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Hiroshi Noguchi

Publications and source records attributed to Hiroshi Noguchi.

62 records · Page 4Linked to original sources
PubMed2002

Adhesion of nanoparticles to vesicles: a Brownian dynamics simulation.

We studied the interaction of bilayer vesicles and adhesive nanoparticles using a Brownian dynamics simulation. The nanoparticles are simple models of proteins or colloids. The adhering nanoparticle induces the morphological change of the vesicle: budding, formation of two vesicles in which only outer monolayers are connected, and fission. We also show that the nanoparticle promotes the fusion process: fusion-pore opening from a stalk intermediate, a neck-like structure that only connects outer monolayers of two vesicles. The nanoparticle bends the stalk, and induces the pore opening.

Biophysics↗
PubMed2002

Hepatocyte growth factor prevents intimal hyperplasia in rabbit carotid expanded polytetrafluoroethylene grafting.

PURPOSE: The major cause of vascular prosthesis failure is anastomotic intimal hyperplasia caused by the proliferation and migration of smooth muscle cells. Hepatocyte growth factor (HGF) is an endothelium-specific growth factor that exerts a mitogenic action on endothelial cells. This study was designed to examine the effect of HGF on the suppression of intimal hyperplasia after small-caliber expanded polytetrafluoroethylene (ePTFE) grafting. METHODS: An ePTFE graft, 2 mm in diameter and 30 mm in length, was implanted in the left common carotid arteries of Japanese white rabbits, after which the animals were fed with a 1.0% cholesterol diet. HGF was infused intravenously immediately and then every day for 7 days at doses of 0.3 mg/body (the 0.3-mg HGF group; n = 20) or 1.0 mg/body (the 1.0-mg HGF group; n = 17). A control group (n = 20) underwent infusion with saline solution. The rabbits were killed on postoperative days (PODs) 1, 2, 3, 5, 7, and 28. RESULTS: The patency rates on POD 28 were 33%, 55%, and 100% in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and the 1.0-mg HGF group (P <.05). Endothelial-like cells were seen on the intraluminal surface of the graft only near the anastomotic site on POD 5 in the 1.0-mg HGF group. Intimal thickness at the distal anastomosis was 284 +/- 140 microm, 106 +/- 18 microm, and 67 +/- 10 microm in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.05). The number of anti-embryonic smooth muscle antibody positive cells at the distal anastomosis was 28.6 +/- 0.8, 3.8 +/- 2.8, and 3.9 +/- 0.9 in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.01). CONCLUSION: HGF might suppress intimal thickness at the anastomotic site and improve the patency rate via rapid reendothelialization by POD 28 in a rabbit carotid ePTFE grafting model.

Animals↗
PubMed2002

Hepatocyte growth factor protects functional and histological disorders of HgCl(2)-induced acute renal failure mice.

Hepatocyte growth factor (HGF) enhances proliferation of renal epithelial cells as well as hepatocytes. HGF accelerates recovery from acute renal failure (ARF) in animal models. However, pharmacological profiles of HGF including its action mechanism has not been studied in detail. An HgCl(2)-induced ARF mouse was used in this study to evaluate the efficacy of HGF. Single administrations of recombinant human HGF or vehicle were given to ARF mice 30 min after HgCl(2) injection. Renal function was monitored by measuring serum creatinine, blood urea nitrogen and creatinine clearance. In the ARF mice, there was a deterioration of renal function biochemical parameters and histological evidence of renal damage including acute tubular necrosis of proximal tubules. These were both significantly ameliorated by a single HGF administration. The effect of HGF was noticeable in the early phase of ARF (1 day after onset) when there was no histological evidence of increased labeling indexes in renal tubular epithelial cells. Western blot analysis of the c-Met/HGF receptor showed that tyrosine phosphorylation was enhanced immediately after HGF administration indicating direct activation of renal epithelial cells. HGF prevented increase of apoptotic nuclei with DNA fragmentation in renal epithelial cells which suggests cytoprotective activity of HGF on renal epithelial cells in the ARF mice.

Acute Kidney Injury↗
PubMed2002

Ameliorative effect of hepatocyte growth factor on glycerol-induced acute renal failure with acute tubular necrosis.

BACKGROUND/AIMS: Hepatocyte growth factor (HGF), a multi-potent growth factor, is known to promote regeneration of damaged renal epithelial cells. Glycerol injection into rats induces severe acute renal failure (ARF) with ischemia and tubular necrosis, a model which shares many features with human ARF or rhabdomyolysis. We investigated the efficacy of HGF in this glycerol-induced ARF rat model. METHODS: ARF was induced by intramuscular injection of glycerol into the hind limbs of male Wistar rats. HGF (0.25 mg/kg/shot) or vehicle was administered intravenously 1 h before and 1, 3, 5, 8, 24 and 36 h after glycerol injection. Biochemical parameters for serum and urine were measured and histological analyses of the kidneys were performed. We also analyzed endogenous HGF expression and phosphorylation of c-Met/HGF receptor in the kidneys of glycerol-induced ARF rats. RESULTS: Glycerol treatment caused severe ARF which invariably led to death of the rats. Repeated administration of HGF protected rats from death caused by severe ARF. Histological analyses revealed that HGF treatment reduced necrosis of tubular cells in the renal cortex. Serum/urine biochemical parameters also showed that renal dysfunction was improved by HGF administration. Intravenous administration of HGF enhanced phosphorylation of the c-Met/HGF receptor and mitogen-activated protein kinase in the kidney. In the vehicle-treated group the renal endogenous HGF concentration decreased and there was no change in c-Met/HGF receptor phosphorylation. CONCLUSION: These results indicate that HGF effectively accelerated the recovery of renal function and improved survival in glycerol-induced ARF rats.

Acute Disease↗
PubMed2002

Prolyl endopeptidase inhibitors from the roots of Lindera strychnifolia F. Vill.

Prolyl endopeptidase (PEP, EC 3.4.21.26) has been proposed to play a role in degradation of proline-containing neuropeptides involved in the processes of learning and memory, e.g., vasopressin, substance P, and thyrotropin-releasing hormone (TRH). In the course of our search for bioactive constituents in medicinal plants, we studied the PEP inhibitory constituents of the roots of Lindera strychnifolia F. VILL and isolated two known tannins, epicatechin (1) and aesculitannin B (2), and four known sesquiterpenes, linderene (3), linderene acetate (4), linderalactone (5) and isolinderalactone (6) as inhibitors. On the inhibitory activities of six compounds against PEP from Flavobacterium meningosepticum and that from rat brain supernatant, compounds 1, 2 and 4 inhibited the enzyme from Flavobacterium more strongly than that from rat brain supernatant. However, compounds 3, 5 and 6 inhibited the enzymes from both origins to the same extent and furthermore, compound 6 was the strongest natural inhibitor against PEP from rat brain supernatant. The kinetic study of these inhibitors indicated that compounds 1, 2 are noncompetitive inhibitors and compounds 3-6 are competitive inhibitors. This is the first example of non-phenolic constituents showing significant competitive inhibitory activity being isolated from natural medicines.

Animals↗
PubMedDate not supplied

Brain-derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice.

Neurotrophins are important regulators in the embryogenesis, development and functioning of nervous systems. In addition to the efficacy of brain-derived neurotrophic factor (BDNF) in neurological disorders, we have found that BDNF demonstrates endocrinological functions and reduces food intake and blood glucose concentration in rodent obese diabetic models, such as C57BL/KsJ-db/db mice. The hypoglycemic effect of BDNF was found to be stronger in younger db/db mice with hyperinsulinemia than in older mice. While BDNF itself did not alter blood glucose in normal mice and streptozotocin (STZ)-treated mice, BDNF enhanced the hypoglycemic effect of insulin in STZ-treated mice. These data indicate that BDNF needs endogenous or exogenous insulin to show hypoglycemic action. In addition, BDNF treatment enhanced energy expenditure in db/db mice. The efficacy of BDNF in regulating glucose and energy metabolism was reproduced through intracerebroventricular administration, suggesting that BDNF acted directly on the hypothalamus, the autonomic center of the brain.

Animals↗
PubMedDate not supplied

Ciliary neurotrophic factor protects rat retina cells in vitro and in vivo via PI3 kinase.

PURPOSE: Neurotrophic factors and neurotrophins are well-known to have neuroprotective efficacy against retinal injury. The aim of this experiment is to investigate the signal transduction pathway of ciliary neurotrophic factor (CNTF) on the upregulation of viability of retinal primary culture and retinal protection against constant light damage in vivo. CNTF is known to enhance the viability of retinal culture and provide protection under constant light exposure conditions, but little is known about how the signal transduction pathways of CNTF affect retina function. METHODS: Primary retinal cultures were prepared from 7-day-old Wistar rats. Brain-derived neurotrophic factor (BDNF) (0.1, 1, 10 ng/ml), CNTF (0.1, 1, 10 ng/ml), PD98059 (10, 100, 1000 nM), or LY294002 (10, 100, 1000 nM) was added to these cultures at the time of cell preparation. After 3 days, the percentage of cells surviving was assessed using alamarBlue. For the in vivo experiment, inhibitors for the MAPKK (PD98059, 10 microg/eye) or PI3K (LY294002, 10 microg/eye) pathways were injected into the vitreous together with CNTF (1 microg/eye) 2 days before constant light exposure. Electroretinogram (ERG) analysis was performed to investigate which pathway was used by CNTF. RESULTS: CNTF at 1, 10, or 100 ng/ml enhanced cell viability in retinal cultures. The cell-survival activity of CNTF was blocked by 10 ng/ml LY294002 (Dunnet's test, p < 0.05). In vivo, the neuroprotective activity of CNTF in constant-light conditions was attenuated by 10 microg/eye LY294002 (Dunnet's test, p < 0.05). CONCLUSIONS: These data suggest that CNTF promotes cell survival via the PI3K signaling pathway in vitro and in vivo.

Animals↗