Sphingosine Induces Apoptosis and Down-regulation of MYCN in PAX3-FOXO1-positive Alveolar Rhabdomyosarcoma Cells Irrespective of TP53 Mutation.

BACKGROUND/AIM: Rhabdomyosarcoma is the most common type of pediatric soft-tissue sarcoma. Among the subsets of this disease, alveolar rhabdomyosarcoma (ARMS) expressing paired box 3 (PAX3) and forkhead box O1 (PAX3-FOXO1) fusion oncoprotein has the worst prognosis. The goal of this study was to investigate the chemotherapeutic effects of sphingosine on PAX3-FOXO1-positive ARMS cells [tumor protein p53 (TP53)-mutated RH30 and TP53 wild-type RH18 cells]. MATERIALS AND METHODS: The proliferation, cell death, apoptosis, cell cycle, and MYCN proto-oncogene (MYCN) expression of RH30 and RH18 cells were determined. RESULTS: Sphingosine inhibited the growth and caused cell death in a dose-dependent manner in both cell lines. Sphingosine triggered cell death by inducing apoptosis without affecting the cell cycle. MYCN expression was down-regulated within 2 and 4 h of sphingosine treatment in both RH30 and RH18 cells. CONCLUSION: Sphingosine exerts antiproliferative and pro-apoptotic effects via MYCN down-regulation independently of TP53 mutation status in PAX3-FOXO1-positive ARMS cells.

Subpontic osseous hyperplasia: a case series and literature review.

A subpontic osseous hyperplasia (SOH) is a slow-growing, non-neoplastic bone growth that uniquely affects mandibular posterior edentulous ridges underneath pontics of fixed partial dentures. An SOH can result in significant periodontal and restorative complications, however, it is usually corrected by surgical excision. This report presents a series of SOH cases, illustrates SOH management approaches, and reviews the literature on SOH clinical presentations.

Infectious pin complication rates in halo vest fixators using ceramic versus metallic pins.

STUDY DESIGN: Retrospective review of database patients. OBJECTIVE: To compare infectious pin complication rates utilizing ceramic pins, an emerging technology, with a large database of complications in halo's using metallic pins. SUMMARY OF BACKGROUND DATA: The halo/vest fixator remains a useful modality of treatment for cervical spine trauma but has been described as having a high incidence of complications, foremost pin-related complications. Ceramic pins and vest modifications have been introduced under the premise of (1) decreasing pin-tract infections compared with metallic pins manufactured from stainless steel or titanium and with the advent of 3T MRI, (2) decreasing brain MRI artifact, and (3) lowering MRI intolerance owing to material overheating. MATERIAL AND METHODS: We retrospectively reviewed a prospectively collected patient data set of the Harborview Medical Center spine trauma registry. A historic control group exclusively utilizing metallic halo pins over a 10-year period was compared with patients who were treated with halo's exclusively utilizing ceramic pins over a recent 14-month period. Complications investigated included aseptic, loosening, and infections graded on a novel 3-tier system adapted from external fixation in long bone and periarticular trauma. Inclusion criteria were the patients with traumatic cervical spine injuries treated with a halo for a period of at least 14 days. RESULTS: Forty-four patients were available for analysis in the ceramic pin group versus 263 in the metallic pin group. Overall pin complications amounted to 40.9% ceramic (C) versus 21.7% metal (M) pins (P<0.05), aseptic loosening rates 13.7% (C) compared with 8.3% (M), and pin site infections 27.3% (C) compared with 13.3% (M) (P<0.05). A grading system for halo pin tract infections was developed. In assessing overall complications and infections specifically, ceramic pins seemed to be associated with a higher incidence of adverse events or complications compared with titanium pins. CONCLUSION: Despite the imbalance of size of our cohort groups, there seems to be a strong trend toward the newer ceramic pin technology not meeting expected minimum performance standards set by the earlier metallic material. Causes for the higher failure rate likely lay in the necessary changes made to the halo vest and specifically the pin design owing to the inherent mechanical property limitations of MRI compatible materials.

Adenylate cyclase-mediated forms of neuronal plasticity in hippocampal area CA1 are reduced with aging.

Beta-adrenergic receptors and the cyclic AMP signaling pathway play an important role in neuronal plasticity and in learning and memory and are known to change with aging. We examined the effects of beta-adrenergic stimulation paired with 5-Hz low frequency stimulation (LFS) of Schaffer collateral-commissural afferents on population spike amplitude in area CA1 of hippocampal slices from young (3 mo) and aged (22 mo) Fischer 344 rats. Application of the beta-adrenergic agonist isoproterenol (1 microM) for 10 min followed immediately by 3 min LFS produced long-lasting potentiation in young hippocampi, but the magnitude of potentiation in aged rats was significantly attenuated and was not long-lasting. In slices prepared from young rats, long-term potentiation (LTP) induced by this protocol occludes subsequent attempts to produce conventional high frequency stimulation-induced LTP, and vice versa, suggesting that these two forms of potentiation share one or more molecular mechanisms. Age-related differences in response to LFS alone were not observed, but significant differences in response to beta-adrenergic stimulation were apparent. Similarly, significant age-related differences in response to direct activation of adenylate cyclase with forskolin (10 microM) were observed. In both age groups, this enhancement produced by isoproterenol or forskolin is only transient, returning to baseline within 60 or 90 min, respectively. Taken together, these studies of adenylate cyclase-mediated forms of potentiation in area CA1 suggest that there is an age-related defect, either upstream or downstream of adenylate cyclase activation, in this important signaling system. Such changes may contribute to the compromised performance on memory tasks that is often observed with normal aging.

Periodontal repair in dogs: a bioabsorbable calcium carbonate coral implant enhances space provision for alveolar bone regeneration in conjunction with guided tissue regeneration.

BACKGROUND: Collapse or compression of a barrier device into a periodontal defect or onto the root surface compromises outcomes following guided tissue regeneration (GTR). Bone biomaterials have been suggested to support regeneration of alveolar bone and to improve space provision with GTR devices. The objective of this study was to evaluate space provision, alveolar bone, and cementum regeneration following use of a bioabsorbable, calcium carbonate biomaterial in conjunction with GTR. METHODS: Routine, critical size, 5 to 6 mm, supraalveolar, periodontal defects were created in 5 young adult beagle dogs. Alternate jaw quadrants in consecutive animals received GTR and the coral biomaterial (cGTR) or GTR alone. The animals were euthanized 4 weeks postsurgery and tissue blocks processed for histometric analysis. RESULTS: The coral implant particles were surrounded by newly-formed bone or immersed in connective tissue and appeared to resorb and be replaced by bone. There was limited, if any, appreciable cementum regeneration. Space provision was enhanced in cGTR compared to GTR sites (6.1 +/- 1.6 versus 2.4 +/- 0.8 mm2; P<0.05). Bone regeneration (height) was significantly increased in cGTR compared to GTR sites averaging 1.9 +/- 0.6 and 1.2 +/- 0.6 mm, respectively (P<0.05). Bone regeneration (area) was 2-fold greater in cGTR sites compared to the GTR control (3.3 +/- 1.8 versus 1.4 +/- 0.5 mm2), however the difference was not statistically significant (P>0.05). CONCLUSIONS: The coral implant significantly enhanced space provision for GTR while alveolar bone formation appeared to be enhanced by its use. Increased healing intervals are needed to fully understand the biologic value of the coral implant as an adjunct to GTR.

Head position modulates activity in the human parietal eye fields.

For us to interact with our environment we need to know where objects are around us, relative to our body. In monkeys, a body-centered map of visual space is known to exist within the parietal eye fields. This map is formed by the modulation of retinal responses by gain fields to gaze position. In humans, no map of body-centered space has yet been discovered but clinical data suggest that the right parietal lobe is predominantly responsible for visuospatial function. Using functional MRI, we have been able to demonstrate that an area in the intraparietal sulcus of humans has properties very similar to the parietal eye fields of monkeys. This area demonstrates BOLD signal changes related to the visual, saccadic, and memory components of saccade tasks that are analogous to the visual, saccadic, and memory responses of neurons within the parietal eye fields of monkeys. More importantly, the amount of signal change seen in this region is modulated by head position relative to the body, suggesting that a gain field dependent body-centered representation of space exists bilaterally within the parietal lobes in humans.

Genes expressed during the IFN gamma-induced maturation of pre-B cells.

Interferon-gamma (IFN gamma) exerts diverse responses in B cell development ranging from growth arrest and apoptosis to proliferation and differentiation. IFN gamma stimulates murine 70Z/3 pre-B cells to express surface immunoglobulin (Ig) and this system serves as a useful model for the pre-B to immature B cell transition in B cell development. To analyze this developmental transition, we used a PCR-based subtractive hybridization in combination with miniarray screening to identify differentially-expressed genes in IFN gamma-stimulated compared with unstimulated 70Z/3 pre-B cells. The majority (44%) of the differentially-expressed genes obtained were known IFN gamma-inducible. These included multiple isolates from each of three multi-gene families, including two guanylate-binding protein (47 and 67kDa GBP) families of GTPases and the hematopoietic IFN gamma-inducible nuclear protein family (HIN-200). These multiple isolates of genes comprised the majority of the total isolated and sequenced clones. Other known IFN gamma-induced genes in this group included Ig kappa light chain and Ly-6, as well as genes with functions in antigen processing, cellular regulation, and cytoskeletal organization. Another 36% of the genes identified were previously known, but not known to be IFN gamma-inducible (e.g. pre-B cell enhancing factor, PBEF). The remaining 20% of the IFN gamma-induced isolates did not match entries in Genbank, and thus, may represent novel genes involved in IFN gamma responses and/or in the pre-B to immature B cell transition. Overall, the majority of the individual genes isolated were either not known to be IFN gamma responsive or were not previously known.