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Biomedical subjects

Seiji Hayashi

Publications and source records attributed to Seiji Hayashi.

At least 19 recordsLinked to original sources
PubMed2006

Measuring water storage fluctuations in lake Dongting, China, by Topex/Poseidon satellite altimetry.

Although satellite radar altimetry was developed and optimized for open oceans, it has been used to monitor variations in the level of inland water-bodies such as lakes and rivers. Here, for the first time, we have further used the altimetry-derived variation of water level for estimating the fluctuation of water storage as an addition to the present in situ water storage estimation systems to be used in remote areas and in emergency situation such as in the events flooding monitoring and for studying the effect of climate change. Lake Dongting, the second largest lake in China, influenced frequently by flooding, was, therefore, chosen to demonstrate the potential of the technique. By using the concept of an "assumed reference point", we converted Topex/Poseidon satellite altimetry data on water level variations in Lake Dongting to "water level" data. The "water level" time-series data and in situ water storage were used to establish a rating curve. From the rating curve, we converted data on "water level" derived from seven years (1993-1999) of Topex/Poseidon data to actual water storage in Lake Dongting. The result reveals that the seasonal and annual fluctuations of water storage occurred during the 1990s with a more frequent flooding at the late 1990s' especially the flooding in whole catchment level in 1998 and 1999. The study supports the usefulness of satellite altimetry for dense and continuous monitoring of the temporal variations in water dynamic in moderate to large lakes.

China↗
PubMed2006

De novo vertebral artery dissecting aneurysm after contralateral vertebral artery occlusion--two case reports.

Two patients developed de novo vertebral artery dissecting aneurysm after contralateral vertebral artery occlusion. A 36-year-old man presented with brainstem ischemia and was treated non-surgically. Subsequent angiography showed spontaneous vertebral artery occlusion at the site of dissection. A 45-year-old man developed subarachnoid hemorrhage due to vertebral artery dissecting aneurysm. He underwent endovascular occlusion of the vertebral artery proximal to the dissecting aneurysm. These patients developed de novo dissecting aneurysm on the contralateral vertebral artery at 13 months and 11 days after unilateral vertebral artery occlusion, respectively. These cases strongly suggest that changes in hemodynamic stress due to unilateral vertebral artery occlusion are related to de novo dissecting aneurysm on the contralateral side. The risk of de novo dissecting aneurysm may be increased by proximal occlusion or trapping of dissecting aneurysm of the contralateral vertebral artery.

Adult↗
PubMed2005

Nitrogen budgets of agricultural fields of the Changjiang River basin from 1980 to 1990.

To assess the fate of the large amounts of nitrogen (N) brought into the agricultural environment by human activities in the Changjiang River basin, we used [China's county level agricultural database of 1980 and 1990. National Resources and Environmental Data Center, China] and published conversion data to set up a complete N budget for the Changjiang River basin. Sources considered include imported N such as atmospheric deposition, inorganic fertilizer, biological fixation and manure. Dominant losses considered include crop harvests, denitrification of soil nitrate and NH3 volatilization, and the budget was estimated from the difference between all inputs and all outputs. Therefore, the geographic distribution of excess N, considered as lost, by N storage in farmland and N transported to water bodies in Changjiang River basin was analyzed. In the Changjiang River basin, the anthropogenic reactive N has far exceeded the terrestrial bio-fixed N in nature, and human activities have significantly altered the N cycle in this region. The total inputs of N in 1980 and 1990 were 8.0 and 12.9 Tg N, respectively. The total N outputs are 4.41 Tg N in 1980 and 6.85 Tg N in 1990. Thus, the excess N that was stored in farmland was 1.51 Tg N at 1980 and 2.67 Tg N at 1990, respectively, and losses through transportation to water bodies in 1980 was 2.08 and 3.38 Tg N in 1990, respectively. Our research shows that from 1980 to 1990, cultivated land increased 5.9%, grain production increased 30% and N fertilizer-use increased 106%, but the N fertilizer-use efficiency decreased 36%, and the variations in the distribution of N fertilizer-use efficiency, N budgets and N transport to water bodies tended to coincide with each other geographically.

Journal Article↗
PubMed2005

Incipient stage of pulmonary Langerhans-cell histiocytosis complicated with pulmonary tuberculosis was examined by high-resolution computed tomography.

A 29-year-old man with a smoking history of 20 pack years was diagnosed with tuberculosis because Mycobacterium tuberculosis was detected in his gastric juice. His chest radiograph showed multiple nodular opacities on left upper lobe. He was treated with anti-tuberculosis drugs in our hospital. Six months after the therapy, he began to complain of dry cough and shortness of breath on exertion. Chest radiograph showed reticular opacities in both upper and middle lung fields. Multiple thick- and thin-walled bizarre-shaped cysts and ill-defined centrilobular opacities were seen mainly in upper and mid-lungs on high-resolution computed tomography (HRCT). He was diagnosed with pulmonary Langerhans-cell histiocytosis (PLCH) by transbronchial lung biopsy specimens from right upper lobe. HRCT findings before the treatment of tuberculosis were retrospectively examined. Several small thin-walled centrilobular cysts were scattered in the right upper and middle lung fields without apparent nodular lesions. We must consider the possibility of PLCH when these findings are detected on HRCT.

Adult↗
PubMed2005

QT PRODACT: a multi-site study of in vitro action potential assays on 21 compounds in isolated guinea-pig papillary muscles.

To construct a non-clinical database for drug-induced QT interval prolongation, the electrophysiological effects of 11 positive and 10 negative compounds on action potentials (AP) in guinea-pig papillary muscles were investigated in a multi-site study according to a standard protocol. Compounds with a selective inhibitory effect on the rapidly activated delayed rectifier potassium current (IKr) prolonged action potential duration at 90% repolarization (APD90) in a concentration-dependent manner, those showing Ca2+ current (ICa) inhibition shortened APD30, and those showing Na+ current (INa) inhibition decreased action potential amplitude (APA) and Vmax. Some of the mixed ion-channel blockers showed a bell-shaped concentration-response curve for APD90, probably due to their blockade of INa and/or ICa, sometimes leading to a false-negative result in the assay. In contrast, all positive compounds except for terfenadine and all negative compounds with IKr-blocking activity prolonged APD30-90 regardless of their INa- and/or ICa-blocking activities, suggesting that APD30-90 is a useful parameter for evaluating the IKr-blocking activity of test compounds. Furthermore, the assay is highly informative regarding the modulation of cardiac ion channels by test compounds. Therefore, when APD90 and APD30-90 are both measured, the action potential assay can be considered a useful method for assessing the risk of QT interval prolongation in humans in non-clinical safety pharmacology studies.

Action Potentials↗
PubMed2005

QT PRODACT: evaluation of the potential of compounds to cause QT interval prolongation by action potential assays using guinea-pig papillary muscles.

Certain compounds that prolong QT interval in humans have little or no effect on action-potential (AP) duration used traditionally, but they inhibit rapidly-activated-delayed-rectifier potassium currents (IKr) and/or human ether-a-go-go-related gene (hERG) currents. In this study using isolated guinea-pig papillary muscles, we investigated whether new parameters in AP assays can detect the inhibitory effects of various compounds on IKr and/or hERG currents with high sensitivity. The difference in AP duration between 60% and 30% repolarization, 90% and 60% repolarization, and 90% and 30% repolarization (APD30-60, APD60-90, and APD30-90, respectively) were calculated as the new parameters. All the 15 IKr and/or hERG current inhibitors that have been reported (9 compounds) or not reported (6 compounds) to inhibit calcium currents prolonged APD30-60, APD60-90, and/or APD30-90; and 8 of the 15 inhibitors prolonged APD30-60, APD60-90, and/or APD30-90 more potently than APD90. The APD30-60, APD60-90, and APD30-90 measurements revealed no difference in sensitivity when evaluating the effects of the IKr and/or hERG current inhibitors on the three parameters. On the other hand, compounds with little or no effect on hERG currents had no effect on APD30-60, APD60-90, or APD30-90. Therefore, it is concluded that in AP assays using isolated guinea-pig papillary muscles, APD30-60, APD60-90, and APD30-90 are useful indexes for evaluating the inhibitory effects of compounds including mixed ion-channel blockers on IKr and/or hERG currents.

Action Potentials↗
PubMed2005

CD9 overexpression suppressed the liver metastasis and malignant ascites via inhibition of proliferation and motility of small-cell lung cancer cells in NK cell-depleted SCID mice.

CD9, a transmembrane protein known as motility-related protein-1, plays a pivotal role in regulating cell adhesion, motility, and proliferation, and has been regarded as an important metastasis-inhibitory factor of various human cancers. However, little information has been obtained regarding the highly metastatic human small-cell lung cancer (SCLC). In the present study, an SCLC cell line (OS3-R5), lacking CD9 expression, was transfected with human CD9 gene to assess the role of CD9 on the metastatic potential of SCLC. CD9 gene transfection into OS3-R5 cells resulted in cell proliferation and motility in vitro. Parental and mock-transfected OS3-R5 cells developed liver metastasis and malignant ascites when they were intravenously inoculated into NK cell-depleted SCID mice. CD9 gene transfection into OS3-R5 cells caused suppression of the liver metastasis and malignant ascites. Immunohistochemical analysis revealed that the number of proliferating tumor cells was significantly fewer in liver lesions produced by CD9 gene-transfected OS3-R5 cells than those produced by parental or mock control OS3-R5 cells. In addition, no detectable levels of CD9 were expressed in metastatic tumor cells in mice bearing CD9 gene-transfected OS3-R5 cells, as well as those in mice bearing parental or mock control OS3-R5 cells. These results suggest that the restored expression of CD9 in SCLC cells may reduce the metastatic spread of SCLC cells via the inhibition of cell proliferation and motility.

Animals↗
PubMed2004

Detecting ATP release by a biosensor method.

Cells release adenosine 5'-triphosphate (ATP) into the extracellular space in response to various stimuli. This released ATP plays an important physiological role in cell-to-cell signal transduction. The bulk ATP concentration can be detected using a conventional luciferin-luciferase assay. However, the ATP concentration in the vicinity of the cell surface is often different from the bulk concentration because of its rapid degradation by ecto-ATPases and because of delayed diffusion due to unstirred layer effects. Here, we describe a simple biosensor method to measure the local ATP concentration on the cell surface in real time. The method is based on the ATP-dependent opening of ligand-gated cation channels of purinergic P2X receptors expressed in undifferentiated pheochromocytoma (PC12) cells or in human embryonic kidney 293 (HEK293) cells stably transfected with recombinant P2X2 purinergic receptors. Under the whole-cell configuration of patch-clamp, a sensor PC12 cell or HEK293 is positioned within the proximity of a target cell, and the P2X-mediated currents induced by ATP released from a given site on the target cell surface is measured. The ATP release is quantified by a calibration procedure utilizing local puff applications of ATP at preset concentrations.

Adenosine Triphosphate↗
PubMed2004

Increased level of soluble E-selectin in the serum from patients with idiopathic pulmonary fibrosis.

To elucidate the biological significance of selectin for idiopathic pulmonary fibrosis, we titrated the serum soluble E-selectin. From 31 cases of idiopathic pulmonary fibrosis patients without signs or symptoms of infection, the serum was obtained and the concentration was titrated by enzyme-linked immunosorbent assay. The serum soluble E-selectin titer was significantly higher than that of healthy controls. However, significant elevation was not observed in the sera from the patients with other pulmonary diseases, such as pulmonary emphysema, sarcoidosis, or bronchiectasis. In the patients with idiopathic pulmonary fibrosis, the number of white blood cells, C-reactive protein or lactate dehydrogenase activity did not show a significant relationship with the soluble E-selectin titer. About 16 out of the 31 idiopathic fibrosis patients, the serum surfactant apoprotein-A titer, which is a parameter of the disease activity of idiopathic pulmonary fibrosis, was also tested. The surfactant apoprotein-A titer was loosely correlated with the soluble E-selectin titer. These observations suggest that E-selectin may be relevant to the pathogenesis of idiopathic pulmonary fibrosis, and it may be a novel clinical parameter for idiopathic pulmonary fibrosis.

Adult↗
PubMed2004

Lymphangiogenesis in lymphangioleiomyomatosis: its implication in the progression of lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells (LAM cells) in the lungs, lymph nodes, and/or other organs. We examined lymphangiogenesis using immunohistochemistry for Flt-4 (VEGFR-3), a new specific marker for lymphatic endothelial cells, as well as the expression of vascular endothelial growth factor (VEGF)-C in LAM. Specimens were obtained from 6 autopsy cases, a single lung transplant case, and 8 surgical cases for analyses. We demonstrated that lymphatics were extremely abundant in both pulmonary and extrapulmonary LAM and that lymphatic endothelial cells not only proliferated encompassing LAM foci but also infiltrated the intra-LAM foci, and that in advanced LAM, lymphangiogenesis involved vascular walls and interstitium surrounding the area where LAM cells proliferate. In contrast, angiogenesis, confirmed with CD31 immunostaining, was observed less in the LAM foci. LAM cells demonstrated positive reactivity against anti-VEGF-C antibody at varying intensities. Significant correlation (P < 0.001) was noted between the degree of lymphangiogenesis in LAM or VEGF-C expression on LAM cells and lymphagioleiomyomatosis histologic score (LHS), which represents the histologic severity of pulmonary LAM and has been reported to have prognostic significance. Our study is likely to provide a novel point of view on the pathophysiologic significance of lymphangiogenesis in LAM.

Adult↗
PubMed2004

WT1 peptide-based immunotherapy for patients with lung cancer: report of two cases.

The Wilms' tumor gene WT1 is overexpressed in various types of solid tumors, including lung and breast cancer and WT1 protein is a tumor antigen for these malignancies. In phase I clinical trials of WT1 peptide-based cancer immunotherapy, two patients with advanced lung cancer were intradermally injected with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant. Consecutive WT1 vaccination at 2-week intervals resulted in a reduction in tumor markers such as chorio-embryonic antigen (CEA) and sialyl Lewis (x) (SLX) and by a transient decrease in tumor size. No adverse effects except for local erythema at the injection sites of WT1 vaccine were observed. These results provided us with the first clinical evidence demonstrating that WT1 peptide-based immunotherapy should be a promising treatment for patients with lung cancer.

Aged↗
PubMed2004

[A case of infected bulla caused by Mycobacterium kansasii].

A 62-year-old man was referred to our hospital because of persistent sub-fever. A pulmonary fungal infection was suspected owing to the elevation of the serum-D-glucan level. Since a chest radiograph and a CT scan revealed intrabullous fluid in the right upper lobe, percutaneous needle aspiration was performed. Although acid-fast bacilli smears of the sputum and intrabullous fluid were negative, their cultures were found to be positive thereafter. M. kansasii was isolated and identified. After chemotherapy with antituberculous drugs, sub-fever improved and intrabullous fluid disappeared completely. Infected bulla caused by mycobacteria is very rare.

Antitubercular Agents↗
PubMed2004

[Application of interlocking detachable coil (IDC) in superselective bronchial artery embolization].

Bronchial artery embolization (BAE) is almost the only effective nonsurgical treatment for massive hemoptysis. Metallic coils with plastic fibers are widely used as embolic materials. We have introduced an interlocking detachable coil (IDC) for BAE. IDC is a mechanically detachable coil, allowing the operator to seek the ideal shape until its final release. We compared hemoptysis patients treated with conventional metallic coils (24 patients, non-IDC group) with those treated with conventional coils and IDCs (26 patients, IDC group). The hemoptysis rate after three months is significantly lower in the IDC group than in the non-IDC group (7.7% vs. 16.3%, p = 0.035 Fisher's exact method). Total procedure time (in staged or repetitive BAE cases, procedure times are added together) is significantly shorter in the IDC group than in the non-IDC group (3.4 +/- 1.4 hours vs. 4.4 +/- 2.5 hours, p = 0.040 unpaired t-test). IDC is a useful device for BAE. This is the first-ever report documenting the usefulness of IDC for BAE.

Aged↗
PubMed2003

Hepatoma-derived growth factor is involved in lung remodeling by stimulating epithelial growth.

Lung epithelial cells have an integral role in the maintenance of lung homeostasis; however, the regulatory mechanism thereof has not been fully clarified. Recently, hepatoma-derived growth factor (HDGF) was reported to be involved in organ development and remodeling through its mitogenic effect. We investigated the biological role of HDGF in lung remodeling. HDGF was more highly expressed in the lungs of idiopathic pulmonary fibrosis, chiefly in the epithelial cells, than in control nonfibrotic lungs. We also confirmed the expression of HDGF protein and mRNA in the lungs of bleomycin-instilled mice, mainly in the bronchial and alveolar epithelial cells, by immunohistochemical analysis and in situ hybridization. We found that recombinant HDGF promoted DNA synthesis in rat alveolar epithelial cells and A549 cells in vitro. Endogenous HDGF overexpressed by gene transfer was translocated into the nucleus and promoted the proliferation of A549 cells. In vivo intratracheal instillation of recombinant HDGF induced the proliferation of bronchial and alveolar epithelial cells without causing marked interstitial inflammation. These findings suggest that HDGF may be involved in lung remodeling after injury by promoting the proliferation of lung epithelial cells, probably in an autocrine manner.

Animals↗
PubMed2003

Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes.

Tetraspanins CD9 and CD81 facilitate the fusion between gametes, myoblasts, or virus-infected cells. Here, we investigated the role of these tetraspanins in the fusion of mononuclear phagocytes. Expression of CD9 and CD81 and their complex formation with integrins were up-regulated when blood monocytes were cultured under normal conditions. Under fusogenic conditions in the presence of Con A, CD9 and CD81 up-regulation was inhibited, and their complex formation with integrins was down-regulated. Anti-CD9 and -CD81 antibodies, which were previously shown to inhibit the fusion of gametes, myoblasts, and virus-infected cells, unexpectedly promoted the fusion of monocytes and alveolar macrophages. However, these effects were not due to altered cell adhesion, aggregation, or cytokine production. When stimulated in vitro or in vivo, alveolar macrophages and bone marrow cells of CD9- and CD81-null mice formed larger numbers of multinucleated cells than those of wild-type mice. Finally, CD9/CD81 double-null mice spontaneously developed multinucleated giant cells in the lung and showed enhanced osteoclastogenesis in the bone. These results suggest that CD9 and CD81 coordinately prevent the fusion of mononuclear phagocytes.

Animals↗
PubMed2003

Macula densa cell signaling involves ATP release through a maxi anion channel.

Macula densa cells are unique renal biosensor cells that detect changes in luminal NaCl concentration ([NaCl](L)) and transmit signals to the mesangial cellafferent arteriolar complex. They are the critical link between renal salt and water excretion and glomerular hemodynamics, thus playing a key role in regulation of body fluid volume. Since identification of these cells in the early 1900s, the nature of the signaling process from macula densa cells to the glomerular contractile elements has remained unknown. In patch-clamp studies of macula densa cells, we identified an [NaCl](L)-sensitive ATP-permeable large-conductance (380 pS) anion channel. Also, we directly demonstrated the release of ATP (up to 10 microM) at the basolateral membrane of macula densa cells, in a manner dependent on [NaCl](L), by using an ATP bioassay technique. Furthermore, we found that glomerular mesangial cells respond with elevations in cytosolic Ca(2+) concentration to extracellular application of ATP (EC(50) 0.8 microM). Importantly, we also found increases in cytosolic Ca(2+) concentration with elevations in [NaCl](L), when fura-2-loaded mesangial cells were placed close to the basolateral membrane of macula densa cells. Thus, cell-to-cell communication between macula densa cells and mesangial cells, which express P2Y(2) receptors, involves the release of ATP from macula densa cells via maxi anion channels at the basolateral membrane. This mechanism may represent a new paradigm in cell-to-cell signal transduction mediated by ATP.

Adenosine Triphosphate↗