous character. During the 4-week study period clinical efficacy was evaluated by using the Hamilton Depression (HAM-D) scale, Beck's Inventory and global ratings. Zimeldine (100 mg b.d.) was shown to have as good an antidepressive effect as imipramine (50 mg t.d.s.) when evaluated on the HAM-D scale. Assessment of the symptom improvement on this rating scale suggested that zimeldine was more effective in improving the patient's insight of the disease. There was no significant difference between zimeldine and imipramine as assessed by a final global improvement rating scale as well as by the patient's own impression. Exploratory data analysis revealed that zimeldine was significantly more effective than imipramine in the following groups; patients over 40 years of age; patients whose initial onset of illness occurred at over 40 years; patients with a history of at least three episodes of depressive illness; patients with mild to moderate depression; and patients who had previously failed to show an appreciable response to other antidepressant treatment. Analysis of global safety ratings revealed that zimeldine is significantly safer than imipramine, with a lower incidence of adverse symptoms involving the autonomic nervous system, especially anticholinergic reactions. No significant difference was observed between the two groups with respect to abnormal laboratory reports. One zimeldine patient developed symptoms suggesting a hypersensitivity reaction (fever, skin eruption and elevation of plasma levels of transaminases), which led to the patient's withdrawal from drug treatment.

Adolescent↗
PubMed1983

Hairy cell leukemia: a report of 10 cases in Japan and characterization of anti-hairy cell sera.

A series of 10 cases of hairy cell leukemia (HCL) in native Japanese patients was studied. The clinicopathological features and the phenotype of the leukemic cells were compared with those of HCL in Western countries. The clinical pictures were similar to those in Western countries but some hematological findings were different. The Japanese patients had more marked leukocytosis, less granulocytopenia and thrombocytopenia, and no dry tap on bone marrow aspiration. The phenotype of hairy cells was much the same in both areas. Two kinds of anti-hairy cell sera were raised in rabbits. One (AHS 406) was obtained from rabbits immunized by injecting whole hairy cells. The other (alpha HC-G and alpha HC-M) was obtained by injection of membrane glycoproteins partially purified from hairy cells. The reactivity of the former antiserum (AHS 406) against leukemic cells from a variety of leukemias including HCL and B-cell chronic lymphocytic leukemia was studied by an immunoprecipitation technique. AHS 406 defined three cell surface antigens on HCL, P-30, P-35 and GP-135 (30,000, 35,000 and 135,000 daltons respectively). These three components are expressed only on neoplastic B lymphocytes. Quantitative differences in expression were observed in different types of leukemia, although all three antigens were most strongly expressed in HCL. alpha HC-G showed reactivity similar to that of OKIa-1. alpha HC-M reacted with hairy cells but not with other leukemic cells except mature granulocytes of chronic myelocytic leukemia. It also reacted with most granulocytes and a few mononuclear cells in normal peripheral blood. Preliminary immunochemical studies suggest that alpha HC-M reacts with a glycoprotein with a molecular weight of 26,000.

Adult↗
PubMed1982

Survival of host mast cells after establishment of hematopoietic chimerism by graft-versus-host reaction in nonirradiated F1 hybrid mice.

Since the tissue mast cell has been shown to be progeny of the multipotential hematopoietic stem cell (CFU-S), and the CFU-S is a sensitive target of graft-versus-host (GVH) reaction, we examined whether or not the mast cell is also the target of GVH reaction. Giant granules of C57BL/6-bgJ/bgJ mice were used as a marker of donor cells. When 10(8) spleen cells of C57BL/6-bgJ/bgJ mice were injected into nonirradiated (C57BL/6 X CBA)F1 hybrid mice, erythrocytes and neutrophils became of donor type in about one-half of the recipient mice. In the bone marrow and spleen of the chimeric mice, the CFU-S was of donor type as well. In contrast, mast cells of host type remained in many tissues of the chimeras. Moreover, mast cell precursors with capabilities of proliferation and differentiation were preserved in the skin of chimeras. The present results suggest that the effect of systemic GVH reaction on mature mast cells and the mast cell precursor fixed in the skin is significantly less severe than that on the CFU-S itself.

Animals↗