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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 19 recordsLinked to original sources
PubMed1999

Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney.

BACKGROUND: Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown. METHODS AND RESULTS: We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of </=10(-10) mol/L reduced renal perfusion pressure in Dahl salt-resistant (R) rats but increased renal perfusion pressure in Dahl salt-sensitive (S) rats (10(-10) mol/L: -10.3+/-0. 6% versus 11.2+/-1.5%, R versus S; P<0.01). BQ-3020 caused a dose-dependent release of NO in both R and S rats, although the level of NO release in S rats was lower, as detected by chemiluminescence (10(-10) mol/L: 10.7+/-0.7 versus 3.1+/-0.4 fmol/min per gram of kidney, R versus S; P<0.01). Similar effects of BQ-3020 were observed in streptozotocin-induced diabetic rats and diet-induced hypercholesterolemic rats. Expression of endothelial NO synthase decreased in S rats but not in diabetic or hypercholesterolemic rats. In contrast, expression of ETBR in the endothelium was decreased in all 3 disease models compared with that in the vascular smooth muscle cell. CONCLUSIONS: These results suggest that impaired NO release in response to stimulation of ETBR is due, at least in part, to a decrease in endothelial ETBR and may play a role in vascular dysfunction usually associated with arteriosclerosis-related diseases.

Animals↗
PubMed1999

Characterization of the carp myosin heavy chain multigene family.

We isolated partial coding sequences for 29 carp myosin heavy chain genes (MyoHCs) and determined the nucleotide sequences around the region encoding the loop 2 of the myosin molecule. The predicted amino acid sequences from the isolated genes all showed very high similarity to those of skeletal and cardiac muscles from higher vertebrates, but not to those of smooth and non-muscle counterparts. Among all clones isolated, carp MyoHC10, MyoHCI-1-3 and MyoHC30 showed exon-nucleotide sequences identical to those of cDNAs encoding the loop 2 region of the 10 degrees C-, intermediate- and 30 degrees C-type fast skeletal isoforms [Hirayama and Watabe, Euro. J. Biochem. 246 (1997) 380-387]. The loop 2 of 28 types of carp MyoHCs was encoded by two exons separated by an intron corresponding to that of the 16th in higher vertebrate MyoHCs, whilst this intron was not found in carp MyoHC30. Although carp MyoHC30 had a gene organization different from those of higher vertebrates and other carp MyoHCs, its predicted amino acid sequence for loop 2 showed the highest homology to those of higher vertebrates among carp MyoHCs. In the 28 carp MyoHCs containing the intron, a combination of different nucleotide sequences for the two resulted in 14 distinct series for the combined coding sequence. These different nucleotide sequences encoded nine distinct amino acid sequences. Phylogenetic analysis for the present loop 2 and light meromyosin previously reported for carp MyoHCs [Imai et al., J. Exp. Biol. 200 (1997) 27-34] revealed that carp MyoHCs have recently diverged and are more closely related to each other than to MyoHCs from other species.

Amino Acid Sequence↗
PubMed1999

Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family.

The semaphorins comprise a large family of membrane-bound and secreted proteins, some of which have been shown to function in axon guidance. We have cloned a transmembrane semaphorin, Sema W, that belongs to the class IV subgroup of the semaphorin family. The mouse and rat forms of Sema W show 97% amino acid sequence identity with each other, and each shows about 91% identity with the human form. The gene for Sema W is divided into 15 exons, up to 4 of which are absent in the human cDNAs that we sequenced. Unlike many other semaphorins, Sema W is expressed at low levels in the developing embryo but was found to be expressed at high levels in the adult central nervous system and lung. Functional studies with purified membrane fractions from COS7 cells transfected with a Sema W expression plasmid showed that Sema W has growth-cone collapse activity against retinal ganglion-cell axons, indicating that vertebrate transmembrane semaphorins, like secreted semaphorins, can collapse growth cones. Genetic mapping of human SEMAW with human/hamster radiation hybrids localized the gene to chromosome 2p13. Genetic mapping of mouse Semaw with mouse/hamster radiation hybrids localized the gene to chromosome 6, and physical mapping placed the gene on bacteria artificial chromosomes carrying microsatellite markers D6Mit70 and D6Mit189. This localization places Semaw within the locus for motor neuron degeneration 2, making it an attractive candidate gene for this disease.

Amino Acid Sequence↗
PubMed1999

Quantitative determination of E5880 in rat plasma by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

A simple and sensitive method is described for the determination of E5880 in rat plasma. The method is based on high-performance liquid chromatography/electrospray ionization mass spectrometry, using deuterated E5880 as an internal standard. Selected reaction monitoring is employed for selectivity and sensitivity, this in turn enables quantification in a short period of time (within 7 minutes) over the extended range of 0.1-1000 ng/ml with acceptable precision and accuracy. The method demonstrated to be suitable for the quantitative analysis of E5880 in rat plasma. The pharmacokinetic profile of E5880 after a single intravenous administration of E5880 was elucidated.

Animals↗
PubMed1999

Cloning and phylogenetic relationship of red drum somatolactin cDNA and effects of light on pituitary somatolactin mRNA expression.

The nucleotide sequence for red drum somatolactin (SL) cDNA was determined and the expression of pituitary SL mRNA was examined in red drum kept under various light conditions. A full length of SL cDNA (1629 bp) was isolated and characterized from a red drum pituitary cDNA library. The SL cDNA has an open reading frame of 696 nucleotides which encodes a 24-amino-acid signal peptide and a 207-amino-acid mature peptide. Red drum SL shares 58-87% amino acid sequence identity and 56-85% nucleotide sequence identity with other teleost SLs. The characteristic seven cysteine residues and one N-glycosylation site of SL are well conserved in the red drum SL mature peptide. Phylogenetic analysis shows that red drum SL is closely related to seabream SL and is also closely related to lumpfish, flounder, halibut, and sole SLs, whereas SLs of Atlantic cod, chum salmon, rainbow trout, and eel are more distantly related to those of the more advanced teleosts. Two SL transcripts, designated as SL I at 1.8 kb and SL II at 1.3 kb, are expressed in red drum pituitaries and correspond to two polyadenylation signal sites in red drum SL cDNA at nucleotide positions 1554 and 1270. Levels of the SL I mRNA were 2- to 4-fold higher in pituitaries of blind red drum and intact fish kept under constant darkness for 1 week than those in control fish sampled during the light phase of the light-dark cycle. Similarly, pituitary levels of SL II mRNA were 9-fold higher in blind fish and 1.6- to 4-fold higher in intact fish kept under constant darkness than in the control fish. Furthermore, these changes in mRNA levels in pituitaries were accompanied by more than 10-fold increases in SL protein concentrations in plasma. The finding that the absence of light perception for extended periods leads to dramatic increases in SL mRNA expression as well as SL secretion in red drum provides further evidence that illumination levels and SL physiology are intimately related in this species.

Amino Acid Sequence↗
PubMed1999

Cloning and characterization of a novel class VI semaphorin, semaphorin Y.

Semaphorins comprise a large family of proteins implicated in axonal guidance. We cloned a novel transmembrane semaphorin, semaphorin Y (Sema Y), which has a class VI sema domain. Sema Y shows growth cone collapsing activity on DRG neurons in vitro, and the target regions of the DRG neurons express sema Y mRNA during development. Sema Y may be a stop signal for these neurons in their target areas. Interestingly, sema Y mRNA was also detected in other neurons and their targets. Two isoforms of Sema Y derived from alternative splicing were identified and their expression was found to be regulated in a tissue- and age-dependent manner. Distribution of sema Y mRNA suggests that Sema Y might also be important during maintenance of axonal connections and/or differentiation and migration of cells. Sequence comparison among class VI semaphorins revealed two short conserved sequence stretches in their cytoplasmic domains, suggesting interaction of these semaphorins with a common intracellular component(s).

Alternative Splicing↗
PubMed1999

Effects of exhaustive exercise on biochemical characteristics of sarcoplasmic reticulum from rat soleus muscle.

This study examined the effects of acute high-intensity and moderate-intensity exercise on Ca2+-stimulated adenosine triphosphatase (ATPase) activity and the Ca2+ and ATP dependence of Ca2+-ATPase of the sarcoplasmic reticulum (SR) in the soleus muscle. The rats were run on 10% grade at 50 m min(-1) or 25 m min(-1) until fatigued (avg. time to exhaustion 2.8 and 87.7 min, respectively). The catalytic activities of SR Ca2+-ATPase were significantly depressed immediately after both types of exercise. Kinetic analyses demonstrated that the Ca2+ affinity of Ca2+-ATPase was elevated by both types of exercise adopted in the present investigation whereas the increase in the ATP affinity was brought about by only high-intensity exercise. These results suggest that exhaustive exercise may induce in slow-twitch muscle fibre the environmental changes, which adversely affect SR Ca2+-ATPase activity and can overcome the positive influence arising from the increase in the Ca2+ and/or ATP affinities of SR Ca2+-ATPase.

Animals↗
PubMed1999

Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase epsilon expression during macrophage differentiation.

We have recently isolated two cDNAs encoding two forms of transmembrane and cytosolic protein tyrosine phosphatase epsilon (PTPepsilon). In this study, the 5' end of the rat PTPepsilon gene was isolated and characterized. Transmembrane PTPepsilon (PTPepsilonM) and cytosolic PTPepsilon (PTPepsilonC) were encoded by a single gene. 5' RACE analysis and RNase protection assay showed that the mRNA of each PTPepsilon isoform was transcribed from different promoters. The putative promoter regions of two alternative first exons lacked a TATA box, but contained potential recognition sites for several transcription factors. Reverse transcription PCR analysis revealed that PTPepsilonC mRNA was up-regulated during interleukin 6-induced differentiation of murine leukemia M1 cells, whereas PTPepsilonM mRNA was down-regulated. With the use of luciferase as a reporter gene, the promoter activities of the 5'-flanking regions were examined during phorbol myristate acetate-induced differentiation of HL-60 cells. In the differentiated HL-60 cells, the activity of the PTPepsilonC promoter, but not that of PTPepsilonM, was dramatically elevated. Furthermore, we found that PTPepsilonC mRNA is highly expressed in mouse peritoneal macrophages and enhanced during activation by lipopolysaccharide. These results suggest that the different promoters control expression of PTPepsilon isoforms during the differentiation and/or activation of macrophages.

Amino Acid Sequence↗
PubMed1999

Developmental competence, after transfer to recipients, of porcine oocytes matured, fertilized, and cultured in vitro.

The objective of this study was to evaluate the developmental ability of early porcine embryos produced in vitro and transferred to recipient gilts. Porcine cumulus-oocyte complexes were matured in modified North Carolina State University-37 solution for 44-46 h (in vitro maturation, IVM). In vitro fertilization (IVF) was performed with frozen-thawed epididymal spermatozoa. Inseminated oocytes were cultured in vitro (IVC) for 0, 24, or 48 h in modified NCSU-37 solution. Embryos were surgically transferred to the oviducts of recipients in which estrus had been synchronized with eCG and hCG. On the 29th day post-IVF, the uteri of some recipients were surgically examined for pregnancy; then pregnant females were hysterectomized in order to examine number and weight of the fetuses. Developmental rates to fetuses for IVM/IVF oocytes cultured for 24 and 48 h were significantly lower (p < 0.05, 1.7% and 2.0%, respectively) than that of IVM/IVF oocytes without IVC (6.7%). However, the weights of fetuses (1.0-1.2 g) did not differ among the experimental groups. The other recipients were examined for pregnancy using an ultrasound pregnancy detector, and pregnant females were allowed to go to term. Healthy piglets were delivered by some recipients to which embryos cultured for 0 or 24 h had been transferred; however, no farrow was obtained from embryos cultured for 48 h before the transfer. The results indicate that the viability of in vitro-produced porcine embryos is decreased by IVC after IVF; however, these embryos have competence to develop to term. An improved IVC system of porcine IVM/IVF oocytes is needed to generate advances in this field.

Animals↗
PubMed1999

Effects of vasodilatory beta-adrenoceptor antagonists on endothelium-derived nitric oxide release in rat kidney.

The mechanisms for the vascular actions of vasodilatory beta-blockers remain undetermined. For some kinds of beta-blockers, the involvement of nitric oxide (NO) has been suggested. We studied the effects of vasodilatory beta-blockers on renal perfusion pressure (RPP) and NO release in the rat kidney. Infusion of bopindolol, celiprolol, and nebivolol caused a dose-dependent reduction in RPP and an increase in NO release (RPP: bopindolol 10(-6) mol/L, -23+/-2%; celiprolol 10(-4) mol/L, -27+/-2%; nebivolol 10(-5) mol/L, -35+/-3%; NO: bopindolol 10(-6) mol/L, +33+/-2; celiprolol 10(-4) mol/L, +41+/-2; nebivolol 10(-5) mol/L, +45+/-5 fmol. min-1. g kidney-1, mean+/-SEM). Metergoline (10(-6) mol/L), a 5-hydroxytryptamine (5-HT)1/2 antagonist, or NAN-190 (10(-6) mol/L), a 5-HT1A antagonist, almost completely abolished the vasorelaxation and NO release caused by bopindolol, celiprolol, and nebivolol. However, neither propranolol nor bisoprolol decreased RPP. Celiprolol and nebivolol caused vasodilation in the rat thoracic aorta, and it was markedly reduced by endothelial denudation, Nomega-nitro-L-arginine methyl ester (10(-4) mol/L), or NAN-190 (10(-6) mol/L). In deoxycorticosterone acetate-salt hypertensive rats, 4-week administration of celiprolol (50 mg. kg-1. d-1 IV) restored the responses regarding RPP and NO release to acetylcholine. These results suggest that several beta-blockers exert their vasodilatory action through the 5-HT1A receptor/NO pathway and that treatment with these beta-blockers may protect against endothelial injury in hypertension.

Adrenergic beta-Antagonists↗
PubMed1999

Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat.

We previously reported that adrenomedullin (AM), a potent vasodilator peptide discovered in pheochromocytoma cells, stimulates nitric oxide (NO) release in the rat kidney. To further investigate whether the NO-cGMP pathway is involved in the mechanisms of AM-induced vasodilation, we examined the effects of E-4021, a cGMP-specific phosphodiesterase inhibitor, on AM-induced vasorelaxation in aortic rings and perfused kidneys isolated from Wistar rats. We also measured NO release from the kidneys using a chemiluminescence assay. AM (10(-10) to 10(-7) mol/L) relaxed the aorta precontracted with phenylephrine in a dose-dependent manner. Denudation of endothelium (E) attenuated the vasodilatory action of AM (10(-7) mol/L AM: intact (E+) -25.7+/-5.2% versus denuded (E-) -7. 8+/-0.6%, P<0.05). On the other hand, pretreatment with 10(-8) mol/L E-4021 augmented AM-induced vasorelaxation in the intact aorta (-49. 0+/-7.9%, P<0.05) but not in the denuded one. E-4021 also enhanced acetylcholine (ACh)-induced vasorelaxation in the rat intact aorta (10(-7) mol/L ACh -36.6+/-8.4% versus 10(-8) mol/L E-4021+10(-7) mol/L ACh -62.7+/-3.1%, P<0.05). In perfused kidneys, AM-induced vasorelaxation was also augmented by preincubation with E-4021 (10(-9) mol/L AM -15.4+/-0.6% versus 10(-8) mol/L E-4021+10(-9) mol/L AM -23.6+/-1.2%, P<0.01). AM significantly increased NO release from rat kidneys (DeltaNO: +11.3+/-0.8 fmol. min-1. g-1 kidney at 10(-9) mol/L AM), which was not affected by E-4021. E-4021 enhanced ACh-induced vasorelaxation (10(-9) mol/L ACh -9.7+/-1.7% versus 10(-8) mol/L E-4021+10(-9) mol/L ACh -18.8+/-2.9%, P<0.01) but did not affect ACh-induced NO release from the kidneys. In the aorta and the kidney, 10(-4) mol/L of NG-nitro-L-arginine methyl ester, an NO synthase inhibitor, and 10(-5) mol/L of methylene blue, a guanylate cyclase inhibitor, reduced the vasodilatory effect of AM. These results suggest that the NO-cGMP pathway is involved in the mechanism of AM-induced vasorelaxation, at least in the rat aorta and kidney.

Adrenomedullin↗
PubMed1999

Depression of peripheral chemosensitivity by a dopaminergic mechanism in patients with obstructive sleep apnoea syndrome.

In the present study, respiratory drives to chemical stimuli and peripheral chemosensitivity were evaluated in patients with obstructive sleep apnoea (OSAS). The effects of oral administration of domperidone, a selective dopamine D2-receptor antagonist, were also examined, to study the respiratory effects of endogenous dopamine on peripheral chemoreceptors. Sixteen patients with OSAS and nine normal control subjects were studied. Respiratory responses to hypercapnia and hypoxia were measured using the rebreathing method and isocapnic progressive hypoxia method, respectively. The hypoxic withdrawal test, which measures the decrease in ventilation caused by two breaths of 100% O2 under mild hypercapnic hypoxic conditions (end-tidal oxygen and carbon dioxide tensions approximately 8.0 kPa and 5.3-6.7 kPa, respectively), was used to evaluate peripheral chemosensitivity. In the patients with OSAS, ventilatory responses to hypercapnia and hypoxia were significantly decreased compared with those of control subjects. Hypoxic withdrawal tests showed that peripheral chemosensitivity was significantly lower in patients with OSAS than in normal subjects. Hypercapnic ventilatory response and peripheral chemosensitivity were enhanced by administration of domperidone in the patients with OSAS, although no changes in either of these were observed in the control subjects. The hypoxic ventilatory response and peripheral chemosensitivity in the patients with OSAS were each significantly correlated with severity of hypoxia during sleep. These findings suggest that peripheral chemosensitivity in patients with obstructive sleep apnoea syndrome may be decreased as a result of abnormality in dopaminergic mechanisms and that the reduced chemosensitivity observed in patients with obstructive sleep apnoea syndrome may affect the severity of hypoxia during sleep.

Adult↗
PubMed1999

Neurocysticercosis without detectable specific antibody.

A 19-year-old girl who had lived in India for five years until 1992 was admitted to Hokuto Hospital after general seizures which lasted for fifteen minutes. Cerebral magnetic resonance imaging (MRI) showed a ring-enhanced lesion of 6 mm in diameter in the right parietal lobe. She underwent surgical resection after diagnosis of the brain tumor. Histopathological examinations revealed that the resected tumor was a cysticercus of Taenia solium (T. solium), and we concluded that her seizures were caused by neurocysticercosis. Serological examinations by enzyme-linked immunosorbent assay (ELISA) and immunoblots to detect specific antibody against the glycoproteins of T. solium showed no detectable antibody response. The patient is under careful observation in our out-patient clinic with no medication.

Adult↗
PubMed1999

Up-regulation of nuclear PP1alpha and PP1delta in hepatoma cells.

Activities of nuclear type 1 protein phosphatase (PP1) were significantly elevated in human HepG2 and rat AH13 hepatoma cells compared with primary cultured hepatocytes. We examined and compared the nuclear PP1 activities during the cell cycle between synchronized HepG2 cells and HGF-stimulated hepatocytes. Nuclear PP1 activity was significantly and more elevated at the G1/S transition in hepatoma cells compared with hepatocytes, although the amounts of PP1 isoforms remained constant. On the contrary, it was found that the basal levels of nuclear PP1 activity were significantly higher in hepatoma cells and that the amounts of PP1alpha and PP1delta were dramatically increased in the nuclear fraction of hepatoma cells.

Animals↗
PubMed1999

Intraoperative stress experienced by surgeons and assistants.

BACKGROUND AND OBJECTIVE: To determine the intraoperative stress on surgeons and assistants during cataract surgery, 12 surgeons and 3 assisting nurses were assessed based on their level of professional experience. METHODS: Surgeons were classified as inexperienced, intermediate, or experienced. Nurse assistants were classified as inexperienced or experienced. The intraoperative heart rates and urine adrenaline levels of each participant were measured. RESULTS: Inexperienced surgeons and nurse assistants had the highest heart rates at the beginning of surgery, and the rates tended to decrease toward the end of surgery. All values were higher than the other two groups throughout surgery. In surgeons with intermediate experience, the heart rates were not as high as in the inexperienced personnel; however, the heart rates were high throughout the surgery. The heart rate in one intermediate surgeon was markedly increased when a surgery was simultaneously broadcast on closed-circuit television. In experienced surgeons and a nurse assistant, the measurements increased slightly. CONCLUSIONS: The variations in heart rates and urine adrenaline levels showed characteristic patterns based on the experience of the surgical personnel.

Adult↗
PubMed1998

Antiemetic effects of sendide, a peptide tachykinin NK1 receptor antagonist, in the ferret.

The antiemetic activity of sendide, a new peptide tachykinin NK1 receptor antagonist, against cisplatin-induced emesis was investigated using ferrets. The frequency of cisplatin (10 mg/kg, i.p.)-induced retching (104.6 +/- 14.3/6 h) and vomiting (19.0 +/- 3.0/6 h) was significantly reduced by pretreatment with sendide (3.0 mg/kg, s.c.) (14.0 +/- 8.1/6 h and 1.8 +/- 1.2/6 h, respectively). Intravenous bolus injection of substance P (1-10 microg/kg) or 5-hydroxytryptamine (5-HT) (10-50 microg/kg) produced a dose-dependent increase in the abdominal afferent vagus nerve activity. The change from pre-injection level in the afferent nerve activity induced by substance P (1 microg/kg, i.v.) (453.7 +/- 51.5%) was significantly reduced by pretreatment with either sendide (100 microg/kg, i.v.) (276.1 +/- 50.1%, P < 0.05) or granisetron, a 5-HT3 receptor antagonist (1 mg/kg, i.v.) (146.3 +/- 14.0%, P < 0.01). The amount of 5-HT released into the solution during a 1-h exposure to 2-methyl-5-HT (10(-6) M), a 5-HT3 receptor agonist, was significantly increased (317.9 +/- 46.7%, P < 0.05) compared with that of the control tissues (160.4 +/- 8.1%). The 2-methyl-5-HT-induced 5-HT release was significantly inhibited by administration of sendide (10(-6) M) (174.0 +/- 21.6%, P < 0.05) or granisetron (10(-6) M) (186.6 +/- 27.3%, P < 0.05). Since sendide does not penetrate the central nervous system, these results suggest that the antiemetic effects of sendide are due to the inhibition of NK1 and 5-HT3 receptors on the emetic peripheral detector sites.

Animals↗