Search PubMed⌕ Search

Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 271 records · Page 15Linked to original sources
PubMed1997

Vasoactive intestinal peptide causes nitric oxide-dependent pulmonary vasodilation in isolated rat lung.

Vasoactive intestinal peptide (VIP) is one of the chief neurotransmitters of nonadrenergic noncholinergic nerve fibers. In this study, we investigated the effect of VIP on the pulmonary circulation in isolated perfused rat lungs. Baseline pressures of the pulmonary artery for the isolated rat lungs were not affected by 3 x 10(-8) M VIP. VIP caused dose-dependent pulmonary vasodilation when the pulmonary vascular bed was constricted with 20 mM KCl. This vasodilative effect of VIP was inhibited by 1 x 10(-6) M L-n omega-nitro-arginine, an endothelium-derived relaxing factor (nitric oxide) inhibitor, and was restored by the addition of 10(-4) M L-arginine, a substrate of nitric oxide. VIP also caused suppression of the ANG II pressor response, and this VIP-induced suppressive effect was reduced when L-N omega-nitro-arginine or 3 x 10(-6) M meclofenamate was added to the perfusate. These results indicate that VIP causes pulmonary vasodilation in isolated rat lung and suggest the possible involvement of NO and/or cyclooxygenase metabolites in VIP-induced pulmonary vasodilation.

Angiotensin II↗
PubMed1997

Norepinephrine stimulates mitogen-activated protein kinase activity in GT1-1 gonadotropin-releasing hormone neuronal cell lines.

The GT1-1 GnRH neuronal cell lines exhibit highly differentiated properties of GnRH neurons. We have used GT1-1 cells to study the roles of norepinephrine (NE), membrane depolarization, calcium influx, and phorbol esters in the regulation of mitogen-activated protein (MAP) kinase. NE, which is known to stimulate the release of GnRH, induced MAP kinase activity, the tyrosine phosphorylation of MAP kinase, and MAP kinase kinase activity. Forskolin led to activation of MAP kinase comparable with that induced by NE, and a selective inhibitor of cAMP-dependent protein kinase, H8, attenuated the NE-induced activation of MAP kinase. On the other hand, elimination of extracellular calcium by EGTA completely blocked NE-induced tyrosine phosphorylation of MAP kinase, and a selective inhibitor of calcium/calmodulin-dependent protein kinase, KN-62, attenuated the NE-induced activation of MAP kinase. Furthermore, depolarization of GT1-1 cells with 75 mM KCl, 10 microM BayK 8644, or 1 microM calcium ionophore (A23187) induced rapid tyrosine phosphorylation of MAP kinase. The omission of calcium from the extracellular medium completely abolished these effects of tyrosine phosphorylation of MAP kinase. Phorbol 12-myristate 13-acetate (PMA) also induced MAP kinase activity, but pretreatment of the cultured cells with PMA to down-regulate protein kinase C did not abolish the activation of MAP kinase by NE. In addition, although phosphorylation of Raf-1 kinase was stimulated by PMA, this phosphorylation was not induced by either NE or A23187. These results demonstrate that NE activates MAP kinase directly in GT1-1 cells, and that the effect of NE is mediated by increase in the cAMP level and by calcium influx, but not by PMA-sensitive protein kinase C or Raf-1 kinase.

Animals↗
PubMed1997

Role of mitogen-activated protein kinase pathway in prostaglandin F2alpha-induced rat puerperal uterine contraction.

In this study, prostaglandin (PG) F2alpha was found to activate mitogen-activated protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal uterine myometrial cells. PGF2alpha stimulation also led to an increase in phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we examined the mechanism by which PGF2alpha induced MAP kinase phosphorylation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase 1 (betaARK1), which specifically blocks signaling mediated by the betagamma subunits of G proteins, blocked the PGF2alpha-induced activation of MAP kinase. Ritodrine (1 microM), which is known to relax uterine muscle contraction, attenuated PGF2alpha-induced tyrosine phosphorylation of MAP kinase. Moreover, to examine the role of MAP kinase pathway in uterine contraction, an inhibitor of MEK activity, PD098059, was used. Although MEK inhibitor had no effect on PGF2alpha-induced calcium mobilization, this inhibitor partially inhibited PGF2alpha-induced uterine contraction. These results provide evidence that PGF2alpha stimulates the MAP kinase signaling pathway in cultured rat puerperal uterine myometrial cells through Gbetagamma protein, suggesting that this new pathway may play an important role in the biological action of PGF2alpha on these cells.

Animals↗
PubMed1997

New polyhydroxylated steroidal saponins from the tubers of Brodiaea californica.

New polyhydroxylated steroidal saponins (1, 2) were isolated from the tubers of Brodiaea californica. The structures were determined by spectroscopic analysis and acid-catalyzed hydrolysis. The bisdesmosidic saponin (2) is unique in structure, and is the first representative of a steroidal saponin bearing 6-deoxy-D-gulopyranose among both the steroidal and triterpene saponins reported up to the present.

Chromatography, High Pressure Liquid↗
PubMed1997

Balloon angioplasty for aortic coarctation--report of a questionnaire survey by the Japanese Pediatric Interventional Cardiology Committee.

The aim of this study was to analyze the results of a questionnaire survey regarding acute and late effects of balloon angioplasty for aortic coarctation in Japan. Considerable controversy still exists regarding the effectiveness and safety of balloon angioplasty in native coarctation. Moreover, little information about this mode of treatment is available from Japan. A questionnaire was sent to 55 Japanese institutions with pediatric cardiology units. A total of 208 patients from 35 institutions were reported and analyzed for indications for balloon angioplasty, acute and late results, and complications. Balloon angioplasty was performed in 56 patients with native coarctation (group I) and in 152 patients with postoperative recoarctation (group II). In group I, the pressure gradient across the coarcted site decreased significantly from 34 +/- 19 to 16 +/- 21 mmHg (p < 0.001), and the diameter of the coarcted site increased significantly from 3.7 +/- 1.7 to 6.0 +/- 2.5 mm (p < 0.001). In group II the pressure gradient significantly decreased from 41 +/- 20 to 15 +/- 15 mmHg (p < 0.001) and the diameter of the coarcted site significantly increased from 4.2 +/- 2.2 to 6.8 +/- 3.1 mm (p < 0.001). The restenosis rate was significantly higher in group I (19/41, 46%) than in group II (25/139, 18%) (p = 0.0006). Redilation was successfully performed in 27 of 29 of the patients with restenosis. Major complications included femoral pulse loss, transient bradycardia, and arrhythmia. No patient died of a cardiac event related to the procedure. The significant risk factors for late restenosis included type of coarctation, age under 4 months, balloon size used, pressure gradient and coarctation diameter before the procedure. Balloon angioplasty is a suitable treatment for aortic coarctation in both native coarctation and postoperative recoarctation. Restenosis was significant after initial balloon angioplasty in native coarctation but redilation was effective in most cases. The most significant risk group for restenosis is young children with native coarctation.

Adolescent↗
PubMed1997

Coil occlusion for patent ductus arteriosus in Japan.

We surveyed Japanese experience of coil occlusion of patent ductus arteriosus up to 30 September 1996 by sending questionnaires to 175 hospitals. Thirty-four hospitals reported outcome data for 231 procedures in 218 patients. Successful implantation was achieved in 94% and acute complete closure of the ductus occurred in 71% of those in whom implantation of the coil was successful. Of the latter, 83% reported late complete closure. When those patients who underwent reocclusion for residual shunt are included, 89% attained complete closure. No life-threatening complications have occurred so far. Late reopening was reported in 3 cases. Although the angiographic type of ductus was significantly related to successful implantation (p < 0.01), there was no significant correlation with complete occlusion. Ductuses with a minimum diameter greater than 3 mm had a decreased chance of successful implantation, whereas those less than 2 mm had a greater incidence of complete closure.

Child↗
PubMed1997

Drug receptor mechanisms in smooth muscle: beta-chloroethylamine-sensitive and -resistant receptor mechanisms.

Both alpha1-adrenoceptors and M3-cholinoceptors can be divided into two subtypes discriminated by the beta-chloroethylamines, chloroethylclonidine and propylbenzilylcholine mustard (PrBCM), only in the presence of GTP. The full agonists interact with both subtypes to induce responses. The partial agonists activate one of them to induce responses but behave as competitive antagonists when they interact with the other. The responses mediated through the receptors that are activated by the partial agonists are resistant to myosin light chain kinase inhibitors, while the response through the activation of the other receptors are suppressed by the inhibitors. The receptor stimulations through alpha1A-adrenoceptor and PrBCM-sensitive M3-cholinoceptor subtypes mainly activate the myosin light chain-phosphorylation-independent pathway mediated through protein kinase C and low molecular weight GTP-binding protein, whereas the stimulations through alpha1B-adrenoceptors and the PrBCM-phosphorylation-dependent pathway are directly related to Ca2+/calmodulin.

Adrenergic Agonists↗
PubMed1997

The beta2- and beta3-adrenoceptor-mediated relaxation induced by isoprenaline and salbutamol in guinea pig taenia caecum.

To understand the receptor subtypes responsible for beta-adrenoceptor-mediated relaxation of guinea pig taenia caecum, we investigated the effects of isoprenaline and salbutamol. Isoprenaline and salbutamol caused dose-dependent relaxation of the guinea pig taenia caecum. Propranolol, bupranolol and butoxamine produced shifts of the concentration response curves for isoprenaline and salbutamol. Schild regression analyses carried out for propranolol against isoprenaline and salbutamol gave pA2 values of 8.43 and 8.88, respectively. Schild regression analyses carried out for butoxamine against isoprenaline and salbutamol gave pA2 values of 6.46 and 6.68, respectively. Schild regression analyses carried out for bupranolol against isoprenaline and salbutamol gave pA2 values of 8.60 and 8.69, respectively. However, in the presence of 3 x 10(-4) M atenolol, 10(-4) M butoxamine and 10(-6) M phentolamine to block the beta1-, beta2- and alpha-adrenoceptor effects, respectively, Schild regression analyses carried out for bupranolol against isoprenaline and salbutamol gave pA2 values of 5.77 and 5.97, respectively. These results suggest that the relaxant responses to isoprenaline and salbutamol in the guinea pig taenia caecum are mediated by both the beta2- and the beta3-adrenoceptors.

Adrenergic beta-2 Receptor Agonists↗
PubMed1997

Roles of the visceral pleura in the production of pleural effusion in permeability pulmonary edema.

We investigated the roles of the mesothelium of the visceral pleura on hydraulic conductivity in dogs under normal conditions and condition of permeability pulmonary edema. Nineteen mongrel dogs were divided into following 4 groups: thoracotomy alone (control group, n = 7); thoracotomy and striping of the mesothelium using Gelfilm (C + G group, n = 4); injection of oleic acid to increase the permeability of the pulmonary vessels (OA group, n = 4); injection of oleic acid and striping of the mesothelium (OA + G group, n = 4). A hemispherical capsule filled with physiological saline was attached to the visceral pleura. The transpleural fluid flow (delta V) was measured at given incremental or decremental hydrostatic pressures (delta Pcap) in the capsule. Hydraulic conductivity was calculated from the slope of linear regression line obtained from relationship between delta Pcap and the fluid flow rate (v) according to the Starling's equation. The conductivity obtained were 1.49 +/- 0.69 (nl.min-1.cmH2O-1.cm-2) in the control group, 1.37 +/- 0.88 in the C + G group, 3.75 +/- 0.74 in the OA + G group, and 7.07 +/- 2.49 in the OA + G group. The hydraulic conductivity was not increased by striping of the mesothelium (1.49 +/- 0.69 [nl.min-1.cmH2O-1.cm-2] vs. 1.37 +/- 0.88, in the control group vs. C + G group, respectively). Visceral pleural hydraulic conductivity following OA injection was increased by striping of the mesothelium (3.75 +/- 0.74 vs. 7.07 +/- 2.49 in OA group vs. OA + G group, respectively). These findings suggest that the wall of pulmonary vessels acts as a barrier to movement of pleural effusion under normal conditions, whereas the mesothelium of the visceral pleura acts as that under condition of permeability pulmonary edema.

Animals↗
PubMed1997

p21WAF1 mutations and human malignancies.

During the past few years, several categories of cyclin-dependent kinase inhibitors (CDKIs), which negatively regulate cyclin/cyclin-dependent kinase (CDK) activities, were cloned. The p21WAF1, also known as CIP1 or SDI1, was the first reported CDKI: it's expression is induced by wild-type p53. The p21WAF1 is a potent inhibitor of most cyclin/CDK complexes and also inhibits the ability of the proliferating cell nuclear antigen (PCNA) to activate DNA polymerase d. Alterations of the cell-cycle can cause cellular transformation. We analysed 471 primary samples from 15 types of human malignancies and 36 cell lines for structural alterations of the p21WAF1 gene. No changes were found in the coding region of p21WAF1 gene by polymerase-chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Many of these tumors had a normal p53 gene. Other investigators showed that p21WAF1 knockout mice did not have an increased incidence of cancer, while p53 knock-out mice did. Taken together, the absence of alterations of p21WAF1 in a series of malignancies suggests that p21WAF1 may not have a role in either onset or progression of most human cancers. Furthermore, p53 probably activates additional, critical tumor suppressor pathways.

Animals↗
PubMed1997

[Diagnostic value of serum soluble interleukin-2 receptor levels in interstitial pneumonia of the patients with hematological disorders].

Serum levels of soluble interleukin-2 receptor (SIL-2R) and C-reactive protein (CRP) were measured in 12 patients with interstitial pneumonia (IP) and 10 patients with bacterial pneumonia (BP) of hematological malignancies. Mean SIL-2R levels (U/ml) were 394 +/- 140 in normal controls, 755 +/- 320 in BP, and 2328 +/- 943 in IP. A significantly higher level was found in IP than BP (p < 0.05). Moreover, the SIL-2R/CRP ratio which was over 260 in all cases of IP completely distinguished IP from BP. Levels of SIL-2R rose before the onset of IP and were closely associated with clinical course in most cases. From these results, measurement of serum SIL-2R may be useful for the diagnosis and monitoring of the clinical course of IP complicated with hematological diseases.

C-Reactive Protein↗
PubMed1997

[Early postirradiation changes in Na+ and fluid transport across alveolar epithelium in rats].

To study changes in Na+ and fluid transport that occur soon after irradiation of the thorax, we used fluid-filled isolated rat lungs. Irradiation 15 Gy of 60Co doubled the fluid absorption rate across the alveolar epithelium within 2 weeks, but fluid absorption had returned to the baseline values by 3 weeks after irradiation. The timing of this change in fluid absorption was parallel to the time course of Na+ escape across alveolar epithelium and the two correlated closely. These data suggest that a dysfunction of alveolar epithelial Na+ transport is involved in the development of pulmonary edema after irradiation of the thorax.

Animals↗
PubMed1997

[Multidrug resistance protein (MRP)].

Two different integral glycoproteins, the 170 kD P-glycoprotein(P-gp) and the 190 kD multidrug resistance protein (MRP), are involved in the acquisition of multidrug resistance phenotypes in cancer cells. These two proteins belong to the ATP-binding cassette (ABC) superfamily but their primary structures are quite dissimilar, sharing only approximately 15% amino acid identity. Nevertheless, MRP and P-gp confer resistance to a similar profile of chemotherapeutic agents. These two proteins seem to play a similar role in the acquirement of multidrug resistance. However, it has recently been demonstrated that MRP can specifically transport the cysteinyl leukotriene, LTC4, and some other glutathione conjugates, suggesting that MRP had a function different from P-gp. This review summarizes the current data on the structural and functional characteristics of MRP, its ability to confer multidrug resistance and its clinical relevance in drug resistant malignant disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Proliferative and differentiative potential of thrombopoietin-responsive precursors: expression of megakaryocytic and erythroid lineages.

We investigated changes in proliferative potential and surface markers during human megakaryocytic differentiation, using megakaryocytic cells grown by thrombopoietin (TPO). Cells grown in response to TPO from CD34+ cord blood cells in a liquid culture system expressed CD41b at a frequency of 92% and CD42b at a frequency of 80% on day 10, whereas cells expressing other lineage markers constituted less than 2.5% of this population. The cultured cells were divided into CD41b-/CD42b-, CD41b+/CD42b-, and CD41b+/CD42b+ cells. Comparison of their respective proliferative potentials showed that CD41b-/CD42b- cells generated megakaryocytic progeny in response to TPO to a lesser extent, but responded to the combination of growth factors (GFs) more intensely than CD41b+/CD42b- cells. Almost all CD41b+/CD42b+ cells failed to undergo cell division. In the culture containing GFs, some CD41b-/CD42b- cells and CD41b+/CD42b- cells gave rise to erythroid as well as megakaryocytic progeny. The potential of these cells to yield erythroid progeny in response to GFs correlated well with their expression of CD34. These results suggest that TPO generates precursors with a potential to differentiate into megakaryocytic and erythroid lineages.

Antigens, CD34↗
PubMed1997

Isolation and analysis of cellular DNA fragments directly binding to c-Myc protein.

c-Myc protein, the product of cellular oncogene c-myc, is thought to play an important role in the control of cell cycle progression by binding to the E-box sequence (CACGTG) of cellular DNA, but only a few target genes are known. We cloned two small human DNA fragments (n16 and r37) that bound to c-Myc protein in vitro by random screening. Both clones contained the E-box sequence, to which c-Myc protein bound directly in vitro. Northern blot analysis showed that a low molecular-weight RNA was transcribed from the region near the n16 c-Myc binding site. The function of this low molecular-weight RNA and the regulatory role of c-Myc protein in related transcription are now under investigation.

Base Sequence↗
PubMed1996

The role of mitogen-activated protein kinase in oxytocin-induced contraction of uterine smooth muscle in pregnant rat.

Oxytocin causes the rapid tyrosine phosphorylation of mitogen-activated protein (MAP) kinase in both human and rat puerperal uterine myometrial cultured cells. The potential role of the MAP kinase pathway in oxytocin action was investigated with the specific MAP kinase kinase (MEK) inhibitor, PD98059. Oxytocin stimulation of the tyrosine phosphorylation of MAP kinase in both human and rat cultured puerperal uterine cells was abolished by pretreatment of the cells with MEK inhibitor in a dose-dependent manner. Although MEK inhibitor had no effect on oxytocin-induced intracellular Ca2+ mobilization in either pregnant human or pregnant rat uterine cells, it partly inhibited oxytocin-induced pregnant rat uterine contraction in a dose-dependent manner. These results suggest that MAP kinase pathway may have some important roles in oxytocin-induced uterine contraction.

Animals↗