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Biomedical subjects

T Tanimoto

Publications and source records attributed to T Tanimoto.

At least 253 records · Page 14Linked to original sources

[Possible modes of action of growth factors and tumor promoters in the activation of the c-myc gene in Swiss 3T3 fibroblasts].

It has been suggested that the c-myc gene may play an important role in the regulation of cell proliferation. We have investigated the transmembrane signaling mechanisms of various growth factors and tumor promoters in Swiss 3T3 fibroblasts and have examined the causal relationship between these mechanisms and c-myc gene activation. Platelet-derived growth factor and FGF (fibroblast growth factor) induced the activation of diglyceride-protein kinase C and Ca2+ systems through phosphoinositide turnover, resulting in the activation of the c-myc gene. Epidermal growth factor did not activate these two systems but stimulated gene activation. Prostaglandin E1 elicited Ca2+ mobilization and cyclic AMP generation followed by c-myc gene activation. In contrast to these growth factors, tumor-promoting phorbol esters induced the direct activation of protein kinase C which led to c-myc gene expression. Bile acids, which are known to be colon tumor promoters, were inactive by themselves but enhanced FGF-induced diglyceride formation and thereby potentiated protein kinase C activation. It has not yet been examined whether bile acids potentiate FGF-induced activation of the c-myc gene. The growth factors described above and the phorbol esters stimulated DNA synthesis in the presence of insulin, whereas the bile acids potentiated FGF-induced DNA synthesis. These results strongly suggest that three messenger systems, diglyceride, Ca2+ and cyclic AMP, may be involved in c-myc gene activation which may be implicated in DNA synthesis in Swiss 3T3 cells.

Animals↗

Formation of a phorbol ester-binding fragment from protein kinase C by proteolytic digestion.

When washed human platelets were disrupted by sonication in the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, both the catalytic and [3H]phorbol-12,13-dibutyrate (PDBu)-binding activities of protein kinase C were recovered in the soluble fraction and were not separable from each other upon several column chromatographies. Platelet protein kinase C required diacylglycerol, Ca2+, and phospholipid for its activation and showed a molecular weight of about 87,000 as estimated by gel filtration analysis. However, when platelets were first incubated with 2 microM Ca2+-ionophore A23187 for 5 min at 37 degrees C in the medium containing 3 mM CaCl2 and then disrupted under the same conditions, the catalytic and [3H]phorbol-12,13-dibutyrate-binding activities were separately recovered in the soluble and particulate fractions, respectively; moreover, the catalytic activity recovered in the soluble fraction became independent of diacylglycerol, Ca2+, and phospholipid, and showed a molecular weight of about 50,000 as estimated by gel filtration analysis. The kinetic properties of this Mr 50,000 enzyme were similar to those of the catalytic fragment of rat brain protein kinase C described previously. In a cell-free system, digestion with trypsin of protein kinase C highly purified from rat brain caused the generation of a fragment which had no catalytic activity but showed full [3H]phorbol-12,13-dibutyrate-binding activity. The molecular weight of this fragment was estimated to be about 35,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicate that protein kinase C consists of at least two functionally different domains, a hydrophobic phorbol ester- or diacylglycerol-binding and hydrophilic catalytic domains.

Binding Sites↗

[The role of brain-stem vasomotor centers on the neurogenic control of cerebrovascular tonus. Part 2: The effect of stimulation of the medullary reticular formation on cerebrovascular tonus].

Acute brain swelling has been proposed to be caused by vasomotor paralysis secondary to disruption of metabolic and/or neurogenic control of cerebrovascular tone. In previous experiments, acute brain swelling was produced by stimulation of the reticular formation of the medulla oblongata (MORF) with destruction of the dorsomedial nucleus of the hypothalamus (DM) and the reticular formation of the midbrain (MBRF) in 2 (out of 56) animals. The purpose of the present study is to clarify the effect of stimulation of the MORF on cerebrovascular tone. Using 32 cats, blood pressure (BP), intracranial pressure (ICP) and cerebral blood volume (CBV) were continuously measured. The animals were divided into 4 groups: those in which the ICP was normal (Group A), those in which the ICP increased after subarachnoid hemorrhage (Group B), those which underwent superior cervical ganglionectomy (Group C) and those in which the spinal cord was transected at the C2 level (Group D). In all animals, the MORF was stimulated after the DM and MBRF were destroyed. Thirty minutes after cessation of stimulation, the BP was increased again by injection of angiotensin II until it reached the same level as with MORF stimulation. The vasomotor index (VI), defined by delta ICP/delta BP, was calculated and compared between the two situations. BP, ICP and CBV increased simultaneously immediately after MORF stimulation. In 29 out of the 32 animals, ICP increased abruptly from 2 to 48 mmHg and after ten seconds or more decreased gradually. The BP rose about 50 mmHg more slowly than the ICP. After cessation of MORF stimulation, BP, ICP and CBV returned to the control value.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

A case of acute renal failure associated with type A acute hepatitis responds dramatically to plasmapheresis.

A case of acute renal failure (ARF) associated with type A acute hepatitis followed by a dramatic response to plasmapheresis is described. A female patient was transferred to our hospital with a diagnosis of ARF associated with acute hepatitis. Since radioimmunoassay for IgM antibody to hepatitis A virus showed a positive reaction, recent infection with hepatitis A virus was suspected. Hemodialysis immediately performed after admission was not effective. Plasmapheresis was started on the 5th hospital day and there was a dramatic improvement in ARF and hepatitis. It is concluded that plasmapheresis is effective in the treatment of ARF associated with liver disease if it is applied in the early stage.

Acute Kidney Injury↗

Enhancement of collagen-induced phosphoinositide turnover by thromboxane A2 analogue through Ca2+ mobilization in human platelets.

In human washed platelets, collagen-induced phosphoinositide turnover was inhibited by indomethacin, an inhibitor of thromboxane A2 (TXA2) formation, particularly at lower doses of collagen. This inhibition was counteracted by the addition of 9,11-epithio-11,12-methano-TXA2 (STA2), a stable analogue of TXA2 as well as by the Ca2+ ionophore A23187. STA2 and A23187 did not stimulate phosphoinositide turnover markedly, but significantly increased cytoplasmic free Ca2+ concentrations. The actions of STA2 were blocked by 13-azaprostanoic acid, a TXA2 receptor antagonist. The results suggest that TXA2 is generated during the action of collagen and increases cytoplasmic free Ca2+ which then stimulates phosphoinositide turnover in cooperation with collagen.

Blood Platelets↗