Over the past several years, significant progress has been made toward understanding the fundamental mechanisms of invasion and metastasis. In the past two decade, investigations in our laboratory have focused on the invasion and spread of cancer via extravascular fluid. In addition, the factors responsible for the progression of invasive tumors have been studied. Recent evidence indicates that, metastasis is caused by oncogenes. However, further studies are needed to predict metastatic aggressiveness, prevent local invasion, and identify and treat clinically silent micrometastases.

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Regarding the action mechanism of nitroglycerin and nitroso-compound which relaxes the vascular smooth muscle, I investigated the effects of the drugs on Ca²⁺-pump ATPase [Ca²⁺(Mg²⁺) - ATPase] activity of microsome prepared from pars arcus and thoraci us of aorta in guinea-pig, and the following results were obtained.
1) Ca2+ (Mg²⁺)- ATPase activity increas ed in a concentration dependent manner of Ca²⁺from 2.5 mM to 20 mM. The addition of Ca²⁺ ion brought about the increase in ATPase activity, which was greater than the Mg²⁺-ATPase activity.
2) Ouabain sensitive Na+, K+ (Mg²⁺-ATPase a ctivity was very little in the microsome of aorta.
3) Nitroglycerine (50 μM to 1.0 mM) and SIN-1 A (10, μM to 1.0 mM) peculiarly increased the Ca²⁺ (Mg²⁺) -ATPase activity (at Ca²⁺ 2.5 mM) of microsome of aorta, but they didn't exert any effect on Mg₂₊-ATPase activity. These drugs may enhance an affinity of Ca ion for the ATPase.
4) The Ca²⁺ (Mg²⁺) -ATPase activity of membrane system, i. e., the membraneous Ca²⁺pump ATPase which transfers intracellular Ca ions across the membrane takes part in the relaxation mechanism of vascular smooth muscle from spasmus by nitroglycerin and nitroso compound.

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It is generally suspected that microhemodynamic changes and hemorheological alterations may play main roles in the pathophysiology of diabetic microangiopathy. Normal subjects, borderline subjects and diabetic subjects were used for this experiment. This study was evaluated from two aspects, first; from the aspect of microhemodynamic change, second; from the aspect of clinical feature. To know the microhemodynamic changes of diabetes mellitus affter 75g-oral glucose tolerance test (75g-OGTT), diabetic subjects were classified into three subgroups; DM-1 group, DM-11 group and DM-111 group. In the increase of blood flow volume, DM-1 group responded to glucose administration more than 200% and DM-11 group responded less than 100%. DM-111 group was placed intermediately between DM-1 group and DM-I1 group. Furthermore, to know the relationship between clinical feature and microangiopathy of diabetes mellitus, diabetic subjects were subdivided into three subgroups; A group, B group and C group. A group was without retinopathy, B group was with simple retinopathy and C group was with proliferative retinopathy. They were examined for microhemodynamic changes of venules on the human bulbar conjunctiva and hemorheologicl alterations in peripheral blood before and after 75-OGTT. Materials and Methods
59 diabetic s ubjects including 23 DM-1,25 DM-11 and 11 DM-111 (23 A,20 B and 16C),11 borderline (borderline group) and 14 normal subjects (normal group) were examine d in this experiment. The venules (average internal diameter of 48 ±2.9 μm) on the bulbar conjunctiva were used for measuring of microhemodynamic changes in internal diameters and flow velocities by using Intra-Vital Video Microscopic System (IVVMS). The Distance Meter Method developed by Tsushima was used to determine blood flow velocities. Blood flow volumes were calculated by multiplying cross sectional area and average flow velocity on the assumption that the vessel cross section was round. Viscosities of whole blood and plasma were measured at 94.5 sec^-1 and 0.376 sec^-1 by using of Contraves Low Shear-30. In order to know the deformability of erythrocyte, the passage time of 40% red cell suspensions through the micropore filtration membrane (pore size of 5μm) under 10 cm H₂O pressure was measured. Factors of hemocoagulation and fibrinolysis were also measured (fibrinogen, antithrombin-111, a₂-macroglobulin, plasminogen and a₂-plasmin inhibitor).

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The influence of alprenolol, carteolol, indenolol, pindolol, practolol, and propranolol on the effect of isoproterenol in isolated guinea-pig atrial contraction rate was examined comparing their beta-blocking actions, and their influence on the responses of guinea-pig cornea and dorsal skin to the mechanical stimulation was tested comparing their local anaesthetic actions. Further, the effect of each drug to prevent the arrhythmic contractions, induced by electrical stimulation in spontaneous rhythmic contractions in isolated guinea-pig atria, was examined and the other effect to prolong the time required to arrest the spontaneous atrial contractions by addition of strophanthin-G in toxic dose, was tested, too.
1) Their beta-blocking actions in the rank order of efficiency were those of carteolol, pindolol, propranolol, alprenolol, indenolol, and practolol.
2) Their local anaesthetic action evaluated in cornea were ranged as those of propranolol, indenolol, and alprenolol in the order of efficiency; those of carteolol, pindolol, and practolol were very weak.
3) Their local anasthetic actions evaluated in dorsal skin were ranged as those of propranolol, alprenolol, indenolol, pindolol, practolol, and carteolol.
4) The effect to prevent the electrically ind uced arrhythmic contractions in the spontaneous atrial contraction was seen in propranolol, pindolol, alprenolol, and indenolol in the order of efficiency.
5) The effect to prolong the time, which is required to arrest atrial spontaneous contractions by strophanthin-G in the toxic dose, was seen in propranolol, alprenolol, pindolol, indenolol, and carteolol in the order of efficiency.
6) The effect of beta-blocking drug to antagonize to strophanthin-G cardiotoxicity is partly caused by its membrane stabilizing action which was tested in the experiment to examine the efficiency to prevent the arrhythmic contractions.

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We successfully treated a patient with duodenal ulcer of probable Dieulafoy's type by local injection of pure ethanol (EtOH). The patient was a 33-year-old male with tarry stool and epigastric pain. On admission, severe anemia, increased BUN, and positive stool occult blood reaction were observed. Emergency endoscopy revealed no marked changes in the esophagus and stomach except exposed blood vessels with pulsating bleeding in the posterior wall of bulbus. Immediately, EtOH was locally injected, and the bleeding stopped. A small and shallow mucosal defect was detected at this site. No rebleeding was observed, and he was discharged on the 21st hospital day. Though no pathohistological evaluation was performed, a diagnosis of exulceratio simplex (Dieulafoy) was made endoscopically. To our knowledge, only 3 patients with duodenal Dieulafoy's ulcer including our patient have been reported. In addition, it is notable that bleeding stopped by local injection of EtOH.

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