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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 91 records · Page 5Linked to original sources
PubMed2001

A possible role of Ku in mediating sequential repair of closely opposed lesions.

One of the hallmarks of ionizing radiation exposure is the formation of clustered damage that includes closely opposed lesions. We show that the Ku70/80 complex (Ku) has a role in the repair of closely opposed lesions in DNA. DNA containing a dihydrouracil (DHU) close to an opposing single strand break was used as a model substrate. It was found that Ku has no effect on the enzymatic activity of human endonuclease III when the substrate DNA contains only DHU. However, with DNA containing a DHU that is closely opposed to a single strand break, Ku inhibited the nicking activity of human endonuclease III as well as the amount of free double strand breaks induced by the enzyme. The inhibition on the formation of a free double strand break by Ku was found to be much greater than the inhibition of human endonuclease III-nicking activity by Ku. Furthermore, there was a concomitant increase in the formation of Ku-DNA complexes when endonuclease III was present. Similar results were also observed with Escherichia coli endonuclease III. These results suggest that Ku reduces the formation of endonuclease III-induced free double strand breaks by sequestering the double strand breaks formed as a Ku-DNA complex. In doing so, Ku helps to avoid the formation of the intermediary free double strand breaks, possibly helping to reduce the mutagenic event that might result from the misjoining of frank double strand breaks.

Antigens, Nuclear↗
PubMed2001

Cell-surface recognition of biotinylated membrane proteins requires very long spacer arms: an example from glucose-transporter probes.

Glucose transporters (GLUTs) can be photoaffinity labelled by (diazirinetrifluoroethyl)benzoyl-substituted glucose derivatives and the adduct can be recognised, after detergent solubilisation of membranes, by using streptavidin-based detection systems. However, in intact cells recognition of photolabelled GLUTs by avidin and anti-biotin antibodies only occurs if the bridge between the photoreactive and the biotin moieties has a minimum of 60--70 spacer atoms. We show that a suitably long bridge can be synthesised with a combination of polyethylene glycol and tartarate groups and that introduction of these spacers generates hydrophilic products that can be cleaved with periodate. Introduction of the very long spacers does not appreciably reduce the affinity of interaction of the probes with the transport system.

Adipocytes↗
PubMed2001

Occupational cancer genetics: infrequent ras oncogenes point mutations in lung cancer samples from chromate workers.

BACKGROUND: Chromium carcinogenicity and mutagenicity are no longer disputed. However, although chromium has various genetic effects that induce cancer, its mechanism of inducing lung cancer in humans is still not fully understood. p53, a tumor suppressor gene, was found to be infrequently mutated in samples of lung cancer in workers with long occupational exposure to chromium, suggesting other cancer-related genes to be targeted in such tumors. METHODS: To assess the contribution of the ras oncogenes in the pathogenesis of chromate-related lung cancer, we studied point mutations at the critical positions of codons 12, 13, and 61 of the Ha-ras and Ki-ras oncogenes in 38 lung cancer samples derived from Japanese patients who worked in the chromate industry for long periods. We used both radioactive isotope and non-radioisotope PCR-SSCP techniques. RESULTS: The results of this study demonstrated that activation of ras genes due to point mutations in chromate-related lung cancer is a rare event. CONCLUSIONS: Ras oncogenes activated by point mutations do not have a major role in the process of tumorigenesis of chromate-related lung cancer.

Adult↗
PubMed2001

Reduced neuritic outgrowth and cell adhesion in neuronal cells transfected with human alpha-synuclein.

Since recent reports have suggested that alpha-synuclein might play a role in neuronal plasticity, the main objective of this study was to determine the effects of alpha-synuclein on neuritic outgrowth. We stably transfected either human (h) alpha- or beta-synuclein cDNA in B103 rat neuronal cells. Expression of h(alpha)-synuclein resulted in reduced neurite extension and weak adhesion compared to vector-transfected and h(beta)-synuclein expressing cells. To investigate the potential pathways involved, we studied the effects of reagents known to modulate B103 proliferation and differentiation. Neither phorbol 12-myristate 13-acetate nor forskolin or antioxidants (catalase, superoxide dismutase, or vitamin E) were able to restore the reduced length of neurites in h(alpha)-synuclein-expressing cells. These results suggest that reduced neuritic activity in the h(alpha)-synuclein-expressing cells might be due, in part, to alterations in cell adhesion capacity. This might be attributed to alpha-synuclein affecting a signal transduction pathway distinct from protein kinase C and protein kinase A.

Animals↗
PubMed2001

Concomitant duodenal and pancreatic metastases from renal cell carcinoma: report of a case.

The pancreas and duodenum are uncommon sites for metastasis from renal cell carcinoma. Pancreatic or small intestinal metastases mainly occur when there is widespread nodal and visceral involvement and evidence of metastatic disease elsewhere in the body. We describe herein the case of a 68-year-old man in whom metastases arising from renal cell carcinoma developed concomitantly in the duodenum and pancreas. The patient presented with duodenal bleeding; but as no other metastatic lesions were observed at the time of surgery, total pancreatectomy with duodenetomy was performed. We believe that metastases may easily develop in the duodenum and pancreas owing to the similar tissue characteristics.

Aged↗
PubMed2001

Changes in functional capacity after portal branch ligation in rats.

Preoperative portal branch embolization is performed to increase residual liver lobe volume so that posthepatectomy liver insufficiency associated with major hepatic resection can be prevented. Although it is essential to evaluate functional liver capacity after portal branch embolization. the timing of hepatectomy from this viewpoint remains unelucidated. The aim of this study was to clarify the optimal timing of hepatectomy after portal branch embolization. We evaluated the functional capacity of the liver after portal branch ligation (PBL) in rats, and studied the correlation between morphological and functional changes. Morphological changes were evaluated on the basis of the liver lobe weight ratio, and the proliferating cell nuclear antigen labeling index. Functional changes were evaluated by the indocyanine green disappearance rate and serum aminopyrine clearance as functional capacity. Although the total liver weight ratio remained unchanged after PBL, the unembolized lobe ratio increased significantly. Although functional capacity was minimal 2 days after PBL, it had recovered to the preoperative value by 8 days after PBL. The functional capacity of the liver after PBL was minimal around the cellular proliferative period but recovered thereafter. These findings suggest that major hepatectomy after portal branch embolization should be perfomed following the cellular proliferative period of the unembolized lobe.

Animals↗
PubMed2001

Vascular compression as a cause of superior oblique myokymia disclosed by thin-slice magnetic resonance imaging.

PURPOSE: To describe a case of superior oblique myokymia in which thin-slice magnetic resonance imaging (MRI) appeared to show vascular compression of the trochlear nerve. METHODS: A 50-year-old woman presented with episodic monocular oscillopsia. Neuro-ophthalmologic examinations showed intermittent intorsional microtremor of her right eye, diagnosed as right superior oblique myokymia. Thin-slice (1.6 mm) MRI, using spoiled gradient recalled acquisition in the steady state, was employed to examine the trochlear nerve in its course through the ambient cistern. RESULTS: Imaging disclosed a branch of the posterior cerebral artery immediately adjacent to the right trochlear nerve. CONCLUSION: These magnetic resonance findings suggest that a cause of superior oblique myokymia may be vascular compression of the trunk of the trochlear nerve.

Cerebral Arteries↗
PubMed2001

Modulating effects of prenatal stress on hyperthermia induced in adult rat offspring by restraint or LPS-induced stress.

The present study was carried out to investigate the effects of prenatal stress on stress-induced hyperthermia in adult rats. Prenatal stress was administered daily for 3 days (embryonic days 15-17) by restraining pregnant rats in a small cage either for 30 or 240 min. After birth, foster mothers raised the pups. Offspring were tested at 9-10-weeks-old. Changes in body temperature and in the plasma concentrations of corticosterone, norepinephrine (NE), and epinephrine (Epi) induced by restraint or lipopolysaccharide (LPS)-induced stress were examined. By comparison with the prenatally nonstressed control group, the 240-min stress group showed a significantly lower hyperthermia in response to restraint stress but a higher fever after injection of LPS. The 30-min stress group showed similar alterations in these hyperthermic responses but did not reach significance. Both the restraint stress and the injection of LPS evoked greater increases in the plasma level of corticosterone in the 240-min stress group than in the control group. Although restraint stress induced significant increases in NE and Epi in the control and 30-min stress groups, the plasma levels of these catecholamines did not increase in the 240-min stress group. These results demonstrate for the first time that prenatal stress has opposite effects on the hyperthermic responses to restraint and LPS injection, suggesting that different mechanisms underlie the modulating effects of prenatal stress on the responses to the two types of stressors.

Animals↗
PubMed2001

Ultrastructural study of a glass ionomer-based, all-in-one adhesive.

OBJECTIVE: Reactmer Bond (Shofu Inc., Kyoto, Japan) is a glass ionomer (GI) based, tri-curable, all-in-one, filled adhesive. Both fluoroaluminosilicate glass (FASG) and fully pre-reacted glass (F-PRG) are used as fillers. This study examined the ultrastructure and elemental composition of resin-dentine interfaces that were treated with this adhesive. METHODS: Dentine disks prepared from human third molars were abraded with either 600- or 60-grit SiC paper to create smear layers of different thickness. They were bonded using Reactmer Bond. Cryo-fractured dentine surfaces devoid of smear layers were also bonded by chemical-activation and GI reaction without additional light-activation, or allowing the GI reaction to proceed for 1min before the adhesive was applied and light-activated. Undemineralised and demineralised sections were processed for TEM examination and STEM/EDX analysis. RESULTS: Resin-dentine interface from specimens with smear layers consisted of a mineral-dense surface layer that resided on top of a partially demineralised dentine. The partially demineralised zone was considerably thicker in the 600-grit than the 60-grit specimens. In smear layer-free specimens that were cured by chemical-activation/GI modes only, the surface layer concurred with the partially demineralised zone, and appeared as an electron-dense layer over the undemineralised intact dentine. Smear layer-free specimens that were cured by the light-activation of the partially neutralised adhesive contained incomplete amorphous surface layers only. Apart from colloidal silica, FASG fillers were the predominant filler type within the resin matrices. Peripheral hydrogel layers that contained electron-dense "seeds" were found around the FASG fillers. F-PRG fillers were only sparsely observed. In specimens that were laboratory demineralised with formic acid, phase separation of the unstained resin matrices into electron-dense and electron-lucent domains occurred. Artefactual dendritic deposits were found within the electron-dense domains. CONCLUSIONS: The presence of a surface interaction layer on top of a partially demineralised zone along the resin-dentine interface suggests that either a GI-type reaction or precipitation of insoluble carboxylate salts around remnant apatite crystallites may occur when this single-step adhesive interacts with dentine. Appearance of artefactual dendritic deposits suggests that continuous ion movement is possible within the hydrophilic portion of the resin matrix in this fluoride-releasing adhesive.

Aluminum Compounds↗
PubMed2001

Relationship between age-related increases in rat liver lipid peroxidation and bile canalicular plasma membrane fluidity.

Aging is associated with increased cellular levels of lipid peroxides and reactive oxygen species. This increase in the radical species may affect membrane fluidity and consequently membrane functions. We attempted to determine whether age-related increases in lipid peroxide and reactive oxygen species levels affect the annular fluidity of the bile canalicular plasma membrane in young (2-3 weeks old), adult (20 weeks old) and old (100 weeks old) rats. Hepatic levels of lipid peroxides measured with thiobarbituric acid reactive substances (TBARS), reactive oxygen species and reduced glutathione were significantly higher in the old rats than in the young and adult rats. Arachidonic acid (AA) levels increased and docosahexaenoic acid (DHA) levels decreased in the isolated canalicular plasma membrane of the old rats, and the ratio of DHA to AA thus decreased significantly with rat aging. Hepatic TBARS levels correlated negatively with molar ratios of DHA to AA. The annular fluidity of the bile canalicular plasma membrane decreased significantly in the old rats compared with that in the young and adult rats. These results suggest that the age-related decrease in DHA content of the bile canalicular plasma membrane and the molar ratio of DHA to AA may be associated with age-related deterioration of membrane annular fluidity.

Aging↗
PubMed2001

The feasibility of retrograde catheterization of the right gastric artery via the left gastric artery.

Retrograde catheterization of the right gastric artery was attempted in 22 patients for the purpose of proximal right gastric artery embolization. Retrograde catheterization was successfully performed in 12 of the 14 patients (86%) with smooth anastomoses. Retrograde catheterization was unsuccessful (n = 1) or time-consuming (n = 1) in two patients (14%) with smooth anastomoses. Right gastric artery embolization was successfully performed with microcoils in 13 of the patients. In all eight patients with tortuous anastomoses, catheterization was unsuccessful. Retrograde catheterization should be considered possible when preliminary angiography indicates a smooth anastomosis with the left gastric artery.

Adult↗
PubMed2001

Effect of cryopreservation period on rat tracheal allografts.

BACKGROUND: The effect of cryopreservation on tracheal allogenicity is still unclear. Therefore, in this study, we assessed the effect of cryopreservation period on tracheal allografts in 62 rats. METHODS: Each transplant consisted of a 3-ring segment of the trachea harvested from 8 Lewis rats, immersed in preservation solution, and cryopreserved and stored in a Bicell biofreezing vessel in a deep freezer at -80 degrees C. Six tracheal grafts without cryopreservation that underwent a heterotopically syngeneic transplantation into the omentum served as controls. Forty-eight tracheal segments were randomly assigned to 8 groups according to period of cryopreservation, which ranged from 0 to 12 months (0, 0.5 [2 weeks], 1, 2, 3, 6, 9 and 12 months). The cryopreserved grafts were then thawed and heterotopically implanted into the omentum of recipient Brown-Norway rats. After 28 days, the tracheal segments were then evaluated histologically. RESULTS: All isografts in Group 1 were intact, whereas the allografts undergoing a particularly shorter period of cryopreservation showed a more stenotic lumen. Prolonged periods of cryopreservation tended to show decreasing tendencies of viability of chondrocytes, mononuclear cell infiltration and sub-epithelial thickness, whereas all allografts showed a uniformly denuded epithelium, irrespective of the length of cryopreservation. CONCLUSIONS: A longer period of cryopreservation may help to maintain a better patency of tracheal allografts by preventing an allogeneic response. Reduced tracheal allogenicity may be associated with a decreased viability of chondrocytes by cryopreservation.

Animals↗
PubMed2001

Involvement of urban living environments in atopy and enhanced eosinophil activity: potential risk factors of airway allergic symptoms.

BACKGROUND: Airway allergic diseases, such as bronchial asthma and allergic rhinitis, have increased, especially in urban areas. These diseases are characterized by airway inflammation with enhanced eosinophil activity, and the risk of disease development has been shown to increase with the prevalence of atopy. METHODS: Questionnaires were administered to 426 healthy adult women aged 30-74 years, living in an urban area of Osaka, Japan, to survey individual living environments and airway allergic symptoms such as cough, sputum, and wheezing. Moreover, serum house-dust-mite (Dermatophagoides pteronyssinus, [Der p])-specific immunoglobulin E (IgE) and serum eosinophil cationic protein (ECP) were examined by radioimmunoassay, and the atopic status (atopic sensitization) and enhanced eosinophil activity were assessed as Der p-specific IgE RAST scores of 2-6 and ECP levels of more than 10 ng/ml, respectively. RESULTS: Intensive use of electric air conditioners in hot weather (odds ratio: 2.07 [95% CI: 1.11-3.87]) and mold proliferation in the kitchen (2.77 [1.34-5.73]) significantly increased the risk of atopic sensitization. Poor home ventilation and family smoking appeared to be positively but not significantly associated with atopic sensitization. Personal smoking and intensive use of the air conditioner appeared to be positively related to enhanced eosinophil activity. Atopic status showed significant involvement in the development of wheezing, and the development of cough was significantly associated with enhanced eosinophil activity. CONCLUSIONS: The results suggest that some urban styles of living are involved in atopic sensitization and enhanced eosinophil activity in the Japanese urban population, probably due to living conditions, such as indoor dampness and poor home ventilation, caused by tight insulation, which increase exposure to indoor air pollutants, such as respirable mite allergens and tobacco smoke.

Adult↗
PubMed2001

High-yield selection and extraction of two promoter-defined phenotypes of neural stem cells from the fetal human brain.

Neural stem and precursor cells reside in the ventricular lining of the fetal forebrain, and may provide a cellular substrate for brain repair. To selectively identify and extract these cells, we infected dissociated fetal human brain cells with adenoviruses bearing the gene for green fluorescence protein (GFP), placed under the control of enhancer/promoters for two genes (nestin and musashi1) that are expressed in uncommitted neuroepithelial cells. The cells were then sorted by fluorescence-activated cell sorting (FACS) on the basis of E/nestin- or P/musashi1-driven GFP expression. Both P/musashi1:hGFP- and E/nestin:EGFP-sorted cells were multipotent: limiting dilution with clonal expansion as neurospheres, in tandem with retroviral lineage analysis and xenograft to E17 and P0-2 rat forebrain, revealed that each phenotype was able to both self-renew and co-generate neurons and glia. Thus, fluorescent genes placed under the control of early neural promoters allow neural stem cells to be specifically targeted, isolated, and substantially enriched from the fetal human brain.

Adenoviridae↗
PubMed2001

Chemical diversity in lipopeptide antifungal antibiotics.

In the course of screening for antifungal antibiotics, we have discovered a novel series of lipopeptide compounds structurally related to, but highly superior to, echinocandin B in terms of their water solubility due to the presence of a sulfate residue. These compounds, WF11899s, WF738s, WF14573s, WF16616 and WF22210, and their derivatives have diversity in their nuclear structures and acyl side chains. The producing strains were classified into two groups, the Coleomycetes group and the Hyphomycetes group. Compound FK463, a derivative of WF11899A, is currently in Phase 3 clinical development as a novel antifungal antibiotic.

Animals↗
PubMed2001

Structural elucidation of a capsular polysaccharide from a clinical isolate of Bacteroides vulgatus from a patient with Crohn's disease.

The structure of a capsular polysaccharide (CPS) from a clinical isolate of Bacteroides vulgatus was elucidated. B. vulgatus IMCJ 1204 was isolated from feces of a patient with Crohn's disease. CPS was prepared by phenol/water extraction of the bacterial cells followed by hydrophobic interaction chromatography and then gel filtration chromatography of the extract. The structure of CPS was determined by chemical analysis and NMR spectroscopy including DQF-COSY, TOCSY, ROESY, HSQC-TOCSY, HMQC and HMBC to be a polysaccharide composed of the following repeating unit: -->3)beta-D-Glcp(1-->6)[alpha-D-GalpNAc(1-->2)beta-D-Galp(1-->4)]beta-D-GlcpNAc(1-->3)alpha-D-Galp(1-->4)beta-D-Manp(1-->.

Bacterial Capsules↗
PubMed2001

Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats.

1. In the present study, we investigated the effect of docosahexaenoic acid (DHA) on spatial memory related learning ability in aged (100 weeks) male Wistar rats. 2. Rats were fed a fish oil-deficient diet through three generations and were then randomly divided into two groups. Over 10 weeks, one group was per orally administered 300 mg/kg per day DHA dissolved in 5% gum Arabic solution and the other group was administered the vehicle alone. Five weeks after the start of the administration, rats were tested with the partially baited eight-arm radial maze to estimate two types of spatial memory related learning ability displayed by reference memory error and working memory error. 3. Chronic administration of DHA significantly decreased the number of reference memory errors and working memory errors. 4. The level of lipid peroxide (LPO) in the hippocampus tended to decrease with chronic DHA administration and demonstrated a positive correlation with the number of reference memory errors. 5. These results suggest that the accumulation of hippocampal LPO reduces spatial memory related learning ability in aged rats. Moreover, chronic administration of DHA was effective in decreasing the level of hippocampal LPO, then improving learning ability.

Aging↗