Biomedical subjects

Y Maeno

Publications and source records attributed to Y Maeno.

At least 73 records · Page 4Linked to original sources

PubMed2000

Direct effects of methamphetamine on hypertrophy and microtubules in cultured adult rat ventricular myocytes.

Morphological alterations occasionally found in the myocardium of methamphetamine (MAP) abusers include hypertrophy, atrophy, disarrangement of myofibrils and fibrosis. These cardiac alterations have been thought to be due to an indirect action of MAP via catecholamines released by MAP administration. However, the direct effect of MAP on cardiomyocytes is not clear. In previous studies, we showed that cell size of isolated adult rat ventricular cardiomyocytes (ARCs) exposed to MAP was larger than that of untreated cells in culture supplemented with 10% fetal calf serum (FCS). In this study, to determine further the direct effect of MAP on cardiomyocytes, cultured ARCs were exposed to 0.05, 0.1 and 0.5 mM MAP for 7 days in culture medium without FCS following 6-day normal culture in medium containing FCS. Myocyte size was measured and microtubular (MT) structures which were associated with functional disorder of hearts were immunohistochemically observed using confocal microscopy. The size in treated ARCs significantly increased time- and dose-dependently as compared with untreated cells, but it decreased 7 days after exposure to 0.5 mM MAP. The increases in cell size, however, were lower than that in serum-supplemented cultures. MT structures in intact ARCs appeared as a filamentous network throughout the cytoplasm and around the nucleus. MAP exposure for 3 days promoted MT assembly, but in 7-day treated cells, MT and actin structures were injured. These results suggested that MAP directly induced cellular hypertrophy and might lead to cardiac functional disorder.

Amphetamine-Related Disorders↗

PubMed2000

Screening and determination of benzodiazepines in whole blood using solid-phase extraction and gas chromatography/mass spectrometry.

Benzodiazepines are one of the most widely prescribed drugs for the treatment of a wide spectrum of clinical disorders. They are used as anticonvulsants, anxiolytics, hypnotics or muscle relaxants with different duration of action. In this paper, a simple and sensitive method for the determination of benzodiazepines in whole blood using solid-phase extraction and gas chromatography/mass spectrometry (GC/MS) is described. The drugs spiked in whole blood were extracted with an Oasis HLB solid-phase extraction cartridge (Waters), which contains a copolymer designed to have a hydrophilic-lipophilic balance. GC/MS analysis was performed using a Shimadzu QP-5000 equipped with a BPX5 capillary column (15 mx0.32 mm I.D., film thickness 0.25 microm, SGE). Nineteen benzodiazepines and two thienodiazepines were well separated from each other on their SIM chromatograms and also on the TIC with the exception of oxazolam to cloxazolam separation. The blank extract from whole blood gave no peaks that interfered with all benzodiazepines and thienodiazepines on the chromatogram. The calibration curves for selected benzodiazepines with fludiazepam as an internal standard showed excellent linearity over the concentration range 5-500 ng/ml blood with a correlation coefficients of >0.995. The detection limits ranged from 0.2 to 20 ng/ml blood. The method is simple and sensitive for the determination of benzodiazepines in whole blood and seems to be useful in the practice of forensic science.

Anti-Anxiety Agents↗

PubMed2000

The effects of sarin-like and soman-like organophosphorus agents on MAPK and JNK in rat brains.

One sarin-like and one soman-like organophosphorus agent [bis(isopropyl methyl)phosphonate, BIMP and bis(pinacolyl methyl)phosphonate, BPMP] were injected intravenously (iv) in rats. An increase in the tyrosine phosphorylation of several proteins in the cytosol fraction of the brain was observed. Activation of c-Jun N-terminal kinase (JNK) and slight activation of mitogen-activated protein kinase (MAPK) in the cytosol were also observed. The activation of these enzymes may be related to the high toxicity of these nerve agents.

Animals↗

PubMed2000

Reconstruction from small-angle neutron scattering measurements of the real space magnetic field distribution in the mixed state of Sr2RuO4.

We have measured the diffracted neutron scattering intensities from the square magnetic flux lattice in the perovskite superconductor Sr2RuO4, which is thought to exhibit p-wave pairing with a two-component order parameter. The relative intensities of different flux lattice Bragg reflections over a wide range of field and temperature have been shown to be inconsistent with a single component Ginzburg-Landau theory but qualitatively agree with a two-component p-wave Ginzburg-Landau theory.

Journal Article↗

PubMed2000

Anisotropic superconducting gap in the spin-triplet superconductor Sr2RuO4: evidence from a Ru-NQR study

We have investigated a gap structure in the spin-triplet superconductor Sr2RuO4 through the measurement of the 101Ru nuclear spin-lattice relaxation rate (101)(1/T1) down to 0.09 K at zero magnetic field. In the superconducting state, 1/T1 in a high-quality sample with T(c) approximately 1.5 K exhibits a sharp decrease without the coherence peak, followed by a T3 behavior down to 0.15 K. This result is in marked contrast to the behavior observed below approximately 0.4 K in samples with lower T(c), where T1T is a constant. This behavior is demonstrated to be not intrinsic. We conclude that the gap structure in Sr2RuO4 is significantly anisotropic, consistent with line-node-like models.

Journal Article↗

PubMed2000

Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium.

Experimental studies have shown that in hypertrophy and heart failure, accumulation of microtubules occurs that impedes sarcomere motion and contributes to decreased ventricular compliance. We tested the hypothesis that these changes are present in the failing human heart and that an entire complex of structural components, including cytoskeletal, linkage, and extracellular proteins, are involved in causing functional deterioration. In explanted human hearts failing because of dilated cardiomyopathy (ejection fraction </=20%), expression of alpha- and beta-tubulin, desmin, vinculin, fibronectin, and vimentin was determined by Northern and Western blot analysis and compared with normal myocardium from explants not used for transplantation. The mRNA for alpha- and beta-tubulin was increased to 2.4-fold (P<0.01) and 1.25-fold (NS), respectively; for desmin, 1.2-fold (P<0.05); for fibronectin, 5-fold (P<0.001); and for vimentin, 1.7-fold (P<0.05). Protein levels for alpha-tubulin increased 2.6-fold (P<0.02); for beta-tubulin, 1.2-fold (P<0.005); for desmin, 2.1-fold (P<0.001); for vinculin, 1.2-fold (P<0.005); for fibronectin, 2.9-fold (P<0.001); and for vimentin, 1.5-fold (P<0. 005). Confocal microscopy showed augmentation and disorganization of all proteins studied. In combination with the loss of myofilaments and sarcomeric skeleton previously reported, these changes suggest cardiomyocyte remodeling. Increased fibronectin and elevated interstitial cellularity (vimentin labeling) indicate progressive fibrosis. The present results suggest a causative role of cytoskeletal abnormalities and myofilament loss for intrinsic contractile and diastolic dysfunction in failing hearts.

Adult↗

PubMed2000

Isolation of antigen from the circulating immune complex in mice infected with Plasmodium berghei.

Circulating immune complex (CIC) is known to play a role in pathological glomerular alterations in malaria. However, the nature of the antigens comprising the CIC is still not fully understood. We report here the isolation of the antigen in CIC and its localisation in mice infected with Plasmodium berghei NK65. The antigen was successfully isolated from CIC extracted from the blood of mice infected with P. berghei, by using C1q-coated microplates. The molecular mass of the antigen separated from CIC bound to C1q was found to be 78 kDa. Furthermore, localisation of the antigen was examined by the fluorescent antibody technique and immunoelectron microscopy. The antigen was detected in the parasitised erythrocyte and the mesangial matrix by both methods. These results suggest that the 78 kDa protein might be associated with the glomerular alterations in malaria infection.

Animals↗

PubMed2000

Cyclotron resonance in the layered perovskite superconductor Sr2RuO4

We have observed cyclotron resonance in the layered perovskite superconductor Sr2RuO4. We obtain cyclotron masses for the alpha, beta, and gamma Fermi surfaces of (4.33+/-0.05)m(e), (5.81+/-0. 05)m(e), and (9.71+/-0.2)m(e), respectively. The appreciable differences between these results and those obtained from de Haas-van Alphen measurements are attributable to strong electron-electron interactions in this system. Our findings appear to be consistent with predictions for an interacting Fermi liquid; indeed, semiquantitative agreement is obtained for the electron pockets beta and gamma.

Journal Article↗

PubMed2000

Detailed topography of the fermi surface of Sr2RuO4

We apply a novel analysis of the field and angle dependence of the quantum-oscillatory amplitudes in the unconventional superconductor Sr2RuO4 to map its Fermi surface (FS) in unprecedented detail and to obtain previously inaccessible information on the band dispersion. The three quasi-2D FS sheets not only exhibit very diverse magnitudes of warping, but also entirely different dominant warping symmetries. We use the data to reassess recent results on c-axis transport phenomena.

Journal Article↗

PubMed2000

Quasi-two-dimensional mott transition system Ca2-xSrxRuO4

We have revealed the phase diagram of Ca2-xSrxRuO4: the quasi-two-dimensional Mott transition system that connects the Mott insulator Ca2RuO4 with the spin-triplet superconductor Sr2RuO4. Adjacent to the metal/nonmetal transition at x approximately 0.2, we found an antiferromagnetically correlated metallic region where non-Fermi-liquid behavior in resistivity is observed. Besides this, the critical enhancement of susceptibility toward the region boundary at x(c) approximately 0.5 suggests the crossover of magnetic correlation to a nearly ferromagnetic state, which evolves into the spin-triplet superconductor Sr2RuO4.

Journal Article↗

PubMed2000

In-plane anisotropy of upper critical field in Sr2RuO4

We investigated the behavior of the spin-triplet superconductor Sr2RuO4 ( T(c) approximately 1.5 K) under the magnetic fields parallel to the quasi-two-dimensional plane. The upper critical field H(c2) exhibits a clear fourfold anisotropy of about 3% at 0.35 K. Furthermore, we detected an additional transition feature below H(c2) in both the ac susceptibility and the specific heat. These second-transition features as well as the pronounced in-plane H(c2) anisotropy disappear above 0.8 K or under intentional field misalignment of less than 1 degrees. Most of these characteristics are consistent with the predicted emergence of the second superconducting phase with a line-node gap.

Journal Article↗

PubMed2000

The role of the cytoskeleton in heart failure.

The cytoskeleton of cardiac myocytes consists of actin, the intermediate filament desmin and of alpha- and beta-tubulin that form the microtubules by polymerization. Vinculin, talin, dystrophin and spectrin represent a separate group of membrane-associated proteins. In numerous experimental studies, the role of cytoskeletal alterations especially of microtubules and desmin, in cardiac hypertrophy and failure (CHF) has been described. Microtubules were found to be accumulated thereby posing an increased load on myocytes which impedes sarcomere motion and promotes cardiac dysfunction. Other groups were unable to confirm microtubular densification. The possibility exists that these changes are species, load and chamber dependent. Recently, damage of the dystrophin molecule and MLP (muscle LIM protein) were identified as possible causes of CHF. Our own studies in human hearts with chronic CHF due to dilated cardiomyopathy (DCM) showed that a morphological basis of reduced contractile function exists: the cytoskeletal and membrane-associated proteins are disorganized and increased in amount confirming experimental reports. In contrast, the contractile myofilaments and the proteins of the sarcomeric skeleton including titin, alpha-actinin, and myomesin are significantly decreased. These changes can be assumed to occur in stages and are here presented as a testable hypothesis: (1) The early and reversible stage as present in animal experiments is characterized by accumulation of cytoskeletal proteins to counteract an increased strain without loss of contractile material. (2) Further accumulation of microtubules and desmin to compensate for the increasing loss of myofilaments and titin represents the late clinical and irreversible state. We suggest, based on a structural basis for heart failure, an integrative view which closes the gap between changes within cardiac myocytes and the involvement of the extracellular matrix, including the development of fibrosis. These factors contribute significantly to structural ventricular remodeling and dilatation finally resulting in reduced cardiac function.

Animals↗

PubMed2000

Development of haemoglobin subtypes and extramedullary haematopoiesis in young rats. Effects of hypercapnic and hypoxic environment.

The influence of repeated hypoxia on the development of haemoglobin (Hb) subtypes and on extramedullary haematopoiesis (EMH) was investigated in young Wistar rats of different ages. The rats were exposed to hypercapnic/hypoxic and to "simple" hypoxic conditions. The results obtained were compared to those of an untreated age-matched control group. Different globin chains were measured using HPLC and time-of-flight (TOF) mass analysis. The number of EMH cells was evaluated by cell counting. By determining the proportions of alpha- and beta-chains, fetal, neonatal and mature types of globin chain composition could be differentiated. The beta-2 chain levels were significantly higher in hypercapnic/hypoxic environments than in the controls and simple hypoxic environments. The numbers of EMH cells in the two groups subjected to hypercapnia/hypoxia decreased significantly more slowly compared to the controls and simple hypoxia groups. Therefore, the development of Hb subtypes and the EMH activity in rats were influenced by both repeated hypercapnia and hypoxia.

Animals↗

PubMed2000

Methamphetamine induces an increase in cell size and reorganization of myofibrils in cultured adult rat cardiomyocytes.

To investigate the direct effects of methamphetamine (MAP) on cardiac lesions seen in MAP abusers, isolated adult rat ventricular cardiomyocytes (ARCs) were exposed to MAP (0.05-1.0 mM) in medium 199 containing 10% fetal calf serum. Isolated ARCs attached to laminin-coated substrata and began to spread into polygonal shapes with pseudopodia at day 6 in normal culture. However, the cell attachment and spreading were inhibited by exposure to MAP (0.5 and 1.0 mM) for the first 7 days in culture. On the other hand, exposure to MAP (0.05 and 0.1 mM) for 7 days after a 6-day period of normal culture, led to a larger cross surface area of cells with more abundant actin bundles compared to control cells (p < 0.05). This development of spreading area resembled that of norepinephrine-treated ARCs. In addition, immunoreactive atrial natriuretic peptide (ANP) granules developed and accumulated around the nuclear region of ARCs exposed to MAP and the number of ANP positive cells tended to increase in a dose-dependent manner. These results suggest that chronic exposure to a high concentration of MAP may directly inhibit development of ARCs in culture and that a continuous exposure to a low concentration of MAP may facilitate the development of cellular hypertrophy. Therefore, hypertrophied cardiomyocytes in MAP abusers may be provoked by multifactorial incidents of direct and indirect actions of MAP.

Animals↗

PubMed2000

IDL can stimulate atherogenic gene expression in cultured human vascular endothelial cells.

Previously, we have reported that the lipoprotein fraction containing intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) isolated from diabetics stimulates an atherogenic cytokine in cultured endothelial cells. To study which lipoprotein fraction isolated from diabetics can modulate the gene expression in endothelial cells, we isolated IDL and LDL fractions from 14 type 2 diabetics and seven age- and BMI- adjusted non-diabetics. We measured the effects of the lipoproteins on mRNA expression of atherogenic molecules in cultured endothelial cells. We found that the IDL fraction stimulated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in endothelial cells as time- and dose-dependent fashions, while the LDL fraction was not effective. IDL isolated from diabetics also increased not only platelet-derived growth factor B-chain, but also intercellular adhesion molecule-1 mRNA contents. Furthermore, the HbA(1c) levels in diabetics were significantly correlated with their abilities of IDL to increase MCP-1 mRNA content in the cells and the increment coincided with the increase in MCP-1 protein release into culture media. These results indicate that qualitative as well as quantitative changes in IDL fraction in diabetes are atherogenic through stimulating gene expression of atherogenic molecules in endothelial cells.

Arteriosclerosis↗

PubMed2000

Superiority of 3-dimensional versus 2-dimensional echocardiography for left ventricular volume assessment in small piglet hearts.

To evaluate the accuracy of 3-dimensional (3D) echocardiography in the estimation of left ventricular (LV) volume in vivo, we studied 15 newborn piglets ranging in weight from 2.6 to 11.8 kg. Measurements of beating LV volumes by 3D echocardiograms were compared with measurements by conductance catheter and transthoracic 2-dimensional (2D) echocardiograms with the use of Simpson's rule. The results of both 3D and 2D echocardiograms correlated strongly with the actual volume (r = 0.98 and 0.95 for LV end-diastolic volume, and 0.998 and 0.95 for LV end-systolic volume, respectively). However, the standard error of estimate (SEE) for 2D echocardiography was larger than for 3D. The SEE values for LV end-diastolic volume for 2D and 3D echocardiograms were 2.30 mL and 1.85 mL, respectively, and 1.52 mL and 0.5 mL for LV end-systolic volume. We conclude that 3D echocardiography not only accurately measures LV volume and systolic function in a newborn heart, it is more precise than measurements from 2D echocardiography in the assessment of small beating hearts.

Animals↗

PubMed2000

Disruption of the klotho gene causes pulmonary emphysema in mice. Defect in maintenance of pulmonary integrity during postnatal life.

Homozygous mutant klotho (KL(-/-)) mice exhibit multiple phenotypes resembling human aging. In the present study, we focused on examining the pathology of the lungs of klotho mice and found that it closely resembled pulmonary emphysema in humans both histologically and functionally. Histology of the lung of KL(-/-) mice was indistinguishable from those of wild-type littermates up to 2 wk of age. The first histologic changes appeared at 4 wk of age, showing enlargement of the air spaces accompanied by destruction of the alveolar walls, and progressed gradually with age. In addition to these changes, we observed calcium deposits in type I collagen fibers in alveolar septa and degeneration of type II pneumocytes in 8- to 10-wk-old KL(-/-) mice. Pulmonary function tests revealed prolonged expiration time in KL(-/-) mice, which is comparable with the pathophysiology of pulmonary emphysema. The expression level of messenger RNA for type IV collagen, surfactant protein-A and mitochondrial beta-adenosine triphosphatase was significantly increased in KL(-/-) mice, which may represent a compensatory response to alveolar destruction. Additionally, the heterozygous mutant klotho mice also developed pulmonary emphysema late in life, around 120 wk of age. These findings indicate that klotho gene expression is essential to maintaining pulmonary integrity during postnatal life. The klotho mutant mouse is a useful laboratory animal model for examining the relationship between aging and pulmonary emphysema.

Aging↗

PubMed2000

Role of apoptosis in the closure of neonatal ductus arteriosus.

Apoptosis regulates the remodeling of tissue during embryonic development by eliminating unwanted cells and structures. The present study investigated smooth muscle cell (SMC) proliferation and apoptosis in the neonatal ductus arteriosus (DA) during closure. In the DA of 39 swine neonates and 5 autopsy human neonates, apoptosis was detected using in situ end-labeling and electron microscopy, and proliferation was evaluated using proliferating cell nuclear antigen. In swine, apoptosis of SMC was first observed at 24h after birth. After 48h, both apoptosis and proliferation quickly increased and became most prominent at 3 days, mainly in the intima and inner media. From 5 days, both apoptosis and proliferation quickly disappeared, and were present to a minor extent at the 2 weeks after birth. During these processes, there was no sign of inflammation or necrosis. In humans, apoptosis was found in tissue specimens obtained from 2 term neonates who died at 1 and 5 days after birth. These findings suggest that SMC contribute to the functional closure of the DA by active constriction, and soon after, they switch to proliferation and apoptosis, which may contribute to the anatomical closure of the DA.

Animals↗