Congenital osteopetrosis is a rare osteosclerotic bone disease characterized by both defect in osteoclastic function and reduced generation of superoxide leukocytes. The frequently fatal during the first decade life. A six-month trial therapy with recombinant human interferon gamma-1b eight patients provided evidence benefit, prompting this study more prolonged therapy.

Superoxide production contributes to osteoclastic bone resorption. Evidence strongly indicates that NADPH oxidase is an enzyme system responsible for superoxide generation in osteoclasts. A membrane-bound subunit, p91, the catalytic domain of oxidase. However, osteoclasts from p91 knockout mice still produce at a rate similar observed wild type mice. This unexpected phenomenon prompted us examine alternative p91-containing In this study, cloning subunit (Nox 4) with 578 amino acids reported....

The S-layer of Bacillus stearothermophilus PV72/p2 shows oblique lattice symmetry and is composed identical protein subunits with a molecular weight 97,000. isolated could bind recrystallize into the on native peptidoglycan-containing sacculi which consist peptidoglycan A1gamma chemotype secondary cell wall polymer an estimated 24,000. be completely extracted from 48% HF, indicating presence phosphodiester linkages between chains backbone. was mainly GlcNAc ManNAc in molar ratio 4:1,...

Abstract Production of superoxide radicals by osteoclasts is necessary for normal bone degradation. White blood cell superoxide, needed bacterial killing, produced activated NADPH oxidase. Since and white cells share a common hematopoietic origin, we initiated experiments to test the hypothesis that at osteoclast-bone interface are Diphenyl iodonium (IDP), an inhibitor oxidase, blocked generation decreased osteoclastic resorption in cultures calvarial explants from mice. Interferon (IFN)...

Abstract A new superoxide‐generating enzyme, NADPH oxidase 4 (Nox4), contributes to osteoclastic superoxide production. In this study, we demonstrated that Nox4 is expressed at a higher level in osteoclasts than precursor cells. This result suggested upregulated during the differentiation and development of osteoclasts. Cotransfection Nox4/P22 DNA resulted enhanced production osteoclasts, indicating P22 may be necessary factor for activity. addition, expression both cathepsin K TRAP...

Abstract Spinal muscular atrophy (SMA) is characterized by degenerating lower motor neurons and an increased incidence of congenital bone fractures. Survival neuron (SMN) levels are significantly reduced due to deletions/mutations in the telomeric SMN1 gene these patients. We utilized Smn −/− SMN2 mouse model SMA determine functional role for SMN remodelling. µCT analysis lumber vertebrae, tibia femur bones from mice revealed osteoporotic phenotype. Histological demonstrated a thin porous...

Oxygen-derived free radicals are produced by osteoclasts. Oxygen radical formation occurs at the osteoclast/bone surface interface. This location next to bone implies that oxygen radicals, including but not limited superoxide, needed for resorption. Compounds scavenge superoxide being developed as pharmaceutical agents inhibit damaging effects of on tissues. One such scavenger is Desferal-manganese complex (DMnC). DMnC reduced amount formazan staining interaction with nitroblue tetrazolium...

ABSTRACT This case emphasizes the role of multidisciplinary involvement and early decision‐making in yew tree ( Taxus baccata ) poisoning. contains taxine alkaloids that predispose to malignant arrhythmia. Here, we present a toxicity presenting with refractory cardiac arrest, salvaged ultimately by VA‐ECMO.

Interferon-gamma (IFN-gamma) treatment increases osteoclastic bone resorption in vivo patients with malignant osteopetrosis (OP). The effect was studied vitro osteoclasts generated by culturing peripheral white blood cells (PWBC) from OP and normal human control subjects. Osteoclasts were treated or without IFN-gamma prior to the end of culture period. subjects large size (161 +/- 18 microm diameter) >10 nuclei per osteoclast. These showed intense staining for tartrate-resistant acid...

Abstract Oral squamous cell carcinomas (OSCC) are malignant tumors with a potent activity of local bone invasion; however, the molecular mechanisms tumor osteolysis unclear. In this study, we identified high level expression chemokine ligand, CXCL13 and RANK ligand (RANKL) in OSCC cells (SCC1, SCC12 SCC14a). cell‐conditioned media (20%) induced osteoclast differentiation which was inhibited by OPG peripheral blood monocyte cultures indicating that produce soluble RANKL. Recombinant hCXCL13...

Recombinant human interleukin‐2 (IL‐2) was studied to determine effects on acid production by individual osteoclasts in situ mouse calvarial bones. This analysis performed using a microspectrofluorimetric technique quantify cells. Radioactive calcium release determined bones standard tissue culture system. allowed us correlate changes with measure of bone resorption. IL‐2 stimulated and resorbing activity. Both were inhibited calcitonin. No stimulation resorption occurred when...

Medical treatments of osteopetrosis have attempted to improve hematologic function, reduce the osteosclerotic condition, and/or immune function. Prednisone therapy has improved function in some patients, but not resulted a reduction bone mass. Calcium deficient diets limited further sclerosis patients. High-dose calcitriol and parathormone infusions stimulated osteoclastic activity. In high-dose clinical improvement. Newer treatments, such as interferon gamma macrophage colony stimulating...

Osteoclasts are the primary cells responsible for bone resorption. Osteoclast formation and resorption activities involve processes tightly controlled by a network of cytokines. The presence interferon gamma (IFN-gamma) receptors on osteoclasts is necessary prerequisite IFN-gamma to directly affect osteoclastic activity. To date, receptor has not been established. This study provides evidence that express receptor. Specific binding stimulates superoxide generation. p91 p47 components NADPH...

Abstract Osteoclasts residing on rims and walls of bony concavities remodeling proximal Libia from growing rats were examined by light microscopy following stripping the periosteal connective tissue layer. Comparison these cells in situ after transfer to glass slides revealed presence numerous mononucleate osteoclasts, as well typical multinucleate forms, all exhibiting a ruffled border acid phosphatase succinic dehydrogenase activity. Macrophage‐like situated adjacent osteoclasts situ....