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Biomedical subjects

Y Okubo

Publications and source records attributed to Y Okubo.

At least 19 recordsLinked to original sources
PubMed2006

A functional MRI study: cerebral laterality for lexical-semantic processing and human voice perception.

BACKGROUND AND PURPOSE: Language dominance research using functional neuroimaging has made important contributions to clinical applications. Nevertheless, although recent neuroimaging studies demonstrated right-lateralized activation by human voice perception, the influence of voice perception in terms of language dominance has not been adequately studied. We aimed to accurately clarify language dominance for lexical-semantic processing in the temporal cortices by focusing on human voice perception. METHODS: Thirty normal right-handed subjects were scanned by functional MR imaging while listening to sentences (SEN), reverse sentences (rSEN), and identifiable nonvocal sounds (SND). We investigated cerebral activation and the distribution of individual Laterality Index under 3 contrasts: rSEN-SND, SEN-SND, and SEN-rSEN. RESULTS: The rSEN-SND contrast, including human voice perception, revealed right-lateralized activation in the anterior temporal cortices. Both SEN-SND and SEN-rSEN contrasts, including lexical-semantic processing, showed left-lateralized activation in the inferior and middle frontal gyrus and middle temporal gyrus. The SEN-rSEN contrast, without the influence of human voice perception, showed no temporal activation in the right hemisphere. Symmetrical or right-lateralized activation was observed in 22 of 27 subjects (81.4%) under the rSEN-SND contrast in the temporal cortices. Although 9 of 27 subjects (33.3%) showed symmetrical or right-lateralized activation under the SEN-SND contrast in the temporal cortices, all subjects showed left-lateralized activation under the SEN-rSEN contrast. CONCLUSION: Our results demonstrated that right-lateralized activation by human voice perception could mask left-lateralized activation by lexical-semantic processing. This finding suggests that the influence of human voice perception should be adequately taken into account when language dominance is determined.

Adult↗
PubMed2005

Tissue reaction at the implantation of recombinant human bone morphogenetic protein-2 into the skeletal muscle.

Bone morphogenetic protein (BMP) is a unique cytokine that induces bony tissue in soft tissue. Tissue reactions at and around the implantation of recombinant human BMP-2 (rhBMP-2) into the soft tissue of rats and nonhuman primates were investigated. At the osteoinduced site of rats, massive trabeculae-lined osteoblasts and rich marrow were observed. At and around the nonosteoinduced sites of nonhuman primates, large clear nuclei were observed in reaction to rhBMP-2 implantation. The surrounding area was visually classified into zones 1, 2 and 3. Zone 3 was near the center of the implant. The area of nuclei, the major axis, the minor axis and the ratio of minor axis per major axis were image-analyzed in the histological views. In zones 1, 2 and 3, the nuclear areas were 18.0 (3.1) mean (SD); unit micron2, 33.4 (5.61) and 110.1 (23.7), respectively. The major axes of nuclear ellipses were 7.45 (0.22) (unit micron), 7.76 (0.26), and 13.9 (1.88), respectively. The minor axes were 3.07 (0.53), 5.59 (0.95) and 10.1 (1.35), respectively. The ratios of minor axis per major axis of nuclear ellipses were 0.4 (0.57), 0.72 (0.11) and 0.73 (0.11) in zones 1, 2 and 3, respectively. These results showed that in zones 2 and 3 cell and tissue reactions were marked against rhBMP-2 implantation.

Animals↗
PubMed2004

Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice.

We established the clonal mesenchymal cell line, GFP-C3 (C3), which differentiates into osteoblasts in response to BMP-2 from calvariae of newborn green fluorescence protein (GFP) transgenic mice. This cell line cultured with control medium expressed low levels of alkaline phosphatase (ALP) activity and osterix mRNA and undetectable ALP and osteocalcin mRNA. Incubation of these cells with rhBMP-2 increased ALP activity dose-dependently and induced substantial levels of ALP, osteocalcin and osterix mRNA expression. C3 cells infected with adenovirus vector encoding BMP-2 (AdBMP-2) or Runx2 (AdRunx2) showed greatly increased ALP mRNA expression in a time-dependent fashion. Transduction with AdRunx2-induced expression of ALP and osteocalcin mRNA, but not osterix mRNA by day 3. Transduction with AdBMP-2 induced apparent expression of ALP and osterix mRNA by day 1 after transduction, but induced only weak expression of osteocalcin mRNA day 3 after transduction. Transplantation of C3 cells transduced with AdBMP-2 into back subfascia in wild-type mice with a complex of poly-d,l-lactic-co-glycolic acid/gelatin sponge (PGS) generated ectopic bone formation involving GFP-positive osteoblasts and osteocytes 2 weeks after transplantation. C3 cells transduced with AdRunx2 or AdLacZ failed to induce ectopic bone formation. Transplantation of C3 cells transduced with AdBMP-2 into craniotomy defects in wild-type mice using PGS as a carrier induced bone formation 2 weeks after transplantation, and replaced defects 4 weeks after transplantation. C3 cells transduced with AdRunx2 failed to induce bone repair after transplantation into craniotomy defects. These results indicate that C3 cells retain differentiation potential into osteoblasts in response to BMP-2. They are useful tools for analyzing the process of osteoblast differentiation in vivo after transplantation.

Animals↗
PubMed2004

Simple and effective osteoinductive gene therapy by local injection of a bone morphogenetic protein-2-expressing recombinant adenoviral vector and FK506 mixture in rats.

We have previously utilized a human bone morphogenetic protein-2 (BMP-2)-expressing recombinant adenoviral vector (AxCAOBMP-2) for osteoinductive gene therapy in rats. However, immunosuppression is essential for osteoinduction by AxCAOBMP-2 and this is one of the major impediments to its clinical use. Injection of AxCAOBMP-2 together with the immunosuppressant FK506 made it possible to markedly reduce the dose of the immunosuppressive agent and still induce ectopic bone reliably. We injected AxCAOBMP-2 and FK506 into the right calf muscle of rats, while the same number of plaque forming units of AxCAOBMP-2 and the same dose of FK506 placebo (vehicle) were injected into the left calf muscle. At 1, 3, 5, 7, 9 days after injection, BMP-2 mRNA expression was significantly higher in the right calf muscle than in the left calf muscle. At 21 days after injection, significantly more ectopic bone was observed in the right calf muscle than in the left calf muscle. These results indicate that coinjection of FK506 significantly promotes osteoinduction. In addition, local injection of FK506 may also make it possible to prevent a decrease of gene expression with other adenoviral vector.

Adenoviridae↗
PubMed2004

Flow cytometric detection of cell-associated interleukin-8 in alveolar macrophages in vivo from patients with hypersensitivity pneumonitis and sarcoidosis.

In comparison with neutrophil-mediated lung diseases, such as acute respiratory distress syndrome, the involvement of IL-8 in lymphocyte-mediated lung diseases has not been fully investigated. Several reports have shown a slight increase in bronchoalveolar lavage fluid (BALF) IL-8 in patients with hypersensitivity pneumonitis (HP) and sarcoidosis (SAR), but the source of the IL-8 has not been clarified. In the present study, the in vivo production of IL-8 by alveolar macrophages (AMs) is examined in these patients by analyzing the cell-associated IL-8, using the flow cytometric method adopted previously. The IL-8 levels in the epithelial lining fluid (ELF) were also assessed. Initially, slight, but significant, increased levels of ELF IL-8 in HP and SAR were confirmed. Using flow cytometric analysis, a significant increase was found in the cell-associated IL-8 of the freshly isolated AMs in HP, but not in SAR, indicating in vivo production of IL-8 by AMs in HP. The cell-associated IL-8 of the AMs cultured with or without lipopolysaccharide was also analyzed. However, in contrast to previous findings in patients with idiopathic pulmonary fibrosis, no differences were found between SAR and HP patients and control subjects. Based on these findings, it is speculated that ELF IL-8 levels are slightly increased in HP and SAR, and they may contribute to the accumulation of neutrophils and possibly lymphocytes. However, the source of IL-8 may be different and AMs are the candidate source of IL-8 in HP, but not in SAR. The flow cytometric method may be useful in assessing cytokines production by AMs.

Adult↗
PubMed2003

Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2.

We investigated the osteogenic potential of skin fibroblasts that overexpressed BMP-2 or Runx2 by using adenoviral vectors. In in vitro experiments, skin fibroblasts infected with adenovirus vector encoding BMP-2 (AdBMP-2) released substantial levels of BMP-2 proteins into culture media, and those infected with adenovirus vector encoding Runx2 (AdRunx2) produced its protein. Transduction of BMP-2 or Runx2, respectively, increased alkaline phosphatase (ALP) activity and induced expression of mRNAs of ALP, osteocalcin, and osterix in skin fibroblasts. In in vivo experiments, we investigated the bone induction activity by transplantation of a complex composed of carrier [poly-D,L-lactic-co-glycolic acid/gelatin sponge (PGS)] and skin fibroblasts (PGS/SF complex). Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2-induced ectopic bone formation when transplanted into the subfascia of back muscle, unlike those infected with AdRunx2. Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2 into craniotomy defects induced bone formation from 2 weeks after transplantation, and almost all PGS was replaced by newly synthesized bone at 6 weeks. To investigate the fate of the transplanted cells, we transplanted skin fibroblasts isolated from green fluorescence protein transgenic mice into craniotomy defects. Transplantation of these skin fibroblasts transfected with AdBMP-2 generated green fluorescence protein-positive osteoblasts and osteocytes, indicating that the transplanted skin fibroblasts differentiated into osteoblastic lineage cells during bone repair. In contrast, transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdRunx2 induced a few ALP-positive cells at 1 week after transplantation, but their number decreased depending on time after transplantation. In addition, transplantation of these complexes was insufficient to induce bone repair. Taken together, our results suggest that skin fibroblasts expressing BMP-2 are more suitable for cell-mediated therapy of bone repair than those expressing Runx2.

Adenoviridae↗
PubMed2003

Preclinical study of recombinant human bone morphogenetic protein-2: application of hyperbaric oxygenation during bone formation under unfavourable condition.

The objective of this study was to evaluate the effect of hyperbaric oxygenation on bone formation by recombinant human bone morphogenetic protein-2 (rhBMP-2) under unfavourable conditions. The calf muscles of 10 rats with low-blood supply were prepared by ligating and cutting the right femoral artery, and 10 micro of rhBMP-2 was implanted in the calf muscle. Five rats each were randomly assigned to the hyperbaric oxygenation group and the control group (untreated). The rats in the hyperbaric oxygenation group were treated with hyperbaric oxygenation at 2.0 atmospheres absolute for 3 weeks. In the histologic evaluation, the number of osteoblasts in the hyperbaric oxygenation group was greater than that in control group. The area of the trabecular bone induced in the hyperbaric oxygenation group was significantly larger than that in the control group. The values of alkaline phosphatase activity and calcium contents in the hyperbaric oxygenation group were significantly higher than those in the control group. The results of the present study suggest that hyperbaric oxygenation increases the partial oxygen pressure in low blood supply tissue and accelerates the activity and rate of osteoinduction by rhBMP-2. Hyperbaric oxygenation therapy may increase the clinical application of rhBMP-2 to unfavourable condition.

Animals↗
PubMed2003

A follow-up study on the association of working conditions and lifestyles with the development of (perceived) mental symptoms in workers of a telecommunication enterprise.

AIM: This study investigated the association of working conditions and lifestyle with mental health in Japanese workers. METHODS: A follow-up study was carried out in the Kanto district of Japan of workers in a telecommunications enterprise who received their first annual health check-up between 1992 and 1996 and were between 20 and 54 years old. Workers who reported mental symptoms, had a past history of disease, or current illness at their first check-up were excluded from the analysis. In total, the study included 23 837 workers. The association between working conditions and lifestyle and the development of mental symptoms was investigated by pooled logistic regression analyses. RESULTS: Working long hours and part-time work, as opposed to normal daytime hours of work, were factors associated with the development of mental symptoms in males, as were smoking, short sleeping hours, little physical exercise, rarely taking three meals a day, frequently eating within 1 h before sleep, much preference for salty meals and little preference for vegetables. Consumption of alcohol was negatively associated with the development of mental symptoms in males. Overall, the results suggested that the lower the Healthy Work and Lifestyle Score, the higher the risk of developing mental symptoms. CONCLUSIONS: Working conditions and lifestyle, especially food preferences, have an apparent influence on the mental health of Japanese workers. Moreover, the Healthy Work and Lifestyle Score indicates that working conditions and lifestyle appear to have a cumulative influence upon the mental health of Japanese workers.

Adult↗
PubMed2002

An association between smoking habits and blood pressure in normotensive Japanese men.

We conducted a cross-sectional study to clarify the dose-effect relationship of smoking habits with blood pressure in Japanese men. The subjects were 2781 normotensive male steelworkers ranging in age from 40 to 54 years. They were classified into five categories according to their smoking habits: non-smokers, ex-smokers, light smokers, moderate smokers and heavy smokers. Age, body mass index, salt intake, physical activity, drinking habits, and levels of gamma-glutamyl transpeptidase, total serum cholesterol, uric acid, creatinine and plasma glucose were analysed as covariates. The association between smoking habits and blood pressure was evaluated using analysis of covariance. Our results showed that there was no significant difference in the adjusted systolic and diastolic blood pressure between non-smokers and ex-smokers. The adjusted systolic and diastolic blood pressures in light, moderate and heavy smokers were significantly lower than in non- and ex-smokers. However, among smokers, no significant difference was observed in correlation with smoking amount. In conclusion, blood pressure of smokers was lower than that of non- and ex-smokers. However, there were no significant dose-effect relationships between smoking amount and blood pressure when lifestyle and other confounding factors were considered.

Adult↗
PubMed2002

Regeneration of defects in the articular cartilage in rabbit temporomandibular joints by bone morphogenetic protein-2.

The purpose of this study was to investigate the therapeutic use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in internally deranged temporomandibular joints (TMJ). Defects (2 mm in diameter) were created in the surface of the condylar head. Lyophilized rhBMP-2 with collagen as the carrier was implanted in the defects in different doses: rhBMP-2 15 microg (n = 5); rhBMP-2 3 microg (n = 5); rhBMP-2 0.6 microg (n = 5). In the two control groups, the defects were either filled with collagen alone (n = 5) or left untreated (n = 5). Three weeks postoperatively the sites of defects were examined under light microscopy. In the 15 micromg and the 3 microg groups, new cartilage had filled the defects; endochondral ossification was also found deep within the defect. In the 0.6 microg group, fibrous tissue was proliferating in most areas of the defect, although cartilage was also found in some parts. In the two control groups, there was either soft tissue repair only or no evidence of tissue repair. These findings suggest that BMP-2 could stimulate the repair of defects in the articular cartilage of the mandibular condyle head during the 3 weeks postoperatively. To observe the progress of endochondral ossification in more detail, it may be necessary to extend the experiment for a longer period of time. However, this study supports the contention that BMP-2 may be useful in the regeneration of cartilage in TMJ disease.

Animals↗
PubMed2002

Identification of a novel gelsolin truncate in the vertical and metastatic phase malignant melanomas.

Examination of 38 human melanoma samples by Western blotting analysis with anti-gelsolin antibodies showed that a new 85 kDa truncated gelsolin (GSNp85), co-expressed with wild-type gelsolin, was frequently expressed in vertical growth phase melanomas (Clark level II-IV) and metastatic growth phase melanomas. The GSNp85 truncate was not expressed in radial growth phase melanomas (Clark level I), acquired naevi, other skin cancers or normal skin tissues. Peptide-sequencing analysis revealed that GSNp85 lacks the C-terminal domain of wild-type gelsolin at the region containing the caspase-8 recognition site IETD. Caspase-8 processing was detected in GSNp85-positive but not GSNp85-negative melanomas. These data suggest that GSNp85 is a cleavage product of caspase-8 and may be useful as a new marker for the vertical or metastatic growth phase of malignant melanoma.

Amino Acid Sequence↗
PubMed2002

Influence of years engaged in agriculture and number of pregnancies and deliveries on mortality of inhabitants of the Jinzu River basin area, Japan.

BACKGROUND: The occurrence of itai-itai disease is thought to be affected by such factors as pregnancy, lactation, hormonal disorders, aging, and calcium deficiency. AIMS: To study the influence of years engaged in agriculture and number of pregnancies and deliveries on the mortality of inhabitants of the Jinzu River basin area, which has been an endemic region for itai-itai disease. METHODS: From 6,667 participants (3,181 men, 3,486 women; participation rate 93.4%) in the 1967 health survey, 3,639 subjects (1,591 men, 2,048 women) whose years engaged in agriculture were established, and 2,559 women/2,410 women with a known number of pregnancies/deliveries were selected as the target population. These data were confirmed on the basis of self reported replies confirmed afterwards by interview. The survival survey was conducted for 6,127 days from 1 August 1967 to 10 May 1984. Subjects were divided according to three water systems: the Jinzu River, non-Jinzu River, and mixed water system; the influence on mortality of the years engaged in agriculture and the number of pregnancies/deliveries was analysed using a Cox's proportional hazards model according to the water systems. RESULTS: The mean years engaged in agriculture and mean number of pregnancies/deliveries were not different among the three water systems. Cox's hazard ratios of these parameters to mortality were not statistically significant in the any of the water systems. CONCLUSIONS: Neither the years engaged in agriculture nor the number of pregnancies/deliveries influenced mortality in subjects living not only in the non-Jinzu River basin but also in the Jinzu River basin using a Cox's proportional hazards model.

Adult↗
PubMed2002

Dysregulation of IGF-I signaling in uterine leiomyoma.

IGF-I expression has been observed in human uterine leiomyomas. To examine whether autocrine IGF-I signaling plays a role in the growth of these tumors, we used an animal model of uterine leiomyoma (the Eker rat) to investigate regulation of IGF-I and the IGF-I receptor (IGF-IR) expression in tumors and normal myometrium. During the normal estrous cycle, myometrial IGF-I expression peaked on the day of proestrus when the rate of proliferation in this tissue is greatest. In leiomyomas, the expression of IGF-I was increased 7.5-fold compared with the age-matched normal tissue. The level of IGF-IR mRNA in both tumor and non-tumor tissues was found to inversely correlate with that of IGF-I. Changes observed in IGF-I signaling components correlated with the activation state of the signal-transducing protein insulin receptor substrate-1 (IRS-1). During diestrus and proestrus when IGF-I levels were increasing, tyrosine phosphorylation of IRS-1 was increased up to 5.7-fold in the normal myometrium relative to estrus, when IGF-I levels were the lowest. Additionally, IRS-1 phosphorylation was 4-fold greater in leiomyomas relative to age-matched normal myometrium. Autocrine stimulation of the IGF-IR may, therefore, play a role in regulating the normal growth of the myometrium, and dysregulation of IGF-I signaling could contribute to the neoplastic growth of uterine leiomyomas.

Animals↗
PubMed2001

The time course study of osteoinduction by bone morphogenetic protein-2 via adenoviral vector.

We evaluated the time course of osteoinduction by an adenoviral vector, AxCAOBMP-2, in normal rats (Group I) and 2 immunosuppressed groups (Groups II and III). Immunosuppression was induced by 125 mg/kg of cyclophosphamide injected intraperitoneally the day before vector injection. Groups I and III received a high dose of AxCAOBMP-2 (25 microl; 8.75 x 10(8) pfu) and Group II a low dose (5 microl; 1.75 x 10(8) pfu). Each dose of AxCAOBMP-2 was injected into the right calf muscle of rats. On days 7, 14 and 21 postinjection, the osteoinducive activity in each group was investigated radiologically, histologically, immunohistochemically and biochemically. Osteoinduction was observed only in Groups II and III on days 14 and 21. The activity of osteoinduction in Group III was higher than that in Group II. There was little difference in the expression of LacZ between Groups I and III on day 3. However, there was a marked difference in BMP-2 protein expression between Groups I and III on day 7 postinjection. We speculated that the reason for this was that most of the infected cells were eliminated by the immune system of the host from days 3 to 7. These results suggest that gene therapy with AxCAOBMP-2 under transient immunosuppression may be useful for bone reconstruction.

Adenoviridae↗
PubMed2001

Gene cloning and characterization of alanine racemases from Shigella dysenteriae, Shigella boydii, Shigella flexneri, and Shigella sonnei.

Alanine racemase genes (alr) from Shigella dysenteriae, Shigella boydii, Shigella flexneri, and Shigella sonnei were cloned and expressed in Escherichia coli JM109. All genes encoded a polypeptide of 359 amino acids, and showed more than 99% sequence identities with each other. In particular, the S. dysenteriae alr was identical with the S. flexneri alr. Differences in the amino acid sequences between the four Shigella enzymes were only two residues: Gly138 in S. dysenteriae and S. flexneri (Glu138 in the other) and Ile225 in S. sonnei (Thr225 in the other). The S. boydii enzyme was identical with the E. coli K12 alr enzyme. Each Shigella alr enzyme purified to homogeneity has an apparent molecular mass about 43,000 by SDS-gel electrophoresis, and about 46,000 by gel filtration. However, all enzymes showed an apparent molecular mass about 60,000 by gel filtration in the presence of a substrate, 0.1 M l-alanine. These results suggest that the Shigella alr enzymes having an ordinary monomeric structure interact with other monomer in the presence of the substrate. The enzymes were almost identical in the enzymological properties, and showed lower catalytic activities (about 210 units/mg) than those of homodimeric alanine racemases reported.

Alanine Racemase↗