Extrahepatic metabolism of 4-methylumbelliferone and lidocaine in the anhepatic rabbit

OBJECTIVE: The initially well-fixed implants of total hip replacement (THR) are in the long-term subject to aseptic loosening. Many cytokines can contribute to osteolysis due to osteoclast recruitment and/or activation. However, in this respect tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role, because it upregulates interleukin-1 and 6 and granulocyte-macrophage colony stimulating factor. The aim of this study was to assess the eventual presence, cellular localization and extent of expression of TNF-alpha in the synovial-like membrane at the implant or at the cement to bone interface compared to control synovial membrane. METHODS: Twenty samples from the synovial-like membrane of the periprosthetic tissues were compared to control samples. TNF-alpha containing cells were visualized using an avidin-biotin-peroxidase complex (ABC) method and analyzed by light microscopy, double labelling and image analysis. RESULTS: TNF-alpha was found in the periprosthetic tissues in fibroblasts and vascular endothelial cells, but mainly in the macrophages was it found to coincide with areas containing implant-derived debris. TNF-alpha containing cells were more numerous in the synovial-like membrane in the interface tissue from the proximal stem area (2816 +/- 318 cells) than in the control synovial membrane (565 +/- 93 cells, p < 0.01). Interestingly, similarly high TNF-alpha expression (3452 +/- 582 cells) was also seen in the synovial-like membrane of the pseudocapsule. CONCLUSION: These findings suggest that the foreign body-type host reaction caused by THR is characterized by the high expression of TNF-alpha. Because such expression occurred in the interface tissue between the implant and surrounding bone, TNF-alpha, due to its pivotal direct and indirect role in the activation and recruitment of osteoclasts, may contribute to periprosthetic osteolysis and to the loosening of THR.     

External surface and lamellarity of lipid vesicles: a practice-oriented set of assay methods

Three methods are presented for the determination of external surface of large lipid vesicles of different lamellarity with 2% absolute accuracy. These methods (referred to as EPR, NBD and TNBS assays) use different marker lipids which provide signals (electron paramagnetic resonance, fluorescence of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) residues, and UV absorption increase of 2,4,6-trinitrobenzenesulfonic acid after reaction with aminolipids, respectively). The signals change upon addition of different membrane-impermeant reagents due to reaction with marker lipids at the external vesicle surface. They were applied to the same vesicle samples, including unilamellar and multilamellar vesicles, both at two different lipid compositions. External surface data matched for the three assays within 2%, but only after appropriate redesign or adaptation of so far published procedures. Main improvements related to slow influx of reagents (TNBS and NBD assays) or to redistribution of marker lipids (EPR assay), obscuring determination of outer vesicle surface from fast reaction between reagent and readily accessible marker lipids. Furthermore, suitable strategies were found to obtain accurate 100% values (reaction of all marker lipids present), required to relate external vesicle surface to total surface. This included corrections for light scattering (NBD assay) and for turbidity (TNBS assay). These three methods appear to close a gap in the methodology to determine external surface of vesicles for typical practical needs. In particular, the reliability range of the NBD assay could be extended to marker lipid densities as low as 1 marker lipid per 3000 lipids.     

Idiopathic hypoparathyroidism--a rare disease?

Five patients with nonfamilial idiopathic hypoparathyroidism were observed in a peripheral hospital. There was no association with other autoimmune disorders such as hypothyroidism, adrenal insufficiency or pernicious anemia. Only in one patient with tetany was the diagnosis clinically obvious; all the others presented with unusual clinical symptoms. These manifestations of chronic hypocalcemia are presented, as well as the diagnostic workup and therapeutic management. We suggest that idiopathic hypoparathyroidism is not a very rare disease, but one which is often missed because of the unusual clinical picture.     

Evidence for McKusick''s hypothesis of deficient collagen cross-linking in patients with homocystinuria

Fractionation of the venom of the spider Phoneutria nigriventer revealed that it was a mixture of several neurotoxic peptides. The peptides so far characterized either inhibited or induced neurotransmitter release. These effects were mediated by Ca2+ channels or increasing Na+ permeability through voltage sensitive Na(+)-channels, respectively. The pooled toxic components (fraction P4) showed stimulatory effects on acetylcholine release from brain cortical slices. In addition, a component of the observed effects resembling that of alpha-latrotoxin was identified, which was characterized by the ability to provoke release of acetylcholine (ACh) at low temperature and in a manner independent of extracellular Ca2+ and of voltage sensitive Na(+)-channels.     

The reliability of a new 12-channel ECG with telephone transmission

BACKGROUND AND OBJECTIVE: Different from the situation in the USA, Canada, Israel, Italy and Great Britain transmission of electrocardiograms (ECG) by telephone plays an unimportant part in Germany because existing technology is at best adequate for the diagnosis of arrhythmias. A new simple system, the size of a mobile phone (P12, Aerotel, Israel), was tested: for the first time in Europe it allows patients themselves to obtain a 12-lead ECG and transmit it via any telephone to a centre for analysis. This system was evaluated for its reliability when used by lay persons. PATIENTS AND METHODS: Qualitative and quantitative parameters of a conventional 12-lead ECG obtained in 217 patients (86 women, 131 men) were compared with those of 12-lead ECGs recorded and stored by lay persons, transmitted via telephone to a computer and then printed out. RESULTS: All ECGs transmitted with the P12 were analysable: quality was good or very good in 86%. Heart rate, transmission time and the various durations agreed with the conventional leads, while P12 underregistered amplitudes by about 15%. This difference was correctable by a constant or by adjusting the ECG machine. Atrial fibrillation (in eight of eight cases), infarct changes (40 of 40), ST elevations or depressions (15 of 15) and T negativities (80 of 82) were also reliably recognized. CONCLUSIONS: The described method proved simple and reliable. Clinically significant information in the ECG can be transmitted within minutes and with high diagnostic reliability to a central station via any telephone. P12 is thus suitable for self-recording of ECGs by patients with potentially dangerous cardiac conditions. However a centre with cardiologically trained personnel should be available where telephone transmission of the ECGs and dialogue with the patients is possible around the clock.     

AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins

Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx within the homeodomain and was identified as a common site of viral integration in myeloid leukemias arising in BXH-2 mice. These integrations result in constitutive activation of Meis1. Furthermore, the Hoxa-9 gene is frequently activated by viral integration in the same BXH-2 leukemias, suggesting a biological synergy between these two distinct classes of homeodomain proteins in causing malignant transformation. We now show that the Hoxa-9 protein physically interacts with Meis1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis1 site (TGACAG) and an AbdB-like Hox site (TTTTACGAC). Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b, while Hox proteins from other paralogs do not appear to interact with Meis1 proteins. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.