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Biomedical subjects

Y Hattori

Publications and source records attributed to Y Hattori.

At least 37 records · Page 2Linked to original sources
PubMed2002

Long-acting calcium channel blocker benidipine suppresses expression of angiogenic growth factors and prevents cardiac remodelling in a Type II diabetic rat model.

AIMS/HYPOTHESIS: Calcium channel blockers, widely used for the treatment of hypertension and angina, could prevent cardiovascular complications in patients with diabetes. They can improve cardiac remodelling in animal models of a variety of cardiovascular diseases. Here, we examined the therapeutic effect of benidipine, a long-acting calcium channel blocker, on cardiac remodelling in Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a Type II (non-insulin-dependent) diabetes mellitus model. METHODS: The methods for morphometric analysis included double staining for coronary capillaries, dye-binding staining for collagen content and Masson's trichrome staining for perivascular fibrosis. Immunohistochemical and in situ hybridization techniques were used for detecting protein and mRNA expressions for vascular endothelial growth factors (VEGF), basic fibroblast growth factors (bFGF) and TGF-beta(1), endothelial nitric oxide synthase (eNOS), and anti- and pro-apoptotic markers. RESULTS: OLETF rats showed an increased coronary capillary density, a reduced venular capillary proportion, an increased cardiac collagen content and prominent cardiac perivascular fibrosis. In OLETF rat hearts, significant increases in vascular expressions for VEGF, bFGF and TGF- beta(1) were found. Furthermore, the apoptosis signalling pathways, involving eNOS and apoptotic markers, were markedly altered, and coronary endothelial cell apoptosis was lower. These alterations with the exception of eNOS expression were significantly blocked by benidipine treatment. CONCLUSION/INTERPRETATION: The suppressive effect of benidipine on overproduction of angiogenic growth factors could prevent cardiac angiogenesis and fibrosis, resulting in an improvement of cardiac remodelling in diabetes. As VEGF and bFGF potently block endothelial cell apoptosis execution, physiological apoptosis revived by benidipine treatment could also contribute to coronary vessel regression.

Animals↗
PubMed2002

Contrast-enhanced MR angiography (enhanced 3-D fast gradient echo) for diagnosis of cerebral aneurysms.

We evaluated contrast-enhanced MRA (enhanced 3-D fast gradient echo, EFGRE3D, with spectral IR) for the identification of unruptured cerebral aneurysms. We examined 22 aneurysms from 15 patients. In its ability to identify aneurysms, contrast-enhanced MRA was superior to 3-D-time of flight (3D-TOF) MRA in 4 instances, equal in 17, and inferior in 1. Contrast-enhanced MRA demonstrated thrombus formation more clearly and accurately than did 3D-TOF MRA. Contrast-enhanced MRA was performed in less than 1 min, and was found to be a useful method for the identification of intracranial aneurysms.

Aged↗
PubMed2002

Viscoelastic properties and residual strain in a tensile creep test on bovine temporomandibular articular discs.

This study was designed to evaluate the creep characteristics and residual strain of bovine temporomandibular joint (TMJ) discs in tension. Twenty discs were divided into three specimens each: central, lateral and medial regions. Tension of 1.0 MPa was applied and sustained for 20 min to the specimens from 10 right-side discs, and tension of 1.5 MPa to specimens from 10 left-side discs. After the period of tension for creep, the specimens were removed from the tension devices and restoration observed for 20 min. Time-dependent creep curves showed a marked change in strain during the initial 5s. The essential time delay in strain ceased after 2 min, and strain reached an almost steady level after 3 min. At a tensile stress of 1.5 MPa, a strain of 14.5% on average was produced after 20 min creep in the central specimens; peripheral specimens showed strains of 12.4% on average. There were significant differences in strain between the central and peripheral specimens. The residual strain after 20 min restoration was 0.93% on average and there were no significant regional differences. This creep feature could be well represented by a generalized linear viscoelastic model. It was concluded that the regional differences in viscoelasticity might be caused by the complicated articulating functions of the TMJ, and that the residual strain caused by sustained stress could be an important factor in disc deformation.

Animals↗
PubMed2002

Biomechanical response of bovine temporomandibular joint disc to prolonged tensile stress.

This study was designed to evaluate the influence of prolonged tensile stress on the viscoelasticity of the temporomandibular joint (TMJ) disc. Twenty discs from 10, 3-year-old cattle were used. Tensile stress of 1.5 MPa was applied to specimens from the discs for 10, 20, 40 and 60 min. Following the prescribed period of tension for creep, the specimens were removed from the tension device and any recovery observed for 20 min. In all specimens, strain increased at the onset of stress application and reached almost steady conditions after 5 min. Although, the strain became slightly larger when the creep time was longer, no significant differences were found in the strains between any two tests with different periods of creep. The residual strain increased significantly with creep duration, and similarly the degree of recovery decreased significantly. In 10- and 20-min creep tests, the residual strains were 0.1 and 1.0%, the specimens in 40- and 60-min tests revealed irreversible changes in length. It was concluded that continuous loading for >40 min causes creep damage in bovine TMJ disc, and that prolonged sustained tension affects the recovery of joint homeostasis.

Animals↗
PubMed2002

Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA): possible involvement of complement in granulocyte cytotoxicity.

Although antineutrophil antibodies are thought to be involved in drug-induced neutropenia, neither the precise mechanisms nor the particular antigens on the neutrophil surface have yet been clarified. Recently, we examined a patient with Graves' disease who developed antineutrophil cytoplasmic antibodies (ANCA) after propylthiouracil treatment and exhibited neutropenia. Because several target antigens of ANCA are expressed on the surface of neutrophils, it was suggested that ANCA might contribute to neutropenia. The patient's serum bound specifically to neutrophils and HL-60 cells differentiated into granulocytes, and lysed the HL-60 cells via a complement-mediated mechanism. Furthermore, two representative ANCA antigens, proteinase 3 and myeloperoxidase, significantly inhibited both the binding and cytotoxicity of the serum. Finally, tumour necrosis factor-alpha, which is known to up-regulate cell surface expression of several ANCA antigens, enhanced both the binding and cytotoxicity of the serum. These findings suggest that ANCA induced by propylthiouracil contributed to leucopenia through a complement-mediated mechanism.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2002

Bilateral elbow flexion reconstruction with functioning free muscle transfer for obstetric brachial plexus palsy.

A child suffered a bilateral obstetric brachial plexus palsy involving the C5 and C6 nerve roots. Abduction of the shoulder joints had recovered by 1 year, but elbow flexion did not recover on either side. Free gracilis muscle transfers were performed on both sides, at an interval of 6 months, to achieve elbow flexion. The spinal accessory nerve was used as the donor nerve.

Accessory Nerve↗
PubMed2001

NGF induces neurite outgrowth via a decrease in phosphorylation of myosin light chain in PC12 cells.

The relationship between phosphorylation of myosin light chain (MLC) and neurite outgrowth induced by nerve growth factor (NGF) was studied in PC12 cells. Inhibitors of Rho kinase, HA-1077 or Y-27632 also induced neurite outgrowth. As already reported botulinum exoenzyme C3 which inactivates Rho protein also induced neurite outgrowth. Calyeulin A, an inhibitor of phosphatase counteracted both NGF- and C3- induced neurite outgrowth. Treatments of both NGF and C3 resulted in significant and transient decrease in phosphorylated MLC. These results suggest that NGF induces neurite outgrowth of PC12 by a transient decrease in phosphorylated MLC which is brought about by activation of MLC phosphatase via inhibition of Rho-Rho kinase pathway.

Animals↗
PubMed2001

Dexamethasone suppresses iNOS gene expression by inhibiting NF-kappaB in vascular smooth muscle cells.

Bacterial lipopolysaccharide (LPS) and other immunostimulants induce an isoform of nitric oxide synthase (iNOS) gene expression in vascular smooth muscle cells (VSMC). This process is dependent on nuclear factor-kappa B (NF-kappaB) activation and is suppressed by glucocorticoids. The aim of this study was to investigate the molecular mechanisms of inhibition of iNOS expression by the synthetic glucocorticoid, dexamethasone (DEX), in rat VSMC. Treatment of VSMC with LPS plus interferon-gamma (LPS/IFN) caused activation of NF-kappaB and the iNOS promoter. LPS/IFN induced iNOS mRNA and NO synthesis. DEX markedly depressed LPS/IFN-stimulated iNOS mRNA expression and NO production. DEX also suppressed LPS/IFN-stimulated activity of a 1.7-kb iNOS promoter, indicating that the inhibition of iNOS expression by DEX occurs at the level of transcription. NF-kappaB activation by LPS/IFN was repressed by DEX. The inhibition of NF-kappaB by DEX exhibited dose-dependent kinetics, which corresponded to DEX suppression of iNOS promoter activation, iNOS mRNA expression, and NO production. However, activation of activator protein-1 (AP-1), which is also contained in the iNOS promoter, was not enhanced by LPS/IFN or inhibited by DEX. Thus, glucocorticoids appear to block iNOS expression, at least in part, through inhibition of NF-kappaB activation, which results in decreased NO production.

Animals↗
PubMed2001

Vascular smooth muscle cell activation and growth by 4-hydroxynonenal.

The present study examines the signal transduction mechanism that is involved in the growth of vascular smooth muscle cells exposed to 4-hydroxynonenal (HNE) in vitro. This aldehyde component of oxidized low-density lipoprotein has been identified in atherosclerotic lesion. Exposure to HNE caused ERK, JNK, and p38 MAP kinase activation as well as the induction of c-fos and c-jun gene expression. AP-1 activity was also significantly induced by HNE treatment. These intracellular activities appear to be the mechanism of HNE-caused mitogenesis. Indeed, HNE induced vascular smooth muscle cell proliferation as determened by Alamar-Blue assay and stimulated DNA synthesis as determined by bromodeoxyuridine incorporation. These observations are consistent with a role of lipid peroxidation products in vascular smooth muscle cell growth in atherogenesis.

Aldehydes↗
PubMed2001

Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue.

Prostate tissue was obtained from 22 radical prostatectomies (performed for clinical management of prostate carcinoma) immediately after surgery. A small piece of tissue was fixed immediately in formalin and used for routine histology while a second piece was frozen in OCT and used for immuno-histochemistry. Another small piece was used for isolation of epithelial and stromal cells. The remainder of the tissue was cut into 2 x 2 mm pieces and incubated in organ culture for 8 days. In organ culture, non-malignant, basal epithelial cells underwent a proliferative response. This was accompanied by de-differentiation of glandular structures and by migration of epithelial cells across the surface of the tissue. Erosion of the basement membrane could also be seen in places, but was not widespread. Invasion of epithelial cells into the adjacent stroma was not evident. Production of matrix metalloproteinases (MMPs) with gelatinolytic activity or collagenolytic activity was assessed in organ culture and compared to expression patterns in fresh tissue. MMP-1 (interstitial collagenase) and MMP-9 (92-kDa gelatinase B) were undetectable or low in fresh tissue specimens. Both enzymes were detected in organ culture and both increased over time. Even after 6 days, however, there was only a low level of gelatin-hydrolytic activity and no measurable collagen-hydrolytic activity. In past studies we used organ cultures of normal skin and malignant skin tumours (basal cell carcinomas) to help elucidate the role of collagenolytic and gelatinolytic MMPs in epithelial cell invasion (Varani et al, 2000). Compared to MMP levels observed in skin, levels of these enzymes in prostate are low. The low level of collagenolytic and gelatinolytic MMPs in fresh prostate tissue and in organ-cultured prostate tissue may help explain why there is little tissue destruction in many primary prostate tumours and why the majority of such tumours remain confined to the prostate for extended periods.

Collagen↗
PubMed2001

Glycated serum albumin-induced vascular smooth muscle cell proliferation through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by protein kinase C.

Proliferation of vascular smooth muscle cells (VSMC) contributes to the pathogenesis of atherosclerosis, and glycated serum albumin (GSA, Amadori adduct of albumin) might be a mitogen for VSMC proliferation, which may further be associated with diabetic vascular complications. In this study, we investigated the involvement of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), and protein kinase C (PKC), in GSA-stimulated mitogenesis, as well as the functional relationship between these factors. VSMC stimulation with GSA resulted in a marked activation of ERK. The MAPK kinase (MEK) inhibitor, PD98059, blocked GSA-stimulated MAPK activation and resulted in an inhibition of GSA-stimulated VSMC proliferation. GSA also increased PKC activity in VSMC in a dose-dependent manner. The inhibition of PKC by the PKC inhibitors, GF109203X and Rottlerin (PKCdelta specific inhibitor), as well as PKC downregulation by phorbol 12-myristate 13-acetate (PMA), inhibited GSA-induced cell proliferation and blocked ERK activation. This indicates that phorbol ester-sensitive PKC isoforms including PKCdelta are involved in MAPK activation. Thus, we show that the MAPK cascade is required for GSA-induced proliferation, and that phorbol ester-sensitive PKC isoforms contribute to cell activation and proliferation in GSA-stimulated VSMC.

Animals↗
PubMed2001

Adsorptive properties of metal oxide dispersed carbon materials and characterization of metal oxide fine particles by XAFS.

Surface modification of activated carbon fiber (ACF) with metal oxide increases the adsorptivity of the ACF for supercritical gas such as NO and CH4. In this study, pitch-based activated carbon fibers (P20) were modified with nickel oxide particles. The adsorptive properties and micropore structures of NiO dispersed P20 (NiO-P20) were investigated by nitrogen adsorption isotherms at 77 K. The isotherm was of type 1, suggesting that the NiO-P20 has microporosity. The micropore volume and surface area for NiO-dispersed P20 were smaller than that of P20 by about 15%. The Ni K-edge X-ray absorption fine structure of NiO-P20 has been investigated in order to characterize the species dispersed on P20. The local structure of the NiO particles on the P20 showed some different features compared with the local structure of powdered NiO.

Journal Article↗
PubMed2001

Biomechanical behaviour of bovine temporomandibular articular discs with age.

The purpose was to evaluate age-associated changes in the creep and restoration properties of bovine temporomandibular joint (TMJ) discs under and after sustained tensile stress. Forty discs were obtained from 7- and 10-year-old cattle, referred to as the adult and mature adult groups, respectively. Tension of 1.0 MPa was applied and sustained for 20 min to specimens from ten right discs and of 1.5 MPa to specimens from ten left discs. After the period of tension for the study of creep, the specimens were removed from the tension devices and their restoration observed for 20 min. For comparative purposes the relevant results for a young adult group were recruited from data on 3-year-old bovine TMJ discs reported in a previous study on viscoelastic properties. In all the specimens the time-dependent creep curves showed a marked change in strain during the initial 5 s, but the elastic moduli at the onset of stress were significantly larger in the mature adult group than in the other groups. After 20-min creep, the strains were decreased in relation to the age of the specimen and were significantly smaller in the mature adult than in the young adult. With regard to regional differences, the medial specimens exhibited significantly smaller strains than the central ones in all three age groups. Furthermore, the residual strains after 20-min restoration also decreased slightly with age. It is concluded that the bovine TMJ disc becomes stiff and acquires the capacity to recover from continuous deformation during growth and maturation. These findings suggest that the TMJ disc can modify its viscoelasticity in order to withstand extrinsic functional stresses.

Aging↗
PubMed2001

Action sites of adrenomedullin in the rat brain: functional mapping by Fos expression.

The effects of intracerebroventricular (icv) administration of adrenomedullin (AM) and proadrenomedullin NH2-terminal 20 peptide (PAMP) on the expression of Fos in the central nervous system (CNS) were examined in conscious rats, using immunohistochemistry. Fos-like immunoreactivity (LI) was detected in various brain areas of the rats, including the supraoptic nucleus, the paraventricular nucleus, the locus coeruleus, the area postrema and the nucleus of the tractus solitarius 90 min after icv administration of AM. Few cells with Fos-LI were found in the CNS 90 min after icv administration of saline. Fos-LI was also detected in the various hypothalamic areas after icv administration of PAMP. These results suggest that centrally administered AM and PAMP may cause physiological responses through the activation of a neural network in the hypothalamus and the brainstem.

Adrenomedullin↗
PubMed2001

Decrease of L-selectin expression on human CD34+ cells on freeze-thawing and rapid recovery with short-term incubation.

In the homing process of hematopoietic progenitor cells (HPCs) to bone marrow, several adhesion molecules play important roles. However, HPCs are subjected to dramatic alteration of freeze-thawing that could affect these molecules. In this study, we investigated the effect of cryopreservation on the expression of adhesion molecules on HPCs. The expression of different adhesion molecules on CD34+ cells was examined by flow cytometry using an immunofluorescence technique. Changes in expression before and after cryopreservation, and that of L-selectin on addition of dimethylsulfoxide (DMSO) or with serum incubation, were investigated. The relationship between expression and function was also determined using a transmigration assay system. L-selectin expression on CD34+ cells derived from mobilized peripheral blood (MPB), bone marrow (BM), and umbilical cord blood (CB) was significantly decreased from 37% to 23%, 48% to 11%, and 67% to 19%, respectively, by the freeze-thawing process, while the expression of other adhesion molecules was not appreciably changed. Within 30 minutes of incubation with DMSO, L-selectin expression on CD34(+) cells significantly decreased from 65% to 22%. Furthermore, this was completely prevented by the matrix metalloproteinase (MMP) inhibitor, KB-R8301, indicating that the loss of L-selectin was due to shedding mediated by an MMP. To determine if L-selectin expression can be upregulated after cryopreservation, thawed samples were cultured overnight with serum. Values were observed to return to or rise higher than those of the fresh samples, this being particularly rapid and pronounced when the CD34+ cells were cocultured with the human BM stromal cell line, HS-27A. Therefore, this adhesion molecule could possibly be restored in vivo after transplantation in a way similar to the in vitro case. Despite considerable damage to HPCs during cryopreservation, changes in these cells are reversible, in line with successful restoration of hematopoiesis after transplantation.

Antigens, CD34↗
PubMed2001

Characterization of the secretable ectodomain of thyrotropin receptor produced by the recombinant baculovirus system.

Thyrotropin receptor (TSHR) is a member of the glycoprotein hormone receptor family and an autoantigen of Graves' disease. Various attempts have been made to obtain a large amount of soluble ectodomain of TSHR in insect or mammalian cells, but most of them failed to secrete the overexpressed ectodomain. In the present study, we observed that about one-third of the ectodomain protein (sTSHR-gp), in which the signal peptide of TSHR was replaced by the baculovirus-encoded glycoprotein 67-signal peptide, was secreted into the culture medium and the remainder stayed within cells in the recombinant baculovirus system. Microsequencing the N-terminal of the purified protein confirmed that the baculovirus signal peptide was cleaved at the expected site. Carbohydrate studies using several glycosidases and lectins revealed that the secreted form of the ectodomain had biantennary carbohydrate, whereas the non-secreted form had high-mannose. Moreover, the secreted form of sTSHR-gp exhibited high-affinity ligand binding, whereas the non-secreted form did not show any significant ligand binding. Regarding the interactions of TSHR ectodomains with anti-TSHR antibodies, both the secreted and non-secreted forms of sTSHR-gp, almost completely neutralized the stimulatory and inhibitory anti-TSHR antibody activities. In conclusion, we succeeded in secreting the ectodomain of TSHR into culture medium, which was capable of binding to TSH and neutralizing anti-TSHR antibody activities.

Amino Acid Sequence↗