S. Aoyama

The study of the experimental peptic ulcer —Histamine and serotonin

Though it has been commonly said tha t it is extremely difficult to produce centra l gas t r ic and duodenal ulcers in dogs, the authors have succeeded in producing such ulcers in 40 exper imental cases. This procedure is to inject small dosis of Toyomycin into the cerebrum with s imultaneous inject ion of reserpin subcutaneously. The details of this method has been reported at the general meet ing of the Japan Gastroenterological Society held th is spring. From our exper iments , it is possible to say tha t ulcer may be produced when the area of s t imula t ionis at the hypothalamus and also by s t imula t ion of the tha lamus. It is also interest ing to note tha t all cases with cortical d is turbances resul ted with format ion of ulcer. Though this experiment was done with s imultaneous inject ion of reserpin, it is difficult to consider tha t the basal nucleus is the only focus for dis turbance of ulcer formation. There were some points of differences on the ulceration in the exper imenta l ulcers in dogs from the autopsy findings of hypertensive in t racerebra l bleeding. Ulcers were mainly l imited to the pyloric an t rum and the upper duodenum. There was no re la t ion between the area of central s t imulat ion and that of ulcer formation.

Fundamental studies of pancreatic secretion (III) the effects of some drugs and the central electric stimulation

Ligation of the thoracic duct resul t s in an edema and marked dilatat ion of lymphat ics of pancreas , while it does not impa i r the secretory funct ion of exocrine pancreas cells. Electron microscopic observations also reveal tha t the s l ight di la tat ion of secretory ducts, s l ight decrease in n u m b e r of zymogen granules, and widening and filling wi th a low density homogenous fluid like lymph of interacinal spaces. Ligation of pancreat ic duct resul ts in a s l ight edema and marked di latat ion of lymphat ics of pancreas, di la tat ion of pancreat ic duct, and sl ight vacuolizat ion of a par t of exocrine pancreas cells. Electron microscopic observations fu r t he r reveal tha t the ductules and interacinal spaces are filled up wi th a relat ively high densi ty homogenous fluid like pancrea t ic juice, but any significant degenera t ion of exoerine pancreas cells and islet cells are observed. In cont ras t with these findings described above, the macroscopic and light microscopic observat ions reveal much grave a l tera t ion of pancreas following ligation of both thorac ic and pancreat ic ducts, and the electron microscopic observat ions also reveal t ha t degenerat ion of qui te many of exocrine pancreas cells, di latat ion of secretory ducts, and infi l tration of intercellu lar and interacinal spaces wi th a relatively high density homogenous fluid like pancreat ic juice. Pancrea t ic juice s tagnated in the ductal system of pancreas due to Iigation of pancreat ic duct alone may be removed quickly th rough the lymphat ics indicating as elevated amylase level in per iphera l blood, while i t would infiltrate into interacinal as well as in tercel lu lar spaces due to impa i rmen t of removal of s tagnated pancreat ic juice following the l igation of bo th thorac ic and pancreat ic ducts. It is thus assumed tha t the lymphat ic s tas i s may play an impor tan t roll in addit ion to chemical effect of proteolytic enzyme of pancreat ic juice on es tab l i shment of degenerat ion of exocrine pancreas cells or pancreat ic necrosis.

Enzymological studies on lipase activity in pancreatic impairments

Studies on lipase act ivi ty par t icular ly with respect to the optimal pH of the enzyme were carr ied out using dogs wi th pancreat ic impai rments . Mater ia ls used were as follows; se ra f rom dog wi th exper imenta l pancreat i t is , wi th l igat ion of Pancreat ic duct or wi th total resect ion of pancreas. Serum, pancreat ic juice, homogenate of pancreat ic or l iver t issue f rom normal dog were also used. Lipase activity was measured by a procedure anologous to tha t which was descr ibed b y Vogel and Zieve, us ing the incubat ion sys tem consisted of refined olive oil and 0.35% deoxycholate Tr i s buffer. Lipase act ivi ty mesured at pH ranging f rom 6.7 to 9.7 at regular in t e rva l s of 0.3, which was confirmed with the use of pH meter . The pancreat ic juice and se rum were aslo subiected to e lect rophoret ic f rac t iona t ion us ing cellulose acetate membrane , upon which l ipase act ivi ty was determined by t i t ra t ion procedure with sodium hydroxide. In normal dogs, lipase act ivi ty in se rum was found to be max imum at pH7.9, whereas irL dogs wi th acute pancreat i t is , l ipase act ivi ty showed a significant elevat ion and the m a x i m u m activi ty was found at pH rang ing f rom 9.1 to 9.7. Wi th a resolut ion of acute change irt pancrease, a pa t t e rn of lipase act ivi ty re tu rned to tha t of normal serum. Lipase act ivi ty in pancreat ic juice f rom normal dog as well as in se rum f rom dog wi th l igat ion of pancreat ic duct were found to be m ax i mum at pH ranging f rom 9.l to 9.7. In con t ras t to this, l ipase act ivi ty in se rum from dog wi th total resect ion of pancreas va r i ed great ly f rom one to the other, never theless , the act ivi ty at pH rang ing f rom 9.1 to 9.7 was not significant to tha t at pH 7.9. Based on these results , i t can be admit tedly s ta ted tha t elevation of lipase in pancrea t i t i~ seems to be a reflex of l ipase act ivi ty in pancreat ic juice and tha t l ipase activity at pH ranging f rom 8.8 to 9.7 appears to be closely re la ted with pancreas. In e lectrophoret ic f rac t ionat ion of pancreat ic juice and serum with the use of cellulose ace ta te membrane , l ipase act ivi t ies were found at 3 or 5 positions.

Clinical significance of urinary amylase determinations in diagnosis of pancreatic diseases

Conclusion1) For evaluating pancreatic diseases with Wohlgemuth’s method of amylase determination, the significant values lie only above 64 unit, and in the low units (2–8) there is no significance suggesting pancreatic abnormalities. 2) Serial determination on urinary amylase excretion is recommended for diagnosing of chronic pancreatic disorders. 3) It is suggested that urinary amylase is more closely related to pancreatic states than serum amylase from the observations of amylase isozyme pattern.

The course of incurable gastric ulcers

137 biopsied l ivers which were 80 alcoholics and 57 viral chronic l iver injuries were examined by hematoxylin and eosin, Alcian blue, chromotrope-2R aniline blue and Gomori si lver impregnation, as well as periodic acid-Schiff (PAS) react ion af te r digestion wi th diastase (DPAS) and counters ta ining wi th hematoxylin. 1) In alcoholic group, a few inflammatory cell infiltration, and l iver cell necrosis with fibrosis were character is t ic in the per ipheral zone of the loble. Fur the rmore , hydropic swelling of l iver cells, alcoholic hyaline and thick collagen fibers in parenchyma were also remarkable. However, in viral group, inflammatory cell infil tration was significantly demonstrable in the per ipheral zone. Alcoholic and viral etiologies were corresponded in 92% to the histories f rom the histological findings of biopsy materials . 2) Histochemically demonstrable neutra l mucopolysaccharide s (DPAS)were seen in injured l iver cells, Kupffer cells and perisinusoidal borders . In alcoholic group, acid mucopolysaccharides were considerably demonstrated in the per iphera l necrotic l iver cells, but in viral group, these materials were few in the inflammatory zone. Thick collagen fibers were not enough stained by Alcian blue. In s i lver impregnation, the re t iculum fibers were conspicuously increased. This was only to a small par t caused by collapse following necrosis of single cells. Mast cells suggested to be related to formation of bibers were found in the inflammatory cell infil tration in the connective tissue, but these were scarcely demonstrable in the area of fresh necrosis. In a word, the histological differences between alcoholic and viral groups are resulted f rom the necrotic fibrosis in alcoholic injuries and inflammatory fibrosis in viral one. From these features, histologic findings are thought to be impor tant for the therapy and etiologic classificat ion of c i r rhosis as well as diagnosis. Mucopolysaccharides are suggested to serve as matr ices for fibers, and, Alcian blue s taining is also use-ful for ascer ta ining the alcoholic or viral etiology. Mast cells in connective tissue are found to be a in teres t ing problem.