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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 883 records · Page 49Linked to original sources

Monoclonal antibodies against human platelet membrane glycoprotein IIIa and collagen-induced platelet activation.

Two monoclonal antibodies against human platelet membrane glycoprotein IIIa (GPIIIa) were obtained. One monoclonal antibody, designated as 1B1, was found to inhibit both collagen-induced platelet aggregation and release reactions. This antibody also inhibited the binding of 125I-labeled collagen to human platelets. On the other hand, the other antibody, designated as B10, had no effect on platelet activation induced by a number of physiological stimulants including collagen. Direct binding studies involving 125I-labeled 1B1 or B10 demonstrated that the binding sites for these antibodies on unstimulated platelets have dissociation constants of 4.2 and 14.0 nM, respectively. The binding of 125I-labeled 1B1 or B10 to platelets was not inhibited by the other antibody. Purified 1B1 and B10 were covalently coupled to Affi-Gel and then proteolytic fragments of GPIIIa were applied to the Affi-Gel immunoadsorbent columns. Of the several proteolytic fragments, the 56 kilodaltons (kDa) fragment obtained on digestion with V8 protease bound to both of the columns. The 69 and 55 kDa fragments obtained with BrCN bound to only the 1B1 Affi-Gel column, while the 63 kDa fragment obtained with chymotrypsin only bound to the B10-Affi-Gel column. Based on the partial amino acid sequences of these fragments and the amino acid sequence of GPIIIa (C. A. Fitzgerald, B. Steiner, S. C. Rall, Jr., S. Lo and D. R. Phillips, J. Biol. Chem., 262, 3936 (1987), the epitopes for 1B1 and B10 were concluded to be located at amino acids 335 to 582 and 206 to 335, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sugar binding specificities of anti-H(O) lectins disclosed by use of fucose-containing human milk oligosaccharides as binding inhibitors.

The binding to normal and sialidase-treated human erythrocytes of six 125I-labeled lectins [Ulex europeus lectin I (UEA-1) and II (UEA-II), Laburnum alpinum lectins I (LAA-I) and II (LAA-II), and Cytisus multiflorus lectins I (CMA-I) and II (CMA-II)], was studied in detail. Quantitative inhibition assays of the lectin binding to the cells were also performed with various human milk oligosaccharides as inhibitors. Based on a comparison of the inhibition constants of the inhibitors thus obtained with the association constants of the lectins to the cells, the relative activities of cell surface blood group antigens toward the lectins are discussed.

Carbohydrate Metabolism↗

Coronary flow reserve and oxygen metabolism of the right ventricle.

The flow reserve of the right coronary artery (RCA) and myocardial oxygen extraction are important tractors in any investigation of the mechanisms of impaired right ventricular function. The present study induced brief coronary occlusions and examined the effect on right coronary blood flow in normal dogs, and the effect on myocardial oxygen metabolism in dogs with right ventricular hypertrophy (RVH). Right coronary flow reserve, represented by occlusion duration causing a half maximum dilatation (T1/2), was greater in the RCA than in the left anterior descending coronary artery of normal dogs; 11.4 +/- 2.3 sec vs 5.9 +/- 1.4 sec. Myocardial oxygen extraction ratio (EO2) of the right ventricle (RV), 51.3 +/- 1.6%, was significantly (p less than 0.05) lower than the index of the left ventricle (LV), 60.6 +/- 1.0%, and the extraction of the RV increased significantly in association with an increase of myocardial oxygen demand. In dogs with RVH caused by chronic banding of the pulmonary artery, this dominant oxygen reserve was lost: the EO2 of the hypertrophied RV was high compared with the EO2 of the normal RV (57.3 +/- 3.4% vs 51.3 +/- 1.6%, p less than 0.05), and no further increase in EO2 was observed in the hypertrophied RV in response to the elevation of the myocardial oxygen requirement. Oxygen usage per 100g of the RV for a certain level of overall RV work, rate-pressure product, was significantly (p less than 0.02) lower in the hypertrophied RV (0.00054 mlO2/beat.mmHg) than in the normal RV (0.0012 mlO2/beat.mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hepatitis B virus markers in patients with schistosomiasis, liver cirrhosis and hepatocellular carcinoma in Khartoum, Sudan.

Markers of hepatitis A and B virus were tested in 88 adult Sudanese subjects in Khartoum, Sudan. The subjects consisted of 25 control hospitalized patients, 21 volunteer blood donors, 23 patients with hepatosplenic schistosomiasis, 13 patients with liver cirrhosis and 6 patients with hepatocellular carcinoma (HCC). Antibody to hepatitis A virus was detected in 96% of the total. Hepatitis B surface antigen (HBsAg) was positive in 4, 24, 22, 31, and 67% of the subject groups, respectively. Antibody against hepatitis B core antigen (HBcAb) of undiluted serum was positive in 60, 57, 65, 77 and 83%, and there was no difference in incidence among the groups. It was positive in 200X diluted serum in 4, 24, 17, 23 and 60%. HBsAg and HBcAb (200X) were detected more often in HCC patients than in the control subjects (p less than 0.01). Hepatitis B virus is an important factor in the etiology of HCC in the Sudan.

Adult↗

The secretion of high molecular weight cathepsin B from cultured human liver cancers.

The biochemical characteristics of cathepsin B secreted from cultured human liver cancer cells were examined. The enzyme activity of culture medium against a synthetic substrate, N-carbobenzoxy-L-arginyl-L-arginine-4-methyl-coumaryl-7-amide, was dependent on the addition of cysteine, and the optimal pH was found to be 6.0. No activity was observed when the enzyme source was fresh medium not used for culture. These results suggest that the enzyme released from liver cancer cells is the thiol-protease cathepsin B. The molecular weight of the enzyme with 90% of the total activity was 40,000. Two cathepsin B molecules were found in liver tissue from patients with hepatocellular carcinoma (HCC); one was equivalent in size to the secreted enzyme, and a smaller one was the same as normal liver cathepsin B (27,000), which was also obtained from HCC-bearing cirrhotic liver. These results demonstrate that two molecules of cathepsin B are synthesized in liver cancer, and that the larger one is released into the surrounding tissue.

Cathepsin B↗

Lipid malnutrition of patients with liver cirrhosis: effect of low intake of dietary lipid on plasma fatty acid composition.

The plasma fatty acid composition of cirrhotic patients and their dietary intake of fatty acids were determined. Significantly lower plasma arachidonic, docosahexaenoic, dihomo-gamma-linolenic and eicosapentaenoic acid levels were observed in cirrhotic patients than in healthy controls. A remarkably low dietary intake of polyunsaturated fatty acids supplied from fish, vegetable oil and pulses was shown in cirrhotic patients. Positive correlations were observed between plasma arachidonic acid concentrations and clearance rate of indocyanine green (KICG) (r = 0.826, p less than 0.05) and between dihomo-gamma-linolenic acid levels and cholinesterase activities (r = 0.841, p less than 0.05). From these results, we conclude that a supply of polyunsaturated fatty acids is necessary for the nutritional treatment of patients with liver cirrhosis.

Cholesterol↗

Effects of valine on 15N incorporation into serum and tissue protein and non-protein fractions following 15N-L-leucine administration to normal and liver-injured rats.

Effect of proportion of three branched-chain amino acids (leucine, valine, and isoleucine:BCAA) for nitrogen utilization was studied in vivo by an intragastric administration of 15N-L-leucine to control rats and liver-injured rats treated with carbon tetrachloride (CCl4-rats). Following the administration of isonitrogenous dose of three amino acid solutions [Standard (15N-L-leucine, L-valine, L-isoleucine, and L-alanine; 11, 8, 6, 18 mg/ml), Low-Val (11, 2, 6, 23 mg/ml), and High-Val (11, 32, 6, 0 mg/ml)], 15N enrichments in serum albumin, liver, skeletal muscle, and brain proteins and non-protein fractions, and urea nitrogen were compared by using 15N-analyzer. In CCl4-rats, the 15N enrichment in liver protein fraction was significantly lower in the High-Val group than in the Low-Val group. However, the difference of 15N enrichment in serum albumin between Low-Val and High-Val groups in CCl4-rats was unclear. The 15N enrichments in non-protein fractions of the brains in CCl4-rats were about twofold those in the skeletal muscles and the highest 15N enrichment was recognized in the Low-Val group. In the non-protein fraction of skeletal muscle in CCl4-rats, significantly low 15N enrichment was shown in the High-Val group compared with the Low-Val group. The 15N enrichment in urinary urea was significantly higher in the High-Val group than in the Low-Val group in CCl4-rats. In the Standard group of control rats, 15N enrichments in serum albumin and protein fraction of skeletal muscle were higher than in other groups. In non-protein fractions of control rats, the lowest 15N enrichment in liver and the highest 15N enrichment in skeletal muscle were recognized in the Standard group. These results suggest that a large amount of valine supplement among BCAA is less useful for leucine utilization in liver-injured rats than in normal rats.

Amino Acids↗

Improvement of reduced coronary vasodilatory response during reactive hyperemia by diltiazem.

This study was performed to reconfirm transiently-reduced vasodilatory responses of the coronary artery in the reactive hyperemic period, and also to study whether an increase in calcium influx into the coronary smooth muscle accounts for the reduced coronary vasodilatory responses. Blood flow in the circumflex coronary artery was measured with an electromagnetic flow transducer in anesthetized open-chest dogs. Two successive occlusions for 3 to 7 s performed in pairs with a brief interval were accompanied by decreasing reactive hyperemia: the maximum reduction of reactive hyperemia appeared when the occlusion period was around 5 s with a 5-s interval. Around 5 s after the release of occlusion, excess arterial inflow almost equaled the blood flow debt incurred during the first occlusion. Pretreatment with diltiazem (150 micrograms/kg), a calcium entry blocker, significantly attenuated the reduction of coronary vasodilatory responses, but glyceryl trinitrate (nitroglycerin) did not affect the phenomenon of coronary reactivity. The results suggest that excess accumulation of calcium in the smooth muscle of small coronary arteries occurred during an early period of post-occlusion hyperemia, which resulted in a reduced vasodilatory reactivity of the vessels to the second ischemic stimulus.

Animals↗

[Morphological classification of the prevention by aldose reductase inhibitor of rat galactosemic cataract].

A morphological classification indicating the stage of the prevention of aldose reductase inhibitor (ARI) on the rat galactosemic cataract was investigated. Three week old rats (body weight 50 g) were fed with a 25% galactose diet. Two kinds of ARIs (ADN-138, FR-74366) were used with a different dose 25% galactose fed each drug. The rats on the 25% galactose diet rapidly developed cataracts in the equatorial region of the lens followed by total cataracts. The morphological processes of the galactose cataracts receiving preventive treatment of ARI were divided into 5 types according to their intensity.

Aldehyde Reductase↗

[Movement of regenerated lens epithelial cells in 50% galactose cataract and an aldose reductase inhibitor].

In experimental galactose cataract of rats, lens fiber cells were gradually destroyed by swelling and liquefaction occurring due to the accumulation of galactitol. In addition to the destruction of lens fiber cells, marked regeneration of lens epithelial cells was universally observed. In this study, we used the technique of 3H-thymidine autoradiography and examined the movement of regenerated (DNA synthesis) lens epithelial cells. On the fourth day from the starting of 50% galactose chow, 3H-thymidine was injected into the anterior chamber. After one week, 3H-thymidine-labelled epithelial cells was observed at the bow region of the equatorial area. After 2 to 4 weeks, labelled cells were found in the regenerated lens fibers of the cortex. After 3 weeks, labelled cells about to be destroyed by swelling and liquefaction were recognized. However, a few labelled cells were still observed in the epithelial cell layer. The same experiments were performed in two groups of normal chow-fed one and 50% galactose + an aldose reductase inhibitor (Statil)-fed one. The movements of 3H-thymidine labelled epithelial cells in the above two groups were almost identical. In addition, the movement of labelled cells was normalized by an aldose reductase inhibitor.

Aldehyde Reductase↗

Exercise body surface mapping in patients with left ventricular hypertrophy: comparison with stress thallium scans (SPECT).

To evaluate exercise-induced myocardial ischemia in patients with electrocardiographic evidence of left ventricular hypertrophy (LVH), including ST.T changes, body surface maps (QRST area maps) were recorded using 87 lead points before and after exercise. The patterns of the subtraction QRST area maps (S-maps) were compared with the findings of stress thallium (T1) scans in 31 patients with hypertrophic cardiomyopathy and in five with essential hypertension. All 18 patients whose S-maps revealed changes less than -40 muVS or only an increase over the anterior chest region showed no positive findings on the stress T1 scans. However, there were clearly positive findings on stress T1 scans in eight (89%) of nine patients whose S-maps revealed changes greater than -40 muVS over a wide precordial region or in six (67%) of nine patients whose S-maps revealed increases over the anterior chest region and had accompanying changes greater than -40 muVS somewhere over the precordial region. These results suggested that exercise QRST area maps could differentiate exercise-induced myocardial ischemia from LVH with ST.T changes.

Aged↗

Nephrotoxicity of pyrroloquinoline quinone in rats.

When pyrroloquinoline quinone (PQQ) was intraperitoneally injected into rats daily for 4 days at a dose of 11.5 mg/kg body weight/injection, functional and morphologic changes of the kidneys were clearly observed. The most prominent finding was necrotic and degenerative changes of the proximal tubular epithelium as well as hematuria and an elevation of serum creatinine concentration.

Animals↗

Immunohistochemical application of monoclonal antibodies to reveal the structure and localization of carbohydrate antigens. N-acetyllactosamine-related carbohydrate antigens in human biliary epithelial cells.

With the use of a panel of monoclonal antibodies against structurally related carbohydrate antigens, finely regulated cellular phenotype of the carbohydrate antigens can be characterized. As a model system, the expression of N-acetyllactosamine-related antigens in human biliary epithelial cells was investigated using 16 murine monoclonal antibodies against different carbohydrate epitopes. Human biliary epithelial cells expressed type 1 backbone-related antigens at all synthetic stages. Type 2 backbone and its monofucosylated structures, i.e., Lex and H, were never detected. More complex type 2 chain antigens, i.e., Ley, A and ALey, were apparently expressed. Types 3 and 4 chain antigens were also shown to be expressed. However, the expression of N-acetyllactosamine-related antigen was polymorphic and differed from one individual to another. Furthermore, in spite of the topographical continuity of the biliary tree, biliary epithelial cells were not always equal in the expression of N-acetyllactosamine-related antigens. As a conclusion, not only the localization but also the structure of carbohydrate antigens can be immunohistochemically studied on the tissue sections with the use of well defined monoclonal antibodies.

ABO Blood-Group System↗

Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors.

The relationship between labeling indices of Ki-67 reactive antigen expressed by cycling cells and BrdUrd incorporated into S-phase cells was investigated in 20 patients with malignant tumors. Both of the labeling indices varied greatly from patient to patient; the labeling index of Ki-67 ranged from 37.5% to 1.9% with an average value of 16%, and the BrdUrd labeling index ranged from 23.4% to 1.6% with an average of 9.3%. The Ki-67 labeling index was higher than the BrdUrd labeling index. In general, the values of the Ki-67 labeling index were parallel to those of the BrdUrd labeling index, and the relation Y = 1.59X + 1.15 (r = 0.89) was obtained. In human solid tumors, therefore, the growth fraction can be easily estimated from the S-phase fraction size, and vice versa.

Adenocarcinoma↗