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Y Kashima

Publications and source records attributed to Y Kashima.

At least 19 recordsLinked to original sources
PubMed2001

Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin secretion.

Incretins such as glucagon-like peptide-1 and gastric inhibitory polypeptide/glucose-dependent insulinotropic peptide are known to potentiate insulin secretion mainly through a cAMP/protein kinase A (PKA) signaling pathway in pancreatic beta-cells, but the mechanism is not clear. We recently found that the cAMP-binding protein cAMP-GEFII (or Epac 2), interacting with Rim2, a target of the small G protein Rab3, mediates cAMP-dependent, PKA-independent exocytosis in a reconstituted system. In the present study, we investigated the role of the cAMP-GEFII--Rim2 pathway in incretin-potentiated insulin secretion in native pancreatic beta-cells. Treatment of pancreatic islets with antisense oligodeoxynucleotides (ODNs) against cAMP-GEFII alone or with the PKA inhibitor H-89 alone inhibited incretin-potentiated insulin secretion approximately 50%, while a combination of antisense ODNs and H-89 inhibited the secretion approximately 80-90%. The effect of cAMP-GEFII on insulin secretion is mediated by Rim2 and depends on intracellular calcium as well as on cAMP. Treatment of the islets with antisense ODNs attenuated both the first and second phases of insulin secretion potentiated by the cAMP analog 8-bromo-cAMP. These results indicate that the PKA-independent mechanism involving the cAMP-GEFII--Rim2 pathway is critical in the potentiation of insulin secretion by incretins.

Animals↗
PubMed2001

Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem.

Voltage-dependent calcium (Ca2+) channels are involved in many specialized cellular functions, and are controlled by intracellular signals such as heterotrimeric G-proteins, protein kinases and calmodulin (CaM). However, the direct role of small G-proteins in the regulation of Ca2+ channels is unclear. We report here that the GTP-bound form of kir/Gem, identified originally as a Ras-related small G-protein that binds CaM, inhibits high-voltage-activated Ca2+ channel activities by interacting directly with the beta-subunit. The reduced channel activities are due to a decrease in alpha1-subunit expression at the plasma membrane. The binding of Ca2+/CaM to kir/Gem is required for this inhibitory effect by promoting the cytoplasmic localization of kir/Gem. Inhibition of L-type Ca2+ channels by kir/Gem prevents Ca2+-triggered exocytosis in hormone-secreting cells. We propose that the small G-protein kir/Gem, interacting with beta-subunits, regulates Ca2+ channel expression at the cell surface.

Animals↗
PubMed2001

ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis.

Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types, including pancreatic beta-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP)) channels and glucose responsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6.2-/- mice. Although pancreatic alpha-cells were functional in Kir6.2-/-, the mice exhibited a severe defect in glucagon secretion in response to systemic hypoglycemia. In addition, they showed a complete loss of glucagon secretion, together with reduced food intake in response to neuroglycopenia. Thus, our results demonstrate that KATP channels are important in glucose sensing in VMH GR neurons, and are essential for the maintenance of glucose homeostasis.

ATP-Binding Cassette Transporters↗
PubMed2001

[Mercury concentration of fish in Tokyo Bay and the surrounding sea area].

Total mercury in the muscles of three fish species was analyzed in fish caught in Tokyo Bay and the surrounding sea areas, Sagami Bay and Choshi. Tokyo Bay is a semi-closed sea area surrounded by Tokyo, Kanagawa and Chiba prefectures. Sagami Bay and Choshi are open to the Pacific Ocean. A total of 412 fish consisting of northern whiting (Sillago japonica), flatfish (Limanda yokohamae) and sardine (Sardinops melanosticta) were caught in these areas over a 6 months period from November 1998 to April 1999. Total mercury concentration ranged from 0.008-0.092 microgram/g (wet wt.) in northern whiting, 0.006-0.065 microgram/g in flatfish and 0.001-0.045 microgram/g in sardine. All concentrations were below the restriction limit of fish mercury in Japan, 0.4 microgram/g of total mercury concentration. A significant correlation was found between mercury concentrations and body length or body weight in northern whiting and flatfish, irrespective of the sea area. A correlation was also found between mercury concentration in fish and their feeding habits: among the 3 species caught in the same area, crustacean feeding northern whiting had the highest, polychaete feeding flatfish moderate, and plankton feeding sardine had the lowest mercury concentration. In a comparison of mercury concentration in the same species caught in different sea areas, a higher concentration was noted in fish caught in the semi-closed sea area of Tokyo Bay, than in fish caught in the open sea areas of Sagami Bay and Choshi. This difference was most marked in fish caught at the bottom of Tokyo Bay and we considered that the mercury concentration of seawater and sediment in these areas was the cause of mercury accumulation in fish. These findings suggest that improved water quality control and environmental monitoring is necessary in semi-closed sea areas such as Tokyo Bay.

Animals↗
PubMed2001

A gene encoding phosphatidylethanolamine N-methyltransferase from Acetobacter aceti and some properties of its disruptant.

Phosphatidylcholine (PC) is a major component of membranes not only in eukaryotes, but also in several bacteria, including Acetobacter. To identify the PC biosynthetic pathway and its role in Acetobacter sp., we have studied Acetobacter aceti IFO3283, which is characterized by high ethanol oxidizing ability and high resistance to acetic acid. The pmt gene of A. aceti, encoding phosphatidylethanolamine N-methyltransferase (Pmt), which catalyzes methylation of phosphatidylethanolamine (PE) to PC, has been cloned and sequenced. One recombinant plasmid that complemented the PC biosynthesis was isolated from a gene library of the genomic DNA of A. aceti. The pmt gene encodes a polypeptide with molecular mass of either 25125, 26216, or 29052 for an about 27-kDa protein. The sequence of this gene showed significant similarity (44.3% identity in the similar sequence region) with the Rhodobacter sphaeroides pmtA gene which is involved in PE N-methylation. When the pmt gene was expressed in E. coli, which lacks PC, the Pmt activity and PC formation were clearly demonstrated. A. aceti strain harboring an interrupted pmt allele, pmt::Km, was constructed. The pmt disruption was confirmed by loss of Pmt and PC, and by Southern blot analyses. The null pmt mutant contained no PC, but tenfold more PE and twofold more phosphatidylglycerol (PG). The pmt disruptant did not show any dramatic effects on growth in basal medium supplemented with ethanol, but the disruption caused slow growth in basal medium supplemented with acetate. These results suggest that the lack of PC in the A. aceti membrane may be compensated by the increases of PE and PG by an unknown mechanism, and PC in A. aceti membrane is related to its acetic acid tolerance.

Acetobacter↗
PubMed2001

The est1 regulation depends on the oxygen concentration in Acetobacter pasteurianus.

The regulation mechanism for expression of the ethanol inducible esterase gene, est1, was investigated in A. pasteurianus. Deletion analysis of the 5' non coding region of est1 showed that the FNR-binding consensus sequence is important in the induction of est1 by ethanol. Cells grown under oxygen starvation produced esterase-1 in not only the presence but also the absence of ethanol. These results suggest that the induction of est1-expression depends on the oxygen concentration, and the gene may be induced by a FNR-like factor activated by a decrease in the intracellular oxygen concentration.

Alcohol Dehydrogenase↗
PubMed2000

A Pediatric Case of Ophthalmoplegic Migraine with Recurrent Oculomotor Nerve Palsy.

Purpose: A young patient of ophthalmoplegic migraine with recurrent oculomotor nerve palsy is reported.Case: A 4-year-old girl came to our hospital complaining of recurrent left ptosis and double vision which completely resolved within a few days. She had a history of drowsiness after vomiting every two months. Left oculomotor nerve palsy with internal ophthalmoplegia was observed. Electroencephalography revealed mild changes, but computed tomography, single photon emission computed tomography, and cerebrovascular Doppler-ultrasound examination demonstrated no abnormalities. This oculomotor nerve palsy completely improved on the next day.Results: Thereafter, left episodic mydriasis and oculomotor nerve palsy occurred twice each. However, the frequency and symptoms of migraine were remarkably reduced by topical administration of 0.25% timolol maleate twice daily to both eyes.Conclusion: In isolated oculomotor nerve palsy in childhood, ophthalmoplegic migraine should be also considered. We emphasize that a detailed case history is very important to its diagnosis.

Journal Article↗
PubMed2000

Role of intracellular esterases in the production of esters by Acetobacter pasteurianus.

Esters are the major flavor compounds produced by Acetobacter sp. during vinegar production. The two genes encoding the esterases in the bacteria were disrupted, and the effects of the disruptions studied. When cultured in the presence of ethanol, the est1 gene-disrupted mutant (DE1K) did not produce any ethyl acetate or isoamyl acetate. However, the disruption of est2 did not affect the ester production. Ethyl acetate production by N-23 (pME122P) and DE1K (pME122P), which contain est1, was 1.7-fold higher than that by the wild type, N-23. On analyzing the relationship between ethyl acetate production and the extracellular ethanol and acetic acid concentrations, we found that the highest amount of ethyl acetate was produced when the molar ratio of ethanol and acetic acid was 1:1. These results indicate that the ester production by Acetobacter sp. is mostly catalyzed by the intracellular esterase, esterase-1, with ethanol and acetic acid used as the substrates.

Journal Article↗
PubMed2000

Group impressions as dynamic configurations: the tensor product model of group impression formation and change.

Group impressions are dynamic configurations. The tensor product model (TPM), a connectionist model of memory and learning, is used to describe the process of group impression formation and change, emphasizing the structured and contextualized nature of group impressions and the dynamic evolution of group impressions over time. TPM is first shown to be consistent with algebraic models of social judgment (the weighted averaging model; N. Anderson, 1981) and exemplar-based social category learning (the context model; E. R. Smith & M. A. Zárate, 1992), providing a theoretical reduction of the algebraic models to the present connectionist framework. TPM is then shown to describe a common process that underlies both formation and change of group impressions despite the often-made assumption that they constitute different psychological processes. In particular, various time-dependent properties of both group impression formation (e.g., time variability, response dependency, and order effects in impression judgments) and change (e.g., stereotype change and group accentuation) are explained, demonstrating a hidden unity beneath the diverse array of empirical findings. Implications of the model for conceptualizing stereotype formation and change are discussed.

Attitude↗
PubMed2000

cAMP-GEFII is a direct target of cAMP in regulated exocytosis.

Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show that cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab3 being a small G protein) and to a new isoform, Rim2, both of which are putative regulators of fusion of vesicles to the plasma membrane. We also show that cAMP-GEFII, through its interaction with Rim2, mediates cAMP-induced, Ca2+-dependent secretion that is not blocked by an inhibitor of cAMP-dependent protein kinase (PKA). Accordingly, cAMP-GEFII is a direct target of cAMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-independent exocytosis.

Animals↗
PubMed2000

[A pediatric case of ophthalmoplegic migraine with recurrent oculomotor nerve palsy].

PURPOSE: A young patient of ophthalmoplegic migraine with recurrent oculomotor nerve palsy is reported. CASE: A 4-year-old girl came to our hospital complaining of recurrent left ptosis and double vision which completely resolved within a few days. She had a history of drowsiness after vomiting every two months. Left oculomotor nerve palsy with internal ophthalmoplegia was observed. Electroencephalography revealed mild changes, but computed tomography, single photon emission computed tomography, and cerebrovascular Doppler-ultrasound examination demonstrated no abnormalities. This oculomotor nerve palsy completely improved on the next day. RESULTS: Thereafter, left episodic mydriasis and oculomotor nerve palsy occurred twice each. However, the frequency and symptoms of migraine were remarkably reduced by topical administration of 0.25% timolol maleate twice daily to both eyes. CONCLUSION: In isolated oculomotor nerve palsy in childhood, ophthalmoplegic migraine should be also considered. We emphasize that a detailed case history is very important to its diagnosis.

Child, Preschool↗
PubMed1999

Cloning and characterization of ethanol-regulated esterase genes in Acetobacter pasteurianus.

The esterase encoding genes, est1 and est2, were cloned from Acetobacter pasteurianus. Nucleotide sequence analysis of est1 revealed a gene of 954 bp, and est1 coded for an arylesterase with a molecular weight of 34863 Da consisting of 317 amino acids. The est2 gene contained an open reading frame composed of 1221 bp encoding an esterase with a molecular weight of 43389 Da consisting of 406 amino acids. The est1 gene showed some similarity, but the est2 gene showed no significant homology to other esterases reported in various microorganisms. Northern blot analysis of total RNA from A. pasteurianus revealed that transcription of the est1 gene was induced only when the cells were grown in a medium containing ethanol, and suggested that the est1 transcript is monocistronic. In contrast, transcription of the est2 gene was repressed in the presence of ethanol. In the absence of ethanol, expression of the est2-mRNA, capable of encoding a multiple number of proteins, was revealed by Northern blot analysis. In addition, deletion analysis indicated that the 5'-region of the est2 gene contained a cis-acting domain for est2 transcriptional regulation. Analysis of the est1 promoter using the chloramphenicol acetyltransferase gene as a reporter gene showed that the promoter within the 305-bp fragment upstream of the ATG initiation codon was responsible for the transcription in cells grown in the presence of ethanol. Primer extension analysis of est1-mRNA showed that the transcription initiation site was 49 bp upstream from the ATG initiation codon. The results of a gel mobility shift assay indicated that there is a regulatory protein related to est1 regulation, which may have some relation to the ethanol resistance of Acetobacter sp.

Journal Article↗
PubMed1999

Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with extensive tumour thrombus through the hepatic vein.

BACKGROUND AND AIMS: Advanced hepatocellular carcinoma (HCC) with extensive tumour growth through the hepatic vein still has an extremely poor prognosis, even after cancer chemotherapy and/or transarterial embolization. Although aggressive surgical treatments using extracorporeal circulation and liver transplantation have been performed by some authors, the reported results were still unsatisfactory. In this study, we report the favourable result of hepatic artery chemoembolization and subsequent surgical resection in three patients with advanced HCC with extensive tumour thrombus through the hepatic vein. METHODS AND RESULTS: Three irresectable patients with HCC with extensive tumour thrombus through the hepatic vein underwent hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam. After the reduction of tumour extent with hepatic artery chemoembolization, two of the three patients underwent surgical resection. These two patients are still alive at 59 and 21 postoperative months, respectively. In the other case, the extent of the tumour and functional reserve of the liver prevented us from performing surgical resection, but the patient is doing well 62 months after the initial treatment. CONCLUSIONS: Hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam might be an effective treatment for irresectable advanced HCC with extensive tumour thrombus into the inferior vena cava or the right atrium through the hepatic vein. Radical surgical resection might be applicable for selected patients without high surgical risk after reducing tumour extent by hepatic artery chemoembolization.

Aclarubicin↗