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Biomedical subjects

S Kuroda

Publications and source records attributed to S Kuroda.

At least 289 records · Page 16Linked to original sources
PubMed1994

The pleckstrin homology domain of RAC protein kinase associates with the regulatory domain of protein kinase C zeta.

Binding proteins to the pleckstrin homology domain of RAC protein kinase were screened by using glutathione S-transferase fusion protein system. Proteins in CHO cell extract of approximate molecular mass of 76 kD and 200 kD bound specifically to the pleckstrin homology domain of RAC protein kinase in vitro. The 76 kD protein was identified as protein kinase C zeta by immunoblot analysis. Studies of the association between the pleckstrin homology domain-truncated mutants and protein kinase C zeta indicated that the amino-terminal portion of the pleckstrin homology domain is essential for the binding and the whole structure of the domain is important for the efficient binding to protein kinase C zeta. The pleckstrin homology domain of RAC protein kinase was shown to recognize the regulatory domain of protein kinase C zeta. The protein-protein interaction between RAC protein kinase and protein kinase C through the pleckstrin homology domain might be important for the regulation of these protein kinases.

Animals↗
PubMed1994

[Intimal hyperplasia growth after stenting of modified gianturco Z stent in an experimental study].

Three types of modified Gianturco Z stents, which included some solder at the bend portion in group 1, a little solder in group 2 and no solder in group 3, were placed in the jugular vein in order to evaluate the degree of intimal hyperplasia growth in five dogs. Four weeks later, venography and histological examination after venectomy were performed. Stenosis was 32.7 +/- 6.9% at the bend portion in group 1, 27.0 +/- 6.0% in group 2 and 14.0 +/- 6.5% in group 3. The results indicate that stents without solder are preferable for the venous system.

Animals↗
PubMed1994

Molecular cloning of rat RAC protein kinase alpha and beta and their association with protein kinase C zeta.

cDNAs of RAC protein kinases (RAC-PK) alpha and beta were cloned from a rat testis cDNA library. The predicted open reading frames encode 480 and 481 amino acids of RAC-PK alpha and beta, respectively, and the rat RAC-PK alpha and beta have sequences conserved among different mammalian species such as the pleckstrin homology domain at their amino-terminal region and the protein-serine/threonine kinase catalytic domain at their carboxyl-terminal region. RNA blot analysis showed wide distribution of two RAC-PK in rat tissues. Immunoprecipitation analysis revealed that RAC-PK alpha and beta associate with protein kinase C zeta through the pleckstrin homology domain in vitro, suggesting the interaction between RAC-PK and protein kinase C.

Amino Acid Sequence↗
PubMed1994

Differential changes in the activities of multiple protein kinase C subspecies in the hippocampal-kindled rat.

In previous studies we demonstrated that the membrane-associated protein kinase C (PKC) activities in the right and left hippocampus (HIPP) of rats kindled from the left HIPP increased significantly 4 weeks and 4 months after the last seizure compared with those in matched control rats. In this study, we investigated the long-lasting effect of HIPP-kindling on the membrane-associated activities of PKC subspecies in the bilateral HIPP 1 and 4 weeks after the last generalized kindled seizure had occurred. The membrane-associated activities of PKC subspecies were found to be subject to differential regulation. The activity of the alpha-subspecies was unchanged, whereas the respective activities of the beta- and gamma-subspecies in the kindled group increased significantly, compared with the controls, one (21%, P < 0.0001 for the beta-subspecies, and 23%, P < 0.001 for the gamma-subspecies) and 4 weeks (19%, P < 0.02 for the beta-subspecies, and 19%, P < 0.05 for the gamma-subspecies) after the last seizure. There were no significant differences in cytosolic PKC activity between the control and kindled groups for any subspecies examined at either time after the last seizure. These results suggest that activation of the PKC beta- and gamma-subspecies may play an important role in the enduring seizure susceptibility associated with kindling.

Animals↗
PubMed1994

Synergistic activation by Ras and 14-3-3 protein of a mitogen-activated protein kinase kinase kinase named Ras-dependent extracellular signal-regulated kinase kinase stimulator.

We have identified, in Xenopus oocyte cytosol, a protein kinase named REKS (Ras-dependent extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase kinase (MEK) stimulator), which phosphorylates and activates recombinant ERK2 through recombinant MEK in a recombinant GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-Ras-dependent manner. We show here that this REKS activity is synergistically enhanced by a combination of mammalian recombinant GTP gamma S-KiRas and 14-3-3 protein purified from rat brain. 14-3-3 protein is known to activate tyrosine and tryptophan hydroxylases, to modulate the protein kinase C activity, to stimulate secretion, and to show phospholipase A2 activity per se. 14-3-3 protein did not affect the MEK activity. 14-3-3 protein neither interacted with Ki-Ras nor affected the neurofibromin activity to stimulate the GTPase activity of Ki-Ras under the conditions where the recombinant N-terminal fragment of c-Raf-1 inhibited it. These results suggest that 14-3-3 protein has an additional function in the regulation of the Ras-MEK-ERK cascade pathway through the activation of REKS.

14-3-3 Proteins↗
PubMed1994

Phosphorylation and activation of mitogen-activated protein kinase by kainic acid-induced seizure in rat hippocampus.

Injection of kainic acid into rat induced a limbic seizure and increased the activities of two protein kinases with Mrs of 42 kDa and 44 kDa in the hippocampus. These two protein kinases were identified as MAP kinases by an anti-MAP kinase antibody. These MAP kinases were phosphorylated at least at a tyrosine residue. The time course of the MAP kinase activation was roughly parallel with that of the seizure. These results indicate that the kainic acid-induced seizure induces MAP kinase activation in rat hippocampus.

Animals↗
PubMed1994

Occurrence of GD3 ganglioside in reactive astrocytes--an immunocytochemical study in the rat brain.

Immunocytochemical study of ganglioside GD3 (II3 alpha(NeuAc alpha 2-8NeuAc)-LacCer) was performed in the cold lesions produced in the cerebral cortex of the rat brain, using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Seven and 15 days after cold lesioning, GD3-like immunoreactivity was observed in reactive astrocytes. Thirty and 50 days after cold lesioning, GD3-like immunoreactivity was observed in the cells that formed glial scars. Normal astrocytes were not immunoreactive. Therefore, it is possible that GD3 may play an important role in the astrocytic functions required for the process of repair of edematous lesions in the central nervous system.

Animals↗
PubMed1994

Novel subtype of human angiotensin II type 1 receptor: cDNA cloning and expression.

Angiotensin II (AII) plays a major role in regulation of cardiovascular function and fluid homeostasis through the action of an AII type 1 receptor (AT1R). The cDNA encoding a novel subtype of human AT1R (AT1bR) was cloned from a human placental cDNA library. The full-length cDNA clone (1563 bp) encoded a polypeptide that consists of 359 amino acid (aa) residues with 97.2% aa identity to the human AT1aR. All the aa replacements between two human AT1Rs reside within the C-terminal half region of AT1R molecule. The 2.4-knt AT1bR mRNA is expressed in the lung, placenta and liver, and differs from AT1aR mRNA in its tissue distribution. The AT1bR expressed in COS-7 cells is pharmacologically distinct from the human AT1aR.

Amino Acid Sequence↗
PubMed1994

Novel subtype of human angiotensin II type 1 receptor: analysis of signal transduction mechanism in transfected Chinese hamster ovary cells.

We examined the intracellular signal transduction of two subtypes of human angiotensin II type 1 receptor (AT1aR and AT1bR) by means of the stable expression of each receptor cDNA in Chinese hamster ovary cells. Both receptors showed a rapid stimulation of phosphatidylinositol hydrolysis, a transient increase of intracellular Ca2+ concentration and an inhibitory action on the forskolin-induced cyclic AMP formation. Interestingly, at high AII concentrations (> 1 microM), these AT1bR-mediated responses were inhibited, whereas the AT1aR-mediated responses were not. Thus, the two AT1Rs are considered to be coupled to the same signal transduction cascades, but to be regulated differently on the post-translational level (presumably desensitization).

Angiotensin II↗
PubMed1994

Antiepileptogenic and anticonvulsant effects of NBQX, a selective AMPA receptor antagonist, in the rat kindling model of epilepsy.

To investigate the role of non-NMDA receptors in epileptic seizures, we examined the antiepileptogenic and anticonvulsant effects of NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline), a potent and selective AMPA receptor antagonist, in the rat kindling model. Systemic administration of 10-40 mg/kg NBQX significantly and dose dependently suppressed previously kindled seizures from the amygdala (AM), assessed in terms of the motor seizure stage and afterdischarge (AD) duration. The maximal effects were observed at 0.5-1 h after drug injection. When the intensity of electrical stimulation was increased to twice the generalized seizure-triggering threshold (GST), the anticonvulsant effects of NBQX on AM-kindled seizures were not reversed, suggesting that the effects were not due to non-specific elevation of the GST. In contrast to AM-kindled seizures, 20-40 mg/kg NBQX significantly suppressed only the motor seizure stage without reducing the AD duration of previously hippocampal-kindled seizures. Daily administration of 15 or 30 mg/kg NBQX prior to each electrical stimulation of the AM markedly and significantly suppressed the development of kindling. During drug sessions, the growth of the AD duration was blocked almost completely, while the waveform of ADs became more complex. These results indicate that NBQX has potent antiepileptogenic and anticonvulsant actions on kindling, at least from the AM and that non-NMDA receptors have an important role in seizure propagation.

Amygdala↗
PubMed1994

Fermentable and nonfermentable carbon sources sustain constitutive levels of expression of yeast triosephosphate dehydrogenase 3 gene from distinct promoter elements.

The triosephosphate dehydrogenase 3 gene (TDH3) is a glycolytic enzyme gene and is abundantly transcribed in Saccharomyces cerevisiae. The promoter region of the TDH3 gene is known to exhibit high transcriptional activity regardless of the fermentability of the carbon source and has been widely utilized to synthesize heterologous gene products in S. cerevisiae. To clarify the mechanism of constitutive transcription by the promoter, we constructed mutant promoters and analyzed the in vivo transcriptional activity of these promoters. The majority of the transcriptional potential is contained within a DNA fragment extending from nucleotides -524 to -255 (-524/-255; relative to the translation initiation codon), which consists of three cis-acting elements: a fermentable carbon source-dependent upstream activation sequence (UAS) 1 (-524/-426), a fermentable carbon source-dependent upstream repression sequence (URS) (-426/-393), and a nonfermetable carbon source-dependent UAS2 (-305/-255). This result indicates that the promoter involves two apparent promoter elements. One is fermentable carbon source-dependent, and another is nonfermentable carbon source-dependent. Southwestern analyses indicated that a novel 20-kDa protein is induced in yeast cells by shifting from a fermentable to nonfermentable carbon source. The protein interacts with two UAS1 13-base pair elements and one URS 13-base pair element, one of which had been previously designated GPE (general regulatory factor 1 (GRF1) binding site potentiator element) (Bitter, G. A., Chang, K. K. H., and Egan, K. M. (1991) Mol. Gen. Genet. 231, 22-32). We therefore termed the 20-kDa protein GPEB (GRF1-binding site potentiator element-binding protein). In addition, mutational analyses strongly suggested that UAS1, URS, and UAS2 interact with GRF1 and GPEB, GPEB, and the GCR1 (glycolysis regulation 1) gene product, respectively. We therefore concluded that constitutive transcription by the TDH3 promoter is sustained by two promoter elements and that the switch between them might be controlled by the nonfermentable carbon source-inducible GPEB.

Base Sequence↗
PubMed1994

Developmental profile of ganglioside GD3 in the central nervous system: an immunocytochemical study in the rat.

Light and electron microscopy observations were made of developing rat brain at gestation days (E) E13, E16, E19, and postnatal days (P) P1, P3, P5, P7 after immunocytochemical staining for ganglioside GD3 (II3 alpha(NeuAc alpha 2-8NeuAc)-LacCer, GD3) using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Immunoreactivity was observed in neuroblasts (E13, E16) and immature neuronal cells (P1, P3, P5, P7), and also in glioblasts (E19). Electron microscopy revealed that at E13 peroxidase reaction product for GD3 (RP) was present on the plasma membrane and in the cytoplasm of neuroblasts, with accentuation in the former. At E16, RP was observed predominantly in the cytoplasm of neuroblasts. At E19, EP was seen mainly in the cytoplasm of glioblasts. At P1, P3, P5, and P7, immature neuronal cells in the cerebrum were immunoreactive. In the cerebellum, immature Purkinje cells and immature neuronal cells in the external and internal granular layers were also immunoreactive for GD3, the reaction product being located in the cytoplasm. The present findings suggest that changes in the localization of GD3 in neuroblasts were correlated with the alteration in their biological functions.

Animals↗
PubMed1994

The effects of perinatal anoxia or hypoxia on hippocampal kindling development in rats.

The effects of anoxia and hypoxia (3% oxygen) at 10-12 post days of age on the development of ventral hippocampal kindling and its transfer to the contralateral ventral hippocampus were studied in adult male Sprague-Dawley rats. During oxygen deprivation, the heart rate decreased to 15% of the prehypoxic value in the animals exposed to anoxia and 40% in those exposed to hypoxia. As is observed in asphyxia of human newborns, our study included both ischemia and hypoxia. The susceptibility to kindling, which was measured by kindling rate, afterdischarge threshold, generalized seizure threshold, and total afterdischarge duration to stage 5, had a tendency to be enhanced in rats exposed to hypoxia compared with controls. The facilitating effects on primary site kindling were enhanced in the animals exposed to hypoxia compared with those exposed to anoxia. Transfer, which was indicated by kindling rate and afterdischarge threshold, was also slightly facilitated in the rats exposed to anoxia or hypoxia in the perinatal period. These results reveal that perinatal oxygen deficiency may not be sufficient to lead to the development of temporal lobe epilepsy. However, it is possible that perinatal hypoxia results in some pathophysiological change in the brain which leads to greater seizure susceptibility in adulthood.

Aging↗
PubMed1994

Hepatic encephalopathy with increased cerebral blood flow in SPECT and MRI abnormalities in the basal ganglia.

A case of hepatic encephalopathy with increased cerebral blood flow in single-photon emission computed tomography (SPECT) and abnormalities upon magnetic resonance imaging (MRI) is reported. SPECT showed increased blood flow exceeding 70 ml/100 g/min in the cerebellum, basal ganglia and cerebral cortex, with hyperammonemia and abnormal electroencephalographic signs showing severe generalized slowing. SPECT data and MRI might reflect abnormal metabolism and neuropathological changes in hepatic encephalopathy.

Antiparkinson Agents↗
PubMed1994

Expression of ganglioside GD3 in choroid plexus.

Immunocytochemical staining for ganglioside GD3 (II3 alpha(Neu Ac alpha 2-8 NeuAc)-LacCer) in the choroid plexus of the adult rat brain was carried out. A peroxidase reaction product for GD3 was predominantly present along the surface of microvilli of the choroidal cells, suggesting that ganglioside GD3 may be concerned with the formation or secretion of the cerebrospinal fluid.

Animals↗
PubMed1994

Severe insulin-resistant diabetes mellitus associated with hypereosinophilic syndrome.

We describe a 52-year-old male manifesting severe insulin resistance associated with hypereosinophilic syndrome (HES). Diabetes mellitus was initially well-controlled by an oral hypoglycemic agent, and thereafter by human insulin. Due to the progression of hypereosinophilia, hepatosplenomegaly and peripheral lymphoadenopathy, severe insulin resistance associated with diabetic ketoacidosis occurred repeatedly, despite intravenous administration of over 1,000 U per day of human insulin. A high plasma insulin-binding capacity as determined by Scatchard analysis was consistent with insulin antibody-mediated resistance. The diagnosis of HES was made due to the persistent elevation of eosinophil count and associated liver and cardiac damage. Glucocorticoid therapy successfully achieved both reducing clinical symptoms and improving glycemic control.

Diabetes Complications↗