Giant cell tumor of bone express p63.

p63 contributes to skeletal development and tumor formation; however, little is known regarding its activity in the context of bone and soft tissue neoplasms. The purpose of this study was to investigate p63 expression in giant cell tumor of bone and to determine whether it can be used to discriminate between other giant cell-rich tumors. Seventeen cases of giant cell tumor of bone were examined to determine the cell type expressing p63 and identify the isoforms present. Total RNA or cell protein was extracted from mononuclear- or giant cell-enriched fractions or intact giant cell tumor of bone and examined by RT-PCR or western blot, respectively. Immunohistochemistry was used to evaluate p63 expression in paraffin embedded sections of giant cell tumor of bone and in tumors containing multinucleated giant cells, including: giant cell tumor of tendon sheath, pigmented villonodular synovitis, aneurysmal bone cyst, chondroblastoma, and central giant cell granuloma. The mononuclear cell component in all cases of giant cell tumor of bone was found to express all forms of TAp63 (alpha, beta, and gamma), whereas only low levels of the TAp63 alpha and beta isoforms were detected in multinucleated cells; DeltaNp63 was not detected in these tumors. Western blot analysis identified p63 protein as being predominately localized to mononuclear cells compared to giant cells. This was confirmed by immunohistochemical staining of paraffin-embedded tumor sections, with expression identified in all cases of giant cell tumor of bone. Only a proportion of cases of aneurysmal bone cyst and chondroblastoma showed p63 immunoreactivity whereas it was not detected in central giant cell granuloma, giant cell tumor of tendon sheath, or pigmented villonodular synovitis. The differential expression of p63 in giant cell tumor of bone and central giant cell granuloma suggest that these two tumors may have a different pathogenesis. Moreover, p63 may be a useful biomarker to differentiate giant cell tumor of bone from central giant cell granuloma and other giant cell-rich tumors, such as giant cell tumor of tendon sheath and pigmented villonodular synovitis.     

Gait speed is more challenging than cognitive load on the stride-to-stride variability in individuals with anterior cruciate ligament deficiency

Background

Several investigations have studied gait variability of individuals with anterior cruciate ligament (ACL) deficiency; however, the effect of dual-tasking on the gait variability of these individuals remained unclear. The aim of the present study was to determine the effect of gait speed and dual-tasking on knee flexion–extension variability in subjects with and without ACL deficiency.

Intrathoracic kidney: A rare presentation of ectopic kidney

The thoracic kidney is the rarest form of renal ectopia. Furthermore, it is usually asymptomatic and discovered incidentally. It is seen as a mass in the posterior mediastinum or juxta-diaphragmatic on chest radiography. A computed tomography scan or magnetic resonance imaging is usually needed for a definitive diagnosis. The thoracic kidney typically exits the retroperitoneal space through the foramen of Bochdalek.     

Automatic Computation of Left Ventricular Volume Changes Over a Cardiac Cycle from Echocardiography Images by Nonlinear Dimensionality Reduction

Curve of left ventricular (LV) volume changes throughout the cardiac cycle is a fundamental parameter for clinical evaluation of various cardiovascular diseases. Currently, this evaluation is often performed manually which is tedious and time consuming and suffers from significant interobserver and intraobserver variability. This paper introduces a new automatic method, based on nonlinear dimensionality reduction (NLDR) for extracting the curve of the LV volume changes over a cardiac cycle from two-dimensional (2-D) echocardiography images. Isometric feature mapping (Isomap) is one of the most popular NLDR algorithms. In this study, a modified version of Isomap algorithm, where image to image distance metric is computed using nonrigid registration, is applied on 2-D echocardiography images of one cycle of heart. Using this approach, the nonlinear information of these images is embedded in a 2-D manifold and each image is characterized by a symbol on the constructed manifold. This new representation visualizes the relationship between these images based on LV volume changes and allows extracting the curve of the LV volume changes automatically. Our method in comparison to the traditional segmentation algorithms does not need any LV myocardial segmentation and tracking, particularly difficult in the echocardiography images. Moreover, a large data set under various diseases for training is not required. The results obtained by our method are quantitatively evaluated to those obtained manually by the highly experienced echocardiographer on ten healthy volunteers and six patients which depict the usefulness of the presented method.     

BMP Stimulation of Alkaline Phosphatase Activity in Pluripotent Mouse C2C12 Cells is Inhibited by Dermatopontin,One of the Most Abundant Low Molecular Weight Proteins in Demineralized Bone Matrix

Demineralized bone matrix (DBM) is a complex mixture of osteoinductive bone morphogenetic proteins (BMPs), as well as BMP-binding proteins that regulate BMP bioactivity and localization. Our aim was to use modern proteomic methods to identify additional BMP-binding proteins in DBM, with initial emphasis on the most abundant. Relatively large, water-soluble noncollagenous proteins (NCPs) were preferentially extracted from DBM with alkalinized urea. The insoluble residue, which contained the BMP activity, was extracted with GuHCl/CaCl₂, dialyzed versus citrate, defatted, resuspended in GuHCl, dialyzed sequentially against Triton X-100 and water, pelleted, and lyophilized. The proteins in this pellet were fractionated by hydroxyapatite affinity chromatography. Proteins that copurified with BMP bioactivity were separated by SDS-PAGE. Distinct bands were excised, and the proteins in them were reduced and alkylated, digested with trypsin, eluted, and subjected to MALDI/ToF MS (matrix-assisted laser-desorption ionization time-of-flight mass spectrometry). Computer-assisted peptide fingerprint analysis of the MS profiles was used to identify C-terminal lysine-6-oxidase; dermatopontin (DPT); histones H2A2, H2A3, and H2B; and trace amounts of γ-actin. DPT is a 22-kDa, tyrosine-rich acidic matrix protein not previously recognized to be among the most abundant small proteins to copurify with BMP bioactivity in DBM. We tested the effects of DPT on BMP-2 stimulation of alkaline phosphatase (ALP) activity in C2C12 cells. BMP-2 stimulated ALP activity in C2C12 cells by 6.2-fold above basal levels. DPT alone had no effect on ALP activity in C2C12 cells. When added with BMP-2, DPT blocked 40% of the stimulatory effect of BMP-2 on ALP activity in C2C12 cells. DPT is an abundant protein in DBM, and it can inhibit the stimulatory effects of BMP-2 on ALP activity in C2C12 cells.     

Microanatomical study of testis in juvenile ostrich (Struthio camelus)

The majority of investigations on the testis, as the main organ of male reproductive system, have been performed in mammalian species, with few studies on bird species. Thus, the structure of the ostrich testis remains largely unknown. The aim of this study was to investigate the microanatomical characteristics of the testis in five juvenile ostriches. A stereological study was performed according to the Delesse principle. The mean volume fraction of the seminiferous tubules was 0.569, and the mean volume of the seminiferous tubules in an average testis was 1.04 cm³. The Paraffin-embedded sections were stained with hematoxylin and eosin, Masson’s trichrome, Alcian blue, and periodic acid–Schiff stains. Histological studies revealed that the spermatogonial stem cells and Sertoli cells were localized inside the seminiferous tubules, close to the basement membrane. Inside the tubules a few meiotic cells up to the spermatozoa stage were located in a centripetal manner. Outside the tubules, one to three layers of euchromatic peritubular myoid cells were present, surrounded by loose interstitial connective tissue. A thick tunica albuginea contained many myoid cells and some rete ducts, with the latter extending from the hilus to the free surface of the testis. Straight seminiferous tubules were distributed in the lateral surfaces and hilar portions of the capsule but were rare in the free surface. These capsular rete ducts may participate in testicular fluid transit from the distal tubules through the capsule.     

Anesthetic Efficacy of Meperidine in Teeth With Symptomatic Irreversible Pulpitis

Achieving adequate pulpal anesthesia in mandibular teeth is always a challenge. Supplementary injections and using drugs in combination are some methods implemented to overcome this hurdle. In this randomized clinical trial, use of meperidine in conjunction with lidocaine in intraligamentary injection did not exhibit significant improvement in anesthesia.Key Words: Periodontal ligament, Meperidine, Irreversible pulpitis, Dental anesthesiaThe failure rate of the inferior alveolar nerve block (IANB) in some experimental studies has been reported up to 75%.^1–4 This lack of success has even increased to a maximum of 81% in some recent studies.^5–7 To overcome this shortcoming, dental clinicians have actively sought measures to improve the patients'' anesthesia during different dental procedures. Apart from the anatomical variations mentioned in the applied anatomy of injections,⁸ several authors have attempted to modify the anesthetic technique,^9–12 and others have compared different anesthetic agents¹³ or their concentrations¹⁴ to improve their efficacy.Activating the opioid receptors peripherally in inflammatory conditions has become a new trend in research to manage postoperative pain.¹⁵ Synergy between local anesthetics and opioids has become an interesting field of research recently.¹⁶ Opioids are frequently added to local anesthetics in a variety of surgical procedures, eg, intrathecal application for minor surgery.¹⁷ Meperidine or its derivatives, eg, pethidine (meperidine chloride) or norpethidine (Pethidine Intermediate B) are agonists of μ-opioid receptors, which block the pathway of pain signals to the trigeminal nucleus. They also activate peripheral opioid receptors and block sodium channels.^17–22 Despite controversy regarding the use of meperidine as an anesthetic,²² recent studies have demonstrated its benefits over prilocaine in arthroscopy with local anesthesia,¹⁶ nasal packing removal,²³ etc.However, only a few studies have investigated the dental anesthetic efficacy of such combinations.^24,25 The effect of the addition of meperidine to lidocaine in IANB for pain management in normal teeth²⁴ and also in teeth with irreversible pulpitis²⁵ has been studied. The aim of our study was to compare the efficacy of local anesthetics with and without meperidine for intraligamentary supplemental injection for teeth with irreversible pulpitis. Our null hypothesis stated that the addition of meperidine to standard lidocaine with epinephrine does not improve the efficacy of supplemental intraligamentary anesthesia in teeth with symptomatic irreversible pulpitis. The specific objectives were to randomly allocate volunteers with complete soft tissue anesthesia following an IANB, yet having positive pulp response, into 2 groups, and then compare the efficacy of lidocaine with epinephrine plus meperidine with that of lidocaine with epinephrine plus an equal volume of sterile water for supplemental periodontal ligament anesthesia.     

Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration

Parkin and the glial cell line–derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson’s disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration. Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. Downregulation of either parkin or RET in neuronal cells impaired mitochondrial function and morphology. Parkin expression restored mitochondrial function in GDNF/RET-deficient cells, while GDNF stimulation rescued mitochondrial defects in parkin-deficient cells. In both cases, improved mitochondrial function was the result of activation of the prosurvival NF-κB pathway, which was mediated by RET through the phosphoinositide-3-kinase (PI3K) pathway. Taken together, these observations indicate that parkin and the RET signaling cascade converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons and their innervation in the striatum. The demonstration of crosstalk between parkin and RET highlights the interplay in the protein network that is altered in PD and suggests potential therapeutic targets and strategies to treat PD.