Search PubMed⌕ Search

Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 181 records · Page 10Linked to original sources

Distinct expression of transforming growth factor-beta receptor subtypes on vascular smooth muscle cells from spontaneously hypertensive rats and Wistar-Kyoto rats.

1. We investigated the characteristics and expression of transforming growth factor-beta (TGFbeta) receptor subtypes on vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. TGFbeta binding assays revealed that VSMC from SHR showed higher number and affinity of TGFbeta receptors than cells from WKY rats. 3. The affinity labelling with [125I]-TGFbeta1 revealed the presence of TGFbeta receptor subtypes with molecular sizes of 280, 85, 70 and 60kDa on VSMC from both strains at high cell density. The abundance of the 85kDa receptor subtype was greater in VSMC from SHR than cells from WKY rats. The 85kDa receptor subtype was not detected on VSMC from both strains at low cell density. 4. These results suggest distinct expression of TGFbeta receptor subtypes on VSMC from SHR and WKY rats, which may account for the exaggerated proliferative response of VSMC from SHR to TGFbeta.

Affinity Labels↗

Molecular basis for the management of secondary hyperparathyroidism in chronic renal failure.

Recent clinical and experimental data suggest that the resistance of parathyroid cells to the physiological concentration of calcitriol plays an important role in the pathogenesis and the progression of secondary hyperparathyroidism in chronic renal failure. This resistance is due to the decreased density of the calcitriol receptor in parathyroid cells, which may result from impaired upregulation of calcitriol receptor. Since patients with larger parathyroid glands were more resistance to calcitriol pulse therapy than those with smaller glands and calcitriol receptor density inversely correlated with gland weight, the size of the parathyroid gland may serve as a marker for the degree of resistance to calcitriol. Furthermore, the possible role of phosphorus in the control of parathyroid function has been suggested recently. Thus, it is most important to prevent the progression of parathyroid hyperplasia in chronic renal failure by the early use of active vitamin D, calcitriol pulse therapy, and dietary phosphorus restriction.

Animals↗

Effect of dietary antioxidants on the susceptibility to hepatic microsomal lipid peroxidation in the rat.

The inhibitory effect of probucol on ferrous-iron-induced microsomal lipid peroxidation was compared to that of alpha-tocopherol and butylated hydroxytoluene (BHT). Male Wistar rats were fed with diets containing 1% probucol, 0.2% BHT or 0.1% alpha-tocopherol for 30 days. There were no effects of dietary antioxidants on growth parameters, although liver weight was significantly higher in the BHT-fed rats. Probucol reduced serum levels of total and free cholesterol, while BHT feeding increased the concentrations of serum thiobarbituric-acid-reactive substances, HDL cholesterol and hepatic phospholipid. alpha-Tocopherol had no effect on these parameters. Incorporation of both, probucol and alpha-tocopherol, decreased the susceptibility of microsomes to lipid peroxidation in vitro, while BHT incorporation increased hepatic microsomal lipid peroxidation. These results suggest the possible usefulness of probucol for treatment of both hypercholesterolemia and elevated hepatic microsomal lipid peroxidation, while alpha-tocopherol decreases only an elevated lipid peroxidation. BHT works as a prooxidant.

Animals↗

Differential effects of geometrical isomers of octadecadienoic acids on ketogenesis and lipid secretion in the livers from rats fed a cholesterol-enriched diet.

The effect of cis,cis (cc)- and trans,trans (tt)-9,12-octadecadienoic (18:2) acids on ketogenesis and lipid secretion was compared in isolated perfused livers from cholesterol-fed rats. The hepatic uptake of 18:2 acids was comparable in both isomers. The livers perfused with cc-18:2 acid in comparison with those perfused without fatty acid substrate produced approximately 4-fold more ketone bodies accompanying the rise of the beta-hydroxybutyrate:acetoacetate ratio, while the tt-acid isomer further increased these parameters. The hepatic secretion rates of triglyceride and phospholipid as well as cholesterol were all elevated on perfusing the cc-18:2 acid as compared to without fatty acid. In contrast, the rates observed with the tt-18:2 acid isomer except for phospholipid were intermediate, indicating a reciprocal response in ketogenesis and lipid secretion by the trans isomer. The rate of incorporation of trans-fatty acid into perfusate triglyceride and cholesterol ester were lower than cis-acid, but vice versa into perfusate phospholipids. On the other hand, the effects of trans-fatty acid on the concentration and composition of hepatic lipids were less clear. These results emphasize the differential effect of geometrical isomers of the 18:2 acids on oxidation and esterification even in the livers containing a high level of cholesterol.

3-Hydroxybutyric Acid↗

Evaluation of left ventricular diastolic hemodynamics from the left ventricular inflow and pulmonary venous flow velocities in hypertrophic cardiomyopathy.

We evaluated the characteristics of left ventricular diastolic hemodynamics in hypertrophic cardiomyopathy (HCM) by measuring left ventricular inflow (LVIF) and pulmonary venous flow (PVF) velocities in 62 patients with asymmetric septal hypertrophy and 34 normal controls. The patients were divided into four groups according to the LVIF pattern and left ventricular end-diastolic pressure (LVEDP): 1) the pseudonormalization group; 13 patients with the ratio of peak atrial systolic (A) to early diastolic (E) LVIF velocity (A/E) < or = 1 and LVEDP > or = 15 mm Hg, 2) the normal pattern group; 10 patients with the A/E < or = 1 and LVEDP < 15 mm Hg, 3) the relaxation failure group; 25 patients with the A/E > 1, and 4) the mid-diastolic wave group; 14 patients with a mid-diastolic wave. The peak early diastolic LVIF velocities in the pseudonormalization, relaxation failure and mid-diastolic wave groups were significantly smaller than in the control group. The deceleration time from the peak of the E wave and the isovolumic relaxation time were significantly prolonged in the relaxation failure and mid-diastolic wave groups. The peak diastolic PVF velocity in the relaxation failure and mid-diastolic wave groups was significantly decreased, and was significantly increased in the pseudonormalization group. The peak atrial systolic PVF velocity was significantly increased in all patients with HCM, particularly in the pseudonormalization group. LVEDP was the highest in the pseudonormalization group, followed by the mid-diastolic wave, relaxation failure and normal pattern groups, in that order. In conclusion, combined analysis of the LVIF and PVF provides useful information regarding various abnormalities of left ventricular diastolic hemodynamics in patients with HCM.

Adult↗

The first heart sound in atrial septal defect with reference to atrioventricular valve motion and hemodynamics.

To clarify the characteristics of the first heart sound in atrial septal defect (ASD) and its pathophysiological basis, 17 patients with ASD associated with incomplete right bundle branch block (IRBBB) and 7 with isolated IRBBB were studied using phonoechocardiography and Doppler echocardiography. Fifteen of the 17 ASD patients also were studied following surgical closure of the defect. Indices were compared among the preoperative ASD, postoperative ASD, and IRBBB groups including: P-Q intervals, loudness of the mitral and tricuspid component of the first heart sound (IM, IT), end-diastolic closing excursions of the mitral and tricuspid valves (Mx, Tx), and mitral and tricuspid inflow velocities during early diastole and atrial contraction. There were no significant differences in the P-Q intervals among these 3 groups. IM was attenuated, and IT was accentuated in ASD compared with IRBBB. Postoperatively, IM was augmented in all but 1 patient and IT was attenuated in all patients. Mx was significantly smaller, and Tx was significantly larger in ASD than in IRBBB. Postoperatively, Mx was significantly increased and Tx was significantly reduced; the maximal mitral inflow velocity during atrial contraction was increased while the maximal tricuspid inflow velocity was significantly reduced. Thus, the first heart sound in ASD is characterized by an attenuated mitral component and an accentuated tricuspid component. Hemodynamic alterations and consequent changes in closing energies of the atrioventricular valves probably account for these features.

Adolescent↗

[Transesophageal echocardiographic study on the mechanisms of mitral regurgitation in hypertrophic cardiomyopathy: comparison with sigmoid septum].

Transesophageal echocardiography was performed to elucidate the mechanisms of mitral regurgitation (MR) in 40 patients with hypertrophic cardiomyopathy with asymmetric septal hypertrophy, 15 obstructive and 25 nonobstructive, and the organic changes of the mitral leaflet were compared to those of 30 patients with sigmoid interventricular septum. Thirty subjects without cardiac diseases served as the control group. Transthoracic and transesophageal echocardiography were performed in all subjects to measure the following: left ventricular dimension, interventricular septal thickness and peak velocity at the left ventricular outflow tract by transthoracic echocardiography; the lengths and the thicknesses of the rough zone of the anterior and posterior mitral leaflets at mid-diastole and the distance between the tip of the posterior papillary muscle and the anterior mitral annulus by transesophageal echocardiography. The presence of systolic anterior motion of the mitral complex, contact between the anterior mitral leaflet and the interventricular septum during diastole, and the occurrence of mitral valve prolapse (MVP) were also investigated. The maximum area and timing of MR during systole was measured by M-mode color Doppler technique. The following results were obtained. 1. MR was observed in 35 (88%) of the 40 patients with hypertrophic cardiomyopathy. The maximum regurgitant area in the obstructive group was significantly greater than in the other groups, and the regurgitation was frequently pansystolic. 2. The lengths of both mitral leaflets at mid-diastole were significantly greater in both groups with hypertrophic cardiomyopathy than in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Changes in pulmonary venous and transmitral flow velocity patterns after cardioversion of atrial fibrillation].

The time course of recovery of left atrial mechanical function after electrocardioversion of atrial fibrillation was examined in 25 patients with atrial fibrillation by recording pulmonary venous and transmitral flow velocities and interatrial septal motion during atrial systole within a day (16 +/- 5 hours) and ten days after cardioversion of atrial fibrillation by transesophageal and transthoracic Doppler and M-mode echocardiography. There were 6 patients with hypertension, 4 with ischemic heart disease, 2 with alcoholic heart, 5 with dilated cardiomyopathy, and 8 without underlying heart disease. The peak velocities of the atrial systolic waves of the transmitral and pulmonary venous flow velocities (A and PVA, respectively) and first systolic wave (PVS1) of pulmonary venous flow, durations of both atrial systolic waves, and amplitude of interatrial septal motion during atrial systole increased significantly ten days after cardioversion compared with those measured within a day of cardioversion in all patients except the 5 patients with dilated cardiomyopathy. Peak velocity of the second systolic wave (PVS2) of pulmonary venous flow increased, and that of the early diastolic and diastolic waves (E and PVD, respectively) of transmitral and pulmonary venous flow decreased ten days after cardioversion compared with those within a day of cardioversion. These results suggested that active atrial systolic (A and PVA) and relaxant (PVS1) parameters obtained from transmitral and pulmonary venous flow velocities are good indicators of left atrial mechanical function after cardioversion of atrial fibrillation.

Adult↗

Deuterium MR in vivo imaging of the rat eye using 2H2O.

In vivo deuterium MR imaging (2H MR) was investigated in rats after intraperitoneal administration of deuterated saline, and a dynamic study of the water movement in rat eyes was performed. Deuterium MR imaging was carried out by means of a gradient-echo (GRE) and a spin-echo (SE) pulse sequence. The rat eye was imaged in 2H MR more selectively by SE than by GRE, but a lower signal-to-noise ratio was obtained in 2H MR imaging using the SE sequence. The MR signal intensity of the rat eye was followed by a 3-compartment model, which enabled determination of the flow rate constant of the water in the eye (0.359/min). Deuterium MR imaging is useful to visualize the dynamic change of water in rat eyes using 2H MR at the same magnetic field (2 T) that can also be used for conventional MR imaging in humans.

Animals↗

[Changes in biological rhythm and sleep structure during the menstrual cycle in healthy women].

It is well known that clinical symptoms such as psychosis, epileptic seizures and sleep disturbances aggravate around the time of menstruation. In some healthy women, subjective sleep feelings or moods have been reported to change throughout the menstrual cycle, which suggests that sleep structure and sleep-wake rhythm may change during the menstrual cycle. We investigated a circadian pattern of plasma melatonin, sleep-wake rhythm and sleep characteristics in the different phases of the menstrual cycle in young healthy women under controlled environmental conditions. The subjects were seven healthy women, aged 18 to 19, with regular menstrual cycles. They stayed in an experimental facility, where temperature and humidity were kept within a narrow range, for three days in successive five weeks. They got up and went to bed at their preferable time. Polysomnography was performed using ambulatory cassette EEG system on the first and second night. Sleep stages were scored according to Rechtshaffen and Kales' criteria. Plasma melatonin was measured at 1-hour intervals for 24 hours on the third day. The menstrual cycle was divided into four phases (menstruation, follicular, early luteal and late luteal). Although the plasma melatonin level in the late luteal phase tended to be higher than in other phases, no significant difference was observed across four phases. The phase in plasma melatonin level did not change. As for sleep-wake rhythm, the time of getting up on the first day was significantly late in the late luteal phase (p < 0.05), although it showed no significant change on the second day. The time of going to bed did not change. Sleep characteristics changed during the menstrual cycle. There was a significant difference in the amount of stage 3 + 4, slow wave sleep (p < 0.05), which was more abundant in the follicular phase than in the luteal phase. TIB (time in bed), SPT (sleep period time), TST (total sleep time) seemed to increase in the menstrual and follicular phases, while stage W increased in the early and late luteal phases. However, there were no significant differences in these parameters. The other parameters did not show any changes. The changes in amount of stage 3 + 4 throughout the menstrual cycle seem to be due to endogenous factors, because environmental factors were controlled in this experiment. It is possible that the menstrual cycle also affect the plasma melatonin level and sleep-wake rhythm.

Adolescent↗

Histopathologic studies of innervation of normal and prolapsed human mitral valves.

We evaluated the distribution of the nerves in valve tissue of humans to clarify the relationship between mitral valve prolapse and autonomic nerve dysfunction. We studied 15 autopsy specimens of normal mitral valve, 10 prolapsed mitral valves, five each of normal tricuspid, aortic, and pulmonary valves, and three prolapsed mitral valves obtained at cardiac surgery. Immunohistochemical studies utilized the avidinbiotin peroxidase complex (ABC) method and several nerve-related antigens: 1) S-100 protein, glial fibrillary acidic protein (GFAP), and neurofilament protein (NFP) as markers of glial and Schwann cells of the nervous system; 2) choline acetyltransferase (ChAT) to identify cholinergic nerve endings; 3) neuropeptide Y (NPY), a neuropeptide that is distributed in accordance with sympathetic nerves; and 4) calcitonin gene-related peptide (CGRP), a neuropeptide that is distributed in accordance with afferent nerves. Distribution of adrenergic nerve fibers was also examined by fluorescence method. Morphology of nerve endings of the normal mitral valve was studied by electron microscopy. In normal valves, distributions of S-100 protein, GFAP, and NFP immunoreactivities were clearly visible along the subendocardial site on the coaptation aspect of the base-to-body portion of each valve, regardless of the kind of valve. In contrast, there was only a scanty distribution of these reactivities on the physiologic coaptation area of the tip. In prolapsed mitral valves, there was no distribution of S-100-positive protein or other nerve-related antigens in areas of the valve with myxomatous degeneration. Distribution of CGRP, ChAT, and NPY immunoreactivities, and adrenergic fluorescence, were the same as those of the nerve-related antigens in both normal and prolapsed mitral valves. Electron microscopic study of the atrial aspect of normal mitral valves revealed numerous small axons with aggregations of small clear vesicles, indicating cholinergic features. The results suggest that the subendocardial site on the atrial aspect at the middle portion of the mitral valve is rich in nerve endings, including the afferent nerves, and that mechanical stimuli from this area caused by abnormal coaptation in mitral valve prolapse may produce an improper circuit in autonomic nerve function between the central and mitral valve nervous systems.

Adult↗

Minimum description principle applied to construction of molecular phylogenetic tree.

Ever since the discovery of a molecular clock (constancy of molecular evolutionary rate), many methods have been developed to estimate the molecular evolutionary phylogenetic trees from the homologous nucleic sequences of different species. In this paper, we deal with this problem from the view point of an inductive inference, and apply Rissanen's minimum description length principle to extract the minimum complexity phylogenetic tree. Five mitochondrial DNA sequences from human, common chimpanzee, pygmy chimpanzee, gorilla, and orangutan are used for investigating the validity of this method. It is found that this method is superior to the traditional method in that it still shows a high degree of accuracy, even near the root of phylogenetic trees.

Animals↗

Ameliorative effect of dietary probucol on polychlorinated biphenyls-induced hypercholesterolemia and lipid peroxidation in the rat.

The hypocholesterolemic and antioxidant activities of probucol (PB) were examined in rats which were fed for 10 days with diets supplemented with or without 0.02% polychlorinated biphenyls (PCB). Dietary intake of PCB caused multiple effects on lipid metabolism, such as increased levels of both serum and HDL cholesterol, and increased TBA-reactive substances (TBARS), in hepatic subcellular fractions. PB 1% in comparison with either control or alpha-tocopherol (Toc) 0.1%, reduced the serum cholesterol levels in normolipemic as well as in PCB-induced hypercholesterolemic rats. In addition, this drug ameliorated the elevated TBARS induced by PCB in the hepatic subcellular fractions, although less antioxidant activity was noted in rats fed PB than in those fed Toc. The microsomes isolated from various groups were incubated for 2h at 37 degrees C in the presence or the absence of ferrous iron in vitro; microsomes from the PB-fed rats were as much resistant against lipid peroxidation in ferrous-free incubation medium as were those from Toc-fed rats, while in the presence of ferrous iron there was a higher antioxidant effect on lipid peroxidation in the latter fraction than in the former. HPLC analyses showed that less PB than Toc was incorporated into the hepatic subcellular fractions, suggesting that the concentration of antioxidants in hepatic subcellular fractions determine the extent of lipid peroxidation in situ. These results suggest that the administration of PB is an effective approach for the treatment of both hypercholesterolemia and elevated lipid peroxidation while Toc ameliorates only an elevated lipid peroxidation.

Animals↗

Serial evaluation of parathyroid size by ultrasonography is another useful marker for the long-term prognosis of calcitriol pulse therapy in chronic dialysis patients.

To clarify whether the changes of parathyroid size have any correlations with the long-term prognosis of calcitriol pulse therapy, we examined the time course of serum levels of parathyroid hormone (PTH) and size of parathyroid glands in 14 chronic dialysis patients during and after the oral calcitriol pulse therapy. In 5 patients without any detectable glands, secondary hyperparathyroidism was easily controlled by calcitriol pulse therapy and then by conventional oral active vitamin D therapy. In 2 patients with detectable gland(s) in whom size of all parathyroid glands as well as PTH hypersecretion regressed to normal by calcitriol pulse therapy, secondary hyperparathyroidism could then remain controlled at least for 12 months after switching to conventional oral active vitamin D therapy. In contrast, in 7 patients in whom size of all parathyroid glands did not regress to normal by calcitriol pulse therapy, secondary hyperparathyroidism relapsed after switching to the conventional therapy, even if PTH hypersecretion could be controlled temporarily. Our findings suggest that the time course of parathyroid hyperplasia detected by ultrasonography is an important determinant of the efficacy and the prognosis of calcitriol pulse therapy. Thus, the change of parathyroid gland size as well as PTH hypersecretion should be taken into account for the management of secondary hyperparathyroidism.

Administration, Oral↗