Biomedical subjects

N Maeda

Publications and source records attributed to N Maeda.

At least 91 records · Page 5Linked to original sources

PubMed2001

[Usefulness of enhanced ultrasonography after administration of intravenous contrast agent in the evaluation of therapeutic effect in treatment of hepatocellular carcinoma, and efficacy of percutaneous ethanol injection therapy (PEIT) for residual tumor].

PURPOSE: To investigate the usefulness of enhanced ultrasonography after the administration of intravenous contrast agent in the evaluation of therapeutic effect in the treatment of hepatocellular carcinoma (HCC) comparison with dynamic CT, and to examine the efficacy of percutaneous ethanol injection therapy (PEIT) for residual tumor. MATERIALS AND METHODS: Thirty patients (22 men, 8 women; age range, 42-76 years; mean age 60 years) underwent enhanced ultrasonography with the intravenous ultrasonographic agents Levovist, after transcatheter arterial embolization (TAE) (n = 15, size range 23-35 mm, mean 25.3 mm) or PEIT (n = 15, 15-35 mm, mean 24.5 mm), to compare the therapeutic effect with dynamic CT. If residual lesions were detected by enhanced ultrasonography, we performed additional PEIT. RESULTS: The evaluation of enhanced ultrasonography correlated almost completely with that of dynamic CT. Two residual lesions could not be detected by dynamic CT due to lipiodol, but enhanced ultrasonography and dynamic MRI showed them clearly. In total, eight residual tumors (3-15 mm, mean 8.3 mm) were seen. We performed PEIT on seven lesions and obtained good control for six months. CONCLUSION: Enhanced ultrasonography with Levovist could be performed to evaluate the therapeutic effect of treatment for HCC, and could serve as be a good marker for additional US-guided therapy.

Adult↗

PubMed2001

Aggregation and sedimentation of mixtures of erythrocytes with different properties.

The rouleau formation of erythrocytes and the erythrocyte sedimentation were examined for mixture of different kinds of the cells suspended in isotonic phosphate-buffered saline containing 1 or 2 g/dl dextran T-70 (MW = 70,400) and 4 g/dl albumin, using a low shear rheoscope and the Westergren method, respectively. The deformability of cells was decreased by treating with diamide, diazene-dicarboxylic acid bis[N,N-dimethylamide], and the sialic acid content of cells, i.e., the surface negative charge, was reduced by treating with neuraminidase. (1) The rate of rouleau formation was decreased in cells with decreased deformability, while it was increased in cells with reduced sialic acid content. The rate changed in proportion to the ratio of the modified cells to normal cells. (2) The erythrocyte sedimentation was also decreased in cells with decreased deformability, while it was increased in cells with reduced sialic acid content. Furthermore, the erythrocyte sedimentation changed almost proportionally to the ratio of the modified cells to normal cells. (3) When normal deformable cells were mixed with cells with decreased deformability, the deformable cells seemed to settle faster than the less deformable cells, though the difference was not significant. (4) When normal cells were mixed with cells with reduced sialic acid content, the cells with less sialic acid settled significantly faster than those with more sialic acid. The present experiment may conclude that erythrocyte aggregation is induced preferentially among more deformable cells and/or among less negatively charged cells with weaker electrostatic repulsive force, and then the formed aggregates settle faster.

Adult↗

PubMed2000

Desipramine induced changes in salivary proteins, cultivable oral microbiota and gingival health in aging female NIA Fischer 344 rats.

Cyclic antidepressants are still a dominating group of psychotherapeutic drugs used in the treatment of depression. One of their major side effect is salivary gland dysfunction (oral dryness, xerostomia), leading in humans to increased oral disease and dysfunction of speech, chewing, swallowing and taste. The purpose of this study was to assess the effects of the long-term administration of the tricyclic antidepressant desipramine and the reversibility of this treatment following a 15 d washout period on specific salivary proteins, composition of oral microbiota, and oral health (gingivitis) of aging female F344 rats. Total salivary proteins showed decreased concentrations with age and desipramine. Similar SDS/PAGE protein profiles appeared in all phases but in different relative amounts with age and treatment. While certain proteins maintained steady levels (lactoferrin) or decreased with age and treatment (amylase), the synthesis of proline-rich proteins, high molecular weight mucin-type glycoproteins, and lysozyme was induced with desipramine and age. The oral microbiota was significantly changed with age and the administration of the antidepressant. The incidence of gingivitis with desipramine was highest in the oldest animals, For the different parameters measured, recovery was delayed with age. These data indicate, that desipramine has profound effects on salivary protein secretion. This may partially explain the changes in microbiota and the increased incidence of gingivitis.

Aging↗

PubMed2000

Improvement of the viability of cultured rat neurons by the non-essential amino acids L-serine and glycine that upregulates expression of the anti-apoptotic gene product Bcl-w.

The non-essential amino acids L-serine (Ser) and glycine (Gly) have recently been shown to exhibit specific actions in the nervous system. In the present study, L-Ser and Gly promoted the survival of cultured rat cerebrocortical neurons in a concentration-dependent manner as revealed by Alamar blue assay and microtubule-associated protein-2 (MAP2) immunoblotting. The maximum effects of the amino acids were detected at the concentrations of 30-100 microM. L-Ser was more effective than Gly. D-Ser failed to promote neuronal survival. L-Ser and Gly upregulated expression of the anti-apoptotic gene product Bcl-w, while they did not affect the expression of Bcl-xL. The promotion of neuronal survival by L-Ser and Gly may be, at least in part, attributable to the upregulated Bcl-w.

Animals↗

PubMed2000

Semi-inclusive lambda and K(S) production in p-Au collisions at 17.5 GeV/c

The first detailed measurements of the centrality dependence of strangeness production in p-A collisions are presented. Lambda and K(S) dn/dy distributions from 17.5 GeV/ c p-Au collisions are shown as a function of "grey" track multiplicity and the estimated number of collisions, nu, made by the proton. The nu dependence of the Lambda yield deviates from a scaling of p-p data by the number of participants, increasing faster than this scaling for nu</=5 and saturating for larger nu. A slower growth in K(S) multiplicity with nu is observed, consistent with a weaker nu dependence of K&Kmacr; production than YK production.

Journal Article↗

PubMed2000

Doubling expression of the low density lipoprotein receptor by truncation of the 3'-untranslated region sequence ameliorates type iii hyperlipoproteinemia in mice expressing the human apoe2 isoform.

The primary receptor mediating clearance of apolipoprotein (apo)E- and apoB100-containing lipoproteins from the circulation is the low density lipoprotein (LDL) receptor. Reduced expression of the LDLR is believed to be a precipitating factor in the pathogenesis of type III hyperlipoproteinemia (HLP) in some humans homozygous for the apoE2 allele (APOE*2). To test the effect of genetic changes in LDL receptor expression on the pathogenesis of type III HLP, we have generated a variant allele at the endogenous mouse Ldlr locus that expresses the human LDL receptor transcript. Transcription of the human LDLR minigene is regulated by the endogenous mouse promoter sequence, but a truncation of 3'-untranslated region results in increased mRNA stability. Consequently, in liver of heterozygotes, steady state levels of mouse and human LDLR transcripts are 50 and 180% the levels of total transcript in wild type mice, respectively. Overall, the 2.3-fold normal level of LDLR message in heterozygotes completely ameliorates type III HLP caused by the homozygosity for the human APOE*2 allele, normalizing their plasma lipoprotein profile. We conclude that a modest increase in expression of the LDLR through message stabilization is sufficient to prevent precipitation of type III HLP in mice.

3' Untranslated Regions↗

PubMed2000

Desipramine changes salivary gland function, oral microbiota, and oral health in rats.

Tricyclic antidepressants are still a dominating group of psychotherapeutic drugs used in the treatment of depression. Oral dryness is one of their major side-effects, leading in humans to increased oral disease and dysfunction of speech, chewing, swallowing and taste. We previously reported that the tricyclic antidepressant desipramine desensitizes beta-adrenergic signal transduction in salivary glands. In this study, we evaluated the effects of this treatment on parotid and submandibular gland function, oral microbiota, and oral health in rats. Total protein secretion and salivary alpha-amylase was not affected by treatment, while cellular alpha-amylase and the content of epidermal growth factor was depressed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed increased secretion for proline-rich proteins and glycoproteins. Surprisingly, flow rates were temporarily increased. These alterations in salivary gland function may partially explain the observed changes in oral microbiota and the increased incidence of gingivitis. Under other nutritional conditions, desipramine might have more severe impacts on oral health.

Adrenergic Uptake Inhibitors↗

PubMed2000

The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system.

Wallerian degeneration is one of the most elementary reactions of the nervous system after transection of axons, leading to the recruitment of mononuclear cells from the systemic circulation. However, the exact mechanisms regulating this cell invasion have not yet been clarified in detail. Chemokines and their receptors play a central role in leukocyte trafficking, in particular the chemokine MCP-1 has been strongly implicated in macrophage recruitment to the injured nervous system. The present study investigates the course of Wallerian degeneration after transection of the sciatic nerve in mice deficient in two chemokine receptors: CCR2, the main receptor for MCP-1, and CCR5, a marker for Th1 T lymphocytes but also present on macrophages. The number of invading macrophages was determined by immunocytochemistry for three typical macrophage antigens (F4/80, Mac-1, LFA-1). The chemokine receptor CCR2 was expressed by infiltrating cells in the transected nerve stumps. Macrophage invasion was significantly impaired in CCR2-knockout mice when compared with wildtype controls and CCR5-deficient mice. Subsequently, there was a corresponding decrease in myelin phagocytosis due to the reduced invasion of phagocytic macrophages. These data demonstrate the involvement of the chemokine receptor CCR2 in macrophage recruitment to the injured nervous system.

Animals↗

PubMed2000

Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase.

Myeloperoxidase (MPO), which is located within neutrophils capable of producing hypochlorous acid, is active in vitro against bacteria and fungi. However, MPO-deficient persons are usually healthy. To define the in vivo contribution of MPO to early host defense against pulmonary infections, MPO-deficient and control mice were intranasally infected with various fungi and bacteria, and the number of residual microorganisms in lungs was compared 48 h later. MPO-deficient mice showed severely reduced cytotoxicity to Candida albicans, Candida tropicalis, Trichosporon asahii, and Pseudomonas aeruginosa. However, the mutant mice showed a slight but significantly delayed clearance of Aspergillus fumigatus and Klebsiella pneumoniae and had comparable levels of resistance to the wild type against Candida glabrata, Cryptococcus neoformans, Staphylococcus aureus, and Streptococcus pneumoniae. These results suggest that the MPO-dependent oxidative system is important for host defense against fungi and bacteria, although the effect varies by pathogen species.

Animals↗

PubMed2000

Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC).

Duffy antigen/receptor for chemokines (DARC) is a promiscuous receptor for chemokines that is required for Plasmodium vivax infection of erythroid cells. This receptor is expressed by subsets of endothelial, as well as erythroid cells. Selection for protection from malaria infection resulted in an erythroid-specific defect, suggesting that DARC may play a critical role in endothelial biology. Mice with targeted disruption of this gene were generated, and the function of DARC in inflammation was explored. RNA from spleens of homozygous mutant mice lacked DARC transcripts, which were abundant in wild-type (+/+) and heterozygote (+/-) mice. DARC(-/-) mice lacked developmental abnormalities and were healthy at 1 year. Whereas hematologic parameters were within normal ranges, erythrocytes from nullizygous mice lacked CXC and CC chemokine-binding activity. Challenge with lipopolysaccharide resulted in significantly increased inflammatory infiltrates in lung and liver of nullizygous mice. These results suggest that DARC modulates the intensity of inflammatory reactions as a sink for chemokines. (Blood. 2000;96:1681-1684)

Animals↗

PubMed2000

Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis: lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine.

The chemokine receptors CCR2 and CCR5 and their respective ligands regulate leukocyte chemotaxis and activation. To determine the role of these chemokine receptors in the regulation of the intestinal immune response, we induced colitis in CCR2- and CCR5-deficient mice by continuous oral administration of dextran sodium sulfate (DSS). Both CCR2- and CCR5-deficient mice were susceptible to DSS-induced intestinal inflammation. The lack of CCR2 or CCR5 did not reduce the DSS-induced migration of macrophages into the colonic lamina propria. However, both CCR5-deficient mice and, to a lesser degree, CCR2-deficient mice were protected from DSS-induced intestinal adhesions and mucosal ulcerations. CCR5-deficient mice were characterized by a greater relative infiltration of CD4+ and NK1.1+ lymphocyte in the colonic lamina propria when compared to wild-type and CCR2-deficient mice. In CCR5-deficient mice, mucosal mRNA expression of IL-4, IL-5, and IL-10 was increased, whereas that of IFN-gamma was decreased, corresponding to a Th2 pattern of T cell activation. In CCR2-deficient mice, the infiltration of Th2-type T cells in the lamina propria was absent, but increased levels of IL-10 and decreased levels of IFN-gamma may have down regulated mucosal inflammation. Our data indicate that CCR5 may be critical for the promotion of intestinal Th1-type immune responses in mice.

Animals↗

PubMed2000

Two-photon microscopy of aorta fibers shows proteolysis induced by LDL hydroperoxides.

Oxidatively modified LDL mimics several aspects of atherogenesis. In this disease, degradation of the matrix proteins' network also occurs. By a new morphological ex vivo approach, not requiring sample processing, we explored the relationship between the degradation of matrix protein and oxidatively modified LDL. Two-photon excitation fluorescence microscopy images of fresh cross-section rings of rat aorta, acquired while the sample was maintained in a glucose- and oxygen-supplemented buffer, showed straight, parallel, thick, long extracellular matrix proteins. Traditional microscopic examination, requiring sample fixation and staining, shows smaller and curved fibers. Instead, we observed curved and broken fibers after a 30-min incubation of aorta with either LDL containing lipid hydroperoxides, or tert-butyl-hydroperoxide. The adhesion of LDL to the endothelium and its internalization was directly visualized by using a lipid fluorophore. The damage to aorta matrix proteins induced by LDL and tert-butyl-hydroperoxide was fully prevented by antioxidants, such as ascorbate or Trolox C, or inhibitors of proteases. The image spectroscopy of the fibers' autofluorescence (polarization and lifetime) revealed an increased mobility of the fluorescent cross-link in fibers. Damaged matrix proteins were also imaged in aorta samples from apolipoprotein E knock-out mice. Our ex vivo images directly visualized the activation of a fast redox-sensitive proteolytic process in the arterial wall triggered by lipid hydroperoxides in LDL.

Animals↗

PubMed2000

Histochemical cytochrome c oxidase activity and caspase-3 in gerbil hippocampal CA1 neurons after transient forebrain ischemia.

We examined the cytochrome c oxidase (COX) activity in gerbil hippocampal CA1 neurons after 5-min ischemia by a histochemical method in the presence or absence of exogenous cytochrome c. In the CA1 neurons, COX activity without exogenous cytochrome c decreased from 1 h after ischemia, but was restored by the addition of exogenous cytochrome c in the following 6 h after ischemia. These results suggest that it is not COX activity but endogenous cytochrome c that is changed in the early phase after ischemia, and that COX activity begins to decrease 9 h after ischemia. We examined caspase-3 in the CA1 region by immunoblotting, as caspase-3 is known to take part in the cell-death cascade downstream from cytochrome c. Although pro-caspase-3 was strongly detected, active caspase-3 was not detected before and until 84 h after 5-min ischemia. Our data suggested that delayed neuronal death is likely to progress via cytochrome c-release but not via caspase-3 activation.

Animals↗

PubMed2000

Surface supercooling and stability of n-alkane films

The surface tension of n-octadecane was studied in the vicinity of the bulk melting point using both the maximum bubble pressure and Wilhelmy plate methods. The bubble surfaces were found to be supercooled below the surface freezing point. The onset of surface freezing is indicated by a sharp drop in surface tension at a constant temperature. This transition is accompanied by an increased film stability resulting in longer bubble lifetimes at the liquid surface. Variations in bubble lifetime reflect changes in the interfacial mechanical properties of the film from liquidlike to solidlike.

Journal Article↗

PubMed2000

Aortic wall damage in mice unable to synthesize ascorbic acid.

By inactivating the gene for L-gulono-gamma-lactone oxidase, a key enzyme in ascorbic acid synthesis, we have generated mice that, like humans, depend on dietary vitamin C. Regular chow, containing about 110 mg/kg of vitamin C, is unable to support the growth of the mutant mice, which require L-ascorbic acid supplemented in their drinking water (330 mg/liter). Upon withdrawal of supplementation, plasma and tissue ascorbic acid levels decreased to 10-15% of normal within 2 weeks, and after 5 weeks the mutants became anemic, began to lose weight, and die. Plasma total antioxidative capacities were approximately 37% normal in homozygotes after feeding the unsupplemented diet for 3-5 weeks. As plasma ascorbic acid decreased, small, but significant, increases in total cholesterol and decreases in high density lipoprotein cholesterol were observed. The most striking effects of the marginal dietary vitamin C were alterations in the wall of aorta, evidenced by the disruption of elastic laminae, smooth muscle cell proliferation, and focal endothelial desquamation of the luminal surface. Thus, marginal vitamin C deficiency affects the vascular integrity of mice unable to synthesize ascorbic acid, with potentially profound effects on the pathogenesis of vascular diseases. Breeding the vitamin C-dependent mice with mice carrying defined genetic mutations will provide numerous opportunities for systematic studies of the role of antioxidants in health and disease.

Animals↗

PubMed2000

Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils.

Cytochrome c was detected by immunoblotting in the cytosolic fraction 3 h after 5-min ischemia in the non-ischemia-tolerant CA1 region in which about 96% of neurons had developed delayed neuronal death, while less cytosolic cytochrome c was detected in the ischemia-tolerance-induced CA1 region where many more neurons survived. In the immunohistochemical study using anti-non-native cytochrome c monoclonal antibody, immunoreactivity was observed throughout the cytoplasm in the non-ischemia-tolerant CA1 neurons, but not in the normal and ischemia-tolerant CA1 neurons. Then we determined whether Bcl-2, Bax, Bcl-xL and Bcl-xS, which regulate the release of cytochrome c from mitochondria, were altered in the ischemia-tolerant CA1 region. Bcl-2 and Bax were up-regulated in the ischemia-tolerant group, but Bcl-xL and Bcl-xS showed no apparent difference in their expression. These results suggest that cytochrome c release is prevented in CA1 neurons in gerbils in which ischemia-tolerance had been induced and that the altered ratio of Bcl-2 to Bax may play a part in this mechanism.

Animals↗

PubMed2000

Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) is characterized by infiltration of various tissues by circulating ATL cells, a finding often associated with a poor prognosis. Leukocyte migration from the circulation into tissues depends on integrin-mediated adhesion to the endothelium, and integrins are tightly regulated by several factors, such as chemokines. In this study, we focused on the interaction between chemokines and chemokine receptors on ATL cells to understand factors involved in ATL cell infiltration of lymphoid organs. We compared freshly isolated ATL cells from patients with and without lymphoid organ involvement for the expression of the chemokine receptor CCR7/EBI1, the functional receptor for secondary lymphoid-tissue chemokine (SLC), which is expressed at high levels by high endothelial venules of lymph nodes and Peyer's patches. Reverse transcriptase-polymerase chain reaction and flow cytometric analysis, using anti-CCR7 monoclonal antibody (CCR7.6B3), revealed that ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than control CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement. Consequently, significantly more ATL cells from patients with lymphoid organ involvement than control CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement adhered to surfaces coated with ICAM-1 and SLC or EBI1-ligand chemokine (ELC), another ligand for CCR7/EBI1, under static and flow conditions and migrated toward SLC or ELC at a low concentration (30 ng/ml). These findings suggest that increased CCR7/EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. (Blood. 2000; 30-38)

Adult↗

PubMed2000

Effect of germinated barley foodstuff administration on mineral utilization in rodents.

Germinated barley foodstuff (GBF), which is derived from the aleurone and scutellum fractions of germinated barley, is rich in water-insoluble dietary fiber, which reportedly modulates mineral absorption in vivo. This study was conducted to examine whether GBF affects mineral absorption. We performed three experiments. In experiment 1, female ICR mice (4 weeks old) were fed a diet supplemented with 10% GBF or cellulose (CE; as a control) for 24 weeks. Body weight and food intake were recorded twice weekly. On the last experimental day, serum biochemical parameters, including electrolyte parameters, were determined, and major digestive organs were examined histopathologically. In experiment 2, male Sprague-Dawley rats (5 weeks old) were fed the CE and GBF diets, with the mineral content of the CE diet adjusted to the same level as that in the GBF diet, for 14 days, and the intake and fecal excretion of minerals (calcium, Ca; magnesium, Mg: Iron, Fe; Phosphate, P) were determined for the last 3 days. In experiment 3, the binding of Ca and Mg to GBF or cellulose and the release of Ca and Mg from GBF or cellulose was measured in phosphate buffer (pH 6.8). Long-term administration of GBF did not affect the growth rate of mice. GBF did not inhibit the absorption of Ca and Mg, and rather promoted the absorption of Ca and Mg by the gastrointestinal tract. The absorption of Fe and P was not attenuated by GBF administration, and GBF contained only a low level of phytic acid. GBF did not inhibit mineral absorption, differing from the effect of other dietary fibers, and is expected to be useful as a dietary source of Ca and Mg.

Absorption↗