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Biomedical subjects

S Ando

Publications and source records attributed to S Ando.

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

Atrial natriuretic peptide augments the variability of sympathetic nerve activity in human heart failure.

OBJECTIVES: Activation of the sympathetic nervous system, decreased heart rate variability (HRV), and loss of modulation of muscle sympathetic nerve activity (MSNA) within the low frequency (LF, 0.05-0.15 Hz) range are three adverse features of advanced congestive heart failure (CHF). In healthy men, atrial natriuretic peptide (ANP) infusion attenuates reflex increases in MSNA and reduces LF components of HRV spectral power. Sympathoinhibitory actions have also been documented in CHF, but effects on the variability of MSNA and HRV have not been described. DESIGN AND METHODS: Heart rate and MSNA were recorded in 10 men (aged 39 +/- 3 years, mean +/- SE) with dilated cardiomyopathy (mean EF 20 +/- 4%) treated with angiotensin converting enzyme (ACE) inhibitors. Subjects received i.v. ANP (50 microg bolus then 50 ng/kg/min) and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. Signals at baseline, and 13-20 min into each infusion were submitted to spectral analysis. RESULTS: ANP had no effect on HRV, but increased MSNA LF (from 7.9 +/- 1.5 to 12.1 +/- 2.6 U2; P< 0.02) and total spectral power (from 47.9 +/- 5.4 to 61.9 +/- 6.8 U2; P < 0.05). NTG had no effect on the variability of MSNA or HRV. CONCLUSIONS: In CHF patients receiving ACE inhibitors, ANP (i) does not suppress HRV and (ii) enhances the modulation of MSNA, particularly within the LF range. This latter action is not observed with NTG. These findings suggest beneficial actions of exogenous ANP on neurogenic circulatory control.

Adult↗
PubMed2001

Ultrasonic six-axis deformation sensing.

In this paper, we describe a newly developed deformation sensing scheme in a soft medium, which is based on precise encoding and decoding of deformation components into ultrasound wavefronts. It can detect three translational components and three rotational components of displacement around a transmitter position nearly simultaneously. We assume a cell structure that consists of a 2 x 2 ultrasonic transmitter matrix and a 2 x 2 ultrasonic receiver matrix, which are placed face to face at a distance of a few tens of wavelengths. All of the transmitter elements are driven sinusoidally and simultaneously, but they are switched into the same, reversed, or quadrature phases to generate a particular shape of wavefront on the receiver matrix. The receiver elements are connected in such a way to obtain amplitude and spatial gradients of the wavefront at a center of the receiver matrix. First, we describe the transduction theory for the six dimensions and show the orthogonality, locality, and simultaneity of this sensing scheme. Then, we describe the fabrication and experimental evaluation of the cell. We also describe a prototype tactile sensor in which a single cell is embedded in a flexible hemispherical fingertip-like body.

Journal Article↗
PubMed2001

Pie1, a protein interacting with Mec1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae.

In eukaryotes, the ATM and ATR family proteins play a critical role in the DNA damage and replication checkpoint controls. These proteins are characterized by a kinase domain related to the phosphatidylinositol 3-kinase, but they have the ability to phosphorylate proteins. In budding yeast, the ATR family protein Mec1/Esr1 is essential for checkpoint responses and cell growth. We have isolated the PIE1 gene in a two-hybrid screen for proteins that interact with Mec1, and we show that Pie1 interacts physically with Mec1 in vivo. Like MEC1, PIE1 is essential for cell growth, and deletion of the PIE1 gene causes defects in the DNA damage and replication block checkpoints similar to those observed in mec1Delta mutants. Rad53 hyperphosphorylation following DNA damage and replication block is also decreased in pie1Delta cells, as in mec1Delta cells. Pie1 has a limited homology to fission yeast Rad26, which forms a complex with the ATR family protein Rad3. Mutation of the region in Pie1 homologous to Rad26 results in a phenotype similar to that of the pie1Delta mutation. Mec1 protein kinase activity appears to be essential for checkpoint responses and cell growth. However, Mec1 kinase activity is unaffected by the pie1Delta mutation, suggesting that Pie1 regulates some essential function other than Mec1 kinase activity. Thus, Pie1 is structurally and functionally related to Rad26 and interacts with Mec1 to control checkpoints and cell proliferation.

Amino Acid Sequence↗
PubMed2001

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans.

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

Adult↗
PubMed2001

Somatic mutation of TRbeta can cause a defect in negative regulation of TSH in a TSH-secreting pituitary tumor.

In patients with TSH-secreting tumors (TSHomas), serum TSH is poorly suppressed by thyroid hormone. The mechanism for this defect in negative regulation of TSH secretion is not known. To investigate the possibility of a somatic mutation of TR causing this defect, we performed mutational analysis of TRbeta by RT-PCR using RNA obtained from five surgically resected TSHomas. In one TSHoma, we identified a somatic mutation in the ligand-binding domain of TRbeta that caused a His to Tyr substitution at codon 435 of TRbeta1 corresponding to codon 450 of TRbeta2. Interestingly, this mutation occurred in the same codon as two mutations (TRbetaH435L and H435Q) previously identified in patients with the syndrome of resistance to thyroid hormone. This mutant TRbeta had impaired T3 binding and T3-mediated negative regulation. It also blocked the negative regulation by wild-type TRbeta2 on glycoprotein hormone alpha-subunit and TSHbeta reporter genes in cotransfection studies. Our results demonstrate that somatic mutation of TRbeta occurred in a TSHoma and was probably responsible for the defect in negative regulation of TSH by thyroid hormone in the tumor.

Adult↗
PubMed2001

Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.

Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T3 and free T4 levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T3 stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TRbeta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T3 and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TRbeta mutant contributed to the extreme RTH phenotype and resistance in our patient.

Bone Development↗
PubMed2001

Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance.

Patients with TSH-secreting pituitary tumors (TSHomas) have high serum TSH levels despite elevated thyroid hormone levels. The mechanism for this defect in the negative regulation of TSH secretion is not known. We performed RT-PCR to detect mutations in TRbeta from a surgically resected TSHoma. Analyses of the RT-PCR products revealed a 135-bp deletion within the sixth exon that encodes the ligand-binding domain of TRbeta2. This deletion was caused by alternative splicing of TRbeta2 mRNA, as near-consensus splice sequences were found at the junction site and no deletion or mutations were detected in the tumoral genomic DNA. This TRbeta variant (TRbeta2spl) lacked thyroid hormone binding and had impaired T3-dependent negative regulation of both TSHbeta and glycoprotein hormone alpha-subunit genes in cotransfection studies. Furthermore, TRbeta2spl showed dominant negative activity against the wild-type TRbeta2. These findings strongly suggest that aberrant alternative splicing of TRbeta2 mRNA generated an abnormal TR protein that accounted for the defective negative regulation of TSH in the TSHoma. This is the first example of aberrant alternative splicing of a nuclear hormone receptor causing hormonal dysregulation. This novel posttranscriptional mechanism for generating abnormal receptors may occur in other hormone-resistant states or tumors in which no receptor mutation is detected in genomic DNA.

Adenoma↗
PubMed2001

New allyl ester linker and solid-phase block synthesis of the serglycin core region.

The prototype glycopeptidyl fragments of serglycin, a proteoglycan with the characteristic peptide sequence of repeating L-seryl-L-glycine, were synthesized by a convergent method involving block condensation on a solid support. In order to facilitate detachment of the protected glycopeptides from the resin, a new allyl ester type of linker, which is cleavable by Pd(O)-catalysis, was designed and used in combination with the commercial acid-labile Sieber amide resin for the solid-phase synthesis. Glycopeptide blocks consisting of [O-(2,3,4-tri-O-acetyl-D-xylosyl)-L-seryl-L-glycine]n (n = 1 - 8) were produced in good yields. Block condensation in a solution was also successful to synthesize up to the hexadecapeptide (n = 8).

Carbohydrate Sequence↗
PubMed2001

Hemodynamic effects of simulated obstructive apneas in humans with and without heart failure.

STUDY OBJECTIVES: To determine whether generation of negative intrathoracic pressure during apnea would cause more pronounced and sustained reductions in cardiac output in patients with congestive heart failure (CHF) than in healthy subjects. DESIGN: Physiologic intervention study. SETTING: Cardiorespiratory physiology laboratory. PARTICIPANTS: Nine patients with CHF and nine healthy control subjects matched for age and sex. INTERVENTIONS: Patients with CHF and healthy subjects generated - 30 cm H(2)O of intrathoracic pressure during 15-s Mueller maneuvers (MMs) to simulate the acute hemodynamic effects and aftereffects of obstructive apneas. RESULTS: In both groups, MMs caused an immediate rise in left ventricular transmural pressure during systole (LVPtmsys) [p < 0.05], but in CHF patients, this immediate increase was followed by a significant drop in LVPtmsys (p < 0.05), associated with significantly greater reductions in systolic BP and cardiac index than in healthy subjects (- 25 +/- 3 mm Hg vs - 11 +/- 2 mm Hg [p < 0.05] and - 0.53 +/- 0.11 L/min/m(2) vs - 0.15 +/- 0.11 L/min/m(2) [p < 0.05], respectively). Healthy subjects recovered promptly, but in CHF patients, these adverse hemodynamic effects were sustained following release of the MM. CONCLUSIONS: CHF patients experience more pronounced and sustained reductions in BP and cardiac output both during and following the MM than do healthy subjects. These findings suggest the potential for adverse hemodynamic effects and aftereffects of negative intrathoracic pressure generation during obstructive sleep apnea in patients with CHF.

Blood Pressure↗
PubMed2001

Closed-loop control using a stretch sensor for restoration of standing with functional electrical stimulation in complete paraplegia.

A closed-loop control system for standing with functional electrical stimulation (FES) using percutaneous intramuscular electrodes in complete paraplegia is described. The system consisted of ultrafine percutaneous intramuscular electrodes, a 32-channel stimulator and a stretch sensor with active current control to detect knee buckling. The closed-loop control system was applied in a T8 completely paraplegic patient. Compared to the stretch sensor with a wide use flexible goniometer for direct current control during standing, the stretch sensor was superior to the flexible goniometer in both ease of use and response. The average time delay from the start of knee buckling until the sensor turned on was 0.56+/-0.19 seconds (Mean+/-S.D.) in the goniometer and 0.21+/-0.06 seconds in the stretch sensor. The average time delay from the start of knee buckling until the recovery from knee buckling was 1.01+/-0.05 seconds in the goniometer and 0.78+/-0.06 seconds in the stretch sensor. The continuous standing ability of the patient increased from 12 minutes with open-loop stimulation to 30 minutes with the closed-loop control. No complications such as falling occurred during clinical use. This system prevented falling due to knee buckling during standing and prolonged upright activities in complete paraplegics.

Adult↗
PubMed2001

Central and peripheral visual reaction time of soccer players and nonathletes.

Visual Reaction Time (RT) was measured by presenting three different sizes of stimulus to the central and peripheral fields of vision in 6 soccer players and 6 nonathletes. An electromyogram was recorded from the flexor digitorum superficialis muscle of the responding forearm. Peripheral visual RT was longer in comparison to central visual RT due to an increment in Premotor Time. The soccer players showed shorter Premotor Times during central and peripheral visual RT tasks than nonathletes, suggesting that the soccer players are better able to respond quickly to a stimulus presented to peripheral as well as central positions.

Adult↗
PubMed2001

Establishment of a simple method for measurement of chronic blood flow in uterine artery of pregnant cows.

Blood flow to the gravid uterine horn of seven multiparous Holstein cows (mean +/- SD, BW = 625.5 +/- 82.4 kg; age = 4.7 +/- 1.7 yr; parity = 2.9 +/- 1.1 yr) was measured from d 225 of gestation to parturition using transit-time ultrasonic blood flow probes placed around the middle uterine artery. Surgery was conducted on d 215 of gestation. The cows were sedated with xylazine and local anesthesia (procaine or bupivacain hydrochloride) during surgery. The surgical operations were conducted at the flank of standing cows. A transit time ultrasonic flow probe ("S" series, diameter 12 or 14 mm, Transonic Systems Inc., Ithaca, NY) was fitted surgically around the uterine artery of each cow. Surgery was completed within 2 h of anesthesia, and the animals recovered rapidly following surgery. Uterine blood flow (UBF, L/min) was recorded at 10-s intervals for 1395 min; these values were averaged to determine UBF. Cows exhibited normal gestation lengths (279.1 +/- 7.4 d), gave birth to normal healthy calves (birth weight = 40.6 +/- 6.6 kg), and had no retained placentas. The UBF increased significantly (P < 0.01) from d 225 (6.67 +/- 2.47) to d 249 (8.23 +/- 2.89) of gestation, but the latter UBF was similar to that of d 266 (8.38 +/- 2.70). The increased UBF after d 225 indicates increased demand of nutrients of fetus with the progress of gestation. The range of mean UBF varied widely among individual cows from 4.1 L/min to 12.2 L/min. Our method is useful for chronic measurement of UBF in cows for nutritional or physiological studies and does not require sophisticated facilities or special surgical technique.

Animals↗
PubMed2001

Attenuated cardiac baroreflex in men with presyncope evoked by lower body negative pressure.

Mechanisms responsible for presyncope during lower body negative pressure (LBNP) in otherwise healthy subjects are poorly understood. Muscle sympathetic nerve activity (MSNA), blood pressure, heart rate (HR), HR power spectra, central venous pressure (CVP) and stroke volume were determined in 14 healthy men subjected to incremental LBNP. Of these, seven experienced presyncope at LBNP >-15 mmHg. Subjects who tolerated LBNP >-15 mmHg had significantly lower CVP (2.6+/-1.0 versus 7.2+/-1.2 mmHg; means+/-S.E.M., P<0.02), HR (59+/-2 versus 66+/-3 beats/min, P<0.05) and MSNA burst frequency (29.0+/-2.4 versus 39.0+/-3.5 bursts/min, P<0.05) during supine rest. LBNP at -15 mmHg had no effect on blood pressure, but caused similar and significant reductions in stroke volume and cardiac output in both groups. Subjects who tolerated LBNP had significant reflex increases in HR, MSNA burst frequency and burst amplitude with LBNP of -15 mmHg. These responses were absent in those who experienced presyncope. The gain of the cardiac baroreflex regulation of MSNA was markedly attenuated in pre-syncopal subjects (1.2+/-0.6 versus 8.8+/-1.4 bursts/100 heart beats per mmHg; P<0.001). Healthy subjects who experience presyncope in response to LBNP appear more dependent, when supine, upon MSNA to maintain preload, and less able to increase sympathetic vasoconstrictor discharge to skeletal muscle reflexively in response to orthostatic stimuli.

Adult↗
PubMed2001

Quantitative estimation of dietary energy deficiency and effects of its supplementation on protein nutritional status of nondiabetic uremic patients undergoing protein restricted dietary regimens.

In chronic renal failure (CRF) patients with a reduced protein intake, if the patients' energy intake could be estimated on the basis of biochemical data together with protein intake, it would be easier to provide them with adequate dietary treatment. Thus, from the relationship among the normalized protein catabolic rate (nPCR) and the intrinsic creatinine generation rate (%GCr) both calculated on the basis of 24-hr urine creatinine, as well as the daily dietary energy intake evaluated by a skilled nutritionist, we devised the following equation to estimate the amount of dietary energy deficiency (delta E) whose supplementation increases the %GCr of patients on protein-restricted dietary regimens to the target level (i.e., the dietary energy deficient amount). This was done by taking the %GCr of average nondiabetic hemodialysis patients of the same age and sex as a temporal target level: delta E = [31.22 - 1.97 (%GCr)0.6]/(nPCR)0.15. In order to examine the clinical usefulness of this equation, the daily dietary energy deficient amount calculated by the equation was supplemented with protein-free jelly. As a result, the %GCr increased from approximately three-fourths of the target level to the target level within 4 months.

Creatinine↗
PubMed2000

Solid-phase synthesis of the glycopeptide of human glycophorin AM bearing the consecutive sialyl-T antigen.

Fmoc solid-phase synthesis of the N-terminal glycopentapeptide of human glycophorin AM, bearing the consecutive sialyl-T antigen, was accomplished using glycosylated amino acid building blocks on a weakly acid-labile resin with high efficiency. The benzylated glycopeptide was treated with TMSOTf-thioanisole in TFA and then with aq NaHCO3 to afford the deprotected glycopeptide in good yield.

Amino Acids↗
PubMed2000

Characteristics and biodistribution of cationic liposomes and their DNA complexes.

We have developed some novel liposome formulations for gene transfection. The formulations consisting of O,O'-ditetradecanoyl-N-(alpha-trimethyl ammonio acetyl) diethanolamine chloride (DC-6-14) as a cationic lipid, phospholipid and cholesterol showed effective gene transfection activity in cultured cells with serum and in vivo, i.e., intraperitoneal injection in mice. In this report, the physicochemical characteristics and biodistribution of the liposomes containing DC-6-14 (DC-6-14 liposomes) as a drug (gene) carrier for gene therapy were investigated in vitro and in vivo. DC-6-14 liposome-DNA complexes were usually thought to have positive surface charge. However, depending on the ratio of DNA to liposomes, zeta-potential of the complexes became negative. The diameter of the complexes also depended on the DNA-liposome ratio, and showed a maximum when their surface potential was neutral. When biodistribution of the complexes was determined after intravenous injection, positively charged complexes showed an immediate lung accumulation. On the other hand, negatively charged complexes did not show lung accumulation. These results have suggested that biodistribution of the DNA-liposome complexes, prepared with DC-6-14 liposomes, depends on their surface charge. Therefore, some surface modification of DC-6-14 liposomes may improve the biodistribution and hence the targetability of their DNA complexes.

Animals↗
PubMed2000

Mutant presenilin 2 transgenic mice. A large increase in the levels of Abeta 42 is presumably associated with the low density membrane domain that contains decreased levels of glycerophospholipids and sphingomyelin.

The N141I mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease in the Volga German families. We previously reported that mouse brains harboring mutant PS2 contained increased levels of amyloid beta protein (Abeta) 42 in the Tris-saline-soluble fraction (Oyama, F., Sawamura, N., Kobayashi, K., Morishima-Kawashima, M., Kuramochi, T., Ito, M., Tomita, T., Maruyama, K., Saido, T. C., Iwatsubo, T., Capell, A., Walter, J., Grünberg, J., Ueyama, Y., Haass, C. and Ihara, Y. (1998) J. Neurochem. 71, 313-322). Here, using a new extraction protocol, we quantitated the Abeta40 and Abeta42 levels in the Tris-saline-insoluble fraction. The insoluble Abeta levels were found to be higher than the soluble Abeta levels, and the insoluble Abeta42 levels were markedly increased in mutant PS2 transgenic mice. To investigate the origin of the insoluble Abeta42, we prepared the detergent-insoluble, low density membrane fraction. This fraction from two independent lines of mutant PS2 transgenic mice contained remarkably increased levels of Abeta42 and significantly low levels of glycerophospholipids and sphingomyelin. This unexpected finding suggests that a large increase in the levels of Abeta42 in mutant PS2 mice is presumably induced through alterations of the lipid composition in the low density membrane domain in the brain.

Amino Acid Substitution↗