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Biomedical subjects

Y Masuda

Publications and source records attributed to Y Masuda.

At least 37 records · Page 2Linked to original sources
PubMed2001

Postnatal development of blood pressure and baroreflex in mice.

Postnatal development of blood pressure, heart rate and their regulation by arterial baroreceptor reflex in mice was examined. We first confirmed that simultaneous recordings of pulsatile blood pressure by the "servo null" method and the conventional catheter method gave almost identical tracings in halothane-anesthetized adult mice. We then measured blood pressure by servo null method together with electrocardiograph in mice of various ages from newborn to adult. Mean blood pressure increased progressively with age from 19 + 2 mm Hg in P0 newborn to 74+/-1 in adult mice, while heart rate initially increased from 365+/-12 bpm in newborn to 441+/-15 in infant (7 days old), and then decreased to 337+/-15 in adult mice. Between 1 and 2 weeks of age, gain of arterial baroreceptor reflex abruptly increased from a newborn value of 0.3 to a near adult value of 1.1 ms/mm Hg. On the other hand, sensitivity to anesthesia did not differ except for P1 and P2 newborns. We conclude that pulsatile blood pressure can be accurately measured by the servo null method even in the newborn mice and that baroreflex heart rate control mature at around 2 weeks after birth in the mice.

Anesthetics, Inhalation↗
PubMed2001

Inhibitory effect of bepridil on hKv1.5 channel current: comparison with amiodarone and E-4031.

Effects of bepridil on the depolarization-activated outward K(+) currents (I(out)) in rat atrial myocytes and the human cardiac K(+) (hKv1.5) channel current stably expressed in human embryonic kidney (HEK) 293 cells were examined, and compared with those of amiodarone and N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl] methanesulphonamide dihydrochloride dihydrate (E-4031). Membrane currents were recorded using patch-clamp techniques in enzymatically isolated rat atrial myocytes and HEK 293 cells expressing hKv1.5 channels. Bepridil potently inhibited I(out) elicited by depolarization pulses and prolonged the action potential in rat atrial cells. Bepridil also inhibited the hKv1.5 channel current with the IC(50) value of 6.6 microM. The inhibitory effects of bepridil on the currents in HEK 293 cells were voltage-dependent. Amiodarone weakly inhibited rat atrial I(out) and hKv1.5 channel current. In contrast, E-4031 at a concentration of 10 microM had little influence on these currents. Thus, bepridil inhibits hKv1.5 channel current and the inhibitory effect may be useful for the treatment of atrial fibrillation.

4-Aminopyridine↗
PubMed2001

Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.

Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.

Amino Acid Sequence↗
PubMed2001

Neostriatal stimulation activates tongue-protruder muscle, but not tongue-retractor or facial muscles: an electrical and chemical microstimulation study in rats.

Whether electrical microstimulation of a rat's striatal jaw region (SJR) in fact induced tongue or facial muscle activity in addition to jaw muscle activity was tested. Microstimulation of SJR-evoked EMG activity in a jaw-opener (anterior digastricus) and tongue-protruder (genioglossus). No activity was evoked in jaw-closers (temporalis or masseter), tongue-retractor (hyoglossus) or in facial muscles. In addition, the EMG effect could still be induced after extensive ablation of the neocortex; it was reproduced by microinjection of 50 mM kainic acid into SJR. The effective sites were histologically localized to a small central striatal region adjoining the anterior commissure. These findings may be of considerable value in understanding the striatal mechanism of orolingual dyskinesia involving involuntary jaw and tongue movements.

Animals↗
PubMed2001

Filamin associates with Smads and regulates transforming growth factor-beta signaling.

Members of the Smad proteins transmit signals triggered by the ligands of transforming growth factor (TGF)-beta superfamily. Ligand-activated receptors induce phosphorylation of so-called receptor-regulated Smads, which then accumulate in the nucleus to participate in target gene transcription, in collaboration with Smad-interacting proteins. We performed yeast two-hybrid screening and identified filamin, a cytoskeletal actin-binding protein 280, as a Smad5-interacting protein. Filamin was found to be associated not only with Smad5 but also with other Smad proteins, including TGF-beta/activin receptor-regulated Smad2. TGF-beta signaling was defective in filamin-deficient human melanoma cells M2 compared with a filamin-transfected subline A7, as determined by TGF-beta-responsive reporter gene activation and Smad2 nuclear accumulation. M2 cells restored TGF-beta responsiveness following transient transfection of full-length filamin encoding vector. The defective TGF-beta signaling in M2 cells seemed to be due to impaired receptor-induced serine phosphorylation of Smad2. These results suggest that filamin plays an important role in Smad-mediated signaling.

Cell Line↗
PubMed2001

Deoxycytidyl transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain.

The REV1 protein is a member of the growing family of translesion DNA polymerases. A cDNA of the human REV1 gene that we had originally isolated encoded 1250 amino acids residues, which was one amino acid shorter than previously reported ones. The shorter form of REV1 was named REV1S. All individuals examined expressed equivalent amounts of REV1S and REV1 mRNA, suggesting that the REV1S mRNA is a splicing variant. We show that the REV1S protein also possesses deoxycytidyl transferase activity that inserts a dCMP opposite a DNA template apurinic/apyrimidinic site. Deletion and point mutation analysis of the REV1S protein revealed that the domain required for deoxycytidyl transferase and DNA binding activities of the REV1S protein are located in a conserved domain of translesion DNA polymerases. This result indicates that the structure of the catalytic site of the deoxycytidyl transferase closely resembles that of the translesion DNA polymerases. Therefore, the molecular mechanism of the dCMP transfer reaction of the REV1S protein and maybe also the REV1 protein might be the same as that of the dNTP transfer reaction of the translesion DNA polymerases.

Amino Acid Sequence↗
PubMed2001

Murine and human SDF2L1 is an endoplasmic reticulum stress-inducible gene and encodes a new member of the Pmt/rt protein family.

We isolated murine and human cDNAs for SDF2L1 (stromal cell-derived factor 2-like1) and characterized the genomic structures. Northern blot analysis of the gene expression in various tissues revealed that both murine Sdf2l1 and human SDF2L1 genes are expressed ubiquitously, with particularly high expression in the testis. The SDF2L1 protein has an endoplasmic reticulum (ER)-retention-like motif, HDEL, at the carboxy (C)-terminus. Interestingly, SDF2L1 protein also shows significant similarity to the central hydrophilic part of protein O-mannosyltransferase (Pmt) proteins of Saccharomyces cerevisiae, the human homologues of Pmt (POMT1 and POMT2) and Drosophila melanogaster rotated abdomen (rt) protein. In a murine hepatocellular carcinoma cell line, Sdf2l1 was strongly induced by tunicamycin and a calcium ionophore, A23187, and weakly induced by heat stress but was not induced by cycloheximide. In conclusion, SDF2L1 protein is a new member of Pmt/rt protein family and Sdf2l1 is a new ER stress-inducible gene.

Amino Acid Sequence↗
PubMed2001

Antinociceptive efficacy of antidepressants: assessment of five antidepressants and four monoamine receptors in rats.

PURPOSE: For assessment of the antinociceptive potency of antidepressants, we compared the antinociceptive effects of serotonin selective reuptake inhibitors (SSRIs) and classical tricyclic antidepressants (TCAs) in rats. We also attempted to elucidate the monoamine receptor subtypes predominantly involved in the antinociceptive effect of antidepressants. METHODS: Male Wistar rats received SSRIs (sertraline, fluvoxamine, and citalopram) or TCAs (imipramine and desipramine) intraperitoneally, and the reaction time until pain response in the hot plate test and licking time in the formalin test were measured 60 min later. We also observed the effects of prazosin (an alpha(1) antagonist), WB-4101 (a selective alpha(1A) antagonist), yohimbine (an alpha(2) antagonist), WAY-100635 (a selective 5-HT(1A) antagonist), and ketanserin (a 5-HT(2) antagonist), which were simultaneously administered with imipramine or desipramine, on the antidepressant-induced antinociceptive effect in the formalin test. RESULTS: In the hot plate test, desipramine, 20 mg.kg(-1), but not imipramine or sertraline, produced a significant increase in reaction time. In the formalin test, desipramine and imipramine produced significant reductions in the licking time at over 5 mg.kg(-1) and at over 10 mg.kg(-1), respectively. These reductions were nearly complete at 20 mg.kg(-1). On the other hand, both SSRIs induced significant reductions in the licking time only at 20 mg.kg(-1). Prazosin, WB-4101, and ketanserin significantly antagonized the antinociceptive effect of 10 mg.kg(-1) of imipramine. However, imipramine-induced antinociception was not affected by yohimbine and WAY-100635. Prazosin and ketanserin also significantly suppressed antinociception by 5 mg.kg(-1) of desipramine. CONCLUSION: These findings suggest that classical TCAs are likely to have a therapeutic advantage over SSRIs for pain control. In addition, it is likely that central alpha(1) adrenoceptors and 5-HT(2) receptors are predominantly involved in imipramine- and desipramine-induced antinociception.

Journal Article↗
PubMed2001

Vascular endothelial growth factor enhances glomerular capillary repair and accelerates resolution of experimentally induced glomerulonephritis.

Vascular endothelial growth factor (VEGF) regulates angiogenesis through endothelial cell proliferation and plays an important role in capillary repair in damaged glomeruli. We tested the hypothesis that VEGF might be beneficial in rats with severe glomerular injury in glomerulonephritis (GN) based on its angiogenic and vascular remodeling properties. Acute GN with severe glomerular destruction was induced in rats by injection of anti-Thy-1.1 antibody (day 0) and Habu-snake venom (day 1). Rats were intraperitoneally injected with recombinant human VEGF(165) (10 microg/100 g body wt/day) or vehicle from day 2 to day 9, and monitored changes in glomerular capillaries, development of glomerular inflammation, and progression to glomerular sclerosis after acute glomerular destruction in both groups. Rats that received anti-Thy-1.1 antibody and Habu-snake venom showed severe mesangiolysis and marked destruction of capillary network on day 2. VEGF was expressed on glomerular epithelial cells, proliferating mesangial cells, and some infiltrating leukocytes, and VEGF(165) protein levels increased in damaged glomeruli during day 5 to day 7. Normal, damaged, and regenerating glomerular endothelial cells expressed VEGF receptor flk-1. However, endothelial cell proliferation and capillary repair was rare in vehicle-treated rats with severe glomerular damage, which progressed to global sclerosis and chronic renal failure by week 8. In contrast, in the VEGF-treated group, VEGF(165) significantly enhanced endothelial cell proliferation and capillary repair in glomeruli by day 9 (proliferating endothelial cells: VEGF(165), 4.3 +/- 1.1; control, 2.2 +/- 0.9 cells on day 7, P < 0.001; and glomerular capillaries: VEGF(165), 24.6 +/- 4.8; control, 16.9 +/- 3.4 capillaries on day 7, P < 0.01). Thereafter, damaged glomeruli gradually recovered after development of capillary network by week 8, and significant improvement of renal function was evident in the VEGF-treated group during week 8 (creatinine: VEGF(165), 0.3 +/- 0.1; control, 2.6 +/- 0.9 mg/dl, P < 0.001; proteinuria: VEGF(165), 54 +/- 15; control, 318 +/- 60 mg/day, P < 0.001). We conclude that the beneficial effect of VEGF(165) in severe glomerular injury in GN emphasizes the importance of capillary repair in the resolution of GN, and may allow the design of new therapeutic strategies against severe GN.

Animals↗
PubMed2001

Pericardial fat accumulation in men as a risk factor for coronary artery disease.

An increment of abdominal visceral fat accumulation has been reported to be a coronary risk factor. We determined the predictive power of pericardial fat (Pfat) accumulation as intra-thoracic visceral fat, in the diagnosis of coronary artery disease (CAD). Among 251 (181 non-obese [body mass index<25], 70 obese [body mass index> or =25]) Japanese male patients who underwent computed tomography (CT), 128 (90 non-obese, 38 obese) patients were suffering from CAD. Pfat volume was determined by the sum of cross-sectional images 1cm thick from the atrial appendage to the apex over the diaphragm. Abdominal visceral fat (Vfat) and subcutaneous fat (Sfat) areas were measured by a single scan at the L4-L5 region. Pfat was most associated with Vfat in body fat distribution. In non-obese patients, Pfat was most associated with CAD among the various risk factors including body fat distribution. Moreover, Pfat was the strongest independent variable for the severity of CAD, determined by coronary angiogram. This result showed that pericardial fat accumulation was a stronger coronary risk factor than the other body fat distributions in non-obese men.

Adult↗
PubMed2001

Relationships between feeding and locomotion behaviors after central administration of CRF in chicks.

The effect of intracerebroventricular injection of corticotropin-releasing factor (CRF) on various behaviors in chicks was determined at 15-min intervals over a 30-min period. Food intake of chicks was significantly decreased, and pecking rhythm was significantly delayed by CRF during the first 15-min post-injection. The similar tendencies were observed in the second 15-min post-injection, but not significantly different. Stepping, as an indicator of locomotion, was not different at 15-min post-injection, but was increased by CRF, thereafter. These results suggest that CRF acts within the central nervous system to decrease food intake and increase locomotion in the chick.

Animals↗
PubMed2001

The effect of public long-term care insurance plan on care management and care planning in Japanese geriatric hospitals.

Japan, a society facing demographic aging at an incomparable speed, decided to introduce a new public long-term care insurance system to meet the expected need for elders to be cared for in the near future. The purpose of this study was to examine the change in knowledgeability on the side of managers of Japanese geriatric hospitals regarding (1) the concept of care-management as the methodology to supply care services to the elderly smoothly, and (2) comprehensive assessment for the elders as the technical skill in the process of materializing care management. Subjects were interviewed and questioned over the telephone according to a structural questionnaire. Managers (directors and office managers) of geriatric hospitals in 1996 and 1999. In 1996, the rate of knowledgeability for care management on the side of managers of geriatric hospitals was 70.0% (28/40) as a whole, increasing to 97.3% (71/73) in 1999. With regard to MDS-RAPs, the knowledgeability rate increased from 57.5% (23/40) in 1996 to 95.9% (70/73) in 1999. However, regarding care planning, almost all of the hospitals that performed care planning were those in the category required to submit care plans to the municipal government. Geriatric hospitals that were not required to submit such plans did not perform such planning either in 1996 or in 1999. It can be concluded that the decision to introduce a long-term care insurance system in Japan has led to a deeper understanding of the methodology of care management and a comprehensive assessment on the side of managers of geriatric hospitals.

Journal Article↗
PubMed2001

Neuronal activity in the putamen and the globus pallidus of rabbit during mastication.

The pattern of jaw movements is changed during a masticatory sequence from ingestion of food to its deglutition. The masticatory sequence is divided into three distinct stages in the rabbit. However, the neural mechanism involved in the alteration of the masticatory stages is still unknown. This study was designed to determine whether neuronal activity in the putamen and globus pallidus is related to the alteration of the masticatory stages. Fifty-three percent of the recorded neurons showed significant alterations of activity during mastication. Of these neurons, 16% changed their firing frequency throughout the masticatory sequence (sequence-related neurons) and 84% changed their firing frequency with the transition of the masticatory stages (stage-related neurons). The stage-related neurons were classified into two groups based on their neuronal activity patterns observed during mastication, i.e. simple type and complex type. The former are the neurons that were either facilitated or inhibited once during mastication, and the latter are those showing the facilitation or inhibition twice or more during mastication. Complex-type neurons were observed more frequently in the globus pallidus than in the putamen. These results suggest that the basal ganglia is involved in mastication and may related to the transition between the masticatory stages.

Animals↗
PubMed2001

Influence of food thickness and hardness on possible feed-forward control of the masseteric muscle activity in the anesthetized rabbit.

The facilitatory masseteric muscle response (FMR) elicited by polyurethane foam strip application between the opposing molars during cortically-induced rhythmic jaw movements (CRJMs) was induced earlier than masticatory force onset. The occurrence of this early response of the FMR (e-FMR) could not be explained by a simple reflex mechanism. One possible mechanism of the e-FMR is the involvement of a feed-forward control mechanism of the masticatory jaw movement. In the present study, experimentally designed polyurethane foam strips with various thickness and hardness were applied during CRJMs and analyzed in terms of how the e-FMR was modulated by the food hardness and thickness. The FMR onset was not related to the strip thickness or the strip hardness. However, the magnitude of the e-FMR increased in a thickness and a hardness-dependent manner. The sensory information of the food properties in the masticatory cycle may make the FMR adequate to chewing of the food in the following cycle, and such modulation may help chewing rhythms remain stable.

Action Potentials↗
PubMed2001

Human fibrinopeptide A mediates allergic reaction in mice in the acute phase.

We detected a human humoral peptide that deglycosylates mouse antibody IgE, and found that this peptide had the amino acid sequence ADSGEGDFLAEGGGV. The peptide synthesized according to the sequence also deglycosylated the antibody IgE. The deglycosylated IgE did not induce mouse systemic anaphylaxis. Human fibrinopeptide A has the amino acid sequence indicated above, and a polypeptide extracted from human urine showed an antiallergic effect on humans and mice, which strongly suggests that fibrinopeptide A mediates allergic reaction via antibody IgE-deglycosylation, and is excreted as a polypeptide in urine.

Acute-Phase Reaction↗
PubMed2001

Synthetic study on novel immunosuppressant KF20444.

The two new synthetic routes to 6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H- benzo[6,7]cyclohepta[1,2-b]-quinoline-8-carboxylic acid (1), a novel immunosuppressant KF20444, are described. The seven-membered ring construction from 2-[4-(2-fluorophenyl)phenyl]-3-(2-carboxyethyl)-4-chloromethyl-6-fluoroquinoline (17c) was achieved by intramolecular Friedel-Crafts reaction under acidic conditions as the key step. Subsequently, the oxidation of 4-chloromethyl group followed by reduction of carbonyl group on the seven-membered ring afforded 1. This route provides a new method for the synthesis of 1.

Biochemistry↗
PubMed2001

Purification, N-terminal amino acid sequence, and some properties of Cu, Zn-superoxide dismutase from Japanese flounder (Paralichthys olivaceus) hepato-pancreas.

Cu, Zn-superoxide dismutase (SOD) has been purified to homogeneity from Japanese flounder Paralichthys olivaceus hepato-pancreas. The purification of the enzyme was carried out by an ethanol/chloroform treatment and acetone precipitation, and then followed by column chromatographies on Q-Sepharose, S-Sepharose and Ultrogel AcA 54. On SDS-PAGE, the purified enzyme gave a single protein band with molecular mass of 17.8 kDa under reducing conditions, and showed approximately equal proportions of 17.8 and 36 kDa molecular mass under non-reducing conditions. Three bands were obtained when the purified enzyme was subjected to native-PAGE, both on protein and activity staining, but the electrophoretic mobility of the purified enzyme differed from that of bovine erythrocyte Cu, Zn-SOD. Isoelectric point values of 5.9, 6.0 and 6.2, respectively, were obtained for the three components. The N-terminal amino acid sequence of the purified enzyme was determined for 25 amino acid residues, and the sequence was compared with other Cu, Zn-SODs. The N-terminal alanine residue was unacetylated, as in the case of swordfish SOD. Above 60 degrees C, the thermostability of the enzyme was much lower than that of bovine Cu, Zn-SOD.

Amino Acid Sequence↗