Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 19 recordsLinked to original sources

PubMed1999

Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice.

The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascular endothelia and aquaporin-4 (AQP4) in airway epithelia. To test whether these water channels facilitate fluid movement between airspace, interstitial, and capillary compartments, we measured passive and active fluid transport in AQP1 and AQP4 knockout mice. Airspace-capillary osmotic water permeability (Pf) was measured in isolated perfused lungs by a pleural surface fluorescence method. Pf was remarkably reduced in AQP1 (-/-) mice (measured in cm/s x 0.001, SE, n = 5-10: 17 +/- 2 [+/+]; 6.6 +/- 0.6 AQP1 [+/-]; 1.7 +/- 0.3 AQP1 [-/-]; 12 +/- 1 AQP4 [-/-]). Microvascular endothelial water permeability, measured by a related pleural surface fluorescence method in which the airspace was filled with inert perfluorocarbon, was reduced more than 10-fold in AQP1 (-/-) vs. (+/+) mice. Hydrostatically induced lung interstitial and alveolar edema was measured by a gravimetric method and by direct measurement of extravascular lung water. Both approaches indicated a more than twofold reduction in lung water accumulation in AQP1 (-/-) vs. (+/+) mice in response to a 5- to 10-cm H2O increase in pulmonary artery pressure for five minutes. Active, near-isosmolar alveolar fluid absorption (Jv) was measured in in situ perfused lungs using 125I-albumin as an airspace fluid volume marker. Jv (measured in percent fluid uptake at 30 min, n = 5) in (+/+) mice was 6.0 +/- 0.6 (37 degrees C), increased to 16 +/- 1 by beta-agonists, and inhibited to less than 2.0 by amiloride, ouabain, or cooling to 23 degrees C. Jv (with isoproterenol) was not affected by aquaporin deletion (18.9 +/- 2.2 [+/+]; 16.4 +/- 1.5 AQP1 [-/-]; 16.3 +/- 1.7 AQP4 [-/-]). These results indicate that osmotically driven water transport across microvessels in adult lung occurs by a transcellular route through AQP1 water channels and that the microvascular endothelium is a significant barrier for airspace-capillary osmotic water transport. AQP1 facilitates hydrostatically driven lung edema but is not required for active near-isosmolar absorption of alveolar fluid.

Animals↗

PubMed1999

Western blotting for ginseng saponins, ginsenosides using anti-ginsenoside Rb1 monoclonal antibody.

Ginsenosides separated by silica gel TLC were blotted to a polyvinylidene difluoride (PVDF) membrane which was treated with a NaIO4 solution followed by bovine serum albumine (BSA), resulting in a ginsenoside-BSA conjugate on a PVDF membrane. The blotted bands were stained with monoclonal antibody (MAb). The newly established Western blotting method was used for the determination of ginsenosides and their distribution in various Panax species.

Antibodies, Monoclonal↗

PubMed1998

Evaluation of left atrial filling using systolic pulmonary venous flow velocity measurements in patients with atrial fibrillation.

BACKGROUND: The pattern of pulmonary venous flow velocity is useful for understanding the hemodynamic relationship between the left atrium and left ventricle in patients with a variety of diseases, and the systolic flow wave, in particular, is considered a clinically important parameter that reflects left atrial filling. HYPOTHESIS: The study was undertaken to determine whether systolic pulmonary venous flow velocity patterns can be used to evaluate left atrial filling in patients with atrial fibrillation. METHODS: We performed transesophageal pulsed Doppler echocardiography and cardiac catheterization in 34 patients with chronic atrial fibrillation (10 with hypertrophic cardiomyopathy, 5 with dilated cardiomyopathy, 7 with previous myocardial infarction, and 12 with isolated atrial fibrillation) and 15 normal controls in sinus rhythm. RESULTS: Mean pulmonary capillary wedge pressure, V-wave height in the pulmonary capillary wedge pressure curve, and left ventricular end-diastolic pressure were significantly higher in the hypertrophic cardiomyopathy and dilated failing heart (previous myocardial infarction and dilated cardiomyopathy) groups than in the isolated atrial fibrillation and normal groups. The peak velocity and time-velocity integral of the systolic pulmonary venous flow velocity, and percent left atrial emptying fraction were significantly lower in the dilated failing heart group than in the isolated atrial fibrillation, hypertrophic cardiomyopathy, and normal groups. The peak velocity and time-velocity integral of the systolic pulmonary venous flow velocity, percent left atrial emptying fraction, and V-wave height were comparatively constant when the preceding R-R intervals were relatively stable in the isolated atrial fibrillation group and in 4 of the 10 patients with hypertrophic cardiomyopathy. However, changes in these variables correlated with the preceding R-R interval in all patients with dilated failing hearts and in 6 of the 10 patients with hypertrophic cardiomyopathy. CONCLUSION: Transesophageal pulsed Doppler echocardiographic measurements of systolic pulmonary venous flow velocity are valid indicators of left atrial filling in patients with atrial fibrillation.

Adult↗

PubMed1998

Common bile duct stones: management strategies in the laparoscopic era.

We reviewed our experience with the treatment of common bile duct (CBD) stones in 70 patients by sequential endoscopic-laparoscopic management and single-stage laparoscopic treatment during the past 7 years. The advantages, disadvantages, and feasibility of the two procedures are discussed to elucidate therapeutic strategies for patients harboring gallbladder stones and associated choledocholithiasis. In 44 patients, sequential endoscopic-laparoscopic management was indicatedd, and was successful in 37 of them but, in seven patients endoscopic stone extraction could not be accomplished. Single-stage laparoscopic treatment was attempted in 26 patients. In practice, laparoscopic transcystic common duct exploration or choledochotomy may not always be feasible if the cystic duct or CBD are not dilated; there is a high risk of intraoperative CBD injury in such circumstances. Laparoscopic management was considered to be especially useful for the treatment of numerous, large or difficult stones, because stone removal could be succesfully performed without any injury to the papilla of Vater. This last issue is of particular importance in patients with dilated CBD, because insufficient opening of the ampulla of Vater made by endoscopic sphincterotomy (EST) may lead to stasis and reflux-related complications such as cholangitis and recurrent stones. We conclude that the most rational management of CBD stones should be decided according to the size of the CBD, which depends on the size, number, and location of stones. Patients with dilated CBD are indicated to under-go laparoscopic single-stage treatment and combined endoscopic-laparoscopic treatment may be best for patients with non-dilated CBD.

Adolescent↗

PubMed1998

A T1083C polymorphism in the human adenosine A2a receptor gene is not associated with essential hypertension.

The adenosine A2a receptor (A2aAR) gene is thought to be involved in essential hypertension because adenosine elicits vasodilation and decreases arterial blood pressure via this receptor, and because disruption of the A2aAR gene increases blood pressure in mice. Therefore, using a restriction fragment length polymorphism (RFLP) of the A2aAR gene, we performed an association study in patients with essential hypertension. One hundred forty-two patients with essential hypertension and 142 age-matched subjects with normal blood pressure were studied. Polymerase chain reaction (PCR) was applied to amplify the T1083C polymorphic site in the A2aAR gene, and restriction analysis of the PCR product was employed to score the T and C alleles. Overall distributions of allele frequencies in the two groups were not significantly different. Thus, the alleles detected by this RFLP polymorphism in the A2aAR gene are not associated with essential hypertension.

Adult↗

PubMed1998

Regulatory roles of MgADP and calcium in tension development of skinned cardiac muscle.

We investigated the regulatory roles of MgADP and free Ca2+ in isometric tension development in skinned bovine cardiac muscle. We found that, in the relaxed state without free Ca2+, MgADP elicited a sigmoidal increase in active tension, as is the case in skeletal muscle (ADP-contraction). The critical MgADP concentration, at which the tension increment became half-maximal, increased in proportion to MgATP concentration, with a slope of approximately 1 for cardiac and 4 for skeletal muscle. Raising the free Ca2+ concentration decreased the critical MgADP concentration in proportion to the free Ca2+ concentration. In addition, the apparent Ca2+ sensitivity of tension development increased with MgADP, while decreasing with inorganic phosphate (Pi); MgADP suppressed the Ca(2+)-desensitizing effect of Pi in a concentration-dependent manner. These activating effects of MgADP were quantitatively assessed by means of a model based upon the kinetic scheme of actomyosin ATPase. These experimental results and model simulation suggest that the state of thin filaments is synergistically regulated by both the binding of Ca2+ to troponin and the formation of the actomyosin-ADP complex.

Actomyosin↗

PubMed1998

Bunazosin hydrochloride inhibits exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats by suppressing the response to growth factors.

Selective alpha1-adrenoreceptor blockers were recently reported to have an in vivo antiproliferative effect on hypertensive cardiovascular organs. Cultured vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive rats (SHRs) show exaggerated growth compared with cells from Wistar-Kyoto (WKY) rats. We investigated the effects of an alpha1-adrenoreceptor blocker, bunazosin hydrochloride (HCl), on the growth of VSMCs from SHRs. In the absence of serum, bunazosin HCl significantly inhibited basal DNA synthesis by VSMCs from SHRs, but not by cells from WKY rats. In the presence of serum, bunazosin HCl significantly inhibited DNA synthesis by VSMCs from both rat strains. Angiotensin (Ang) II, platelet-derived growth factor (PDGF)-AA, and epidermal growth factor (EGF) dose-dependently increased DNA synthesis by VSMCs from SHRs, but not by VSMCs from WKY rats. Bunazosin HCl significantly suppressed the response of DNA synthesis to PDGF-AA and EGF, but not to Ang II, in VSMCs from SHRs. Expression of basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGFbeta1), and PDGF messenger RNA (mRNA) was markedly greater in VSMCs from SHRs than in cells from WKY rats. Bunazosin HCl significantly inhibited the expression of bFGF and TGFbeta1 mRNA in VSMCs from SHRs, but not in cells from WKY rats. These findings suggest that the inhibition of growth factor hyperresponsiveness and inhibition of the expression of growth factors in VSMCs from SHRs are associated with the antiproliferative effect of bunazosin.

Adrenergic alpha-Antagonists↗

PubMed1998

Gender differences in self-evaluated sleep quality and activity of middle-aged and aged subjects.

In order to investigate the gender difference of sleep and activity in middle-aged and aged individuals, home-based sleep was self-evaluated for sleep quality and activity for 5 nights in 20 healthy adults (50-76 years old; 11 women, nine men). There was no significant gender difference for subjective sleep quality. However, the activity level and movement index at night were significantly higher in men than in women, and the activity level during the day was significantly lower in men than in women. The objective sleep quality of men was significantly worse than that of women, however, subjective sleep quality does not differ.

Activity Cycles↗

PubMed1998

Gender differences in the sleep of middle-aged individuals.

The study was designed to investigate gender differences in the sleep-wake patterns of healthy middle-aged individuals in their home environment. Polysomnography showed that daytime napping was more common in men than in women. Men had lower sleep efficiency index and experienced more stage 1 sleep. Males had significantly less stages 3 + 4 sleep, less stage REM sleep, and more transitions to wake from REM sleep. Men could not maintain stage REM as well as women. This study indicates that the gender differences in the sleep-wake patterns have appeared in a group of middle-aged individuals.

Aged↗

PubMed1998

Motor activity rhythm in dementia with delirium.

Using an actigraph, the activity patterns in 13 demented patients with delirium were examined. We analyzed the data of the eight patients, wearing the actigraphs for more than 10 days. They were classified into four types: type A, nocturnal delirium type; type B, wandering type; type C, hypobulia type; and type D, lying down type. The day to day activity variation was most prominent in type A and seemingly the least in type B. The dominant period of activity rhythm was nearly 24 h in all cases. Additional 12-h period was observed in type C. Actigraphs might become useful in making therapeutic decisions regarding demented patients with delirium.

Activity Cycles↗

PubMed1998

Effects of short duration morning bright light in healthy elderly subjects. I: subjective feeling and ophthalmological examinations.

Seven aged subjects aged 61-78 years were exposed to 6000 lx bright light for 30 min during morning hours at their homes for 1 week. Visual analog scale was recorded before bedtime and after rising to assess subjective feelings. Ophthalmological examinations were made before and after light exposure, to exclude pre-existing ocular disorders and to detect ocular damage. Furthermore, ocular fatigue was self-evaluated immediately before and after exposure. Visual analog scale results indicated that alertness reduced significantly before bedtime. Ophthalmological abnormalities were not found after exposure. These findings suggest that short duration morning bright light exposure reduces night-time vigilance.

Aged↗

PubMed1998

Effects of short duration morning bright light in healthy elderly. II: sleep and motor activity.

Subjective sleep feelings and motor activity were measured in seven healthy elderly subjects for 6 days. The subjects were exposed to bright light (6000 lux) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. The average level of motor activity during the night was significantly decreased in the bright light condition, compared with the controlled condition. However, daytime motor activity did not show significant differences between the two conditions. From these findings, even a short duration of morning bright light is effective in maintaining sleep without changing daytime activity.

Activity Cycles↗

PubMed1998

Relationship between left atrial function and plasma level of atrial natriuretic peptide in patients with heart disease.

To investigate the relationship between left atrial function and secretion of atrial natriuretic peptide (ANP), we analyzed left ventricular inflow and pulmonary venous flow, left atrial dynamics, intracardiac pressures, and plasma ANP level in 92 patients with various cardiac diseases. From the apical four-chamber view, maximal left atrial volume and percent fractional change of the left atrial area during atrial systole (LA-%AC) were calculated. The ratio of peak early filling velocity to peak atrial systolic velocity (E/A) in the left ventricular inflow and the ratio of peak systolic velocity to peak diastolic velocity (S/D) in the pulmonary venous flow were measured with the pulsed Doppler method. A significant linear correlation was found between plasma ANP levels and pulmonary capillary wedge pressure. Significant linear correlations were also found between left ventricular end-diastolic pressure and both maximal left atrial volume and LA-%AC. Plasma ANP level was significantly correlated with maximal left atrial volume, LA-%AC, E/A, and S/D. A multivariate analysis revealed that only LA-%AC was significantly correlated with the plasma ANP level. These results suggest that left atrial systolic dysfunction associated with a left atrial afterload mismatch is closely related to the ANP secretion.

Aged↗

PubMed1998

Abnormal regulation of transforming growth factor-beta receptors on vascular smooth muscle cells from spontaneously hypertensive rats by angiotensin II.

The effects of angiotensin II (Ang II) on the expression and characteristics of transforming growth factor-beta (TGF-beta) receptors on vascular smooth muscle cells (VSMC) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were investigated. TGF-beta-induced stimulation of DNA synthesis by VSMC from WKY rats was abolished with Ang II, whereas basal and TGF-beta-stimulated DNA synthesis by VSMC from SHR was increased with Ang II. Ang II stimulated DNA synthesis by VSMC from WKY rats in the presence but not in the absence of neutralizing antibody to TGF-beta1. Antibody to TGF-beta1 enhanced the stimulatory effect of Ang II on DNA synthesis by VSMC from SHR. Ang II increased the specific binding of TGF-beta to VSMC from WKY rats by increasing both the expression of the lower-affinity of TGF-beta receptors as well as the total number of TGF-beta binding sites. In contrast, VSMC from SHR showed a higher affinity and number of TGF-beta receptors in the absence of Ang II than did cells from WKY rats, and these parameters were not affected by Ang II. Ang II increased the expression of TGF-beta type I receptor mRNA in VSMC from WKY rats but had no effect of TGF-beta receptor type I or II mRNA in VSMC from SHR, which predominantly express the type II receptor. These results indicate that an increase in the expression of the TGF-beta type I receptor by Ang II may facilitate the ability of endogenous TGF-beta to counteract the stimulatory effect of Ang II on growth in VSMC from WKY rats, whereas endogenous TGF-beta induced by Ang II cannot counteract the growth-promoting action of Ang II in VSMC from SHR. The abnormal regulation of TGF-beta receptors by Ang II may be associated with the exaggerated growth of VSMC from SHR.

Angiotensin II↗

PubMed1998

Echocardiographic assessment of right atrial function in patients with myocardial infarction with reference to obstructive lesions of the coronary arteries.

We assessed the relationship between right atrial (RA) function and obstructive lesions of the coronary arteries in 29 patients with recent or old myocardial infarction (MI). Patients were divided into 3 groups according to the location of obstructions as follows: obstruction at the proximal right coronary artery (segments 1 and 2) (RCA proximal group, n=9); obstruction at the distal RCA (segments 3 and 4) (RCA distal group, n=6); and obstruction at the left anterior descending coronary artery (LCA group, n=14). The RA volume and the fractional change in the RA area during atrial contraction (RA %AC) were evaluated by apical 2-dimensional echocardiography. The right ventricular (RV) end-diastolic pressure (RVEDP) was measured in 4 patients in the RCA proximal group and 4 patients in the LCA group. The ejection fraction of the right ventricle (RVEF) was measured by radionuclide angiography or 2-dimensional echocardiography in 7 patients in the RCA proximal group, 5 patients in the RCA distal group, and 7 patients in the LCA group. The RVEF tended to be lower in the RCA proximal group than in the RCA distal and LCA groups. The RA volume was significantly greater in the RCA proximal group than in the LCA group. The RA %AC was significantly smaller in the RCA proximal group than in the RCA distal and LCA groups. There were no significant differences in the early diastolic RV inflow velocity among groups, but the late diastolic RV inflow velocity was significantly lower in the RCA proximal group than in the RCA distal and LCA groups. There was no significant difference in the RVEDP between the RCA proximal and LCA groups. Thus, RA dysfunction in the RCA proximal group appeared to be due to myocardial damage rather than to afterload mismatch. These findings suggest that RA dysfunction may occur in patients with an inferior MI who have an obstructive lesion of the proximal RCA.

Aged↗

PubMed1998

Difference in systolic motion velocity of the left ventricular posterior wall in patients with asymmetric septal hypertrophy and prior anteroseptal myocardial infarction. Evaluation by pulsed tissue Doppler imaging.

The left ventricular (LV) posterior wall in patients with asymmetric septal hypertrophy or prior anteroseptal myocardial infarction (A-MI) frequently demonstrates normal or supernormal motion to compensate for hypokinesis of the interventricular septum. This study evaluated the systolic motion velocity of the posterior wall in these conditions using a pulsed tissue Doppler imaging system. The study population consisted of 30 patients with hypertrophic cardiomyopathy (HC) and asymmetric septal hypertrophy, 25 with prior A-MI and 30 normal controls. The systolic excursion of the posterior wall was obtained by M-mode echocardiography. The endocardial motion velocities of the posterior wall were obtained by pulsed tissue Doppler imaging. The systolic excursion of the posterior wall was significantly greater in the A-MI and HC groups than in the control group, and was significantly greater in the A-MI group than in the HC group. The peak systolic velocity of the posterior wall was significantly lower in the HC group than in the control and A-MI groups, and the time from the electrocardiographic Q wave to the peak of the systolic wave of the posterior wall was significantly longer in the HC group than in the other groups. There were rough negative and positive correlations between the LV end-diastolic pressure and the peak systolic velocity and time from the Q wave to the peak of the systolic wave, respectively. In conclusion, LV myocardial contractility in HC patients was impaired when compared to A-MI patients despite similar posterior wall motion on the M-mode echocardiogram. Pulsed tissue Doppler imaging method may provide new insights and allow further evaluation of myocardial dysfunction.

Cardiac Catheterization↗

PubMed1998

Right heart flow dynamics after tricuspid valve annuloplasty. Characteristics and time course.

To evaluate the effect of tricuspid annuloplasty (TAP) on right heart flow dynamics, we analyzed tricuspid inflow velocity pattern, jugular venous pulse and color Doppler flow signal of tricuspid regurgitation (TR) before and after surgery in 16 patients who underwent TAP (TAP group). Cardiac rhythm was atrial fibrillation in all patients. Twelve patients with lone atrial fibrillation served as controls (AF group). Patients in the TAP group were studied before and serially after surgery with a mean follow-up period of 2.7 years. TAP was performed according to the modified De Vega technique in all patients. In a comparison of the most recent data in the TAP group and the data in the AF group, the maximum tricuspid inflow velocity was significantly increased, and both the deceleration time of the tricuspid inflow velocity wave and the y-h interval of the jugular venous pulse were significantly prolonged in the TAP group compared to the AF group. Immediately after surgery, in the TAP group, the area of the TR jet was markedly decreased, and the deceleration time of the tricuspid inflow velocity wave was significantly prolonged compared to those before surgery. The area of the TR jet was dramatically decreased and remained small during the follow-up period. Thus, TAP may produce mild tricuspid stenosis but may also confer sustained preventive effects against TR.

Adult↗

PubMed1998

Relationship between flow dynamics in the left atrium and hemostatic abnormalities in patients with nonvalvular atrial fibrillation.

To investigate the relationship between left atrial (LA) flow dynamics and hemostatic markers in nonvalvular atrial fibrillation (AF), 45 patients with nonvalvular AF who had not received anticoagulants were evaluated by transesophageal echocardiography. We determined the LA appendage flow and the presence of LA spontaneous echo contrast (SEC) or thrombus. We measured plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 in peripheral blood as hemostatic markers. The patients were divided into a low-velocity group (n = 19; sum of peak emptying and filling LA appendage flow velocities < 40 cm/s) and a high-velocity group (n = 26; > or = 40 cm/s). The maximum LA diameter was significantly greater and the LA expansion fraction was significantly smaller in the low-velocity group than in the high-velocity group. LA SEC or thrombus was observed in 11 patients (58%) in the low-velocity group, but not in any patients in the high-velocity group (p < 0.001). The plasma levels of TAT, fibrinopeptide A, D-dimer, beta-thromboglobulin, and platelet factor 4 were significantly higher in the low-velocity group than in the high-velocity group. The plasma levels of TAT, fibrinopeptide A, beta-thromboglobulin, and platelet factor 4 were significantly higher in 8 patients without LA SEC or thrombus in the low-velocity group than in 26 patients in the high-velocity group. Patients with nonvalvular AF accompanied by an enlarged and dysfunctioning LA and a decreased LA appendage flow velocity had increased intravascular coagulation-fibrinolysis activity and platelet activation. These abnormalities may be closely related to the thrombogenetic state in patients with nonvalvular AF.

Adult↗