Phospholipase A2 and arthritis

Over the last 30 years, interest in PLA2 has grown beyond its enzymatic capacity to cleave phospholipids. It has been recognized as the rate-limiting step in the release of arachidonic acid and subsequent formation of prostaglandins, leukotrienes, and other bioactive lipids. Subsequently, PLA2 has not only been found to be present in high concentrations in inflammatory arthritis, but also to induce inflammation when injected into animals. At the same time, investigators into mechanisms of signal transduction demonstrated that a variety of cytokines including IL-1 and TNF, which are found in high concentrations in synovial fluid from patients with RA, stimulate PLA2 activity. These investigations demonstrated further the central role for PLA2 in inflammatory events, especially inflammatory arthritis. Numerous other PLA2 proteins, in addition to the low molecular weight synovial fluid/platelet enzyme, also have been characterized. Their clinical role in arthritis is yet to be elucidated. Human proteins which either inhibit or stimulate PLA2 have also been identified, characterized, and cloned. More recently, exciting investigations, primarily from biotechnology and pharmaceutical companies, into inhibitors of PLA2 have been reported. New PLA2-regulating compounds, which will hopefully move from the laboratory and through clinical trials and then be used to treat patients with arthritis, are on the horizon.     

Implementing clinical paths in a managed care environment

The survival of health care institutions depends upon a delivery system focusing on appropriate use of resources and controlling length of stay while monitoring clinical progress toward identified outcomes. Using a clinical path as a tool for managing resources, research activities, continuous quality improvement, and increased collaborative practice can enhance the professional practice environment and benefit patient care.     

Magnetomechanical damping in giant magnetostriction alloys

Magnetomechanical damping in the giant magnetostriction material Terfenol-D has been investigated by quasi-static stress-strain measurements and modeled theoretically. The damping capacity is a strong function of applied stress amplitude, increasing to a maximum at some finite stress and then decreasing slowly at still larger applied stresses. Maximum damping capacities greater than 1.0 were observed for the lowest magnetic bias fields and prestresses at applied stress amplitudes of 4 MPa. Both the qualitative behavior of the damping and its magnitude are successfully described by a model of abrupt magnetization jumps within individual domains driven by the applied stress. This article is based on a presentation given in the Mechanics and Mechanisms of Material Damping Symposium, October 1993, in Pittsburgh, Pennsylvania, under the auspices of the SMD Physical Metallurgy Committee.     

Quantum catalysis in enzymes: beyond the transition state theory paradigm. A Discussion Meeting held at the Royal Society on 14 and 15 November 2005.

How do enzymes work? What is the physical basis of the phenomenal rate enhancements achieved by enzymes? Do we have a theoretical framework that accounts for observed catalytic rates? These are the foremost questions-with particular emphasis on tunnelling phenomena-debated at this Discussion Meeting by the leading practitioners in the field.     

An experimental study into the acousto-mechanical effects of invading the cochlea.

The active and nonlinear mechanical processing of sound that takes place in the mammalian cochlea is fundamental to our sense of hearing. We have investigated the effects of opening the cochlea in order to make experimental observations of this processing. Using an optically transparent window that permits laser interferometric access to the apical turn of the guinea-pig cochlea, we show that the acousto-mechanical transfer functions of the sealed (i.e. near intact) cochlea are considerably simpler than those of the unsealed cochlea. Comparison of our results with those of others suggests that most previous investigations of apical cochlear mechanics have been made under unsealed conditions, and are therefore likely to have misrepresented the filtering of low-frequency sounds in the cochlea. The mechanical filtering that is apparent in the apical turns of sealed cochleae also differs from the filtering seen in individual auditory nerve fibres with similar characteristic frequencies. As previous studies have shown the neural and mechanical tuning of the basal cochlea to be almost identical, we conclude that the strategies used to process low frequency sounds in the apical turns of the cochlea might differ fundamentally from those used to process high frequency sounds in the basal turns.     

Neural unit activity in the trigeminal complex with interpositus or red nucleus inactivation during classical eyeblink conditioning.

During classical conditioning, many neurons in the trigeminal complex of rabbits exhibit activity that is related to the conditioned stimulus (tone), the unconditioned stimulus (airpuff), or to the conditioned response (eyeblink). For these reasons the trigeminal complex has been hypothesized to be a brainstem locus for the neuronal plasticity associated with conditioning. In this experiment, the learning-related activity (unit activity associated with the conditioned response) in the trigeminal is abolished when either the red nucleus or interpositus nucleus of the cerebellum is temporarily inactivated by cooling, but the stimulus-evoked activity is unaffected by cooling. This study and previous results support the suggestion that the learning-related activity seen in the trigeminal is driven by the interpositus by way of the red nucleus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Persistent papillomavirus infection in a cat

The purpose of this study was to further define the cellular response to titanium and polymethylmethacrylate (PMMA) particles in aseptic loosening, and to determine if the use of pamidronate may be effective in inhibiting bone resorption associated with this response. Macrophages and osteoblasts were cocultured to simulate the environment around an aseptically loose prosthesis. Macrophages were plated on the bottom of six well plates and osteoblasts were plated on culture dish inserts, and placed into the wells with the macrophages. Incubation of macrophages with PMMA in this system led to release of prostaglandin E (PGE2), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-6 (IL-6). Incubation with titanium led to release of tumor necrosis factor (TNF) and IL-6. Exposure of calvaria to media from cells exposed to either PMMA or titanium led to release of calcium 45. Incubation of calvaria with pamidronate was able to inhibit release of calcium 45 associated with exposure to the macrophage/osteoblast/particle conditioned medium. Bone resorption at the interface between implant and bone is a consistent feature leading to loosening of orthopedic implants. By inhibiting bone resorption associated with the inflammatory response to implant particulates, pamidronate or other bisphosphonates may have clinical utility in the treatment or prevention or aseptic loosening.