Biomedical subjects

A Ohtahara

Publications and source records attributed to A Ohtahara.

16 recordsLinked to original sources

PubMed1999

Hypertensive left ventricular hypertrophy is linked to an enhanced catecholamine response to submaximal exercise.

BACKGROUND: The serial plasma catecholamine response to exercise has not been studied fully in relation to left ventricular hypertrophy (LVH) in patients with hypertension (HT). This study determined whether plasma catecholamine responses to exercise are altered in essential HT in the presence or absence of LVH. MATERIALS AND METHODS: Plasma noradrenaline (NA) and plasma adrenaline (A) were measured at rest, during and after treadmill exercise in 59 hypertensive subjects and 22 age-matched control subjects. Patients were divided into LVH(-) (n = 20) and LVH(+) (n = 39) stratified by left ventricular mass index [LVMI: control subjects, LVH(-), LVH(+): 114 +/- 4, 105 +/- 3, 151 +/- 3 g m-2]. RESULTS: Exercise time (9.9 +/- 0.6, 7.6 +/- 0.7, 7.3 +/- 0.6 min) was shorter in patients with HT. Both systolic and diastolic blood pressures were higher in patients with HT, and no difference was observed between LVH(-) and LVH(+) patients. Resting plasma NA was not different (157 +/- 16, 173 +/- 17, 167 +/- 14 pg mL-1), but plasma NA at stage I (300 +/- 30, 342 +/- 40, 469 +/- 40 pg mL-1) was higher in LVH(+) patients than in LVH(-) patients or control subjects. Plasma A response to exercise was similar among the three groups. There was a positive correlation (r = 0.38, P < 0.001) between LVMI and Deltaplasma NA at stage I in all subjects. CONCLUSIONS: Patients with essential HT with LVH had augmented plasma NA response during submaximal exercise, whereas patients without LVH did not exhibit this augmentation. The positive correlation between LVMI and Deltaplasma NA suggested a possible association between the degree of cardiac hypertrophy and sympathetic activation during exercise.

Epinephrine↗

PubMed1998

Evaluation of changes in sympathetic nerve activity and heart rate in essential hypertensive patients induced by amlodipine and nifedipine.

OBJECTIVE: To compare the effects of amlodipine and nifedipine on heart rate and parameters of sympathetic nerve activity during the acute and chronic treatment periods in order to elucidate their influence on cardiovascular outcome. DESIGN: A randomized and single-blind study. METHODS: We performed 24 h ambulatory electrocardiography and blood pressure monitoring of 45 essential hypertensive inpatients. Plasma and urinary catecholamine levels were measured during the control (pretreatment) period, on the first day (acute period) and after 4 weeks (chronic period) of administration of amlodipine and of short-acting nifedipine or its slow-releasing formulation. The low-frequency and high-frequency power spectral densities and low-frequency: high-frequency ratio were obtained by heart rate power spectral analysis. RESULTS: Blood pressure was significantly and similarly reduced by administrations of amlodipine, short-acting nifedipine and slow-releasing nifedipine during the chronic period. The total QRS count per 24 h, which remained constant during the chronic period of administration of slow-releasing nifedipine and was increased by administration of nifedipine, was decreased by 2.8% by administration of amlodipine. Administration of amlodipine decreased the plasma and urinary norepinephrine levels during the chronic period, whereas the levels were significantly increased by administration of short-acting nifedipine and not changed by administration of slow-release nifedipine. Although low-frequency: high-frequency ratio was increased significantly by administration of short-acting nifedipine and slightly by administration of slow-releasing nifedipine, administration of amlodipine reduced it during the acute and chronic periods. CONCLUSIONS: Administration of amlodipine did not induce an increase in sympathetic nerve activity in essential hypertensive patients during the chronic period, suggesting that beneficial effects on essential hypertension can be expected after its long-term administration. Administration of slow-releasing nifedipine induces milder reflex sympathetic activation than does that of short-acting nifedipine.

Adult↗

PubMed1998

Control of AMP deaminase 1 binding to myosin heavy chain.

AMP deaminase (AMPD) plays a central role in preserving the adenylate energy charge in myocytes following exercise and in producing intermediates for the citric acid cycle in muscle. Prior studies have demonstrated that AMPD1 binds to myosin heavy chain (MHC) in vitro; binding to the myofibril varies with the state of muscle contraction in vivo, and binding of AMPD1 to MHC is required for activation of this enzyme in myocytes. The present study has identified three domains in AMPD1 that influence binding of this enzyme to MHC using a cotransfection model that permits assessment of mutations introduced into the AMPD1 peptide. One domain that encompasses residues 178-333 of this 727-amino acid peptide is essential for binding of AMPD1 to MHC. This region of AMPD1 shares sequence similarity with several regions of titin, another MHC binding protein. Two additional domains regulate binding of this peptide to MHC in response to intracellular and extracellular signals. A nucleotide binding site, which is located at residues 660-674, controls binding of AMPD1 to MHC in response to changes in intracellular ATP concentration. Deletion analyses demonstrate that the amino-terminal 65 residues of AMPD1 play a critical role in modulating the sensitivity to ATP-induced inhibition of MHC binding. Alternative splicing of the AMPD1 gene product, which alters the sequence of residues 8-12, produces two AMPD1 isoforms that exhibit different MHC binding properties in the presence of ATP. These findings are discussed in the context of the various roles proposed for AMPD in energy production in the myocyte.

AMP Deaminase↗

PubMed1998

Hematuria in patients with renal hypouricemia.

The characteristics of urate metabolism in renal hypouricemic patients with hematuria were studied to clarify the risk factors for hematuria in patients with renal hypouricemia. In 16 Japanese patients with isolated renal hypouricemia, urate metabolism was measured using the urate clearance study and the subtype of renal hypouricemia [defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion) and defective presecretory and postsecretory reabsorption (Pre&Post)] were determined by the pharmacological tests. Hematuria was seen in 7 out of the 16 patients (44%), all of whom were females (58%). Serum urate and urinary urate concentrations were significantly higher in the group with hematuria (Sur = 1.76 +/- 0.31 mg/dl and Uur/Ucr = 0.75 +/- 0.12: p<0.05) than in the group without hematuria (Sur = 1.44 +/- 0.46 mg/dl and Uur/Ucr = 0.56 +/- 0.04), although there was no difference in the urate excretion rate between the two groups. Hematuria was more likely to be accompanied by Post (75%) and Secretion (75%), which showed significantly higher urinary urate concentration (Uur/Ucr = 0.75 +/- 0.1 and 0.69 +/- 0.13, respectively) than by Pre (25%) and Pre&Post (0%), which showed lower urinary urate concentration (0.61 +/- 0.06 and 0.62 +/- 0.05, respectively). The risk factors for hematuria in patients with renal hypouricemia are the elevation of urinary urate concentration and the subtypes of Post and Secretion.

Adult↗

PubMed1998

Expression of Shaker-type voltage-gated potassium channel genes in the guinea-pig.

Few potassium channel genes have been isolated in the guinea-pig despite detailed electrophysiological characterization of potassium channels in the guinea-pig heart. We obtained partial clones of Shaker-type potassium channel genes in the guinea-pig and demonstrated their tissue distribution. Partial clones of the Shaker-type potassium channel genes were obtained by RT-PCR or genomic PCR. mRNA expression was measured by RNase protection assays in the heart, brain, and skeletal muscle. Three of the five obtained channel genes were expressed in the guinea-pig heart; Kv1.2, Kv1.3, and Kv1.6. Kv 1.6 expression was markedly at a higher level in the atrium than in the ventricle. Expression of the channel genes in the guinea-pig was different from that in human and rat, which may contribute to the species-specific action potential waveform.

Animals↗

PubMed1997

Characteristics of 161 patients with cardiac tumors diagnosed during 1993 and 1994 in Japan.

We investigated clinical and pathologic characteristics of 161 patients with primary or secondary cardiac tumors diagnosed between 1993 and 1994 in Japan. The increased use of cardiovascular imaging, especially echocardiography, contributed to the early identification of small cardiac tumors, resulting in a reduction of the serious complications such as embolization.

Adolescent↗

PubMed1997

Influence of extracellular H+ and Ca2+ on Ro 22-9194-induced block of sodium current in cardiac myocytes.

1. Ro 22-9194 reduced the Na current in ventricular myocytes in either a tonic block or phasic block manner. 2. Ro 22-9194 had a higher affinity to the inactivated state (Kdi = 10.3 microM) than to the rested state (Kdrest = 180 microM). 3. Extracellular acidification enhanced the tonic block but reduced the phasic block. 4. Elevation of extracellular Ca2+ inhibited the enhancing effects of extracellular acidification. 5. These findings suggest that Ro 22-9194 strongly inhibits Na+ channels of the ventricular myocytes of the diseased hearts, characterized by the depolarized cell membranes and by acid conditions.

Animals↗

PubMed1997

A novel mutation causing complete deficiency of thyroxine binding globulin.

OBJECTIVE: Thyroxine binding globulin (TBG) is a serum protein that transports thyroxine. Three naturally occurring mutations have been reported to produce complete deficiency of TBG (TBG-CD). The first to be reported was TBG-CD5 in caucasian families of French-Canadian origin and consists of substitutions in exons 2 and 3. TBG-CD of English ethnic origin (TBG-CD6) is characterized by a thymine deletion in codon 165 (exon 1). In Japanese families with TBG-CD (TBG-CDJ), a variant has been characterized with a deletion of the first base of the codon for amino acid 352 (exon 4) in the common type TBG. In this communication we report a new type of TBG-CD in a family of Japanese ethnic origin that is characterized by a single nucleotide substitution in place of two nucleotides in exon 1. This is an uncommon mutation which we have been unable to find in other genes. DESIGN: Exons of the TBG gene amplified by the polymerase chain reaction (PCR) were subcloned and sequenced. To examine for the presence of the same mutation in potentially affected individuals, we performed PCR using primer-directed mutagenesis or allele-specific amplification. PATIENTS: The index case was of Japanese ethnic origin, and was diagnosed as having TBG deficiency on the basis of undetectable serum TBG. The patient consented to this evaluation and the protocol was in accordance with IRB standards. MEASUREMENTS: Serum thyroid hormones, thyrotrophin binding inhibitory immunoglobulin and TBG concentrations were measured by conventional radio-immunoassay. Genomic DNA was extracted from white blood cells. RESULTS: In the index case exons 2, 3 and 4 were normal, but nucleotides 144 (cytosine) and 145 (thymine) in exon 1 were substituted with a single base (adenine) which induced a frame shift in the reading frame, resulting in an early stop codon at codon 51. The patient and his daughters were confirmed as having this mutation using primer-directed mutagenesis or allele-specific amplification. CONCLUSIONS: We have described a novel mutation in the TBG gene in a Japanese family. This results in a frame shift and premature stop codon, and was associated with undetectable serum TBG in the index case.

Exons↗

PubMed1996

A new type of familial central diabetes insipidus caused by a single base substitution in the neurophysin II coding region of the vasopressin gene.

We studied the genetic basis of familial neurohypophyseal diabetes insipidus in a Japanese family. The members had polyuria and a deficiency of plasma vasopressin (AVP). Polymerase chain reaction (PCR) amplified exons of the AVP-neurophysin-II gene were subcloned and sequenced. Exons 1 and 3 were normal, but nucleotide 1884 Guanine (G) in exon 2 was substituted with Thymine (T), which induced a substitution of glycine (Gly) for valine (Val). To examine the presence of this mutation in the affected subjects, we designed two mutated primers. One of them induced a new endonuclease restriction site in the PCR fragments from normal, and the other induced a new endonuclease restriction site from patients with the mutation. DNA fragments from two affected members of this family were amplified with this primer, and the PCR products were digested by endonuclease and resolved by electrophoresis. The results indicated that these subjects had both normal and mutant alleles, indicating that the mutation was heterozygous. We concluded that this mutation caused neurohypophyseal diabetes insipidus in this family.

Arginine Vasopressin↗

PubMed1996

Renal handling of urate in a patient with familial juvenile gouty nephropathy.

We encountered a case of familial juvenile gouty nephropathy (FJGN) with an autosomal dominant transmission pattern. Hyperuricemia in the propositus was caused by renal underexcretion of urate although his erythrocyte purine enzyme was normal. A renal biopsy specimen from the propositus showed interstitial fibrosis with tubular atrophy. On pyrazinamide and probenecid tests, the tubular secretion of urate selectively decreased without changes in either presecretory or postsecretory reabsorption of urate when his renal function was normal. Probenecid increased the urinary urate excretion and Cur/Ccr. The serum urate concentration was poorly controlled by allopurinol. When his renal function deteriorated, the uricosuric effects of both probenecid and benzbromarone were attenuated. However, the combined administration of probenecid with allopurinol decreased the serum urate concentration. These data suggest that the tubular secretion of urate is selectively impaired in FJGN and at the stage of renal failure, the combination of an uricosuric agent with allopurinol might be effective in treating hyperuricemia in FJGN.

Adolescent↗

PubMed1996

Cardiac angiosarcoma.

Angiosarcoma is one of the most common cardiac tumors, but early detection of this tumor is often difficult, as exemplified by our patient, a 55-year-old woman whose cardiac tumor was first detected by echocardiography. Surgical removal of the tumor was impossible due to its extensive pericardial invasion. Pathological diagnosis was not complete before autopsy because of the wide occupied necrotized area of the tumor. There is no diagnostic imaging technique available to detect such a necrotized area. An imaging technique more powerful than echocardiography and able to diagnose angiosarcoma earlier is needed.

Biopsy↗

PubMed1996

[Clinical incidence of primary cardiac tumors].

Recently, clinical diagnostic methods for heart disease, especially echocardiography, have remarkably progressed and the incidence of cardiac tumors increased. This study investigated the characteristics of tumors in 115 patients with primary cardiac tumor, diagnosed histologically in 1993-1994, in collaboration with 126 university hospitals in Japan. Histological diagnosis, location, initial clinical manifestations and prognosis of cardiac tumors are reported. Of the 115 patients, 98 (85%) had primary benign tumor. Myxoma was the most common histological group (91 cases). Primary malignant cardiac tumors occurred in 17 patients (15%) of which rhabdomyosarcoma was the most frequent (5 cases). Sixty percent of patients with myxoma were female, a similar ratio to the proportion of female patients with other primary cardiac tumors. Most patients with myxoma had the tumor in the left side of the heart [76 cases (84%) in left side, 12 (13%) in right side, 3 (3%) in both sides]. In contrast, the primary malignant cardiac tumors occurred more in the right side of the heart rather than in the left side (eight in right side, six in left side). Embolization was the characteristic initial clinical manifestation for myxoma. There were no patients with initial manifestation of embolization in the other histological groups. Reflecting the recent progress and spread of clinical diagnostic methods, 17% of all patients were discovered asymptomatically. All patients with myxoma who were asymptomatic underwent operation, and there were no surgical deaths. In contrast, only one patient with primary malignant cardiac tumor could survive longer than a year. In conclusion, the progress and the spread of cardiovascular imaging has contributed to the early diagnosis of primary cardiac tumors. These data demonstrate new clinical and pathological characteristics of primary cardiac tumors seen in recent cardiologic practice in Japan.

Adolescent↗

PubMed1995

Cardiovascular effects of intracerebroventricularly administered growth hormone-releasing factor in spontaneously hypertensive rat.

1. We investigated the cardiovascular effects of intracerebroventricularly administered (ICV) growth hormone-releasing factor (GRF) in both spontaneously hypertensive rats (SHR) and Wistar rats (WR) with reference to the involvement of adrenergic mechanisms and plasma AVP concentration. 2. The ICV GRF induced biphasic changes of mean arterial pressure (MAP) in SHR. In the first phase, maximum pressor response was observed 2-3 min after injection. In the second phase, maximum depressor response was observed 12-13 min after injection, and lasted up to 21-22 min. In WR, there were no significant changes in MAP. 3. ICV phentolamine attenuated the GRF-induced pressor response, but did not affect the depressor response. ICV bunazosine had no effect in both responses. ICV yohimbine attenuated the GRF-induced pressor response, but did not affect the depressor response. 4. In SHR, plasma AVP concentration was not affected by ICV GRF. 5. These data suggest that central GRF plays an important role in the maintenance of hypertension in SHR, since ICV GRF caused a significant depressor effect in SHR but not in WR. ICV GRF induced biphasic changes of MAP in SHR. The pressor response was mediated through central alpha2-adrenoceptors. The depressor response was not mediated through central alpha-adrenoceptors. The depressor effect of ICV GRF was not mediated by the changes of plasma AVP concentration.

Animals↗

PubMed1995

Mechanism of inhibition of the sodium current by bepridil in guinea-pig isolated ventricular cells.

1. Effects of bepridil, a sodium-, calcium-, and potassium-antagonistic agent, on the Na+ current were studied by the whole cell voltage clamp technique (tip resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol l-1 at 20 degrees C). 2. Bepridil produced tonic block (Kdrest = 295.44 mumol l-1, Kdi = 1.41 mumol l-1; n = 4). 3. Bepridil (100 mumol l-1) shifted the inactivation curve in the hyperpolarization direction by 13.4 +/- 2.7 mV (n = 4) without change in the slope factor. 4. In the presence of 50 mumol l-1 bepridil, bepridil showed use-dependent block at 2 Hz, whereas changes in pulse duration did not significantly effect this use-dependent block (81% +/- 2% at 10 ms, 84% +/- 3% at 30 ms, 86% +/- 3% at 100 ms; n = 4). 5. After removal of fast inactivation of the Na+ current by 3 mmol l-1 tosylchloramide sodium, bepridil (50 mumol l-1) still showed use-dependent block which was independent of the holding potential. 6. The recovery time constant from the bepridil-induced use-dependent block was 0.48 s at holding potential of -100 mV and 0.51 s at holding potential of -140 mV. 7. These results indicate that bepridil could bind to the receptor in the sodium channel through the hydrophobic and the hydrophilic pathway and leave the receptor through the hydrophobic pathway in the lipid bilayer. The binding and dissociation kinetics of this drug were shown to be fast, and the accumulation of the drug in the sodium channel appeared to be small. Bepridil is presumed to be safe in terms of adverse effects that result from drug-accumulation in the sodium channel.

Animals↗

PubMed1987

Inhibition of Ca2+ inward current in rabbit sinoatrial node by bunazosin, an alpha-adrenoceptor antagonist.

The electrophysiological effects of bunazosin, a novel alpha-adrenoceptor antagonist, were examined on isolated spontaneously beating sinoatrial node preparations of the rabbit by means of a double-microelectrode voltage clamp method. Bunazosin (above 10 microM) reduced the beating frequency, and the maximum rate of rise and the amplitude of action potentials. The slope of the diastolic depolarization (phase 4) was also decreased by the drug whereas the action potential duration at 50% repolarization was prolonged. Bunazosin decreased the slow inward current (Isi) and the time-dependent potassium outward current (IK). However, the major effect was the reduction of Isi. The results indicate that bunazosin, an alpha-adrenoceptor antagonist, depresses the action potential and automaticity of the sinoatrial node by inhibition of Ca channels.

Action Potentials↗

PubMed1987

Complete atrioventricular block with a 22-month history of ocular sarcoidosis: a case report.

A 52-year-old woman with acute uveitis associated with ocular sarcoidosis developed complete atrioventricular block 22 months after the initial diagnosis was made. Cardiac sarcoidosis is a serious and, not infrequently, a fatal disease. Although it is difficult to establish the clinical diagnosis of cardiac sarcoidosis, a serial ECG is considered necessary in patients with any kind of sarcoidosis.

Cardiomyopathies↗