Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Imaging of follicular dendritic cell tumours of the liver

Follicular dendritic cell tumour of the liver is a recently recognized entity. To date, only two cases have been described, both in the pathology literature. Histologically, it resembles an inflammatory pseudotumour and immunohistochemical and ultrastructural studies are required for its diagnosis. The ultrasound, computed tomography and angiographic features of two cases of follicular dendritic cell tumour of the liver are described in detail. One of the patients had multiple recurrences of this tumour. The imaging features are very similar to those of hepatocellular carcinoma. As follicular dendritic cell tumour is considered to be of low-grade malignant potential, in contrast to the dismal prognosis for hepatocellular carcinoma, it is important to be able to accurately distinguish between the two types of tumour prior to initiating definitive therapy.     

Intraocular pressure fluctuations during scleral buckling surgery

PURPOSE: The purposes of this study are to measure real-time intraocular pressure (IOP) during scleral buckling and to determine the effects of elevated IOPs on ocular perfusion. PATIENTS AND METHODS: A standard 4-mm, 20-gauge infusion cannula was inserted through the pars plana, connected to a standard hemodynamic monitoring unit with an electronic pressure transducer, and calibrated. The authors measured real-time IOP in 20 eyes undergoing scleral buckling surgery for primary rhegmatogenous retinal detachments and determined the IOP required to close the central retinal artery. Pressure measurements were read from the monitor videoscreen intraoperatively and from a continuous paper tracing postoperatively. RESULTS: The patients ranged in age from 24 to 88 years (mean, 59.7 years). The highest IOP elevations occurred during scleral depression and cryopexy, ranging up to 210 mmHg (mean, 116 mmHg). Pressures at which the central retinal artery closed ranged from 48 to 110 mmHg (mean, 79.2 mmHg). Manipulations of the globes caused IOPs greater than the central retinal artery perfusion pressures in 13 of the 20 patients. The duration of pressures in excess of the central retinal artery perfusion pressure ranged from 6 to 402 seconds (mean, 118.8 seconds). There were no intraoperative or postoperative complications from the infusion cannula. CONCLUSIONS: Conventional scleral buckling surgery causes wide fluctuations in IOP and may impair ocular perfusion. Additional studies are needed to determine the long-term consequences of these pressure elevations.