Search PubMed⌕ Search

Biomedical subjects

T Osanai

Publications and source records attributed to T Osanai.

At least 73 records · Page 4Linked to original sources

[Clinical study on the effect of intra-arterial injection of mitoxantrone-lipiodol emulsion for hepatocellular carcinoma].

To investigate the effect of intra-arterial injection of mitoxantrone emulsified with ethiodized oil, forty-eight patients with hepatocellular carcinoma were evaluated. After the treatment, ten of the patients underwent hepatectomy. In the thirty-eight unresected cases, there were 15 (39%) partial responses, which continued 1.2 to 11.8 months (mean, 5.8 months). The 1- and 2- year survival rates were 67% and 38%, respectively. The response rate was higher in cases with tumor under 5 cm in diameter. In the remaining 10 resected cases, the necrotic areas in main nodules ranged from 65% to 100% (mean, 85%). This treatment might be applied effectively to patients with small hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

A case of primary cystic mediastinal hemangiopericytoma.

We describe a 35-year-old man with a primary cystic mediastinal hemangiopericytoma who presented with the complaint of progressive dysphagia for 6 months. The computed tomography and magnetic resonance imaging findings revealed that a well-defined, fluid-filled mass (measuring approximately 10 x 10 cm) was located posterior to the heart and inferior to the carina of the bronchus. Tumor puncture showed translucent yellow fluid with normal concentrations of carcinoembryonic antigen, squamous cell carcinoma-related antigen, and carbohydrate antigen 19-9 and a high concentration of carbohydrate antigen 125. After removal of the tumor, microscopic examination revealed a malignant hemangiopericytoma. To our knowledge, this is the first case of a primary mediastinal hemangiopericytoma with cystic formation. Moreover, we showed the specific biochemical findings of the cystic fluid that were useful for differentiation from other cystic mediastinal tumors.

Adult↗

Evaluation of oxidized low-density lipoprotein and large molecular size low-density lipoproteins in atherosclerosis.

To study the roles of modified low-density lipoprotein (LDL) and the molecular size of LDL in atherogenesis, the following studies were carried out. Eight white male rabbits fed a standard oriental diet with 1% cholesterol were used to isolate LDL and to observe changes in the molecular size of LDL due to cholesterol feeding. The tissue LDLs in the aorta were analyzed to confirm the existence of modified LDL (namely, LDL with peroxidized cholesteryl ester) by thin-layer chromatography. In addition, plasma LDLs were isolated from 18 patients with myocardial infarction and 11 patients with angina pectoris to confirm the existence of LDL with peroxidized cholesteryl ester. Each LDL separated consisted of 3 fractions; namely, IDL (1.006-1.018), LDL1 (1.019-1.052) and LDL2 (1.053-1.063) by sequential ultracentrifugation. The molecular sizes of LDL were measured by a planimeter from electron microscopic photographs, with negative staining. The estimation of peroxidized cholesteryl linoleate in LDL was performed using our method. The modified LDLs with peroxidized cholesteryl ester were poorly estimated in the LDL separated from the plasma of cholesterol-fed rabbits and from the aorta extraction after 16 weeks of feeding. The peroxidized cholesteryl ester was clearly identified in the plasma LDLs of the patients with myocardial infarction and angina pectoris, and in whole extracts from human aortic atheroma, although it was not clearly identified in the tissue LDL fraction. The molecular sizes of LDL1 enlarged week by week with cholesterol feeding, but two fractions of IDL and LDL2 did not change in size. The infusion of cholesterol-rich LDL of large molecular size or LDL with peroxidized cholesteryl ester into the vessels led to fixation, on the surface of the arteries of many platelets, red cells, and white cells, and to marked irregularities in the endothelial folds. The evidence suggests that atheromas, formed in a short period in rabbits with cholesterol feeding, are caused mainly by the increase in LDL1 of large molecular size, and that foam cells, formed in human atheromas, are caused mainly by the production of modified LDL with peroxidized cholesteryl ester.

Animals↗

[Effect of aging on sensitivity of blood pressure to salt].

We investigated the correlation between aging and sensitivity of blood pressure to salt. 88 non-treated essential hypertensives were divided into four groups: less than 40 years old (n = 20), 40-49 years old (n = 20), 50-59 years old (n = 39), and greater than 60 years old (n = 11). Changes of blood pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma norepinephrine (PNE), and plasma epinephrine (PE) due to salt load were compared among four groups. Salt sensitivity of blood pressure was increased with aging, and there was a positive correlation between them (r = 0.30, p < 0.01). Decrement of PRA due to salt load was decreased with aging, and there was a negative correlation between them (r = -0.35, p < 0.05). PCA and PNE were suppressed by salt load, and the decrement degrees did not change with age. PE did not change by salt load. We conclude that salt sensitivity is increased with age in essential hypertensives, and renin-angiotensin system might be involved in it.

Adult↗

Phospholipase C responses in cells from spontaneously hypertensive rats.

We tested the hypothesis that increased systemic vascular resistance in spontaneously hypertensive rats may be secondary to enhanced phospholipase C activity in response to vasoconstrictor stimuli. Activation of phospholipase C by angiotensin II (Ang II), thromboxane A2, arginine vasopressin, and endothelin-1 was compared in cultured glomerular mesangial cells and mesenteric vascular smooth muscle cells taken from 13- to 14-week-old hypertensive and normotensive Wistar-Kyoto rats (blood pressure, 185 +/- 1 versus 135 +/- 2 mm Hg). Phospholipase C was assessed by measuring cytosolic free calcium and by the accumulation of radiolabeled inositol phosphates. Basal cytosolic calcium did not differ between mesangial cells taken from both strains but was greater in smooth muscle cells from hypertensive rats (210.1 +/- 8.2 versus 149.2 +/- 4.7 nM). The responsiveness of cytosolic calcium and inositol phosphate accumulation to Ang II was significantly enhanced in mesangial cells from hypertensive rats (10(-7) M Ang II: peak increase of calcium, 1,266 +/- 181 versus 603 +/- 93 nM; percent increment of inositol phosphates at 1 minute, 266 +/- 26 versus 98 +/- 10%). Vascular smooth muscle cells from hypertensive rats, when compared with normotensive rats, showed a similar augmentation of Ang II-stimulated intracellular calcium and inositol phosphates. Thromboxane A2-induced enhancement of intracellular calcium and inositol phosphate accumulation in vascular smooth muscle cells was also greater in hypertensive animals. However, the responses to vasopressin and endothelin in mesangial or vascular smooth muscle cells did not differ between the normotensive and hypertensive animals. There was no significant difference in Ang II receptor number and affinity between hypertensive- and normotensive-derived mesangial cells. We conclude that genetically increased blood pressure in rats may be secondary to enhanced post-receptor signaling in glomerular mesangial cells activated by Ang II and to enhanced signaling in vascular smooth muscle cells stimulated by either Ang II or thromboxane A2.

Angiotensin II↗

Dose-dependent enzyme suppression in spleen induced by GM1 (monosialoganglioside 1) administration to mice.

Our previous studies suggested that the administration of exogenous gangliosides to the body modulates enzymatic networks in the brain. In the present study, we tested whether that is the case with another organ, spleen. By testing the dose response relationship, we found that there is a optimum dose for the effect of enzymatic modulation of GM1 (monosialoganglioside 1) administration. Although the optimum level varied depending on each of the examined hydrolytic enzymes, it usually fell in the range around 50 micrograms/kg body weight. The findings led us to conclude that the enzyme-modulating actions of gangliosides come not merely from the bizarre actions in vivo of high molecular exogenous substances.

Animals↗

Effects of sex hormones on fulminant hepatitis in LEC rats: a model of Wilson's disease.

LEC rats, which have hereditary hepatitis and have recently been proposed as an animal model for Wilson's disease, were examined to determine the effects of sex hormones on fulminant hepatitis. After the rats had undergone ovariectomies or orchidectomies (castration) and were compared with intact rats, the age at the onset of fulminant hepatitis was not substantially altered but the survival rates decreased from 50% to 12.5% for females and 75% to 14.3% for males, indicating that sex hormones did not influence the occurrence of fulminant hepatitis but influenced mortality due to fulminant hepatitis. When testosterone was administered to the ovariectomized or orchidectomized rats, the survival rate increased to over 90% in both sexes. In contrast, estradiol did not affect the survival rate of either sex but affected the onset of fulminant hepatitis. That is, with the administration of estradiol, the age at which serum GPT activity reached its maximum was delayed 4 weeks in ovariectomized rats and 6 weeks in orchidectomized rats as compared with intact rats. A similar but somewhat weaker tendency appeared in rats given progesterone. The results of our study indicate that sex hormones have no effect on the rate of occurrence of hepatitis but affect the progression of hepatitis. In particular, testosterone increased the survival rate of rats with fulminant hepatitis, and exogenous estradiol delayed the onset of hepatitis for several weeks.

Alanine Transaminase↗

Localization of blood coagulation factors and fibrinolysis factors within lymphoid germinal centers in human lymph nodes.

The presence of nineteen blood coagulation factors and fibrinolysis factors was immunohistochemically evaluated in human lymph node germinal centers (GCs). Twelve of these factors were detected within lymphoid GCs. The predominant pattern was dendritic with occasional crescent-shaped, ring-shaped or 'moth-eaten' appearance. Immunostains of factor VIII-related antigen, factor I, protein C, tetranectin, antithrombin III, type 2-plasminogen activator inhibitor, and alpha 2-plasmin inhibitor were almost entirely absent from GCs, although they reacted in vascular wall and lumen, respectively. The immunostaining to high molecular weight kininogen, kallikrein, factors XII, X, V, II, XIIIa, XIIIs, plasminogen, tissue-plasminogen activator, and type 1-plasminogen activator inhibitor more frequently revealed a positive dendritic pattern. Immuno-electron microscopy demonstrated factor X and factor XIIIa attached to the cell surfaces of lymphocytes, macrophages, and follicular dendritic cells (FDCs); and in the intercellular space within GCs, especially attached to the labyrinthine-like structure of FDCs. No reaction products were observed in the perinuclear cisternae and rough endoplasmic reticulum in either lymphocytes or FDCs. Our data demonstrate that human lymphoid GCs really contain some of the proteins related to the blood coagulation and fibrinolysis cascades.

Dendritic Cells↗

Effects of endothelin on cultured human and rat glomerular mesangial cells.

Figure 5 summarizes our results and the data in the literature with regard to both short-term signalling and long-term signalling induced by endothelin. Short-term signalling, which induces vasoconstriction, is undoubtedly mediated by multiple signals including increments of cytosolic calcium, stimulation of protein kinase C and alkalinization of the cytosol. Endothelin also activates negative feedback pathways including arachidonate release with the synthesis of vasorelaxant prostaglandins and potentiation, in a prostaglandin-dependent manner, of beta-adrenergic-stimulated adenylate cyclase. Long-term signalling is less well understood and may depend not only on phospholipase activation with subsequent changes of calcium and protein kinase C but also stimulation of other protein kinases which phosphorylate key intermediates. Endothelin stimulates the transient appearance of protooncogenes that might play a role in the induction of cellular proliferation.

Animals↗

Role of renomedullary thromboxane A2 in development of doca-salt hypertension.

To clarify the role of renal thromboxane (TX)A2 in the development of deoxycorticosterone acetate (DOCA)-salt induced hypertension, relationship between systolic blood pressure and the synthesis of renal TXA2 was investigated in 18 rats without and with OKY-046 administration which suppressed the synthesis of renal TXA2. Systolic blood pressure was significantly higher in DOCA-salt group than in control and OKY groups. The synthesis of 6-keto-prostaglandin(PG)F1 alpha and TXB2 in both renal arteries and cortical slices were more enhanced in DOCA-salt and OKY groups than in control group, but there was no significant difference between DOCA-salt and OKY groups. In contrast, the synthesis of 6-keto-PGF1 alpha in renomedullary slices did not vary significantly among three groups, and that of TXB2 was more increased in DOCA-salt group than in control and OKY groups. The cumulative sodium retention was significantly greater in DOCA-salt group than in control group. Administration of OKY-046 reduced the cumulative sodium retention in DOCA-salt rats by 45% toward that of the control group. These results might suggest that the enhanced production of renomedullary TXB2 was important to the development of DOCA-salt induced hypertension.

Animals↗

The effects of endothelin on cytosolic calcium in cultured human and rat glomerular mesangial cells.

Isopeptides of the endothelin gene family, including sarafotoxin, caused a concentration-dependent increase in intracellular-free calcium (cytosolic calcium) in cultured human and rat glomerular mesangial cells. The calcium increments had two components, a spike increment resulting from mobilization of intracellular calcium and a sustained calcium increment as a result of endothelin activation of calcium influx. ET-dependent calcium influx occurred through dihydropyridine-insensitive calcium channels which were blocked by NiCl and allowed entry of Mn2+. In human mesangial cells, ET stimulated periodic oscillations of cytosolic Ca2+ that reflect synchronous signalling in localized populations. Calcium signalling evoked by the ET isopeptides showed cross-desensitization among the four ET-peptides tested. Although protein kinase C activation acutely reduced ET-induced calcium signalling, the desensitization by ET isopeptides was independent of protein kinase C. If ET was added to cells incubated with an inhibitor of the endoplasmic reticulum calcium ATPase, it became apparent that ET activated a calcium efflux pathway which reduced cytosolic calcium. These data, therefore, demonstrate that calcium signalling is a common response in both human and rat cultured mesangial cells incubated with different ET isopeptides.

Animals↗

Gangliosides administration causes sugar moiety-specific enzymatic changes in brain.

Exogenous gangliosides are known to affect the metabolism when administered to the body. To study the mechanism of this effect three types of gangliosides were administered intraperitoneally to mice and the changes in the enzyme activity of the cerebral tissues studied. The effect of GM2 from bovine brain was characterized by a decrease in the activity of various aminopeptidases, while GD3 from cow's milk caused an increase in the activity of sugar-related enzymes such as sialidase, glucosidase, and fucosidase. GM3 from horse erythrocytes showed intermediate effects between GM2 and GD3. Multivariate analysis showed that the effects of the three gangliosides are clearly separable statistically. These results which demonstrate the sugar moiety-specificity of gangliosides are discussed in relation to the A and B pathways of ganglioside synthesis.

Amino Acid Sequence↗