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K Inoue

Publications and source records attributed to K Inoue.

At least 541 records · Page 30Linked to original sources
PubMed1999

Molecular mechanisms for CMT1A duplication and HNPP deletion.

As the best characterized human genomic disorders, CMT1A and HNPP illustrate several common mechanistic features of genomic rearrangements. These features include the following: (1) Recombination occurs between homologous sequences flanking the duplicated/deleted genomic segment. (2) The evolution of the mammalian genome may result in an architecture consisting of region-specific low-copy repeats that predispose to rearrangement secondary to providing homologous regions as substrate for recombination. (3) Strand exchange occurs preferentially in a region of perfect sequence identity within the flanking repeat sequences. (4) Double-strand breaks likely initiate recombination between the flanking repeats. (5) The mechanism and rate of homologous recombination resulting in DNA rearrangement may differ for male and female gametogenesis. (6) Homologous recombination resulting in DNA rearrangement occurs with high frequency in the human genome. (7) Genomic disorders result from structural features of the human genome and not population specific alleles or founder effects; therefore, genomic disorders appear to occur with equal frequencies in different world populations.

Charcot-Marie-Tooth Disease↗
PubMed1999

Osteocalcin-immunoreactive primary sensory neurons in the rat spinal and trigeminal nervous systems.

Osteocalcin-immunoreactivity (OC-ir) was examined in spinal and trigeminal primary sensory neurons of the adult rat. Sixteen percent of dorsal root ganglion (DRG) neurons were immunoreactive (ir) for this protein. These neurons were mostly large and measured 594-4583 microm(2) (mean+/-S.D.=2243+/-748 microm(2)). Thirty-four percent of DRG neurons >1200 microm(2) and 4% of those in the range 600-1200 microm(2) showed the ir. Virtually all DRG neurons <600 microm(2) were devoid of OC-ir. In the trigeminal ganglion (TG), 25% of neurons exhibited the ir. Such neurons were of various sizes (range=156-2825 microm(2), mean+/-S.D.=1234+/-543 microm(2)). Forty-five percent of TG neurons >800 microm(2) and 6% of those <400 microm(2) were immunoreactive for this protein. Twelve percent of TG neurons in the range 400-800 microm(2) showed the ir. In the mesencephalic trigeminal tract nucleus (Mes5), 63% of primary sensory neurons contained OC-ir. Virtually all OC-ir DRG and Mes5 neurons co-expressed parvalbumin-ir but not CGRP-ir. On the other hand, only 31% of OC-ir neurons co-expressed parvalbumin-ir and 10% co-expressed CGRP-ir in the TG. The present study indicates that DRG and Mes5 primary sensory neurons co-expressing OC- and parvalbumin-irs are spinal and trigeminal proprioceptors. OC-ir TG neurons which co-express parvalbumin- and CGRP-irs appear to include low-threshold mechanoreceptors and nociceptors, respectively.

Animals↗
PubMed1999

Inhibition of cholesteryl ester formation in macrophages by azole antimycotics.

Cultured macrophages take up and metabolize cholesterol-containing liposomes, resulting in massive accumulation of cholesteryl esters in the cells. Using this system, the effects of azole antimycotics on cholesteryl ester formation were studied. Incubation of mouse peritoneal macrophages with ketoconazole, miconazole, or econazole (0.1-10 microM) resulted in concentration-dependent inhibition of cholesteryl ester synthesis from endocytosed cholesterol. IC50 values (concentration resulting in 50% inhibition) were 1.4 +/- 0.1 microM, 4.1 +/- 0.2 microM, and 3.6 +/- 0.2 microM for ketoconazole, miconazole, and econazole, respectively. Complete inhibition was observed with 10 microM ketoconazole, and miconazole and econazole, each at 10 microM, caused 70 and 75% inhibition, respectively, of cholesteryl ester synthesis. The mechanism underlying the inhibition by ketoconazole was further studied. Ketoconazole did not appreciably block the uptake of liposomes or formation of triacylglycerol up to 10 microM. Interestingly, ketoconazole suppressed only 30% of 25-hydroxycholesterol-induced endogenous cholesterol esterification under conditions where esterification of endocytosed cholesterol was completely inhibited. Cytochemical studies with filipin-cholesterol staining revealed that ketoconazole induced massive accumulation of endocytosed cholesterol in macrophage phagolysosomes. These results indicate that ketoconazole inhibits cholesteryl ester formation in macrophages by blocking the intracellular transport of endocytosed cholesterol from lysosomes to the endoplasmic reticulum.

Animals↗
PubMed1999

Trace analysis of carbonyl compounds by liquid chromatography-mass spectrometry after collection as 2,4-dinitrophenylhydrazine derivatives.

This study describes the utilization of carbonyl- 2,4-dinitrophenylhydrazine (DNPH) derivatives for the determination of a micro amount of carbonyl compounds in air by liquid chromatography-mass spectrometry (LC-MS). After the carbonyl compounds are collected using a Waters Sep-Pak C18 cartridge column with-impregnated DNPH on octadecylsilica, they are eluted by acetonitrile as carbonyl-DNPH derivatives. A 20-mm3 aliquot of eluent is injected into the LC-MS system. The four derivatives (formaldehyde-, acetaldehyde-, acrolein- and acetone-DNPH) were eluted within 7 min with acetonitrile-water (60:40, v/v) as the mobile phase. The proposed method offers sub-ppb sensitivity and good reproducibility and was applied to the determination of these carbonyl compounds in actual air samples from store rooms, laboratories and offices. The relative standard deviations for these samples (n = 6) were 1 to 3%.

Acetaldehyde↗
PubMed1999

cDNA cloning and expression of human lactosylceramide synthase.

Lactosylceramide synthase is an enzyme that catalyzes the transfer of galactose from UDP-Gal to glucosylceramide, and thus participates in the biosynthesis of most glycolipids in mammals. We have isolated and sequenced the cDNA clone encoding human lactosylceramide synthase. The deduced amino acid sequence of the human lactosylceramide synthase showed 94.2% identity with rat lactosylceramide synthase. Northern blotting analysis revealed that lactosylceramide synthase mRNA was expressed in various tissues, with the highest level in brain and adrenal gland.

Amino Acid Sequence↗
PubMed1999

An alternative splicing form of phosphatidylserine-specific phospholipase A1 that exhibits lysophosphatidylserine-specific lysophospholipase activity in humans.

Phosphatidylserine-specific phospholipase A1 (PS-PLA1), which acts specifically on phosphatidylserine (PS) and 1-acyl-2-lysophosphatidylserine (lyso-PS) to hydrolyze fatty acids at the sn-1 position of these phospholipids, was first identified in rat platelets (Sato, T., Aoki, J., Nagai, Y., Dohmae, N., Takio, K., Doi, T., Arai, H., and Inoue, K. (1997) J. Biol. Chem. 272, 2192-2198). In this study we isolated and sequenced cDNA clones encoding human PS-PLA1, which showed 80% homology with rat PS-PLA1 at the amino acid level. In addition to an mRNA encoding a 456-amino acid product (PS-PLA1), an mRNA with four extra bases inserted at the boundary of the exon-intron junction was detected in human tissues and various human cell lines. This mRNA is most probably produced via an alternative use of the 5'-splicing site (two consensus sequences for RNA splicing occur at the boundary of the exon-intron junction) and encodes a 376-amino acid product (PS-PLA1DeltaC) that lacks two-thirds of the C-terminal domain of PS-PLA1. Unlike PS-PLA1, PS-PLA1DeltaC hydrolyzed exclusively lyso-PS but not PS appreciably. Any other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and their lyso derivatives were not hydrolyzed at all. These data demonstrated that PS-PLA1DeltaC exhibits lyso-PS-specific lysophospholipase activity and that the C-terminal domain of PS-PLA1 is responsible for recognizing diacylphospholipids. In addition, human PS-PLA1 gene was mapped to chromosome 3q13.13-13.2 and was unexpectedly identical to the nmd gene, which is highly expressed in nonmetastatic melanoma cell lines but poorly expressed in metastatic cell lines (van Groningen, J. J., Bloemers, H. P., and Swart, G. W. (1995) Cancer Res. 55, 6237-6243).

Alternative Splicing↗
PubMed1999

Percutaneous microwave coagulation therapy for patients with small hepatocellular carcinoma: comparison with percutaneous ethanol injection therapy.

BACKGROUND: The authors compared the efficacy of percutaneous microwave coagulation therapy (PMCT) and percutaneous ethanol injection therapy (PEIT) in the treatment of patients with cirrhosis and a solitary nodular hepatocellular carcinoma (HCC) < or = 2 cm in greatest dimension. METHODS: Of 43 patients with well-differentiated HCC, 23 were treated with PMCT and 20 with PEIT. Of the 47 patients with moderately or poorly differentiated HCC, 25 were treated with PMCT and 22 with PEIT. In a retrospective, nonrandomized study, the prognoses of 90 patients during the 12-72 months preceding the study were analyzed according to histologic tumor grade. RESULTS: The overall 5-year survival rates for patients with well-differentiated HCC treated with PMCT (70%) and PEIT (78%) were not significantly different. No difference between the patterns of recurrence was observed. Among the patients with moderately or poorly differentiated HCC, overall survival with PMCT (5-year survival rate: 78%) was significantly better than with PEIT (5-year survival rate: 35%) (P = 0.03). Nine of 22 patients with moderately or poorly differentiated HCC treated with PEIT experienced recurrence in the original target subsegment. Only 2 of 25 patients treated with PMCT had a recurrence in the same subsegment as the initial tumor. CONCLUSIONS: PMCT may be superior to PEIT for the local control of moderately or poorly differentiated small HCC.

Aged↗
PubMed1999

Block and unblock by imipramine of cloned and mutated P2X2 receptor/channel expressed in Xenopus oocytes.

Effects of imipramine on the cloned P2X2 receptor/channel and its mutants expressed in Xenopus oocytes were examined. Imipramine (100 microM) partially blocked an ionic current mediated through the wild-type P2X2 receptor/channel. With a higher concentration (300 microM) of imipramine, the current block was attenuated, suggesting that the second, lower affinity, 'unblocking' binding-site for imipramine exists in addition to the 'blocking' binding-site. These profiles of the modulation by imipramine were influenced by the substitution of negatively charged or polarized amino acid residues near the outer mouth of the channel pore (Asp315, Thr330 and Asn333) with neutral amino acid residues (Val or Ile). With the neutralization of Asp315, the current 'block' by 100 microM imipramine was attenuated. With the neutralization of Thr330, the current 'block' by 100 microM imipramine was enhanced. With the neutralization of Asn333, the 'unblock' by 300 microM imipramine disappeared. The results suggest that imipramine modulates P2X2 receptor/channels by interacting these amino acid residues.

Animals↗
PubMed1999

Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1.

Expression of the DMP1 transcription factor, a cyclin D-binding Myb-like protein, induces growth arrest in mouse embryo fibroblast strains but is devoid of antiproliferative activity in primary diploid fibroblasts that lack the ARF tumor suppressor gene. DMP1 binds to a single canonical recognition site in the ARF promoter to activate gene expression, and in turn, p19(ARF) synthesis causes p53-dependent cell cycle arrest. Unlike genes such as Myc, adenovirus E1A, and E2F-1, which, when overexpressed, activate the ARF-p53 pathway and trigger apoptosis, DMP1, like ARF itself, does not induce programmed cell death. Therefore, apart from its recently recognized role in protecting cells from potentially oncogenic signals, ARF can be induced in response to antiproliferative stimuli that do not obligatorily lead to apoptosis.

3T3 Cells↗
PubMed1999

Cholestanol induces apoptosis of cerebellar neuronal cells.

Cerebrotendinous xanthomatosis (CTX) is a hereditary lipid storage disease characterized by hyper-cholestanolemia, cerebellar ataxia, xanthoma, and cataract. We hypothesized that cholestanol in serum of CTX patients might induce neuronal cell death in the cerebellum and eventually lead to cerebellar ataxia. To gain support for this hypothesis we developed hyper-cholestanolemia rats by feeding cholestanol. Neuronal cells, especially Purkinje cells in the cerebellum were stained by Sudan black B only in the cholestanol-fed rats, indicating the deposit of cholestanol in cerebellum. To examine effects of cholestanol in vitro, cerebellar neuronal cells were cultured with cholestanol. The cholestanol concentration increased and the viability decreased in cells cultured with cholestanol. Apoptosis was evident in cells cultured with cholestanol more frequently than in control cells, determined using the terminal deoxynucleotidyl transferase (TdT) dUTP nick end-labeling (TUNEL) method. As activities of interleukin-1beta-converting enzyme (ICE) and CPP32 protease were increased in cells cultured with cholestanol, all these data taken together suggest that cholestanol induced apoptosis of cerebellar neuronal cells. Our observations may explain the mechanism of cerebellar ataxia of CTX patients.

Animals↗
PubMed1999

Signal transduction pathways mediated by glycoprotein Ia/IIa in human platelets: comparison with those of glycoprotein VI.

Human platelets were activated either by glycoprotein (GP) Ia/IIa agonist (rhodocytin) or by a GPVI agonist (collagen-related peptide, CRP), and the intracellular signal transduction pathways were compared in the presence of various inhibitors. Rhodocytin isolated from Calloselasma rhodostoma venom was verified as a GPIa/IIa agonist, based on the inhibitory effects of three mAbs directed against GPIa. Platelet activation mediated by GPIa/IIa led to overt platelet aggregation, elevation of intracellular Ca2+, and tyrosine phosphorylation of several proteins, similar to that of GPVI. p72(syk) and phospholipase Cgamma2 (PLCgamma2) tyrosine phosphorylation were also observed with GPIa/IIa-mediated platelet aggregation, although they peaked slightly later than that of GPVI. In contrast to GPVI-mediated platelet activation, most of these phenomena induced by GPIa/IIa activation were markedly suppressed by acetylsalicylic acid (ASA) or cytochalasin D. These findings suggest that the requirements for thromboxane A2 (TXA2) production and actin polymerization, which are the characteristics of collagen-induced platelet activation, are derived from the GPIa/IIa-mediated signal transduction, but not from that of GPVI.

Antibodies, Monoclonal↗
PubMed1999

Effects of nocistatin on nociceptin-induced impairment of learning and memory in mice.

We investigated the effects of nociceptin/orphanin FQ and nocistatin on learning and memory function as measured in a step-down type passive avoidance task and spontaneous alternation of Y-maze with mice. Nociceptin (0.5-5.0 nmol/mouse, i.c.v.) 30 min before the training session or Y-maze test, dose dependently shortened the step-down latency and impaired spontaneous alternation, while there was no significant effect of nocistatin (0.5-5.0 nmol/mouse). Interestingly, nocistatin (5.0 nmol) significantly improved the nociceptin (5.0 nmol)-induced impairment of learning and memory without changing motor activity or response to electric shocks. These results suggest that nocistatin, a new biologically active peptide now found to also counteract the impairment of learning and memory induced by nociceptin, plays an important role in the regulation of learning and memory process in the central nervous system.

Animals↗
PubMed1999

Cloning of a bovine orphan transporter and its short splicing variant.

We have isolated a cDNA (bv7-3) encoding a member of the Na+,Cl(-)-dependent transporter family and its short splicing variant (bv7-3s) by screening a bovine retina cDNA library. Sequence analysis revealed that bv7-3 encodes a protein of 729 amino acids and is a bovine homologue of the rat orphan transporter v7-3-2. bv7-3s contains 265 amino acids, sharing 252 N-terminal amino acids with bv7-3. Both mRNAs for bv7-3 and bv7-3s were detected in nervous system by Northern blot analysis. In immunofluorescence analysis in transfected HEK 293T cells, myc-tagged bv7-3 was mainly detected on the plasma membrane, whereas myc-tagged bv7-3s showed a pattern of intracellular membrane staining.

Alternative Splicing↗
PubMed1999

Antecedent angina pectoris as a predictor of better functional and clinical outcomes in patients with an inferior wall acute myocardial infarction.

We examined whether angina pectoris (AP) occurring shortly before the onset of acute myocardial infarction (AMI) can render the right ventricle and the conducting tissue resistant to ischemia in 75 patients with an inferior wall AMI. Each patient had total occlusion in the proximal right coronary artery and underwent successful coronary angioplasty < or =24 hours from the onset. We divided patients into 2 groups based on presence or absence of antecedent AP < or =24 hours before the system onset: group 1 (absent) = 57 patients; group 2 (present) = 18 patients. Collateral circulation was more frequently observed in group 2 than in group 1 (group 1 vs 2, 28% vs 61%, p <0.01). Elevation in ST segment > or =1 mm in lead V4R, hemodynamic right ventricular dysfunction, and frequency of high-degree heart block were more frequent in group 1 than in group 2 (75% vs 44%, 79% vs 39%, 53% vs 11%, p <0.05, respectively). Multivariate analysis demonstrated that antecedent AP is the only factor related to these complications. Thus, episodes of AP occurring shortly before onset may restrain development of ischemic damage of the right ventricle and conducting tissue, and are associated with better clinical and functional outcomes among patients with an inferior wall AMI.

Acute Disease↗