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Biomedical subjects

N Endo

Publications and source records attributed to N Endo.

At least 19 recordsLinked to original sources

Vitamin D and intact PTH status in patients with hip fracture.

INTRODUCTION: The prevalence of hypovitaminosis D in patients with acute hip fracture was examined in a population on Sado Island in Japan. There were 85 cases of hip fracture among this population in 2004, giving an overall incidence of hip fracture of 121.4 per 100,000 population per year. This study included 50 of the 85 cases, and these cases were defined as the hip fracture group. Patients older than 70 years without established osteoporosis who were admitted to the hospital on the island during almost the same period for treatment of an orthopedic condition other than a hip fracture were defined as the control group. MATERIALS AND METHODS: The levels of serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (intact PTH), alkaline phosphatase (ALP), albumin, and the number of remaining teeth were examined in each group. In the hip fracture group, serum calcium, serum phosphorus, urine N-terminal cross-linking telopeptide of type I collagen (NTx), bone mineral density (BMD) of the nonfractured hip, the presence of a vertebral fracture on X-ray, severity of dementia, and physical activity level were also examined. RESULTS: Both the serum 25-OHD and serum albumin levels were significantly lower in patients with hip fracture than in controls, and the intact PTH level was significantly higher in patients with hip fracture. The number of remaining teeth was correlated with age, and was also significantly correlated with 25-OHD. In the hip fracture group, 62% of the subjects had hypovitaminosis D (25-OHD <20 ng/ml) and one-fifth of cases with hypovitaminosis D showed elevated PTH levels (>65 pg/ml). On the other hand, in the control group, hypovitaminosis D occurred in 18.9% of the subjects, and only one case showed elevated PTH. The serum 25-OHD level showed a decrease as the severity of dementia progressed and the activity level decreased. CONCLUSION: Our results indicate that about two-thirds (62%) of hip fracture patients had vitamin D insufficiency, suggesting that this condition may be closely associated with hip fracture in elderly people. Therefore, the serum 25-OHD level may be a useful index for the risk of hip fracture in elderly people.

Aged↗

Long-term outcome of radial shortening with or without ulnar shortening for treatment of Kienbock's disease: a 13-25 year follow-up.

Fourteen of 35 patients who underwent radial shortening with or without ulnar shortening for the treatment of Kienbock's disease were followed up for a median of 19 (range, 13-25) years. Radial shortening was performed for patients with ulnar negative or neutral variance, and combined shortening of radius and ulna for those with ulnar positive variance. Overall the clinical situation was significantly improved at the final follow-up. There was no significant advanced collapse of the wrists and Lichtman's stage of disease increased in only three cases. Although osteoarthritic changes in the distal radio-ulnar joint progressed in five patients, this may have little influence on clinical outcome. Radial shortening osteotomy is a reliable method for treatment of Kienbock's disease.

Adolescent↗

Congenital dermatofibrosarcoma protuberans with fibrosarcomatous and myxoid change.

This report describes a case of congenital dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous (FS) and myxoid areas. Immunohistochemical results showed that tumour cells in ordinary DFSP areas were diffusely positive for CD34, whereas in the FS and myxoid areas, few tumour cells were positive for this antigen. Ki-67 positive tumour cell numbers were greater in the FS (11.8%) and myxoid areas (19.8%) relative to ordinary DFSP areas (2.2%). Reverse transcription polymerase chain reaction and sequence analysis showed the presence of an identical COL1A1-PDGFB fusion transcript in ordinary DFSP (plaque-like area), FS, and myxoid areas of DFSP. These results indicate that the three components of DFSP have a common histogenesis. This study documents the first application of gene analysis involving the myxoid area of DFSP.

Adult↗

Extracorporeal irradiated autogenous osteochondral graft: a histological study.

We examined osteochondral autografts, obtained at a mean of 19.5 months (3 to 48) following extracorporeal irradiation and re-implantation to replace bone defects after removal of tumours. The specimens were obtained from six patients (mean age 13.3 years (10 to 18)) and consisted of articular cartilage (five), subchondral bone (five), external callus (one) and tendon (one). The tumour cells in the grafts were eradicated by a single radiation dose of 60 Gy. In three cartilage specimens, viable chondrocytes were detected. The survival of chondrocytes was confirmed with S-100 protein staining. Three specimens from the subchondral region and a tendon displayed features of regeneration. Callus was seen at the junction between host and irradiated bone.

Adolescent↗

Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation.

The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.

Animals↗

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

Adenoviridae↗

Increase in serum 1,25-dihydroxyvitamin D and hypercalcaemia in a patient with inflammatory myofibroblastic tumour.

Hypercalcaemia complicates the clinical course of a substantial number of patients with advanced cancer. This report describes a patient with an inflammatory myofibroblastic tumour in soft tissue who developed an inflammatory reaction, hypercalcaemia, and a high serum concentration of 1,25 dihydroxyvitamin D. Serum concentrations of 25-hydroxyvitamin D, parathyroid hormone, and parathyroid hormone related protein were normal. Histological examination of the tumour revealed fibrosarcoma with abundant macrophage infiltration. mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase was identified in the tumoral tissue. In view of this case, inflammatory myofibroblastic tumour should be added to the list of diseases that are responsible for vitamin D mediated hypercalcaemia.

Aged↗

6-formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation.

The chemical property of 6-formylpterin and its biological functions were examined. Polarographic studies revealed that 6-formylpterin reacted with NAD(P)H and consumed oxygen. In contrast, other conjugated pterins, such as biopterin and neopterin, showed no consumption of oxygen. The production analysis using high-performance liquid chromatography documented that 6-formylpterin catalyzes the conversion from NADH to NAD. Electroparamagnetic resonance spin trapping experiments demonstrated that this reaction is accompanied with the generation of reactive oxygen species (ROS), superoxide anion and hydrogen peroxide. When 6-formylpterin was administered to HL-60 cells, intracellular ROS generation was observed and apoptosis was induced. In contrast, other conjugated pterins induced neither intracellular ROS generation nor apoptosis in HL-60 cells. The intracellular ROS generation by 6-formylpterin was observed in other cells, such as PanC-1 cells and Jurkat cells. 6-formylpterin suppressed cell proliferation in PanC-1 cells and inhibited Fas-mediated apoptosis in Jurkat cells. These findings indicate that, among conjugated pterins, 6-formylpterin has the unique property to transfer electron from NAD(P)H to oxygen and that the property brings about intracellular ROS generation, which exerts various biological functions such as induction of apoptosis, suppression of cell proliferation, and inhibition of Fas-mediated apoptosis.

Apoptosis↗

Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia.

Phosphaturic mesenchymal tumor is a rare neoplasm which causes osteomalacia or rickets. The tumor typically follows a benign clinical course. Even in the rare malignant cases, local recurrence and distant metastasis are uncommon. We report on an example of a malignant phosphaturic mesenchymal tumor which recurred several times over 16 years concurrently causing hypophosphatemia, bone pain, and osteomalacia. Following each surgery, symptoms and hypophosphatemia improved. The patient died of disease 17 years after the first surgery. Histologically, the initial tumor was composed of small spindle cells with clusters of giant cells, prominent blood vessels, poorly formed cartilaginous areas, and crystalline material. Cytological atypia was minimal. Following multiple recurrences, the tumor demonstrated areas of high-grade sarcoma exhibiting marked pleomorphism, numerous mitotic figures, and p53 overexpression. This case illustrates the potential lethality of incompletely removed phosphaturic mesenchymal tumors.

Bone Neoplasms↗

Parathyroid hormone increases the expression level of matrix metalloproteinase-13 in vivo.

Parathyroid hormone (PTH) increases serum calcium (Ca) by enhancing bone resorption and renal Ca reabsorption. However, detailed mechanisms of enhanced bone resorption by PTH remain to be elucidated. Although PTH has been shown to increase the expression level of osteoblastic matrix metalloproteinase (MMP)-13 in vitro, only limited results are available regarding the in vivo regulation of MMP expression. In the present study, we have examined expression levels of MMPs in PTH-infused rats. Infusion of 1.5 or 2.0 nmol/kg/day rat PTH(1-34) for 3 days resulted in a dose-dependent increase in serum Ca. PTH infusion also decreased serum phosphate levels and increased urinary excretion of Ca and phosphate. Infusion of PTH for 7 days resulted in less severe hypercalcemia and hypophosphatemia. Urinary Ca and phosphate excretion in rats infused for 7 days was less than that in rats infused for 3 days. Northern blot analysis showed that PTH infusion increased the expression level of MMP-13 in calvaria, although it did not affect MMP-2 expression. Furthermore, the time-course and severity of hypercalcemia and hypercalciuria correlated with the expression level of MMP-13. In situ hybridization also showed that PTH infusion increased the expression level of MMP-13 in femora. These results indicate that PTH enhances MMP-13 expression in vivo and suggest that PTH stimulates bone resorption at least partly by enhancing MMP-13 expression.

Animals↗

In vivo bone-forming capacity of human bone marrow-derived stromal cells is stimulated by recombinant human bone morphogenetic protein-2.

In the present study, we investigated whether the in vivo bone-forming capacity of human bone marrow-derived stromal cells (HMSCs) could be enhanced by recombinant human bone morphogenetic protein-2 (rhBMP-2). The HMSCs obtained from seven donors (5-54 years of age) were passaged three to six times. Passaged HMSCs exhibited the osteoblastic phenotype in vitro, including: (a) an increase in alkaline phosphatase (ALP) activity in response to dexamethasone, ascorbic acid, and beta-glycerophosphate: and (b) mRNA expression for markers of osteoblastic lineage (ALP, osteopontin, osteocalcin, and parathyroid hormone-receptor) and BMP-2, -4, and -6 detected by reverse transcription-polymerase chain reaction. For the in vivo assay, transplants were subcutaneously implanted into nude mice as follows: group A (vehicle); group B (rhBMP-2); group C (HMSCs with vehicle); and group D (HMSCs with rhBMP-2). Transplants were obtained 2 and 4 weeks after implantation. Correlated radiographic findings, histological observations, and in situ hybridization using species-specific probes showed that the group B transplants contained bone tissue of mouse origin, which was observed at the periphery of the transplants. Four weeks after implantation, small amounts of HMSCs-derived bone tissue were detected at the periphery in two of seven transplants in group C. In contrast, five of seven group D transplants exhibited HMSCs-derived bone tissue, which was located at the center of the transplants and was surrounded by mouse bone tissue. Furthermore, HMSCs-derived chondrogenesis was detected in two of seven group D transplants. The results of the present study demonstrate that culture-expanded HMSCs preserve the osteoblastic phenotype, and the in vivo bone-forming capacity can be promoted by rhBMP-2.

Adolescent↗

A PCR-ELISA assay for the detection of disseminated osteosarcoma cells in a mouse metastatic model.

Circulating tumor cells in the blood play a central role in the metastatic process. There have been no reports describing the relationship between lung metastasis and circulating osteosarcoma cells. We developed a system with a polymerase chain reaction assay based on an enzyme-linked immunosorbent assay (PCR-ELISA) to detect circulating osteosarcoma cells in a mouse metastatic model. Osf2/Cbfa1, hereafter called Osf2, a member of the runt family of transcription factors, was used as a target gene. One splicing variant of Osf2 mRNA was identified and its expression was restricted to the bones and osteosarcomas. The amount of the splicing variant of Osf2 mRNA was significantly higher in the blood of mice with metastasis than in the blood of the control group. The PCR-ELISA using Osf2 mRNA is a potential method to detect circulating osteosarcoma cells in peripheral blood.

Alternative Splicing↗

Immunohistochemistry of atrial natriuretic peptide in brain infarction.

Atrial natriuretic peptide (ANP) was originally isolated from cardiac atria, and has potent natriuretic, diuretic, and vasorelaxant properties. It has been localized in neurons and astrocytes in the cerebral cortex and the white matter. We hypothesize that glial ANP may contribute to the regulation of cerebral blood flow in brain infarction. In order to elucidate this possible role, the immunohistochemistry of ANP was studied in cases of brain infarction and in other cases of brain trauma for comparison. A statistically significant increase in the number of ANP-immunoreactive glial cells (mainly astrocytes) was observed in the white matter surrounding the brain infarction compared with the intact area. No statistically significant increase in ANP-immunoreactive glial cell number was observed in the cerebral white matter from brain haemorrhage, contusion and control cases. Our results indicate that glial ANP may increase in number in brain infarction, and that it may be involved in the regulation of the cerebral blood flow in the infarcted area.

Adult↗