Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1.

Dlk-1/Pref-1 was identified as a novel regulator of human skeletal stem cell differentiation. Dlk1/Pref-1 is expressed in bone and cultured osteoblasts, and its constitutive overexpression led to inhibition of osteoblast and adipocyte differentiation of human marrow stromal cells. INTRODUCTION: Molecular control of human mesenchymal stem cell (hMSC) differentiation into osteoblasts and adipocytes is not known. In this study, we examined the role of delta-like 1/preadipocyte factor-1 (Dlk1/Pref-1) in regulating the differentiation of hMSCs. MATERIALS AND METHODS: As a model for hMSCs, we have stably transduced telomerase-immortalized hMSC (hMSC-TERT) with the full length of human Dlk1/Pref-1 cDNA and tested its effect on hMSC growth and differentiation into osteoblasts or adipocytes as assessed by cytochemical staining, FACS analysis, and real time PCR. Ex vivo calvaria organ cultures assay was used to confirm the in vitro effect of Dlk/Pref-1 on bone formation. RESULTS: Dlk1/Pref-1 was found to be expressed in fetal and adult bone, hMSCs, and some osteoblastic cell lines. A retroviral vector containing the human Dlk1/Pref-1 cDNA was used to create a cell line (hMSC-dlk1) expressing high levels of Dlk1/Pref-1 protein. Overexpression of Dlk1/Pref-1 did not affect the proliferation rate of hMSC, but the ability to form mature adipocytes, mineralized matrix in vitro, and new bone formation in neonatal murine calvariae organ cultures was reduced. These effects were associated with inhibition of gene expression markers of late stages of adipocyte (adipocyte fatty acid-binding protein [aP2], peroxisome proliferator-activated receptor-gamma2 [PPARgamma2], and adiponectin [APM1]) and osteoblast differentiation (alkaline phosphatase [ALP], collagen type I [Col1], and osteocalcin [OC]). Lineage commitment markers for adipocytes (adipocyte determination and differentiation factor -1 [ADD1]) and osteoblasts (core binding factor/runt-related binding factor 2 [Cbfa1/Runx2]) were not affected. CONCLUSION: During hMSC differentiation, Dlk1/Pref-1 maintains the size of the bipotential progenitor cell pool by inhibiting the formation of mature osteoblasts and adipocytes.     

Spinal Cord Stimulator Relieves Neuropathic Pain in a Patient With Radiation-Induced Transverse Myelitis

▪ Abstract:   We present a patient with intractable neuropathic pain because of radiation-induced transverse myelitis unresponsive to medical treatment. After a successful trial of spinal cord stimulation, a permanent stimulator was implanted. Improvement was noted in verbal pain score, medication usage and function. Spinal cord stimulation may offer a therapeutic option for patients with neuropathic pain resulting from transverse myelitis and should be considered when other treatments fail. ▪     

Stereotactic radiosurgery for IDH wild type glioblastoma: an international,multicenter study

Journal of Neuro-Oncology - Isocitrate dehydrogenase (IDH) mutation status is recommended used for diagnosis and prognostication of glioblastoma patients. We studied efficacy and safety of...     

Outcomes of Stage I and II Breast Cancer with Nodal Micrometastases Treated with Mastectomy without Axillary Therapy

Breast Cancer Research and Treatment - Studies that report equivalent oncologic outcomes of sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for T1-2N1mi breast...     

Neuroimaging of migrational disorders in pediatric epilepsy

Seizures in children are common and represent a final pathway for a variety of brain insults. Although most children with seizures do not require imaging, when indicated, imaging plays an important role in the clinical workup. Imaging in the pediatric seizure population is reserved for a particular subset of patients depending on factors, such as age of onset, symptomatology, physical examination findings, and specific electroencephalography changes to name a few. The etiologies of seizures are extensive and include disorders of cortical migration and organization. Cortical migration and organization disorders are multifactorial and complex and a major cause of seizure disorders. Although magnetic resonance imaging is the most common imaging modality used to identify the seizure focus, positron emission tomographic and/or diffusion tensor imaging are beginning to provide complementary information about the involved areas. Early and accurate detection is key to better treatment and overall improved patient prognosis.     

Autoimmune cholangitis: A variant of primary biliary cirrhosis

The term autoimmune cholangitis is used for a disease with clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative anti-mitochondrial antibody (AMA) and positive anti-nuclear antibody (ANA) tests. In order to characterize autoimmune cholangitis and to determine whether this truly differs from PBC, we reviewed 200 cases morphologically consistent with PBC in which data on AMA and ANA status were available to us. Of these, 64 (32%) had a negative AMA, 114 (57%) had a positive ANA, and 40 (20%) had negative AMA and positive ANA (autoimmune cholangitis). The AMA-negative group was slightly younger on average (50 vs 55 years) than AMA positives (P<0.05). There were no significant differences in gender (15.5% male overall), hepatic histopathology, or other laboratory tests between the groups of patients with any of the 4 possible combinations of AMA and ANA. Since the only consistently distinguishing feature among these patients is the autoantibody (AMA and ANA) profile, and they otherwise have virtually identical clinical and histopathologic features, autoimmune cholangitis can be considered to be the same as AMA-negative PBC.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.