The axonal guidance proteins semaphorin (Sema)4D and Sema3A play important roles in communication between osteoclasts and osteoblasts. As stimulation of adenosine A receptors (A2AR) regulates both osteoclast and osteoblast function, we asked whether A2AR regulates both osteoclast and osteoblast expression of Semas. In vivo bone formation and Sema3A/PlexinA1/Neuropilin-1, Sema4D/PlexinB1 protein expression were studied in a murine model of wear particle-induced osteolysis. Osteoclast/osteoblast differentiation were studied in vitro as the number of tartrate-resistant acid phosphatase/Alizarin Red cells after challenge with CGS21680 (A2AR agonist, 1 µM) or ZM241385 (A2AR antagonist, 1 µM), with or without Sema4D or Sema3A (10 ng/ml). Sema3A/PlexinA1/Neuropilin-1, Sema4D/PlexinB1, and receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) expression was studied by RT-PCR and Western blot. β-Catenin activation and cytoskeleton changes were studied by fluorescence microscopy and Western blot. In mice with wear particles implanted over the calvaria, CGS21680 treatment increased bone formation in vivo, reduced Sema4D, and increased Sema3A expression compared with mice with wear particle-induced osteolysis treated with vehicle alone. During osteoclast differentiation, CGS21680 abrogated RANKL-induced Sema4D mRNA expression (1.3 ± 0.3- vs. 2.5 ± 0.1-fold change, P < 0.001, n = 4). PlexinA1, but not Neuropilin-1, mRNA was enhanced by CGS21680 treatment. CGS21680 enhanced Sema3A mRNA expression during osteoblast differentiation (8.7 ± 0.2-fold increase, P < 0.001, n = 4); PlexinB1 mRNA was increased 2-fold during osteoblast differentiation and was not altered by CGS21680. Similar changes were observed at the protein level. CGS21680 decreased RANKL, increased OPG, and increased total/nuclear β-catenin expression in osteoblasts. Sema4D increased Ras homolog gene family, member A phosphorylation and focal adhesion kinase activation in osteoclast precursors, and CGS21680 abrogated these effects. In summary, A2AR activation diminishes secretion of Sema4D by osteoclasts, inhibits Sema4D-mediated osteoclast activation, and enhances secretion of Sema3A by osteoblasts, increasing osteoblast differentiation and diminishing inflammatory osteolysis.-Mediero, A., Wilder, T., Shah, L., Cronstein, B. N. Adenosine A receptor (A2AR) stimulation modulates expression of semaphorins 4D and 3A, regulators of bone homeostasis.

Urinary tract infection (UTI) in children is a common diagnosis in general pediatric practice. Because of the potential severity and proven morbidity of such infections, the American Academy of Pediatrics (AAP) developed guidelines to better direct clinicians in the workup. This retrospective study sought to evaluate the uniformity of adherence to these guidelines at our teaching institution. A total of 104 charts were reviewed, and data were collected based on the parameters outlined by the AAP. It is found that at the authors' teaching institution, there is at least 70% adherence to the recommendations for method of urine collection and 97% adherence to performance of urinalysis. However, imaging workup, which may be the most important follow-up of a first-time UTI, has only a 61% adherence rate.

Two resin injection studies of the lumbar extradural space were performed to elucidate its size and shape. To counteract the lack of cerebrospinal fluid pressure in the cadaver, the subarachnoid space was filled with water. In group 1, the extradural injection of resin caused an immediate increase in subarachnoid pressure. The casts produced varied in thickness, but were situated predominantly in the dorsomedial and dorsolateral regions of the spinal canal. Thin anterior spread occurred in 40% of cases. In group 2, resin was injected to the subarachnoid space before the extradural injection of dyed resin. The resulting extradural casts were thinner than in group 1, but the distribution of resin was similar. The problems of interpreting resin casts are discussed in relation to the results obtained, with reasons for suggesting that the extradural space is only potential.

No abstract

Metastatic cancer to the pancreas accounts for less than 2% of all pancreatic malignancies. In contrast to other metastatic tumors, renal cell carcinoma (RCC) has a propensity to metastasize as a solitary pancreatic lesion. While symptomatic patients may present with obstructive jaundice, abdominal pain, or gastrointestinal bleeding, the diagnosis of metastatic pancreatic involvement is often made in asymptomatic patients, during follow-up evaluation in the aftermath of an initial diagnosis of renal cell carcinoma. Microcystic serous cystadenoma of the pancreas is an uncommon pancreatic exocrine neoplasm that morphologically resembles conventional (clear cell) RCC, in so far as both tumors are characterized by neoplastic cells with clear cytoplasm, relatively uniform nuclei and scant associated tumor stroma. Herein, we report 2 immunohistochemically confirmed cases of unsuspected metastatic RCC to the pancreas, with the metastatic tumor in each case confined to a preexisting microcystic serous cystadenoma of the pancreas.