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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 253 records · Page 14Linked to original sources
PubMed1998

Renal sympathetic nerve activity in mice: comparison between mice and rats and between normal and endothelin-1 deficient mice.

Recently generated knockout mice with disrupted genes encoding endothelin (ET)-1 showed an elevation of arterial blood pressure (AP) and supplied an evidence for intrinsic ET-1 as one of the physiological regulators of systemic AP. Little is yet known, however, why deficiency of ET-1, which was originally found as a potent vasoconstrictor, led to higher AP in these mice. To address this apparent paradox, we first developed a method to measure renal sympathetic nerve activity (RSNA) in mice using rats as reference and successively compared it between normal and ET-1 deficient mice. RSNA was successfully recorded in urethane-anesthetized and artificially ventilated mice by a slight modification of the method used for rats. At basal condition, mean AP (MAP) and RSNA in ET-1 deficient mice (105+/-2 mmHg and 9.71+/-1.49 muVs, n=20) were significantly higher than those in wild-type mice (96+/-2 mmHg and 5. 07+/-0.70 muVs, n=25). Basal heart rate (HR) and baroreflex-control of HR was not significantly different between the two. On the other hand, resting RSNA, RSNA range, and maximum RSNA were significantly greater in ET-1 deficient mice, and thus MAP-RSNA relationship was upwards reset. Hypoxia-induced increase in RSNA was not different between ET-1 deficient (73.4+/-9.4%) and wild-type mice (91.2+/-12.0%), while hypercapnia-induced one was significantly attenuated in ET-1 deficient mice (18.8+/-3.6 vs. 39.1+/-5.2% at 10% CO2). These results indicate that endogenous ET-1 participates in the central chemoreception of CO2 and reflex control of the RSNA. Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice.

Animals↗
PubMed1998

Localization of mRNAs for trkB isoforms and p75 in rat retinal ganglion cells.

Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of retinal ganglion cells (RGCs). To better understand the potential role of BDNF receptors in the survival of RGCs, we studied the expression and localization of transcripts for trkB isoforms and p75, using reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization with digoxigenin-labeled RNA probes in the adult rat retina. We found that truncated trkB and p75 were expressed in RGCs, as well as full-length trkB, in the adult rat retina. The localization patterns of full-length and truncated trkB mRNAs suggest that a subpopulation of RGCs expresses both full-length and truncated trkB. The localization pattern of p75 mRNA suggests that it is expressed in a subpopulation of RGCs. Expression of both trkB isoforms in RGCs raises the possibility that truncated trkB lessens BDNF effect on RGCs by forming nonfunctional heterodimers with full-length trkB. This possibility was supported by our observation that apoptosis of RGCs detected by the TUNEL method followed close on the onset of truncated trkB mRNA expression in the ganglion cell layer of the developing rat retina.

Animals↗
PubMed1998

Antiplatelet effect of Z-335, a new orally active and long-lasting thromboxane receptor antagonist.

We investigated the pharmacological characteristics of Z-335 ((+/-)-sodium[2-[4-(chlorophenylsulfonylaminomethyl)indan-5-yl]ace tate monohydrate), a new indan derivative. Z-335 inhibited the specific binding of [3H]SQ-29548 to human platelets and guinea pig platelet membranes. The IC50 values of Z-335 for human platelets and guinea pig platelet membranes were 29.9 +/- 3.1 nM with a slope of 1.09 +/- 0.05 and 32.5 +/- 1.7 nM with a slope of 1.07 +/- 0.02, respectively. Z-335 inhibited thromboxane A2 receptor-mediated human and guinea pig platelet aggregation in vitro and oral administration of this drug to guinea pigs inhibited U-46619- and collagen-induced platelet aggregation for 24 h. Z-335 dose-dependently prevented the occurrence of U-46619-induced pulmonary thromboembolism in mice and the protective effect of this drug (0.3 and 3 mg/kg, p.o.) lasted for 24 h. These results strongly suggest that Z-335 is a potent, orally active and long-lasting thromboxane A2 receptor antagonist, which may be useful as an antiplatelet drug.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

A new thromboxane receptor antagonist, Z-335, ameliorates experimental thrombosis without prolonging the rat tail bleeding time.

We investigated the antithrombotic activity of Z-335, a new thromboxane A2 receptor antagonist, using experimental thrombosis models, and also tested its effect on the rat tail bleeding time. Z-335 (0.1, 0.3, and 1 mg/kg, p.o.) dose-dependently prevented the occurrence of arachidonic acid-induced pulmonary thromboembolism in mice. During photochemically induced thrombosis in the femoral artery of guinea pigs, Z-335 (0.3, 1, and 3 mg/kg, i.v.) dose-dependently prolonged the time required to form thrombi. Moreover, Z-335 (10 mg/kg/day, p.o.) strongly suppressed lauric acid-induced hind limb injury in rats. Z-335 (0.3, 3, 30, and 300 mg/kg, p.o.) did not prolong the tail bleeding time in rats. These results strongly suggest that Z-335 ameliorates experimental thrombosis without prolonging the rat tail bleeding time, and may therefore be a useful antithrombotic drug.

Animals↗
PubMed1998

The novel cyclopropapyrroloindole(CPI) bisalkylators bearing 3,3'-(1,4-phenylene)diacryloyl group as a linker.

The novel cyclopropapyrroloindole(CPI) bisalkylators were synthesized and their antitumor activity was evaluated. Among these derivatives, AT-760 (5a) in which the two 3-methoxycarbonyl-2-trifluoromethylCPI (MCTFCPI) moieties are connected with a 3,3'-(1,4-phenylene)diacryloyl group, was found to exhibit more prominent cytotoxicity and antitumor activity than U-77,779 (bizelesin) (1).

Adenocarcinoma↗
PubMed1998

Molecular cloning and characterization of human caspase-activated DNase.

Caspase-activated DNase (CAD) cleaves chromosomal DNA during apoptosis. Here, we report isolation of two classes of human CAD cDNAs from a human KT-3 leukemic cell cDNA library. One class of cDNA encoded a protein comprising 338 amino acids, which showed a marked similarity to its murine counterpart. In vitro transcription and translation of this cDNA resulted in a functional CAD protein when the protein was synthesized in the presence of its inhibitor (inhibitor of CAD). The other cDNA class contained many deletions, insertions, and point mutations in the sequence corresponding to the coding region, suggesting that it is derived from a pseudogene. The functional CAD gene was localized to human chromosome 1p36.3 by fluorescent in situ hybridization. The CAD mRNA was expressed in a limited number of human tissues, including pancreas, spleen, prostate, and ovary. The expression of the CAD mRNA in human cell lines correlated with their ability to show DNA fragmentation during apoptosis. Overexpression of CAD potentiated DNA fragmentation by apoptotic stimuli in these cell lines, indicating that CAD is responsible for the apoptotic DNA degradation.

Amino Acid Sequence↗
PubMed1998

Novel combretastatin analogues effective against murine solid tumors: design and structure-activity relationships.

A series of combretastatin A-4 (CA-4) analogues were synthesized, and their cytotoxic effects against murine Colon 26 adenocarcinoma and inhibitory activity on tubulin polymerization were evaluated. Since CA-4 has limited aqueous solubility, the target compounds were designed to improve solubility by introduction of a nitrogen-containing group. Among the compounds synthesized, those with an amino moiety in place of the phenolic OH of CA-4 showed potent antitubulin activity and cytotoxicity against murine Colon 26 adenocarcinoma in vitro. Some of the compounds which were potent in vitro were evaluated in the murine tumor model Colon 26 in vivo. Among these, 13bHCl, 21aHCl, and 21bHCl showed significant antitumor activity in the animal model, while CA-4 was ineffective. 13bHCl and 21aHCl were further evaluated in two murine tumor models (Colon 38 and 3LL) and human xenografts HCT-15. These compounds showed potent antitumor activity comparable or superior to that of CDDP. The structure-activity relationships of this series of compounds are also discussed.

Acrylonitrile↗
PubMed1998

Prepulse facilitation of auditory startle response in hamsters.

A visual prepulse was applied just before a burst of white noise with various lead intervals ranging from 50 to 400 ms in hamsters. After habituation each hamster received 120 trials of the auditory noise with or without the prepulse. Amplitude of startle response increased significantly at 100 ms and 200 ms (n = 10). This enhancement disappeared in blind controls (n = 6). The amplitude of startle response decreased during exploratory behavior, grooming, sniffing or other movements. However, the facilitatory effects of the visual prepulse were consistent, regardless of the animal's behavioral states, except sniffing. The authors conclude that visual prepulse task is useful for studying the ability to detect visual signals in hamsters, and that further study is necessary to elucidate the factors affecting the enhancement of startle response in hamsters.

Acoustic Stimulation↗
PubMed1998

Serum DNA polymerase beta as an indicator for fatal liver injury of rat induced by D-galactosamine hydrochloride and lipopolysaccharide.

DNA polymerase beta (pol beta) is a nuclear enzyme that is tightly bound to chromatin. Release of the pol beta activity into serum, therefore, may indicate the occurrence of massive destruction of cell nuclei in organs or tissues. In the present study, we made a liver injury model rat by the intraperitoneal injection of D-galactosamine hydrochloride (GalN, 500 mg/kg) and lipopolysaccharide (LPS, 100 microg/kg). Serum from the GalN/LPS-treated rats showed a high level of pol beta activity up to 118 pmol/0.5 microl serum (4700 cpm) at 12 h after the treatment, while the control rat serum showed the back ground level (3.8 pmol/0. 5 microl, 150+/-70 cpm). The serum pol beta activity was sensitive to inhibition by 2',3'-dideoxyTTP and by an anti-rat pol beta antibody. Among 30 rats treated with GalN/LPS, 10 rats died within 120 h (dead group). Serum pol beta activity in the dead group was as high as 23.0+/-19.5 pmol/0.5 microl (925+/-778 cpm) at 10 h after the treatment, while in alive group (n=20), it was 3.7+/-3.2 pmol. Levels of the serum pol beta activity correlated well with the prognosis of GalN/LPS-treated rats based on an analysis of the receiver-operator characteristic curves.

Alanine Transaminase↗
PubMed1998

Design of and metrological results from a bent parabolic mirror.

This article describes the successful design and fabrication of, and metrological results from, an elastically bent parabolic mirror. The mirror is equipped with a bending structure that allows the mirror to be bent meridionally to a parabolic shape. This bent parabolic mirror is the key component of the extremely high-quality monochromators designed for the SPring-8 figure-8 soft X-ray undulator and the 2.0 GeV high-brilliance synchrotron radiation source (VSX).

Journal Article↗
PubMed1998

In vitro changes in capacitative Ca2+ entry in neuroblastoma X glioma NG108-15 cells.

Changes in capacitative Ca2+ entry were studied in neuroblastoma x glioma NG108-15 cells with fura-2 fluorescence measurements in the following three culture conditions. The application of thapsigargin (250 nM) with a Ca2+-free solution depleted intracellular Ca2+ stores and the capacitative Ca2+ entry was induced by the addition of extracellular Ca2+ in the cells cultured in the medium for proliferation. The capacitative Ca2+ entry decreased in the cells cultured in the medium for neuronal differentiation. When these cells resumed proliferation after changing the culture media to the initial medium for proliferation, the capacitative Ca2+ entry increased again and exceeded the level in the initial proliferation state. These results suggested that the capacitative Ca2+ entry occurred more intensely at the proliferation state than at the neuronally differentiated state.

Animals↗
PubMed1998

Liver-type arginase in serum during and after liver transplantation: a novel index in monitoring conditions of the liver graft and its clinical significance.

We quantified liver-type arginase in sera of 47 patients undergoing partial liver transplantation with use of an ELISA method. The level of liver-type arginase fluctuated slightly beyond the normal range in successful liver recipients, while it changed more drastically or precipitously in unsuccessful ones, accompanying or unaccompanying elevation of AST and ALT levels. A higher elevation pattern of the arginase level (above 100 ng ml-1) was observed in each of the unsuccessful recipients with critical condition, except for one patient. Other hepatic markers (LDH, ALP, and T-BIL) remained relatively unchanged until the terminal stage of deceasing patients. The finding that the liver-type arginase emerged in large quantity in the blood stream immediately after reperfusion of the liver graft indicates that the enzyme leaks out of hepatocytes damaged, presumably, by storage in the absence of circulation. A half-life of the liver-type arginase in the human blood was estimated to be 1 h, that is clearly shorter than that of AST. The short half-life of the arginase appears to be ascribable, at least partly, to formation of an immune complex with circulating autoantibody which appears in many liver recipients. These results suggest that liver-type arginase behaves uniquely in the serum among many hepatic enzymes, and could serve as a distinct marker of hepatic lesions, particularly during and after liver transplantation.

Adolescent↗
PubMed1998

Effect of GB virus C/hepatitis G virus coinfection on the course of HIV infection in hemophilia patients in Japan.

OBJECTIVE: A novel virus, GB virus C (GBV-C)/hepatitis G virus (HGV), has been isolated. This virus is parenterally transmissible, but its effect on various diseases remains to be disclosed. We investigated the effect of GBV-C/HGV coinfection on the course of HIV infection. METHODS: GBV-C/HGV RNA was measured by nested reverse transcription polymerase chain reaction (RT-PCR) in 41 HIV-infected hemophilia patients in Japan. Patient characteristics, HIV RNA concentrations, and rates of progression to AIDS and to death were compared in patients with and without GBV-C/HGV coinfection. HIV RNA was quantified by the Amplicor HIV Monitor test (Roche Molecular Systems, Somerville, NJ, U.S.A.), and progression to AIDS and to death was analyzed using Kaplan-Meier plots. RESULTS: GBV-C/HGV infection was present in 11 of 41 of patients (26.8%). Mean HIV RNA concentration was lower in patients with GBV-C/HGV coinfection (3.52+/-4.81 x 10(4) copies/ml) than in patients without coinfection (5.76+/-14.78 x 10(4) copies/ ml) and progression to AIDS and to death were slower in patients with GBV-C/HGV coinfection than patients without it, although the differences were not statistically significant. CONCLUSION: In Japanese hemophilia patients, coinfection with GBV-C/HGV does not have an adverse effect on the course of HIV infection.

Adolescent↗
PubMed1998

Adenovirus vector-mediated gene transfer into rat retinal neurons and Müller cells in vitro and in vivo.

The ability and efficiency of human type V adenovirus-originated vector with CAG promoter to transfer foreign genes was examined in the rat retina. We introduced the adenovirus vector, AxCALacZ with the reporter gene LacZ (beta-galactosidase gene) into cultured retinal cells, and then injected the vector suspension into the vitreous cavity of the eye. Beta-galactosidase staining was observed in both glial and neuronal cells in vitro and in Müller cells near the injection site in vivo. Adenovirus vectors with CAG promoter are useful and efficient for the expression of foreign genes in retinal cells.

Adenoviridae↗
PubMed1998

Development of glutamate-induced intracellular Ca2+ rise in the embryonic chick retina.

Neurotransmitters affect neuronal development by regulating intracellular Ca2+ concentrations. We studied spatiotemporal pattern of the development of glutamate-induced intracellular Ca2+ rise in the embryonic chick retina, where developmental changes in mitotic activity, cell death, and synapse formation have been well established. Glutamate was bath-applied to the central part of the retina dissected at embryonic day 3 (E3) to E13, and changes in intracellular Ca2+ concentration were measured with Fura-2 fluorescence. The Ca2+ rise to glutamate first appeared at E6, reached a maximum at E9-10, and then declined before the appearance of synaptic structures (E12). Ca2+ rises to kainate (KA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) appeared earlier and were larger in amplitude than those to N-methyl-D-aspartic acid. The KA/AMPA receptor of the E9 chick retina was permeable for Ca2+, suggesting the functional expression of Ca2+-permeable KA/AMPA receptors at the stage of retinal cell death. The Ca2+ rise to glutamate and KA occurred intensely at the inner plexiform layer, the inner part of inner nuclear layer, and the ganglion cell layer, where the cell death occurs. The Ca2+ rise to high K+, in contrast, occurred intensely at the nerve fiber layer and the ganglion cell layer, developing continuously from E3 until E11. Our study shows that the Ca2+ rise to glutamate develops with the decline of the mitotic activity of the retinal cells and is transiently enhanced during the period of cell death in the embryonic chick retina.

Animals↗