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Biomedical subjects

Y Toyama

Publications and source records attributed to Y Toyama.

At least 73 records · Page 4Linked to original sources
PubMed2000

Age-related changes in cortical bone in men: metacarpal bone mass measurement study.

Metacarpal cortical bone mass was measured in 507 healthy Japanese men aged 40-95 years, using a microdensitometer to determine age-related changes in cortical bone in these middle-aged and elderly men. Total bone mass showed a significant negative correlation with age (r = -0.281; P < 0.0001). While bone width showed no significant correlation with age, bone marrow width showed a significant positive correlation (r = 0.210; P < 0.0001), and cortical bone width and cortical bone density showed a significant negative correlation with age (r = -0.265; P < 0.0001; r = -0.268; P < 0.0001, respectively). On the other hand, cortical bone width and cortical bone density showed a significant positive correlation with total bone mass (r = 0.814; P < 0.0001; r = 0.474, P < 0.0001, respectively). These findings suggest that cortical bone mass decreases significantly with aging in middle-aged and elderly men, perhaps as a result of two factors - decreased cortical bone width, ie, cortical bone thinning due to bone loss at the endosteal side of the cortex, and decreased cortical bone density due to progression of intracortical porosity. Cortical bone thinning may influence age-related cortical bone loss more than decreasing cortical bone density.

Adult↗
PubMed2000

Contribution of each caffeoyl residue of the pigment molecule of gentiodelphin to blue color development.

To clarify the function of each caffeoyl residue in the diacylated anthocyanin gentiodelphin, a pigment from the blue flower of Gentiana makinoi, two mono-deacyl derivatives were compared for both color development and stability. In neutral solution, 3,5-di-O-beta-D-glucopyranosyl-3'-O-(6-O-caffeoyl-beta-D- glucopyranosyl)delphinidin was both bluer and more stable than 3,3'-di-O-beta-D-glucopyranosyl-5-O-(6-O-caffeoyl-beta-D- glucopyranosyl)delphinidin. Conformational analysis of each derivative under acidic conditions revealed only the 3'-O-caffeoylglucopyranosyl derivative to demonstrate intramolecular stacking. Additionally, the acyl residue in the B-ring contributed more to blue color development than that in the A-ring.

Acylation↗
PubMed2000

Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts.

Bone morphogenetic proteins (BMPs) play an important role in various kinds of pattern formation and organogenesis during vertebrate development. In the skeleton, BMPs induce the differentiation of cells of chondrocytic and osteoblastic cell lineage and enhance their function. However, the action of BMPs on osteoclastic bone resorption, a process essential for pathophysiological bone development and regeneration, is still controversial. In this study, we examine the direct effect of BMPs on osteoclastic bone-resorbing activity in a culture of highly purified rabbit mature osteoclasts. BMP-2 caused a dose- and time-dependent increase in bone resorption pits excavated by the isolated osteoclasts. BMP-4 also stimulated osteoclastic bone resorption. The increase in osteoclastic bone resorption induced by BMP-2 was abolished by the simultaneous addition of follistatin, a BMP/activin binding protein that negates their biological activity. Just as it increased bone resorption, BMP-2 also elevated the messenger RNA expressions of cathepsin K and carbonic anhydrase II, which are key enzymes for the degradation of organic and inorganic bone matrices, respectively. Type IA and II BMP receptors (BMPRs), and their downstream signal transduction molecules, Smad1 and Smad5, were expressed in isolated osteoclasts as well as in osteoblastic cells, whereas type IB BMPR was undetectable. BMPs directly stimulate mature osteoclast function probably mediated by BMPR-IA and BMPR-II and their downstream molecules expressed in osteoclasts. The results presented here expand our understanding of the multifunctional roles of BMPs in bone development.

Animals↗
PubMed2000

Decapitated and decaudated spermatozoa in man, and pathogenesis based on the ultrastructure.

The ultrastructure of decapitated tails and decaudated heads of ejaculated spermatozoa from an infertile man were investigated. The decaudated heads had the nucleus and acrosome, but neither the implantation fossa nor the basal plate were observed at the caudal pole of the nucleus. The nuclear membrane at this portion showed numerous nuclear pores. The decapitated tails contained the proximal centriole at the proximal end. In addition, most decapitated tails had segmented columns, outer coarse fibres, axoneme, mitochondrial sheath and fibrous sheath in the normal position. The ultrastructure reflects the high motility of the decapitated tails of the spermatozoa. Drastic abnormalities were found in the developing spermatids in the biopsied testes. In spermatids later than the Golgi phase, the pair of centrioles were floating in the cytoplasm of the spermatid, but the distal centriole elongated the flagellum. Neither the implantation fossa nor the basal plate were observed at the caudal pole of the nucleus. It is concluded that the tail might be separated from the head before or after completion of tail formation in spermatids. The explanation for why the proximal centriole failed to connect to the nucleus is unknown.

Adult↗
PubMed2000

Diagnostic value of TI-201 and three-phase bone scintigraphy for bone and soft-tissue tumors.

PURPOSE: Although TI-201 is highly sensitive for detecting bone and soft-tissue tumors, its uptake is not specific for malignant lesions. This study assessed the differentiation of malignant and benign lesions and evaluated the sensitivity, specificity, and accuracy of TI-201 imaging and three-phase bone scans. MATERIALS AND METHODS: Forty bone and soft-tissue tumors (16 malignant and 24 benign) were evaluated. TI-201 static images were acquired 10 minutes (early) and 2 hours (delayed) after injection of the radionuclide. Within 14 days, three-phase bone scintigraphy was performed using Tc-99m HMDP with the patient in the same position. The count ratio of the lesion compared with the normal contralateral or adjacent site (L:N ratio) was measured. RESULTS: With TI-201 scintigraphy, mean (+/- SD) values of early and delayed L:N ratios were 3.36 +/- 1.25 and 2.88 +/- 1.20, respectively, in malignant lesions; and 1.88 +/- 1.14 and 1.48 +/- 0.76, respectively, in benign lesions. TI-201 accumulation in benign lesions was significantly less than that of malignancies on early and delayed images. However, an overlap of both ratios between malignant and benign lesions was seen. No such significance was detected on three-phase bone scintigraphy (L:N ratios of malignant and benign tumors were 2.57 +/- 1.22 and 2.24 +/- 2.11, respectively, for blood flow imaging; 2.41 +/- 0.78 and 2.26 +/- 1.54, respectively, for blood pool imaging; and 2.80 +/- 2.10 and 2.89 +/- 4.55, respectively, for bone imaging). When we assumed that the tumor was malignant when the delayed TI-201 L:N ratio exceeded the blood pool phase L:N ratio with bone scintigraphy, the sensitivity rate was 81%, specificity rate was 100%, and accuracy rate was 93%. CONCLUSIONS: TI-201 imaging for bone and soft-tissue tumors was better than three-phase bone scintigraphy alone but was not good enough to clearly differentiate malignant lesions from benign ones. TI-201 scintigraphy, performed in combination with three-phase bone scintigraphy, may be superior to either one of the two imaging procedures alone for bone and soft-tissue tumor diagnosis.

Adolescent↗
PubMed2000

Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells.

In situ detection of neural progenitor cells including stem-like cells is essential for studying the basic mechanisms of the generation of cellular diversity in the CNS, upon which therapeutic treatments for CNS injuries, degenerative diseases, and brain tumors may be based. We have generated rat monoclonal antibodies (Mab 14H1 and 14B8) that recognize an RNA-binding protein Musashi1, but not a Musashi1-related protein, Musashi2. The amino acid sequences at the epitope sites of these anti-Musashi1 Mabs are remarkably conserved among the human, mouse, and Xenopus proteins. Spatiotemporal patterns of Musashi1 immunoreactivity in the developing and/or adult CNS tissues of frogs, birds, rodents, and humans indicated that our anti-Musashi1 Mabs reacted with undifferentiated, proliferative cells in the CNS of all the vertebrates tested. Double or triple immunostaining of embryonic mouse brain cells in monolayer cultures demonstrated strong Musashi1 expression in Nestin(+)/RC2(+) cells. The relative number of Musashi1(+)/Nestin(+)/RC2(+) cells increased fivefold when embryonic forebrain cells were cultured to form 'neurospheres' in which stem-like cells are known to be enriched through their self-renewing mode of growth. Nestin(+)/RC2(-) cells, which included Talpha1-GFP(+) neuronal progenitor cells and GLAST(+) astroglial precursor cells, were also Musashi1(+), as were GFAP(+) astrocytes. Young neurons showed a trace of Musashi1 expression. Cells committed to the oligodendroglial lineage were Musashi(-). Musashi1 was localized to the perikarya of CNS stem-like cells and non-oligodendroglial progenitor cells without shifting to cell processes or endfeet, and is therefore advantageous for identifying each cell and counting cells in situ.

Amino Acid Sequence↗
PubMed2000

Effects of transfusion on gastrointestinal anastomotic wound healing and leukocyte function in rats.

BACKGROUND: This study was done to investigate the effects of blood transfusion on gastrointestinal anastomotic wound healing and leukocyte function. METHODS: Closed-colony male Wistar rats were divided into five groups in a group-mixed fashion and underwent laparotomy (the CONT and WB groups) or gastrectomy and gastroduodenostomy (the GAST, GAST/WB and GAST/LDRWB groups). Immediately, they received 3 ml of saline (the CONT and GAST groups) or blood from Wistar donors (the WB and GAST/WB groups, whole blood; the GAST/LDRWB group, a transfusion of irradiated and leukocyte-depleted whole blood). The animals were killed 7 days after surgery. RESULTS: The GAST/WB group had a higher incidence of anastomotic abscess, a lower level of factor XIII and a lower maximum breaking strength than the GAST group. Gastrectomy decreased L-DCL (luminol-dependent chemiluminescence) more than whole-blood transfusion. In the GAST/WB group, L-DCL was severely reduced, while in the GAST/LDRWB group it was roughly equivalent to the level in the GAST group. CONCLUSIONS: Whole-blood transfusion increased the incidence of anastomotic abscess and impaired anastomotic wound healing, and these might relate to the reduction of L-DCL. Irradiated and leukocyte-depleted transfusion can improve these effects.

Anastomosis, Surgical↗
PubMed1999

Comparison of nerve growth factor mRNA expression in cardiac and skeletal muscle in streptozotocin-induced diabetic mice.

To address the role of nerve growth factor (NGF) in diabetes mellitus (DM)-induced cardiac autonomic neuropathy, we quantitated and compared the expression of NGF mRNA in the cardiac and the skeletal muscle in experimental DM mice with the RT-PCR-HPLC method, which we have developed previously, using a NGF deletion mutant RNA as an internal standard. DM was induced in ICR mice via intraperitoneal injection of streptozotocin. RT-PCR was performed using total RNA extracted from left ventricle and soleus muscle, and the levels of NGF mRNA were quantitated by HPLC analysis. NGF mRNA content of the cardiac muscle was 17-fold higher than the skeletal muscles in control mice. NGF mRNA content of the cardiac muscle in diabetic mice at 6 weeks was 4.0-fold higher than that in the control mice, while that of the skeletal muscle in diabetic mice was not different from the controls. These results indicated that the DM-induced increase in NGF mRNA content was higher in cardiac muscle than skeletal muscle, and that NGF might play an important role in cardiac autonomic neuropathy.

Animals↗
PubMed1999

Ependymomas of the spinal cord and cauda equina: An analysis of 26 cases and a review of the literature.

STUDY DESIGN: Retrospective review. OBJECTIVES: To clarify the clinical features of patients with spinal ependymomas and to compare the clinical results between the patients in whom microsurgical technique and spinal cord monitoring were used intraoperatively and the patients in whom they were not used. SETTING: Keio University Hospital, Tokyo, Japan. METHODS: Twenty-six consecutive patients with spinal ependymomas were treated surgically between 1958 and 1995. All patients underwent tumor resection through a posterior approach. Complete tumor resection was possible in 15 patients (57. 7%), and subtotal tumor resection (more than 90%) was done in two patients (7.7%). Only a partial tumor resection (less than 90%) was performed in the remainder of the patients (34.6%). The operative results of the patients were evaluated by the Japanese Orthopaedic Association Scoring System (JOA score) and its recovery rate. RESULTS: The overall average recovery rate was 18.3%. The mean recovery rate was 14.4% in cervical lesion, 11.1% in thoracic lesion and 40% in lumbar lesion. The recovery rate of eight patients with cervical ependymomas who underwent tumor resection under both microscopic surgical procedure and intraoperative spinal cord monitoring was 37.1% although the recovery rate of the rest of the patients was -1.6%. There was a statistical difference between the two groups (P<0.02). The survival rate of patients following complete excision was statistically better compared to that of patients after incomplete resection. CONCLUSION: Both microsurgical technique and spinal cord monitoring are indispensable to achieve total removal of ependymomas and to obtain improvement of neurological recovery.

Adolescent↗
PubMed1999

Histological characterization of defective spermatogenesis in mice lacking the basigin gene.

Basigin is a transmembrane protein belonging to the immunoglobulin superfamily. In the light of the fact that knockout mice lacking the basigin gene (Bsg) are azoospermic, the phenotype in the male reproductive system was extensively examined in this study. Spermatogenesis in Bsg (-/-) mice was found to be disrupted, and arrested at the metaphase of the first meiotic division. A few germ cells differentiated into young spermatids, but they were exfoliated. The lumens of the male reproductive system were filled with round degenerated cells. Using the TUNEL method and electron microscopy, some of the degenerated cells in the testis and epididymal head were shown to be apoptotic. Crystalloids of fine tubules and unusual ectoplasmic specializations were also observed in the Sertoli cells of Bsg (-/-) mice. These specializations displayed unusual 'circular' structures. Furthermore, unusual ectoplasmic specializations covering the spermatocytes rather than the mature spermatids were found. These structures were formed as a result of the lack of mature spermatids in the Bsg (-/-) testis. Results from analyses of azoospermia in the Bsg (-/-) mice suggest that basigin, through the interactions between germ cells and Sertoli cells, is an essential factor in the growth and/or survival of spermatids.

Animals↗
PubMed1999

Expansive laminoplasty for myelopathy in ossification of the longitudinal ligament.

Laminectomy, which had long been used for treatment of cervical spondylotic myelopathy, including ossification of the longitudinal ligament in the cervical spine, had numerous complications such as postoperative malalignment of the cervical spine and vulnerability of the spinal cord caused by total removal of the posterior structures. In 1977 Hirabayashi devised an open door expansive laminoplasty, which is a relatively easier and safer procedure than laminectomy, that eliminated such problems by preserving the posterior elements. The decompression effect of the expansive laminoplasty against a compressed spinal cord is comparable with that of laminectomy and anterior decompression followed by fusion, whereas the expansive laminoplasty has no structural problems and adverse effects on adjacent disc levels that often are associated with anterior decompression followed by fusion. Average recovery rate of expansive laminoplasty for cervical spondylotic myelopathy has been reported to be approximately 60% (Japanese Orthopaedic Association score) and with long term stability. At present, authors consider all patients with cervical spondylotic myelopathy candidates for expansive laminoplasty except for those having preoperative kyphosis and single level lesion without canal stenosis. Two remaining problems of expansive laminoplasty to be solved are prevention of C5,C6 radicular pain and/or paresis, the most frequent complication that occurs in approximately 5% to 10% of the patients, although most complications resolve spontaneously within 2 years, and correction of nonlordotic alignment to lordosis which are essential for posterior decompression effect of expansive laminoplasty by allowing the spinal cord to shift dorsally.

Cervical Vertebrae↗
PubMed1999

Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene.

Subclones of the human osteosarcoma cell line SaOS-2 were established by transfecting with an expression vector containing the human PTH/PTH-related protein (PTHrP) receptor, and their abilities to support osteoclast-like multinucleated cell (OCL) formation were examined in coculture with mouse or human hemopoietic cells. Of four subclones examined, SaOS-2/4 and SaOS-4/3 bound high levels of [125I]-PTH and produced a significant amount of cAMP in response to PTH. OCLs were formed in response to PTH in the cocultures of mouse bone marrow cells with either SaOS-2/4 cells or SaOS-4/3 cells. Human OCLs were also formed in response to PTH in the coculture of SaOS-4/3 cells and human peripheral blood mononuclear cells. Adding dexamethasone together with PTH greatly enhanced PTH-induced human OCL formation. Like mouse OCLs, human OCLs formed in response to PTH were tartrate-resistant acid phosphatase positive, expressed abundant calcitonin receptors and vitronectin receptors, and formed resorption pits on dentine slices. Other osteotropic factors such as 1alpha,25-dihydroxyvitamin D3, prostaglandin E2, and interleukin 6 plus soluble interleukin 6 receptors failed to induce mouse and human OCLs in cocultures with SaOS-4/3 cells. Both mouse and human OCL formation supported by SaOS-4/3 cells were inhibited by either adding an antibody against macrophage-colony stimulating factor or adding granulocyte/macrophage-colony stimulating factor. Thus, it is likely that human and mouse OCL formation supported by SaOS-4/3 cells are similarly regulated. These results indicate that the target cells of PTH for inducing osteoclast formation are osteoblast/stromal cells but not osteoclast progenitor cells in the coculture. This coculture model will be useful for investigating the abnormalities ofosteoclast differentiation and function in human metabolic bone diseases.

Acid Phosphatase↗
PubMed1999

Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta.

We had previously identified the cDNA for a novel protein called osteoblast-specific factor 2 (OSF-2) from an MC3T3-E1 cDNA library using subtraction hybridization and differential screening techniques. Here we describe the localization, regulation, and potential function of this protein. Immunohistochemistry using specific antiserum revealed that in adult mice, the protein is preferentially expressed in periosteum and periodontal ligament, indicating its tissue specificity and a potential role in bone and tooth formation and maintenance of structure. Based on this observation and the fact that other proteins have been called OSF-2, the protein was renamed "periostin." Western blot analysis showed that periostin is a disulfide linked 90 kDa protein secreted by osteoblasts and osteoblast-like cell lines. Nucleotide sequence revealed four periostin transcripts that differ in the length of the C-terminal domain, possibly caused by alternative splicing events. Reverse transcription- polymerase chain reaction analysis revealed that these isoforms are not expressed uniformly but are differentially expressed in various cell lines. Both purified periostin protein and the periostin-Fc recombinant protein supported attachment and spreading of MC3T3-E1 cells, and this effect was impaired by antiperiostin antiserum, suggesting that periostin is involved in cell adhesion. The protein is highly homologous to betaig-h3, a molecule induced by transforming growth factor beta (TGF-beta) that promotes the adhesion and spreading of fibroblasts. Because TGF-beta has dramatic effects on periosteal expansion and the recruitment of osteoblast precursors, this factor was tested for its effects on periostin expression. By Western blot analysis, TGF-beta increased periostin expression in primary osteoblast cells. Together, these data suggest that periostin may play a role in the recruitment and attachment of osteoblast precursors in the periosteum.

Amino Acid Sequence↗
PubMed1998

Regional differences in alpha1-adrenoceptor subtypes and mechanisms in rabbit arteries.

Contractility mediated through alpha1-adrenoceptor subtypes and the maximum binding site (Bmax value) and the dissociation constant (Kd value) for [125I]HEAT ([125I]iodo-2-(beta-(4-hydroxyphenyl)ethylaminomethyl)tetralone) were determined in the following rabbit arteries: thoracic and abdominal aorta, mesenteric, renal and iliac arteries, and the alpha1-adrenoceptor subtypes mediating contractile mechanisms in vascular smooth muscle were studied. The pD2 values for norepinephrine differed considerably among the arteries in the presence of nicardipine (10(-5) M), while the pA2 values for 5-methylurapidil against norepinephrine were identical at low affinity in all the arteries used. In Ca2+-free physiological saline solution (Ca2+-free PSS), the pA2 values for 5-methylurapidil were also similar except for the renal artery, in which there were no stable contractions. In normal PSS, the concentration-response curves for norepinephrine with chloroethylclonidine-pretreatment were shifted to the right (pD2 values of 5.58, 5.70, 5.74, 5.98 and 6.38 for thoracic and abdominal aorta, mesenteric, renal and iliac arteries, respectively). In the [125I]HEAT binding study using membrane preparations obtained from chloroethylclonidine-treated strips, the Bmax values (33.2-105.2 fmol/mg protein) for [125I]HEAT varied considerably among arteries, while the Kd values (0.20-0.26 nM) were identical. The logarithm of Bmax values is proportional to the pD2 values for norepinephrine (slope=0.69, r=0.961). These observations suggest that the regional differences in potency (pD2 value) of the alpha1-adrenoceptor agonist, norepinephrine, are a result of the differences in population and density of alpha1-adrenoceptor subtypes in rabbit arteries.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1998

Osteoclast differentiation factor (ODF) induces osteoclast-like cell formation in human peripheral blood mononuclear cell cultures.

We have reported that osteoclast differentiation factor (ODF) expressed on the plasma membrane of osteoblasts/ stromal cells is a ligand for osteoclastogenesis inhibitory factor (OCIF). A genetically engineered soluble form of ODF (sODF) induced osteoclast-like multinucleated cells (OCLs) in the presence of M-CSF in mouse spleen cell cultures. Osteoblasts/stromal cells were not required in this process. To elucidate the mechanism of human osteoclastogenesis, human peripheral blood mononuclear cells (PBMCs) were cultured for 7 days with sODF and human M-CSF in the presence or absence of dexamethasone. Treatment of human PBMCs with sODF together with M-CSF induced OCLs, which expressed tartrate-resistant acid phosphatase and vitronectin receptors, produced cAMP in response to calcitonin, and formed resorption pits on dentine slices. OCLs were also formed from the adherent cell population of human PBMCs. Dexamethasone was required for human OCL formation in culture of whole PBMCs but not in culture of the adherent cell population. OCL formation was strongly inhibited by OCIF simultaneously added. These results clearly indicate that like in mouse osteoclastogenesis, ODF is a critical factor for human osteoclastogenesis. The present study also indicates that OCIF acts as a naturally occurring decoy receptor for ODF in inhibiting signal transduction in human osteoclast formation.

Animals↗