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Biomedical subjects

S Fukuda

Publications and source records attributed to S Fukuda.

At least 55 records · Page 3Linked to original sources

Regenerative repair of the mandible using a collagen sponge containing TGF-beta1.

INTRODUCTION: Alveolar bone resorption and atrophy of the mandible are a major challenge for regeneration medicine. In the present investigation, a collagen sponge that contained TGF-beta1 was placed at a mandibular defect and the osteogenic effects of collagen-TGF-beta1, complex were evaluated. MATERIAL AND METHODS: The Pm2, Pm3, and Pm4 teeth on both sides of the mandibles of 12 adult beagle dogs (9.0-12.0 kg) were extracted. After the extraction-site wounds healed, a bone defect (10.0 x 15.0 mm-wide, 10.0 mm-deep or 10.0 x 10.0 mm-wide, 10.0 mm-deep) was created on the mandible. A collagen sponge (10.0 x 10.0 x 10.0 mm) that contained TGF-beta1 (1.0 microg, 5.0 microg, or 10.0 microg, in physiological saline) was placed at the bottom of the defect and the overlying mucous membrane was sutured with 4-0 prolene. As a control, a collagen sponge that contained physiological saline only was placed in a defect on the opposite side. Two weeks after the surgery the wounds above the bone defects on both the control and TGF-beta1-treated sides had healed completely. RESULTS: At four, six, or eight weeks post-operatively animals were killed. Soft X-ray and bone-salt measurement analyses confirmed clearly that there was greater calcified bone formation in the defects into which TGF-beta1 had been incorporated than with the control defects. The implanted collagen sponges were fully resorbed and the bone tissue had regenerated from the bottom of the defects on the TGF-beta1, side by four weeks. On the control side, no such regeneration was observed. CONCLUSIONS: These results indicate that TGF-beta1, released slowly from a collagen sponge was effective in promoting bone remodeling when applied to mandibular defects in adult dogs.

Alveolar Bone Loss↗

[Lateral femoral circumflex artery for coronary artery bypass surgery in a patient receiving hemodialysis: report of a case].

A 59-year-old man receiving hemodialysis had a 2-vessel coronary disease. We performed double coronary artery bypass grafting with the left internal thoracic artery to the left anterior descending artery, and the composite graft of right internal thoracic artery and lateral femoral circumflex artery to the right coronary artery. Postoperative coronary angiogram showed that the LFCA bypass graft was widely patent and supplied sufficient blood to the anastomosed vessel. There was no stenosis at the anastomotic site. He had no postoperative complication. Long-term follow-up and more cases is necessary to establish the usefulness of LFCA as an arterial free graft for coronary revascularization in patients receiving hemodialysis.

Coronary Artery Bypass↗

Anti-apoptotic protein survivin plays a significant role in tubular morphogenesis of human coronary arteriolar endothelial cells by hypoxic preconditioning.

Brief exposure of endothelial cells to oxidative stress induced by hypoxia followed by reoxygenation enhances tube formation. Our study provides evidence that hypoxic preconditioning accelerates tubular morphogenesis along with the activation of reactive oxygen species-inducible nuclear transcription factor-kappaB (NF-kappaB), phosphatidylinositol 3-kinase (PI3-kinase) and broad-spectrum anti-apoptotic protein survivin in human coronary arteriolar endothelial cells (HCAEC). The formation of tubular morphogenesis was inhibited by using the PI3-kinase and NF-kappaB antagonists LY294002 and SN50 respectively. The activation of survivin by hypoxic preconditioning was also inhibited by LY294002 and SN50 along with increased apoptosis in HCAEC. These data demonstrate a crucial role of PI3-kinase/Akt/NF-kappaB/survivin signaling in tubular morphogenesis of HCAEC triggered by hypoxic preconditioning.

Apoptosis↗

Cancer-prone syndrome of mosaic variegated aneuploidy and total premature chromatid separation: report of five infants.

Five infants (two girls and three boys) from four families all had severe pre- and postnatal growth retardation, profound developmental delay, microcephaly, hypoplasia of the brain with Dandy-Walker complex or other posterior fossa malformations, and developed uncontrollable clonic seizures. Four infants developed Wilms tumors, and one showed cystic lesions in bilateral kidneys. All five infants showed variegated mosaic aneuploidy in cultured lymphocytes. In two infants whose chromosomes were prepared by us, 48.5%-83.2% lymphocytes showed total premature chromatid separation (PCS). Their parents had 3.5%-41.7% of their lymphocytes in total PCS. The remaining three infants and their parents, whose chromosomes were prepared at outside laboratories, tended to show lower frequencies of total PCS. Another five infants reported with the disorder were reviewed together with the five infants we described. Together, their clinical and cytogenetic manifestations were similar enough to suggest a syndrome. Seven of the 10 infants developed proven or probable Wilms tumors. The age at diagnosis of the tumors was younger than usual at 2-16 months. The tumors were bilateral in four infants and unilateral in three infants, and cystic changes were present in six infants. Two infants developed botryoid rhabdomyosarcoma. The carriers of the syndrome are thus liable to tumorigenesis. The possible role of mitotic checkpoint defects, proven in two infants with the syndrome (Matsuura et al. [2000: Am J Hum Genet 69:483-486]), was discussed in connection with tumor development and progression.

Abnormalities, Multiple↗

Various cells retrovirally transduced with N-acetylgalactosoamine-6-sulfate sulfatase correct Morquio skin fibroblasts in vitro.

Gene therapy may provide a long-term approach to the treatment of mucopolysaccharidoses. As a first step toward the development of an effective gene therapy for mucopolysaccharidosis type IVA (Morquio syndrome), a recombinant retroviral vector, LGSN, derived from the LXSN vector, containing a full-length human wildtype N-acetylgalactosamine-6-sulfate sulfatase (GALNS) cDNA, was produced. Severe Morquio and normal donor fibroblasts were transduced by LGSN. GALNS activity in both Morquio and normal transduced cells was several fold higher than normal values. To measure the variability of GALNS expression among different transduced cells, we transduced normal and Morquio lymphoblastoid B cells and PBLs, human keratinocytes, murine myoblasts C2C12, and rabbit synoviocytes HIG-82 with LGSN. In all cases, an increase of GALNS activity after transduction was measured. In Morquio cells co-cultivated with enzyme-deficient transduced cells, we demonstrated enzyme uptake and persistence of GALNS activity above normal levels for up to 6 days. The uptake was mannose-6-phosphate dependent. Furthermore, we achieved clear evidence that LGSN transduction of Morquio fibroblasts led to correction of the metabolic defect. These results provide the first evidence that GALNS may be delivered either locally or systematically by various cells in an ex vivo gene therapy of MPS IVA.

Animals↗

Developmental and functional analyses of CD8(+) NK1.1(+) T cells in class-I-restricted TCR transgenic mice.

Using a class-I-restricted T cell receptor (TCR) transgenic mice (Tgm), 2C (Valpha3.1/Vbeta 8.2, specific for L(d) + LSPFPFDL), the development and cytokine production of tg-TCR(+) NKT cells were analyzed. We found that CD8(+) or double negative (DN) NKT cells constituted a major population of NKT cells in the H-2(b/b) 2C Tgm (positive selecting background) or the H-2(b/d) 2C Tgm (negative selecting background), respectively. Virtually no NKT cells were generated in the H-2(k/k) 2C Tgm (neutral selecting background). CD8(+) NKT cells in the H-2(b/b) 2C Tgm expressed CD8alphabeta heterodimers, whereas those in the H-2(b/d) 2C Tgm expressed CD8alphaalpha homodimers. These findings suggest that development of a subpopulation of NKT cells is influenced by the H-2 molecules. Upon stimulation with anti-CD3 mAb, tg-TCR(+) NKT cells generated in the H-2(b/b) and H-2(b/d) backgrounds produced IFN-gamma, but not IL-4.

Animals↗

Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34(+) cells by hematopoietic growth factors: implication of survivin expression in normal hematopoiesis.

The inhibitor-of-apoptosis protein survivin is expressed in most cancers and leukemias and during fetal development, but not in most normal adult tissues. Survivin expression was analyzed in umbilical cord blood (UCB) and adult bone marrow CD34(+) cells and in the factor-dependent MO7e cell line; also investigated was whether survivin expression was regulated by hematopoietic growth factors. Survivin messsenger RNA (mRNA) and protein were expressed in fresh UCB and marrow CD34(+) cells. The combination of thrombopoietin, Flt3 ligand, and stem cell factor upregulated survivin expression in CD34(+) cells within 24 hours; survivin expression was cell-cycle related and highest during G2/M, whereas growth-factor withdrawal resulted in decreased survivin expression. Cell-cycle fractionation of UCB CD34(+) with Hoechst-33342/pyronin-Y demonstrated that survivin message was undetectable in freshly isolated G0 cells, but present in G1 cells. After cytokine stimulation, survivin mRNA and protein expression were observed in both G0 and G1 CD34(+) cells as well as in cells that had progressed to S and G2/M phase, indicating that survivin expression is regulated in all phases of the cell cycle. This contrasts with the expression of survivin predominantly during G2/M in cancer cells. In CD34(+) cells and MO7e cells, growth factor-mediated upregulation of survivin was associated with inhibition of apoptosis, and downregulation of survivin was coincident with increased apoptosis. Furthermore, an inverse correlation between survivin and active caspase-3 was observed in CD34(+) cells. These findings demonstrate that survivin is not a cancer-specific antiapoptotic protein and plays a regulatory role in normal adult hematopoiesis.

Antigens, CD34↗

Medication for hearing loss after fractionated stereotactic radiotherapy (SRT) for vestibular schwannoma.

PURPOSE: To investigate the effectiveness of corticosteroid treatments for patients showing decreases in hearing levels after stereotactic radiotherapy for vestibular schwannoma. METHODS AND MATERIALS: Twenty-one patients experienced a hearing loss in pure-tone average at greater than 20 dB or less than 10 dB within 1 year after irradiation administration of 44 Gy/22 fractions followed by a 4 Gy boost. Eight received oral prednisone at a daily dose of 30 mg, which was gradually decreased (medicated group), and 13 received none (nonmedicated group). The average observation period was 26.7 +/- 16.6 (range: 6--69) months. RESULTS: Hearing recovery was seen after initial onset of the hearing loss in all 8 patients in the medicated group and in 2 of 13 patients in the nonmedicated group (p = 0.001). The hearing recovery, that is, the change in pure-tone average (dB) at the last follow-up from the onset of hearing loss, was 9.8 +/- 6.9 dB (recovery) in the medicated group and -9.4 +/- 12.8 dB (further loss) in the nonmedicated group (p = 0.0013). The hearing recovery rate, normalizing to the degree of the hearing loss before medication, was also significantly higher in the medicated group than in the nonmedicated group (p = 0.0014). CONCLUSIONS: Corticosteroidal intake is suggested to be effective in improving hearing loss after stereotactic radiotherapy, at least in young patients having a useful pretreatment hearing level, if the treatment for hearing loss is administered immediately after the hearing loss is first detected.

Adult↗

Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.

Journal Article↗

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Journal Article↗

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗

Murine and human SDF2L1 is an endoplasmic reticulum stress-inducible gene and encodes a new member of the Pmt/rt protein family.

We isolated murine and human cDNAs for SDF2L1 (stromal cell-derived factor 2-like1) and characterized the genomic structures. Northern blot analysis of the gene expression in various tissues revealed that both murine Sdf2l1 and human SDF2L1 genes are expressed ubiquitously, with particularly high expression in the testis. The SDF2L1 protein has an endoplasmic reticulum (ER)-retention-like motif, HDEL, at the carboxy (C)-terminus. Interestingly, SDF2L1 protein also shows significant similarity to the central hydrophilic part of protein O-mannosyltransferase (Pmt) proteins of Saccharomyces cerevisiae, the human homologues of Pmt (POMT1 and POMT2) and Drosophila melanogaster rotated abdomen (rt) protein. In a murine hepatocellular carcinoma cell line, Sdf2l1 was strongly induced by tunicamycin and a calcium ionophore, A23187, and weakly induced by heat stress but was not induced by cycloheximide. In conclusion, SDF2L1 protein is a new member of Pmt/rt protein family and Sdf2l1 is a new ER stress-inducible gene.

Amino Acid Sequence↗

Regeneration of canine peroneal nerve with the use of a polyglycolic acid-collagen tube filled with laminin-soaked collagen sponge: a comparative study of collagen sponge and collagen fibers as filling materials for nerve conduits.

A novel artificial nerve conduit was developed and its efficiency was evaluated on the basis of promotion of peripheral nerve regeneration across an 80-mm gap in dogs. The nerve conduit was made of a polyglycolic acid-collagen tube filled with laminin-soaked collagen sponge. Conduits filled with either sponge- or fiber-form collagen were implanted into an 80-mm gap of the peroneal nerve (five dogs for each form). Twelve months postoperatively nerve regeneration was superior in the sponge group both morphometrically (percentage of neural tissue: fiber: 39.7 +/- 5.2, sponge: 43.0 +/- 4.5, n=3) and electrophysiologically (fiber: CMAP 1.06 +/- 0.077, SEP 1.32 +/- 0.127 sponge: CMAP 1.04 +/- 0.106, SEP 1.24 +/- 0.197, n=5), although these differences were not statistically significant. The observed regeneration was complementary to successful results reported previously in the same model, in which collagen fibers exclusively were used. The results indicate a possible superiority of collagen sponge over collagen fibers as filling materials. In addition, the mass-producibility, superior scaffolding potential, and capacity for gradual release of soluble factors of the sponge provide make it an attractive alternative to fine fibers, which are both technologically difficult and costly to produce. This newly developed nerve conduit has the potential to enhance peripheral nerve regeneration across longer gaps commonly encountered in clinical settings.

Animals↗

The acquisition of complex predicates in japanese specifically language-impaired and normally developing children.

Japanese exhibits two different types of morphological processes. Some morphologically complex predicates are generated within the domain of the lexicon, whereas others are generated outside the domain of the lexicon. An elicited production task involving both types of complex predicates was administered to six Japanese children with specific language impairment (JSLI) and six children with normal language development (JNLD). The JSLI children experienced significant difficulty forming the lexicon-external complex predicates but much less difficulty with the lexicon-internal complex predicates while the performance of the JNLD children exhibited no such asymmetry. These preliminary results suggest that the deficit of SLI affects the ability to construct implicit procedural rules for morphology that are generated outside the lexicon while their lexical operations for morphology that are generated within the domain of the lexicon remain relatively unimpaired.

Child↗

Local fundus response to blue (LED and laser) and infrared (LED and laser) sources.

Light damage research began during the early years of laser light exploration. There is a clear and significant literature that identifies an easily demonstrated retina-pigment epithelium pathology which is associated with short wavelength exposures below 520 nm. Recent interest has expanded because of the growing evidence for a blue light contribution to the retina aging process by way of a poorly understood chemical process(es) that involve circulation, oxidative reactions and the spectral absorption properties of the pigment epithelium. New powerful sources of relatively inexpensive blue energy have become available as a family of light emitting diodes. In this experiment, we examined funduscopic, angiographic and scanning laser tomographic measures of the retinal-pigment epithelium response to LED and laser spectral blue and infrared emissions closely matched in wavelengths and delivered under carefully matched circumstances. Ten retinas in normal young rhesus monkeys were locally exposed to various energy density values at 458 nm (Argon laser) ranging from 5 to 54 J cm(-2). Eight rhesus eyes were exposed to LED irradiation with a peak wavelength of 460 nm ranging from 9 to 62 J cm(-2). Similarly, a matched infrared (IR) laser and IR LED pair were used to expose an additional ten eyes for comparison of the long wavelengths. IR irradiance ranged from 21 to 306 J cm(-2). There was no response to IR exposure in any of the eyes. Blue light exposure results were measured from the color fundus photographs, scanning laser tomographs and early- and late-phase fluorescein angiogram responses at 2 and 30 days after the exposure. Results scores were accumulated for the four measures at the two time periods. The resulting lesion scores when plotted against the exposure in J cm(-2)showed no demonstrable effect at irradiance lower than 10 J cm(-2)and near 100% effectiveness for irradiance greater than 30 J cm(-2). The most sensitive and enduring indicator of change was the late fluorescein angiograms. Nonparametric statistical analysis of the scores from the two samples support the conclusion that there is no difference in the consequences of LED and laser light exposures under these matched conditions.

Analysis of Variance↗

Regulation of H(+)-ATPase synthesis in response to reduced pH in ruminal bacteria.

The capacity of ruminal bacteria to regulate H(+)-ATPase synthesis in response to reduced pH was investigated to explain acid tolerance. The activity of H(+)-ATPase in Streptococcus bovis, an acid-tolerant bacterium, was 2.2-fold higher at pH 4.5 than at pH 5.5. The increase in the amount of H(+)-ATPase protein was similar, suggesting that the increase in H(+)-ATPase activity is owing to the increase in H(+)-ATPase synthesis. The level of atp-mRNA at pH 4.5 was 2.5-fold higher than at pH 5.5, indicating that H(+)-ATPase synthesis is regulated at the transcriptional level, responding to low pH. In Ruminococcus albus, an acid-sensitive bacterium, H(+)-ATPase activity, the amount of H(+)-ATPase protein, and the level of atp-mRNA at pH 7.0 were similar to the values at pH 6.0, the lowest pH permitting growth. This result suggests that R. albus is incapable of enhancing H(+)-ATPase synthesis at low pH. Thus, acid tolerance appeared to be related to the capacity to augment the synthesis of H(+)-ATPase responding to low pH.

Animals↗

Computational analysis of full-length mouse cDNAs compared with human genome sequences.

Although the sequencing of the human genome is complete, identification of encoded genes and determination of their structures remain a major challenge. In this report, we introduce a method that effectively uses full-length mouse cDNAs to complement efforts in carrying out these difficult tasks. A total of 61,227 RIKEN mouse cDNAs (21,076 full-length and 40,151 EST sequences containing certain redundancies) were aligned with the draft human sequences. We found 35,141 non-redundant genomic regions that showed a significant alignment with the mouse cDNAs. We analyzed the structures and compositional properties of the regions detected by the full-length cDNAs, including cross-species comparisons, and noted a systematic bias of GENSCAN against exons of small size and/or low GC-content. Of the cDNAs locating the 35,141 genomic regions, 3,217 did not match any sequences of the known human genes or ESTs. Among those 3,217 cDNAs, 1,141 did not show any significant similarity to any protein sequence in the GenBank non-redundant protein database and thus are candidates for novel genes.

Algorithms↗