Search PubMed⌕ Search

Biomedical subjects

S Mochizuki

Publications and source records attributed to S Mochizuki.

At least 73 records · Page 4Linked to original sources

Noninvasive measurement of aortic pressure waveform by ultrasound.

At present, the aortic pressure (Pa) waveform can only be measured invasively. In this paper, we describe a new noninvasive method of measuring Pa. The aortic diameter (Da) pulse waveform was measured noninvasively from the suprasternal fossa using an echo-tracking system that was applied to the anterior and posterior aortic wall echoes. To eliminate viscoelastic distortion, the measured Da was converted to an estimate of Pa, named P beta, using the stiffness parameter beta, which revealed the viscoelastic relationship between the vessel diameter and its internal pressure. P beta was then compared with the Pa pattern that was measured directly. Eight patients with ischemic heart disease who had undergone cardiac catheterization were examined by this method. Results showed that (1) the Da and Pa waveforms were similar; (2) the P beta waveform resembled the Pa waveform more closely than did the Da waveforms for a single cardiac cycle (r = 0.970); and (3) in particular, P beta resembled Pa most closely during the upslope phase of the ejection period (r = 0.996). Our results suggest that the Pa waveform can be accurately estimated from noninvasive measurements by this method.

Adult↗

Estimation of myofibrillar responsiveness to Ca2+ in isolated rat ventricular myocytes.

To estimate myofibrillar responsiveness to Ca2+, we used the relation between cell length and intracellular [Ca2+] ([Ca2+]i) during tetanic contractions of isolated ventricular myocytes. Enzymatically isolated rat ventricular myocytes were loaded with fura-2 AM (4 microM for 10 min) and excited alternately at 340 nm and 380 nm. The ratio (R) of fura-2 fluorescence at these wavelengths [F(340)/F(380), an index of [Ca2+]i] and cell length (L) were measured simultaneously. Following treatment with thapsigargin (0.2 microM), myocytes were stimulated at 10 Hz for 10 s to produce a tetanic contraction every min and an instantaneous plot of R vs L (R-L trajectory) was constructed. The R-L trajectory followed the same path during cell shortening and re-lengthening, suggesting that dynamic equilibrium between R and L was achieved during tetanus. Increasing the extracellular [Ca2+] from 1 to 8 mM extended the R-L trajectory without a substantial shift of the relation. The Ca2+-sensitizing thiadiazinone derivative, EMD57033 (1 microM), shifted the R-L trajectory to the left (sensitization of the myofibrils to Ca2+), whereas the non-selective phosphodiesterase inhibitor, 3-isobutyl-1-methylxantine (200 microM), shifted the R-L trajectory to the right (desensitization of the myofibrils to Ca2+), in agreement with previous results obtained using skinned preparations. We conclude that the R-L trajectory is useful for estimating the myofibrillar responsiveness to Ca2+ in isolated myocytes and may be beneficial for the evaluation of inotropic agents.

1-Methyl-3-isobutylxanthine↗

Limited reproducibility of circadian variation in blood pressure dippers and nondippers.

The relation between blood pressure (BP) variation and hypertensive organ damage is controversial. The reproducibility of the circadian variation pattern acceptable as the standard for discriminating between "dippers" and "nondippers" has not yet been evaluated. We evaluated the reproducibility of "dipper" and "nondipper" patterns in essential hypertensives by monitoring BP for 48 h. Noninvasive ambulatory BP and heart rate (HR) monitoring for 48 h every 30 min were performed in 253 untreated patients with mild-to-moderate essential hypertension. Mean daytime (awake) and nighttime (sleeping) systolic BP, diastolic BP, and HR values were analyzed by reviewing the patients' diaries. Patients were divided into two groups by presence (dippers) and absence (nondippers) of a reduction of both systolic and diastolic BP during the night of > 10% of the daytime pressure. A subject who was a dipper on day 1 remained a dipper on day 2 in 41% (n = 103, DD group) and changed to nondipper in 16% (n = 41, DN group). A subject who was a nondipper on day 1 remained a nondipper on day 2 in 30% (n = 75, NN group) and changed to a dipper in 13% (n = 34, ND group). Our findings indicate that there is a high risk of false-positive or false-negative results when 24-h recordings are used to identify dipper and nondipper profiles.

Adult↗

Antihypertensive activity and pharmacokinetics of KD3-671, a nonpeptide AT1-receptor antagonist, in renal hypertensive dogs.

The antihypertensive activity and pharmacokinetics of KD3-671 (previously named KT3-671), a nonpeptide AT1-receptor antagonist, were investigated in renal hypertensive dogs with normal or high plasma renin activity (PRA). A single administration of KD3-671 at 3 and 10 mg/kg, p.o., to the hypertensive dogs with high PRA dose-dependently reduced mean blood pressure (MBP), which was not correlated with plasma KD3-671 concentration. Significant increases in PRA and plasma angiotensin (Ang) II occurred 2 h after KD3-671 dosing. Enalapril at 3 mg/kg, p.o., also reduced MBP. Neither KD3-671 nor enalapril affected heart rate. When given orally once a day for 29 days to the hypertensive dogs with normal PRA, KD3-671 at 3 and 10 mg/kg/day dose-dependently reduced MBP, which was smaller than that in the dogs with high PRA. This was the case for enalapril. The hypotension induced by the first dose of KD3-671 or enalapril was consistently observed after doses 8, 15, 22, and 29. After cessation of repeated dosing, no rebound phenomenon in MBP was observed. Pharmacokinetic parameters of KD3-671 were not influenced by repeated dosing. KD3-671 markedly increased both PRA and plasma Ang II concentration at 2 h after dosing. These results suggest that KD3-671 may be useful for the treatment of hypertension.

Aldosterone↗

Band 3 Tokyo: Thr837-->Ala837 substitution in erythrocyte band 3 protein associated with spherocytic hemolysis.

We report a case of spherocytosis associated with erythrocyte band 3 deficiency. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of erythrocyte membrane proteins showed that the patient's band 3 was reduced to about 80% of the control level. Molecular analysis revealed that this quantitative alteration was accompanied by a novel base change at codon 837 (ACG-->GCG) of the AE1 gene, resulting in substitution of alanine for threonine. In bone marrow mononuclear cells, both mutant and wild-type mRNA were comparably detected, suggesting that this mutation interfered with band 3 processing or assembly, leading to impaired accumulation of mutant band 3 in the plasma membrane.

Adult↗

Hypocalcemic effect of osteoclastogenesis inhibitory factor/osteoprotegerin in the thyroparathyroidectomized rat.

Osteoclastogenesis inhibitory factor (OCIF), also termed as osteoprotegerin (OPG), is a soluble member of the tumor necrosis factor receptor family. Although OCIF/OPG is shown to inhibit osteoclast formation in vitro and prevent ovariectomy-induced bone loss in vivo, its effect on serum calcium level remains to be determined. In this study we examined the acute effect of OCIF on thyroparathyroidectomized rats whose serum calcium concentrations were raised either by exogenous PTH or 1,25-(OH)2D3. When OCIF was administered at the start of PTH infusion, it attenuated the initial rise in serum calcium. When OCIF was administered into rats with established hypercalcemia, it decreased serum calcium rapidly (within 2 hr) and dramatically. OCIF did not increase urinary calcium excretion. These findings, especially the rapid onset of its hypocalcemic effect, suggest that OCIF not only inhibits the formation of osteoclasts but also affects the function and/or survival of mature osteoclasts at doses used in this study.

Animals↗

Left coronary artery-left ventricle fistula with right coronary artery spasm.

A 72-year-old woman was admitted to our hospital for evaluation of chest pain. Coronary angiography showed a left coronary artery-left ventricle fistula. An acetylcholine provocation test induced vasoconstriction of the right but not the left coronary artery. Her chest pain was not relieved by combined therapy with isosorbide dinitrate, diltiazem and nicorandil. Because of the coronary spasm, beta-blockers could not be used. However, her chest pain was relieved after the administration of a minor tranquilizer. Thus, the patient's chest pain was unlikely to be associated with either the fistula or the coronary spasm.

Acetylcholine↗

Unusual turns of the conical colon of swine.

Anomalous arrangements of the conical colon were found in 38 cases out of 731 swine. These anomalies divided into the following five types: 1) additional loop running perpendicular to the turns (8 cases), 2) two or four changes in the centripetal turns (6 cases), 3) two changes in the centrifugal turns (2 cases), 4) one to three changes in both the centripetal and centrifugal turns (21 cases), and 5) two independent conical colons (1 case). The double conical colon (Type 5) was the only one case and seems to be rare. The total of the anomalous types made up approximately 5.2% and not appear to be rare.

Animals↗

Differences in intestinal length between specific-pathogen-free (SPF) and conventional swine.

The length of the small intestine, cecum, and the rest of the large intestine of specific-pathogen-free (SPF) swine was compared with that of conventional swine. The average length of the small intestine of SPF swine was shorter than that of conventional swine. The difference was significant for female SPF swine. There was no difference between SPF and conventional swine in the length of the cecum, colon and rectum.

Animal Feed↗

Na+/Ca++ exchanger and myocardial ischemia/reperfusion.

Myocardial hypoxia and ischemia are characterized by the depletion of ATP and the development of intracellular acidosis, which alter cellular ionic homeostasis. Specifically, elevated cytosolic free Ca++ concentrations cause cellular injury during hypoxia/ischemia and lead to irreversible myocardial damage during reoxygenation/reperfusion. An increase in the intracellular Na+ concentration has been shown to correlate with Ca++ overload. Although inhibition of Na+/K+ exchange because of decreased ATP production may be involved, it is more likely that intracellular acidosis drives Na+ into the cells via Na+/H+ exchange. Experimental evidence supports the notion that Na+/H+ exchange is primarily responsible for Na+ influx during hypoxia/ischemia. The accumulation of intracellular Na+ may then activate the Na+/Ca++ exchanger causing Ca++ overload. Therefore, the Na+/Ca++ exchanger plays a crucial role in cellular injury during hypoxia/ischemia and in cell death during reoxygenation/reperfusion. In the past few years, the Na+/Ca++ exchanger has been cloned and the structure/function relationship studied intensively. Agents which inhibit the Na+/Ca++ exchanger may have therapeutic potential for the treatment of ischemic heart disease. These advances will greatly accelerate the understanding of the cellular and molecular mechanisms underlying the role of the Na+/Ca++ exchanger in the development of myocardial damage during hypoxia/ischemia and reoxygenation/reperfusion.

Adenosine Triphosphate↗

Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.

A factor which inhibits osteoclast-like cell formation was found in the conditioned medium of human embryonic lung fibroblasts, IMR-90. The factor, termed osteoclastogenesis inhibitory factor, OCIF, was purified to homogeneity. OCIF is a heparin-binding basic glycoprotein and has been isolated as a monomer with an apparent molecular weight (Mr) of 60,000 and a homodimer with a Mr of 120,000. The N-terminus of OCIF is blocked and the determination of internal amino acid sequences revealed that OCIF has no homology to known proteins. OCIF inhibited in a dose-dependent manner osteoclastogenesis elicited through three distinct signaling pathways stimulated by 1 alpha,25-dihydroxy vitamin D3, parathyroid hormone, and interleukin-11, respectively, in a dose range of 1 to 40 ng/ml (IC50 = 4 to 6 ng/ml). OCIF neither inhibits bone resorption by mature osteoclasts nor exerts any other biological activities. These data strongly suggest that OCIF is a novel cytokine which specifically inhibits osteoclastogenesis.

Acid Phosphatase↗

Ultrastructural and confocal laser scanning microscopic examination of TUNEL-positive cells.

TdT-mediated dUTP-biotin nick end labelling (TUNEL) has been widely used for detecting cells with DNA fragmentation or apoptotic cells. However, since the concept of apoptosis is based on cellular ultrastructure, it is important to identify the morphological features of TUNEL-positive cells. In this study, we performed TUNEL and electron microscopic observation on serial semithin and ultrathin sections of pancreas from bilaterally adrenalectomized rats with caerulein-induced pancreatitis. TUNEL-positive cells were identified with two different ultrastructural patterns. One was characteristic of apoptosis, with condensed nuclei, intact mitochondria, and zymogen granules. The other pattern was one of marked cellular degeneration, possibly representing the end stage of cell death. Cells which did not demonstrate these ultrastructural patterns were not labelled by the TUNEL method. The three-dimensional structure of TUNEL-positive cells was also investigated by confocal laser scanning microscopy (CLSM), which showed the apoptotic nuclei exhibited various three-dimensional structures. These results confirm the utility of the TUNEL method in detecting apoptosis; application of the technique reported in this study will contribute to the further characterization of individual TUNEL-positive cells.

Acute Disease↗

Effects of hypoxia and metabolic inhibition on increases in intracellular Ca2+ concentration induced by Na+/Ca2+ exchange in isolated guinea-pig cardiac myocytes.

We have assessed if the sarcolemmal Na+/Ca2+ exchange of isolated cardiac myocytes becomes inhibited when the cells are subjected to hypoxia and metabolic inhibition. Function of the exchange was assessed by exposing single cardiac myocytes to Na+-free solutions and measuring the increases in [free Ca2+]i using the fluorescent indicator Fura-2. Removal of extracellular Na+ reverses the Na+ gradient and causes Ca2+ influx via Na+/Ca2+ exchange. This influx may trigger further Ca2+ release from the sarcoplasmic reticulum. Hypoxia and metabolic inhibition produced either by (1) vigorously bubbling glucose-free Tyrode with N2, or (2) bubbling with N2 and adding 10 mm 2-deoxy-D-glucose to the Tyrode or (3) using 0.1-1.0 mm sodium dithionite (sodium hyposulphite, Na2S2O4) in glucose-free Tyrode caused a significant decline in the rates of increase in [free Ca2+]i during Na2+-free superfusion. The decreases in [free Ca2+]i on re-application of Na+ were also significantly slowed. This suggests that reverse-mode Na+/Ca2+ exchange and the processes leading to release of Ca2+ from the sarcoplasmic reticulum are inhibited in hypoxia and metabolic inhibition.

Animals↗

Development of the undulation pump total artificial heart.

The undulation pump is a small size continuous flow displacement type blood pump that has been developed for an artificial heart. Using undulation pumps, 2 types of implantable total artificial hearts (TAHs), the undulation pump TAH (UPTAH) type 1 (UPTAH 1) and UPTAH type 2 (UPTAH 2) were developed. Both UPTAHs were designed to be small enough to implant into the chest of a goat, the experimental animal. UPTAH 1 could be reduced in size to 75 mm in diameter and 78 mm in length. The weight was 520 g. UPTAH 2 could be reduced in size to 75 mm in diameter and 80 mm in length. The weight was 650 g. UPTAH 2 could be tested in an animal experiment using an adult female goat weighing 52.3 kg. The UPTAH 2 could be implanted successfully into the goat's chest with a good fit. The goat stood after the surgery and extubation and survived for 3 h and 40 min; thus, the potential of the UPTAH for a practical implantable TAH was demonstrated.

Animals↗

A possible role of a blood vessel in formation of the fat area in the quadrate lobe of porcine liver.

Approximately a half of swine examined had a fat storing area (F-area) in the quadrate lobe of the liver. This area was stained strongly by Sudan Black B (fat staining) and PAS (carbohydrate staining). The area was light brown to greyish yellow in appearance due to the deposition of lipid droplets. In cross section the F-area was wedge-shaped, and had a specific venous supply which directly connected it to the right gastric vein. The larger the connecting vein the wider the F-area, indicating that the connecting vein, not reported so far, is a key factor in the formation of the F-area. This would be a good model for the formation of partial fatty liver.

Adipose Tissue↗

[Circadian variation of blood pressure and heart rate in normotensive pre- and postmenopausal women].

The aim of this study was to assess the effect of menopause on circadian profile of blood pressure (BP) and heart rate (HR) in the normotensive pre- and postmenopausal women. Systolic BP (SBP), diagnostic BP (DBP) and HR were monitored every 30 min for 48 hrs using noninvasive ambulatory BP monitoring in 24 premenopausal and 40 postmenopausal women. Mean 48-hours, daytime (awake), and nighttime (sleeping) SBP, DBP and HR values were analyzed by reviewing the patients' diaries, and the nocturnal reduction rate (NRR) of SBP, DBP and HR were calculated according to the following formula. NRR (%9 = [(daytime mean-nighttime mean)/daytime mean] x 100. The study subjects were then divided into two groups according to the presence (dipper) or absence (nondipper) of a significant reduction in nocturnal BP (> 10%). Mean SBP, DBP and HR measured over 48 hours were similar between the premenopausal and the postmenopausal group. The NRR of DBP and HR in the postmenopausal group were significantly smaller than those in the premenopausal group (17.1 +/- 6.0% vs. 13.5 +/- 7.0%, 241.1 +/- 6.0% vs. 19.8 +/- 9.0%: p < 0.05). There tended to be higher prevalence of nondipper in the postmenopausal (37%) than in the premenopausal group (29%).

Adult↗

Chromosome changes associated with growth potential of HTLV-I infected human lymphocytes.

The association between chromosomal changes and cellular growth potential was investigated in HTLV-I infected human lymphocytes. Cell lines studied include Coculture-5 (HTLV-I infected immortalized cells dependent of IL-2), Coculture-15 and -18 (semi-transformed Coculture-5 cells following cocultivation with transformed Coculture-5 cells), UV-5 (Coculture-5 cells transformed following UV irradiation), and MNNG-1 (Coculture-5 cells transformed following MNNG treatment). Immortalized cells were grown in IL-2 medium (IL-2+PHA+TPA), whereas semi-transformed and transformed cells were grown in RPMI medium. By G-band karyotyping, double band formation was seen in 3-33% of spreads at the centromeric region of chromosomes 1 and 7 to which structural abnormalities were found to cluster. The double band formation was also seen by FISH using alpha satellite DNA probe in Coculture-5 and -15 thus far examined. The ploidy of immortalized, semi-transformed, and transformed cell lines, was 4n, 4n to 2n, and 2n range, respectively. These findings suggest that chromosomal rearrangements cause abnormalities in cell division kinetics resulting in numerical and structural abnormalities of chromosomes, and render host cells growth advantage.

Cell Division↗

Cytokine mediated growth inhibition of HTLV-I infected transformed human lymphocytes.

The interaction between HTLV-I infected immortalized cells and transformed cells was studied. HTLV-I infected immortalized human lymphocytes (Coculture-5) dependent of IL-2 medium (IL-2+PHA+TPA) and transformed cells (UV-5) derived from Coculture-5 following UV irradiation were cocultured in equal numbers in IL-2 medium. UV-5 cells were suppressed and disappeared about 1 month in cocultivation. UV-5 cells were not suppressed in IL-2 medium. Coculture-5 cells and UV-5 cells were seeded in Transwell dishes that were separated by membrane with pores 0.4 micron in diameter and cultured in IL-2 medium. UV-5 cells were suppressed indicating that cell-cell contact was not required for the observed suppression. UV-5 cells were markedly suppressed in IL-2 medium harvested from Coculture-5 cells when recombinant interferon alpha (1000 U/ml) was added to the medium. These findings demonstrated that growth of HTLV-I infected transformed cells could be suppressed by cytokine(s) released by HTLV-I carrier lymphocytes.

Cell Division↗