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Biomedical subjects

H Fujimori

Publications and source records attributed to H Fujimori.

At least 37 records · Page 2Linked to original sources
PubMed1998

Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells.

Several thrombogenic abnormalities are associated with diabetes. To investigate the underlying molecular mechanisms, we examined the effects of advanced glycation endproducts (AGE), non-enzymatically glycated protein derivatives, on the production of prostacyclin (PGI2), an anti-thrombogenic prostanoid, and of plasminogen activator inhibitor-1 (PAI-1), a fast-acting serine protease inhibitor of fibrinolysis, in human microvascular endothelial cells (EC). Firstly, AGE-bovine serum albumin (BSA) but not non-glycated BSA, was found to considerably decrease the production of PGI2 to about two-thirds of the control value. Secondly, quantitative reverse transcription-polymerase chain reaction showed that AGE-BSA increased the EC levels of mRNA coding for PAI-1, this being associated with a concomitant increase in the immunoreactive PAI-1 contents and the anti-fibrinolytic activity. Thirdly, the effects of AGE on PGI2 and PAI-1 syntheses in EC were found to be mediated by a receptor for AGE (RAGE) because antisense DNA against RAGE mRNA could reverse the AGE effects. Further, it was found that AGE decreased the intracellular cyclic AMP concentrations in EC and that cyclic AMP agonists such as dibutyryl cyclic AMP, forskolin and PGI2 analogue reduced the AGE-stimulated PAI-1 production, suggesting the involvement of cyclic AMP in the AGE-signalling pathway. The results thus suggest that AGE have the ability to cause platelet aggregation and fibrin stabilization, resulting in a predisposition to thrombogenesis and thereby contributing to the development and progression of diabetic vascular complications.

Cyclic AMP↗
PubMed1998

Long-term results of endarterectomy, anatomic bypass and extraanatomic bypass for aortoiliac occlusive disease.

Over the past 20 years, 214 patients in our hospital were operated on for aortoiliac occlusion, including an endarterectomy for 88 legs in 64 patients, an anatomic bypass for 178 legs in 105 patients, and an extraanatomic bypass for 51 legs in 45 patients. The extraanatomic group was older than the other two groups (70 years versus 64 years), and also showed a higher instance of critical ischemic symptoms than the other groups (49% versus 16%). The 10-year primary patency rate was 88% for an endarterectomy, 91% for an anatomic bypass, and 73% for an extraanatomic bypass. The 10-year survival rate was 71% for an endarterectomy, 49% for an anatomic bypass, and 24% for an extraanatomic bypass. The possible complications related to each surgical method included sexual dysfunction resulting from endarterectomy, and graft infection and anastomotic aneurysm in the prosthetic bypass. No ischemic symptoms in the donor limb were noted following an extraanatomic bypass. The selection of the appropriate surgical method for aortoiliac occlusion should thus be made after a careful review of the patient's general condition, the morphology of arterial occlusion, and the risk of possible complications for each type of surgery.

Adult↗
PubMed1998

Nitric oxide modulates T-lymphocyte migration in Peyer's patches and villous submucosa of rat small intestine.

BACKGROUND & AIMS: Although nitric oxide (NO) is known to influence the recruitment of neutrophils in inflamed tissue, its role in lymphocyte-endothelial cell interactions remains poorly understood. The objectives of this study were to assess the effects of NO synthesis inhibition on T-lymphocyte migration in microvessels of rat small intestine and to define the role of adhesion molecules in this process. METHODS: T lymphocytes collected from rat intestinal lymph were labeled with carboxyfluorescein diacetate succinimidyl ester and injected into the jugular vein of recipient rats. The migration of T lymphocytes into normal and NG-nitro-L-arginine methyl ester (L-NAME)-treated intestinal microvessels was monitored by using an intravital microscope. RESULTS: L-NAME significantly increased rolling and adherence of lymphocytes in postcapillary venules of Peyer's patches and submucosal venules without significantly decreasing red blood cell velocity. The subsequent appearance of lymphocytes in the initial lymphatics was also accelerated by L-NAME. Anti-4-integrin antibody markedly inhibited the L-NAME-induced lymphocyte-endothelial cell interaction. Anti-P-selectin monoclonal antibody also significantly attenuated these adhesive interactions in both vascular regions. CONCLUSIONS: These data suggest that NO is an important modulator of lymphocyte migration in Peyer's patches and in nonlymphoid regions of the intestine.

Animals↗
PubMed1998

Distribution of scattered radiation during intraoral radiography with the patient in supine position.

OBJECTIVE: The purpose of this study was to investigate the spatial distribution of scattered radiation during intraoral radiography with the patient in a supine position to determine the exposure to an operator without a suitable barrier. STUDY DESIGN: A phantom was placed in the supine position on a dental chair with the occlusal plane perpendicular to the floor, and four intraoral periapical radiographic examinations in the anterior and posterior regions of the maxilla and mandible were performed. The scattered radiation was measured with an ionization chamber at distances ranging from 25 to 200 cm at 25 cm increments and at intervals of 45 degrees. Measurements were made at two different heights: level with the occlusal plane and 30 cm below it. The exposure was converted to an air-kerma/absorbed dose in air. RESULTS: The distribution of scattered radiation was symmetric during examinations of the anterior region. Circular iso-exposure curves of up to 0.5 microGy were observed at the level of the occlusal plane, and curves of up to 0.1 microGy were observed 30 cm below the plane. The lowest exposures were measured 30 cm below the occlusal plane and behind the chair. The distribution of scattered radiation was not symmetric during examinations of the posterior region. Iso-exposure curves of up to 0.25 microGy were observed at the level of the occlusal plane during exposure of the maxilla, and curves of up to 0.5 microGy were observed during exposure of the mandible. Circular iso-exposure curves of up to 0.1 microGy were observed 30 cm below the occlusal plane. Lower values for scattered radiation were observed 30 cm below the occlusal plane between 135 and 180 degrees behind the phantom. CONCLUSION: The spatial distribution of scattered radiation with the patient in a supine position was not the same in eight directions around the chair. Although the preferred position for the operator is behind a suitable barrier, the preferred position in the absence of a barrier is 200 cm behind the patient.

Dental Auxiliaries↗
PubMed1998

Manganese-metalloporphyrin (ATN-10) as a tumor-localizing agent: magnetic resonance imaging and inductively coupled plasma atomic emission spectroscopy study with experimental brain tumors.

OBJECTIVE: We examined whether selective tumor accumulation of a novel manganese-metalloporphyrin (ATN-10) occurs in Fisher rats bearing intracerebral 9L gliomas. METHODS: After intravenous administration of ATN-10, magnetic resonance imaging of brains with tumors or nontumoral vasogenic brain edema was performed. Tissue manganese concentrations were measured by inductively coupled plasma atomic emission spectroscopy until 48 hours after administration of ATN-10, to evaluate its uptake in tumor, normal brain, and peritumoral brain tissue. RESULTS: In magnetic resonance imaging scans, early enhancement was observed in both tumor tissue and regions of nontumoral vasogenic brain edema at 5 minutes after ATN-10 administration. However, delayed enhancement was noted only in tumor tissue, at 24 hours after intravenous injection of ATN-10. Comparison of rat brain specimens and 24-hour magnetic resonance imaging scans revealed that only the viable portions of tumors were enhanced with ATN-10; necrotic regions and areas of peritumoral brain tissue and nontumoral vasogenic edema were not. Significantly greater uptake of ATN-10 was found in tumor samples, compared with normal and peritumoral brain tissue, at 24 hours. A high tumor/normal brain tissue ratio (10.4) was achieved at 24 hours. CONCLUSION: ATN-10, a manganese-metalloporphyrin, is a potentially useful tumor-localizing agent that accumulates and is preferentially retained in viable tumor tissue.

Animals↗
PubMed1998

Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis.

BACKGROUND: Increased production of reactive metabolites of oxygen and nitrogen has been implicated in chronic inflammation of the gut. The object of this study was to examine the magnitude and location of nitric oxide synthase (NOS) activity and peroxynitrite formation in the colonic mucosa of patients with ulcerative colitis in relation to the degree of inflammation. SUBJECTS: Thirty three patients with active ulcerative colitis (17 with mild or moderate inflammation, 16 with severe inflammation). METHODS: Inducible NOS activity was determined in the colonic mucosa by measuring the conversion of L-arginine to citrulline in the absence of calcium. The localisation of NOS and nitrotyrosine immunoreactivity was assessed immunohistochemically using the labelled streptavidin biotin method. RESULTS: Inducible NOS activity increased in parallel with the degree of inflammation of the mucosa. Expression of inducible NOS was found not only in the lamina propria, but also in the surface of the epithelium. Peroxynitrite formation as assessed by nitrotyrosine staining was frequently observed in the lamina propria of actively inflamed mucosa. CONCLUSIONS: Nitric oxide and peroxynitrite formation may play an important role in causing irreversible cellular injury to the colonic mucosa in patients with active ulcerative colitis.

Acute Disease↗
PubMed1998

A specific and rapid method for determination of adenosine 3'-monophosphate (3'-AMP) content and 3'-AMP forming enzyme activity in rat liver mitochondria, using reversed-phase HPLC with fluorescence detection.

To study the physiological significance of adenosine 3'-monophosphate (3'-AMP), an intracellular P-site inhibitor of adenylate cyclase, in rat liver mitochondria, a specific, rapid and reliable assay method for determination of 3'-AMP and the activity of its forming enzyme is required. 3'-AMP in rat liver was determined to be ca. 23+/-7 nmol/g wet weight, but no 2-deoxy-3'-AMP, another P-site inhibitor of adenylate cyclase, was detected, even when using a reversed-phase HPLC column with a fluorescent-reaction, as established in this study. By using the optimized assay method developed here, 3'-AMP forming enzyme activity in rat crude mitochondrial extract was found to be enhanced by EDTA and inhibited by p-chloromercurybenzoate. The optimum pH was ca. 5.8 and no divalent cation was required for activity. From these results, 3'-AMP forming enzyme(s) in rat liver mitochondria could be classified as acid exoribonuclease, which mainly existed in an active form. The results obtained in this study will help to gain more insight into the physiological roles of 3'-AMP in living systems.

Adenosine Monophosphate↗
PubMed1998

Formation of adenosine 3'-monophosphate in rat liver mitochondria.

An unknown adenine-related compound (UKC) in rat liver mitochondria was characterized. Based on the sensitivity to periodate oxidation, nuclease P1 digestion, property of fluorescence derivatization, elution behavior on different separation modes of HPLC columns and the mass spectrum of purified UKC, the UKC was identified as adenosine 3'-monophosphate (3'-AMP), an intracellular P-site inhibitor of adenylate cyclase. 3'-AMP may be enzymatically produced from RNA in rat liver mitochondria in temperature- and time-dependent manners. A partial characterization of 3'-AMP forming enzyme is included.

Adenosine Monophosphate↗
PubMed1998

Correlation between NO-induced ATP depletion and cytotoxicity in PC12 cells.

To ascertain whether NO-elicited cell death is mediated by decreased intracellular ATP, the effect of sodium nitroprusside (SNP), a NO-generator, on ATP content in PC12 cells was examined. After treatment with SNP, the ATP content in PC12 cells was found to decline in a time- and concentration-dependent manner. The decline of ATP content in PC12 cells caused by SNP was found to occur before the appearance of cytotoxicity estimated by MTT staining. In addition, the ATP content of neuronally differentiated PC12 cells, which has been shown to have a higher resistance to SNP than the undifferentiated cells (Nakamura et al., 1997), was less affected by SNP treatment than the undifferentiated cells. These findings suggest that reduction of intracellular ATP content may be one of the mechanisms responsible for the NO toxicity in PC12 cells.

Adenosine Triphosphate↗
PubMed1998

NO depletes cellular ATP contents via inactivation of glyceraldehyde-3-phosphate dehydrogenase in PC12 cells.

Recently, we demonstrated that nitric oxide (NO) reduces ATP generation via oxidative phosphorylation coupled with the mitochondrial respiratory chain in PC12 cells resulting in induction of apoptotic cell death. To further study the correlation between NO-induced ATP depletion and neuronal death, we examined the effect of NO on glycolytic ATP generation in PC12 cells, a neuronal model. When the oxidative phosphorylation was maximally suppressed by DNP and oligomycin, which are inhibitors of the mitochondrial respiratory chain, the cellular ATP contents were reduced by sodium nitroprusside (SNP). In addition, the cellular ATP contents were further decreased along with a decrease in the activity of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), a key enzyme in the glycolytic pathway. Benzamide, an inhibitor of poly (ADP-ribose) synthetase, could protect the depletion of NAD but had no effect on the depletion of ATP in PC12 cells induced by NO. These results suggest that the depletion of ATP in PC12 cells caused via the inhibition of G3PDH by NO is one of the mechanisms responsible for NO neurotoxicity.

Adenosine Triphosphate↗
PubMed1998

Characterization of platelet abnormalities of Tester Moriyama (TM) rats with storage pool deficiency.

Platelet abnormalities of Tester Moriyama (TM) rats, which have prolonged bleeding time with normal platelet count, were characterized by comparison with those of fawn-hooded (FH) rats with platelet storage pool deficiency (SPD). Morphologically, the dense granules were virtually lacking in platelets from TM and FH rats. Platelets from TM and FH rats aggregated in response to adenosine diphosphate (ADP), but failed to have secondary aggregation. In contrast, platelet aggregation was completely absent in response to 1 to 20 micrograms of collagen/ml, although partial aggregation was observed at the higher dosage of 50 micrograms/ml. Normal amounts of platelet membrane glycoproteins IIb/IIIa were expressed in TM and FH rats, but platelet adenosine triphosphate (ATP) and ADP contents were lower than those in platelets from control Wistar rats. Platelet ATP-to-ADP ratio of TM and FH rats was significantly higher than that of Wistar rats. Serotonin content in platelets from TM and FH rats was 20 to 25% that of Wistar rat platelets. These results suggested that platelet abnormalities of TM rats are a typical characteristic of platelet SPD and are similar to those of FH rats, which are genetically different from TM rats. Therefore, TM rats may serve as a useful animal model for the study of platelet SPD.

Adenosine Diphosphate↗
PubMed1998

Morphologic and hematologic characteristics of storage pool deficiency in beige rats (Chédiak-Higashi syndrome of rats).

Characterization of beige rats as having a platelet storage pool deficiency (SPD) was undertaken. Platelets from beige rats, an animal model of Chédiak-Higashi syndrome (CHS), completely lacked the ability to aggregate when stimulated with high dosages of collagen (50 micrograms/ml), and lacked secondary aggregation induced by adenosine diphosphate (ADP). Concentrations of ADP, ATP, and serotonin in the platelets of beige rats were significantly lower than those of control rats. However, platelet count remained within normal values. Electron microscopy revealed that platelets had fewer dense granules, whereas other organelles had normal structure. This morphologic and functional evidence confirms that platelets of beige rats have the typical characteristics of SPD.

Adenosine Diphosphate↗
PubMed1998

[Mucosal immune system of the intestine].

Gut-associated lymphoid tissue is the major inductive site of mucosal immune system, functionally independent of the systemic immune system. Particulate antigens are mainly uptaken from M cell of Peyer's patches, inducing IgA production in the intestinal mucosa. Lymphocytes are continuously recirculating through the intestinal mucosa to facilitate intestinal immune response. Dysregulation of lymphocyte migration and cytokine imbalance in the intestinal mucosa may be largely involved in the pathogenesis of inflammatory bowel diseases including intestinal allergy and Crohn's disease. There is also a possibility that dietary components especially long chain fatty acid could influence immune cell function of the intestinal mucosa. Because dietary components are closely associated with immunological function of intestinal mucosa, the importance of dietary manipulation for the management of inflammatory bowel diseases should be concerned.

Animals↗
PubMed1997

Nucleotide sequence and expression of the organomercurial-resistance determinants from a Pseudomonas K-62 plasmid pMR26.

pMRA17 cloned from Pseudomonas K-62 plasmid pMR26 specified the resistance to both organic and inorganic mercurials. DNA sequence of this broad-spectrum resistant mer operon was determined. The 5504-bp sequence includes six open reading frames (ORFs), five of which were identified as merR, merT, merP, merA and merB in order by analysis of deletion mutants and by comparison with the DNA and amino acid (aa) sequences of previously sequenced mer operons. The merB encoding organomercurial lyase showed a less identity than the other mer genes with those from other broad-spectrum resistance operons. The remaining ORF named merE, located between merA and merB, had no significant homology with the published mer genes and seemed to be a new gene which may involve in phenylmercury resistance. Induction experiments and maxicell analyses of the mer-polypeptides revealed that pMRA17 mer operon expressed mercurial-inducible phenotype and the merB and merE as well as the merA were under the control of MerR which could activate not only by mercuric ion but also by organomercurials.

Amino Acid Sequence↗
PubMed1997

Tumor specific contrast enhancement study of Mn-metalloporphyrin (ATN-10)--comparison of rat brain tumor model, cytotoxic and vasogenic edema models.

ATN-10, Mn-metalloporphyrin, has been developed as a tumor selective contrast agent for magnetic resonance (MR) imaging. To investigate the tumor specificity of ATN-10, we produced three experimental in vivo models; rat bran tumor (9L glioma) model, vasogenic (cold injury) and cytotoxic brain edema (24-hour MCA occlusion) models. The time course of contrast enhancement was compared after intravenous injection of ATN-10 or Gd-DTPA, measuring the signal intensity of the region of interest. After ATN-10 administration, the 9L glioma model showed early (5 min) and delayed (24 hr-) peak enhancement whereas the cold injury model showed only early enhancement and the 24-hour MCA occlusion model did not show significant enhancement. After Gd-DTPA administration, all three models showed similar pattern of only early enhancement. As a contrast agent for MR imaging, ATN-10 showed different behavior than Gd-DTPA in demonstrating the blood-brain barrier disruption and moreover ATN-10 showed selective enhancement in experimental brain tumors.

Animals↗
PubMed1997

Cytotoxic effect of sodium nitroprusside on PC12 cells.

To investigate the biochemical mechanism responsible for NO-induced neurotoxicity, the effect of sodium nitroprusside(SNP), a NO-generating agent, on PC12 cells was studied. The cell density was dose-dependently inhibited by SNP. Neuronally differentiated PC12 cells showed a higher resistance to SNP than the undifferentiated cells. The inhibitory effect was enhanced by 8-Br-cGMP, and reduced by methylene blue. However, 8-Br-cGMP alone had no significant cytotoxicity. SNP also inhibited [3H]-thymidine incorporation into the cells in a dose-dependent manner. The dose response curves for reducing cell density and for inhibiting thymidine incorporation, were found to be virtually superimposable. These results suggested that cytotoxicity elicited by NO seemed to be due to inhibition of DNA synthesis in PC12 cells.

Animals↗
PubMed1995

Lack of involvement of merT and merP in methylmercury transport in mercury resistant Pseudomonas K-62.

To clarify whether the merT and merP genes play a role in the transport of methylmercury, we constructed a deletion plasmid, pMRD141 which lacked the genes conferring the organomercurial lyase and the mercuric reductase from plasmid, pMRA17 containing the entire broad-spectrum mercury resistance determinants of the 26 kb-plasmid from Pseudomonas K-62. Plasmid, pMRD141 showed hypersensitivity to Hg2+ but still expressed a normal sensitivity to methylmercury. The mercury-induced hypersensitive cells carrying pMRD141 took up appreciably more 203Hg2+ than the induced resistant cells with pMRA17 and the sensitive cells with cloning vector, Bluescript II SK(+) but no difference in the uptake of CH3(203)Hg2+ among these three strains was found. These results suggested that the merT and merP are only involved in the Hg2+ transport but do not participate in the transport of methylmercury.

Bacterial Proteins↗