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Biomedical subjects

N Fukuda

Publications and source records attributed to N Fukuda.

At least 199 records · Page 11Linked to original sources
PubMed1994

Effects of dietary fat levels on the absorption and tissue accumulation of probucol in the rat.

The effects of dietary fat level on the absorption and tissue accumulation of probucol (PB, CAS 23288-49-5) were studied in male Wistar rats. Addition of 1% PB (w/w) to the diets as compared to the diets without an addition (P) resulted in a decrease in the concentration of both serum and high-density lipoprotein (HDL) cholesterol as well as TBA-reactive substances (TBARS), without influencing food intake or growth. When rats were fed with the PB diet, the apparent intestinal absorption of PB was 7.9%, while the serum PB level was 5 micrograms/ml. The tissue distribution of PB, when expressed per g of tissue, was highest in the adrenal glands, followed by the liver, heart, epididymal adipose tissues, kidneys, lung, spleen, and testes. The addition of 10% olive oil (PBO) to the PB diet (w/w) appeared to double the PB diet-induced increase in apparent intestinal absorption and the serum concentration of PB. Furthermore, compared with the PB diet, the PBO diet caused 3- to 4-fold higher accumulation of PB in the liver and its subcellular fractions and 2-fold higher accumulation in the spleen. However, there was no further accumulation of the drug in the heart, kidneys, lungs, and testes. Incorporation of the drugs into adipose tissues was significantly lower with the PBO diet than with the PB diet. These results suggest that dietary manipulation leads to changes in the intestinal absorption and serum level of PB.

Animals↗
PubMed1994

Comparative phonocardiographic, echocardiographic and Doppler echocardiographic evaluation of normally functioning Medtronic Hall and Björk-Shiley mitral prosthetic valves.

Although data from cardiac catheterization and in vivo studies are available, phonocardiographic and ultrasonic characteristics of the Medtronic Hall valve in the mitral position have not been adequately established. Phonomechanocardiographic, echocardiographic and Doppler echocardiographic examinations were performed in 15 patients (Medtronic Hall group) with a Medtronic Hall mitral valve prosthesis to elucidate the phonocardiographic and ultrasonic characteristics of the normally functioning Medtronic Hall valve in the mitral position. These findings were compared with those obtained from 20 patients (Björk-Shiley group) with a normally functioning Björk-Shiley 60 degrees mitral valve prosthesis. Simultaneous recordings of the phonocardiogram and M-mode echocardiogram of the prosthetic valve in patients in the Medtronic Hall group revealed three opening clicks relating to disc motion. The timing of the three opening clicks correlated with the onset of disc opening, the completion of disc opening, and a notch which appeared about 30 msec after the completion of disc opening. Similar recordings performed in patients in the Björk-Shiley group revealed that the third opening click was detected in only half of the patients and that its timing was nearly twice as early as that noted in the Medtronic Hall group. The Medtronic Hall group had significantly shorter durations of the apical diastolic rumble and the slow filling wave on the apexcardiogram, as well as significantly reduced peak mitral inflow velocity during early diastole and shortened pressure half-time on the mitral inflow velocity curve. Transesophageal Doppler echocardiography demonstrated slight mitral regurgitation in all patients in both the Medtronic Hall and the Björk-Shiley groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Chromogranin A like immunoreactivity in respiratory tissues of ovalbumin-sensitized guinea pigs].

Chromogranin A like immunoreactivity (CGA-IR) was measured by a specific radioimmunoassay using N-terminal specific antiserum R-0763 in respiratory tissues of guinea pigs. All guinea pig were actively immunized by recurrent Ovalbumin (OA)-inhalation and divided into two groups; one was challenged by OA, and the other inhaled saline as a control. These groups were studied for respiratory resistance and sacrificed for measurement of CGA-IR concentrations in the trachea, major bronchus and lower lung. In the control group, CGA-IR level was 0.4-2 pmol/g wet weight of tissue, and its distribution order was lower lung > trachea > major bronchus. In the OA-challenged group, provocation clearly induced significant elevation of CGA-IR in the trachea and main bronchus coinciding with elevation of respiratory resistance. In the lower lung, on the other hand, the increase in CGA-IR was not significant. These results suggest that experimental immediate asthmatic response (IAR) possibly acts as a stressor to the sympathetic nervous systems in guinea pig air-ways.

Airway Resistance↗
PubMed1993

Spontaneous tension oscillation (SPOC) of muscle fibers and myofibrils minimum requirements for SPOC.

Several years ago, we found a new chemical condition for the spontaneous oscillatory contraction of glycerinated skeletal muscle and named it "SPOC". The condition was such that MgATP coexists with its hydrolytic products, MgADP and inorganic phosphate (Pi). Micromolar concentrations of free Ca2+ were not necessarily required for this oscillation. Here, we summarize our recent work on the mechano-chemical properties of SPOC not only in glycerinated single fibers and myofibrils of skeletal muscle (fast type) but also in glycerinated small bundles of cardiac muscle; the isometric tension and its oscillation were examined at various concentrations of MgATP, MgADP and Pi while controlling the concentration of free Ca2+; we constructed a three-dimensional "state diagram" taken against the concentrations of MgADP, Pi and free Ca2+. The 3-D state diagram clearly showed the existence of three regions corresponding to three muscular states; the SPOC region was located in between the regions for contraction (without oscillation) and relaxation. Based on these results, we discuss the mechanism of SPOC, especially the minimum requirements for its occurrence. Finally, we suggest that slow shortening and quick lengthening repeatedly occur every half-sarcomere through the transition between the two states, where weak-force-generating complexes or strong-force-generating complexes are dominant; the transition may be induced by a coupling with the mechanical states of cross-bridges and/or thin filaments.

Animals↗
PubMed1993

Discriminative stimulus properties of a new anxiolytic, DN-2327, in rats.

In an operant learning lever-pressing procedure on an FR10 schedule of milk reinforcement, male Wistar rats were trained to discriminate between saline and 3 mg/kg IP DN-2327, a new anxiolytic which acts on benzodiazepine receptors, 3 mg/kg IP diazepam or 15 mg/kg IP pentylenetetrazol (PTZ). More than 80% appropriate lever responding was established after 27, 38 and 44 daily training sessions with DN-2327, diazepam and PTZ, respectively, as the training drug. Although rats trained with DN-2327 dose-dependently generalized to various doses of DN-2327 and diazepam, the cue of DN-2327 was more potent than that of diazepam: ED50 values of DN-2327 and diazepam for stimulus generalization were 0.30 and 0.66 mg/kg, respectively. These animals partially generalized to pentobarbital (1-10 mg/kg) but did not generalize to buspirone (0.1-10 mg/kg). Rats trained with diazepam dose-dependently generalized to various doses of DN-2327, diazepam and pentobarbital with ED50 values of 0.51, 0.47 and 4.5 mg/kg, respectively, but did not generalize to buspirone. In rats trained with PTZ, DN-2327 and diazepam antagonized the discriminative stimulus produced by 15 mg/kg PTZ in a dose-dependent manner with ED50 values of 0.27 and 0.83 mg/kg, respectively, but buspirone neither antagonized nor was able to substitute for the PTZ-induced stimulus. The cue of DN-2327 was antagonized by flumazenil dose-dependently as was that of diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Genesis of the Austin Flint murmur: relation to mitral inflow and aortic regurgitant flow dynamics.

OBJECTIVES: This study was designed to elucidate the genesis of the Austin Flint murmur. BACKGROUND: The Austin Flint murmur is an apical diastolic rumble associated with significant aortic regurgitation. The precise mechanism of the murmur remains unclear. METHODS: The relation between the Austin Flint murmur and mitral inflow and aortic regurgitant flow dynamics was evaluated nonivasively in 13 patients with moderate to severe aortic regurgitation and 15 control subjects using phonocardiographic and pulsed and color-coded Doppler echocardiographic techniques. The severity of aortic regurgitation was determined by color-coded Doppler echocardiography on the basis of the maximal distance of the regurgitant signal. RESULTS: The direction of aortic regurgitant flow was unrelated to the presence of the Austin Flint murmur. The severity of aortic regurgitation was greater in patients with than in those without this murmur. The peak mitral inflow velocity during early diastole (E) was significantly increased, and both peak mitral inflow velocity at atrial contraction (A) and the A/E ratio were significantly decreased in patients with the Austin Flint murmur compared with values in those without this murmur or in control subjects. However, the maximal amplitude of the Austin Flint murmur did not coincide temporally with the peak mitral inflow velocity. The murmur continued both after rapid mitral inflow had ended and during diastolic mitral regurgitation. CONCLUSIONS: The increased velocity of early diastolic mitral inflow in patients with the Austin Flint murmur is due to aortic regurgitation, but rapid mitral inflow is not an essential requirement for production of the murmur. In some cases, the Austin Flint murmur may be generated by aortic regurgitant flow alone.

Adult↗
PubMed1993

Effect of thyrotropin-releasing hormone on pentobarbitone-induced sleep in rats: continuous treatment with a sustained release injectable formulation.

The mode of action and the time course of the effects of continuous thyrotropin-releasing hormone (TRH) treatment using a two-week sustained release injectable formulation of TRH-containing copoly((+/-)-lactic/glycolic acid) microspheres (TRH-SR) on pentobarbitone-induced sleeping time were studied in rats. Subcutaneous treatment with TRH-SR at doses corresponding to 0.05 and 0.2 mg of TRH kg-1 day-1 caused a dose-related shortening of pentobarbitone-induced sleeping time with a minimum effective dose (MED) of 0.05 mg kg-1 day-1, without affecting the body weight gain. On the other hand, the MED of TRH when given as a bolus subcutaneous injection was 40 mg kg-1. The effect of TRH-SR treatment was blocked by intraperitoneal scopolamine (0.1 mg kg-1) and mecamylamine (2 mg kg-1) but not by scopolamine methyl bromide (0.1 mg kg-1). The results indicate that continuous TRH treatment using TRH-SR causes shortening of pentobarbitone-induced sleeping time at doses lower than those required using bolus injection and probably by a mechanism involving the central cholinergic system.

Amino Acid Sequence↗
PubMed1993

Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients.

The resistance of parathyroid cells to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in uremic hyperparathyroidism is thought to be caused, in part, by a 1,25(OH)2D3 receptor (VDR) deficiency in the parathyroids. However, results of biochemical studies addressing VDR numbers in the parathyroids are controversial. Several studies have found VDR content to be decreased in the parathyroids of uremic patients and animals, while others have found no such decrease in the parathyroids of uremic animals. To clarify the role of VDR, we investigated VDR distribution in surgically-excised parathyroids obtained from chronic dialysis patients by immunohistochemistry. We classified the parathyroids as exhibiting nodular or diffuse hyperplasia. Our studies demonstrated a lower density of VDR in the parathyroids showing nodular hyperplasia than in those showing diffuse hyperplasia. Even in the parathyroids showing diffuse hyperplasia, nodule-forming areas were present; these areas were virtually negative for VDR staining. A significant negative correlation was found between VDR density and the weight of the parathyroids. These findings indicate that the conflicting results of biochemical studies may be caused by the heterogeneous distribution of VDR; the decreased VDR density in parathyroids may contribute to the progression of secondary hyperparathyroidism and to the proliferation of parathyroid cells that is seen in uremia.

Chronic Disease↗
PubMed1993

Assessment of left ventricular diastolic function and potential by quantitative analysis of left ventricular filling curves in patients with atrial fibrillation. A new algorithm for Doppler echocardiographic study.

To evaluate left ventricular (LV) diastolic function and potential, LV filling curves for 18 patients with atrial fibrillation (Af) were constructed and their positions and appearance were evaluated quantitatively by analysis of 95% maximal filling volume points and maximal curvature alteration points. The LV filling curves of group A (Af only) lay left superiorly, while those of group B (impaired LV diastolic function) were situated right inferiorly, all bending steeply. The LV filling curves of group C (mitral stenosis) bent slightly. The lowest normal filling volume points and compensation areas were calculated to evaluate LV diastolic function and were demonstrated to be very different in groups A and B. The lowest normal filling volume points of group C were similar to those of group A, but compensation areas were smaller, indicating a lower LV diastolic potential. It is concluded that the 95% maximal filling volume point, maximal curvature alteration point, lowest normal filling volume point and compensation area are effective indices for evaluating not only LV diastolic function but also the diastolic potential.

Algorithms↗
PubMed1993

Platelets, growth factors, and vascular smooth-muscle cells in hypertension and diabetes.

Inappropriate vascular smooth-muscle cell (VSMC) growth is the hallmark of vascular pathology in essential hypertension and diabetic macroangiopathy, whereas platelets constitute an important regulator of vessel wall homeostasis because of their content of various growth factors. Numerous abnormalities exist in platelet functions in diabetes and hypertension, such as enhanced activity and altered adhesion and aggregation. Increased thromboxane (TX2) production is characteristic of diabetes, and an elevation of intracellular free Ca2+ is found in platelets of hypertensive patients. By studying the growth patterns of VSMC from spontaneously hypertensive rats (SHRs) vs. those obtained from their normotensive counterparts, Wistar-Kyoto (WKY) rats, we have demonstrated that VSMC from SHRs exhibited a higher specific growth rate, abnormal contact inhibition, and accelerated entry into the S phase of the cell cycle. Moreover, they were hyperresponsive to many growth factors such as calf serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF beta 1), and insulin. Additive effects were observed for EGF and PDGF or EGF and insulin. These intrinsic growth anomalies in cells of hypertensive origin persist in culture indicating their putative primary role in the pathogenesis of hypertension. Endogenous TGF beta 1 revealed an augmented expression of its message levels in SHR VSMC, the difference in mRNA between both strains being more pronounced at high cell density. Further, TGF beta 1 protein synthesis and secretion in VSMC culture were confirmed by immunoprecipitation of de novo labeled TGF beta 1. At high cell density, which most likely represents the physiological state of VSMC, plasmin, an activator of TGF beta 1, significantly stimulated DNA synthesis of VSMC in both strains. The reverse effect was obtained at low cell density. Yet, the fold stimulation was higher in WKY rats, suggesting that TGF beta 1 may be partially activated in SHR VSMC. This is supported by the inhibition of baseline DNA synthesis by TGF beta 1 neutralizing antibody in VSMC of hypertensive origin and not of normotensive controls. TGF beta 1 antisense oligodeoxynucleotide (ODN) nearly normalized the increased proliferation of SHR VSMC in culture. On the other hand, growth-promoting activity (GPA) in platelets of either diabetic or hypertensive patients was higher than in platelets of healthy controls and was found to be normalized by intensive insulin therapy in insulin-dependent diabetic patients. In hypertensive patients, however, hydrochlorothiazide (HCTZ)--even in low doses (25 mg/day)--enhanced the GPA in platelets, whereas other antihypertensive agents such as indapamide, atenolol, and captopril, had neutral effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

[Evaluation of pulmonary venous flow patterns in left heart failure: a study using transesophageal Doppler echocardiography].

Pulmonary venous flow (PVF) patterns in left heart failure were evaluated using transesophageal pulsed Doppler echocardiography in 30 patients with dilated hearts (DH) and 30 normal subjects. Eighteen patients had myocardial infarction and 12 patients had dilated cardiomyopathy. The diagnostic criteria by using M-mode echocardiography were left ventricular end-diastolic dimensions (LVDd) of 5.5 cm or more and % LV fractional shortening (%FS) of less than 30%. Peak velocities of the first systolic (PVS1) and second systolic (PVS2) forward waves of PVF, %FS and total amplitude of mitral annular motion in the patient group were significantly decreased compared with the normal group. However, there were no differences in these parameters between the 22 patients (DH-1 group) with a mean pulmonary capillary wedge pressure (PCWP) of less than 18 mmHg and 8 patients (DH-2 group) with a PCWP of 18 mmHg or greater. Peak velocities of the diastolic forward wave of PVF and the early diastolic wave (D) of the LV inflow velocity in the DH-1 group were significantly decreased, and the peak velocity of the atrial contraction wave (A) of the LV inflow velocity was increased compared with those of the normal group. D of the LV inflow velocity, peak velocity of the diastolic forward wave, and peak velocity of the atrial systolic backward wave of the PVF in the DH-2 group were significantly increased compared with those of the DH-1 group. Significant positive correlations were observed between peak velocity of the diastolic forward wave and D or PCWP in the patient group, but the latter relationship was not linear. The A/D ratio of the LV inflow velocity was significantly decreased, and the ratio of the amplitudes of atrial contraction wave to total vertical deflection on the apexcardiogram of the DH-2 group were significantly increased compared with those of the DH-1 group. A patient with extensive myocardial infarction associated with development of severe LV dysfunction (PCWP = 23 mmHg) and a "pseudonormalization" pattern of LV inflow velocity demonstrated markedly increased peak velocities of the diastolic and atrial systolic forward wave, and decreased PVS2. However, the peak velocities of the diastolic and atrial systolic forward wave were decreased, and that of PVS2 was increased with fair improvement of LV dysfunction (PCWP = 10 mmHg) and with compensatory augmentation of the atrial contraction wave A of LV inflow velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiomyopathy, Dilated↗
PubMed1993

[Suppression of the exaggerated growth of vascular smooth muscle cells from SHR by antisense oligodeoxynucleotide to TGF beta].

Faster growth is observed in cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to cells from normotensive Wistar Kyoto (WKY) rats. It has been reported that transforming growth factor-beta (TGF beta), a bifunctional growth factor, shows higher mRNA accumulation in VSMC from SHR. Antisense oligodeoxynucleotide (ODN) complementary to TGF beta 1 mRNA significantly suppressed DNA synthesis of VSMC from SHR at high cell density in a dose-dependent manner, but elicited little inhibition of VSMC from WKY rats. Antisense ODN resulted in a depression of the cell number increase in SHR VSMC only. While DNA synthesis of VSMC was inhibited by antisense ODN at high cell density, it was stimulated at low cell density in both strains. In the presence of antisense ODN, plasmin, an activator of TGF beta, was unable to stimulate DNA synthesis of VSMC. These findings implicate a role of endogenous TGF beta in the exaggerated growth of VSMC from SHR.

Animals↗
PubMed1993

[One family having 5 members with hypertrophic cardiomyopathy with similar pattern of left ventricular inflow and distribution of hypertrophy].

We examined, in one family, 5 cases of hypertrophic cardiomyopathy (HCM) with a similar pattern of left ventricular inflow (LVIF) and distribution of hypertrophy. Its clinical background and significance were discussed. Because a variety of morphologic expressions of HCM may be observed in the same family, distribution of left ventricular hypertrophy (LVH) varies in even first-degree relatives of the family. In all five cases in this study, however, LVH was localized between the anterior wall and the interventricular septum. On the other hand, typical pattern of LVIF in HCM is "decreased peak velocity and prolonged deceleration time of the early diastolic wave (E), and compensatory augmentation of the atrial contraction wave (A)". All of the five cases in this study had a pattern of three characteristic peaks of LVIF, which showed the mid-diastolic wave between the E and A waves. The above findings suggested that the myocardial characteristics of the five cases in this family were very similar, and could be important clues clarifying the mode of inheritance of HCM.

Adult↗