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"Sobel, D A"
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The Influence of the Proinflammatory Cytokine, Osteopontin, on Autoimmune Demyelinating Disease
Multiple sclerosis is a demyelinating disease, characterized by inflammation in the brain and spinal cord, possibly due to autoimmunity. Large-scale sequencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcripts for osteopontin (OPN). Microarray analysis of spinal cords from rats paralyzed by experimental autoimmune encephalomyelitis (EAE), a model of MS, also revealed increased OPN transcripts. Osteopontin-deficient mice were resistant to progressive EAE and had frequent remissions, and myelin-reactive T cells in OPN-/-mice produced more interleukin 10 and less interferon-γ than in OPN+/+mice. Osteopontin thus appears to regulate T helper cell-1 (TH1)-mediated demyelinating disease, and it may offer a potential target in blocking development of progressive MS.
Journal Article
Chronic Disease Self-Management Program: 2-Year Health Status and Health Care Utilization Outcomes
Objectives. To assess the 1- and 2-year health status, health care utilization and self-efficacy outcomes for the Chronic Disease Self-Management Program (CDSMP). The major hypothesis is that during the 2-year period CDSMP participants will experience improvements or less deterioration than expected in health status and reductions in health care utilization. Design. Longitudinal design as follow-up to a randomized trial. Setting. Community. Participants. Eight hundred thirty-one participants 40 years and older with heart disease, lung disease, stroke, or arthritis participated in the CDSMP. At 1- and 2-year intervals respectively 82% and 76% of eligible participants completed data. Main Outcome Measures. Health status (self-rated health, disability, social/role activities limitations, energy/fatigue, and health distress), health care utilization (ER/outpatient visits, times hospitalized, and days in hospital), and perceived self-efficacy were measured. Main Results. Compared with baseline for each of the 2 years, ER/outpatient visits and health distress were reduced (P <0.05). Self-efficacy improved (P <0.05). The rate of increase is that which is expected in 1 year. There were no other significant changes. Conclusions. A low-cost program for promoting health self-management can improve elements of health status while reducing health care costs in populations with diverse chronic diseases.
Journal Article
Detecting Blickets: How Young Children Use Information about Novel Causal Powers in Categorization and Induction
Three studies explored whether and when children could categorize objects on the basis of a novel underlying causal power. To test this we constructed a \"blicket detector,\" a machine that lit up and played music when certain objects were placed on it. First, 2-, 3- and 4-year-old children saw that an object labeled as a \"blicket\" would set off the machine. In a categorization task, other objects were demonstrated on the machine. Some set it off and some did not. Children were asked to say which objects were \"blickets.\" In an induction task, other objects were or were not labeled as \"blickets.\" Children had to predict which objects would have the causal power to set off the machine. The causal power could conflict with perceptual properties of the object, such as color and shape. In an association task the object was associated with the machine's lighting up but did not cause it to light up. Even the youngest children sometimes used the causal power to determine the object's name rather than using its perceptual properties and sometimes used the object's name rather than its perceptual properties to predict the object's causal powers. Children rarely categorized the object on the basis of the associated event. Young children also sometimes made interesting memory errors-they incorrectly reported that objects with the same perceptual features had had the same causal power. These studies demonstrate that even very young children will easily and swiftly learn about a new causal power of an object and spontaneously use that information in classifying and naming the object.
Journal Article
Effects of using a surgical clamp to hold tension while tying knots with commonly used orthopedic sutures
Purpose
Tendon repairs are often performed under some degree of tension, and in these instances the use of a clamp to temporarily secure a knot following the first throw can lessen gap formation while subsequent suture throws are made. The effect of clamping on the ultimate tensile load, stiffness, elongation, and mechanism of failure of suture loops has not been investigated for several commonly used orthopedic sutures, and it was the purpose of this study to investigate this issue.
Methods
Seven different types/sizes of braided nylon or polyblend (PB) suture were uniformly tied around an isolated 35-mm glass cylinder in a laboratory setting using no clamp, a smooth needle holder, or a serrated clamp to hold a surgeon’s knot following the first throw. Knots were secured with four alternating half-hitches with reversed posts, and the suture loops were then loaded on custom hooks in an MTS axial loading frame, preloaded, cycled, and loaded to failure. Elongation, ultimate tensile load (UTL), stiffness, and mechanism of failure were recorded.
Results
Six of seven suture loops tied with either clamp showed statistically significant but clinically minimal (<1 mm) increased elongation following cycling. The UTL of No. 2 ForceFiber suture loops tied with serrated clamps were reduced approximately 21% compared to those tied with no clamp (227 N vs. 289 N,
P
= 0.003) and approximately 18% compared to those tied with a smooth clamp (227 N vs. 278 N,
P
= 0.016). The use of clamps did not affect the UTL for the other six sutures. Clamp use also had no effect on suture loop stiffness for four suture types/sizes, but decreased stiffness for three. Suture loops tied with a serrated clamp were more likely to fail by untying compared to those tied without a clamp, but showed no difference in mechanism of failure from those tied with a smooth clamp.
Conclusions
Biomechanical parameters of suture loops were not significantly affected when clamped during tying. Surgeons wishing to temporarily clamp a knot to keep it from slipping during the tying process may do this without concern for weakening the suture.
Journal Article
The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease
Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are approved for cholesterol reduction, may also be beneficial in the treatment of inflammatory diseases
1
,
2
,
3
. Atorvastatin (Lipitor) was tested in chronic and relapsing experimental autoimmune encephalomyelitis, a CD4
+
Th1-mediated central nervous system (CNS) demyelinating disease model of multiple sclerosis
4
,
5
. Here we show that oral atorvastatin prevented or reversed chronic and relapsing paralysis. Atorvastatin induced STAT6 phosphorylation and secretion of Th2 cytokines (interleukin (IL)-4, IL-5 and IL-10) and transforming growth factor (TGF)-β. Conversely, STAT4 phosphorylation was inhibited and secretion of Th1 cytokines (IL-2, IL-12, interferon (IFN)-γ and tumour necrosis factor (TNF)-α) was suppressed. Atorvastatin promoted differentiation of Th0 cells into Th2 cells. In adoptive transfer, these Th2 cells protected recipient mice from EAE induction. Atorvastatin reduced CNS infiltration and major histocompatibility complex (MHC) class II expression. Treatment of microglia inhibited IFN-γ-inducible transcription at multiple MHC class II transactivator (CIITA) promoters and suppressed class II upregulation. Atorvastatin suppressed IFN-γ-inducible expression of CD40, CD80 and CD86 co-stimulatory molecules.
l
-Mevalonate, the product of HMG-CoA reductase, reversed atorvastatin's effects on antigen-presenting cells (APC) and T cells. Atorvastatin treatment of either APC or T cells suppressed antigen-specific T-cell activation. Thus, atorvastatin has pleiotropic immunomodulatory effects involving both APC and T-cell compartments. Statins may be beneficial for multiple sclerosis and other Th1-mediated autoimmune diseases.
Journal Article
Levels of Matrix Metalloproteinase–9 within Cerebrospinal Fluid in a Rabbit Model of Coccidioidal Meningitis and Vasculitis
Matrix metalloproteinase (MMP)–9 is produced by the central nervous system and inflammatory cells in a variety of inflammatory conditions in both animals and humans. MMP-9 promotes inflammation, breakdown of the blood-brain barrier, and vasculitis. Because vasculitis is seen frequently in patients with coccidioidal meningitis (CM), this study evaluated the presence of MMP-9 within the cerebrospinal fluid (CSF) of rabbits infected intracisternally with Coccidioides immitis arthroconidia. Infected rabbits demonstrated systemic and neurological sequelae to infection, including CSF pleocytosis. Levels of MMP-9 within CSF were assayed by use of zymography and compared with MMP-2 levels, which served as an internal control. Elevated levels of MMP-9 were detectable by day 3, continued to increase through day 10, and declined by day 15 after infection. MMP-9 may contribute to inflammation and vasculitis in this animal model. Future work can focus on evaluation of MMP inhibitors, to gain a better perspective of the role of this MMP in CM
Journal Article
Reflections on the retreat
Sobel details the American Judicature Society Commission's inaugural retreat in Greensboro NC on Mar 31- Apr 2. During the retreat, the 38-member Commission reflects the American Judicature Society's non-partisan philosophy of bringing together nationally prominent and eminently qualified persons, representing a wide variety of perspectives, to address important issues confronting the American judicial system.
Journal Article
Formation of Commission on Forensic Science and Public Policy completed
Sobel highlights the completion of the American Judicature Society Commission on Forensic Science and Public Policy. The American Judicature Society (AJS) has established this world class commission to advise the AJS Institute of Forensic Science and Public Policy regarding its research agenda and to consider the very best ways to bring and apply the knowledge of science to the job of improving the administration of justice.
Journal Article