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Biomedical subjects

Hiroshi Hasegawa

Publications and source records attributed to Hiroshi Hasegawa.

At least 19 recordsLinked to original sources
PubMed2007

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.

Age of Onset↗
PubMed2007

Appearance of noncompaction-like remodeling of the anatomical right ventricle in a middle-aged subject with modified transposition of the great arteries who did not undergo surgery.

We describe noncompaction-like remodeling of the anatomical right ventricle (ARV) in a middle-aged subject with modified transposition of the great arteries (TGA). A 54 year-old male had been diagnosed with modified TGA at age 40, but no surgery was performed. Enhanced multislice CT revealed the ascending aorta coursing left of the anterior pulmonary trunk. Furthermore, the myocardium of the ARV appeared thickened, but contrast material could be observed in the ARV myocardium, which resembled noncompaction of the left ventricle (LV). We speculated trabecular development of the ARV, such as a Chiari network, and with TGA, the ARV provided systemic circulation through the aorta. The ARV wall may have thickened due to systemic pressure load, resulting in reduction of wall motion of the ARV on transthoracic echocardiogram. Recent advances in multislice CT imaging have revolutionized the exploration of RV anatomy, especially for depicting the three-dimensional appearance of noncompaction-like remodeling of the ARV in modified TGA in addition to transposition of the great arteries.

Humans↗
PubMed2007

Value of laparoscopic appendectomy in perforated appendicitis.

BACKGROUND: The purpose of this clinical study was to evaluate the efficacy of laparoscopic appendectomy in patients with perforated appendicitis. METHODS: This study involved a total of 73 consecutive patients who had undergone appendectomy for perforated appendicitis between January 1999 and December 2004. While 39 patients underwent open appendectomy (OA) during the first 3 years, the remaining 34 patients underwent laparoscopic appendectomy (LA) during the last 3 years. RESULTS: There was no case of LA converted to OA. No significant difference was found in the operating time between the two groups. Laparoscopic appendectomy was associated with less analgesic use, earlier oral intake restart (LA, 2.6 days; OA, 5.1 days), shorter median hospital stay (LA, 11.7 days; OA, 25.8 days), and lower rate of wound infections (LA, 8.8%; OA, 43.6%). CONCLUSIONS: These results suggest that LA for perforated appendicitis is a safe procedure that may prove to have significant clinical advantages over conventional surgery.

Abscess↗
PubMed2006

Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction.

BACKGROUND: This study examined feasibility and safety of granulocyte colony-stimulating factor (G-CSF) treatment for patients with acute myocardial infarction (AMI). METHODS: Forty patients with AMI related with the left anterior descending coronary artery, who underwent successful percutaneous coronary intervention (PCI), were randomized into G-CSF group (n=18) or Control group (n=22). G-CSF treatment was started within 24 h after PCI. 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) was performed at 4 days and 6 months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial perfusion. RESULTS: LVEF at 6 months was significantly better than that at 4 days in G-CSF group (p=0.013), but not changed in Control group (p=0.245). Although no significant difference was observed for LVEDV between the two groups, LVESV tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6 months after AMI was not significantly different between the two groups. CONCLUSIONS: G-CSF treatment for patients with AMI was effective and did not have any clinical and angiographic adverse effects.

Aged↗
PubMed2006

Adsorption of platinum (IV), palladium (II) and gold (III) from aqueous solutions onto L-lysine modified crosslinked chitosan resin.

Crosslinked chitosan resin chemically modified with L-lysine has been used to investigate the adsorption of Pt(IV), Pd(II) and Au(III) from aqueous solutions. Batch adsorption studies were carried out with various parameters, such as initial metal ion concentration, contact time, pH and temperature. The maximum adsorption capacity was found at pH 1.0 for Pt(IV), at pH 2.0 for Au(III) and Pd(II). Langmuir and Freundlich isotherm models were applied to analyze the experimental data. The best interpretation for the experimental data was given by the Langmuir isotherm and the maximum adsorption capacity was found to be 129.26 mg/g for Pt(IV), 109.47 mg/g for Pd(II) and 70.34 mg/g for Au(III). The kinetic data was tested using pseudo-first-order and pseudo-second-order kinetic models. Kinetic data correlated well with the pseudo-second-order kinetic model, indicating that the chemical sorption was the rate-limiting step. Thermodynamic parameters like Gibbs free energy (DeltaG degrees), enthalpy (DeltaH degrees) and entropy (DeltaS degrees) were evaluated by applying the Van't Hoff equation. The thermodynamic study indicated that the adsorption process is spontaneous and exothermic in nature. The desorption studies were carried out using various reagents. The maximum percent desorption of precious metal ions were obtained when the reagent 0.7 M thiourea-2 M HCl was used.

Adsorption↗
PubMed2006

Prediction of measurement uncertainty in isotope dilution gas chromatography/mass spectrometry.

An equation is theoretically derived which describes the relative standard deviation (RSD) of the amount ratios of analyte to its isotope-labeled variant in gas chromatography/mass spectrometry (GC/MS) using the stable isotope dilution method. The determination of methyltestosterone is taken as an example. The uncertainty equation proposed is justified by comparing the theoretical RSD values with the experimental RSD values obtained by replication over a wide range of analyte amount. The detection limit and quantitation limit are estimated from the continuous plot (precision profile) of the theoretical RSD against analyte amount.

Deuterium↗
PubMed2006

Response of spinach and komatsuna to biogas effluent made from source-separated kitchen garbage.

Recycling of kitchen garbage is an urgent task for reducing public spending and environmental burdens by incineration and/or landfill. There is an interesting regional effort in Ogawa, Saitama prefecture, Japan, in which source-separated kitchen garbage is anaerobically fermented with a biogas plant and the resultant effluent is used as a quick-release organic fertilizer by surrounding farmers. However, scientific assessments of fertilizer values and risks in the use of the effluent were lacking. Thus, a field experiment was conducted from 2003 to 2004 in Tohoku National Agricultural Research Center to grow spinach (Spinacia oleracea L.) and komatsuna (Brassica rapa var. perviridis L. H. Bailey) for evaluating the fertilizer value of the kitchen garbage effluent (KGE), nitrate, coliform group (CG), Escherichia coli, fecal streptococci (FS), and Vibrio parahaemolyticus concentrations of KGE and in the soil and the plant leaves. A cattle manure effluent (CME) and chemical fertilizers (NPK) were used as controls. Total nitrogen (N) and ammonium N concentrations of the KGE were 1.47 and 1.46 g kg(-1), respectively. The bacteria tested were detected in both biogas effluents in the order of 2 to 3 log CFU g(-1), but there was little evidence that the biogas effluents increased these bacteria in the soil and the plant leaves. At the rate of 22 g N m(-2), yield, total N uptake, apparent N recovery rate, and leaf nitrate ion concentration at harvest of spinach and komatsuna in the KGE plot were mostly comparable to those in the NPK and CME plots. We conclude that the KGE is a quick-release N fertilizer comparable to chemical fertilizers and does not cause contamination of CG, E. coli, FS, or V. parahaemolyticus in the soil and spinach and komatsuna leaves.

Brassica rapa↗
PubMed2006

Potent free radical scavenger, edaravone, suppresses oxidative stress-induced endothelial damage and early atherosclerosis.

OBJECTIVE: Effects of potent free radical scavenger, edaravone, on oxidative stress-induced endothelial damage and early atherosclerosis were investigated using animal models and cultured cells. METHODS AND RESULTS: Endothelial apoptosis was induced by 5-min intra-arterial exposure of a rat carotid artery with 0.01 mmol/L H(2)O(2). Edaravone treatment (10mg/kg i.p.) for 3 days suppressed endothelial apoptosis, as evaluated by chromatin staining of en face specimens at 24h, by approximately 40%. Similarly, edaravone dose-dependently inhibited H(2)O(2)-induce apoptosis of cultured endothelial cells in parallel with the inhibition of 8-isoprostane formation, 4-hydroxy-2-nonenal (4-HNE) accumulation and VCAM-1 expression. Next, apolipoprotein-E knockout mice were fed a high-cholesterol diet for 4 weeks with edaravone (10mg/kg i.p.) or vehicle treatment. Edaravone treatment decreased atherosclerotic lesions in the aortic sinus (0.18+/-0.01 to 0.09+/-0.01 mm(2), P<0.001) and descending aorta (5.09+/-0.86 to 1.75+/-0.41 mm(2), P<0.05), as evaluated by oil red O staining without influence on plasma lipid concentrations or blood pressure. Dihydroethidium labeling and cytochrome c reduction assay showed that superoxide anions in the aorta were suppressed by edaravone. Also, plasma 8-isoprostane concentrations and aortic nitrotyrosine, 4-HNE and VCAM-1 contents were decreased by edaravone treatment. CONCLUSIONS: These results suggest that edaravone may be a useful therapeutic tool for early atherosclerosis, pending the clinical efficacy.

Aldehydes↗
PubMed2006

Gene expression and localization of diacylglycerol kinase isozymes in the rat spinal cord and dorsal root ganglia.

The dorsal root ganglion (DRG) and dorsal horn of the spinal cord are areas through which primary afferent information passes enroute to the brain. Previous studies have reported that, during normal neuronal activity, the regional distribution of a second messenger, diacylglycerol (DG), which is derived from phosphoinositide turnover, is diverse in these areas. However, the way that DG is regulated in these organs remains unknown. The present study was performed to investigate mRNA expression and protein localization of DG kinase (DGK) isozymes, which play a central role in DG metabolism. Gene expression for DGK isozymes was detected with variable regional distributions and intensities in the spinal cord. Among the isozymes, most intense signals were found for DGKzeta and DGKiota in the DRG. By immunohistochemical analysis, DGKzeta immunoreactivity was detected heterogeneously in the nucleus and cytoplasm of small DRG neurons with variable levels of distribution, whereas it was detected exclusively in the cytoplasm of large neurons. On the other hand, DGKiota immunoreactivity was distributed solely in the cytoplasm of most of the DRG neurons. Double-immunofluorescent imaging of these isozymes showed that they coexisted in a large population of DRG neurons at distinct subcellular sites, i.e., DGKzeta in the nucleus and DGKiota in the cytoplasm. Thus, DGK isozymes may have different functional roles at distinct subcellular sites. Furthermore, the heterogeneous subcellular localization of DGKzeta between the nucleus and cytoplasm implies the possible translocation of this isozyme in small DRG neurons under various conditions.

Animals↗
PubMed2006

TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity.

The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins, including the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can be generated by reconstituting these four proteins in yeast and Spodoptera frugiperda (sf9) cells. However, a critical but unanswered question about the biology of the presenilin complexes is how their activity is modulated in terms of substrate specificity and/or relative activities at the gamma and epsilon sites. A corollary to this question is whether additional proteins in the presenilin complexes might subsume these putative regulatory functions. The hypothesis that additional proteins might exist in the presenilin complexes is supported by the fact that enzymatically active complexes have a mass that is much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650 kDa observed, compared with about 220 kDa predicted). To address these questions we undertook a search for presenilin-interacting proteins that differentially affected gamma- and epsilon-site cleavage events. Here we report that TMP21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage without affecting epsilon-secretase activity.

Amyloid Precursor Protein Secretases↗
PubMed2006

Granulocyte colony stimulating factor directly inhibits myocardial ischemia-reperfusion injury through Akt-endothelial NO synthase pathway.

OBJECTIVE: Granulocyte colony stimulating factor (G-CSF) has been reported recently to prevent cardiac remodeling and dysfunction after acute myocardial infarction through signal transducer and activator of transcription 3 (STAT3). In this study, we examined acute effects of G-CSF on the heart against ischemia-reperfusion injury. METHODS AND RESULTS: Rat hearts were subjected to global 35-minute ischemia and 120-minute reperfusion in Langendorff system with or without G-CSF (300 ng/mL). G-CSF administration was started at the onset of reperfusion. Triphenyltetrazolium chloride staining revealed that G-CSF markedly reduced the infarct size. G-CSF strongly activated Janus kinase 2 (Jak2), STAT3, extracellular signal-regulated kinase (ERK), Akt, and endothelial NO synthase (NOS) in the hearts subjected to ischemia followed by 15-minute reperfusion. The G-CSF-induced reduction in infarct size was abolished by inhibitors of phosphatidylinositol 3-kinase, Jak2, and NOS but not of mitogen-activated protein kinase kinase (MEK). CONCLUSIONS: These results suggest that G-CSF acts directly on the myocardium during ischemia-reperfusion injury and has acute nongenomic cardioprotective effects through the Akt-endothelial NOS pathway.

Animals↗
PubMed2006

G-CSF prevents the progression of atherosclerosis and neointimal formation in rabbits.

Granulocyte colony-stimulating factor (G-CSF) prevents left ventricular remodeling after myocardial infarction, but its effect on atherosclerosis is unknown. We examined two kinds of rabbit atherosclerosis models. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHL-MI) rabbits were treated with G-CSF or saline for 7 days from 14 months old. The vascular injury models were created by inflating angioplasty balloon in the iliac artery of rabbits and were divided into G-CSF and saline group. G-CSF significantly reduced the stenosis score of coronary artery and lipid plaque area of thoracic aorta in WHHL-MI rabbits at 4 weeks after the treatment. In the vascular injury model, G-CSF significantly prevented an increase in neointima/media ratio at 4 weeks after the treatment. G-CSF accelerated the reendothelialization of denuded arteries, and the pretreatment with nitric oxide synthase inhibitor significantly inhibited it. These results suggest that G-CSF has a therapeutic potential for the progression of atherosclerosis.

Animals↗
PubMed2006

Cardioprotective effects of granulocyte colony-stimulating factor in swine with chronic myocardial ischemia.

OBJECTIVES: The aim of this study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) on chronic myocardial ischemia in swine. BACKGROUND: We recently have reported that G-CSF prevents cardiac remodeling and dysfunction after acute myocardial infarction in mice and swine. It remains unclear whether G-CSF has beneficial effects on chronic myocardial ischemia. METHODS: An ameroid constrictor was placed on left circumflex coronary artery of swine. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were randomly assigned into the following two groups: 1) administration of vehicle (control group, n = 10), and 2) administration of G-CSF (10 microg/kg/day) for seven days (G-CSF group, n = 10). RESULTS: Echocardiographic examination revealed that the G-CSF treatment prevented left ventricular dilation and dysfunction at eight weeks after the operation. Stress echocardiography revealed that G-CSF ameliorated the regional contractility of chronic myocardial ischemia. Morphological analysis revealed that the extent of myocardial fibrosis of the ischemic region was less in the G-CSF group than in control group. There were more vessels and less apoptotic cells at the ischemic region of the heart of the G-CSF group than control group. Moreover, Akt1 was more strongly activated in the heart of the G-CSF group than control group. CONCLUSIONS: These findings suggest that G-CSF improves cardiac function of chronic myocardial ischemia through decreases in fibrosis and apoptotic death and an increase in vascular density in the ischemic region.

Animals↗
PubMed2006

Effects of G-CSF on left ventricular remodeling and heart failure after acute myocardial infarction.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that promotes proliferation and differentiation of neutrophil progenitors. G-CSF also possesses immunomodulatory properties. G-CSF-induced hematopoietic stem cell mobilization is widely used clinically for transplantation. After it was recently reported that G-CSF mobilizes bone marrow stem cells (BMSCs) into the infarcted hearts and accelerates the differentiation into vascular cells and cardiac myocytes, myocardial regeneration utilizing mobilization of BMSCs by G-CSF is attracting the attention of investigators. In animal models, G-CSF prevents left ventricular remodeling and dysfunction after acute myocardial infarction, at least in part, through a decrease in apoptotic cells and an increase in vascular cells. Although it is controversial whether BMSCs mobilized by G-CSF can differentiate into cardiac myocytes, G-CSF-induced angiogenesis is indeed recognized in infarcted heart. The cardioprotective effects of G-CSF are recognized even in isolated perfused heart. In addition, G-CSF activates various signaling pathways such as Akt, extracellular signal-regulated kinase, and Janus kinase 2/signal transducer and activator of transcription 3 through G-CSF receptors in cardiac myocytes. These observations suggest that G-CSF not only induces mobilization of stem cells and progenitor cells but also acts directly on cardiomyocytes. Therefore, G-CSF may be utilized as a novel agent to have protective and regenerative effects on injured myocardium. Although the effects of G-CSF on the progression of atherosclerosis are still unclear, there is a possibility that G-CSF will become a promising therapy for ischemic heart diseases.

Animals↗
PubMed2006

Involvement of recognition and interaction of carnitine transporter in the decrease of L-carnitine concentration induced by pivalic acid and valproic acid.

PURPOSE: Prodrugs with pivalic acid and valproic acid decrease L-carnitine concentration in plasma and tissues by urinary excretion of acylcarnitine as pivaloylcarnitine (PC) and valproylcarnitine (VC), respectively. We investigated the role of the Na+/L-carnitine cotransporter in the porcine kidney epithelial cell line, LLC-PK1 for the decrease of L-carnitine concentration. METHODS: The uptake of L-[3H]carnitine, acetyl-L-[3H]carnitine (AC), L-[3H]PC and L-[3H]VC were investigated in LLC-PK1 cells seeded in a 6-well culture plate. RESULTS: L-Carnitine and AC uptake in LLC-PK1 cells exhibited Na+ dependency. The Km values for L-carnitine and AC uptake were 11.0 and 8.18 microM, respectively. These results indicated expression of Na+/ L-carnitine cotransporter in LLC-PK1 cells. PC and VC inhibited Na+/L-carnitine cotransporter in the competitive (Ki = 90.4 microM) and noncompetitive (Ki = 41.6 microM) manners, respectively. PC and VC uptake by Na+/L-carnitine cotransporter were not observed in LLC-PK1 cells. CONCLUSIONS: These data suggested that PC and VC formed in the body could not be reabsorbed in the kidney, resulting in the decrease of L-carnitine concentration. In addition, inhibition of L-carnitine reabsorption by VC with lower Ki value could induce the decrease of L-carnitine concentration. Collectively, the recognition and interaction of Na+/L-carnitine cotransporter are important factors for carnitine homeostasis.

Acetylcarnitine↗
PubMed2006

Distinct effects of folate and choline deficiency on plasma kinetics of methionine and homocysteine in rats.

Both folate and betaine, a choline metabolite, play essential roles in the remethylation of homocysteine to methionine. We have studied the effects of folate and choline deficiency on the plasma kinetics of methionine, especially remethylation of homocysteine to methionine, by means of stable isotope methodology. After a bolus intravenous administration of [(2)H(7)]methionine (5 mg/kg body weight) into the rats fed with folate-, choline-, folate + choline-deficient or control diets, the plasma concentrations of [(2)H(7)]methionine, demethylated [(2)H(4)]homocysteine, and remethylated [(2)H(4)]methionine were determined simultaneously with endogenous methionine and homocysteine by gas chromatography-mass spectrometry-selected ion monitoring. The total plasma clearance of [(2)H(7)]methionine was not significantly different among groups, suggesting that the formation of [(2)H(4)]homocysteine from [(2)H(7)]methionine was not influenced by deficiencies of folate and choline. The area under concentration-time curve of [(2)H(4)]homocysteine significantly increased in the folate- and folate + choline-deficient group as compared with the control, but not in the choline-deficient group. The time profile of plasma concentrations of [(2)H(4)]methionine in the folate-deficient group was the same as the control group, whereas the appearance of [(2)H(4)]methionine in plasma was delayed in the choline- and folate + choline-deficient group. These results suggested plasma levels of remethylated methionine were influenced by choline deficiency rather than folate deficiency.

Animals↗