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T Tsukada

Publications and source records attributed to T Tsukada.

378 records · Page 21Linked to original sources
PubMedDate not supplied

Biosynthesis of pancreatic islet hormones.

We have outlined the various strategies used to characterize the precursors of three pancreatic islet hormones--somatostatin, pancreatic polypeptide and VIP. In each case, isolation of the cDNA clones was facilitated by the use of gastrointestinal tissues that were extremely rich in specific mRNA. Characterization of the structures of the precursors is clearly only the first step in understanding the regulation of pancreatic hormone biosynthesis. It is likely that the availability of the cDNA clones will allow us to define the actual mechanisms underlying hormone production within the pancreas.

Animals↗
PubMedDate not supplied

Antiarrhythmic effects of bupuranolol against canine ventricular arrhythmias induced by halothane-adrenaline or two-stage coronary ligation.

We compared the beta-adrenoceptor blocking actions of bupuranolol and propranolol using the response to isoprenaline of the strength of contraction of the canine blood-perfused ventricular muscle, of the rate and strength of contraction of the isolated guinea pig heart and of a guinea pig tracheal ring preparation. The potency ratios of bupuranolol to propranolol were 3.6, 3.0, 3.4, and 2.4, respectively. Bupuranolol decreased the maximum dV/dt of the canine ventricular action potential and had no sympathomimetic action. Bupuranolol effectively suppressed halothane-adrenaline ventricular arrhythmias in the dog, reflecting its potency as a beta-adrenoceptor antagonist. In contrast, bupuranolol did not suppress ventricular arrhythmias induced by two-stage coronary ligation in the dog. Compared to propranolol and certain other antiarrhythmic drugs, bupuranolol had weaker effects on prolonging the effective refractory period than on the maximum dV/dt of canine ventricular muscle. This suggests that lengthening of the refractory period may be important for suppressing the two-stage coronary ligation arrhythmia and that the mechanism of this arrhythmia might be reentry.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Immunocytochemical analysis of cellular components in atherosclerotic lesions. Use of monoclonal antibodies with the Watanabe and fat-fed rabbit.

We have performed immunocytochemical investigations into the distribution of smooth muscle cells and macrophages in the atherosclerotic lesions of the Watanabe heritable hyperlipidemic (WHHL) and fat-fed rabbits. We used monoclonal antibodies specific for muscle cells and macrophages, the latter with a new macrophage-specific monoclonal antibody designated RAM11. Scattered macrophages were observed in the subendothelium in areas of grossly normal aorta. Raised lesions were divided into four major groups, based on qualitative aspects of cell localization: fatty streak, composed predominantly of macrophages; intimal thickening, composed predominantly of smooth muscle cells that displayed considerable morphological heterogeneity with an admixture of macrophages; early fibrous plaques, characterized by approximately equal numbers of smooth muscle cells and macrophages; advanced fibrous plaques, composed of a fibrous cap containing flat smooth muscle cells overlying a macrophage-rich zone of atheromatous debris. These studies demonstrate the nature of the lesions in the two rabbit models and the usefulness of monoclonal antibodies in analyzing the cellular composition of atherosclerotic lesions.

Animals↗
PubMedDate not supplied

Fatty streak expansion and maturation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits.

This study focuses on the expansion and maturation of the fatty streak in the aorta of Watanabe Heritable Hyperlipemic rabbits and comparably hypercholesterolemic fat-fed rabbits between 2 and 6 months duration of hypercholesterolemia. In both groups of animals, the fatty streaks expanded due to: 1) the formation of multiple layers of a mixed population of macrophage-derived foam cells and lipid-containing smooth muscle cells, 2) the hypertrophy of the macrophage-derived foam cells, 3) the continued accumulation of extracellular matrix, 4) the insudation of plasma components. Immunocytochemical studies utilizing macrophage-specific and muscle-actin-specific monoclonal antibodies indicated that the expanding and mature fatty streaks in both the Watanabe and fat-fed rabbits were primarily composed of macrophage-derived foam cells. Hypertrophy of those foam cells situated immediately beneath the endothelium was associated with retraction of the endothelium and exposure of the intimal foam cells to the circulation. Endothelial retraction with exposure of intimal foam cells may facilitate entry of blood cells and lipoproteins into the lesions and formation of mural thrombi on the surfaces of the exposed cells. Biochemical analyses of the cholesterol content of the arteries indicated that both unesterified cholesterol and cholesteryl esters were deposited to a comparable degree in both the Watanabe and fat-fed rabbits. Thus, the absence of the low density lipoprotein receptor in Watanabe rabbits does not appear to directly influence the accumulation of cholesterol in the artery wall.

Animals↗
PubMedDate not supplied

Fatty streak initiation in Watanabe Heritable Hyperlipemic and comparably hypercholesterolemic fat-fed rabbits.

Morphologic and immunocytochemical studies were conducted to determine the sequence of cellular interactions that occur during the initiation of the fatty streak in the aorta of Watanabe Heritable Hyperlipemic rabbits and comparably hypercholesterolemic fat-fed rabbits. Watanabe rabbits from 3.5 weeks gestation to 2 months of age and fat-fed rabbits from 1 week to 2 months duration of hypercholesterolemia were compared utilizing light microscopic and scanning and transmission microscopic techniques. In both groups of animals, the earliest detectable events were an increase in monocyte adherence and subendothelial migration followed by formation of a single layer of intimal macrophage-derived foam cells. Immunocytochemical studies using macrophage-specific and muscle-actin-specific monoclonal antibodies support the morphologic data which suggests that the early fatty streak in both the Watanabe and fat-fed rabbits is predominantly composed of macrophage-derived foam cells. Thus, the absence of functional low density lipoprotein receptors in the Watanabe rabbit and differences in the distribution of cholesterol among the lipoproteins in the Watanabe and fat-fed rabbits do not appear to alter the initial responses of the cells of the artery wall to chronic hypercholesterolemia.

Animals↗
PubMedDate not supplied

A possible route to large-scale production of SWNTs through a combination of the substrate and floating catalyst methods.

We describe a possible route for large-scale synthesis of single wall carbon nanotubes (SWNTs) by a combination of the substrate and floating methods. The template prohibits metal particle aggregation, resulting in high-purity SWNT growth, and the three-dimensional floating seeded state of the template induces improved yields of SWNTs in a semi-continuous system. The SWNTs obtained by this method exhibit large variations of texture (isolated tubes and bundles) and a wide range of diameters (0.4-4 nm).

Catalysis↗
PubMedDate not supplied

An adult case of acute lymphoblastic leukemia with necrotizing leukoencephalopathy.

A 19-year-old man with common acute lymphoblastic leukemia (ALL) developed necrotizing leukoencephalopathy (NL) after extensive chemotherapy and irradiation. Clinicians should exercise care in the treatment of leukemia, since chemotherapy has shown a trend of becoming more intensive, and the survival time of patients with leukemia is being extended.

Adult↗
PubMedDate not supplied

Lipolytic and lipoprotein lipase (LPL)-inhibiting activities produced by a human lung cancer cell line responsible for cachexia induction.

Previous studies have shown that five human cancer cell lines, LS180, MKN-1, MMG-1, C32 and LX-1, induced remarkable weight loss in tumor-bearing nude mice. With the aim of identifying novel molecules involved in lipid catabolism, conditioned media of these cancer cell lines were analyzed in terms of lipoprotein lipase (LPL)-inhibiting or lipolytic activities. All conditioned media from the five cell lines significantly suppressed LPL activity in 3T3-L1 cells, while media from LX-1 and C32 promoted lipolytic activity in a dose-dependent manner. RT-PCR and ELISA demonstrated that the major factors responsible for LPL inhibition and lipolysis were not IL-1beta, IL-6, IL-11, TNF-alpha, TGF-beta1 or LIF in all the cancer cell lines except for MMG-1 cells. Preliminary biochemical analysis showed that the LPL-inhibiting factor produced by LX-1 cells was approximately 65 kD and vulnerable to heat, whereas the lipolytic factor was less than 1 kD and heat stable. These results suggested that unknown factors are partially involved in the pathogenesis of cancer cachexia in tumor-bearing nude mice and further purification will be needed.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

15-Deoxyspergualin, an antiproliferative agent for human and mouse leukemia cells shows inhibitory effects on the synthetic pathway of polyamines.

The mechanism of the antitumor action of 15-deoxyspergualin (DSG) was investigated. DSG inhibited spermidine synthase noncompetitively with putrescine, spermine synthase competitively with spermidine and polyamine oxidase in vitro. Induction of ornithine decarboxylase (ODC) activity observed after subculture of human leukemia cells was blocked by the addition of DSG to the culture medium. In DSG-treated leukemia cells, putrescine, spermidine and spermine levels were markedly depressed. The synthesis of protein was also greatly diminished in these polyamine-depleted leukemic cells, whereas the depressions of DNA and RNA syntheses were minimum. In in vivo experiments, DSG depressed polyamine levels in P388 leukemic ascites cells, and prolonged the survival times of mice bearing the leukemia cells. These results suggest that inhibition of polyamine and protein biosyntheses by DSG is substantially responsible for its antitumor action on the tumor cells.

Acetyltransferases↗
PubMedDate not supplied

Role of smooth-muscle cells and macrophages in cardiac allograft arteriosclerosis in rabbits.

Accelerated coronary arteriosclerosis is one of the major complications in allogeneic cardiac transplantation, despite the significant improvement in immunosuppressive therapy. In this study we sought to clarify the cellular components in cardiac allograft arteriosclerotic lesions with monoclonal antibodies specific to either the muscle cell (HHF-35) or the macrophage (RAM-11). Four kinds of heterotopic transplantations were performed in the rabbit: (1) low cholesterol-fed (n = 5), (2) 1% cholesterol-fed (n = 5), (3) low cholesterol-fed and immunosuppressed (n = 6), and (4) 1% cholesterol-fed and immunosuppressed (n = 6). The donor hearts were removed after cardiac arrest in groups 1 and 2, and at 5 weeks after transplantation in groups 3 and 4. In groups 1 and 2 acute rejection was associated with slightly thickened intimal lesions composed of abundant infiltrating mononuclear cells and sparsely intermingled smooth-muscle cells. In group 3 the arterial intima were moderately thickened with the predominant proliferation of smooth-muscle cells. In group 4 coronary lumina were almost completely occupied with the intimal foam cells, which were derived mostly from macrophages and some from smooth-muscle cells. These data suggest that the proliferation of smooth-muscle cells might be a major factor contributing to arteriosclerosis in chronic cardiac rejection and that long-term exposure to hypercholesterolemia could induce the accumulation of smooth-muscle cells or macrophage-derived foam cells.

Animals↗
PubMedDate not supplied

Dioxopiperazine derivative potentiates antitumor effect of methylglyoxal bis(cyclopentylamidinohydrazone) on human and mouse leukemia cells.

Antiproliferative effects of 1,1'-ethylenedi-4-isobutoxy-carbonyloxymethyl-3,5-d iox opiperazine (MST-16), an inhibitor of topoisomerase II, in combination with methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP), an inhibitor for polyamine biosynthetic enzymes, were investigated using cultured human lymphoid cells and leukemic mice. The combined treatment of human Molt 4B lymphoid cells with MST-16 and MGBCP resulted in greater suppressions of cellular polyamine and protein biosyntheses and decrease of cell number than in the cells treated with either drug alone. Inhibition of macromolecule biosyntheses by MGBCP was additively potentiated by simultaneous treatment with MST-16. In vivo experiments, the combination of MST-16 and MGBCP markedly prolonged the survival time of mice bearing P388 or L1210 leukemia. These results suggest that good antitumor activity of combined treatment with MST-16 and MGBCP resulted from the diminution of DNA condensation and cellular proliferation caused by inhibition of topoisomerase II with MST-16 and by polyamine depletion with MGBCP.

Animals↗