Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants

The effects of mechanical injury on the metabolism of cartilage matrix are of interest for understanding the pathogenesis of osteoarthrosis and the development of strategies for cartilage repair. The purpose of the present study was to examine the effects of injury on matrix turnover in a calf articular cartilage explant system for which the effects of mechanical loading on cell activity and the cell-mediated pathways of matrix metabolism are already well characterized. New methods of quantitative autoradiography were used in combination with established biochemical and biomechanical techniques for the analysis of cell and matrix responses to acute mechanical injury, with particular attention to the processes of localized matrix turnover in the cell-associated matrices of individual chondrocytes. Matrix deposition and turnover around cells in control explants was spatially dependent, with the highest rates of proteoglycan deposition and turnover and the lowest rates of collagen deposition (as indicated by [3H]proline autoradiography) occurring in the pericellular matrix. Injurious compression was associated with (a) an abrupt decrease in the tensile load-carrying capacity of the collagen matrix, apparently associated with mechanical failure of the tissue, (b) a considerable but subtotal decrease in cell viability, marked by the emergence of an apparently inactive cell population interspersed within catabolically active but abnormally large cells, and (c) sustained, elevated rates of proteoglycan turnover, particularly in the cell-associated matrices of apparently viable cells, which involved the increased release of aggregating species in addition to a spectrum of degradation fragments that were also in controls. These results may represent an in vitro model for the responses of chondrocytes and the cartilage extracellular matrix to mechanical injury.     

Sulfation of endogenous compounds and xenobiotics--interactions and function in health and disease

Sulfation is a major detoxication mechanism for endogenous compounds and xenobiotics performed by a family of sulfotransferase isoenzymes. Understanding the normal cellular functions of these different sulfotransferases and the way in which endogenous and exogenous factors are able to influence their activity and expression will provide us with the information necessary to develop novel therapeutic strategies for conditions where sulfation may be implicated. This concept is discussed and is illustrated by examples including adverse drug reactions, fetal development and cancer.     

Association of risk factor variables and coronary artery disease documented with angiography

Stepwise linear discrimination was used to analyze risk factors in 431 consecutive patients who underwent coronary angiography to determine which variables were most closely associated with coronary artery disease. Twenty-one risk factors were considered: total plasma cholesterol and triglycerides; the cholesterol and triglyceride content of high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very low density lipoproteins (VLDL); and the percentage of total cholesterol and triglycerides in each fraction. Age, smoking history, family history, hypertension, diabetes mellitus and relative weight were also considered. Coronary artery disease was assessed using three standard grading scores. There were significant differences in risk factors between males and females. In males, LDL cholesterol and age were selected by multivariate analysis. In females, the ratio of HDL cholesterol to total cholesterol, as well as relative weight, family history, age and smoking were selected. The discriminating value of HDL cholesterol as the percentage of total cholesterol was significantly greater than that of HDL cholesterol itself. Despite highly significant associations between risk factors and the presence of coronary artery disease, the discrimination did not provide sufficient separation of the groups to give results that are useful diagnostically in individual patients.     

Adjuvants--a balance between toxicity and adjuvanticity

Adjuvants have been used to augment the immune response in experimental immunology as well as in practical vaccination for more than 60 years. The chemical nature of adjuvants, their mode of action and the profile of their side effects are highly variable. Some of the side effects can be ascribed to an unintentional stimulation of different mechanisms of the immune system whereas others may reflect general adverse pharmacological reactions. The most common adjuvants for human use today are still aluminium hydroxide, aluminium phosphate and calcium phosphate although oil emulsions, products from bacteria and their synthetic derivatives as well as liposomes have also been tested or used in humans. In recent years monophosphoryl lipid A, ISCOMs with Quil-A and Syntex adjuvant formulation (SAF) containing the threonyl derivative of muramyl dipeptide have been under consideration for use as adjuvants in humans. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side effects.     

Pressor response to isometric exercise in patients with multiple sclerosis

The purpose of this study was to determine whether patients with multiple sclerosis (MS) would show attenuated heart rate and/or pressor responses to isometric handgrip exercise. Patients with MS (30 males, 74 females, aged 23-61 yr) and control subjects (9 males, 16 females, aged 25-47 yr) performed isometric handgrip exercise at 30% of maximal voluntary contraction (MVC) to fatigue. Systolic, diastolic, and mean arterial pressure (MAP) increased linearly in both groups, but were significantly lower (P < 0.05) in patients with MS at 20%, 40%, 60%, 80%, and 100% of exercise duration. Mean change in MAP at fatigue was +47.9 mm Hg for controls and +28.2 mm Hg for patients with MS, with 18 patients with MS between -6 mm Hg and +15 mm Hg. Heart rate increased normally in patients with MS. To predict change in MAP at fatigue in patients with MS, stepwise regression analysis using six variables yielded an R2 of 0.26. These data suggest that in some patients MS lesions exist in areas of autonomic cardiovascular control that result in attenuated pressor responses to exercise. In 17% of patients tested, attenuation was profound. Data also suggest an abnormal dissociation between the heart rate and pressor response to static work in patients with MS.     

Trends in silicon-on-silicon multichip modules

Three example applications of silicon-on-silicon multichip modules are discussed: a module used in a parallel processor, a low-cost silicon module for a high-volume consumer product application, and a high-performance digital telecommunications module. These applications illustrate the changes occurring in this technology and the forces that are driving these changes