Platelet adhesiveness is generally measured by a glass-beads column method (GBC method), as other available methods using collagen and subendothelium are too complex for clinical use.
We have studied a new method of measuring platelet adhesiveness to collagen fibers supported on sepharose (CS method).
The results of fundamental st udies on platelet adhesiveness using CS method were as follows:
1. W ith increasing collagen concentration, platelet adhesiveness increased.
2. Platelet adhesiveness was not change at a stirring speed of 150 to 15,00 rpm and at a stirring time of over one minitue.
3. Platelet adhesivenes s was not change in the presence of above 0.5 mM EDTA which inhibited platelet aggregation.
4. The influen ce of the platelet count at 10-40×10⁴/μl on the platelet adhesiveness did not observed, but at above 60×10⁴/μl, platelet adhesiveness slightly decreased.
5. After storage for 72 hr at room temperature, platelet adhesiv eness to collagen was slightly decreased and markedly decreased (below 50% of control values) after 7 days.
6. Platelets adhered normally to collagen fibers without extracellular von Willeb rand factor and divalent cations, and by pretreatment of platelets with neuraminidase reducing platelet surface negative charge.
7. The data o btained with the GBC and CS methods in healthy adults correlated signif i cantly. This CS method is simpler than other methods employing collagen and closer to in vivo conditions than the GBC method. Thease results suggeste d that the mechanism of platelet adhesiveness to collagen fibers differ from that of adhesion to glass.

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We have studied a new technique of measuring platelet adhesiveness to using collagen fibers supported on sepharose (CS m ethod). This was compared with glass beads column method (GBC method) and Baumgartner's method in measuring platelet adhesiveness in patients with platelet function abnormalities and assessing the effect of antiplatelet drugs.
The results were as follows:
1. In thrombasthenia, plate let adhesiveness was 0% in the GBC method and normal in the CS and Baumgartner's method. In Bernard-Soulier syndrome and von Willebrand's disease, it was decreased in all methods especially in Baumgartner's method.
2. In liver cirrhosis, renal failure, and multiple myelom a, platelet adhesiveness was decreased in all diseases using the GBC method and in liver cirrhosis using the CS method.
3. In myeloproliferative disorders, it was significantly decreased in the GB C method, but normal in the other two. In Baumgartner's method, thrombi were increased.
4. Platelet adhesiveness was not inhibited by antiplatelet dru gs at concentrations that inhibited platelet aggregation. Clinically, an inhibitory effect was found in the GBC method but not in the CS method after two or three months of administration of aspirin.
5. In cerebral infarction, platelet adhesiveness was significantly increa sed in the GBC and CS metheds, but there was no correlation between the two methods.
6. In diabetes mellitus (DM) without nephropathy, it w as significantly increased in both methods, and normal in Baumgartner's method. In DM with nephropathy, it was significantly decreased in the GBC method, and normal in the other two. Measurement of platelet adhesiveness by CS and GBC method proved effective for diagnosis platelet function disorders.

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Phospholipase (PLase) activity in the gastric mucosa and intragastric total bile acids both were assayed in experimentally produced rat acute gastric mucosal lesions (AGML) and in human AGML, and the following results were obtained.
1. Rats with duodenal ligation in which bi le acids are involved in the development of AGML showed a lower PC content and higher contents of lyso bodies, FFA and PLase in the gastric mucosa, and a higher ulcer index than those with pyloric ligation without the involvement of bile acids.
2. In rats w ith duodenal ligation, the PLase activity changed in parallel with the intragastric total bile acids concentration.
3. In rats orally adm inistered with bile acids, PLase activity increased in the early period after the administration in parallel with the concentration and acidity of the bile acids.
4. In the human control group, PLase activity was high in the antral mucosa. Its activity showed no sex difference, but tended to increase with age, indicating the involvement of atrophic gastritis. In this group, the intragastric total bile acids concentration also showed no sex difference, but tended to increase with age.
5. PLase activity in the human gastric mucosa correlated with the intragastric total bile acids concentration, especially in the antrum.
6. In in vitro experiments using h uman gastric mucosa and bile, PLase activity increased with the increase of total bile acids concentration.
7. The human AGML group show ed the significantly higher PLase activity and intragastric total bile acids concentration than those in the control group. These results showed that PLase activity is markedly inc reased by the action of bile acids contained in the reflux of intestinal juice, enhancing the degradation of lipids (phospholipids)in the gastric mucosa. This is the initial stage in the process of breakage of the gastric mucosal barrier. Since the action of the bile acids seems principally the activation of PLase, this enzyme can be regarded as a gastric mucosal barrier breaker.

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The alteration in sinusoidal and bile canaliculus surface of hepatocyte plasma membrane in intrahepatic cholestasis was assessed biochemically and by electron microscopy. Asialoglycoproteinreceptor (ASGP-RP) was used as an indicator for sinusoidal surface and 5'-nucleotidase (5'-N), a maker enzyme, for bile canaliculus surface. Changes in ASGP-RP and 5'-N of hepatic cell microsome as well as isolated hepatic cell membrane were analysed. Cytochrome b₅ (b₅) and NADPH cytochrome C reductase (reductase) activities were also analysed.¹²⁵I-asialoorosomucoid (asialo α1 AG) was used to evaluate the hepatic clearance, and changes in serum asialoglycoprotein (ASGP), transaminase, alkalinephosphatase (ALP) and total bilirubin (T. Bil) were measured. Alteration in sinusoidal and bile canaliculus surface structures were observed by electron microscopy.
Alpha-naphthylisothioc yanate (ANIT) 200mg/kg was injected in the stomach by stomach tube to produce ANIT intrahepatic cholestasis. Hepatic cell microsome was prepared by Ehrenreich's method and isolated hepatic cell membrane by Oscar's method, ASGP-RP was maesured by Aschwell's method, serum ASGP by Sawamura's method, b₅ and reductase by Oomura-Takesue's method and 5'-N by Heppel-Hilmoe's method.
Following results were obtained:
1) There was no significant cha nge in hepatic cell microsome ASGP-RP after administration of ANIT, while 5'-N activity diminished 50% on the first day.
2) Although there was no significant change in ASGP-RP of p lasma membrane preparation, significant redUction (48%) was obserbed in 5'-N activity on the first day.
3) No significant difference in half life of ¹²⁵I-asialo α1AG was ob served between ANIT administrated rats and the control group.
4) There was no significant cha nge in ASGP throughout this study.
5) Slight decrease (28%) in b₅ activity was observed on the t hird day.
6) There was no significant change in the reductase activity.
7) T. Bil, GOT, GPT, and ALP reached the peak value on the third day (22 times normal,3.5 times normal,4.6 times normal and 2.7 times normal, respectively) but only the ALP remained slightly elevated on the seventh day.
8) DilatatiOn of bile canaliculi and the decrease in microvilli weie otoerved On the first day by electron microscopy, while disappearance and swelling of inicrovilli were observed on the third day. Microvilli in the Disse's cavity decreased and shortened but was not a significant amount. Changes in bile canaliculi became minimal or recovered to the control and the microvilli in the, Disse's cavity was completly normal on the fifth and the seventh day.
These data indicates that sinusoidal surface is notaffected in ANIT acute in trahepatic cholestasis and the hepatic cell damage was minimal.

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Previous studies have shown that there is an interogan cycle of glutathione metabolism in which glutathione is translocated from liver into the blood plasma and bile. Recent studies indicate that the level of total glutathione (GSH GSSG) in rat plasma was found to be 22 to 27 nM GSH equivalents. Plasma glutathione is removed mainly by the kidney, which has high γ-gluta. myl transpeptidase actlvity.
A direct examination o f the inter-organ cycle of Glutathione metabolism was made by determining Glutathione levels in plasma and bile of rats. We sought here direct evidence for transport of Glutathione by examining the Glutathione levels of blood plasma and bile.
1) Plasma glutathione level in different blood vessels. Hight levels of Glutathione were founded in he patic vein plasma, relative to arterial and systemic venous levels. Thus Glutahtione synthesized in the liver is translocated to the plasma. It appears that GSH is continuously transported into the plasma and used in reactions which lead to formation of GSSG and other products.
2) Effect of administration of salin e, dbcAMP,8Brc AMP and Glucagon in plasma glutathione on different blood vessels. Administration of dbcAMP,8BrcAM P and Glucagon to rats caused marked decrease of liver glutathione contents. Glutathione contents of plasma was higher after injection dbcAMP,8BrcAMP and Glucagon than after injection of saline. It was seemed that cAMP activate the consum tion of Glutathione in the peripheral tissue.
3) Effect of administration of saline, dbcAMP,8BrcAMP and Glucagon on Glutathion e ofbile. Glutathion is translocated out of liver cells into the bile same as blood plasma. It was seemed that this decrease in the glutathione level of bile after injectio n of dbcAMP,8BrcAMP and Glucagon was accompanied by increase of γ-Glutamyltransferase activity on cell membrane. The results suggested that cAMP can induce glutathione degarda2ion and that this may be mediated by increase in T-glutamyltransferase activity.

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Myocardial reperfusion after ischemia and anoxia produces some changes in myocardial metabolism and ultrastructure which may lead to myocardial dysfunction known as reperfusion injury. However the pathogenesis of reperfusion injury is multifactorial and clear m echanisms responsible for its manifestation have not been presented. The present study was designed to investigate if reperfusion injury could be avoid or reduced by an appropriate pretreatment just before reperfusion.
Isolated hearts from fourty seven mongrel dogs were exposed to 30 minutes normothermic global ischemia in the Ringer-lactate solution maintained at 37°C. According to the types of a pretreatment just before reperfusion, the experiment was classified into four groups (Group I of no pretreatment as control group, Group II of pretreatment with 500ml of hyperkalemic (K 25mEq/l), alkalotic (pH7.8) Ringer lactate solution, Group III of pretreatment with hyperkalemic (K 25mEq/l), alkalotic (pH7.8) diluted autologus blood (Ht 20%), and Group IV of pretreatment with calcium-anntagonist (Verapamil) contained in hyperklemic (K 25mEq/l)alkalotic (pH 7.8) Ringer lactate solution. Moreover, Group IV was divided into four subgroups depending on the volume of Verapamil (IV of 0.04mg/l of Verapamil, IV b of 0.02mgit, IV c of 0.015mg/l, IV d of 0.01mg/t). After the pretreatment of 5 minutes infusion to the coronary arteries in each group except Group I,30 minutes reperfusion and one hour working were performed with the cardiac perfusion apparatus for isolated heart.
In Group I reperfused with diluted oxygenated blood of 20 to 25% of Ht and of pH7.4 at 37 °C, oxygen extraction was higher, but excess lactate was positive and redox potential (ΔEh) was negative at the early period of reperfusion. Positive excess lactate with negative ΔEh continued in the reperfusion period, although oxygen extraction was significantly low. These results suggest that augumented oxygen uptake in the initial reperfusion results in reperfusion injury. The value of CPK-MB in coronary venous blood was significantly higher and myocardial ATP was lower with increased myocardial calcium content and poor mitochondrial calcium uptake all through the period of reperfusion and working. Left ventricular function could not achieve to measure at the period. of 30 to 60 minutes after the beginning of working in some case of group I and it showed the poorest recovery if it could be measured. These results also suggest that these prolonged impairments arise from reperfusion injury. Electronmicroscopically, destruction of mitochondria with margination of nuclear chromatin and sometimes with a deposit of calcium in mitochondria was demonstrated. These morphological changes were irreversible even the period of working. In contrast, group II showed persistently higher oxygen extraction with negative excess lactate and positive ΔEh except the initial period of reperfusion, improved preservation of myocardial ATP, rapid decrease in myocardial calcium content with good mitochondria' calcium uptake, and best recovery of left ventricular function indicating best protective effect for reperfusion injury. Particularly, the value of myocardial calcium content returned to normal at the working period, although those in other 3 groups were significantly higher. Apparently, group II showed significantly better mitochondrial calcium uptake and exhibited greatest left ventricular stroke work index at lower left atrial pressure at the working period. Electron-microscopically, structural integrity was well preserved and essentially normal at the end of working period in this group.

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To investigate the etiology of essential hypertension, microcirculatory parameters (internal diameters of arterioles and venules, flow velocities and flow volumes) in human bulbar conjunctiva and blood viscosity were examined before and after administration of nifedipine (10 mg sublingually) and prazosin (1.0 mg per os). In addition, blood viscosity, blood pressure and heart rate were measured. Three groups were used: EH: 25 essential hypertensives with diastolic pressure >95 mmHg; C-I: 11 normotensives with transient hypertension or familial history of hypertension; C-: 21 normal controls.
Microcirculatory changes were observed u sing Tsushima's Intravital Video-Microscopic system, and flow velocities were measured by the Distance Meter method. Blood viscosities were measured by Low Shear 30 R (CONTRAVES).
Arterioles in the EH group were found significantly dilated when measured in the period from 30 to 60 minutes following nifedipine administration. Arterioles in the C- I group showed a trend toward dilation, whereas no changes were observed in the C-II group. The similarity in the responses of the EH and C- I groups to a Ca²⁺ antagonist indicates that Ca²⁺ dynamics play a role in the onset of the disease. This similarity also suggests the existence of hereditary factors in essential hypertension and that subjects of the C- I group are likely to become hypertensive in the future.
Because arterioles in the EH group showed a greater tendency to dilate than the C- I group in the period from 60 to 90 minutes following prazosin administration, and because no difference was found between the C- I and C- I groups, it is likely that al-receptors play an important role in the maintenance of hypertensive blood pressure by controlling arteriole tonicity.
The results from blood viscosity measurements indicate that viscosity is not a factor in the etiology of essential hypertension.
The question of whether microvessels in the human conjunctiva are “resistance vessels” or not, was investigated by studying changes in mean blood pressure and internal microvessel diameter. If the vessels are “resistance vessels”, their dilation should occur in parallel with a decreasing mean blood pressure. This pattern was seen in all 6 subjects tested in the EH group (arterioles, after nifedipine),3 of 4 in the C-I group, and only 1 out of 9 in the C-II group. In our study it is probable a large majority of subjects in the C- II group demonstrated autoregulation that prevented an excessive increase in blood flow volume, however, only a few subjects in the C-I group, and no subjects from the EH group demonstrated autoregulation.

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Pancoast's syndrome is characterized clinically by pain around the shoulder and down the arm, Horner's syndrome and atrophy of the muscles of the hand. This syndrome is, for the most part, caused by cancer of the apex of lung.
We report a case of esophageal carcinoma with typical Pancoast's syndrome.
A 67-year-old woman visited our hospital because of pain around the shou lder and down the arm.
Physical examinations revealed Horner's syndrome and a painless large tumor measuring about 8×10cm in size at right supraclavicular area.
Chest X-ray film showed paralysis of right phrenic nerve.
The upper gastrointestinal series revealed esophageal carcinoma and endoscopic examination revealed tumor measuring about 5×3×2cm at the level of c. a.25cm below the incisors.
Radiation therapy was effective on large tumor of supuraclavicular lesion and esophge al tumor.
The present case is considered to be valuable to report, because records of Pancoast's syndrome caused by esophageal carcinoma are very rare.

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Small early cancers have been rarely found at the esophago-gastric junction. We report a case of early cancer at this area after radiation therapy for esophageal cancer.
A 78-year-old man visited our hospital because of discomfort in swallowing.Twe yea rs ago he received the radiation therapy because of esophageal cancer.
The upper gastrointestinal series revealed no partic ular lesions at the esophago-gastric junction, but a small lesion of depressed type carcinoma in this area was found by the endoscopy plus biopsy technics. Histologically, the specimen revealed adenocarcinoma.

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