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Biomedical subjects

Y Takei

Publications and source records attributed to Y Takei.

At least 91 records · Page 5Linked to original sources

Renin-angiotensin system in elasmobranch fish: A review.

The renin-angiotensin system (RAS) has been identified recently in elasmobranch fish, and the structure of angiotensin II (ANG II) is unusual ([Asp(1),Pro(3),Ile(5)]-ANG II) compared to other vertebrates. Receptors for ANG II have been identified in blood vessels and in a variety of osmoregulatory tissues including the gill, kidney and rectal gland. In addition, there is considerable binding to the interrenal gland and the stimulation of 1alpha-hydroxycorticosterone production in vitro suggests a physiological role in corticosteroidogenesis. ANG II is a potent vasoconstrictor and this effect does not appear to be mediated by sympathetic activation or catecholamine release. Although the RAS may not be involved in maintaining basal blood pressure, it may be important in situations in which blood pressure is reduced. Understanding of the role of ANG II as an osmoregulatory hormone is only just emerging with putative roles in the control of gill, rectal gland and perhaps, drinking. In addition, the stimulation of corticosteroid secretion may provide another means of controlling osmoregulation. J. Exp. Zool. 284:526-534, 1999.

Amino Acid Sequence↗

Impairment of inhibitory synaptic transmission in mice lacking synapsin I.

Deletion of the synapsin I genes, encoding one of the major groups of proteins on synaptic vesicles, in mice causes late onset epileptic seizures and enhanced experimental temporal lobe epilepsy. However, mice lacking synapsin I maintain normal excitatory synaptic transmission and modulation but for an enhancement of paired-pulse facilitation. To elucidate the cellular basis for epilepsy in mutants, we examined whether the inhibitory synapses in the hippocampus from mutant mice are intact by electrophysiological and morphological means. In the cultured hippocampal synapses from mutant mice, repeated application of a hypertonic solution significantly suppressed the subsequent transmitter release, associated with an accelerated vesicle replenishing time at the inhibitory synapses, compared with the excitatory synapses. In the mutants, morphologically identifiable synaptic vesicles failed to accumulate after application of a hypertonic solution at the inhibitory preterminals but not at the excitatory preterminals. In the CA3 pyramidal cells in hippocampal slices from mutant mice, inhibitory postsynaptic currents evoked by direct electrical stimulation of the interneuron in the striatum oriens were characterized by reduced quantal content compared with those in wild type. We conclude that synapsin I contributes to the anchoring of synaptic vesicles, thereby minimizing transmitter depletion at the inhibitory synapses. This may explain, at least in part, the epileptic seizures occurring in the synapsin I mutant mice.

Animals↗

Identification of the sequence responsible for the nuclear localization of human Cdc6.

The Cdc6 is the essential protein for the initiation of DNA replication. Cdc6 is localized in the G1 nucleus, and abnormal nuclear localization of this protein induces irregular initiation of DNA replication. We identified here that amino acids K57 and R58 in the human Cdc6 protein play an important role in the nuclear localization of the protein. The fundamental features of the mechanism regulating the localization of Cdc6 seem to be maintained in yeast, Xenopus, and human, since the amino acid sequence surrounding K57 and R58, (S/T)PXKR(L/I), is conserved in these species. Substitution of amino acid residue S54 with E and not Q blocked partially the nuclear localization of the protein, implying that the phosphorylation at S54 is involved in the regulating mechanism of the cell cycle-dependent localization of Cdc6.

Amino Acid Sequence↗

Molecular cloning of CLC chloride channels in Oreochromis mossambicus and their functional complementation of yeast CLC gene mutant.

We have cloned two members of the CLC chloride channel family (OmCLC-3 and OmCLC-5) from gill cDNA libraries of the euryhaline tilapia Oreochromis mosammbicus. At the amino acid level, OmCLC-3 is 90.5% identical to rat CLC-3 and OmCLC-5 is 79.2% identical to rat CLC-5. Ribonuclease protection assay revealed that OmCLC-5 was mainly expressed in the gill, kidney, and intestine in both freshwater- (FW) and seawater- (SW) adapted tilapia. Although the mRNA of OmCLC-3 was broadly expressed in tissues of FW- and SW-adapted tilapia, the most intense signals were observed in the gill, kidney, intestine, and brain. Injection of OmCLC-3 and OmCLC-5 cRNAs into Xenopus oocytes did not elicit chloride currents, but these clones did functionally complement the gef1 phenotype of YPH250(gef), a yeast strain in which a single CLC channel (GEF1) has been disrupted by homologous recombination. These results clearly indicated that CLC channels closely related to the mammalian CLC-3, -4, and -5 subfamily exist also in tilapia and that OmCLC-3 and OmCLC-5 function as intracellular chloride channels.

Amino Acid Sequence↗

Teleost-type angiotensin is present in Australian lungfish, Neoceratodus forsteri.

Angiotensin I (ANG I) was produced from the incubation of lungfish plasma with homologous kidney extracts. The purified peptide was found to have the sequence of H-Asn-Arg-Val-Tyr-Val-His-Pro-Phe-Thr-Leu-OH, which is homologous for the first eight residues with all teleost angiotensins so far sequenced, although lungfish generally possess tetrapod-type hormones. The lungfish decapeptide (ANG I) induced dose-dependent increases in arterial pressure in the rat. The lungfish octapeptide (ANG II) released aldosterone from kidney-adrenal tissue in vitro in a dose-dependent manner and induced dose-dependent increases in arterial pressure of the lungfish. Substitution of asparagine with aspartic acid in the first position (tetrapod-type ANG II) did not alter the blood pressure response significantly, but a second substitution of the valine in the (5)-position with isoleucine (ANG II form found in human and rat) abolished the rise in arterial pressure in lungfish over the same dose range.

Angiotensin I↗

Cardiovascular control via angiotensin II and circulating catecholamines in the spiny dogfish, Squalus acanthias.

The contributions of circulating angiotensin II (Ang II) and catecholamines to cardiovascular control in the spiny dogfish were investigated by monitoring the effects of exogenous and endogenous dogfish [Asn1, Pro3, Ile5]-Ang II (dfAng II) on plasma catecholamine levels and blood pressure regulation. Bolus intravenous injections of dfAng II (30-1200 pmol kg-1) elicited dose-dependent increases in plasma adrenaline and noradrenaline concentrations, caudal artery pressure (PCA), and systemic vascular resistance (RS), and a decrease in cardiac output (Q). Similar injections of Ang II in dogfish pre-treated with the alpha-adrenoceptor antagonist yohimbine (4 mg kg-1) also elicited dose-dependent increases in plasma catecholamine levels yet the cardiovascular effects were abolished. Dogfish treated with yohimbine were hypotensive and had elevated levels of plasma Ang II and catecholamines. Intravenous injection of the smooth muscle relaxant papaverine (10 mg kg-1) elicited a transient decrease in PCA and RS, and increases in plasma Ang II and catecholamine levels. In dogfish first treated with lisinopril (10(-4) mol kg-1), an angiotensin converting enzyme inhibitor, papaverine treatment caused a more prolonged and greater decrease in PCA and RS, an attenuated increase in plasma catecholamines, and no change in plasma Ang II. By itself, lisinopril treatment had little effect on PCA, and no effect on RS, plasma Ang II or catecholamines. In yohimbine-treated dogfish, papaverine treatment elicited marked decreases in PCA, RS, and Q, and increases in plasma Ang II and catecholamines. Among the three papaverine treatments, there was a positive linear relationship between plasma Ang II and catecholamine concentrations, and the cardiovascular and hormonal changes were most pronounced in the yohimbine + papaverine treatment. Therefore, under resting normotensive conditions, while Ang II does not appear to be involved in cardiovascular control, catecholamines play an important role. However, during a hypotensive stress elicited by vascular smooth muscle relaxation. Ang II indirectly contributes to cardiovascular control by dose-dependently stimulating catecholamine release.

Adrenergic alpha-Antagonists↗

Effects of nitric oxide synthase inhibition on the cerebral circulation and brain damage during kainic acid-induced seizures in newborn rabbits.

The nitric oxide (NO) synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), was used to investigate the effect of endogenous NO on the cerebral circulation and brain damage during kainic acid (KA)-induced seizures in newborn rabbits. The cerebral blood flow (CBF), by laser doppler flowmetry, cerebral oxygenation (concentrations of oxy-(HbO2), deoxy-(HbR) and total hemoglobin (tHb) in brain tissue), by near-infrared spectroscopy (NIRS), mean arterial blood pressure (MABP), electroencephalography (EEG), and hippocampal neuronal damage were evaluated. Pretreatment with L-NAME caused significant decreases in CBF, HbO2, and tHb, and a significant increase in HbR during KA-induced seizures, compared with pretreatment with saline (P < 0.05), without a significant difference in MABP. Our study also demonstrated that pretreatment with L-NAME reduced the seizure activity and neuronal cell death in the hippocampus elicited by the systemic administration of KA in the neonatal brain. These results suggest that NO is of major importance in the neurodestructive process in spite of its roles in maintaining both the CBF and cerebral oxygenation during KA-induced seizures in the neonatal brain.

Animals↗

Cloning, properties and tissue distribution of natriuretic peptide receptor-A of euryhaline eel, Anguilla japonica.

During the course of cloning and characterization of natriuretic peptide receptor-A (NPR-A) from the euryhaline fish eel, Anguilla japonica, we identified a splice variant with unique structural properties that affect ligand-inducible intrinsic guanylate cyclase activity. The variant, generated from a splice between a cryptic donor site and the normal acceptor site, lacked nine amino acid residues (VFTKTGYYK) in the kinase-like regulatory domain. This deletion of a very short segment resulted in the complete loss of the ligand inducibility of the cyclase activity. The nine-amino acid segment may therefore be useful as a target for studies aimed at clarifying the mechanism of activation of the guanylate cyclase domain. Characterization of the normal form of eel NPR-A also led to the following interesting findings. Although eel NPR-A had a domain structure very similar to that of mammalian counterparts, it lacked the third cysteine residue in the extracellular domain which is conserved among mammalian NPR-A molecules. The eel receptor bound both amidated and nonamidated eel atrial natriuretic peptide (eANP) with high affinity but, when assayed for ligand-inducible cGMP generation, it responded efficiently only to physiological concentrations of the amidated ligand, suggesting that the biologically active form is the amidated eANP, and the nonamidated form acts as a partial antagonist; similarly, nonhomologous rat ligands behaved like antagonists toward the eel receptor in the concentration range 0.1-10 nm. The receptor message was found to be relatively abundant in the osmoregulatory organs such as the gill, kidney, intestine and urinary bladder.

Adaptation, Physiological↗

Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3.

Ulcerative colitis (UC), a common form of inflammatory bowel disease, is a multifactorial disorder with significant genetic influence. Recently, evidence of linkage on chromosome 7q near the intestinal mucin gene MUC3 was reported by an affected sib-pair analysis. Previous reports indicate a possible mucin abnormality in UC patients, but whether genetic differences in a specific mucin gene are associated with UC is unknown. Here we analysed polymorphisms of variable number of tandem repeats (VNTRs) within this gene using DNAs obtained from 243 Japanese (75 patients with UC and 168 controls), and to confirm the result we undertook a two-stage examination using 328 Caucasian samples (72 and 85 with UC in the first and second stages, respectively, and 171 controls). When the frequency of patients carrying one or two rare VNTR alleles was compared with that of controls, a significant increase was found first in Japanese patients (odds ratio 2.72, 95% CI 1.17-6.32, P = 0. 0308). In Caucasians, the odds ratio was 2.80 (95% CI 1.36-5.75, P = 0.0079) in the first stage, 2.43 (95% CI 1.20-4.92, P = 0.0196) in the second stage and 2.60 (95% CI 1.41-4.80, P = 0.0024) in total. The overall odds ratio was 2.64 (95% CI 1.60-4.33, P = 0.0001). This result suggests that rare alleles of the MUC3 gene may confer genetic predisposition to UC.

Alleles↗

How useful is the detection kit for antibody to Helicobacter pylori in urine (URINELISA) in clinical practice?

OBJECTIVE: Increased knowledge of the significance of Helicobacter pylori (H. pylori) infection in gastric disorders has accelerated the trend of screening patients with dyspepsia for its infection. Serological examination of antibody for H. pylori has been widely performed. Recently, a urine-based enzyme-linked immunosorbent assay (URINELISA) kit for detection of antibody for H. pylori has been developed. Accordingly, we evaluated its diagnostic accuracy in clinical practice. METHODS: Subjects of this study were 132 patients who presented at our university hospital because of dyspeptic symptoms (81 men, 51 women; age, 41.5+/-1.4 yr). 13C urea breath test, blood drawing for serological antibody for H. pylori infection by four different kits, and urine collection for the URINELISA test for detection of the antibody were performed. Diagnostic accuracy of the commercially available antibodies in serum and in urine were investigated using the results of the 13C urea breath test as the gold standard. RESULTS: Sensitivity, specificity, and accuracy of URINELISA were 86.3% (95% confidence intervals [CI], 76-93%), 91.5% (95% CI, 81-97%), and 88.6% (95% CI, 82-93%), respectively, which were comparable to those of imported serological kits. CONCLUSIONS: The URINELISA kit for detecting anti-H. pylori antibody in urine provides diagnostic accuracy comparable to that of imported kits for detecting antibodies in serum and is considered to be clinically useful for the diagnosis of H. pylori infection.

Adult↗

Mediation of humoral catecholamine secretion by the renin-angiotensin system in hypotensive rainbow trout (Oncorhynchus mykiss).

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.

Acute Disease↗

[Attenuation of reperfusion phenomenon by reperfusion using leukocyte-depleted blood during direct percutaneous transluminal coronary angioplasty for acute myocardial infarction].

Leukocytes are important in the occurrence of reperfusion injury in coronary intervention for acute myocardial infarction (AMI). This study compared reperfusion injury caused by reperfusion using leukocyte-depleted blood (LD) and that by conventional angioplasty (control) through the reperfusion phenomenon including reperfusion arrhythmia and additional ST elevation during direct percutaneous transluminal coronary angioplasty (PTCA) in 41 patients with 21 left anterior descending artery (LAD) lesions and 20 right coronary artery (RCA) lesions. LD was prepared from 20 ml of venous blood, 20 ml of mixed blood and 60 ml of arterial blood from the patients (LD group; LAD-LD: n = 10, RCA-LD: n = 10) which was passed through a leukocyte removal filter. The blood was injected from the tip of the balloon catheter at 10 ml/min during inflation for 10 min before balloon deflation. The control group (LAD-control: n = 11, RCA-control: n = 10) underwent conventional angioplasty. The appearance of reperfusion arrhythmia [atrioventricular block (AVB) > II, accelerated idioventricular rhythm (AIVR), ventricular tachycardia (VT), ventricular fibrillation (Vf)] and measurements of STmax deviation before and after reperfusion, the differences of the STmax deviation (delta ST) and additional ST elevation (LAD: > or = 0.5 mV increase of sigma ST in lead V1-V6, RCA: > or = 0.3 mV increase of sigma ST in lead II, III and aVF) were studied. The appearance of reperfusion arrhythmias was as follows; LAD-LD: AVB 0, AIVR 1, VT 1, Vf 0, LAD-control: AVB 0, AIVR 4, VT 2, Vf 1, NS, and RCA-LD: AVB 0, AIVR 0, VT 0, Vf 0, RCA-control: AVB 2, AIVR 0, VT 1, Vf 0, NS. There was no reperfusion arrhythmia in the RCA-LD group. There was no significant difference in the appearance of reperfusion arrhythmias between the LAD-LD and LAD-control or RCA-LD and RCA-control groups. Before reperfusion the STmax deviation (mV) was LAD-LD 0.86 +/- 0.46 vs LAD-control 0.74 +/- 0.49 and RCA-LD 0.29 +/- 0.18 vs RCA-control 0.15 +/- 0.09 and after reperfusion LAD-LD 0.63 +/- 0.35 vs LAD-control 0.81 +/- 0.49 and RCA-LD 0.13 +/- 0.15 vs RCA-control 0.20 +/- 0.12, respectively. There were no significant differences between LAD-LD and LAD-control or RCA-LD and RCA-control groups. delta ST (mV) was LAD-LD 0.23 +/- 0.56 vs LAD-control 0.07 +/- 0.60, p = 0.09 and RCA-LD 0.16 +/- 0.12 vs RCA-control 0.06 +/- 0.14, p = 0.002, respectively. The number of patients with additional ST elevation soon after reperfusion was LAD-LD 3 vs LAD-control 10, p < 0.05 and RCA-LD 0 vs RCA-control 8, p < 0.001, respectively.

Angioplasty, Balloon, Coronary↗

[Ethanol-induced hepatic microcirculatory disturbance].

Alcoholic liver injury predominates in the pericentral region, in which oxygen tension is physiologically lowest. The enhanced injurious effect of ethanol at this site is postulated to be due to hypoxia, resulting from an enhanced oxygen demand of hepatocytes for the oxidative metabolism of ethanol. Moreover, we found that ethanol at higher concentrations induces hypoxia in the liver by causing microcirculatory disturbance. Upon initiation of ethanol infusion into the portal vein of isolated perfused rat liver at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phase). Sodium nitroprusside, a known vasodilator, diminished the ethanol-induced increase in portal pressure, increased oxygen consumption leading to inhibition of the reduction of the respiratory cytochromes of the liver, and diminished liver injury. The data indicate that the ethanol-induced hepatic vasoconstriction disturbs hepatic microcirculation, leading to hepatic hypoxia and hepatocellular injury. Endothelin-1 antiserum inhibited significantly hepatic vasoconstriction induced by ethanol. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, following the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phase the sustained the vasoconstriction. Based on the current results, we propose that the sinusoidal tone in the presence of ethanol is regulated predominantly by the actions of the two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide.

Animals↗

Isolation and characterization of a novel TP53-inducible gene, TP53TG3.

We applied the differential mRNA display method to isolate genes regulated by wild-type TP53 in cells of a colon-cancer line (SW480) in which we had established an inducible TP53 expression system under the control of the lactose operon. Here we report isolation and characterization of a novel TP53-inducible gene, termed TP53TG3 (TP53 target gene 3). Its DNA sequence was identical to sequences present in two BAC clones that had been mapped to chromosome band 16p13. The gene expressed several transcripts by alternative splicing; the two major transcripts, TP53TG3a and TP53TG3b, encoded 124- and 132-amino-acid peptides that were expressed predominantly in testis. Immunohistochemical analysis using cancer cells (HeLa or H1299) that had been transfected with plasmid DNA designed to express the MYC-fused TP53TG3 proteins indicated that these products were present mainly in the cytoplasm 20 hr after transfection. However, 40 hr after transfection, the recombinant proteins had accumulated in the nuclei of some cells. Because no known nuclear localization domain was present in the amino acid sequence, we suspect that this protein plays an important role in the TP53-mediated signaling pathway, when it forms complexes with other protein(s) and is transferred by them into the nucleus. Genes Chromosomes Cancer 26:329-335, 1999.

Amino Acid Sequence↗

[A case of relapsing polychondritis with oculobulbar symptoms and successful treatment of respiratory failure with BiPAP].

A 66-year-old man developed diplopia, ptosis, dysphagia, and acute respiratory failure. The initial diagnosis was myasthenia gravis and prednisolone had been administrated for three years. Because of recurrent upper respiratory infections, prednisolone was tapered off. Two months later, auricular chondritis, arthritis, and conjunctivitis appeared. He was diagnosed as having relapsing polychondritis on the basis of histological findings of the ear lobe biopsy. Reinstituted prednisolone had the effect on the auricular chondritis, arthritis, and conjunctivitis, but no effect on dysphagia, hoarseness, and respiratory failure caused by the deformity of the pharynx and airway. Tracheal collapse usually causes rapid death, so early tracheostomy and the use of endotracheal prostheses have been recommended in patients with airway obstruction from relapsing polychondritis, but such surgical management can only partially open up the large airways and has no effect on smaller airways. In this case tracheostomy and endoluminal stent placement have helped improve the patient's respiratory failure, but have had little effect on its aggravation at night in the supine position. The use of BiPAP after surgical management can be an effective treatment for airway involvement in relapsing polychondritis probably because it keeps the narrowed airways from collapsing, especially at night.

Acute Disease↗

Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system.

We applied a differential display method to screen mRNAs isolated from a newly established cell line that carried a wild-type p53 transgene under control of the lactose operon. To investigate the p53 signaling pathway, we looked for genes whose expression was significantly induced or suppressed by induction of wild-type p53 protein, and identified seven. DNA sequence analyses revealed that the two genes that were upregulated encoded isozyme 6 of aldehyde dehydrogenase (ALDH6) and subunit I of cytochrome c oxidase (COI). The five genes that were downregulated encoded protein-tyrosine kinase (Syk), high mobility group chromosomal protein 17 (HMG-17), transferrin receptor, human alpha-tubulin, and sds22-like protein. The results indicated that genes related to cell cycle regulation, cell respiration, and cytoskeletal structure are involved in the process of growth arrest induced by wild-type p53.

Cell Cycle↗