The incidences of esophageal, gastric, and colon cancers throughout the world are reviewed, together with epidemiological information on their causes. Trace elements including zinc, selenium, and molybdenum, and vitamins including A, C, and E are also discussed with respect to their roles as inhibitory agents of cancer and their possible assay in biological fluids as prognostic indicators in patients with cancer of the gastrointestinal tract. Animal experiments based on epidemiological evidence suggest that the carcinogenesis of the gastrointestinal tract is influenced by dietary factors.

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Viral oncolysis has been clinically observed for a long time without practical application, because it has lacked basic study of its mechanism and needed special conditions between tumor and virus. Since Asada reported improvements of 79 patients from 90 terminal cancer cases with administration of mumps virus (MV) (1974), many good results of following trials have appeared in the literature, which have never included papers on the tumors of the central nervous system. The author planned to apply this attractive therapy by the administration of MV vaccine in the malignant brain tumors. So this paper reported the author's experimental results about whether MV had the affinity with tumors in the central nervous system and what was the mechanism of oncolytic effects of MV if it existed.
Materials and methods: MV was used as the purified M V solution for vaccinal injection and target cells were cultured human glioma cells of an established cell line (MG-178) and cultured brain tumor cells taken from operative specimens of 49 tumors of 12 kinds. The trypsinized cells were cultured in monolayer sheet and challenged to MV. Thereafter, intracellular MV antigen by the direct fluorescein antibody methods was checked and followed by the measurements of virus titer, which were indicated as MV proliferation curve. MV-infected cultured brain tumor cells were chronologically sampled for cell growth curve by trypan blue exclusion method, viability tests using the fluorescein diacetate, cell kinetic studies with the propidium iodide through a flow cytometry, and morphological studies. Human brain tumor cells were cultivated on the chorioallantoic membrane (CAM) of fertile chicken eggs and challenged to MV in the same manner. After nodule formation of cultured cells, MV antigens and proliferation of MV were studied with morphological observation.
Results and summary:
1) M V antigens were demonstrated in 19 cases of 20 sampled tumors. Three days after the inoculation of MV, morphologically cytolytic changes began to appear in the infected tumor cells in parallel with proliferation of MV. This phenomenon resulted in the growth inhibition of cultured brain tumor cells in MG-178 cells and 39 cases of 49 sampled tumors (79.6%).2 ) In this experimental model, MV showed a good affinity with brain tumor cells and monophasically excellent proliferation. It is thought to be more sensitive to the cells with more cellular activities. Brain tumor cells showed cytolytic changes in parallel with the decrease of viability of cultured tumor cells. These biomorphological changes of brain tumor cells might come from the disappearance of the cells in S and G2 M phase followed by no progression to S phase, showing a quite different pattern from that of known anticancer agents.3) This phenomenon might be considered as the mechanism of destruction of cultured brain tumor cells by MV inoculation, i. e., oncolysis by MV'. MV in tumor nodules on CAM did not cause morphological changes in cultivated brain tumors, so this experiment gave us the knowledge of antitumor effects (oncolytic) of MV, and, moreover, suggested that we have to develop the method for administration of more dosis of MV for nodule-type brain tumors.

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Alpha 1-adrenoceptor stimulation of the rat left ventricular papillary muscle of phenylephrine in the presence of propranolol resulted in rapid breakdown of phosphatidyl-inositol-4,5bisphosphate (PI-4,5-P₂) and formation of inositol trisphosphate (IP₃) with a triphasic inotropic response; a transient positive inotropic effect (PIE) followed by a transient negative inotropic effect (NIE) and a sustained PIE.
Inhibition of PI-4,5-P₂ hy drolysis by the α₁-adrenoceptor antagonist, prazosin, or the PI-4,5-P₂ phosphodiesterase inhibitor, neomycin, blocked all components of inotropic responses.
A combined addition of 2,3-diphosphoglyceric acid, a competitive inhibitor of IP3 p hosphatase, with phenylephrine doubled IP3 formation and potentiated the initial phases of inotropic responses, but had no effect on the sustained phase of PIE. Nifedipine and Mn²⁺ did not block the trans ient PIE but inhibited the sustained PIE.
An addition of phorbol-12,13-dibutyrate (PDBu) alone or in combination with caffeine or A-23187 failed to provoke a sustained PIE, but pretreatment with this phorbol ester (1-100nM) for 30 minutes resulted in dose-dependent potentiation of α₁-adrenoceptor-mediated sustained PIE.
Alpha 1 -adrenoceptor agonist, phenylephrine, in the presence of propranolol restored contractile activity in the high K-depolarized papillary muscle preparation in a time course similar to that of the development in the sustained PIE. The restored contractile activity was markedly potentiated by pretreatment with PDBu.
These results suggest that th e inotropic effects mediated by cardiac ai-adrenoceptor stimulation occur through the phosphodiesteratic cleavage of PI-4,5-P₂, such that IP₃ may produce transient inotropic effects by mobilizing intracellular Ca²⁺, while diacylglycerol, concomitant with IP₃-induced Ca²⁺ mobilization or in the presence of an unknown co-factor (s)that is also generated on α₁-adrenoceptor stimulation, may provoke a sustained PIE by potentiating slow Ca²⁺ channels through the activation of protein kinase C.

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The purpose of the present study was to determine the involvement of Ca²⁺ (Mg²⁺)-ATPase, guanylate cyclase, PGI₂ synthesis and/or glutathion in mechanism of vascular smooth muscle relaxation by nitro- and nitroso-vasodilator drugs. Vasodilators used in the experiment were nitroglycerin (GTN), isosorbide dinitrate (ISD), N-nitroso-morpholino aminoacetonitrile (SIN-1A, an active metabolite of molsidomine) and sodium nitroprusside (SN P).
Guinea-pig thoracic aorta strips were suspended in tissue bath which permitt cotinuous recording of isometric tension. Relaxation was measured in submaximally contracted strips with noradrenaline (NA,30 μM) or PGF₂α (5 μM) and dose-relaxation curves were constructed to show the effects or IC₅₀ ovalues of vasodilators.
The cumulative concentrations of GTN from 0.001 to 100.0 μM and ISD from 0.01 to 100.0 μM relaxed the contracted strips in a concentration dependent manner. IC₅₀values in GTN and ISD were 0.26 μM and 4.8 μM, respectively in the NA-contracted preparation. When tranylcypromine (TC), indomethacin (IDM) and/or 15 HPETE, each 10 μM which inhibit the production of PGI₂, were added to the bath 20 min before NA application, the relaxation by GTN or ISD was attenuated to cause a significant shift of dose-relaxation curves to the right and IC₅₀ values obtained from the curves was larger than the control one in each case. On the other hand, TC, IDM and 15 HPETE failed to alter the enhancement by GTN and ISD in Ca²⁺ (Mg²⁺)-ATPase activity in the microsome fraction from guinea pig thoracic aorta smooth muscle.
The tension develope d by NA or PGF₂α was decreased by the cumulative concentrations of SIN-1A from 0.001 to 100.0 μM or SNP 0.001 to 100.0 μM in a concentration dependen t manner. The relaxation was attenuated in the presence of methylene blue (MB) or 6-anilino-5,8-quinolinedione (AQD), which is reported as a guanylate cyclase inhibitor. SIN-1A was found to stimulate the activity of Ca²⁺ (Mg²⁺)-ATPase in the microsome fraction from guinea pig aorta. Inorganic nitroso complex salt SNP in the low concentration exerted a similar effect on Ca²⁺ (Mg²⁺)-ATPase activity to SIN-1A, but not in the high concentration of the drug. MB inhibited the stimulatory effect of SIN-1A in the Ca²⁺ (Mg²⁺) -ATPase activity, while AQD had no effect on the ATPase activity. The addition of SNP to the strips in the high concentration caused a depression of contractions obtained with NA even after removal of SNP from the bath.
This depression was completely reversible upon the addition of glutathion 100 μM or MB 1.0 μM. The effects of SNP on vascular tissue may be, in part, account for the decrease in glutathion content in the smooth muscle of the tissue.
These results suggest that GTN and ISD elicit vasodilation, partially through the stimulation of Ca²⁺ pump ATPase activity and also through the accelerated production of PGI₂ in arterial blood vessel, and that SIN-1A and SNP dilate the blood vessel by the stimulatory effect on the Ca²⁺ pump ATPase as well as guanylate cyclase activity, although the glutathion content in the vascular tissue may decrease after the application of SNP because of a possible interaction between Fe³⁺-prussiate and SH-group of this active peptide.

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Anti-anginal vasodilator trimetazidine and it's derivatives [n₂-TMZ 2HCL, N-2-hydroxyethoxyethyl-N' - (2",3",4"-trimethoxybenzyl) -piperazine dihydrochloride; n₂-DMZ 2HCL, N-2hydroxyethoxyethyl-N"- (3",4"- dimethoxybenzyl) -piperazine dihydrochloride] were comparatively studied with special reference to the inhibitory effects on Ca²⁺ mobilization of guinea pig thoracic aorta (in vitro), rabbit coronary vessel (in vivo) and human platelets (in vitro), and the following results were obtained.
1) Pre-treatment with trimetaz idine (3×10^-4M), procaine (3×10^-4M) and n₂-TMZ (10^-3M)inhibited Ca- and noradrenaline-induced contractions, but failed to affect PGF_2α-in duced contractions in the guinea pig thoracic aorta.
2) ST-T wave changes on the ECG induce d by an intravenous administration of vasopressin were inhibited within 10 minutes after an intravenous administration of 15 to 20 mg/kg of trimetazidine and/or 20 to 40 mg/kg of n₂-TMZ in the rabbits.
3) Trimetazidine (3×10^-3M) strongly inhibited the primary human platelet agglutination induced by ADP, while n2-TMZ (3×10^-4M) strongly inhibited the secondary a gglutination induced by arachidonic acid.
4) Trimetazidine (3×10M ), procaine (3×10^-4M) and n2-TMZ (10^-3M) had little effect on the basic activity of Ca²⁺ ( Mg²⁺) - ATPase in microsomes from the guinea pig tho r acic aorta, but completely inhibited the enzyme activity stimulated by nitroso-compo und, SIN-1A (1.0 mM).
These results suggest that the primary pharmacologic action of trimetazidine and n₂-TMZ on blood vessel occurs because of an affinity to the smooth muscle cell membrane and the membrane stabilization through an inhibitory effect on Ca²⁺ mobilization. In this regard, the action of these drugs may be similar to that of procaine.

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In Blepharospasm, irregular spasms of orbicularis oculi and continuous spasms of M. levator palpebrae superioris were recorded by needle EMG. But, in spite of severe spasms of M. orbicularis oculi, M. levator palpebrae superioris was recorded cyclic spasms in Meige syndro me. This difference between Blepharospasm and Meige syndrome is not clear today. There were the prolonged latency and the increased amplitude in R2 compoment of blink reflex of Meige syndrome. The basal ganglia influences trigeminal nerve, and so, diseases of the basal ganglia affect the blink reflex. Several studies have shown relationship between the blink reflex and the dopamine activity. Our results indicate that there is an abnormal excitatory drive of facial muscle from the abnormal basal ganglia.

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