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Biomedical subjects

S Fukuda

Publications and source records attributed to S Fukuda.

At least 37 records · Page 2Linked to original sources

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↗

KAI1, CAR, and Smad4 expression in the progression of colorectal tumor.

PURPOSE: The abnormal expression of several genes is involved in the development of colorectal tumors. The aim of this study was to examine the expression of KAI1, CAR, and Smad4, which has been associated with the progression of other cancers. METHODS: We examined 12 adenomas, 38 primary carcinomas, 10 liver metastases, and 7 adenocarcinoma cell lines, by fluorescent multiplex reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: KAI1 expression was higher in adenomas (2.55 +/- 0.61; P < 0.05) and primary carcinomas (3.30 +/- 0.42; P < 0.005) than in normal mucosa, but it was not correlated with tumor stage. CAR expression was lower in Dukes' B (1.28 +/- 0.53) than in Dukes' A (2.38 +/- 0.48) (P < 0.05), but increased with tumor progression; Dukes' C (1.45 +/- 0.25), Dukes' D (1.53 +/- 0.14), and metastases (2.09 +/- 0.39) (P < 0.05). Smad4 expression increased in adenomas (2.30 +/- 0.46; P < 0.05), but decreased with tumor progression; Dukes' A (2.14 +/- 0.37), Dukes' B (1.65 +/- 0.41), Dukes' C (1.57 +/- 0.25), Dukes' D (1.08 +/- 0.18), and metastases (0.82 +/- 0.21) (P < 0.05). CONCLUSIONS: These results suggest that the upregulation of CAR and down-regulation of Smad4 are associated with the progression of colorectal tumors, while the upregulation of these genes and of KAI1 seems to be involved in the early stage.

ATPases Associated with Diverse Cellular Activitie↗

Ecabet sodium inhibits the ability of Helicobacter pylori to induce neutrophil production of reactive oxygen species and interleukin-8.

The pathogenic role of human neutrophils has been implicated in Helicobacter pylori-associated gastritis. Ecabet sodium, a locally acting antiulcer drug, has anti-H. pylori actions. The aim of this study was to examine the effects of ecabet on the ability of H. pylori to stimulate human neutrophils. H. pylori were added to 1 x 10(5) neutrophils and incubated for 30 min in the presence of ecabet. Bacterial suspensions which had been incubated with ecabet for 30 min were also used to stimulate neutrophils. The intracellular production of reactive oxygen species was measured with a FACScan. Bacterial suspensions were also added to neutrophils in the presence of ecabet and incubated at 37 degrees C for 12 h to measure interleukin (IL)-8 production by enzyme-linked immunosorbent assay. The mean fluorescence intensity was found to be attenuated dose-dependently by ecabet (P < 0.01). Ecabet also inhibited IL-8 production by neutrophils in a dose-dependent manner (P < 0.001). Bacteria with prior incubation with ecabet induced significantly lower IL-8 production than those without this incubation (P < 0.05). Ecabet sodium has preventive effects on the ability of H. pylori to stimulate human neutrophils. It may lead to reduced gastritis activity and decreased oxidative damage of the gastric mucosa in H. pylori-associated gastritis.

Abietanes↗

Unusual liver carcinomas with sarcomatous features: analysis of four cases.

We recently examined the clinicopathological and immunohistochemical features of four cases of primary hepatic carcinoma with sarcomatoid elements. Three of the four patients had associated ordinary hepatocellular carcinoma (HCC) and one had a sarcomatoid carcinoma with no apparent elements of HCC. The presenting symptoms were high fever and hypochondralgia in three patients, and right hypochondralgia without a high fever in one. The preoperative diagnoses were liver abscess in two patients, HCC in one, and cholangioma in one. Preoperative imaging showed necrotic change or abscess formation in the tumors. The sarcomatous elements showed a positive reaction to vimentin in three patients, but the ordinary HCC cells did not. Macroscopically, the tumors appeared as a single nodule with pericapsular growth. The prognoses of these patients were poor due to the early development of intrahepatic or distal metastases. We conclude that symptoms such as a high fever or hypochondralgia are characteristics of these tumors and that they may be histogenetically derived from a dedifferentiation of HCC, although no elements of HCC were found in one of our cases.

Aged↗

Carcinoma arising in the pancreas 17 years after primary excision of a choledochal cysts: report of a case.

We report herein the case of a 42-year-old woman in whom a pancreatic carcinoma was found 17 years after excision of a choledochal cyst with Roux-en-Y hepaticojejunostomy. Although the incidence of biliary carcinoma associated with choledochal cyst is high, reports of cancer developing in the remaining intrapancreatic biliary tract or pancreas in patients who have previously undergone primary excision of a choledochal cyst are extremely rare. Long-term follow-up is recommended even for patients who have undergone excisional surgery for a choledochal cyst, in consideration of the possibility that cancer associated with the intrapancreatic biliary tract or pancreas may develop.

Adult↗

Malignant sarcomatoid tumor of the liver: report of a case.

A 65-year-old man was referred to our hospital for treatment of a liver tumor. Abdominal ultrasonography (US) demonstrated a low echoic mass in the S2-S4 region of the liver, which was confirmed by abdominal computed tomography (CT). In the delayed phase of angio-CT, the inside of the mass was not enhanced. Abdominal angiography showed a hypovascular area in the liver. An extended left lobectomy was performed. Macroscopically, the tumor was 9.5 x 9.5 cm in size, and on cross section, it was white and clearly demarcated from the surrounding tissue. Microscopic observation of hematoxylin-eosin-stained specimens did not show any glandular or trabecular formation. Histologically, there was diffuse proliferation of atypical spindle cells that had hyperchromatic, short, spindle-shaped nuclei, and pale cytoplasm with poor intercellular adhesion. The nontumorous tissue was almost normal with no sign of cirrhosis. Immunohistochemical examination showed that the spindle cells were positive for vimentin and cytokeratins (AE1/AE3, CAM 5.2), but negative for all other markers. The final diagnosis was a sarcomatoid carcinoma, the origin of which was not able to be confirmed immunohistochemically. This case of a primary hepatic tumor composed of malignant cells with sarcomatous features is described, and the immunohistochemical findings are discussed.

Aged↗

Tricuspid valve supra-annular implantation in adult patients with Ebstein's anomaly.

BACKGROUND: Tricuspid valve supra-annular implantation (TVSI) has been performed for adult patients with Ebstein's anomaly at our hospital for several decades. TVSI is characterized by reliable reduction of tricuspid annulus size without affecting the conduction system; by prevention of residual tricuspid regurgitation (RTR) through preservation of the native tricuspid valve; and by implantation of the bioprosthesis at a supra-annular site. METHODS: Ten adult patients with Ebstein's anomaly underwent TVSI. The right ventricular diameter and residual tricuspid regurgitation were evaluated by echocardiography preoperatively, at discharge, 1 year after the operation, and over the long term (12.4 +/- 5.5 years). Actuarial survival rate, actuarial freedom from structural valve deterioration rate, and postoperative occurrence of arrhythmia were also evaluated. RESULTS: The actuarial survival rate at 19 years was 76 +/- 15%. Tricuspid regurgitation disappeared in 8 patients just after operation. Right ventricular diameter was significantly smaller at discharge than preoperatively (63 +/- 11 vs 37 +/- 9, p < 0.01), and there were no significant differences between values at discharge and at follow-up. The actuarial freedom from structural valve deterioration rate and the reoperation rate were both 100%. There were no fatal complications related to arrhythmia or thromboembolism. CONCLUSIONS: TVSI is useful for adult patients with Ebstein's anomaly. The absence of complications related to fatal arrhythmia and thromboembolism, good durability of the bioprosthesis, and a simple operative procedure are merits of this therapy.

Actuarial Analysis↗