c-myc is required for osteoclast differentiation.

The role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-a tumor necrosis factor (TNF)-related cytokine-in osteoclast formation has been established clearly. However, the downstream signaling pathways activated by this cytokine remain largely unknown. To identify genes that play a role in osteoclastogenesis, we used RAW 264.7 mouse monocytes as a model system for the differentiation of multinucleated osteoclasts from mononucleated precursors. RAW 264.7 cells were induced with RANKL to form multinucleated giant osteoclast-like cells (OCLs) that expressed a number of osteoclast-specific markers and were able to form resorption pits on both calcium phosphate films and bone slices. This system was used to identify genes that are regulated by RANKL and may play a role in osteoclast differentiation. The proto-oncogene c-myc was strongly up-regulated in RANKL-induced OCLs but was absent in undifferentiated cells. Expression of Myc partners Max and Mad, on the other hand, was constant during OCL differentiation. We expressed a dominant negative Myc in RAW 264.7 cells and were able to block RANKL-induced OCL formation. Northern Blot analysis revealed a delay and a significant reduction in the level of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K. We conclude that c-myc is a downstream target of RANKL and its expression is required for RANKL-induced osteoclastogenesis.     

Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.     

Diagnostik des Synovialsarkoms Simultane t(X;18) FISH- und SYT/SSX-RT-PCR-Analyse

Synovialsarkome sind mitunter schwierig von anderen Spindelzellsarkomen zu unterscheiden. In diesen Fällen kann der Nachweis einer t(X;18) Translokation unter Verwendung der FISH und RT-PCR helfen. Die vorliegende Arbeit wurde unter der Fragestellung durchgeführt, ob bei Synovialsarkom-verdächtigen Tumoren der simultane Einsatz beider Methoden zum Translokationsnachweis erforderlich ist oder ob eine der Methoden ausreicht.In die Studie wurde Paraffin-eingebettetes Tumorgewebe von 53 Patienten einbezogen, bei denen nach Lichtmikroskopie und Immunhistochemie der Verdacht auf das Vorliegen eines Synovialsarkoms bestand. Es erfolgte der Nachweis von t(X;18) mittels FISH und RT-PCR.     

Finite element analysis of a bone-implant system with the proximal femur nail.

Static analysis with finite element of a realistic femur nail bone-implant system in a typical proximal femoral fracture under physiological load bearing situations provides results for stress, displacement and strain. The question to be answered is, if simulation with the finite element analysis is able to explain biomechanically clinical observed patterns of failure. Surface-Reconstruction with CT database of a proximal femur and reconstruction with CT based density data was done. Next steps were to unite the bone structure with the Proximal Femoral Nail and to model two relevant fractures (31-A2.2 and A2.3 according AO). After modelling of geometry, isotropic material behaviour and load application numeric calculation of the femur-nail system with FE-software was performed. FE simulation mainly shows an axial dislocation of the femoral head screw with nearly no dislocation of the antirotation screw. This so-called z-effect therefore means: (1) Tilting of the proximal main fragment around the sagittal axis between the screws and (2) relative movement of both screws in the frontal plane. Relative movement of the two screws against each other could be the reason for implant failure, the so called cut out. Furthermore simulation shows different gliding of the screws explaining the so called z-telescoping. The analyzed stress patterns have to be relativized, because isotropic material behaviour of cancellous bone was assumed. Further examinations for this issue are necessary.     

Long-term Results of Primary Stent Placement to Treat Infrarenal Aortic Stenosis

OBJECTIVE: To determine the safety and the long-term results of primary stent placement for localized distal aortic occlusive disease. DESIGN: Retrospective observational study. PATIENTS AND METHODS: From July 1998 to July 2005 17 patients (14 female and 3 men, mean age 57 years (39-80)) were treated for intermittent claudication. Five of these patients underwent additional endovascular treatment of focal iliac lesions. RESULTS: Technical success defined as residual stenosis of less than 50% or a trans-stenotic systolic pressure gradient <10% was achieved in 14 of 17 (82%) patients. Major complications included dissection at the puncture site in one patient and thrombosis of additional iliac stents in another patient. Both of these complications were successfully treated. During a mean follow-up of 27 months (range 1-86), four patients had recurrence of symptoms due to in-stent restenoses (n=2), femoral (n=1) or iliac occlusion (n=1), respectively. By Kaplan-Meier analysis, primary aortic hemodynamic patency was 83% at 3 years. Secondary aortic hemodynamic patency was 100%. The primary clinical patency was 68% at 3 years. CONCLUSION: Primary stent placement for distal aortic stenoses is an alternative to surgical treatment because of its high patency and relatively low complication rates.