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Biomedical subjects

K Arakawa

Publications and source records attributed to K Arakawa.

At least 19 recordsLinked to original sources

Apolipoprotein E1 Lys-146----Glu with type III hyperlipoproteinemia.

During the screening of samples obtained from 5 individuals with type III hyperlipidemia, we identified a variant of apolipoprotein (apo) E which exhibited a discrepancy in apo E phenotype showing the E3/E1 isoform on isoelectric focusing (IEF) analysis and E3/E3 on gene analysis. Sequence analysis of the DNA of the proband that was amplified by PCR and subcloned, revealed a single substitution of one lysine (AAG) for one glutamic acid (GAG) at position 146, thereby adding two negatively charged units to apo E3. This defect had been described only for apo E1 to date (Mann et al. (1989) Clin. Res. 37, 520A (abstract)). In this case, PCR-mediated site-directed mutagenesis was used to identify the structural alterations forming the abnormal E1 genotype in the proband's family. Purified apo E1 Lys-146----Glu showed less than 10% of binding activity to apo B, E receptor on human skin fibroblasts compared with apo E3. This substitution demonstrates that Lys-146 is essential for the binding of apo E to the receptor.

Adult

A fast Fourier transform analysis of coronary reperfusion-induced ventricular fibrillation and the modification by dibutyryl cyclic AMP in a cat model.

To investigate the effect of dibutyryl cyclic AMP (dbcAMP) on ventricular fibrillation after coronary reperfusion, the proximal portion of the anterior descending branch of left coronary artery was reperfused 20 min after ligation in 24 cats. McFee X Y Z electrocardiograms were recorded and ventricular fibrillation was analyzed using a fast Fourier transform analysis (FFT). Ventricular fibrillation occurred in 20 of 24 cases. Sixty seconds after the occurrence of ventricular fibrillation, an intracardiac infusion of dbcAMP was administered. Nine of the 20 were defibrillated and converted to sinus rhythm or junctional rhythm after the administration of dbcAMP. The amplitude and frequency of the main power spectrum of the ventricular fibrillation waves were analyzed by FFT before and after the infusion of saline or dbcAMP. In the saline group there was no significant change in FFT. However, in the dbcAMP group, the amplitude increased significantly from 0.036 +/- 0.015 (MV--2) to 0.054 +/- 0.013 (MV--2) (p < 0.01) and the frequency decreased significantly from 4.22 +/- 1.37 (Hz) to 1.33 +/- 0.91 (Hz) (p < 0.01). Those results indicate that dbcAMP increased the amplitude and decreased the frequency of the main power spectrum of ventricular fibrillation analyzed by FFT. These distinctive changes in FFT analysis were associated with defibrillation in 9 of 20 cases.

Animals

Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects.

A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO2 max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO2 max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.

Adrenergic beta-Antagonists

Effects of niceritrol on levels of serum lipids, lipoprotein(a), and fibrinogen in patients with primary hypercholesterolemia.

Thirty-three consecutive unselected patients with primary hypercholesterolemia received niceritrol 1.5 g daily for 12 weeks, with the effect of administering divided dose (twice daily (b.i.d.) and three times daily (t.i.d.)) evaluated. The serum concentrations of lipoprotein(a) (Lp(a)), lipids, the major apolipoproteins (apo), cholesteryl ester transfer activity and fibrinogen were determined before and after treatment. The b.i.d. and t.i.d. regimens each significantly reduced the serum levels of total cholesterol and triglyceride. The mean changes in serum lipids and lipoproteins did not differ significantly between the two groups. After 12 weeks of treatment, there was a significant decrease in total plasma cholesterol, triglyceride, low density lipoprotein cholesterol, apo A-II, apo B and fibrinogen and an increase in the high density lipoprotein cholesterol levels. Although the serum level of Lp(a) did not change in every patient, niceritrol significantly reduced the serum Lp(a) level in those with an initially high level of Lp(a) (greater than or equal to 20 mg/dl).

Adult

Rapid and slow changes in the human cone electroretinogram during light and dark adaptation.

Changes in the response characteristics of the human cone electroretinogram (ERG) during light and dark adaptation were studied in two visually normal subjects. Cone ERG responses were isolated under all adaptation conditions through the use of 31 Hz flicker. To determine the time-course of changes in the cone ERG during adaptation, responses to stimuli of constant luminance were measured repeatedly during 15 min of exposure to an adapting field of 2.0 log cd/m2 and during 30 min of dark adaptation following adapting field termination. In addition, luminance-response functions were obtained before and immediately after adapting field onset, as well as before and immediately after adapting field termination. The results indicate that the human cone ERG is influenced by two major processes. One process has a relatively rapid time-course and serves to reposition the luminance-response function along the luminance axis following changes in ambient light levels. The second process, which has a slow time-course, scales response amplitudes during light and dark adaptation by the same proportion at all stimulus luminances. The results provide a framework for predicting the manner in which the cone ERG will change with alterations in the state of retinal adaptation.

Adaptation, Ocular

Analysis of HLA class II genes in Japanese patients with idiopathic membranous glomerulonephritis.

Thirty unrelated Japanese adult patients with idiopathic membranous glomerulonephritis (IMG) and 50 unrelated Japanese normal controls were examined for HLA class II genes. Both the 3.0 kb DQB and the 6.2 kb DQA restriction fragments were simultaneously identified in 86.7% of the patients. These were significantly different from the 14% frequency of the fragments in controls (relative risk = 39.9; P = 1.7 x 10(-10)). The haplotype DR2-DQwl associated with IMG seemed to be Dw2 which was essentially different from the haplotype common to the normal Japanese population. Dw12. This was because most of the restriction fragment length polymorphism (RFLP) of DQB and DQA of the patients coincided with that of homozygous cell lines with Dw2. The DRB probe showed no significant differences in the hybridization patterns between the patient group and HLA-matched controls. These findings indicate that the specific HLA-DQ polymorphism correlates primarily with Japanese IMG.

Adult

Reduced left ventricular diastolic asynchrony after captopril in single vessel coronary artery disease.

Impaired left ventricular diastolic function is often found preceding systolic functional abnormality in coronary artery disease. To assess whether captopril improves diastolic function, radionuclide ventriculography was performed before and 1 h after captopril administration in 10 stable effort angina patients with severe isolated stenosis of the left anterior descending coronary artery and in 8 controls. Resting global peak filling rate (PFR) was significantly (p < 0.05) reduced in association with significantly (p < 0.01) increased left ventricular diastolic asynchronous index (delta t) in patients with angina pectoris. Neither global PFR nor regional cardiac function was affected by captopril, although delta t was significantly (p < 0.05) reduced from 70 +/- 18 (SD) to 51 +/- 25 ms in patients with angina pectoris. A significant (p < 0.01) correlation was observed between percentage changes in peak ejection rate and in PFR in all subjects. Thus, captopril improves left ventricular asynchrony in patients with stable angina, although global diastolic function affected by systolic function remains unchanged.

Aged

Mild exercise decreases plasma endogenous digitalislike substance in hypertensive individuals.

Changes in a plasma endogenous digitalislike substance were investigated in relation to the antihypertensive mechanism of mild exercise. Fifteen women with mild essential hypertension and seven normotensive female volunteers were divided into exercised hypertensive (n = 10), nonexercised hypertensive (n = 5), and nonexercised normotensive (n = 7) groups. A 4-week general clinical observation period preceded the study period of 10 weeks. The exercised hypertensive individuals were treated with a lactate threshold exercise that corresponded to approximately 50% of the maximum oxygen consumption three times a week, whereas the nonexercised groups were observed at the outpatient clinic as control groups. In the exercised group, systolic blood pressure fell by 7 mm Hg (p = 0.05), diastolic by 6 mm Hg (p less than 0.01), and mean blood pressure by 7 mm Hg (p less than 0.01) after 10 weeks. The reduction in the plasma endogenous digitalislike substance was significant after 7 (-1.02 ng/ml, p less than 0.05) and 10 (-1.04 ng/ml, p less than 0.05) weeks in this group. It positively correlated with the reduction in diastolic (r = 0.70, p less than 0.05) or mean (r = 0.66, p less than 0.05) blood pressure and with changes in plasma norepinephrine (r = 0.76, p less than 0.05). The mean corpuscular volume of erythrocytes decreased (-1.7 fl, p less than 0.01) after 10 weeks of exercise, and the plasma volume index tended to decrease (-108 ml/m2, p = 0.28). In the control groups, significant changes in blood pressure and plasma endogenous digitalislike substance were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

Effects of flumazenil on intravenous lidocaine-induced convulsions and anticonvulsant property of diazepam in rats.

We investigated the effect of flumazenil on intravenous (IV) lidocaine-induced convulsions with and without diazepam pretreatment in rats. Wistar rats (200-250 g) were divided into four groups of seven each and were pretreated with IV diazepam or normal saline solution at 6 min and flumazenil or normal saline solution at 3 min before lidocaine infusion. The control group received normal saline solution; the diazepam group received 0.2 mg/kg of diazepam and normal saline solution; the diazepam+flumazenil group received 0.2 mg/kg of diazepam and 0.1 mg/kg of flumazenil; and the flumazenil group received normal saline solution and 0.1 mg/kg of flumazenil. After surgical preparation and recovery from anesthesia, all groups received a continuous IV infusion of lidocaine (15 mg/mL) at a rate of 4 mg.kg-1.min-1 until tonic/clonic convulsions occurred. The values of pH and blood gases were maintained within physiologic ranges. Heart rate was significantly decreased after 5 min of lidocaine infusion, but arterial blood pressure did not change until convulsions occurred in all groups. Pretreatment with diazepam alone increased both cumulative convulsant doses and plasma concentrations of lidocaine at the onset of convulsions. Flumazenil reversed these effects of diazepam. Pretreatment with flumazenil alone changed neither cumulative convulsant doses nor plasma concentrations of lidocaine at the onset of convulsions. Our data show that IV flumazenil reverses the anticonvulsant property of IV diazepam against lidocaine-induced convulsions and that flumazenil itself has no effect on lidocaine-induced convulsions in rats.

Animals

Bunazosin enhances receptor-mediated endocytosis of low-density lipoproteins.

The effects of bunazosin, an alpha 1-adrenergic receptor antagonist, on low-density lipoprotein (LDL) receptor activity have been studied in cultured cells. Human skin fibroblasts, swine aortic smooth muscle cells and a human hepatoma cell line (Hep G2) were used for this study. Bunazosinm, at a concentration of 5 x 10(-5) to 10(-4) M, increased 125I-LDL uptake with all of the cell lines and 125I-LDL degradation with human skin fibroblasts and swine aortic smooth muscle cells. However, in human skin fibroblasts pretreated with lipoprotein deficient serum and Hep G2 cells, the degradation of 125I-LDL was decreased by bunazosin. These results suggest that bunazosin increases LDL receptor activity.

Adrenergic alpha-Antagonists

Ultrasonodiagnosis of subclinical heart failure by increasing afterload with angiotensin II.

In an attempt to diagnose latent heart failure, a transient increase of afterload to left ventricle was produced by angiotensin II, and the ventricular movement was assessed by echocardiography. Angiotensin II was administered in a dose of 0.075 micrograms/kg body weight. Blood pressure was elevated by 40.5 +/- 14.5 mmHg in 38 cases with latent heart failure and by 41.2 +/- 4.5 mmHg in 30 normal subjects. Yet, only in the former group, posterior wall excursion of left ventricle reduced from 11.4 +/- 2.4 mm to 7.3 +/- 2.3 mm and mean posterior wall velocity from 41.4 +/- 10.1mm/sec to 26.5 +/- 8.8 mm/sec. The rates of these reductions were inversely correlated to the rate of elevation of left ventricular endodiastolic pressure as determined in 5 cases by cardiac catheterization. There was no change in 30 subjects. The data indicate the usefulness of angiotensin-induced echocardiographic changes in detecting latent cadiac failure.

Adult