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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 145 records · Page 8Linked to original sources
PubMed2000

Sympathetic control of arterial membrane potential by ATP-sensitive K(+)-channels.

Stimulation of perivascular nerve terminals leads to a release of various neurotransmitters such as norepinephrine, epinephrine, acetylcholine, nitric oxide, and calcitonin gene-related peptide (CGRP). Because some of these substances have been shown to cause smooth muscle hyperpolarization by direct or endothelium-dependent mechanisms, we hypothesized that the liberation of 1 or more of these transmitters may lead to neurogenic hyperpolarization in arterial muscle cells. The present study was designed to determine the presence or absence of neurogenic hyperpolarization and, if present, its underlying mechanisms in isolated rat mesenteric resistance arteries, through the use of conventional microelectrode techniques. The experiments were performed under the combined blockade of alpha-adrenoceptors and purinoceptors with phentolamine and suramin to eliminate depolarizing responses to nerve stimulation. Under these conditions, perivascular nerve stimulation (5 Hz, 30 seconds) evoked smooth muscle hyperpolarization (-3.3+/-0.3 mV, n=15), which was abolished by tetrodotoxin, indicating the neurogenic origin of the response. This neurogenic hyperpolarization was resistant to atropine, nitro-L-arginine, or CGRP8-37, a CGRP antagonist, but was abolished by guanethidine and beta-blocker propranolol. This hyperpolarization was also abolished by glibenclamide, an ATP-sensitive K(+) channel (K(ATP)) blocker, but was unaffected by apamin, a Ca(2+)-activated K(+) channel blocker. In separate experiments, exogenous norepinephrine caused glibenclamide-sensitive hyperpolarization in the presence of phentolamine. On the other hand, norepinephrine-induced depolarization in the absence of phentolamine was enhanced by propranolol. These findings suggest that neurally released catecholamines cause membrane hyperpolarization through the activation of K(ATP) by beta-adrenoceptors. Such hyperpolarization may play an important role in the control of arterial membrane potential by opposing alpha-adrenergic depolarization.

Adenosine Triphosphate↗
PubMed2000

Renin-angiotensin system blockade improves endothelial dysfunction in hypertension.

Angiotensin-converting enzyme (ACE) inhibitor improves the impaired hyperpolarization and relaxation to acetylcholine (ACh) via endothelium-derived hyperpolarizing factor (EDHF) in arteries of spontaneously hypertensive rats (SHR). We tested whether the angiotensin type 1 (AT(1)) receptor antagonist also improves EDHF-mediated responses and whether the combined AT(1) receptor blockade and ACE inhibition exert any additional effects. SHR were treated with either AT(1) receptor antagonist TCV-116 (5 mg. kg(-1). d(-1)) (SHR-T), enalapril (40 mg. kg(-1). d(-1)) (SHR-E), or their combination (SHR-T&E) from 8 to 11 months of age. Age-matched, untreated SHR (SHR-C) and Wistar Kyoto (WKY) rats served as controls (n=8 to 12 in each group). Three treatments lowered blood pressure comparably. EDHF-mediated hyperpolarization to ACh in mesenteric arteries in the absence or presence of norepinephrine was significantly improved in all treated SHR. In addition, the hyperpolarization in the presence of norepinephrine was significantly greater in SHR-T&E than in SHR-E (ACh 10(-5) mol/L with norepinephrine: SHR-C -7; SHR-T -19; SHR-E -15; SHR-T&E -22; WKY -14 mV). EDHF-mediated relaxation, assessed in the presence of indomethacin and N:(G)-nitro-L-arginine, was markedly improved in all treated SHR. Hyperpolarization and relaxation to levcromakalim, a direct opener of ATP-sensitive K(+)-channel, were similar in all groups. These findings suggest that AT(1) receptor antagonists are as effective as ACE inhibitors in improving EDHF-mediated responses in SHR. The beneficial effects of the combined AT(1) receptor blockade and ACE inhibition appears to be for the most part similar to those of each intervention.

Acetylcholine↗
PubMed2000

Angiotensin-converting enzyme inhibitor prevents age-related endothelial dysfunction.

Vascular relaxation via endothelium-derived hyperpolarizing factor (EDHF) declines in association with aging and also with hypertension, and antihypertensive treatment improves the endothelial dysfunction connected with hypertension. We tested whether the angiotensin-converting enzyme inhibitor improves EDHF-mediated responses in normotensive rats, with special reference to the age-related process. Wistar-Kyoto rats (WKY) were treated with either 20 mg. kg(-1). d(-1) enalapril (WKY-E group) or a combination of 50 mg. kg(-1). d(-1) hydralazine and 7.5 mg. kg(-1). d(-1) hydrochlorothiazide (WKY-H group) from 9 to 12 months of age. Twelve-month-old WKY (WKY-O) and 3-month-old WKY (WKY-Y) served as controls (n=6 to 10 in each group). The 2 treatments lowered systolic blood pressure comparably. EDHF-mediated hyperpolarization to acetylcholine (ACh) in mesenteric arteries was significantly improved in WKY-E, but not in WKY-H, compared with WKY-O, and the hyperpolarization in WKY-E was comparable to that in WKY-Y (hyperpolarization to 10(-)(5) mol/L ACh in the presence of norepinephrine: WKY-O, -14+/-2 mV; WKY-E, -22+/-3 mV; WKY-H, -15+/-2 mV; and WKY-Y, -28+/-0 mV). EDHF-mediated relaxation, as assessed by relaxation to ACh in norepinephrine-precontracted rings in the presence of indomethacin and NO synthase inhibitor, was also significantly improved in WKY-E, but not in WKY-H, to a level comparable to that in WKY-Y (maximum relaxation: WKY-O, 45+/-6%; WKY-E, 63+/-8%; WKY-H, 43+/-4%; and WKY-Y, 72+/-4%). Hyperpolarization and relaxation to levcromakalim, an ATP-sensitive K(+) channel opener, were similar in all groups. These findings suggest that the angiotensin-converting enzyme inhibitor prevents the age-related decline in EDHF-mediated hyperpolarization and relaxation in normotensive rats, presumably through an inhibition of the renin-angiotensin system.

Acetylcholine↗
PubMed2000

The Arabidopsis floral homeotic gene PISTILLATA is regulated by discrete cis-elements responsive to induction and maintenance signals.

PISTILLATA is a B-class floral organ identity gene required for the normal development of petals and stamens in Arabidopsis. PISTILLATA expression is induced in the stage 3 flowers (early expression) and is maintained until anthesis (late expression). To explore in more detail the developmentally regulated gene expression of PISTILLATA, we have analyzed the PISTILLATA promoter using uidA (beta)-glucuronidase gene) fusion constructs (PI::GUS) in transgenic Arabidopsis. Promoter deletion analyses suggest that early PISTILLATA expression is mediated by the distal region and that late expression is mediated by the proximal region. Based on the PI::GUS expression patterns in the loss- and gain-of-function alleles of meristem or organ identity genes, we have shown that LEAFY and UNUSUAL FLORAL ORGANS induce PISTILLATA expression in a flower-independent manner via a distal promoter, and that PISTILLATA and APETALA3 maintain PISTILLATA expression (autoregulation) in the later stages of flower development via a proximal promoter. In addition, we have demonstrated that de novo protein synthesis is required for the PISTILLATA autoregulatory circuit.

Arabidopsis↗
PubMed2000

Effect of Choto-san, a Kampo medicine, on the cerebral blood flow autoregulation in spontaneously hypertensive rats.

To clarify the mechanism of the benefical effect of Choto-san on cerebral circulation in hypertensive patients, the influence of Choto-san on cerebral blood flow (CBF) during hemorrhagic hypotension was evaluated in 10- to 11-month-old spontaneously hypertensive rats. The lower limit of CBF autoregulation, defined as the mean arterial blood pressure at which CBF decreased by 10% of the baseline value, was dose-dependently lowered when Choto-san (0.5 - 2.0 g/kg per day, p.o.) was administered for 14 consecutive days. Uncariae Ramulus et Uncus (150 mg/kg per day, p.o.), one of the crude drug components of Choto-san, showed an effect equivalent to that of Choto-san. The action of Choto-san (2.0 g/kg per day, p.o.) or Uncariae Ramulus et Uncus on the autoregulatory response of cerebral vessels was eliminated by treatment with N(G)-nitro-L-arginine methyl ester (10 mg/kg, i.v.), an inhibitor of nitric oxide synthase. These results suggested that the activation of nitric oxide synthase by Uncariae Ramulus et Uncus contributed to at least part of the improvement in the cerebral circulation caused by Choto-san.

Animals↗
PubMed2000

Molecular modeling study of highly branching (1-->3)-alpha-D-glucan, a model polysaccharide for cariogenic glucan, using the N-H mapping method.

A systematic search for possible regular helical structures of a highly branching (1-->3)-alpha-D-glucan was done using the n-h mapping technique, combined with MM3-generated relaxed-residue energy map calculations with respect to the conformations of the backbone glycosidic linkages. The alpha-D-glucan, consisting of a (1-->3)-alpha-linked backbone with alpha-D-glucose side residues attaching to an O6 atom of every second backbone residue, was considered as a model polysaccharide of a branching part of the glucan produced by oral bacteria, which was known to be related to dental plaque formation and to contribute to dental caries. The potential energy surfaces of the trisaccharide repeating unit of the branching alpha-D-glucan indicated that (1-->6)-alpha-linked side residues did not appear to interfere significantly with the backbone stereochemistry, probably due to a further separation of the three-bond-linked side residue compared with an ordinary two-bond-linked residue. Based on the n-h maps of the branching alpha-D-glucan, the side residues, when involved in a complete helix, mostly contributed additional stabilizations to particular helical structures. It was found by checking the typical helix models that formation of hydrogen bonds involving side residues was probably a major cause of the stabilization. This hydrogen bonding was expected to increase insolubility for the glucan chain--a typical, physical property observed for the bacterial alpha-D-glucan--by introducing its backbone stereochemistry as an additional stiff feature.

Carbohydrate Conformation↗
PubMed2000

Establishment and characterization of a cell line from a chemically-induced mouse hepatoblastoma.

We established a cell line (MHB-2) from a hepatoblastoma (HB) induced by diethylnitrosamine (DEN) and sodium phenobarbital (PB) in male B6C3F1 mice and examined the biological characteristics of MHB-2. MHB-2 cells grew as monolayers in culture and showed a spindle or polygonal shape. Immunohistochemically, the original tumor cells and MHB-2 cells were negative for keratin, alpha-fetoprotein and albumin. Electron microscopically, MHB-2 cells had irregular-shaped nuclei with prominent nucleoli, abundant free ribosomes, myelinosomes, desmosomes and surface microvilli. Growth of this cell line was significantly accelerated by hepatocyte growth factor (HGF) and expression of its receptor c-met was confirmed by the reverse transcription-polymerase chain reaction (RT-PCR). MHB-2, however, was not found to be tumorigenic when transplanted into the subcutaneous tissue of syngeneic, nude or scid mice. To our knowledge, this is the first report on the establishment of a cell line derived from a mouse HB. MHB-2 would be useful for further studies to clarify the biological characteristics of mouse HB.

Animals↗
PubMed2000

The prevalence of serum GB virus C/hepatitis G virus RNA and anti-E2 in Japanese children without a history of blood transfusion.

The prevalence of serum GB virus C (GBV-C)/Hepatitis G virus (HGV) RNA and anti-E2 was investigated in Japanese children younger than 16 years of age without a history of blood transfusion and the family members of serum GBV-C/HGV RNA-positive children. The prevalences of serum GBV-C/HGV RNA and anti-E2 were 0.5% (5/1000) and 0% (0/330), respectively. Viral RNA was also detected in the mothers of all five GBV-C/HGV RNA-positive children and in two of their siblings. Sequence determinations indicated the likelihood of mother-to-infant transmission in all cases. The presence of the virus persisted for at least 10-18 months in all 5 children, without any appearance of anti-E2.

Adolescent↗
PubMed2000

Detection rates of TT virus DNA in serum of umbilical cord blood, breast milk and saliva.

To date, the routes of mother-to-infant transmission of TT virus (TTV) have not been fully elucidated. The present study examines the detection rates of TTV DNA in the serum of pregnant Japanese women and in cord blood at the time of delivery, as well as in the saliva and breast milk of mothers one-month postpartum. Primers derived from the well-known translated region N22 (N22 system), as well as the untranslated region (UTR system) were used. The prevalence of TTV DNA in the serum of pregnant women was found to be 11.9% (19/160) using the N22 system and 72.4% (55/76) using the UTR system. No TTV DNA was detected in the cord blood samples (0/160) when the N22 system was used for detection but TTV DNA was detected in 11.8% (7/76) of samples studied with the UTR system. Using the N22 system, TTV DNA was not detected in breast milk, but was detected in saliva. However using the UTR system, TTV DNA was detected in both specimens. These results imply that some babies are vertically infected with TTV via cord blood at the time of delivery or via breast milk or saliva. However, further research is necessary to confirm this hypothesis. polymerase chain reaction; pregnant women; horizontal route of transmission

Adult↗
PubMed2000

TT virus infection in Japanese children: isolates from genotype 1 are overrepresented in patients with hepatic dysfunction of unknown etiology.

The pathogenecity of the TT virus (TTV) especially during childhood remains obscure. We investigated the prevalence of TTV in 40 patients with non-A to C hepatic dysfunction (non-A to C hepatic dysfunction group). Five patients with fulminant hepatitis of unknown etiology were enrolled in this group. We also examined 380 children without a history of transfusion or liver disease (control group). Subsequently, the genotypes of TTV strains isolated were analyzed in terms of their nucleotide sequences including 222 bp in the open reading frame 1 region. The prevalence of serum TTV DNA was 10/40 (25%) in the non-A to C hepatic dysfunction group and 25/380 (7%) in the control group. Sixty-six percent (23/35) of all examined cases exhibited either genotype 1 or 2. However, assessment of genotype in the non-A to C hepatic dysfunction group (10 cases) revealed a higher prevalence of genotype 1 than of all other genotypes (80% vs. 20%). This result differed significantly from that of the control group (25 cases; 32% vs. 68%). Such overrepresentation of genotype 1 suggests that this type of TTV strain is associated with the development of hepatic dysfunction of unknown etiology in Japanese children.

Adolescent↗
PubMed2000

[Transient enlargement and spontaneous regression of interhemispheric cysts--a case report].

We report a 5-year-old male patient with interhemispheric cysts which showed spontaneous reduction in size. The patient was consulted to our hospital at 2 days of life for the evaluation of intracranial cysts found by fetal ultrasonography. Magnetic resonance imaging (MRI) on admission disclosed multiple cysts in the interhemispheric region and agenesis of the corpus callosum. MRI performed later disclosed the association of pachygyria and heterotopia. On follow-up MRIs, the cysts peaked in size at 5 month of age and gradually reduced thereafter. He showed transient hypertonia but had neither neurological deficits nor signs of increased intracranial pressure except transient hypertonia throughout the course. The present case is the first with interhemispheric cysts showing spontaneous reduction in size. While the present case suggested that an interhemispheric cyst dose not necessarily need a surgical treatment, and that it is difficult to determine surgical indication based on clinical manifestations.

Brain Diseases↗
PubMed2000

[Effect of olprinone hydrochloride on cerebral blood flow in patients after cardiac surgery].

This study was designed to investigate the effect of olprinone hydrochloride on cerebral blood flow in ten patients after cardiac surgery by transcranial Doppler sonography (TCD). We assessed cerebral blood flow in the middle cerebral artery by transtemporal approach and in the carotid siphon by transorbital approach. We measured the mean blood flow velocity in the left middle cerebral artery (Vmca) and the left carotid siphon (Vlca) and calculated the pulsatility index in the left middle cerebral artery (PImca) and the left carotid siphon (PIlca) using 2 MHz transcranial Doppler ultrasound system (DWL Multidop-P). After baseline measurement, the olprinone hydrochloride loading dosage was increased from 0.15 to 0.3 microgram.kg-1.min-1 every 60 minutes. The mean blood flow velocity was measured at each point. Vmca and Vlca significantly increased, and PImca and PIlca significantly decreased at the infusion rate of 0.3 microgram.kg-1.min-1. There were significant linear correlations between CI and Vmca, CI and Vlca, SVRI and Vmca, as well as SVRI and Vlca. Dose-response relationships were observed in CI, SVRI, Vmca, and Vlca. In conclusion, we demonstrated that olprinone hydrochloride led to an increase of cerebral blood flow in the patients after cardiac surgery.

Aged↗
PubMed2000

Antifungal activity of plant extracts against Arthrinium sacchari and Chaetomium funicola.

Various plant extracts were examined for antifungal activity with the objective of improving the commercial sterility of aseptically filled tea beverage products in PET bottles. When the hot water extract and the methanol extract of 29 samples were measured for their antifungal activity against Arthrinium sacchari M001 and Chaetomium funicola M002 strains, five samples, Acer nikoense, Glycyrrhiza glabra, Lagerstroemia speciosa, Psidium guajava and Thea sinensis, showed high activity. Of these, the extracts from A. nikoense, G. glabra and T. sinensis were fractionated by extraction with CHCl3, and the CHCl3-soluble fractions from G. glabra showed antifungal activity with minimum inhibitory concentrations (MICs) between 62.5 and 125 microg/ml against the above-mentioned two fungi. When the EtOAc-soluble fraction of A. nikoense was used, the MIC against A. sacchari M001 was 62.5 microg/ml. However, none of the fractions from A. nikoense or T. sinensis showed high activity against C. funicola M002 and their MICs were greater than 500 microg/ml. A licorice preparation made from the commercially available oil-based extract of G. glabra showed a low MIC of 25 microg/ml against five tested strains of filamentous fungi, but not against Aspergillus fumigatus M008, in a blended tea. Consequently, the possibility of adding a licorice preparation made from the oil-based extract of G. glabra to tea beverages (aseptically filled into PET bottles) was suggested.

Journal Article↗
PubMed1999

Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight.

Orexins are recently identified neuropeptides, and have been shown to increase food intake when administered intracerebroventricularly. We examined the effects of chronic administration of orexin in rats by continuous intracerebroventricular administration by means of an osmotic minipump. Continuous administration of orexin-A (0.5 nmol/h) for 7 days in rats resulted in a significant increase in food intake in the daytime. Daytime food intake increased to 180% of the control value. However, it resulted in a slight decrease nighttime food intake as compared with vehicle-treated rats. The total amount of food intake per day was almost comparable with that of vehicle-administered rats. The gain of body weight and blood glucose, total cholesterol and free fatty acid levels were normal. Chronic orexin-A treatment did not cause obesity in rats. We observed abnormal behavior during the daytime after starting administration of orexin-A; these rats kept awake during the daytime. Our present observation showed that continuous administration of orexin-A could not overcome the regulation of energy homeostasis and body weight. However, orexin-A might be implicated in short-term, immediate regulation of feeding behavior.

Animals↗
PubMed1999

A pair of related genes with antagonistic roles in mediating flowering signals.

Flowering in Arabidopsis is promoted via several interacting pathways. A photoperiod-dependent pathway relays signals from photoreceptors to a transcription factor gene, CONSTANS (CO), which activates downstream meristem identity genes such as LEAFY (LFY). FT, together with LFY, promotes flowering and is positively regulated by CO. Loss of FT causes delay in flowering, whereas overexpression of FT results in precocious flowering independent of CO or photoperiod. FT acts in part downstream of CO and mediates signals for flowering in an antagonistic manner with its homologous gene, TERMINAL FLOWER1 (TFL1).

Amino Acid Sequence↗