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Biomedical subjects

S Kume

Publications and source records attributed to S Kume.

At least 73 records · Page 4Linked to original sources
PubMed1994

Indications for local excision of ampullary lesions associated with familial adenomatous polyposis.

BACKGROUND: The relative risk of periampullary carcinoma is high in patients with familial adenomatous polyposis (FAP). We examined the possibility of local treatment of the ampullary lesion of these patients in an early stage. STUDY DESIGN: From August 1991 to April 1993, 37 patients with FAP underwent endoscopic examination and biopsy of the ampulla. Local excision of the ampulla was performed in seven patients. RESULTS: Two of the seven patients were diagnosed with carcinoma in situ; the ages of the patients were 35 and 46 years. A 38-year-old woman had ampullary carcinoma infiltrating into the muscle of the sphincter of Oddi. These three cases showed a protruding change or deformity of the ampulla endoscopically. The laboratory data, cholangiogram, and abdominal ultrasonography were within normal limits. The superficial change of the ampulla along with the young age of the patients were considered to be factors that warranted further observation. Postoperative complications in two cases were treated successfully. CONCLUSIONS: Indications for local excision of the ampulla of patients with FAP would be protruding change of the ampulla, biopsy showing adenoma with severe atypia or carcinoma, in situ, no jaundice with or without subclinical abnormality of laboratory data, no apparent dilatation in the bile duct, and age of more than 35 years.

Adenomatous Polyposis Coli↗
PubMed1994

Effects of the prior activation of protein kinase C on human platelet activation induced by thrombin.

Effects of the prior activation of protein kinase C (PKC) on the responses induced by thrombin were studied using human blood platelets, in which PKC is abundantly expressed. At a concentration of 25 nM, 12-O-tetradecanoyl-phorbol 13-acetate (TPA) induced little aggregation or release by itself but selectively elicited PKC activation in a time-dependent manner, as monitored by 47-kDa protein phosphorylation. Increases in the intracellular Ca2+ concentration of human platelets caused by thrombin, at any concentration, were markedly inhibited by the prior addition of 25 nM TPA in a time-dependent manner. However, the effects of TPA on platelet aggregation and secretion induced by thrombin varied, depending upon the agonist concentration; the PKC activator markedly enhanced the aggregation and secretion induced by lower concentrations of thrombin but had a tendency to weakly inhibit those induced by higher concentrations of thrombin. TPA enhanced the ionomycin effect upon aggregation and release without obvious effects on the ionophore-induced Ca2+ mobilization, suggesting that PKC potentiates platelet function by increasing intracellular sensitivity to Ca2+. There was a good time-dependent correlation of the TPA effects among the three parameters, namely, the phosphorylation of the 47-kDa protein, inhibition of the [Ca2+]i increase induced by thrombin, and enhanced ionomycin effects in aggregation and release. It is most likely that the final responses of agonist-activated platelets depend upon the balance of two factors induced by PKC; inhibition of Ca2+ signals and enhancement of intracellular sensitivity to Ca2+.

Blood Platelets↗
PubMed1994

[Disorders of coagulation/fibrinolysis and bleeding tendency].

The liver produces almost all the factors involved in coagulation and fibrinolysis. The hepatic reticuloendothelial system also plays an important role in disposing activated coagulation/fibrinolysis-related factors and inhibitors. In liver cirrhosis, the production of coagulation/fibrinolysis-related factors is diminished, as well as its inhibitors. Moreover, the hematological profile is complicated by a decreased rate of clearance, thrombocytopenia induced by hypersplenism, and some qualitative abnormalities of the coagulation factor. Hence, treatment for bleeding tendency observed in cirrhotic patients is diverse.

Antithrombin III↗
PubMed1993

Effects of genistein, a tyrosine kinase inhibitor, on platelet functions. Genistein attenuates thrombin-induced Ca2+ mobilization in human platelets by affecting polyphosphoinositide turnover.

Genistein, a tyrosine kinase inhibitor, had no or only slight inhibitory effects on platelet aggregation or serotonin release induced by thrombin, while intracellular Ca2+ concentration ([Ca2+]i) elevation was substantially attenuated. It also inhibited the cyclooxygenase pathway, but this effect was not directly related to the suppressive effect of genistein on [Ca2+]i elevation. In order to clarify the mechanism by which genistein suppresses Ca2+ mobilization, its effect was examined on inositol phospholipid metabolism. The production of inositol-1,4,5-trisphosphate was inhibited by genistein in a dose-dependent manner, while 47 kDa protein phosphorylation or phosphatidic acid formation was not affected, suggesting that genistein does not inhibit phospholipase C activity. Pretreatment of unstimulated platelets with genistein increased the amount of phosphatidylinositol-4-monophosphate [PI(4)P], while that of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] was reduced. Thrombin stimulation of genistein-pretreated cells intensified this tendency, i.e. a further increase in the amount of PI(4)P and a decrease in the amount of PI(4,5)P2 in an inversely proportional manner. Taken together, these findings imply that genistein acted at the step of PI(4)P 5-kinase which produces PI(4,5)P2 from PI(4)P. Protein tyrosine phosphorylation induced by thrombin was not affected by genistein, suggesting that the inhibitory effect of genistein on polyphosphoinositides was unrelated to tyrosine kinase inhibition.

Arachidonic Acid↗
PubMed1993

Anti-CD9 monoclonal antibody elicits staurosporine inhibitable phosphatidylinositol 4,5-bisphosphate hydrolysis, phosphatidylinositol 3,4-bisphosphate synthesis, and protein-tyrosine phosphorylation in human platelets.

Phosphoinositide metabolism elicited by anti-CD9 monoclonal antibody, a well-characterized platelet activator, was studied using acetylsalicylic acid-treated human platelets. TP82, which is an anti-CD9 monoclonal antibody, induced classical phosphatidylinositol 4,5-bisphosphate hydrolysis, as monitored by intracellular Ca2+ mobilization and phosphatidic acid production, and synthesis of phosphatidylinositol 3,4-bisphosphate, which is a major component of newly-described 3-phosphorylated inositol phospholipids produced during platelet activation. These changes were severely inhibited by 1 microM staurosporine, a potent, though non-selective, protein kinase inhibitor, which also abolished TP82 induction of tyrosine phosphorylation of multiple platelet proteins. Protein-tyrosine phosphorylation appears necessary to initiate both the classical phosphoinositide turnover and synthesis of the newly-described 3-phosphorylated inositol phospholipids in anti-CD9 monoclonal antibody-induced platelet activation.

Alkaloids↗
PubMed1993

The Xenopus IP3 receptor: structure, function, and localization in oocytes and eggs.

To study the role of the IP3 receptor (IP3R) upon egg activation, cDNA clones encoding IP3R expressed in the Xenopus oocytes were isolated. By analyses of the primary structure and functional expression of the cDNA, Xenopus IP3R (XIP3R) was shown to have an IP3-binding domain and a putative Ca2+ channel region. Immunocytochemical studies revealed polarized distribution of XIP3R in the cytoplasm of the animal hemisphere in a well-organized endoplasmic reticulum-like structure and intensive localization in the perinuclear region of stage VI immature oocytes. In ovulated unfertilized eggs, XIP3R was densely enriched in the cortical region of both hemispheres in addition to its polarized localization. After fertilization, XIP3R showed a drastic change in its distribution in the cortical region. These results imply the predominant role of the XIP3R in both the formation and propagation of Ca2+ waves at fertilization.

Amino Acid Sequence↗
PubMed1993

Protein kinase C inhibitors suppress disc-sphere changes of human platelets, as assessed with the shape-change parameter.

Changes in the shape of human platelets and the biochemical mechanism responsible were evaluated, using the shape-change parameter. Neither the Na+/H+ exchanger, nor intracellular or extracellular calcium ions (Ca2+) affected disc-sphere changes induced by low doses of thrombin. Treatment with inhibitors of Ca2+ mobilization, calmodulin or mysoin light-chain kinase had no significant effect on the shape change of platelets. Staurosporine and H-7, both of which are inhibitors of protein kinase C, inhibited disc-sphere changes at low concentrations. Moreover, calphostin C, a specific inhibitor of protein kinase C, effectively inhibited thrombin-induced shape change, as assessed by the shape-change parameter, in a dose-dependent manner. 1-Oleoyl-2-acetyl-glycerol and 1,2-dioctanoyl-glycerol, which are synthetic protein kinase C activators, induced shape changes similar to those induced by thrombin. A decrease in the surface area of platelet images on scanning electron micrographs was used to quantify the disc-sphere transformation. The mean platelet areas was significantly decreased after stimulation with thrombin or 1-oleoyl-2-acetyl-glycerol. Pretreatment with H-7 inhibited the thrombin-induced disc-sphere change, as assessed by changes in the platelet surface area. Our results obtained with various inhibitors suggest that thrombin-induced platelet change, as assessed by the shape-change parameter, are associated with activation of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Low concentrations of sodium fluoride inhibit Ca2+ influx induced by receptor-mediated platelet activation.

Sodium fluoride (NaF) alone below the concentration of 10 mM had no effect on platelet intracellular Ca2+ ([Ca2+]i). When platelets were incubated with low concentrations of NaF (< 10 mM) prior to thrombin stimulation, the second phase of [Ca2+]i elevation which is attributable to Ca2+ influx was suppressed, while the initial rapid peak of [Ca2+]i which is attributable to internal Ca2+ release was unaffected. Ca2+ influx assessed by the addition of extracellular Ca2+ to cells preactivated by thrombin in the absence of extracellular Ca2+ was also inhibited by NaF in a dose-dependent manner. NaF was also effective in inhibiting thrombin- or U-46619-induced Mn2+ entry. This inhibitory effect of NaF on Ca2+ influx occurred after a lag of at least 30 s. However, Ca2+ influx induced by ionomycin-induced Ca2+ depletion or by thapsigargin, a Ca(2+)-ATPase inhibitor, was only partially suppressed by NaF treatment. It is suggested that Ca2+ entry induced by receptor-mediated activation is NaF-sensitive and that the depletion of Ca2+ storage sites by artificial procedures facilitates the opening of Ca2+ channels via NaF-insensitive pathways.

Blood Platelets↗
PubMed1993

Wheat germ agglutinin-induced intracellular calcium mobilization in human platelets: suppression by staurosporine and resistance to cyclic AMP inhibition.

The lectin wheat germ agglutinin (WGA) elicited a prompt and sharp increase in intracellular Ca2+ concentration in human platelets. The WGA-induced Ca2+ mobilization was markedly inhibited by a protein kinase inhibitor staurosporine, whereas Ca2+ mobilization by receptor-mediated agonists, including thrombin, platelet-activating factor, and arginine-vasopressin, was not. In contrast, the lectin-induced Ca2+ mobilization was resistant to cyclic AMP inhibition, compared with that induced by receptor-mediated agonists. These findings indicate that the mechanism of intracellular Ca2+ mobilization, or possibly phospholipase C activation, induced by WGA is different from that induced by receptor-mediated agonists in human platelets.

Alkaloids↗
PubMed1993

Effect of parity on colostral mineral concentrations of Holstein cows and value of colostrum as a mineral source for newborn calves.

Colostrum samples for 93 Holstein cows and blood samples of 49 newborn calves fed only colostrum for 1 wk postpartum were collected to clarify the effect of parity on colostral and plasma mineral concentration. The concentrations of colostral Ca, P, Mg, Na, Fe, Zn, Cu, and Mn were highest at parturition and decreased rapidly by 24 h postpartum. Three cows had an extremely low concentration of colostral Ca and P. Colostral Ca, P, and Mg at parturition decreased as lactation number increased and stabilized after the third lactation. Colostral Zn of primiparous cows at parturition tended to be higher than that of multiparous cows, but no effect on colostral Fe, Cu, and Mn was due to parity. Blood hematocrit and hemoglobin of newborn calves increased with greater lactation number of the dams, and the blood values were lowest at d 6 postpartum for calves born from primiparous cows. Plasma Ca of calves born from primiparous cows tended to be higher than those of calves from multiparous cows, and blood hemoglobin and plasma inorganic P concentrations of female calves were higher than those of males at d 1 postpartum. Blood hematocrit and hemoglobin and plasma Mg decreased with time postpartum, but plasma Zn and Cu increased. In general, lactation number was a major factor for alteration of colostral minerals of cows and mineral status of newborn calves.

Animal Nutritional Physiological Phenomena↗
PubMed1993

[A case report of surgical treatment of ruptured coronary artery aneurysm].

A 63-year-old women experienced acute heart failure due to a ruptured aneurysm resulting from the coronary artery fistula which originated from the left anterior descending artery. On surgery, the pericardial cavity was found filled with massive hemorrhagic fluid and perforation was detected on the surface of the aneurysm, sphere-shaped with a approximate diameter of 50 mm. Operation was done by closure of fistula and subsequent aneurysmectomy under extracorporeal circulation. Post operative course had been uneventful. Coronary artery fistula accompanied with aneurysm had been thought to have a high risk of rupture and to be in indication of surgical intervention. This case report was undertaken with bibliographical consideration, since there had been only a few reports of actual ruptures.

Aneurysm, Ruptured↗
PubMed1993

Effects of dilazep on platelet functions and volume change in patients with diabetes mellitus.

Dilazep (CAS 35898-87-4), a vasodilating agent, was administered to patients with diabetes mellitus (300 mg/day for a minimum of two weeks). Various parameters of platelet function were evaluated both pre- and post-therapy. While dilazep affected neither aggregation nor intracellular Ca++ mobilization, it had a tendency to attenuate arachidonic acid metabolism induced by 0.1 U/ml thrombin (p = 0.1). The rate of platelet volume increase induced by weak acid loading was significantly higher post-therapy than pre-therapy. Since platelet volume change is generally suppressed in diabetic patients, dilazep administration appeared to normalize volume change induced by acid loading. It is implicated that dilazep reduced the membrane rigidity of platelets from diabetic patients, thereby allowing easy expansion of platelet volume.

Aged↗
PubMed1992

Effects of oral hypoglycaemic agents on platelet functions.

The in vitro effects of three oral hypoglycaemic agents, gliclazide (1-(4-methylbenzensulfonyl)-3-[3-azabicylo(3,3,0)octyl]urea) , glibenclamide (1-[4-[2-(chloro-2-methoxybenzamide)-ethyl]-phenyl- sulfonyl]-3-cyclohexyl-urea) and glimepiride (1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-carboxamide)- ethyl]-phenylsulphonyl]3-(4-methylcyclohexyl)-urea), on functions of human platelets were evaluated. None of these agents up to a concentration of 40 microM inhibited platelet aggregation induced by thrombin. Glibenclamide and glimepiride in the range of 20-40 microM suppressed Ca2+ release from internal Ca2+ stores induced by thrombin. Gliclazide showed no effect on arachidonic acid metabolism of human platelets. Glimepiride selectively inhibited the cyclooxygenase pathway, while the activities of 12-lipoxygenase and phospholipase A2 were unaffected. Glibenclamide inhibited both the cyclooxygenase and 12-lipoxygenase pathways. It also attenuated arachidonic acid release from phospholipase A2. Oral hypoglycaemic agents with inhibitory effects on arachidonic acid metabolism may prove useful for the treatment of diabetic patients with enhanced platelet functions.

Arachidonic Acid↗
PubMed1992

Synthesis of phosphatidylinositol 3,4-bisphosphate but not phosphatidylinositol 3,4,5-trisphosphate is closely correlated with protein-tyrosine phosphorylation in thrombin-activated human platelets.

Synthesis of D-3-phosphorylated phosphoinositides and its correlation with protein-tyrosine phosphorylation were examined using human platelets. Thrombin stimulation of platelets resulted in time- and dose-dependent production of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), which is absent from resting platelets. In contrast, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) was detected in resting platelets, but remained unaffected by thrombin treatment. The production of PtdIns(3,4)P2 but not PtdIns(3,4,5)P3 was inhibited by pretreatment with staurosporine or dibutyryl cyclic adenosine monophosphate (dbcAMP). Protein-tyrosine phosphorylation, which is reportedly involved in generation of 3-phosphorylated phosphoinositides, was elicited in thrombin-activated platelets. The tyrosine phosphorylation was suppressed by pretreatment with staurosporine or dbcAMP. These observations suggest that synthesis of PtdIns(3,4)P2 but not PtdIns(3,4,5) P3 is closely correlated with protein-tyrosine phosphorylation in human platelets.

Alkaloids↗
PubMed1992

Suppression by wortmannin of platelet responses to stimuli due to inhibition of pleckstrin phosphorylation.

Studies were made of inhibition by wortmannin, a fungal metabolite, of human platelet responses to various stimuli. Wortmannin at concentrations as low as 1-100 nM inhibited several receptor-agonist-induced 5-hydroxytryptamine release from platelets, without affecting agonist-induced increases in the intracellular concentration of Ca2+. Phorbol 12-myristate 13-acetate (PMA), an active tumour promoter, caused 5-hydroxytryptamine release when combined with a low concentration of ionomycin, and platelet aggregation by itself; these effects of the phorbol ester were also inhibited by wortmannin as well as by staurosporine, a potent, although non-specific, protein kinase C (PKC) inhibitor, in a similar molar concentration range. The platelet responses to the receptor agonists or PMA were accompanied by increased incorporation of [32P]Pi into pleckstrin, a protein selectively expressed in platelets and other blood cells arising from haematopoietic stem cells, as a result of PKC activation in the intact cells. The pleckstrin phosphorylation was inhibited by wortmannin in ways mostly similar to those in which it inhibited the 5-hydroxytryptamine-release responses. Nevertheless, wortmannin failed to inhibit PKC activity measurable in a cell-free assay system which is highly susceptible to staurosporine. Nor did it inhibit the translocation of cytosolic PKC to membranes induced by addition of PMA to platelet cells. Thus wortmannin, which is not a direct inhibitor of PKC, could interfere with the kinase-dependent phosphorylation of pleckstrin, which may play an important role in the cellular responses to receptor stimulation.

Alkaloids↗
PubMed1992

Phosphorylation of the inhibitory guanine-nucleotide-binding protein as a possible mechanism of inhibition by protein kinase C of agonist-induced Ca2+ mobilization in human platelet.

Increases in the intracellular Ca2+ concentration of human platelets caused by receptor agonists, such as thrombin, 9,11-epithio-11,12-methanothromboxane A2 (STA2), platelet-activating factor (PAF) and arginine-vasopressin, were inhibited by prior addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) in time-dependent and concentration-dependent manners. The inhibitions were mostly reversed by staurosporine, and inhibitor of protein kinase C, added 1 min before TPA. Prior treatment of platelets with thrombin or STA2, the efficacious Ca2+ mobilizer, suppressed the increase in the intracellular Ca2+ concentration of the cells to other agonists, but treatment with less efficacious PAF or vasopressin did not. The heterologous receptor desensitizations were also reversed by staurosporine. The antibody, directed against the carboxy-terminal region of the alpha subunits 1 and 2 of the inhibitory guanine-nucleotide-binding proteins (Gi1 alpha and Gi2 alpha), was raised in rabbit and was used to immunoprecipitate Gi alpha in 32P-labeled platelets. The radioactivity was detected in Gi alpha after incubation of 32P-labeled platelets with TPA, thrombin or STA2, but not in the cells incubated with PAF or vasopressin. The time-dependency or concentration-dependency of TPA-induced phosphorylation of Gi alpha was similar to the dependency of its inhibitory action on agonist-induced Ca2+ mobilization. Thus, strong activation of Ca2+/phospholipid-dependent protein kinase C by phorbol ester or agonists of certain Ca(2+)-mobilizing receptors leads to phosphorylation of the alpha subunit of guanine-nucleotide-binding protein, thereby impairing the coupling of the G protein to receptors as a feedback regulatory component of the receptor-triggered intracellular Ca(2+)-mobilizing system.

Alkaloids↗