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Biomedical subjects

M Fujita

Publications and source records attributed to M Fujita.

At least 163 records · Page 9Linked to original sources
PubMed2001

Strut fracture of Björk-Shiley convexo-concave valve in Japan--risk of small valve size--.

BACKGROUND: The Björk-Shiley convexo-concave (BSCC) prosthetic valve was introduced in 1979. Between 1979 and 1986, approximately 86,000 BSCC valves were implanted. By December 31, 1994, 564 complete strut fractures had been reported to the manufacture. We experienced a case of an outlet strut fracture and investigated the risk of BSCC prosthetic valve fractures in Japan. METHODS AND RESULTS: To investigate the risk factor of a strut fracture in Japan, we investigated published cases of strut fractures. Between 1979 and 1986, 2021 BSCC valves were implanted in Japan. By January 31, 2000, 11 complete strut fractures of 60-degree BSCC valves including our case had occurred. The patients were eight males and three females. The average age at valve replacement was 42.4+/-8.1 years, and nine of eleven (81.8%) were patients < 50 years-old. The average age of the patients when the BSCC valve fractured was 47.7+/-6.4 years, and eight of eleven (72.7%) were patients <= 50 years old. All patients were implanted in the mitral position. The sizes of the BSCC valve were 27 mm (n=5) (45.5%), 29 mm (n=3) (27.2%), and 31 mm (n=3) (27.2%). Four patients died and seven patients survived. CONCLUSIONS: Although only 11 BSCC valve struts fractured and statistical analysis could not be performed, our findings suggest that the high risk group for a strut fracture in Japan is young male patients with a mitral valve, >= 27 mm in size with BSCC models manufactured before March 1982. When following-up patients with BSCC models manufactured before March 1982, the possibility of a strut fracture in all BSCC valve sizes should be kept in mind.

Adult↗
PubMed2001

Development of a routine analytical procedure for nonylphenol polyethyoxylates and their biodegradation products in sludge from sewage treatment plants.

A method of quantitative analysis of nonylphenol polyethoxylates (NPnEOs) and their biodegration products (NPE-BDPs) in sewage sludge, which is effective, economical, and applicable to a high performance liquid chromatography was developed and actual sludge samples collected from Japanese sewage treatment plants (STPs) were analyzed using the method to confirm its effectiveness. Soxhlet extraction showed better recovery in a spike and recovery test than shaking extraction. Among the four pretreatments for Soxhlet extraction tested, the condition in which samples were freeze-dried, ultrasonicated, and extracted with methanol showed the best recovery efficiency. Quantitative analysis of NPE-BDPs in STP sludge resulted in 6.1 microg/g, 4.3 microg/g, and 8. microg/g in average concentration for NPnEOs (n=1-3), NPnEOs (n=4-18), and nonylphenol ethoxycarboxylates (NPnECs (n=1-3)), respectively, and the values of concentration were 100-1000 times higher than those in effluent at Japan's STPs. The results implied importance of quantitation of NPE-BDPs in sewage sludge to assess the risk to the environment.

Biodegradation, Environmental↗
PubMed2001

Bioflocculation production from lower-molecular fatty acids as a novel strategy for utilization of sludge digestion liquor.

We propose the bioproduction of a bioflocculant from lower-molecular fatty acids as an innovative strategy for utilizing waste sludge digestion liquor. Fundamental studies on the production, characterization and application of a novel bioflocculant were performed. Citrobactersp. TKF04 was screened out of 1,564 natural isolates as a bacterial strain capable of a bioflocculant from acetic and propionic acids. TKF04 produced the bioflocculant during the logarithmic growth in the batch cultivation, and it could be recovered from the culture supernatant by ethanol precipitation. The fed-batch cultivation with feeding of acetic acid: ammonium 10;1 (mole) to maintain pH 8.5 led to the hyper-production of the bioflocculant. The bioflocculant was found to be effective for flocculating a kaolin suspension, when added at a final concentration of 1-10 mg/l, over a wide range of pHs (2-8) and temperatures (3-95 degrees C), while the addition of cations was not required. It could flocculate a variety of inorganic and organic suspended particles including kaolin, diatomite, bentonite, activated carbon, soil and activated sludge. These indicated that the bioflocculant possesses flocculating activity comparable or superior to that of synthetic flocculants. The bioflocculation was identified as a chitosan-like biopolymer.

Bioreactors↗
PubMed2000

Deficiency of the initiation events of sporulation in Bacillus subtilis clpP mutant can be suppressed by a lack of the Spo0E protein phosphatase.

Previous results have shown that the Bacillus subtilis clpP gene is required for developmental processes such as sporulation and competence development. Little is known about its function during the initiation of sporulation. We studied the effect of clpP mutation on the early events of sporulation. The expression of the spo0A and spoIIG genes, whose active transcription requires the phosphorylated Spo0A protein (Spo0A approximately P) as the transcription activator, was significantly decreased in the clpP mutant at the onset of sporulation. The expression of spo0H gene encoding sigma(H) protein was also greatly reduced. As expected from these results, the sigma(H) and Spo0A protein levels in the clpP mutant were also decreased during the initiation of sporulation, indicating that the accumulation of Spo0A approximately P was inhibited in the clpP mutant. We, therefore, introduced the mutation of the spo0E gene, which codes for the Spo0A approximately P-specific phosphatase, into the clpP mutant and found that this double mutant restored the expression of the spo0A as well as spoIIG genes. These results suggest that ClpP had an indirect influence on the intracellular concentration of Spo0A approximately P by regulating the activity of the Spo0E phosphatase during the initiation of sporulation.

Adenosine Triphosphatases↗
PubMed2000

Down-regulation of monocyte chemotactic protein-3 by activated beta-catenin.

Accumulation of intracellular beta-catenin, as a result of inactivation of the adenomatous polyposis coli (APC) gene or by mutation of the beta-catenin gene (CTNNB1) itself, is involved in a wide range of human cancers. By means of fluorescent differential display using a murine fibroblast cell line (L-MT), which expresses an activated form of beta-catenin that accumulates in the cells, we found that expression of murine monocyte chemotactic protein-3 (mMCP-3) was suppressed by activated beta-catenin. Inversely, expression of MCP-3 in human colon cancer cells was induced by depletion of beta-catenin after adenovirus-mediated transfer of wild-type APC genes into the cells. A reporter-gene assay indicated that the accumulation of beta-catenin in the nucleus suppressed activity of the MCP-3 promoter through a putative T-cell factor/lymphocyte enhancer factor (Tcf/LEF)-binding site, ATCAAAG; but when the promoter sequence contained a two-base substitution in the binding site, it failed to suppress reporter-gene (luciferase) activity. An electrophoretic mobility-shift assay using the putative Tcf/LEF-binding sequence revealed interaction of the candidate sequence with the beta-catenin complex. Furthermore, induction of MCP-3 cDNA into HT-29 colon cancer cells increased expression of two markers of differentiation: alkaline phosphatase and carcinoembryonic antigen. Our results implied that activation of beta-catenin through the Tcf/LEF signaling pathway may participate in colonic carcinogenesis by inhibiting MCP-3-induced differentiation of colorectal epithelial cells.

Animals↗
PubMed2000

Effects of posture on sympathetic nervous modulation in patients with chronic heart failure.

We investigated which recumbent position is preferred by patients with chronic heart failure (CHF) and whether sympathetic nervous modulation differs in three recumbent positions. We assessed 12 patients with CHF by spectral analysis of heart-rate variability and measurement of plasma norepinephrine concentrations. The right lateral decubitus position was preferred for significantly longer periods than the left lateral decubitus and supine positions. Sympathetic nervous modulation was most attenuated in the right lateral decubitus position. The right lateral decubitus position preferred by patients with CHF may be a self-protective mechanism to control increased sympathetic nervous modulation.

Heart Failure↗
PubMed2000

Novel method to enhance sternal healing after harvesting bilateral internal thoracic arteries with use of basic fibroblast growth factor.

BACKGROUND: Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) in coronary bypass surgery, especially for diabetic patients. We have reported that basic fibroblast growth factor (bFGF) enhanced regeneration of the skull. This study was designed to evaluate the effects of topical use of bFGF on sternal healing after removing the BITAs. METHODS AND RESULTS: Forty-five Wistar rats were subjected to median sternotomy and were divided into 3 groups: 15 had the BITAs removed and had a bFGF sheet applied on the posterior table of the sternum (group A), 15 had just the BITAs removed (group B), and 15 had intact BITAs (group C). Five and 10 rats were euthanized 2 and 4 weeks after surgery, respectively, in all 3 groups. Peristernal blood flow, measured with use of a noncontact laser flowmeter, decreased after removal of the BITAs (P:<0.001). Four weeks after the surgery, PBF markedly increased only in group A (9.7+/-1.2, 6.5+/-0.6, and 8.2+/-0.5 mL x min(-1) x 100 g(-1) for groups A, B, and C, respectively; P:<0.01 by ANOVA). Four weeks after surgery, the following findings were obtained only in group A: (1) nearly completely healed sternum filled with regenerated bone tissue, (2) marked angiogenesis around the sternum, and (3) osteoblasts in an active form around the edge of the sternum. CONCLUSIONS: The results suggest that use of the bFGF sheet offset the sternal ischemia and accelerated sternal healing. This method may help to decrease sternal necrosis in high-risk patients or allow extended use of BITAs in coronary bypass surgery.

Administration, Topical↗
PubMed2000

Human tumor necrosis factor-alpha mutant RGD-V29 (F4614) shows potent antitumor activity and reduced toxicity against human tumor xenografted nude mice.

The antitumor effects of human tumor necrosis factor-alpha (TNF) mutant RGD-V29 (code no. F4614), that includes the cell adhesive sequence (4)Arg-(5)Gly-(6)Asp and (29)Arg-->Val substitution, were evaluated. The therapeutic index, a measure of the extent of the therapeutically-effective range, using three constitutive administrations of RGD-V29 in Meth A-bearing mice was 4.8, whereas that of recombinant human TNF (rhTNF) ((1)SSS(4)RTPSDK...(29)RR...(155)L) was 2.8, clearly indicating that the effective RGD-V29 dose-range was extended. Furthermore, RGD-V29 showed potent antitumor activity against human lung cancer Mqnu-1 xenografted nude mice without severe gastrointestinal and other organ toxicities, even when administered at the maximal tolerated dose (MTD). In contrast, rhTNF induced severe toxicity at the MTD. Direct cytotoxicity of RGD-V29 against Mqnu-1 cells was similar to that of rhTNF. In addition, a cytotoxicity assay using a tumor-derived endothelial-like cell (tEC)/normal endothelial cell (nEC) system used to study TNF antitumor effects on tumor-associated endothelial cells, suggested that RGD-V29 showed preferential cytotoxicity toward tumor-associated endothelial cells compared with rhTNF. Thus, RGD-V29 appears to be a low-toxicity mutant of rhTNF that shows preferential activity towards tumors, and therefore merits further investigation in pre-clinical and clinical studies.

Amino Acid Sequence↗
PubMed2000

Imaging serotonergic neurotransmission in depression: hippocampal pathophysiology may mirror global brain alterations.

The recent development of [carbonyl-(11)C]WAY-100635 for serotonin (5-HT)(1A) and [(18)F]setoperone and [(18)F]altanserin for 5-HT(2A) positron emission tomography receptor imaging has allowed studies of 5-HT neurotransmission in depressive disorders. The hippocampus is likely to be an important brain structure in the pathophysiology of depression because it may mediate both cognitive deficits and hypercortisolemia found in this disorder. Decreased 5-HT(1A) binding was reported in the medial temporal cortex, which receives dense 5-HT innervation, and also throughout neocortical regions. Because the 5-HT(1A) antagonist pindolol may hasten antidepressant effects of selective serotonin reuptake inhibitor medications, its receptor occupancy has been measured in both presynaptic and postsynaptic sites. The results are controversial but suggest that pindolol has preferential occupancy of somatodendritic autoreceptors in the raphe. The results of 5-HT(2A) receptors are mixed, with one showing a significant decrease in the right orbitoinsular cortex and three not detecting a significant change. The disparate findings in patients with depression almost certainly reflect the heterogeneity of the disorder, and we highlight the utility of the hippocampus as a useful target region not only to compare depressed subjects with healthy subjects but also to correlate findings with cognitive function and activity of the limbic-hypothalamic-pituitary axis system.

Atrophy↗
PubMed2000

Bidirectional function of coronary collateral channels in humans.

To investigate the bidirectional functional adequacy of collateral perfusion, we performed percutaneous transluminal coronary angioplasty (PTCA) on highly stenosed or occluded coronary arteries visualized by the collateral circulation,which were fed by the contralateral coronary artery with severe stenosis. After successful PTCA in all three patients, the contralateral artery was reversely filled by good collateral circulation originating from the dilated coronary artery. These findings indicated that dilation of the receiving coronary artery reversed the pressure gradient across the collateral network, establishing collateral flow in the opposite direction. It was concluded that human collateral channels serve as a bidirectionally functional conduit.

Aged↗
PubMed2000

Co-expression of human chaperone Hsp70 and Hsdj or Hsp40 co-factor increases solubility of overexpressed target proteins in insect cells.

The insect-baculovirus expression system has proved particularly useful for producing recombinant proteins that are biologically active. Overexpression of foreign proteins using the recombinant baculovirus system is often accompanied by aggregation of the overexpressed protein, which is thought to be due to a limitation of the translated protein folding in the infected cells. Co-infection of a recombinant baculovirus capable of expressing the human chaperone Hsp70 slightly increased the solubility of the overexpressed Epstein-Barr virus replication protein, BZLF1. Co-expression of Hsp70 and its co-factor, Hsdj or Hsp40, was here found to improve the solubility of the target protein several fold. Thus, a baculovirus expression system producing these molecular chaperones may find application for improved production of target foreign gene products in insect cells.

Animals↗
PubMed2000

Tyrosine phosphorylation and cellular redistribution of ezrin in MDCK cells treated with pervanadate.

Ezrin is a key protein in membrane-cytoskeleton interaction and is expressed primarily in actin-rich surface projections. Activation in protein tyrosine phosphorylation apparently regulates the structure and function of ezrin. In this study, we found that pervanadate (PV, the complexes of vanadate with hydrogen peroxide) caused an increase in tyrosine phosphorylation of ezrin and affected its cellular redistribution. Treatment of Madin-Darby canine kidney (MDCK) cells with pervanadate resulted in a dramatically increased tyrosine phosphorylation of ezrin within two to five min and the level reached the maximum after 60 min. This was accompanied by an alteration in the subcellular distribution of ezrin. Immunofluorescence and scanning laser confocal microscopy analysis revealed that, after PV stimulation, ezrin was redistributed from cytosol to the apical and lateral membrane domains. This occurred within five min, and more obvious redistribution to the lateral membrane domain was observed after 30 min. Furthermore, immunoblotting of ezrin in cell fractionation experiments showed that, in PV-treated MDCK cells, cytosolic ezrin was translocated to the membrane fraction, while there was no change in the level of ezrin associated with the actin-cytoskeleton. Therefore, cytoplasmic signaling may result in activation of ezrin in tyrosine phosphorylation, which is induced by PV stimulation. These results suggest that ezrin has qualities that might play a role in modulation of cell shape and adhesion.

Amino Acid Sequence↗
PubMed2000

Molecular cloning and expression of a novel chondroitin 6-O-sulfotransferase.

A novel human chondroitin 6-O-sulfotransferase, designated C6ST-2, was identified by BLAST analysis of expressed sequence tag using the sequence of a previously described human chondroitin 6-O-sulfotransferase (C6ST-1) as a probe. The new cDNA sequence revealed an open reading frame coding for a protein of 486 amino acids with a type II transmembrane protein topology. The amino acid sequence displayed 24% identity to the human C6ST-1, and the highest sequence identity was found in the COOH-terminal catalytic domain. The expression of a soluble recombinant form of the protein in COS-1 cells produced an active sulfotransferase with marked specificity for polymer chondroitin. In contrast, keratan sulfate and oligosaccharides containing the Galbeta1-4GlcNAc sequence, which are good acceptor substrates for the C6ST-1, hardly served as acceptors. The identification of the reaction product indicated that the enzyme is a novel chondroitin 6-O-sulfotransferase (C6ST-2) that mainly transfers sulfate to N-acetylgalactosamine. The coding region of C6ST-2 was contained in a single exon and localized to chromosome Xp11. Northern blot analysis of human brain poly(A)(+) RNA revealed a single transcript of 2.4 kilobase pairs. Reverse transcription-polymerase chain reaction analysis showed that C6ST-2 is developmentally regulated in various tissues with expression persisting through adulthood in the spleen. Thus, we demonstrated the redundancy in chondroitin 6-O-sulfotransferases capable of forming chondroitin 6-sulfate, which is important for understanding the mechanisms leading to specific changes in the sulfation profile of chondroitin sulfate chains in various tissues during development and malignant transformation.

Adult↗
PubMed2000

Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor alpha and beta pathways.

Although it is well established that estrogen deficiency causes osteoporosis among the postmenopausal women, the involvement of estrogen receptor (ER) in its pathogenesis still remains uncertain. In the present study, we have generated rats harboring a dominant negative ERalpha, which inhibits the actions of not only ERalpha but also recently identified ERbeta. Contrary to our expectation, the bone mineral density (BMD) of the resulting transgenic female rats was maintained at the same level with that of the wild-type littermates when sham-operated. In addition, ovariectomy-induced bone loss was observed almost equally in both groups. Strikingly, however, the BMD of the transgenic female rats, after ovariectomized, remained decreased even if 17beta-estradiol (E(2)) was administrated, whereas, in contrast, the decrease of littermate BMD was completely prevented by E(2). Moreover, bone histomorphometrical analysis of ovariectomized transgenic rats revealed that the higher rates of bone turnover still remained after treatment with E(2). These results demonstrate that the prevention from the ovariectomy-induced bone loss by estrogen is mediated by ER pathways and that the maintenance of BMD before ovariectomy might be compensated by other mechanisms distinct from ERalpha and ERbeta pathways.

Animals↗
PubMed2000

Isolation and characterization of a novel human gene, DRCTNNB1A, the expression of which is down-regulated by beta-catenin.

Beta-catenin plays significant roles in cell-to-cell adhesion and the Wnt/Wg signal transduction pathway. Accumulation of this protein in the cytoplasm and nucleus as a result of mutations of the adenomatous polyposis coli tumor suppressor gene or of the beta-catenin gene itself is often seen in a wide variety of tumors including carcinomas of the colon, liver, uterus, and brain. Interaction of accumulated beta-catenin with Tcf/Lef transcription factors is known to deregulate expression of some downstream genes, but the precise mechanisms whereby beta-catenin contributes to carcinogenesis remain to be disclosed. Here we report isolation of a novel murine gene, Drctnnb1a (down-regulated by Ctnnb1, a), the expression of which was experimentally down-regulated in response to the activated form of beta-catenin. To investigate a possible role of DRCTNNB1A in cancers, we also isolated the human homologue, DRCTNNB1A, the deduced product of which was 91% identical to the murine protein. The transcript was expressed in all human tissues examined, and we assigned the genomic location of DRCTNNB1A to chromosomal band 7p15.3 by in situ hybridization. Expression of DRCTNNB1A in SW480 colon cancer cells was significantly increased in response to reduction of intracellular beta-catenin by adenovirus-mediated transfer of the beta-catenin-binding domain of the adenomatous polyposis coli gene into the cells. Furthermore, we documented reduced expression of DRCTNNB1A in 12 of 15 primary colorectal cancers examined, compared with corresponding adjacent noncancerous mucosae. Our results implied that DRCTNNB1A is one of the genes involved in the beta-catenin-Tcf/Lef signaling pathway, and that reduced expression of DRCTNNB1A may have some role in colorectal carcinogenesis.

Animals↗