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Biomedical subjects

Hiroyuki Hashimoto

Publications and source records attributed to Hiroyuki Hashimoto.

30 records · Page 2Linked to original sources
PubMed2003

Circulating adhesion molecules are correlated with ultrasonic assessment of carotid plaques.

The relationship between levels of circulating intercellular cell-adhesion molecule-1 (cICAM-1) or P-selectin (cP-selectin) and the severity of carotid atherosclerosis was examined in 301 outpatients undergoing duplex ultrasonographic examination. Carotid plaque was defined as an intima-media thickness greater than 1.0 mm, and a plaque score (PS) was calculated from the plaque thickness in both carotid arteries. Multivariate analysis demonstrated significant positive associations between cICAM-1 and the number of plaques [beta = 0.11; confidence interval (CI), 0.007-0.213], maximum intima-media thickness (beta = 0.11; CI, 0.01-0.219), and PS (beta = 0.10; CI, 0.001-0.205). In contrast, no significant association was found for cP-selectin. cP-selectin did not increase until atherosclerosis was advanced (PS > 10), showing a marked increase in patients with >/= 50% stenosis. The circulating levels of both proteins are related to real measurements of plaque formation in the carotid arteries independently of classical risk factors. Marked elevation of cP-selectin occurs in advanced carotid atherosclerosis after gradual elevation of cICAM-1.

Adult↗
PubMed2003

Computational flow visualization in vibrating flow pump type artificial heart by unstructured grid.

Computational flow visualization in the casing of vibrating flow pump (VFP) was made for various conditions based on the novel techniques of fluid dynamics. VFP type artificial heart can generate the oscillated flow and can be applied to the left ventricular assist device. Flow pattern of blood in an artificial heart is closely connected to mechanical performance and serious biomechanical problems such as hemolysis and blood coagulation. To effectively design the VFP for a left ventricular assist device, the numerical codes for solving Navier-Stokes equations were developed for three-dimensional blood flow based on the finite volume method. Furthermore, the simulation techniques based on the artificial compressibility method and the unstructured grid were also developed here. The numerical calculations were based on the precise configurations and the flow conditions of the prototype device. From the viewpoint of computational fluid dynamics (CFD), the detailed discussion of flow patterns in the casing of VFP, which were closely connected with hemolysis and blood coagulation, was made and the computational results were visualized by the use of the recent technique of computational graphics. Some useful design data of VFP were presented.

Blood Flow Velocity↗
PubMed2003

Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury.

Ischemia-reperfusion is closely associated with tissue damage in various organs, including kidney. Despite clinical investigations, useful therapy for renal ischemia-reperfusion injury is not available so far. This study evaluated therapeutic effects of gene therapy expressing an amino-terminal deletion mutant of MCP-1 called 7ND to inhibit monocyte chemoattractant protein (MCP)-1/CCR2 signaling in vivo on renal ischemia-reperfusion injury. 7ND gene was transferred into the femoral muscle of Balb/c mice. Renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. A large number of infiltrated cells were observed, as was marked acute tubular necrosis in outer medulla after renal ischemia-reperfusion injury in control mice, while these lesions were significantly decreased in 7ND gene-transfected mice. Macrophages in the interstitial region, most of which were CCR2-positive, were markedly decreased in 7ND gene-transfected mice after reperfusion. Although macrophages infiltrated around MCP-1-positive cells in control mice, the smaller number of F4/80-positive cells could infiltrate into the neighbor of MCP-1-positive cells in 7ND-treated mice. These results provide evidence that gene therapy by 7ND is potentially a powerful therapeutic approach to inhibit MCP-1/CCR2 signaling, resulting in rescue from renal ischemia-reperfusion injury.

Animals↗
PubMed2003

CCR2 signaling contributes to ischemia-reperfusion injury in kidney.

Examined were CCR2-deficient mice to clarify the contribution of macrophages via monocyte chemoattractant protein 1 (MCP-1 or CCL2)/CCR2 signaling to the pathogenesis of renal ischemia-reperfusion injury. Also evaluated was the therapeutic effects via the inhibition of MCP-1/CCR2 signaling with propagermanium (3-oxygermylpropionic acid polymer) and RS-504393. Renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. A large number of infiltrated cells and marked acute tubular necrosis in outer medulla after renal ischemia-reperfusion injury was observed. Ischemia-reperfusion induced the expression of MCP-1 mRNA and protein in injured kidneys, followed by CCR2-positive macrophages in interstitium in wild-type mice. The expression of MCP-1 was decreased in CCR2-deficient mice compared with wild-type mice. The number of interstitial infiltrated macrophages was markedly smaller in the CCR2-deficient mice after ischemia-reperfusion. CCR2-deficient mice decreased the number of interstitial inducible nitric oxide synthase-positive cells after ischemia-reperfusion. The area of tubular necrosis in CCR2-deficient mice was significantly lower than that of wild-type mice after ischemia-reperfusion. In addition, CCR2-deficient mice diminished KC, macrophage inflammatory protein 2, epithelial cell-derived neutrophil-activating peptide 78, and neutrophil-activating peptide 2 expression compared with wild-type mice accompanied with the reduction of interstitial granulocyte infiltration. Similarly, propagermanium and RS-504393 reduced the number of interstitial infiltrated cells and tubular necrosis up to 96 h after ischemia-reperfusion injury. These results revealed that MCP-1 via CCR2 signaling plays a key role in the pathogenesis of renal ischemia-reperfusion injury through infiltration and activation of macrophages, and it offers a therapeutic target for ischemia-reperfusion.

Animals↗
PubMed2003

Ipsilateral hemiplegia in a lateral medullary infarct--Opalski's syndrome.

A 42-year-old man was admitted complaining of the sudden onset of headache, vomiting, vertigo, and gait disturbance. The authors found hemiparesis of his right limbs, right Homer's syndrome, and decreased pain and temperature sensation of his right face and left limbs. Diffusion-weighted imaging (DWI) showed an acute small infarct located on the right side of the lateral lower medulla. This is the first report of Opalski's syndrome with lower medullary infarction detected by DWI.

Adult↗
PubMed2003

Non-steroidal anti-inflammatory drug, nabumetone, prevents indometacin-induced gastric damage via inhibition of neutrophil functions.

Nabumetone is a non-steroidal anti-inflammatory drug (NSAID). It works as a prodrug and is extensively metabolized to an active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). It is well known that neutrophil infiltration and activation are critical in the pathogenesis of NSAID-induced gastric injury, and nabumetone shows less incidence of gastrointestinal irritancy. We examined the effects of nabumetone on neutrophil activation and on indometacin-induced gastric damage. In the indometacin-induced gastric mucosal injury, rats were treated with indometacin and then nabumetone or 6MNA was orally administered. Nabumetone prevented gastric damage accompanied by the reduction of neutrophil infiltration into gastric mucosa, but such an effect was not observed with 6MNA. Nabumetone reduced the formyl methionyl leucyl phenylalanine (fMLP)-induced respiratory burst of human neutrophils to 30% of the control level in-vitro, but 6MNA did not. In addition, nabumetone prevented the fMLP-induced migration of neutrophils. Nabumetone did not inhibit O2- generation in the xanthine-xanthine oxidase system. These results suggest that nabumetone prevents gastric damage induced by the active metabolite, 6MNA, via the suppression of neutrophil activation in gastric mucosa.

Animals↗
PubMed2003

Purification and characterization of a new type of alpha-glucosidase from Paecilomyces lilacinus that has transglucosylation activity to produce alpha-1,3- and alpha-1,2-linked oligosaccharides.

A fungus producing an alpha-glucosidase that synthesizes alpha-1,3- and alpha-1,2-linked glucooligosaccharides by transglucosylation was isolated and identified as Paecilomyces lilacinus. The cell-bound enzyme responsible for the synthesis was extracted by suspension of mycelia with 0.1 M phosphate buffer (pH 8.0), and the extract was purified. The molecular weight and the isoelectric point were estimated to be 54,000 and 9.1, respectively. The enzyme was most active at pH 5.0 and 65 degres C. The enzyme hydrolyzed maltose, nigerose, and kojibiose. The enzyme also hydrolyzed soluble starch and amylose with the rate toward maltose. p-Nitro-phenyl alpha-glucoside and isomaltose were not good substrates. The enzyme had high transglucosylation activity to synthesize oligosaccharides containing alpha-1,3- and alpha-1,2-linkages. At an early stage of the reaction, considerable maltotriose, 4-O-alpha-nigerosyl-D-glucose, and 4-O-alpha-kojibiosyl-D-glucose were synthesized. Afterwards, nigerose and kojibiose were accumulated gradually with glucose as an acceptor.

Carbohydrate Sequence↗
PubMed2002

Involvement of ICAM-1 in the progression of atherosclerosis in APOE-knockout mice.

Recent clinical evidence has indicated that the level of soluble ICAM-1 (sICAM-1) is correlated with the severity of atherosclerosis and can predict future cardiovascular events. Here, using apolipoprotein E (APOE)-deficient mice, we investigated the level of sICAM-1 in parallel with endothelial ICAM-1 expression and aortic atherosclerosis. We also examined the effect of ICAM-1 deficiency during the progression of atherosclerosis using double knockout mice. The level of sICAM-1 increased significantly in parallel with the progression of atherosclerosis in APOE-deficient mice, while the sICAM-1 level remained constant in wild-type mice from 3 to 10 months of age. ICAM-1 staining was detected in virtually all endothelial cells, however, ICAM-1 was expressed strongly in the endothelium overlying atheromatous palque in APOE-deficient mice. Deficiency of ICAM-1 in APOE-deficient mice significantly reduced lesions after 5 and 10 months. The present study supported the notion that the level of sICAM-1 is closely related with the severity of atherosclerosis and cardiovascular events, and also suggested that inhibition of ICAM-1 can delay the progression of atherosclerosis.

Animals↗
PubMed2002

Mass treatment with nevirapine to prevent mother-to-child transmission of HIV/AIDS in sub-Saharan African countries.

OBJECTIVE: In 2001, an estimated 800000 children were newly infected with HIV, almost all through mother-to-child transmission (MCTC), and 90% of these children were born in Africa. In such resource-poor settings, cheaper and more easily administered antiretroviral drugs should be available for use. Mass treatment of an intrapartum and neonatal single dose of nevirapine regimen has been suggested as an effective strategy to prevent MCTC, yet this strategy has never been conducted in clinical trials. By discussing the advantages and disadvantages of it, we analyze the possibility of implementing this regimen. METHODS: We reviewed public health strategies to prevent MCTC in resource-poor settings, and discuss whether or not mass treatment of an intrapartum and neonatal single dose of nevirapine regimen can be recommended as one therapy in sub-Saharan Africa due to its simplicity of distribution and use, long-term efficacy, and cost-effectiveness. RESULT: Recent studies in Uganda showed the high efficacy and cost-effectiveness of a single dose of nevirapine only to HIV/AIDS-positive pregnant women. The characteristics of nevirapine also meet the requirements of mass treatment. Mass treatment of nevirapine would increase access to antiretroviral drugs among pregnant women because they can access nevirapine without volunteer counseling and testing, which 31% of pregnant women in developing countries refused to accept due to the fear of stigmatization. No serious adverse effects or drug resistance to this regimen were reported through the studies in Uganda. CONCLUSION: Mass treatment of a single-dose nevirapine can be recommended as one alternative therapy, and further research is recommended to obtain more information about the efficacy, side-effects, drug resistance, and compliance of this strategy.

Adult↗
PubMed2002

Spontaneous rupture of a presumed colloid cyst of the third ventricle--case report.

An 83-year-old man presented with gait disturbance, dementia, and urinary incontinence that had progressed over 2 months. Computed tomography (CT) of the brain revealed hydrocephalus due to a well-demarcated, round hyperdense mass in the third ventricle, which was not enhanced by contrast agent. Ten days after the initial evaluation, CT revealed that the cyst in the third ventricle had disappeared. Magnetic resonance imaging revealed spontaneous rupture of the lesion and remnants of cyst wall anchored to the anterior roof of the third ventricle. Thereafter, the symptoms of hydrocephalus subsided. However, 6 months later the patient's condition gradually deteriorated and the ventricles dilated without any evidence of tumor regrowth. Surgical intervention was not performed as the family of the patient withheld consent. The natural history of colloid cysts of the third ventricle remains unclear. Spontaneous rupture of a presumed colloid cyst of the third ventricle should be considered when planning treatment.

Aged↗
PubMedDate not supplied

Hematologic findings associated with thrombocytopenia during the acute phase of exanthem subitum confirmed by primary human herpesvirus-6 infection.

PURPOSE: To elucidate the mechanism underlying thrombocytopenia during the acute phase of exanthem subitum (ES), the associated hematological findings were investigated. PATIENTS AND METHODS: Five infants with thrombocytopenia during the acute phase of ES serologically confirmed by primary human herpesvirus-6 (HHV-6) were examined and followed-up. RESULTS: Thrombocytopenia was accompanied by neutropenia, leukopenia, and decreased reticulocyte fraction during the acute phase. These changes were self-limiting, and the sequential changes of platelet, neutrophil count, and reticulocyte fraction were closely linked. Slight but significant decreases in hemoglobin in the convalescent phase and mild increases in atypical lymphocytes after subsidence of the fever were observed. Hemophagocytosis and increase in atypical lymphocytes in the bone marrow suggested that bone marrow cells were influenced by primary HHV-6 infection. Platelet-associated immunoglobulin G and indirect antiplatelet antibody were negative. Plasma levels of fibrinogen and D-dimer of fibrinogen degradation products were within normal ranges. CONCLUSIONS: Thrombocytopenia is a complication of ES, and this may result from bone marrow suppression rather than from immune-mediated peripheral consumption seen in acute idiopathic thrombocytopenic purpura or from disseminated intravascular coagulation.

Acute Disease↗