Search PubMed⌕ Search

Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 109 records · Page 6Linked to original sources

Dose-response relationship for induction of solid tumors in female B6C3F1 mice irradiated neonatally with a single dose of gamma rays.

Our previous studies showed that mice during infancy are highly susceptible to the induction of several types of solid tumors. The present study was designed to elucidate the dose-response relationships for induction of solid tumors after exposure to 0.48-5.70 Gy of 137Cs gamma rays in the neonatal period in female mice. A total of 2988 mice were allowed to live out their life span under a specific pathogen free condition and lifetime incidences of liver, pituitary, ovarian, lung and bone tumors were recorded. The dose-response curves for liver, pituitary, ovarian and lung tumors were convex upward in the dose range examined, and were composed of three parts: an initial rapid increase of incidence at doses below 1 Gy, a gradual increase to the highest incidence, and a decrease in incidence with increasing dose in the higher dose range. The dose which induces neoplasm at the highest incidence seemed to be different for each type of solid tumor. The shape of the dose-response curve for induction of bone tumors was quite different from that for other solid tumors; the initial slope of the curve was concave upward. Dose-response relationships were analyzed using a model that allows for tumorigenic effect, inactivation of potentially tumorigenic cells and competing risks. The results showed that the tumorigenic effect was proportional to the dose of gamma rays for induction of liver, pituitary, ovarian and lung tumors; whereas the tumorigenic effect for bone tumors was proportional to the square of the dose. A significant increase in incidence was also found for gastrointestinal tumors, kidney tumors, adrenal tumors and hemangiomas of spleen, although dose-response relationships could not be analyzed.

Animals↗

Effect of dietary sesamin on metabolic fate of an exogenous linolelaidic acid in perfused rat liver.

To estimate the relative significance of exogenous and endogenous fatty acid substrates in decreasing hepatic triacylglycerol secretion after sesamin feeding, livers from rats fed diets supplemented with and without sesamin (sesamin: episesamin, 1:1, w/w) were perfused in the presence and absence of an exogenous di-trans isomer of linoleic acid (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Both exogenous trans fatty acid and dietary sesamin, as compared with respective controls, resulted in a marked increase in hepatic ketogenesis; however, the beta-hydroxybutyrate to acetoacetate ratio was elevated by exogenous fatty acid and decreased by dietary sesamin. On the other hand, hepatic secretions of triacylglycerol, phospholipid and cholesterol were markedly lowered in rats fed sesamin, especially when exogenous fatty acid substrate was provided. The relative significance of the exogenous fatty acid was observed in the dietary sesamin-induced decrease in hepatic secretion of triacylglycerol. These results suggest that increased fatty acid oxidation by dietary sesamin, as reflected by enhanced ketone body production, leads to decreased partition of fatty acid substrates to the esterification pathways, and this in turn reduces the synthesis and secretion of triacylglycerol. The altered metabolism of exogenous fatty acids in the liver was therefore a major determinant for the synthesis and secretion of triacylglycerol.

Animals↗

[Hypertensive heart disease with left ventricular diastolic dysfunction demonstrating restrictive hemodynamics: a case report].

A 47-year-old man with hypertensive heart disease and left heart failure due to left ventricular diastolic dysfunction was admitted to our hospital because of emergent hypertension. Chest radiography on admission showed slight cardiomegaly and mild pulmonary congestion with right pleural effusion Echocardiography showed concentric hypertrophy and normal contraction of the left ventricular wall Pulsed Doppler left ventricular inflow velocity wave and pulmonary venous flow velocity wave disclosed restrictive filling patterns. After Ca antagonist, nitrate, and diuretics were administered, blood pressure was normalized, and left ventricular inflow velocity wave showed the relaxation abnormality pattern and pulmonary venous flow velocity wave showed the normal pattern. Radioiodinated iodine-123 metaiodobenzyl guanidine (123I-MIBG) imaging in the state of normalized blood pressure showed decreased heart to mediastinum ratio and increased washout rate. Left heart catheterization and angiography revealed normal end-diastolic pressure and coronary arteries, but coronary flow reserve evaluated with Doppler flow wire and intracoronary adenosine triphosphate administration was impaired: Plasma level of atrial and brain natriuretic peptides, which were markedly elevated on admission, decreased with the improvement of heart failure. Doppler flow velocity patterns, plasma levels of atrial natriuretic peptide and brain natriuretic peptide, cardiac sympathetic nerve activity, and coronary flow reserve might be useful for evaluating the severity of left ventricular diastolic dysfunction in patients with hypertensive heart disease.

Atrial Natriuretic Factor↗

[Surgical treatment of 2 cases of irradiation induced constrictive pericarditis].

A 72-years-old man underwent radiation therapy (62 Gy) for esophageal carcinoma. Twelve months later, symptoms of heart failure such as syncope, cough and hepatomegaly manifested. On catheter study, a dip and plateau pattern of right ventricular pressure curve was evident. Pericardiectomy without extracorporeal circulation was performed. Operative findings and pathological results were compatible with radiation-induced constrictive pericarditis. He recovered from the heart failure, and has been doing well 3 months after the surgery. A 54-years-old man underwent thymectomy for malignant thymoma. He underwent a radiation therapy (52 Gy) postoperatively. After 12 months from the irradiation, syncope and dyspnea manifested. On catheter study, a dip and plateau pattern of right ventricular pressure curve was observed. Pericardiectomy with extracorporeal circulation was performed. He recovered from the heart failure after pericardiectomy, however he died of radiation-induced pneumonitis 6 months later.

Aged↗

[Epidural anesthesia and general anesthesia using the cuffed oropharyngeal airway for an obese patient with Duchenne's muscular dystrophy].

Duchenne's muscular dystrophy is a genetic disorder whose features include abnormal responses to muscular relaxants and possible respiratory dysfunction after general anesthesia. The purpose of this report is to describe one management strategy used successfully to anesthetize an obese man with this disorder for atypical mastectomy. The anesthetic management during surgery involves epidural anesthesia using 2% mepivacaine and general anesthesia using the cuffed oropharyngeal airway. Postoperatively 0.25% bupivacaine was infused for epidural analgesia. The patient was observed in the intensive care unit until the first postoperative day and showed an uncomplicated intra- and post-operative course.

Analgesia, Epidural↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗