Publications by authors named "Mark Birnbaum"

Background: The treatment modalities for pediatric femoral shaft fractures are determined by their age, weight, and fracture pattern. Rigid intramedullary nailing (RIN) is usually recommended for patients >11 years of age, and elastic intramedullary nailing (EIN) has been used for patients under 10 years. However, little is known about the use of RIN in patients aged 8 to 10 years.

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Histone acetyltransferases of the MYST family are recruited to chromatin by BRPF scaffolding proteins. We explored functional consequences and the therapeutic potential of inhibitors targeting acetyl-lysine dependent protein interaction domains (bromodomains) present in BRPF1-3 in bone maintenance. We report three potent and selective inhibitors: one (PFI-4) with high selectivity for the BRPF1B isoform and two pan-BRPF bromodomain inhibitors (OF-1, NI-57).

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The fusion of monocyte/macrophage lineage cells into fully active, multinucleated, bone resorbing osteoclasts is a complex cell biological phenomenon that utilizes specialized proteins. OC-STAMP, a multi-pass transmembrane protein, has been shown to be required for pre-osteoclast fusion and for optimal bone resorption activity. A previously reported knockout mouse model had only mononuclear osteoclasts with markedly reduced resorption activity in vitro, but with paradoxically normal skeletal micro-CT parameters.

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Purpose: Stable slipped capital femoral epiphysis (SCFE) has been shown to have a lower rate of avascular necrosis than unstable SCFE. A recent study found increased intracapsular hip pressures in the setting of unstable SCFE, thus increasing the risk of osteonecrosis. The purpose of this study was to measure the intracapsular pressure in stable SCFE and compare it to the intracapsular pressure in normal hips and in unstable SCFE.

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Background: The painful dislocated hip in the setting of cerebral palsy is a challenging problem. Many surgical procedures have been reported to treat this condition with varying success rates. The purpose of this study is to retrospectively evaluate and compare the outcomes of 3 different surgical procedures performed at our institution for pain relief in patients with spastic quadriplegic cerebral palsy and painful dislocated hips.

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A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory providing students, within a framework of bone cell biology, with a modern approach to gene discovery. Students are introduced to the topics of bone cells, bone synthesis, bone resorption, and osteoporosis.

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The septoclast is a specialized, cathepsin B-rich, perivascular cell type that accompanies invading capillaries on the metaphyseal side of the growth plate during endochondral bone growth. The putative role of septoclasts is to break down the terminal transverse septum of growth plate cartilage and permit capillaries to bud into the lower hypertrophic zone. This process fails in osteoclast-deficient, osteopetrotic animal models, resulting in a progressive growth plate dysplasia.

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Background: Osteonecrosis of the femoral head is the most dreaded complication associated with an unstable slipped capital femoral epiphysis (SCFE). We hypothesize that the hip joint pressure will be increased in unstable slips, confirming that emergent treatment and decompression are warranted.

Methods: Thirteen unstable SCFE hips were evaluated.

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Microarray and real-time RT-PCR were used to examine expression changes in primary bone marrow cells and RAW 264.7 cells in response to RANKL. In silico sequence analysis was performed on a novel gene which we designate OC-STAMP.

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Escherichia coli beta-galactosidase (beta-gal), encoded by the lacZ gene, has become an essential tool in studies of gene expression and function in higher eukaryotes. lac-Z is widely used as a marker gene to detect expression of transgenes or Cre recombinase driven by tissue-specific promoters. The timing and location of promoter activity is easily visualized in whole embryos or specific tissues using the cleavable, chromogenic substrate, 5-bromo-4-chloro-3-indolyl-D-galactopyranoside (X-gal).

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Osteoclasts differentiate from hematopoietic mononuclear precursor cells under the control of both colony stimulating factor-1 (CSF-1, or M-CSF) and receptor activator of NF-kappaB ligand (RANKL, or TRANCE, TNFSF11) to carry out bone resorption. Using high density gene microarrays, we followed gene expression changes in long bone RNA when CSF-1 injections were used to restore osteoclast populations in the CSF-1-null toothless (csf1(tl)/csf1(tl)) osteopetrotic rat. We found that ovarian cancer G-protein-coupled receptor 1 (OGR1, or GPR68) was strongly up-regulated, rising >6-fold in vivo after 2 days of CSF-1 treatments.

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Bone disease is a side effect of concern regarding chronic glucocorticoid (GC) administration. Most GC-treated patients exhibit a process of bone loss, frequently leading to osteoporosis, with increased fracture risk, especially in spinal vertebrae. Some GC-treated patients will develop osteonecrosis, a disease with distinct clinical and histopathological features, most often occurring underneath the articular surface of the femoral head.

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