Masaichi Fukase

A Clinical Evaluation of Serum Monoamine Oxidase, with Special Reference to Hepatic Fibrosis

Serum levels of monoamine oxidase (SMO) have been determined in 16 normal adults, in 76 patients with hepatic diseases and in 44 patients with non-hepatic diseases. Elevated enzyme levels were found i

Pathogenic Mechanisms and Prevention of Stroke in Stroke-prone Spontaneously Hypertensive Rats

Publisher Summary The establishment of stroke-prone spontaneously hypertensive rats (SHRSP), of which more than 80% died of stroke, has led to extensive study on the mechanisms of cerebrovascular lesions. Studies have revealed that hypertension is the most important systemic factor for stroke. Other possible factors are the alteration of the physical characteristics of the arterial wall, and involvement of humoral factors such as renin. Further, the angioarchitectural studies have clarified that the predilection sites of stroke are the boundary zone of the three main cerebral arterial supplies and the areas fed by recurrent arteries. This chapter presents the assay of norepinephrine in the brain quantitatively or by fluorescent histochemical methods. regional cerebral blood flow (rCBF) tends to increase under hypertensive state below 200 mm Hg but decreases abruptly in SHRSP with severe hypertension over 220 mm Hg.

T Cells and B Cells in HBsAg-Positive Patients with Chronic Persistent Hepatitis and Asymptomatic Carriers

Excerpt Human lymphocytes in the peripheral blood that form rosettes spontaneously with sheep erythrocytes (E rosettes) are thymus-derived. Bone marrow-derived lymphocytes (B cells), can bind antig...

Incidence of Thyroglobulin and Microsomal Antibodies in Normal Subjects

In the course of studies on the occurrence of antithyroid antibodies in various thyroid disorders, serum antibodies to microsome of thyroid epithelial cells, as well as circulating antibodies to thyroglobulin, are demonstrated by tanned red cell hemaggulutination. These thyroglobulin and microsome-coated tanned red blood cells can be efficiently demonstrated with a commercially prepared reagent. (Fuji-Zoki Co.) The sera of 2,350 normal subjects were tested by these thryoid autoantibodies tests. Fifty-one (2.3 per cent) of the sera of 2,350 normal subjects showed a positive reaction for thyroglobulin antibodies, and fifty-nine (2.5 per cent) persons showed a positive reaction for microsomal antibodies. The incidence of thyroglobulin and microsomal antibodies in males and females were progressively greater with age, particularly between ages 60 to 69.

Hypertension, Stroke and Atherogenesis in Experimental Models

By the establishment of proper animal models for hypertension, stroke, and ath-erogenesis, it has been possible to greatly accelerate studies on not only the pathogenesis but also the interrelation of these pathologic states.

AUTOIMMUNE DISEASES INVOLVING MULTIPLE ORGAN SYSTEMS WITH SPECIAL REFERENCE TO SLE

A. まえがき 現在自己免疫性疾患(以下 自免症 と略),な い し は病気の進展或は慢性化に自己免疫現象が関与す ると考え られている疾患は表1に 示す ようである が,更 に年々一,二 の疾患が これに加え られつつ ある.こ れを病気のひろが り,乃 至は病因などを 勘考 して大ざつばに分類 してみると,1) 全身の 組織ないしは臓器が系統的に侵されるものと,2) 臓器限局性すなわち或る特定の臓器または組織が 限定 して侵されるものに分けられ,ま た機能的に 見ると機能の低下を招来するものが大部分である が,Basedow病 の如 く逆に機能の亢 進を示す もの も認められる.一 方病因的に見ると,細 菌とかウ ィルスに よる感染症に関係するもの,腫 瘍に関係 するもの等に分け られる.更 に免疫学的な見地か らいえば,そ の組織障害に主 として血中抗体或は 細胞性免疫の関与するものおよびその両者の関与 するものに分類出来よう.し か しこれは程度の差 であつて,ほ とんどすべての自免症ではこの両者 がか らむ ことが次第に明らかになつてきた. 著者は第14回 日本臨床血液学会1)お よび第46回 日本内分泌学会2)そ の他の特別講演で2~3の 臓 器限局性自免症について既に触れたので,今 回は 全身性の自免症,特 にその代表 とされるSLEを 中心 として述べる. B.SLEの 診断基準について SLEは 自免症の代表的な疾患 とされているが 表1.Autoimmune disease in internal medicine.

Biochemical studies on hepatic fibrosis (XII) Multiple forms of monoamine oxidase in serum, liver mitochondria and various connective tissues

Previous experiment showed that serum monoamine oxidase (MAO) level was moderately elevated in hepatic fibrosis and in serious hepato-cellular necrosis. Present study describes the partial purification of MAO in serum, liver mitochondria and various connective tissues such as granuloma, bone and lung by starch block electrophoresis and by ammonium sulfate fractionation. MAO from liver mitochondria has a different properties in heat sensitiveness and in lathyrogen inhibition from that of serum and various connective tissues. Three types of seurm MAO are determined electrophoretically. One of them are markedly elevated in the serum of liver cirrhosis. MAO fi-om liver mitochondria moves towards anode with two peaks. On the other hand MAO from various connective tissues moves towards cathod with two peaks. MAO in the saturation from twenty to thirty-five percent of ammonium sulfate markedly elevated in the serum of liver cirrhosis. Serum MAO in hepatoceUular necrosis can not be completely inhibited by 0 . I / t mole of aminoacetonitrile in vitro and has a similar electrophoretic pattern like that of liver mitochondria On the contrary, serum MAO in hepatic fibrosis has a different electrophoretic pattern from that of liver mitochondria and completely inhibited by lathyrogens. These results suggest that (i) elevation of serum MAO in hepatic fibrosis and in serious hepatocellular necrosis may be depend on the elevation of different component of isozyme. (ii) Serum MAO in hepatic fibrosis may be responsible with that of connective tissue. (iii) Serum MAO in hepatocellular necrosis may be originated from that of liver mitochondria.

Biochemical studies on hepatic fibrosis (x) clinical use of lathyrogen (β-mercaptoethylamine), and characteristics of plasma monoamine oxidase related to collagen metabolism

It was shown tha t a monoamine oxidase was closely involved in cross-link format ion o f collagen fibrils. In this paper, some charac ter is t ics of monoamine oxidase derived f rom connect ive tissue, l iver-mitochondria and plasma was compared wi th each other. It was found tha t monoamine oxidases f rom connective t issue and plasma were non-flavin and copper containing, inhibi ted by several la thyrogens and moved toward cathode in s t a rch gel electrophoresis . Contrar i ly , monoamine oxidase derived f rom mitochondria of l iver have flavin and copper, and the act ivi ty of the enzyme was accelerated by the lathyrogens. Electrophoret ical ly, t he enzyme showed the mobil i ty toward anode. In previous repor ts it was demonstrated, the act ivi ty of monoamine oxidase in p lasma was elevated moderate ly in chronic hepati t is and markedly in l iver cirrhosis . In clinical t r ial , ~-mercaptothylamine, one of lathyrogens, was adminis t ra ted to about 30 pat ients wi th l iver c i r rhosis or chronic hepati t is . In these patients , p lasma OH-proline increased up to 2 or 3 weeks and then decreased below the level before the adminis t ra t ion. Ur ina ry OH-proline was remained unchanged. The act ivi ty of p lasma monoamine oxidase decreased gradual ly f rom the begin af te r the adminis t ra t ion. In addit ion to these resu l t s above mentioned, there was observed to be a tendency to decrease wi th S-GOT and S-GPT, but not wi th S-alkal ine phosphatase.

Diagnostic significancg of serum copper-containing monoaminc oxidase in liver fibrosis

It was demonstrated recently that serum monoamine oxidase (S-MAO) is very similar enzyme to MAO in connective tissue in nature. Both of them are Copper-containing and non-flavin enzymes. On the other hand, the MAO in rnitochondria is flavin enzyme. It has been shown that lathyrogens inhibit the activity of MAO in serum and connective tissue, but not of MAO in mitochondria. The facts above mentioned suggest that determination of the activity of S-MAO may be useful for the diagnosis of hepatic fibrosis. In eight patients with acute hepatitis, the activities of S-MAO were within normal range at all. In 3 out of 11 patients with inactive form and 7 out of 16 patients with active form of chronic hepatitis, the activities of S-MAO were increased moderately over upper limits of normals. In 18 out of 28 patients with liver cirrhosis, the activities were markedly elevated. Comparing the activities of S MAO in correspondence with the grade of hepatic fibrosis observed by needle biopsies, there was a tendency that portal or central fibrosis, invasion of fibrosis into the parenchym, porto-portal or porto-central fibrosis and annular fibrosis around the pseudolobule showed in this order the more elevated activities in S-MAO. There were a slight positive correlation between S-MAO activity and portal hypertension and a close negative correlation between the activity and hepatic blood flow. The activities of S-MAO in pheochromocytoma and fulminant hepatitis, also in SLE and rheumatoid ar thr i t is were within normal range. Contrarily, the activities in the patients with hyperthyroidism and with scleroderma were moderately elevated and one patient with acromegaly had a greatly increased S MAO activity. These results indicate that S MAO activity reflects a existence of active collagen metabolism independently on various causes, even in connective tissue disorders as well as hepatic fibrosis, but not of enhanced amine metabolism. Finally it was shown that fl-mercaptoethylamine inhibits the S-MAO activity in vitro and the administration of fl-mercaptoethylamine to several patients with chronic hepatitis let the S MAO activity decrease.

Clinical diagnosis of Gilbert’s syndrome with reference to patients with compensated hemolytic states

Carbohydrate metabol i sms of the isolated perfused l iver f rom normal rat , and ra ts with fatty, fibrotic and c i r rhot ic l iver derived from choline deficiency, were studied. The isolated ra t l iver perfusions were carr ied out dur ing 2 hours with 200 ml of saline diluted, heparinized ra t blood, using Sellers-Okuyamas perfusion apparatus. Glucose, lactic acid, pyruvic acid and urea concentrat ion in perfusate were determined respectively. In the normal l iver perfusion, glucose level in perfusate increased as a resul t of glycogenolysis and gluconeogenesis. Then, lactic acid level decreased according as the s t imula t ion of gluconeogenesis. In the diseased l iver perfusion, in accordance with the development of histologic findings f rom fat ty l iver via fibrosis to cirrhosis , glucose level tended to decrease and lactic acid level tended to increase. Urea format ion in the diseased liver perfusion was lower than in the normal l iver perfusion. These data suggest tha t according as the development of l iver injuries, carbohydrate metabolism, especially gluconeogenesis is suppressed m.arkedly.