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Biomedical subjects

N Itoh

Publications and source records attributed to N Itoh.

At least 487 records · Page 27Linked to original sources

RNA synthesis in starfish embryos: developmental consequences of its inhibition by formycin.

Embryos of the starfish Asterina pectinifera were examined with regard to their ability to undergo the early events of embryonic development in the presence of formycin, an analogue of adenosine and a reported inhibitor of RNA synthesis. It was shown that in normal embryos the pool of ribonucleoside 5'-triphosphates increased during the period of blastula formation. The increase of the UTP pool was blocked nearly completely by 25 micrograms/ml formycin, and that of the CTP pool was inhibited partially by the same concentration of the drug. On the other hand, the pools of ATP and GTP were the same for both control and formycin-treated embryos. The development of embryos cultured in the presence of 25 micrograms/ml formycin stopped at the early blastula stage. Addition of 100 micrograms/ml each of uridine and cytidine to cultures of embryos that had been placed in 25 micrograms/ml formycin at the onset of blastulation allowed gastrulation to occur, suggesting that the developmental arrest produced by formycin is due primarily to the inhibition of pyrimidine nucleotide biosynthesis.

Animals↗

Angiotensinogen production by rat hepatoma cells is stimulated by B cell stimulatory factor 2/interleukin-6.

Angiotensinogen has been identified as one of the acute-phase reactants. In vitro studies were carried out using the Reuber H35 hepatoma cell line to identify the species of cytokines contributing to the increased synthesis of angiotensinogen in the liver. Angiotensinogen secretion by H35 cells was maximally increased 4-fold by the addition of 10(-7) M dexamethasone. Under this condition, angiotensinogen secretion was further stimulated by B cell stimulatory factor 2/interleukin-6 (IL-6, 50 U/ml), but not by interleukin-1 or interferon-alpha. In the absence of glucocorticoid, IL-6 did not affect angiotensinogen secretion by H35 cells, indicating that the presence of glucocorticoid is required for the stimulatory activity of IL-6. These results suggest that IL-6 is a mediator responsible for the increased synthesis of angiotensinogen in the liver during acute inflammation.

Angiotensinogen↗

Induction of endogenous tumor necrosis factor by OK-432 in ovarian cancer patients with ascites.

To four ovarian cancer patients with malignant ascites, 10 KE of OK-432 was intraperitoneally administered four times at 2 day intervals for priming, and 40 KE of OK-432 was given on the 13th day after the first injection for triggering. The changes in blood monocyte and peritoneal macrophage levels and the production of tumor necrosis factor (TNF) by blood mononuclear cells (BMCs) and ascitic lymphoid cells (ALCs) were examined. In the two patients in whom TNF was induced in the ascites, TNF production by BMCs and ALCs was noted during priming. After triggering, increases in both the number of peritoneal macrophages and TNF production by ALCs were noted. In the other two patients, in whom TNF was not detected in the ascites, the ratio of peritoneal macrophages to ALCs did not change throughout the study period, and TNF production by the ALCs was not augmented. These findings suggest that OK-432 can exert a primary effect on both peritoneal macrophages and blood monocytes, and that OK-432 triggering can promote an increase in primed peritoneal macrophages and the release of TNF from these cells.

Ascites↗

Changes in activity of the renin-angiotensin system of the rat by induction of acute inflammation.

Angiotensinogen is the precursor of biologically active peptide angiotensin II and its hepatic synthesis is increased by the induction of acute inflammation. Studies were carried out to know whether the rise in plasma angiotensinogen is actually involved in the activity of the renin-angiotensin system during acute inflammation. The plasma level of angiotensinogen in rats was increased to 2.5 times the normal level 16 h after the induction of acute inflammation by administration of lipopolysaccharide (LPS). The plasma renin concentration (PRC) was decreased to about 40% of the normal level concomitantly with a reduction of plasma renin activity (PRA) at 4 h after LPS administration. In contrast, 16 h after LPS injection, when plasma angiotensinogen showed a high level and PRC had recovered to the normal range, PRA was increased to 1.7 times the normal level. These results indicate that acute inflammation induced by LPS causes a biphasic change in the generation of angiotensin I, i.e., an early decrease depending upon the reduction of PRC and later increase depending upon elevation of the angiotensinogen concentration.

Acute Disease↗

An autopsy case of tuberous sclerosis associated with primary pericardial mesothelioma.

Tuberous sclerosis (Bourneville-Pringle phacomatosis) has been known to be associated with cardiac rhabdomyoma, but apparently never previously with primary pericardial mesothelioma. We present an autopsy case of this condition in a 59-year-old man, who had been diagnosed as having tuberous sclerosis in view of the presence of facial sebaceous adenoma, mental retardation, intracranial calcification, cerebral ventricular dilatation and renal tumor. During the clinical course, characterized by heart failure due to cardiac tamponade, cardiac sarcoma was diagnosed by imaging techniques. Autopsy revealed biphasic-type primary pericardial mesothelioma. As to the tuberous sclerosis, atypical giant cells in the tubers of the cerebral cortex and the lateral ventricular wall were found, which were considered to be derived from neurons rather than glial cells on the basis of staining with Bodian, Holzer, and antibodies against NSE, GFA and S-100 protein. In old tubers protruding into the lateral ventricles, fibrous glias were present with dense calcospherite deposits, coinciding with the CT findings. The renal tumors were angiomyolipomas, which were present bilaterally and showed partially infiltrative growth, but seemed to have a benign nature because of the lack of metastasis and atypism of the leiomyocytes.

Autopsy↗

Morphometric changes in glomerular anionic sites during aminonucleoside nephrosis.

Changes in glomerular anionic sites were examined morphometrically in nephrotic rats receiving daily subcutaneous injections of puromycin aminonucleoside (PAN). The high-iron diamine-thiocarbohydrazide-silver proteinate method showed that anionic sites composed of heparan sulfate proteoglycans formed a continuous band within the lamina rara externa of the glomerular basement membrane (GBM) in control rats. Only one day after the first injection of PAN, anionic site loss was already detectable, preceding the morphological changes in the epithelial cells. The number and size of the anionic sites decreased greatly between days 7 and 10, when urinary protein excretion began to appear. The number of anionic sites in the paramesangial regions (epithelial side of the mesangium) was slightly more reduced than that in the capillary walls. These results suggested that PAN directly injured the glomerular anionic sites and increased the permeability of the glomerulus to macromolecules. However, there was no complete correlation between the number of lost anionic sites and the level of urinary protein excretion. Thus protein excretion into the urinary space may be related not only to the loss of subepithelial anionic sites but also to dysfunction of the protein absorption mechanism in epithelial cells due to excessive permeation of macromolecules through the GBM.

Animals↗

Induction of endogenous cytokines in ascites of patients with ovarian cancer by OK-432, a streptococcal preparation.

To clarify the action mechanism of OK-432, OK-432 was intraperitoneally (i.p.) administered to 4 ovarian cancer patients with malignant ascites. In 2 of the 4 patients, 4 types of cytokines (tumor necrosis factor, interleukin 1 beta, interleukin 2, and interferon gamma) were induced in ascites after intraperitoneal injection of OK-432 (i.p. OK-432). In one of these patients, the ascitic supernatant after i.p. OK-432 significantly inhibited colony formation of autologous ascitic tumor cells; the amount of ascites decreased markedly, and the ascitic cytology became negative. In the other 2 patients, only interferon gamma was induced in ascites after i.p. OK-432. In these 2, ascitic supernatant did not inhibit colony formation of autologous ascitic tumor cells. These results indicated that i.p. OK-432 can induce various endogenous cytokines in malignant ascites and that these induced cytokines may contribute to the antitumor effect of i.p. OK-432.

Ascites↗

Effects of a selective inhibitor of cyclic AMP phosphodiesterase on the pial microcirculation in feline cerebral ischemia.

We evaluated the effects of cilostazol, a selective inhibitor of cyclic adenosine monophosphate phosphodiesterase, on the pial vessels of adult cats subjected to endothelial damage followed by middle cerebral artery occlusion. Six cats were treated with cilostazol and four with 30% N,N-dimethylformamide in 70% saline (solvent). The brain surface was irradiated with ultraviolet rays through a cranial window for 3 minutes to selectively damage the endothelium of the pial vessels in both groups. Beginning 32 minutes after termination of the irradiation, the middle cerebral artery was occluded for 30 minutes. Thirty minutes before occlusion, intravenous infusion of 30 micrograms/kg/min cilostazol or 0.1 ml/kg/min solvent was begun and continued until the end of the study. Before occlusion, the infusion of cilostazol induced a significant (p less than 0.05) dilatation while the infusion of solvent produced no significant changes in the diameter of the pial arteries. The pial veins of solvent-treated cats showed significant (p less than 0.05) constriction during occlusion, whereas cilostazol-treated cats exhibited only mild constriction of the pial veins. The formation of platelet thrombi after occlusion was significantly (p less than 0.05) inhibited in the pial veins of cilostazol-treated compared with solvent-treated cats. Similarly, the microcirculation of the pial veins was effectively restored after reopening of the middle cerebral artery in cilostazol-treated compared with solvent-treated cats. Our data suggest that cilostazol is an effective antithrombotic agent as well as a potent vasodilator acting on vascular smooth muscle.

Animals↗

Demonstration of interleukin-1 beta on perifollicular endothelial cells in the thyroid glands of patients with Graves' disease.

We examined the presence of interleukin-1 (IL-1) in the thyroid glands of 20 patients with Graves' disease and 10 control subjects, using anti-IL-1 monoclonal antibodies in conjunction with immunohistochemical techniques. In 13 (65%) Graves' disease patients, IL-1 beta, but not IL-1 alpha, was demonstrated on the capillary endothelial cells (EC) around follicles (perifollicular EC). However, the EC of arteries and veins were negative for both IL-1 beta and IL-1 alpha. In the control group, none of the thyroid glands showed positive staining for IL-1 beta or IL-1 alpha. There was a significant correlation (P less than 0.025) between the presence of IL-1 beta on perifollicular EC and the presence of serum antimicrosomal antibodies. These results provide an important insight into the involvement of IL-1 beta in the development of Graves' disease.

Adolescent↗

Mechanism of cerebral vasospasm--contractile proteins in smooth muscle of bovine cerebral artery.

Understanding of the pathogenesis of cerebral vasospasm requires basic study of the contraction mechanism of cerebral arteries. In this study, the morphological and biochemical properties of actomyosin from bovine cerebral arteries were examined. Arrays of thick and thin filaments were clearly seen on electron micrographs of a cross section of a muscle strip stretched to 1.5 times its normal length in Krebs-Ringer solution. The diameters of the thick and thin filaments were 110.0 +/- 19.9 A and 51.0 +/- 8.0 A, respectively. The average ratio of thick to thin filaments was about 1:15 to 1:16. The gel pattern of Ca2+-sensitive actomyosin extracted from bovine cerebral arteries revealed the presence of myosin, actin, and tropomyosin, but not skeletal troponin. The Mg-ATPase activity of actomyosin was greatly enhanced in the presence of Ca2+. Rapid superprecipitation occurred after the clearing phase, when 1 mM Mg-ATP was added to a suspension of actomyosin with 10(-5) M Ca2+. This superprecipitation did not occur with a lower Ca2+ concentration of 10(-8) M. Intracellular free Ca2+ appears to play a crucial role in the regulation of contraction and relaxation of cerebral arterial smooth muscle.

Actins↗