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Biomedical subjects

M Iwai

Publications and source records attributed to M Iwai.

At least 199 records · Page 11Linked to original sources

The effect of a cystamine derivative, bis[2-(E-2-hexenoylamino)ethyl] disulfide, on rat platelet aggregation.

Bis[2-(E-2-alkenoylamino)ethyl] disulfides (compds. I), synthesized from cystamine and 2-trans fatty acids, inhibited collagen-induced rat and rabbit platelet aggregation. The most potent compound was bis[2-(E-2-hexenoylamino)ethyl] disulfide (compd. I-1), and this compound suppressed thromboxane B2 formation from arachidonic acid in rat platelets. The results suggested that compd. I-1 has an inhibitory effect on cyclooxygenase.

Alkenes↗

The inhibitory effect of bis[2-[(E)-2-octenoylamino]ethyl] disulfide on the cyclooxygenase pathway.

Bis[2-[(E)-2-octenoylamino]ethyl] disulfide (compd. I-3) inhibited collagen- and arachidonic acid-induced rat platelet aggregation, although not adenosine 5'-diphosphate (ADP)-induced rat platelet aggregation. Based on these results, we then investigated the inhibitory effect of compd. I-3 on thromboxane B2 formation from arachidonic acid in rat platelets, and prostaglandin I2 formation in rat aortae. Compound I-3 inhibited both thromboxane B2 and prostaglandin I2 formation, suggesting that it has an inhibitory effect on cyclooxygenase. The inhibitory effect of compd. I-3 was confirmed in experiments using a crude preparation of sheep seminal vesicle microsomal prostaglandin synthetase. These findings suggested that compd. I-3 has an inhibitory effect on cyclooxygenase activity, like nonsteroidal anti-inflammatory drugs.

Animals↗

[Application of isocyanate separating agent for acrylic resin].

The most widely used agents for separating acrylic resin from gypsum molds are the water-soluble alginates, which produce a very thin water- and organic solvent-insoluble calcium alginate film on the gypsum surface. In the present study, a new type of separating agent, an isocyanate type coating agent, was developed and it's properties were investigated. This coating agent is composed mainly of trimethylol-propane-tolylenediisocyanate and ethyl-acetate, with a small amount of bis-tributyl-tin oxide as catalyst. At first, a thin film was formed on the surface by application of the agent, and then alkyl-phosphate was applied to this film to ensure easy separation of the cured resins from the molds. The molds treated with this separating agent had a glossy, hard surface. The surface of the cured resins treated in this way was glossier and smoother than that of resin treated with the water-soluble alginates.

Acrylic Resins↗

[Primary tissue culture of nevus cell nevus--in comparison with the findings from neurofibroma culture].

Forty-two nevus cell nevi excised surgically from 40 patients were processed for primary culture. The characteristic features of cultured nevi were compared with those of neurofibroma reported previously. 1) Based on phase-microscopic findings, S-100 protein staining, and slow motion picture, most of the cultured macrophage-like cells or cells with dendrites were considered to be nevocytes. 2) The emigration of nevocytes was observed in 31 of the 42 nevus cultures (73%). Nevocytes classified histologically as the intradermal type with fatty degeneration and nevi obtained from the face and aged patients exhibited higher tendencies to ward emigration when they were cultured. 3) The cultured Schwann cells in neurofibroma and the nevus cell nevus, mainly c-type nevocytes, are both of neural crest origin. They were observed to have closely similar morphological and S-100 protein staining features.

Adolescent↗

Potential role for prostaglandin F2 alpha, D2, E2 and thromboxane A2 in mediating the metabolic and hemodynamic actions of sympathetic nerves in perfused rat liver.

In isolated rat liver perfused at constant pressure perivascular nerve stimulation caused an increase of glucose and lactate output and a reduction of perfusion flow. The metabolic and hemodynamic nerve effects could be inhibited by inhibitors of prostanoid synthesis, which led to the suggestion that the effects of nerve stimulation were, at least partially, mediated by prostanoids [Iwai, M. & Jungermann, K. (1987) FEBS Lett. 221, 155-160]. This suggestion is corroborated by the present study. 1. Prostaglandin D2, E2 and F2 alpha as well as the thromboxane A2 analogue U46619 enhanced glucose and lactate release and lowered perfusion flow similar to nerve stimulation. 2. The extents, the kinetics and the concentration dependencies of the metabolic and hemodynamic actions of the various prostanoids were different. Prostaglandin F2 alpha and D2 caused relatively stronger changes of metabolism, while prostaglandin E2 and U46619 had stronger effects on hemodynamics. Prostaglandin F2 alpha elicited greater maximal alterations than D2 with similar half-maximally effective concentrations. Prostaglandin F2 alpha mimicked the nerve actions on both metabolism and hemodynamics best with respect to the relative extents and the kinetics of the alterations. 3. The hemodynamic effects of prostaglandin F2 alpha could be prevented completely by the calcium antagonist nifedipine without impairing the metabolic actions of the prostanoid. Apparently, prostaglandin F2 alpha influenced metabolism directly rather than indirectly via hemodynamic changes. The present results, together with the previously described effects of prostanoid synthesis inhibitors, suggest that prostanoids, probably prostaglandin F2 alpha and/or D2, could be involved in the actions of sympathetic hepatic nerves on liver carbohydrate metabolism. Since prostanoids are synthesized only in non-parenchymal cells, nervous control of metabolism appears to depend on complex intra-organ cell-cell interactions between the nerve, non-parenchymal and parenchymal cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Leukotrienes increase glucose and lactate output and decrease flow in perfused rat liver.

In isolated perfused rat liver leukotriene C4 and D4 but not B4 and E4 enhanced glucose and lactate output and lowered perfusion flow similar to the thromboxane A2 analogue U46619, extracellular ATP and prostaglandin F2 alpha. The kinetics of the metabolic changes caused by leukotriene C4 and D4 resembled those effected by U46619 and ATP but not those elicited by prostaglandin F2 alpha; the kinetics of the hemodynamic changes were similar only to those caused by U46619. The results show that leukotrienes could be important modulators of hepatic metabolism and hemodynamics and point to a complex intra-organ cell-cell communication between non-parenchymal and parenchymal cells.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Immunocytochemical investigation of hepatitis B virus-associated antigens in cases of liver cirrhosis and HBsAg antigenemia and their relationship to development of hepatocellular carcinoma.

Using light and ultrastructural immunoperoxidase techniques, we examined the distribution of hepatitis B virus (HBV)-associated antigens and the subcellular localization of hepatitis B surface antigen (HBsAg) in liver biopsies of HBsAg-positive patients with cirrhosis. The localization patterns of HBsAg in hepatocytes were membranous, cytoplasmic, festoon and inclusion body types. Cytoplasmic and festoon types were seen more often than the membranous type in pseudolobules, and hepatitis B core antigen (HBcAg)-positive cells with cytoplasmic type were distributed in the periphery of pseudolobules with active inflammation. Immunoelectron microscopy in the cytoplasmic or festoon type of HBsAg showed immunoreaction in the cisternae and on virus-like particles in the cisternae in patients with hepatitis B e antigen (HBeAg) antigenemia. Simultaneous staining of HBsAg and HBcAg revealed that hepatocytes with cytoplasmic or festoon type of HBsAg contained HBcAg-immunoreactivity. The inclusion body type of HBsAg was characteristic of liver cirrhosis with hepatocellular carcinoma (HCC); the subcellular localization of HBsAg was seen in clusters of the endoplasmic reticulum around the nucleus, and HBsAg-immunoreactivity was observed on many virus-like particles in most of the cisternae in those with HBeAg antigenemia. These findings suggest that the synthesis of HBsAg is active in patients with liver cirrhosis and that the formation of HBV is also active in those with HBeAg antigenemia and that HBV may be retained more in cirrhotic livers with hepatocellular carcinoma after proliferation than in those without it.

Antigens, Viral↗

Demonstration by light and ultrastructural immunoperoxidase study of alpha-fetoprotein-positive non-hepatoma cells and hepatoma cells during 3'-methyl-4-dimethylaminoazobenzene hepatocarcinogenesis.

Immunoreaction of alpha-fetoprotein (AFP) has been described in cholangiolar "oval" cells in the early stage of 3'-methyl-4-dimethylaminoazobenzene hepatocarcinogenesis. The subcellular location of AFP in the oval cells was in the perinuclear space, rough endoplasmic reticulum and Golgi apparatus. In livers with hyperplastic nodules there were two different types of foci containing AFP-positive cells. One type had a normal nucleocytoplasmic ratio and was seen in well-preserved hepatic trabecular structures, and the other had less cytoplasm and occurred in trabecular structures in disarray. AFP-immunoreactivity in the former type was visible in the perinuclear space and rough endoplasmic reticulum but scarce in the Golgi apparatus, and in the latter type it was present in the proliferative smooth endoplasmic reticulum and in several parts of Golgi apparatus in the submembranous or pericanalicular areas. In livers with hepatocarcinoma, AFP immunoreaction was detected in well-differentiated hepatocellular carcinomas, and the subcellular location of AFP was in the perinuclear space, rough endoplasmic reticulum and many developed Golgi complexes. Therefore, AFP-positive cells in livers with hyperplastic nodules are a new cell population in hepatocarcinogenesis, and each type is morphologically different from the oval cell.

Animals↗

Effect of CS-514 (pravastatin) on VLDL-triglyceride kinetics in rats.

The effect of CS-514 (pravastatin; Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, on triglyceride turnover, was studied in male Wistar rats. CS-514 (15 +/- 1 mg/day per rat) was administered as a 0.04% solution in drinking water for 14 days. Triglyceride and cholesterol in very low density lipoprotein (VLDL) and plasma triglyceride were reduced by treatment with CS-514. Plasma cholesterol level was not suppressed by CS-514. The CS-514 treated rats had a significantly suppressed triglyceride secretion rate (TgSR) during the fed state compared to control rats (0.85 +/- 0.1 vs. 1.07 +/- 0.3 mg/min, P less than 0.05). By contrast, CS-514 treatment did not suppress TgSR after an overnight fast. These data demonstrate that CS-514, an inhibitor of cholesterol biosynthesis can suppress VLDL-triglyceride secretion in rats and that this effect can be modified by dietary manipulation.

Animals↗

Effects of CS-514 on plasma lipids and lipoprotein composition in hypercholesterolemic subjects.

The effect of CS-514 (eptastatin, Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was investigated in 47 patients with hypercholesterolemia (WHO type IIa: 27, IIb: 20). Ten or 20 mg of CS-514 was administered daily for 3 months. In both types of patient, total cholesterol and phospholipid levels were significantly reduced by CS-514. The triglyceride, cholesterol and phospholipid content of low density lipoprotein (LDL) and the plasma levels of apolipoprotein B were also decreased in both groups. In contrast, total triglyceride, very low density lipoprotein (VLDL)-triglyceride and apolipoprotein C-II were decreased only in type IIb subjects. Also the levels of high density lipoprotein (HDL)-cholesterol and apolipoproteins A-I and A-II were increased by CS-514 in IIb but not in IIa patients. In both groups, no change occurred in either the cholesterol/triglyceride or phospholipid ratio in any lipoprotein fraction, nor in the ratio of HDL-cholesterol to apolipoprotein A-I or A-II, respectively. Therefore, CS-514 suppresses plasma levels of cholesterol in hypercholesterolemic patients without modifying lipoprotein composition. Moreover, this drug has different effects on the levels of plasma triglyceride and HDL-cholesterol of type IIa and IIb patients.

Adult↗

Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats.

The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine aminotransferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VMH) in CCl4-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VMH stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl4 injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve (hepatic nerves), possibly by affecting liver metabolism more than the blood flow change to the liver.

Alanine Transaminase↗

Liver phosphorylase activation during early phase of feeding behavior: a neurohumoral regulation.

The mechanisms of liver glycogen depletion during the early phase of spontaneous feeding were examined in adult rats. A 40% increase in the activity of phosphorylase a, the active form of a key glycogenolytic enzyme, was detected 5 min after the onset of feeding, with a concomitant decrease of glycogen in the liver after 5 and 15 min. Within 60 min after the onset of feeding, the enzyme activity returned to the basal level and the glycogen content was restored. These metabolic responses were impaired by hepatic sympathetic denervation or by bilateral adrenodemedullation. It was concluded that the onset of meals may evoke an arousal of the sympathoadrenal system including the hepatic innervation, and that activation of this system is important in stimulating liver phosphorylase activity and glycogenolysis during the early phase of spontaneous feeding.

Adrenal Medulla↗

Leukotriene C4 metabolism during its action on glucose and lactate balance and flow in perfused rat liver.

Rat livers were perfused in a non-recirculating mode at constant pressure via the portal vein with media containing 5 mM glucose, 2 mM lactate, and 0.2 mM pyruvate. [3H]LTC4 was infused for a period of 5 min to a final concentration of 20 nM; it increased glucose and lactate output and reduced perfusion flow. 1) Leukotriene radioactivity was recovered 10 min after the onset of [3H]LTC4 infusion to about 40% in the effluent, to 20% in the bile, and to 40% in the liver. 2) Radioactivity in the effluent increased to a maximum 4-5 min after the onset and decreased again to essentially zero 3 min after completion of [3H]LTC4 infusion. [3H]LTC4 and [3H]LTD4 were the major labeled components in the effluent accounting for 45% and 38%, respectively, of the effluent radioactivity. 3) [3H]LTC4 and [3H]LTD4 were also the major components in bile; they accounted for 50% and 30%, respectively, of the radioactivity excreted, while more polar [3H]leukotriene metabolites accounted for the remainder. 4) In the liver, [3H]LTC4 and [3H]LTD4 were the major and [3H]LTE4, N-acetyl-[3H]LTE4 as well as omega-hydroxy-N-acetyl-[3H]LTE4 and omega-carboxy-N-acetyl-[3H]LTE4 were minor components detected 5 min after completion of [3H]LTC4 infusion. It is concluded from the present findings that during a 5 min infusion period about one third each of the infused LTC4 remained unchanged, was converted to LTD4, and was further degraded to LTE4 and polar metabolites including omega-oxidation products of N-acetyl-LTE4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cholestatic liver disease in a 20-yr-old woman with histiocytosis X.

A 20-yr-old woman with known diabetes insipidus complained of high fever and jaundice. Liver specimens biopsied under peritoneoscopy showed proliferating histiocytic or foamy cells in periportal areas. Immunocytochemical investigation demonstrated the presence of S-100 protein, but the absence of lysozyme in their histiocytic cells, and ultrastructural study revealed Birbeck granules in them. Vinblastine therapy reduced jaundice and high fever, and diabetes insipidus was controlled. Clinical, immunohistological, and cytological features suggested Letter-Siwe disease with jaundice, which responded well to treatment.

Adult↗

[Cytophotometric analysis of the nuclear DNA content in oral squamous cell carcinoma--relation between nuclear DNA content and clinico-pathologic findings].

Cytophotometric analysis has been performed on Feulgen-stained nuclei in smears taken from 48 biopsy specimens of squamous cell carcinoma of the oral cavity. The results were correlated with the clinico-pathologic findings of the tumor. DNA histograms were graded into three patterns: P-I (2C-2C), P-II (2C-6C) and P-III (2C-beyond 6C). DNA patterns of the carcinoma of the clinical stage I, II tended to be P-I, II and those of stage III, IV were mostly P-II, III. DNA patterns of carcinomas which were well differentiated and poorly pleomorphic with a few number of mitoses, were mostly P-I, whereas those which were poorly differentiated and remarkably pleomorphic with a many number of mitoses were mostly P-III.

Carcinoma, Squamous Cell↗