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K Irie

Publications and source records attributed to K Irie.

At least 109 records · Page 6Linked to original sources
PubMed1997

Technetium-99m-sestamibi scintimammography of benign and malignant phyllodes tumors.

We presented two cases of phyllodes tumor of the breast examined by 99mTc-sestamibi (MIBI) two-phase scintimammography. In the case with malignant phyllodes tumor, 99mTc-MIBI accumulation was recognized on both early and delayed images. In the case with benign phyllodes tumor, however, 99mTc-MIBI accumulation was recognized on only the early image. 99mTc-MIBI delayed imaging may have the potential to distinguish between benign and malignant phyllodes tumors.

Breast Neoplasms↗
PubMed1997

Role of nitric oxide, prostaglandins and tyrosine kinase in vascular endothelial growth factor-induced increase in vascular permeability in mouse skin.

We investigated role of nitric oxide (NO), prostaglandins (PG) and tyrosine kinase in vascular endothelial growth factor (VEGF)-induced increase in vascular permeability in mouse skin. Subcutaneous injection of VEGF (0.5-2.0 ng/site) induced dose- and time-dependent increase in vascular permeability at the injection site determined by a leakage of Pontamine sky blue. VEGF (1 ng/site)-induced dye leakage was partially inhibited by N(G)-nitro-L-arginine methyl ester (an inhibitor for both constitutive and inducible NO synthase) (5 and 10 mg/kg, i.v.) and by aminoguanidine (a selective inducible NO synthase inhibitor) (5-20 mg/kg, i.v.), but not by an inactive enantiomer, N(G)-nitro-D-arginine methyl ester (10 mg/kg, i.v.). Pretreatment with an intraperitoneal injection of indomethacin (a nonselective cyclooxygenase inhibitor) (5 mg/kg) or N-(2-cyclohexyloxy-4-nitrophenyl) methanesulphonamide (a cyclooxygenase-2 selective inhibitor) (1-100 microg/kg) almost completely inhibited the effect of VEGF (1 ng/site). Coadministration of PGE2 (3 and 30 nmol/site) with VEGF did not restore the inhibitory effect of indomethacin on VEGF (1 ng/site)-induced increase in vascular permeability. Lavendustin A (a selective tyrosine kinase inhibitor) (10 and 50 microg/kg, s.c.) dose-relatedly inhibited the VEGF (1 ng/site)-induced increase in dye leakage, whereas its negative control, lavendustin B (10 microg/kg, s.c.) had no effect. Another tyrosine kinase inhibitor, genistein (2.5 mg/kg, s.c.) also inhibited the response. Cycloheximide (a protein biosynthesis inhibitor) (35 mg/kg, s.c.) suppressed the response of VEGF (1 ng/site). Histologically, no cellular infiltration was observed in the area of VEGF injection. These results suggest that increased vascular permeability induced by VEGF is mediated by local production of NO and arachidonic acid metabolites other than PGE2, which are most probably produced by inducible NO synthase and cyclooxygenase-2, respectively. Protein tyrosine kinase-mediated phosphorylation and synthesis of any new proteins are likely to be required in this effect of VEGF in mouse skin.

Animals↗
PubMed1997

Comparison of chemical characteristics of the first and the second cysteine-rich domains of protein kinase C gamma.

Protein kinase C (PKC) is a key enzyme family involved in cellular signal transduction. The binding of endogenous diacyl glycerol (DAG) to the cysteine-rich domain (CRD) of PKC is associated with normal cell signaling and function. In contrast, the binding of exogenous phorbol esters to the CRD of PKC is considered to be a key initiating event in tumor promotion. Conventional PKC isozymes (PKC alpha, beta I, beta II, and gamma) contain two CRDs, both of which are candidates for the phorbol ester binding site. In order to elucidate the binding requirements of phorbol esters and to obtain information on the phorbol ester binding site in native PKC gamma, several key chemical characteristics of the first and the second CRDs consisting of ca. 50 amino acids of rat PKC gamma (gamma-CRD1 and gamma-CRD2) were examined. In the presence of Zn2+ and phosphatidylserine (PS), both CRDs gave similar Kd values (65.3 nM for gamma-CRD1, 44.1 nM for gamma-CRD2) in phorbol 12,13-dibutyrate (PDBu) binding assays. In comparison, the binding affinity of PDBu for native rat PKC gamma was found to be 6.8 nM. Zn2+ was shown to play an important role in the folding and PDBu binding of both CRDs. A Zn(2+)-induced conformational change was observed for the first time by CD spectroscopic analysis of the complexed and uncomplexed CRDs. Relative to the pronounced Zn2+ effect, most divalent first row transition metal ions along with Ca2+, Mg2+, and Al3+ were ineffective in folding either CRD. Notably, however, Co2+ exhibited a gamma-CRD1-selective effect, suggesting that metal ions, not unlike extensively used organic probes, might also become effective tools for controlling isozyme selective activation of PKC. Moreover, group Ib (Cu2+ and Ag+) and group IIb element ions other than Zn2+ (Cd2+ and Hg2+) were found to abolish PDBu binding of both CRDs. Importantly, these inhibitory effects of Cu2+, Ag+, and Cd2+, and Hg2+ were also observed with native PKC gamma. These results indicate that recent reports on the modulation of conventional PKC by heavy metal ions could be explained by their coordination to the CRDs. While the similar affinities of gamma-CRD1 and gamma-CRD2 for PDBu suggest that either site qualifies as the PDBu binding site, new molecular probes of these CRD3 have now been identified that provide information on the preferred site. These novel ligands (5a and 5b) were synthesized by aza-Claisen rearrangement of (-)-N13-desmethyl-N13-allylindolactam-G (4). These compounds did not significantly affect the specific PDBu binding of gamma-CRD1 but did inhibit that of gamma-CRD2 with similar potency to (-)-indolactam-V. Moreover, these new probes did not significantly inhibit the PDBu binding of native PKC gamma. (-)-Indolactam-V itself bound almost equally to gamma-CRD1, gamma-CRD2, and native PKC gamma. These results suggest that the major PDBu binding site in native PKC gamma is the first CRD, not the second CRD, unlike the novel PKCs.

Amino Acid Sequence↗
PubMed1997

Xenopus cyclin A1 can associate with Cdc28 in budding yeast, causing cell-cycle arrest with an abnormal distribution of nuclear DNA.

BACKGROUND: Cyclins play a regulatory role in cell cycle progression, associated with cyclin-dependent kinases. We have investigated the structure-function relationships of cyclin A, mainly using Xenopus egg extracts in vitro. To further analyse the function and structure of cyclin A in vivo, we expressed Xenopus cyclin A1 in the budding yeast Saccharomyces cerevisiae. RESULTS: We herein show that vertebrate cyclin A1 can associate with endogenous Cdc28 to form histone H1 kinase. The growth of the yeast was inhibited by the expression of indestructible cyclin A1, but not by a non-Cdk binding cyclin A1 mutant. The induction of cyclin A1 expression in yeast caused cell cycle arrest with an abnormal distribution of nuclear DNA to the daughter bud. Suppressors of the cyclin A1-mediated growth arrest were identified as new alleles of the cdc28 mutation that reduced the binding of cyclin A1 and possessed different affinities for the cyclin-Cdc28 complexes. The temperature-sensitivity of the cdc28 mutation was thus preferentially suppressed by the endogenous cyclins CLN2 and CLB2. CONCLUSIONS: These results suggest that the Cdc28 protein kinase activity mediated by vertebrate cyclin A1 may be involved in the process of nuclear movement in the yeast, and thereby affect the dependence of the M phase on the completion of the S phase through a preferential binding affinity of the cyclin-Cdc28 complex.

Amino Acid Sequence↗
PubMed1997

Functional analyses of mammalian protein kinase C isozymes in budding yeast and mammalian fibroblasts.

BACKGROUND: The PKC1 gene of Saccharomyces cerevisiae encodes a homologue of mammalian protein kinase C (PKC) that is required for yeast cell growth. Pkc1 has been proposed to regulate a protein kinase cascade which includes the Bck1, Mkk1/Mkk2 and Mpk1 kinases. The functional relationship between Pkc1 and mammalian PKCs is unknown. Another signal transduction in Saccharomyces cerevisiae, the mating pheromone signalling pathway, is mediated by a heterotrimeric G protein, and causes cell cycle arrest in the G1 interval. It is not clear whether PKC is involved in this pathway. The effects of overexpression of PKCs in mammalian cells have been widely studied to analyse the function of PKCs in vivo. RESULTS: We isolated a human cDNA which encodes a protein kinase C type eta (PKC-eta) by complementation of pkc1 mutations in Saccharomyces cerevisiae. The human PKC-eta was able to complement the growth defect caused by the deletion of PKC1, whereas PKC-eta was unable to suppress the defect caused by deletion of BCK1. We also isolated human cDNAs that can suppress the adaptation defect of sst2. One of them encodes a protein kinase C type delta (PKC-delta). Expression of this gene in yeast stimulated an adaptation to the pheromone response. Human PKC-delta suppressed the adaptation defect of a pheromone receptor mutation lacking its C-terminal domain, but not that of a G protein beta-subunit mutation eliminating signal-induced phosphorylation, and not the lethality of the gpa1 null mutation. Moreover, overexpression of PKC-eta in NIH3T3 cells induced anchorage-independent growth. CONCLUSIONS: PKC-eta has a biological activity which is closely related to Pkc1, and PKC-eta activates the Pkc1-mediated pathway through an activation of the Bck1 kinase that is a homologue of MAP kinase kinase kinase. PKC-eta appears to play a critical role in growth control of yeast and mammalian cells. Suppression experiments with PKC-delta suggest that PKC-delta desensitizes the pathway by regulating an aspect of G protein function.

Adaptation, Biological↗
PubMed1997

Possible involvement of differential splicing in regulation of the activity of Arabidopsis ANP1 that is related to mitogen-activated protein kinase kinase kinases (MAPKKKs).

Three types of Arabidopsis cDNA (cANP1, cANP2 and cANP3) have been isolated that encode putative protein kinases, designated ANP1, ANP2 and ANP3. These kinases exhibit a high degree of homology to NPK1, a tobacco protein that is a member of the family of mitogen-activated protein kinase kinase kinases (MAPKKKs), which appears to function in the proliferation of tobacco cells. The predicted amino acid sequences of the kinase domains in the amino-terminal halves of the ANPs were more than 80% identical to that of NPK1, while the kinase-unrelated regions in the carboxy-terminal halves exhibited relatively low homology. Two species of cANP1 were identified, ANP1L cDNA (cANP1L) and ANP1S cDNA (cANP1S), which were derived from a single ANP1 gene: the former had an intron-like sequence in the coding region for the kinase-unrelated region, while the latter did not include such an intron-like sequence. cANP1L encoded a putative protein with both kinase and kinase-unrelated domains, resembling NPK1, whereas cANP1S encoded only the amino-terminal kinase domain because the intron-like sequence was absent, with resulting elimination of most of the kinase-unrelated region. Genetic analysis with mutant yeast cells showed that over-expression of cANP1L or of cANP1S activated the mating pheromone-responsive signal pathway which is mediated by a MAP kinase cascade. Moreover, the extent of such activation by cANP1S was greater than that by cANP1L. These results predict that differential splicing of the intron-like sequence in the ANP1 transcript might be at least one of the molecular mechanisms involved in the generation of active ANP1 protein kinase.

Alternative Splicing↗
PubMed1997

Dominant mutations of Drosophila MAP kinase kinase and their activities in Drosophila and yeast MAP kinase cascades.

Eight alleles of Dsor1 encoding a Drosophila homologue of mitogen-activated protein (MAP) kinase kinase were obtained as dominant suppressors of the MAP kinase kinase kinase D raf. These Dsor1 alleles themselves showed no obvious phenotypic consequences nor any effect on the viability of the flies, although they were highly sensitive to upstream signals and strongly interacted with gain-of-function mutations of upstream factors. They suppressed mutations for receptor tyrosine kinases (RTKs); torso (tor), sevenless (sev) and to a lesser extent Drosophila EGF receptor (DER). Furthermore, the Dsor1 alleles showed no significant interaction with gain-of-function mutations of DER. The observed difference in activity of the Dsor1 alleles among the RTK pathways suggests Dsor1 is one of the components of the pathway that regulates signal specificity. Expression of Dsor1 in budding yeast demonstrated that Dsor1 can activate yeast MAP kinase homologues if a proper activator of Dsor1 is coexpressed. Nucleotide sequencing of the Dsor1 mutant genes revealed that most of the mutations are associated with amino acid changes at highly conserved residues in the kinase domain. The results suggest that they function as suppressors due to increased reactivity to upstream factors.

Alleles↗
PubMed1997

Delayed triphenyltetrazolium chloride staining remains useful for evaluating cerebral infarct volume in a rat stroke model.

Sixteen of 24 Sprague-Dawley rats with permanent middle cerebral artery occlusion for 24 hours were subjected to immediate or 8-hour delayed 2,3,5-triphenyltetrazolium chloride (TTC) staining (n = 8 at each time point); the other 8 animals were subjected to immediate or 8-hour delayed measurement of succinate dehydrogenase activity (n = 4 at each time point). The TTC staining was of good quality good in all animals, and the infarcted region could be distinguished easily from normal tissue. There was no significant difference in corrected infarct volume between the two groups (263.8 +/- 43.1 versus 264.4 +/- 54.8 mm3 [mean +/- standard deviation]). The activity of succinate dehydrogenase was not significantly different when normal or infarcted tissue was measured immediately after death or with an 8 hour delay, although less activity was detected at both time points in the infarcted tissue. These results demonstrate that an 8-hour delay of TTC staining is reliable for evaluating brain infarct volume in a rat stroke model and this probably is attributable to the slow deterioration of mitochondrial enzyme activity in nonischemic brain over this time period.

Animals↗
PubMed1997

Diffuse fibromatosis on the scalp in infancy: a variant of juvenile hyaline fibromatosis.

Various types of fibromatosis have been reported in infancy and early childhood. We describe an infant with diffuse fibromatosis on the scalp. A one year and five months-old girl showed a diffuse and hard mass 3 x 5 cm in diameter and no tenderness on the scalp. Two months later, the size of the mass had increased and several other tumors appeared on the lateral head. The magnetic resonance imaging (MRI) disclosed that a large and diffuse tumor had spread from the frontal to occipital head; a 'helmet-like' configuration of the tumor was exhibited on sagittal MR images. The tumor showed high signal intensity on T2-weighted images and was enhanced with Gd-DTPA. Histological examination showed a fibroblastic proliferation with intervening thick collagen bundles. The patient was diagnosed as having diffuse fibromatosis. The tumor at the resection site immediately recurred, whereas the tumor in the frontal head showed marked regression. Three months after the resection, new tumors appeared in the occipital head. The size and number of these tumors have remained unchanged for more than 18 months. The sites and appearance of the tumors were identical to that of juvenile hyaline fibromatosis (JHF) in this patient. However, JHF usually includes fibroblasts associated with large amounts of hyalinized collagen-like material, which were not present in our patient. The different histology of JHF comparing our case and other reported cases may depend on the different phase of the disease progression at resection. Long-term observation is necessary for the appropriate diagnosis and evaluation of prognosis in this patient.

Female↗
PubMed1997

Characterization of a serum response factor-like protein in Saccharomyces cerevisiae, Rlm1, which has transcriptional activity regulated by the Mpk1 (Slt2) mitogen-activated protein kinase pathway.

The Mpk1 (Slt2) mitogen-activated protein (MAP) kinase has been implicated in several biological processes in Saccharomyces cerevisiae. The Rlm1 protein, a member of the MADS box family of transcription factors, functions downstream of Mpk1 in the pathway. To characterize the role of Rlm1 in mediating the transcriptional activation by the Mpk1 pathway, we constructed a LexA-Rlm1 deltaN chimera in which sequences, including the MADS box domain of the Rlm1 protein, were replaced by the LexA DNA binding domain and tested the ability of this chimera to activate a LexA operator-controlled reporter gene. In this assay, the Rlm1 protein was found to activate transcription in a manner regulated by the Mpk1 pathway. The Mpk1 protein kinase phosphorylated Rlm1 deltaN in vitro and the LexA-Rlm1 deltaN chimera protein was phosphorylated in vivo in a Mpk1-dependent manner. These results suggest that Mpk1 regulates the transcriptional activity of Rlm1 by directly phosphorylating it. We identified a Mpk1-like protein kinase, Mlp1, as an Rlm1-associated protein by using the yeast two-hybrid system. Overexpression of MLP1 suppresses the caffeine-sensitive phenotype of the bck1 delta mutation. The additivity of the mlp1 delta defect with the Mpk1 delta defect with regard to the caffeine sensitivity, combined with the results of genetic epistasis experiments, suggested that the activity of Rlm1 is regulated independently by Mpk1 MAP kinase and the Mlp1 MAP kinase-like kinase.

Amino Acid Sequence↗
PubMed1997

Synthesis and biological activities of indolactone-V, the lactone analogue of the tumor promoter (-)-indolactam-V.

The tumor promoter (-)-indolactam-V (1) exists in two stable conformers (twist and sofa) due to isomerization of the amide group. Indolactone-V (2), the lactone analogue of 1, has been synthesized to investigate the effects of the amide group on its conformation and biological activities. Indolactone-V (2) existed only as the inactive sofa-like conformer, indicating that the amide group of 1 plays a critical role in formation of the active twist conformation.

Carcinogens↗
PubMed1997

Endovascular treatment of a partially thrombosed giant basilar tip aneurysm using interlocking detachable coils--case report.

A 65-year-old female presented with visual acuity loss. Magnetic resonance imaging confirmed the presence of a partially thrombosed giant aneurysm on the basilar tip. Cerebral angiography showed the opacified lumen of the aneurysm was 25 x 15 mm with a broad-based neck. Using a transfemoral approach, a microcatheter was guided through the vertebral artery and placed directly into the aneurysm under local anesthesia. Interlocking detachable coils were deposited into the patent portion of the aneurysm, resulting in 95% obliteration of the aneurysm and preservation of the parent artery. No complication was observed during or after surgery. Follow-up angiography 2 months later demonstrated the aneurysm was 95% occluded. No coil compaction was observed. Endovascular coil embolization therapy provides a therapeutic option for management of basilar tip aneurysms.

Aged↗
PubMed1997

Intraarterial infusion of papaverine in experimental cerebral vasospasm.

PURPOSE: To determine the effectiveness of intraarterial infusion of papaverine hydrochloride (PPV) in an experimental model of cerebral vasospasm and to measure the mean blood flow velocity of the middle cerebral artery (MCA). METHODS: Seven Japanese monkeys were divided into three groups: those studied 3 days-after surgery (the third-day group, n = 3); those studied 7 days after surgery (the seventh-day group, n = 3); and a control group (n = 1). Vasospasm was induced in the experimental groups by placing a blood clot in the subarachnoid space around the top of the internal carotid siphon. PPV (5 mg/kg) was infused (over 60 minutes) into the internal carotid artery (ICA). The vascular diameters of the ICA and MCA were measured on angiograms before and after infusion. The mean blood flow velocity in the MCA was measured on transcranial Doppler sonograms before and 24 hours after infusion. After fixation, the MCA was dissected out, stained, and examined microscopically. RESULTS: After vasospasm induction, both arteries were narrowed more than 30% in the third-day group and more than 50% in the seventh-day group. After PPV infusion in both groups, vascular dilatation of about 20% was seen. The mean increase in blood flow velocity in the third-day group (30%) was smaller than in the seventh-day group (70%). The mean blood flow velocity in the MCA decreased by about 30% in both groups, but increased again after 24 hours nearly to the level before PPV infusion. The intimal layer was more corrugated in the seventh-day group, and hypertrophy in the smooth muscle layer was also seen. Clinical examination showed no neurologic deficit in the third-day group 24 hours after PPV infusion; neurologic deficits were observed in the seventh-day group. CONCLUSION: PPV infusion may be more effective in early stages of vasospasm when vascular walls have fewer histologic changes.

Animals↗
PubMed1997

[A case of cavernous dural arteriovenous fistula resulting in intracerebral extravasation during transvenous embolization].

Cortical venous drainage has been described as one of the major risk factors for dural arteriovenous fistula, which may induce venous hypertension leading to venous ischemia or intracerebral hemorrhage. However, it is rather rare to observe cortical venous drainage manifesting in this way in the cavernous sinus region. We report a case of a 55-year-old gentleman with a right cavernous dural arteriovenous fistula, presenting with conjunctival chemosis, exophthalmus and ocular hypertension on the affected side. Magnetic resonance imaging showed a small intracerebral hemorrhage in the right frontal lobe. Cerebral angiography revealed a dural arteriovenous fistula in the right cavernous sinus draining into the right olfactory vein via the uncal vein, as well as into the superior and inferior ophthalmic veins. This unusual cortical venous reflux was thought to be consistent with the intracerebral hemorrhage found on the magnetic resonance imaging. The patient underwent transvenous embolization for the dural arteriovenous fistula using an inferior petrosal catheterization into the uncal vein was difficult, and the cortical venous reflux through the vein seemed to be slight. However, extravasation of the contrast material occurred in the right frontal lobe after obliteration of the ophthalmic veins during the procedure. The cause of the extravasation was suspected to be the same olfactory vein that had been involved in the previous intracerebral hemorrhage. The obliteration of the dural fistula was continued rapidly, and the fistula disappeared after the embolization. Neurologically, the patient had no noticeable troubles, except for a mild headache. The pretreatment symptoms were alleviated within several days, and the patient was discharged in a week. We emphasize the following points from this rare case in order to facilitate a safer procedure during transvenous embolization for cavernous dural arteriovenous fistula. It is important to obliterate the cortical venous drainage as early as possible, even if the reflux is small or the catheterization is difficult. Repeated, careful sinography is useful for the evaluation of the drainage pattern at certain stages during the transvenous embolization procedure.

Arteriovenous Fistula↗