Biomedical subjects
Publications and source records attributed to T Iijima.
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It has long been discussed why dihydropyridine calcium antagonists are less cardioactive than other calcium antagonists at doses equally effective on vascular smooth muscle [5, 12]. Recently, it has been reported that dihydropyridine calcium antagonists, unlike other calcium antagonists, inhibit adenosine 3',5'-cyclic monophosphate phosphodiesterase in various tissue preparations [2, 8, 10]. It has also been reported that intracellularly applied adenosine 3',5'-cyclic monophosphate increases the slow inward current in heart cells [1, 11, 13]. Therefore, present experiments were carried out to elucidate the effects of intracellularly applied calcium antagonists on the slow inward current of single ventricular cells with the patch-clamp, 'whole-cell recording', technique [3]. Nifedipine, nicardipine and isobutylmethylxanthine, when applied intracellularly using the patch-clamp microelectrode, increased the plateau and the duration of action potentials of single ventricular heart cells of the guinea-pig. The augmentation of the action potential was abolished by superfusing the cell with nifedipine. D600 and diltiazem when applied either intra- or extra-cellularly decreased the plateau and the duration of the action potential. Under voltage clamp conditions, intracellularly applied nifedipine, nicardipine and isobutylmethylxanthine increased the slow inward current, whereas D600 and diltiazem decreased the current. The holding current and the current at the end of 200-ms clamp pulses were not modified. Thus, dihydropyridine calcium antagonists probably increase the slow inward current from the inside of the cell and attenuate the calcium entry blocking activities in heart cells. This must partly be a reason why dihydropyridine calcium antagonists are less cardioactive than D600 and diltiazem at doses equally effective on vascular smooth muscle.
Mode and mechanism of action of 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212) were investigated exclusively on dogs both in vivo and in vitro. When assessed by intra-arterial administration in isolated, blood-perfused papillary muscle, sinoatrial node and atrioventricular (AV) node preparations, OPC -8212 produced a positive inotropic effect scarcely causing either positive or negative chronotropic and coronary vasodilator effects. AV nodal conduction was slightly facilitated with OPC -8212, whereas ventricular automaticity was rather suppressed. No arrhythmias were produced. Thus, OPC -8212 is highly specific for force. In heart-lung preparations OPC -8212 improved cardiac function depressed with pentobarbital, and caused bradycardia. In trabecular muscles of the right ventricle (hereafter simply called ventricular muscles) OPC -8212 produced a concentration-dependent positive inotropic effect in the presence of the beta 1-adrenoceptor antagonist, atenolol. This indicates that the positive inotropic effect of OPC -8212 is not mediated through a beta-adrenoceptor mechanism. In ventricular muscles OPC -8212 increased plateau potentials of normal action potentials in the presence of atenolol. In K+-depolarized ventricular muscles OPC -8212 increased overshoot potentials and durations of slow response action potentials in the presence of atenolol. These suggest an increase in the slow inward current to underlie the positive inotropic effect of OPC -8212. In ventricular muscles OPC -8212 shortened total duration of contraction and time to peak tension in the presence of atenolol. In ventricular muscles OPC -8212 increased force of contraction and intracellular concentrations of cyclic AMP in a parallel way in time course in the presence of atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)
The fine structure of microgametogenesis and fertilization in Leucocytozoon caulleryi was studied. When the peripheral blood of chickens containing mature gametocytes was withdrawn or ingested by Culicoides arakawae , differentiation of the microgametocytes began immediately. The cytoplasm of host cell and the outer membrane of the microgametocyte disappeared. Axoneme formation began in the cytoplasm and the condensed chromatin masses were observed at the periphery of the nucleus of microgametocyte after disappearance of the nuclear membrane. The axonemes and chromatin masses migrated to the surface of the microgametocyte and participated in the formation of flagellar buds. The flagellar buds passed through interruptions of the inner membrane and were surrounded by the outer membrane of the microgametocyte . The microgametocyte formed eight slender microgametes. The microgamete was a long undulated thread-like structure and composed of a single axoneme and a nucleus. The nucleus was located at the mid to anterior region of the microgamete . The axoneme consisted of nine peripheral doublets arranged around two central microtubules. Penetration of the macrogamete by the microgamete occurred rapidly after ingestion. The axoneme and nucleus of the microgamete were seen free in the cytoplasm and nucleus of a fertilized macrogamete.
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The changes in rat serum protein distribution after partial hepatectomy were examined using two-dimensional electrophoresis, utilizing isoelectric focusing in polyacrylamide gel in the first dimension and pore gradient polyacrylamide gel electrophoresis in the second dimension. Drastic decreases in amount of protein were observed at more than twenty spot positions, and drastic increases in amount or newly appeared proteins were observed at eight spot positions. The amounts of albumin, immunoglobulin M and alpha 2-macroglobulin did not change relatively after hepatectomy. The time course of the changes was examined using a densitometer, and it was observed that almost all the serum proteins changed drastically at 24 h after hepatectomy.
The morphological changes induced in the autonomic nerves of the rat anococcygeus muscle after the injection of quinacrine (QC, 100 or 200 mg/kg) were examined by electron microscopy in order to clarify the nature of QC-binding nerves seen at the fluorescence-microscopic level. A correspondence between granular QC fluorescence and many lysosomal dense bodies is observed both in the cytoplasm of muscle cells and in non-adrenergic, non-cholinergic (NANC) axons during the first few days following injection. A number of brilliantly fluorescent fibres is observed 1 week after injection. At the ultrastructural level, these fibres seem to correlate with NANC axons which are crowded with many dense bodies and large granular vesicles. Notably, some lysosomal dense bodies contain many large granular vesicles. The effects of QC injection on the ultrastructure of adrenergic axons have also been observed, but are not so marked as in the NANC axons. The administration of QC did not cause complete degeneration of the NANC nerves, though degenerating axons were sometimes observed. The present data indicate that most, if not all, QC-binding nerves observed at the fluorescence-microscopic level correspond to NANC nerves at the electron-microscopic level. Furthermore, NANC axons appear to contain a considerable amount of ATP concentrated in the large granular vesicles.
Immunotherapy with levamisole (LMS) and combined splenectomy were performed in the cases of stages III and IV gastric cancer of the upper and middle stomach and associated with total gastrectomy. The cell-mediated immunity and the survival rates for both groups were compared with controls. Combined splenectomy was not effective for cases of stage III gastric cancer, but was effective for those in stage IV. Comparing the cumulative survival rates of the immunotherapy group with the controls, cases of stages III and IV gastric cancer without splenectomy, the survival rate of those with immunotherapy was higher than that of the control group in the cases of the stage III, but the result was reverse in cases of stage IV gastric cancer. Changes in the cell-mediated immunity correlated with the survival rates.
Effects of Mn2+ (10(-4) to 10(-3) M) and diltiazem (10(-7) to 10(-6) M) on the spontaneous action potential were studied in small preparations of the canine atrio-ventricular (A-V) node. Mn2+ and diltiazem decreased the maximum rate of rise (Vmax), amplitude of the action potential and rate of depolarization of the slow diastolic depolarization in a concentration-dependent manner. The spontaneous action potentials were depressed by the drugs, and were changed into abortive action potentials. Decrease in the rate of depolarization of the slow diastolic potential was much more prominent with Mn2+ than with diltiazem. These results indicate that the slow inward current may not play an important role in the initiation of the slow diastolic depolarization of the A-V node cell.
Using the histochemical method by Karnovsky and Roots, localization of acetylcholinesterase (AChE) activity has been examined in the autonomic nerves of the rat anococcygeus muscle. The SPG fluorescence method for adrenergic nerves was also employed. By light microscopy the anococcygeus muscle received a much scarcer innervation of lightly stained fibres displaying the AChE reaction than it did of adrenergic fibres. At the ultrastructural level, occasional axons of both adrenergic and non-adrenergic categories were faintly stained for the AChE reaction after 5-15 min incubation and moderately stained after 30-60 min incubation at 0 degrees C. The present findings support the previous colorimetric data reported on the presence of AChE activity in the muscle. However, the typical cholinergic axons observed at the ultrastructural level did not show a heavy enough AChE activity to suggest their cholinergic nature.
In animal experiment, 5 X 10(5) MH-134 tumor cells were transplanted s.c. on the back of the C3H/He mice. Three, seven, 14 and 21 days after tumor transplantation, splenectomy or sham operation were performed and the tumor growth and survival days were examined in each group. As the results, the tumor growth was inhibited and the survival days prolonged not only in the group splenectomized three days but also 21 days after tumor transplantation. Clinically, the effect of splenectomy in combination with immunotherapy on cell-mediated immunity and the survival rates were studied in the gastric cancer patients of upper and middle stomach with 90 cases of stage III and 48 cases at stage IV, totalling 138 cases who underwent total gastrectomy during 1965 and 1981. Immunotherapy was conducted with immunomodulator levamisole at a daily dose of 150 mg, three consecutive days every other week. As a result, splenectomy was not effective for advanced gastric cancer at stage III and in the patients spleen should be retained for immunotherapy. Splenectomy for gastric cancer at stage IV, particularly in combination with immunotherapy, produced augmentation of cell-mediated immunity and longer survival as well. Complications caused by splenectomy were small.
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