Search PubMed⌕ Search

Biomedical subjects

H Matsuo

Publications and source records attributed to H Matsuo.

At least 145 records · Page 8Linked to original sources

Mutational analysis of the anion exchanger 3 gene in familial paroxysmal dystonic choreoathetosis linked to chromosome 2q.

Familial paroxysmal dystonic choreoathetosis (PDC) is an autosomal dominant neurological disorder characterized by episodes of involuntary movement precipitated by caffeine, alcohol, or emotional stress. The locus for PDC has recently been mapped to chromosome 2q32-36, but its causative gene has not yet been identified. PDC is most likely a kind of channelopathy, as suggested by the fact that other paroxysmal neurological disorders are caused by various ion channel mutations. Although no ion channel is located in this candidate region, anion exchanger 3 (AE3) has been mapped to 2q36 and has also been reported to be the most promising candidate gene of PDC. In this study we performed sequencing of the coding region of the AE3 gene in patients with familial PDC linked to chromosome 2q and excluded the AE3 gene as the causative gene for PDC. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:733-737, 1999.

Amino Acid Sequence↗

Ghrelin is a growth-hormone-releasing acylated peptide from stomach.

Small synthetic molecules called growth-hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH). We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide 'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.

Acylation↗

Quantitative evaluation of left ventricular regional wall motion using a real-time wall thickness curve system with two-dimensional echocardiography.

The real-time wall thickness curve system was newly developed for recording left ventricular (LV) wall thickening (WT) on a 2-dimensional echocardiogram recorded in an arbitrary direction because of the scarcity of quantitative data on wall motion change during dobutamine-induced ischemia. This study tested the feasibility of this system for quantitative evaluation of wall motion. In normal subjects, accuracy and reproducibility of measurements were evaluated by comparison with measurements on a conventional M-mode echocardiogram and examination of inter- and intraobserver variability. In 28 patients with coronary artery disease, percent systolic wall thickening (%WT) was measured during dobutamine infusion in incremental doses of 6 microg/kg/min, from 6 to 30 microg/kg/min. Percent change in %WT by dobutamine was compared with percent coronary stenosis derived from quantitative coronary angiography. Analysis of the mean difference and 95% confidence intervals demonstrated good accuracy and reproducibility: 0.0 mm and intervals of -0.5 to 0.5 mm in diastolic wall thickening of LV posterior wall (PW) between both methods, -1% and -4% to 2% in %WT of IVS and LVPW between both observers, and -1% and -3% to 2% in that between both measurements. During dobutamine infusion, the percent change in %WT was significantly correlated with percent stenosis (r = 0.75, p<0.0001). The WT curve system enabled us to assess regional wall function as %WT and was available for quantitative observation of wall motion change during pharmacologic intervention. This system may reduce the effects of heart movement and may be of great clinical benefit in evaluating regional wall function.

Aged↗

Effect of batroxobin on spontaneous echo contrast and hemorheology in left atrial appendage in atrial fibrillation assessed by transesophageal echocardiograpy.

Controversy exists regarding the effect of defibrination on spontaneous echo contrast and flow dynamics in left atrial appendage (LAA) in atrial fibrillation. We aimed to investigate the effect of batroxobin, which decreases plasma fibrinogen level, on the echo intensity of spontaneous echo contrast in LAA. In 36 patients with atrial fibrillation (duration 7 +/- 4 years), transesophageal echocardiography was performed at baseline and 24 hours after batroxobin administration (0.2 U/kg). At the orifice of the LAA, integrated backscatter of echo contrast and peak velocity of LAA emptying flow were measured. Plasma fibrinogen and whole blood viscosity were also measured. Fibrinogen and viscosity were significantly lower after batroxobin administration (96 +/-38 mg/dl and 4.35 +/- 0.56 cp) than those at baseline (320 +/- 61 mg/dl and 4.71 +/- 0.61 cp, both p <0.001). A significant positive correlation between changes in plasma fibrinogen and whole blood viscosity (r = 0.49, p = 0.002) was shown. The integrated backscatter significantly decreased from 14 +/- 3 to 12 +/- 3 decibels after batroxobin (p <0.001), and the changes in integrated backscatter and plasma fibrinogen was significantly correlated. Therefore, batroxobin administration improved blood rheology and decreased blood cell aggregation, which are effective in preventing left atrial thrombus formation.

Aged↗

Effects of adrenomedullin on cultured rat cardiac myocytes and fibroblasts.

The direct effects of adrenomedullin, a novel vasorelaxant peptide, on protein synthesis and atrial natriuretic peptide release in myocytes and on DNA and collagen syntheses in fibroblasts were examined using cultured ventricular cardiocytes. The protein synthesis of cardiac myocytes was not affected by adrenomedullin under non-stimulated conditions. Endothelin-1-induced protein synthesis in myocytes was slightly but significantly elevated by adrenomedullin. Likewise, the secretion of atrial natriuretic peptide from myocytes stimulated by endothelin-1 was increased by adrenomedullin. In cardiac fibroblasts, adrenomedullin clearly inhibited DNA synthesis and collagen production in a dose-dependent manner under both basal and angiotensin II-stimulated conditions. DNA and collagen syntheses by cardiac fibroblasts were suppressed by both 8-bromo cAMP and forskolin. Furthermore, a cAMP-specific phosphodiesterase inhibitor decreased DNA and collagen syntheses in fibroblasts and enhanced the inhibitory effects of adrenomedullin on these syntheses. Our observations suggest that adrenomedullin has opposite effects on cultured cardiac myocytes and fibroblasts and that the effects of adrenomedullin at least on fibroblasts are probably mediated through a cAMP-dependent pathway. As adrenomedullin is produced and secreted from both types of cardiac cells, adrenomedullin may play a role as an autocrine/paracrine modulator in the process of cardiac remodeling, mainly by suppressing mitogenesis and collagen synthesis in fibroblasts.

Adrenomedullin↗

Induced hypertension treatment to improve cerebral ischemic injury after transient forebrain ischemia.

The effect of induced hypertension treatment on cerebral ischemia is still controversial. We investigated the preferred blood pressure manipulation level and pressor agent required to reduce cerebral ischemic injury following transient forebrain ischemia induced by bilateral occlusion of the common carotid arteries in anesthetized gerbils. Following 60-min cerebral ischemia, we evaluated the preferred blood pressure manipulation level and pressor agent required to treat cerebral ischemic injury after reperfusion by examining the effects of different levels of mean arterial blood pressure (MABP), increased with phenylephrine or angiotensin II or decreased by blood withdrawal, on cerebral blood flow (CBF), survival ratio, cerebral edema, and brain energy metabolism following transient forebrain ischemia in gerbils. Mild phenylephrine-induced hypertension treatment (21+/-4 mmHg) during post-cerebral ischemia-reperfusion improved the survival ratio and reduced cerebral edema, which was also associated with an increase in local CBF and a recovery of brain energy metabolism. However, intense phenylephrine-induced hypertension, angiotensin II-induced hypertension, or hypotension worsen the survival rate and produced extra cerebral edema, that were also associated with deterioration of brain energy metabolism. These results demonstrate that a mild induced hypertension with phenylephrine (21+/-4 mmHg above the baseline level) results in reduction of the cerebral edema and improves the survival ratio and brain energy metabolism. Furthermore, angiotensin II may have neurotoxic effect to use as the pressor agent for induced hypertension after cerebral ischemia.

Adenosine Triphosphate↗

Heightened IgE response to mite antigens in inflammatory neuropathies.

In order to clarify the IgE response to common environmental antigens, we measured the serum total IgE and allergen-specific IgE in 50 patients with Guillain-Barré syndrome (GBS), nine patients with Fisher syndrome (FS), 14 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 18 patients with mononeuritis multiplex (MNM), 43 patients with neurodegenerative disorders and 82 healthy controls by ELISA. The total IgE level was significantly higher in patients with GBS (median = 135 U/ml, P<0.05), CIDP (median = 175 U/ml, P<0.05) and MNM (median= 199 U/ml, P<0.05), than in the healthy controls (median = 79 U/ml), but not in those patients with neurodegenerative disorders. The specific IgE to Dermatophagoides pteronyssinus was significantly higher in the patients with GBS (56%, P<0.01) and MNM (72%, P<0.005) than in the healthy controls (32%). The level of specific IgE to Dermatophagoides farinae tended to be higher in the patients with GBS than in the healthy controls (0.05<P<0.1). The patients with CIDP and MNM also showed a similar increase in the frequency of mite antigen-specific IgE. As a result, the heightened IgE responses to mite antigens may therefore in part be related to the mechanism of inflammatory neuropathies. On the other hand, such heightened IgE responses in these inflammatory neuropathies may be a reflection of Th2 cell overactivity, which may induce an intense synthesis of autoantibodies against the peripheral nerves.

Adolescent↗

Thermodynamic Quantities of Surface Formation of Aqueous Electrolyte Solutions.

The surface tensions of aqueous salt solutions of LiCl, KCl, and CsCl were measured as a function of concentration and temperature. By analyzing the results, the thermodynamic quantities of surface formation such as entropy (Deltas), Helmholtz free energy (Deltaf), and energy of surface formation (Deltau) were evaluated. Addition of salts into aqueous solution leads to an increase in Deltaf but decreases in Deltas and Deltau. The variations of Deltas, Deltaf, and Deltau with the change of salt concentration are almost the same for all alkali metal chlorides in spite of their large difference in hydration force. Copyright 1999 Academic Press.

Journal Article↗

Effect of cyclosporin A or tacrolimus on the function of blood-brain barrier cells.

Recently, it has been reported that continuous treatment with cyclosporin A or tacrolimus induces encephalopathy in transplant patients. The mechanism of immunosuppressant-induced encephalopathy is unclear. We investigated the cytotoxicity to brain capillary endothelial cells and the effect of these two drugs on P-glycoprotein function using mouse brain capillary endothelial (MBEC4) cells. The transcellular transport of [3H]sucrose was significantly increased and the cellular viability, based on 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and trypan blue exclusion test, was decreased by cyclosporin A (approximately 50% at 5 microM; P<0.005), while tacrolimus showed a much smaller effect. These findings indicate that the toxicity of cyclosporin A was greater than that of tacrolimus. The uptake of [3H]vincristine, a substrate of P-glycoprotein, was increased by these two drugs. The expression of P-glycoprotein in MBEC4 cells was reduced, but there was no effect on mdr1b mRNA levels. The decrease in the expression of P-glycoprotein may be due to the inhibition of the turnover of P-glycoprotein, which involves translation. In conclusion, the direct cytotoxic effect on the brain capillary endothelial cells and the inhibition of P-glycoprotein may be partly involved in the occurrence of immunosuppressant-induced encephalopathy.

ATP Binding Cassette Transporter, Subfamily B↗

Scanning a DRB3*0101 (DR52a)-restricted epitope cross-presented by DR3: overlapping natural and artificial determinants in the human acetylcholine receptor.

A recurring epitope in the human acetylcholine receptor (AChR) alpha subunit (alpha146-160) is presented to specific T cells from myasthenia gravis patients by HLA-DRB3*0101-"DR52a"-or by DR4. Here we first map residues critical for DR52a in this epitope by serial Ala substitution. For two somewhat similar T cells, this confirms the recently deduced importance of hydrophobic "anchor" residues at peptide p1 and p9; also of Asp at p4, which complements this allele's distinctive Arg74 in DRbeta. Surprisingly, despite the 9 sequence differences in DRbeta between DR52a and DR3, merely reducing the bulk of the peptide's p1 anchor residue (Trp149-->Phe) allowed maximal cross-presentation to both T cells by DR3 (which has Val86 instead of Gly). The shared K71G73R74N77 motif in the alpha helices of DR52a and DR3 thus outweighs the five differences in the floor of the peptide-binding groove. A second issue is that T cells selected in vitro with synthetic AChR peptides rarely respond to longer Ag preparations, whereas those raised with recombinant subunits consistently recognize epitopes processed naturally even from whole AChR. Here we compared one T cell of each kind, which both respond to many overlapping alpha140-160 region peptides (in proliferation assays). Even though both use Vbeta2 to recognize peptides bound to the same HLA-DR52a in the same register, the peptide-selected line nevertheless proved to depend on a recurring synthetic artifact-a widely underestimated problem. Unlike these contaminant-responsive T cells, those that are truly specific for natural AChR epitopes appear less heterogeneous and therefore more suitable targets for selective immunotherapy.

Alleles↗

Bone morphogenetic protein-3b (BMP-3b) gene expression is correlated with differentiation in rat calvarial osteoblasts.

BMP-3b (also called GDF-10) is a novel BMP-3-related protein recently discovered in rat femur tissue. Gene expression of BMP-3b in osteoblastic cells and its regulation by prolonged culture, BMP-2 and transforming growth factor beta1 (TGF-beta1) were examined. The BMP-3b gene was highly expressed in rat osteoblasts obtained from calvarial bones but not in the osteoblastic cell lines (MC3T3-E1 and U2-OS). BMP-3b mRNA increased during osteoblastic differentiation in prolonged culture and was associated with increased alkaline phosphatase (ALPase) activity. When BMP-2, an enhancer of ALPase activity, was added to the primary osteoblast culture, BMP-3b mRNA increased 6.9-fold after 24 h. In contrast, TGF-beta1 treatment, which suppresses ALPase activity, rapidly and completely inhibited gene expression of BMP-3b. The regulation of BMP-3 mRNA differed from that of BMP-3b, even though both proteins share 81% identity. These findings indicate that BMP-3b gene expression is regulated by osteoblastic differentiation and BMP-3b functions in highly differentiated osteoblasts.

Alkaline Phosphatase↗

Quantitative analysis of myocardial response to dobutamine by measurement of left ventricular wall motion using omnidirectional M-mode echocardiography.

Although dobutamine stress echocardiography is important for assessing cardiac ischemia and viability, analysis of wall motion is qualitatively performed. We quantitatively evaluated left ventricular wall motion using a newly developed omnidirectional M-mode echocardiography that can depict the M-mode at the site of region of interest on the 2-dimensional image in real time, and established its usefulness for analyzing the myocardial response to dobutamine infusion. Dobutamine stress echocardiography with omnidirectional M-mode was performed in 57 patients with coronary lesions. In 38 of these patients, exercise stress single-photon emission computed tomographic thallium scintigraphy (Tl-201 SPECT) was performed. Endocardial excursion of 103 regions was measured from omnidirectional M-mode at baseline, low-dose (6 microg/kg/min), and at peak dose (30 microg/kg/min) dobutamine. A decrease and increase in wall excursion was scored (from -3 to 3) for a changes of every 2 mm, and a quantitative wall motion score (QWMS) was calculated as a summation of the scores from baseline to low dose and from low to peak doses. Quantitative coronary stenosis score (QCSS) was calculated as a summation of stenotic and collateral scores. The stenosis scores were graded as: 1 = 0% to 50%, 2 = 50% to 75%, 3 = 75% to 90%, 4 = 90% to 95%, 5 = 95% to 100%; collateral scores were graded as: -1 = poor collateral, -2 = good collateral. Based on the QWMS at each dose of dobutamine, the serial changes in wall motion were divided into 4 groups: augmented, biphasic, no change, and worsening. The QCSS was clearly different among these groups. QWMS was significantly correlated with QCSS (r = 0.657, p <0.001). The incidence of redistribution in Tl-201 SPECT was high in the region with low score of QWMS. In conclusion, omnidirectional M-mode is useful for quantitatively determining the grade of cardiac ischemia by assessing the serial change of ventricular wall motion during dobutamine infusion.

Adrenergic beta-Agonists↗

Thermodynamic Quantities of Surface Formation of Aqueous Electrolyte Solutions.

The surface tensions of aqueous solutions of sodium, magnesium, and lanthanum chlorides were measured as a function of concentration and temperature. By analyzing the results, the concentration dependence of the thermodynamic quantities of surface formation such as entropy (Deltas), Helmholtz free energy (Deltaf), and energy of surface formation (Deltau) were evaluated. The Deltaf increased almost linearly with increasing concentration, and the degree of the increase is mainly determined by the net charges of the salts. The Deltas decreased with the addition of salt into the solution. It was found that the net charge of salts determines the degree of the decrease in Deltas. On the other hand, a slight change in the Deltau is observed because of the opposite contribution of Deltaf and TDeltas to the Deltau value. Copyright 1999 Academic Press.

Journal Article↗

Thermodynamic Quantities of Surface Formation of Aqueous Electrolyte Solutions.

The surface tensions of binary salt mixtures made up from NaCl and MgCl2 in aqueous solution were measured as a function of concentration and temperature. By analyzing the results, the thermodynamic quantities of surface formation such as entropy (Deltas), Helmholtz free energy (Deltaf), and energy of surface formation (Deltau) were evaluated. The Deltaf of the mixtures positively deviates from the straight line connecting those of NaCl and MgCl2 aqueous solutions. On the other hand, Deltas shows negative deviation from the linear relation. Copyright 1999 Academic Press.

Journal Article↗

Familial paroxysmal dystonic choreoathetosis: clinical findings in a large Japanese family and genetic linkage to 2q.

BACKGROUND: Paroxysmal dystonic choreoathetosis (PDC) is a rare familial movement disorder that has been mapped to chromosome 2q31-36. OBJECTIVE: To study the first Japanese family with PDC clinically and genetically. PATIENTS AND METHODS: We studied a large Japanese family in which at least 17 members in 6 generations have been affected by PDC. We interviewed and examined 26 family members, 8 of whom revealed choreoathetosis-like and dystonialike involuntary movement and 1 of whom revealed no involuntary movement but only muscle stiffness such as the aura of paroxysmal dystonic choreoathetosis (PDC). Genetic linkage studies of this family were carried out with polymorphic DNA markers. RESULTS: The attacks of involuntary movement or muscle stiffness were precipitated by ovulation, menstruation, emotional stress, or caffeine or alcohol ingestion. Magnetic resonance imaging of the brain revealed no abnormalities. Clonazepam therapy was effective for reducing the attacks, and ingestion of garlic was believed by patients to be effective for softening the attacks. An affected woman with only muscle stiffness showed remission after hysterectomy for hysteromyoma. This woman also had the disease haplotype and transferred it to her typical PDC-affected daughter. Maximal pairwise logarithm of odds scores exceeding 2.00 were obtained at D2S2250, D2S1242, D2S377, D2S2148, and D2S126. The PDC gene was demonstrated by linkage analyses to be located in a 15.3-centimorgan interval lying between D2S371 and D2S339 based on pairwise and multipoint logarithm of odds scores and obligate recombination events in affected individuals. CONCLUSIONS: Linkage of PDC to chromosome 2q32-36 was confirmed in a Japanese family. The clinical characterizations of this family with PDC include that ovulation seems also to be a precipitating factor of the attacks and that hysterectomy seems to be effective for softening the attacks. Although low-dose clonazepam treatment was most effective, garlic use was believed by affected members to be effective for softening the attacks. Furthermore, based on the results of clinical and genetic analyses, we suggest that muscle stiffness without involuntary movement may represent a forme fruste of PDC.

Athetosis↗

Contribution of P-glycoprotein to bunitrolol efflux across blood-brain barrier.

In this study, we investigated the mechanism of the blood-brain barrier (BBB) transport of bunitrolol (BTL), as a model of beta-blocker, in vivo and in vitro. In order to define the contribution of P-glycoprotein (P-gp) to the active efflux of BTL from brain to blood, we examined the in vivo brain distribution of BTL in mdr1a(-/-) mice with a disrupted mdr1a gene. After intravenous administration of BTL to mdr1a(-/-) mice, the brain concentration and Kp value of BTL were significantly increased as compared with those in mdr1a(+/+) mice. Next, the contribution of the mdr1a P-gp to in vitro uptake of BTL was compared in LV500 cells and L cells (mouse mdr1a-expressing cells and host cells, respectively). The intracellular accumulations of [3H]vinblastine and BTL by LV500 cells were lower than those by L cells, but were significantly increased by verapamil, a P-gp inhibitor. Furthermore, the BTL uptake by KB-VJ300 cells, which express human P-gp, was also significantly lower than that by KB host cells, and was increased by verapamil. The steady-state uptake of BTL by LLC-GA5-COL300 cells, expressing human P-gp, was significantly increased in the presence of 20 microM cyclosporin A (another P-gp inhibitor), which had no effect in the LLC-PK1 host cells. On the other hand, the steady-state intracellular accumulation of BTL by MBEC4 cells, which express mdr1b P-gp instead of mdr1a P-gp, was not significantly changed in the presence of verapamil. This finding suggested that BTL is not a good substrate for mdr1b P-gp. In conclusion, our results suggest that BTL is transported from brain to blood by mdr1a P-gp in mice and by MDR1 in humans, and this presumably accounts for the low brain distribution of BTL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cross-restriction of a T cell clone to HLA-DR alleles associated with rheumatoid arthritis: clues to arthritogenic peptide motifs.

OBJECTIVE: To identify distinctive sequence motifs required for productive peptide presentation by those HLA-DR alleles/DR4 subtypes that predispose to rheumatoid arthritis (RA). METHODS: We tested 10 different HLA-DR4 subtypes for presentation of acetylcholine receptor peptides to 8 different DR4-restricted T cell lines/clones in proliferation assays. RESULTS: Seven of the 8 T cells depended absolutely on either the autologous Lys71 (in Dw4) or Arg71 (e.g., Dw14), despite these alleles' similar charge and RA associations. In contrast, the PM-A T cell was only mildly affected by this interchange. Moreover, after minor modifications, peptides were presented to this unusual T cell preferentially by all the RA-associated subtypes of DR4 as well as by 2 other DR alleles (DR1 and DR1402) that predispose to RA. CONCLUSION: This coincident cross-restriction to all the RA-associated HLA-DR alleles except DR10 shows that there could even be a single arthritogenic peptide; we now suggest a possible consensus motif.

Alleles↗