A flexible PC-based physiological monitor for animal experiments

We have developed a flexible physiological monitoring and analysis system for physiological studies in which data are obtained over extended periods. Our system uses low-cost personal computer hardware to concentrate data from existing multiple monitoring devices. All monitored parameters are displayed on a single screen and recorded in a single file. The system automates the process of physiological record keeping by providing continuous displays of vital signs. In addition, audible and visual alarms are produced when vital signs are outside of acceptable ranges, prompting the experimenter to take corrective actions. The central element of the system is a program running in a dedicated manner on an IBM PC-compatible computer. The program is written in the C language and makes use of a graphics library to display traces and analysis results in real time on any standard display for the PC. This program assigns the analog channels of an A/D board to particular physiological parameters by initially reading a configuration file, which also describes the alarm conditions and analysis routine for each parameter. All hardware specific code is isolated into well-defined modules. The program is both highly flexible with regard to different sets of parameters and highly portable for different experimental and computer environments.     

Prevention of T cell anergy by signaling through the gamma c chain of the IL-2 receptor

When stimulated through their antigen receptor without requisite costimulation, T cells enter a state of antigen-specific unresponsiveness termed anergy. In this study, signaling through the common gamma chain of the interleukin-2 (IL-2), IL-4, and IL-7 receptors in the presence of antigen was found to be sufficient to prevent the induction of anergy. After culture with IL-2, IL-4, or IL-7, Jak3 kinase was tyrosine-phosphorylated, which correlated with the prevention of anergy. Therefore, a signal through the common gamma chain may regulate the decision of T cells to either clonally expand or enter a state of anergy.     

Temporal expression of pro-inflammatory cytokines and inducible nitric oxide synthase in experimental acute Chagasic cardiomyopathy

Pelizaeus-Merzbacher disease (PMD) is a dysmyelinating disease resulting from mutations, deletions, or duplications of the proteolipid protein (PLP) gene. Distinguishing features of PMD include pleiotropy and a range of disease severities among patients. Previously, we demonstrated that, when expressed in transfected fibroblasts, many naturally occurring mutant PLP alleles encode proteins that accumulate in the endoplasmic reticulum and are not transported to the cell surface. In the present communication, we show that oligodendrocytes in an animal model of PMD, the msd mouse, accumulate Plp gene products in the perinuclear region and are unable to transport them to the cell surface. Another important aspect of disease in msd mice is oligodendrocyte cell death, which is increased by two- to threefold. We demonstrate in msd mice that this death occurs by apoptosis and show that at the time oligodendrocytes die, they have differentiated, extended processes that frequently contact axons and are expressing myelin structural proteins. Finally, we define a hypothesis that accounts for pathogenesis in most PMD patients and animal models of this disease and, moreover, can be used to develop potential therapeutic strategies for ameliorating the disease phenotype.     

Peroxynitrite reaction with carbon dioxide/bicarbonate: kinetics and influence on peroxynitrite-mediated oxidations

A method of stratifying the data according to the patterns of missing observations, summarizing each subject's repeated measurements by a summary measure and then comparing the treatment groups with the help of a distribution-free test based on the summary measure, is used here to compare the efficacy of tacrine dose regimens with that of placebo in a recent trial in Alzheimer's disease patients. The usefulness of the method of meta-analysis for comparing the treatment groups, in the presence of missing data, is also investigated.     

The nutrition implications of cardiac cachexia

Weight loss is a frequent sequela in patients with congestive heart failure and is commonly referred to as cardiac cachexia. This weight loss is unlike that seen in simple starvation because it preferentially involves the depletion of lean body mass. In addition, the presence of cardiac cachexia can have profound clinical implications for patients in terms of complications, clinical outcome, and overall cost. The mechanism for the alterations in body composition is multifactorial, but a major cause may be the cytokine-mediated host response to the underlying disease. This article reviews the syndrome of cardiac cachexia in light of recent evidence regarding the role of cytokines, as well as potential therapies.