Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma.

BACKGROUND: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. METHODS: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo. The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. RESULTS: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro. The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. CONCLUSION: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo. Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.

Basic fibroblast growth factor in the bone microenvironment enhances cell motility and invasion of Ewing's sarcoma family of tumours by activating the FGFR1-PI3K-Rac1 pathway.

BACKGROUND: Ewing's sarcoma family of tumours (ESFT) is a malignant small round-cell tumour of the bone and soft tissues. It is characterised by a strong tendency to invade and form metastases. The microenvironment of the bone marrow is a large repository for many growth factors, including the basic fibroblast growth factor (bFGF). However, the role of bFGF in the invasive and metastatic phenotype of ESFT has not been investigated. METHODS: The motility and invasion of ESFT cells were assessed by a wound-healing assay, chemotaxis assay, and invasion assay. The expression and activation of FGF receptors (FGFRs) in ESFT cell lines and clinical samples were detected by RT-PCR, western blotting, and immunohistochemistry. The morphology of ESFT cells was investigated by phase-contrast microscopy and fluorescence staining for actin. Activation of Rac1 was analysed by a pull-down assay. RESULTS: bFGF strongly induced the motility and invasion of ESFT cells. Furthermore, FGFR1 was found to be expressed and activated in clinical samples of ESFT. Basic FGF-induced cell motility was mediated through the FGFR1-phosphatidylinositol 3-kinase (PI3K)-Rac1 pathway. Conditioned medium from bone marrow stromal cells induced the motility of ESFT cells by activating bFGF/FGFR1 signalling. CONCLUSION: The bFGF-FGFR1-PI3K-Rac1 pathway in the bone microenvironment may have a significant role in the invasion and metastasis of ESFT.

[Comparison of activities of daily living (ADL), medical treatment and blood pressure of elderly participants and non-participants in health examinations].

A study was conducted to determine the characteristics of the elderly who do not participate in health examinations, and to obtain basic health data on the elderly for developing a community health care plan. Elderly persons aged 60 or over who had not participated in mass health examinations in 1991 were interviewed regarding their conditions of activities of daily living (ADLs), and medical treatment, and their blood pressure was measured. Participation rate for health examinations in the elderly was 66%. Of the total 245 elderly who did not participate in health examinations, data from 215 (88%; 92 men and 123 women) were obtained. 1) The average age of the elderly who did not participate in health examinations was 3 years higher in men and 5 years higher in women than that of those who did participate (p < 0.01), and there were a larger number of persons aged 80 years or over. 2) The percentage of persons with a history of adult diseases such as cardiovascular disease was 63% which was 10% higher than those who participated in examinations (p < 0.01). 3) The percentage of persons requiring help in walking and/or mobility (13%) and bathing (10%) was higher than those who participated in examinations (p < 0.01). For seeing and hearing there were no differences between groups in the percentage of disabled persons. 4) There were more hypertensive people (> 160/95 mmHg) in those who did not participate in examinations (p < 0.01), but the percentage of the people who needed treatment (> 180/100 mmHg) was not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Smooth tubular aggregates associated with plasmalemmal invagination in alveolar soft part sarcoma.

The ultrastructure of four alveolar soft part sarcomas was examined to search for ultrastructural signs of myogenic or neural origin. A new ultrastructural structure, an unusual tubular structure, was found in two of four cases. The structure appeared as a large, smooth, tubular aggregate in the cytoplasm of some tumor cells but did not show a honeycomb arrangement of tubules. The aggregate was composed of long, serpentine, branching, smooth, irregularly arranged tubules without ribosomes that ran in various directions. The aggregates intermingled with small amounts of cytoplasmic organelles. Because the aggregated tubules were at times continuous with cell membranes, it was shown that they were the complex extensions or invaginations of cell membranes. Neither myelin-axon complexes nor myofilaments, including Z band material, were seen in any case. There was a possibility that the smooth tubular aggregate was a T-tubule-like structure, suggesting that the tumors were derived from skeletal muscle cells.

Ultrastructural study of a perineurioma.

A case of soft tissue tumor in the left brachialis muscle of a 49-year-old Japanese female patient was studied by electron microscopy. The tumor was diagnosed as intramuscular myxoma by light microscopy, but electron microscopic observation revealed that the tumor almost entirely consisted of cells similar to normal perineurial cells. The tumor cells possessed long, slender cytoplasmic processes covered by well-developed but discontinuous basal laminae, clusters of pinocytotic vesicles, and infrequent intercellular junctions. Perineurial cells have also been observed in other peripheral nerve lesions: neurofibromas, nerve sheath myxomas, and localized hypertrophic neuropathies. However, the term "perineurioma" or "perineurial cell tumor" should be reserved for discrete tumorous masses that are almost entirely composed of perineurial cells without evidence of residual axons, Schwann cells, fibroblasts, or tactile corpusclelike structures. Perineurioma may represent a third category of peripheral nerve sheath tumors, ultrastructurally distinct from schwannomas and neurofibromas.

An unusual coronal fracture of the body of the hamate bone.

A coronal fracture of the body of the hamate is described. Treatment consisted of open reduction and internal fixation with Kirshner wires, and the clinical result was good.

Epidemiological features of HTLV-I carriers and incidence of ATL in an ATL-endemic island: a report of the community-based co-operative study in Tsushima, Japan.

To extend the epidemiological study on adult T-cell leukemia-lymphoma (ATL) in Japan, the geographical and demographic characteristics of carriers of human T-lymphotropic virus type I (HTLV-I) and patients with ATL were analyzed in Tsushima Island, which is one of the typical endemic areas of ATL in Kyushu, Japan. Even on the small island of Tsushima (710 km2; pop. 48,875; 123 villages), the positive rates of anti-HTLV-I antibody among the 58 villages studied varied from 2% to 50%, a fact that is probably associated with the historical events affecting the movement of the indigenous population of Tsushima Island. The positive rate of anti-HTLV-I antibody in males increased little with age; however, the female rate increased distinctly with age in moderate and high HTLV-I-endemic villages where more than 15% of the inhabitants had positive anti-HTLV-I antibody. Analysis of anti-HTLV-I antibody positivity between spouses confirmed that HTLV-I was more contagious from husband to wife than from wife to husband, which corresponded to the fact that the positive rate of anti-HTLV-I antibody in females older than 30 years was higher than that in males. Recently the rate of carrier children from HTLV-I carrier mothers was estimated at around 20%. The recent annual incidence rates of ATL among 1,000 HTLV-I carriers older than 40 years living in Tsushima Island was estimated at 2.2 in males, 0.8 in females.

Cadmium-induced osteopathy: clinical and autopsy findings of four patients.

Clinical and autopsy findings of 4 patients with chronic cadmium toxication by peroral uptake of cadmium are reported. Cadmium toxication was liable to occur in multiparous postmenopausal women, and it began with proteinuria, glycosuria, lumbago and bone pain. Then, renal function gradually decreased being accompanied with renal tubulopathy. Autopsy disclosed renal tubulopathy, which consisted of the flattening of the epithelium of proximal convoluted tubules at the peripheral portion and the mild thickening of the tubular basement membrane. There was no primary change in the glomerulus and renal interstitium. Osteomalacia was observed in the vertebrae and several other bones. The degree of osteomalacia was in good agreement with chronic renal tubular dysfunction. A decrease of the estrogen content, in addition to renal tubulopathy due to biological saturation of cadmium, seems to play an important role in the pathogenesis of cadmium-induced osteomalacia.