Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice.

The effect of CD44-phenotypic expression on metastasis to the lung was studied using a spontaneous murine osteosarcoma-derived cell line, POS-1, stimulated with lipopolysaccharide (LPS). POS-1 cells were inoculated into the hind paws of 20 C3H/HeJ mice and produced a visible mass in all mice in 5 weeks, and these transplanted tumors resulted in lung metastasis in all mice. The number of metastatic foci in the lungs was 12.0+/-2.1 (mean+/-SD) with LPS-stimulated cells, which was significantly higher than that of unstimulated cells (5.8+/-1.4; N=10 for each; P<0.05). Hyaluronate (HA), a ligand of CD44, inhibited a number of lung metastases in a dose-dependent manner (0.5% HA, 3.0+/-1.1; 0.005% HA, 5.1+/-1.5; without HA, 8.6+/-1.7; N=10 for each; P<0.05, each group with HA versus the group without HA). Adhesion assay by coculturing POS-1 cells and lung microvascular endothelial cells on culture plate showed that the adhesion was significantly lower in HA treated POS-1 than those without HA (1.18+/-0.12 and 2.74+/-0.17, respectively, P<0.05). These results suggest that lung metastasis was accelerated by up-regulation of CD44.

Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors.

Bone marrow harvested by aspiration contains connective tissue progenitor cells which can be induced to express a bone phenotype in vitro. The number of osteoblastic progenitors can be estimated by counting the colony-forming units which express alkaline phosphatase (CFU-APs). This study was undertaken to test the hypothesis that human aging is associated with a significant change in the number or prevalence of osteoblastic progenitors in the bone marrow. Four 2-ml bone marrow aspirates were harvested bilaterally from the anterior iliac crest of 57 patients, 31 men (age 15-83) and 26 women (age 13-79). A mean of 64 million nucleated cells was harvested per aspirate. The mean prevalence of CFU-APs was found to be 55 per million nucleated cells. These data revealed a significant age-related decline in the number of nucleated cells harvested per aspirate for both men and women (P = 0.002). The number of CFU-APs harvested per aspirate also decreased significantly with age for women (P = 0.02), but not for men (P = 0.3). These findings are relevant to the harvest of bone marrow derived connective tissue progenitors for bone grafting and other tissue engineering applications, and may also be relevant to the pathophysiology of age-related bone loss and post-menopausal osteoporosis.

Characterization of human bone marrow stromal cells with respect to osteoblastic differentiation.

Human bone marrow was harvested by means of iliac crest aspiration and cultured under conditions that promote an osteoblastic phenotype. Human bone marrow aspirates from 30 normal subjects, ages 8-80 years, with no systemic illness, yielded a mean of 92 +/- 65 x 10(6) nucleated cells per 2 ml of aspirate. The prevalence of potential osteoblastic progenitors was estimated by counting the number of alkaline phosphatase-positive colonies. This assay demonstrated a mean of 43 +/- 28 alkaline phosphatase-positive colonies per 10(6) nucleated cells, which was about one per 23,000 nucleated cells. The prevalence of these colonies was positively correlated with the concentration of nucleated cells in the original aspirate (p = 0.014) and was negatively correlated with donor age (p = 0.020). The population of alkaline phosphatase-positive colonies in this model sequentially exhibited markers of the osteoblastic phenotype; essentially all colonies (more than 99%) stained positively for alkaline phosphatase on day 9. Matrix mineralization, which was associated with the synthesis of bone sialoprotein, was demonstrated on day 17 with alizarin red S staining. On day 45, cells that were stimulated with 1,25-dihydroxyvitamin D3 synthesized and secreted osteocalcin at concentrations consistent with known osteoblastic cell lines. This model provides a useful method for the assay of progenitors of connective tissue from human subjects, examination of the effects of aging and selected disease states on this progenitor population, and investigation into the regulation of human osteoblastic differentiation.

Giant intrasacral cellular schwannoma treated with high sacral amputation.

STUDY DESIGN: A case report of a man with a gigantic cellular schwannoma in the sacrum treated with high sacral amputation accompanied by careful nerve root-sparing dissection. OBJECTIVES: To describe the atypical clinical course of an intrasacral cellular schwannoma and the surgical procedure of high sacral amputation performed in a way to prevent needless sacrifice of functionally essential nerve roots. SUMMARY OF BACKGROUND DATA: Fundamentally, a cellular schwannoma is a benign tumor, but the clinical course is atypical. The symptoms are mild and the clinicopathologic features often mislead us to make a diagnosis of malignancy. The occurrence rate of intraosseous cellular schwannoma was reported to be 0.2% of all bony tumors, and the main location was the retroperitoneal space in the pelvis. Forty-one cases of giant intrasacral schwannomas have been reported so far. Among them, large sacral schwannoma with anterior cortex erosion and associated intrapelvic extension was extremely rare. METHODS: The patient presented with a 5-year history of right leg and buttock pain, which did not disturb his daily activities. After a histopathologic diagnosis and a complete set of image studies, high sacral amputation with preservation of uninvolved nerve roots was performed at S1-S2 through a combined anterior and posterior approach. Both S1 nerve roots and the right S2-S3 nerve roots were saved using a threaded saw. The lumbar spine was stabilized to the pelvic girdle using spinal instrumentation with posterolateral fusion. RESULTS: Eighteen months after the tumor was resected the patient had a very good clinical outcome, and there were no radiologic signs of instability or recurrence of the tumor. Locomotor function of both lower extremities and bowel and urinary functions were well maintained. The patient returned to his previous work. CONCLUSIONS: High sacral amputation following a combined anteroposterior approach provided good results without causing any disability. A detailed preoperative planning and careful dissection of uninvolved nerve roots prevented unnecessary neurologic impairment in locomotion and the detrusor and anorectal function.

Eccrine nevus with epidermal changes.

A 22-year-old woman with papular lesions on the extensor aspect of the left leg, present since childhood, with linear distribution is described. Histology of the lesion showed malformed eccrine sweat apparatus with ductal hyperplasia, in addition to the serrated configuration of the epidermis. It appears that the lesions of the eccrine apparatus in this case represent a nevus.

[Trichogenic trichoblastoma]. / Trichogenes Trichoblastom.

A case of rare follicular tumor, which occurred on nasal root of a 73-year-old man, is presented. Histologically one finds a tumor, localized in dermis and subcutaneous tissue, consisting of keratinous cysts, irregular shaped or antlerlike epithelial cell nests and surrounding stroma. The cell nest consists of basaloid cells. Moreover rudimentary hair matrix structures, sebaceous gland lobules and apocrine sweat ducts are observed. This tumor corresponds to trichogenic trichoblastoma as proposed by Headington.

Merkel cell tumor.

A Merkel cell tumor appeared on the left cheek of an 83-year-old female was reported. The tumor was located mainly in the dermis and infiltrated to the subcutaneous adipose tissue with an involvement of the blood vessels and lymphatics at the periphery. Electron-microscopically, few of the dense-cored granules and the single globular aggregates of intermediate filaments at the nuclear indentations were observed. Electron-microscopic uranaffin reaction proved positive reaction on the dense-cored granules. Half of the cytoplasmic border was smooth, while the rest had short projections. Desmosomes or junctional complexes were not detected among the tumor cells. Immunohistochemically, the cytoplasm of tumor cell showed positive reaction to both neuron-specific enolase (NSE) and keratin. The single globular positive spots of the latter were localized in accordance with the aggregates of intermediate filaments. These findings suggested a neurogenic origin with double differentiation, epithelial and neuroendocrine, of the Merkel cell tumor.

Influence of stability and mechanical properties of a spinal fixation device on production of wear debris particles in vivo.

A prospective and quantitative animal study was performed to evaluate the production of wear particles from a spinal fixation device, and to test the hypothesis that the concentration of wear debris particles adjacent to spinal fixation hardware is correlated with the stiffness of the spinal fusion construct and local bone formation at the fusion site. An established canine segmental spinal fusion model with three interfacet fusions was used in this study. Several bone substitute materials were grafted to the area of the interfacet fusion. Internal fixation was performed on both sides of the spinous processes at each site using a stainless steel plate system in 19 dogs. After 12 weeks, spinal segments were excised, then 3-dimensional computerized tomography was used to measure bone volume and bone area of the individual fusion sites. The stiffness of each segment was tested using a servohydraulic materials testing machine. Biopsies were obtained from the soft tissues immediately around the plate system, and wear particles were collected and characterized using an electrical resistance particle analyzer, light and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX). Biopsies from para-spinal tissue from adjacent, unoperated spinal levels served as negative controls. Histologically, 24 of 57 specimens (42.1%) showed only fibrous tissue with no recognizable macrophages, inflammation, or debris. Fourteen of 57 specimens (24.6%), however, contained many particles that were composed of Fe, Cr, and Ni, corresponding to elements found in the fixation hardware. Another 19 specimens showed only occasional particles. The mean concentration of particles from the tissue around the plate system was 2.8 x 10(9) per gram dry tissue weight, compared to 0.5 x 10(9) particles per gram for controls (p < 0.05). Statistical analyses showed significant inverse correlation between the log particle number and stiffness (r = -0.41, p < 0.01), bone volume (r = -0.28, p < 0.05), and bone area (r = -0.34, p < 0. 05) of the corresponding segments. The concentration of particles in the tissue showed a significant inverse correlation with stiffness, bone volume, and bone area of the fusion constructs.

Angiolymphoid hyperplasia with eosinophilia presenting multinucleated cells in histology: an ultrastructural study.

A case of angiolymphoid hyperplasia with eosinophilia arising on the face of a woman is reported. Histologically, the uniqueness of this case is the presence of multinucleated cells (MNCs), besides the conventional dermal changes. Electron microscopy showed that some of the apparent MNCs are clusters of endothelial cells forming immature vascular lumens with numerous microvilli, and the other MNCs displayed the recognized features of fibrohistiocytic or myofibroblastic cells. Immunohistochemically, some MNCs were positive for Ulex europaeus agglutinin and Factor VIII-related antigen. From these findings, some of the MNCs are histologically endothelial sprouts, and the others are fibrohistiocytic cells in the present case.

Immunofluorescence study of cutaneous blood vessels of 16 patients with systemic lupus erythematosus.

In 16 patients with systemic lupus erythematosus, blood vessels in the affected region of the skin were examined regarding localization of immune complexes. Deposition of IgG, IgA, IgM, IgE, beta 1C and fibrin in the vessel walls was more frequently observed in intramural and perivascular sites than in intimal sites. IgM and fibrin were usually detected in intramural sites only. In large caliber arteries of the skin the intima was the main site of deposition of immune reactants, whereas, in small-caliber vessels, including capillaries, immune reactants were more often found in intramural and perivascular sites.