Rat cytomegalovirus and Listeria monocytogenes infection enhance chronic rejection after allogenic rat lung transplantation

The role of infection in the pathomechanism of obliterative bronchiolitis (OB) after human lung transplantation is controversial. In a rat lung transplantation model, we analyzed the effect of viral [rat cytomegalovirus (RCMV)] and bacterial infection [Listeria monocytogenes (LM)] on the development of chronic allograft rejection. Fisher rats underwent single left lung transplantation with allografts from Lewis rats. Postoperatively, animals were infected with either RCMV or LM, or served as noninfected controls. Animals were killed on day 120 and both lungs were evaluated histopathologically for chronic airway and chronic vascular rejection. Infection with RCMV produced a significant increase in the incidence of chronic airway rejection (66.7% vs. 20%), compared with noninfected long-term surviving animals. In rats with bacterial infection (LM) a similar increase of chronic airway changes as in viral infection (50% vs. 20%) was observed. Chronic rejection of allografts infected with either RCMV or LM was associated with significantly enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelium. More infiltrating leukocytes (CD18, CD11a, CD44) and ED1-positive macrophages were found in allografts of infected animals. In this experimental model of chronic airway rejection in long-term surviving rats, not only viral but also bacterial infection resulted in enhanced development of chronic airway and vascular rejection. These results support our hypothesis that infectious complications have a substantial influence on the development of OB in human lung allografts.     

Inverse relationship between colonic (Na+ + K+)-ATPase activity and degree of mucosal inflammation in inflammatory bowel disease

In inflammatory bowel disease (IBD), mucosal damage and loss of colonic function are regarded as major consequences of inflammation. Decreased colonic (Na⁺ + K⁺)-ATPase activities with diminished reabsorption of sodium and water have been found in active stages of ulcerative colitis. In this study, we report an inverse relationship between colonic (Na⁺ + K⁺)-ATPase activity and the degree of mucosal inflammation in 19 patients with IBD of mild to moderate disease activity. Various macroscopic and histologic types of mucosal lesions were differently associated with the (Na⁺ + K⁺)-ATPase activities. 5-nucleotidase activity was not associated with the degree of mucosal inflammation or the kind of macroscopic or histologic lesions. Our findings support the view that, in contrast to 5-nucleotidase, (Na⁺ + K⁺)-ATPase activity may better reflect the severity of mucosal damage and the degree of inflammation in IBD.     

Insulin-mediated immune dysfunction in the development of preeclampsia

Journal of Molecular Medicine - Epidemiological observations implicate insulin resistance as a predisposing factor in the development of preeclampsia (PE). It is also well established that PE...     

Heart wall myofibers are arranged in minimal surfaces to optimize organ function

Heart wall myofibers wind as helices around the ventricles, strengthening them in a manner analogous to the reinforcement of concrete cylindrical columns by spiral steel cables [Richart FE, et al. (1929) Univ of Illinois, Eng Exp Stn Bull 190]. A multitude of such fibers, arranged smoothly and regularly, contract and relax as an integrated functional unit as the heart beats. To orchestrate this motion, fiber tangling must be avoided and pumping should be efficient. Current models of myofiber orientation across the heart wall suggest groupings into sheets or bands, but the precise geometry of bundles of myofibers is unknown. Here we show that this arrangement takes the form of a special minimal surface, the generalized helicoid [Blair DE, Vanstone JR (1978) Minimal Submanifolds and Geodesics 13-16], closing the gap between individual myofibers and their collective wall structure. The model holds across species, with a smooth variation in its three curvature parameters within the myocardial wall providing tight fits to diffusion magnetic resonance images from the rat, the dog, and the human. Mathematically it explains how myofibers are bundled in the heart wall while economizing fiber length and optimizing ventricular ejection volume as they contract. The generalized helicoid provides a unique foundation for analyzing the fibrous composite of the heart wall and should therefore find applications in heart tissue engineering and in the study of heart muscle diseases.     

Holding an object: neural activity associated with fingertip force adjustments to external perturbations

When you hold an object, a sudden unexpected perturbation can threaten the stability of your grasp. In such situations grasp stability is maintained by fast reflexive-like grip-force responses triggered by the somatosensory feedback. Here we use functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms involved in the grip-force responses associated with unexpected increases (loading) and decreases (unloading) in the load force. Healthy right-handed subjects held an instrumented object (of mass 200 g) between the tips of right index finger and thumb. At some time during an interval of 8 to 45 s the weight of the object was suddenly increased or decreased by 90 g. We analyzed the transient increases in the fMRI signal that corresponded precisely in time to these grip-force responses. Activity in the left primary motor cortex was associated with the loading response, but not with unloading, suggesting that sensorimotor processing in this area mediates the sensory-triggered reflexive increase in grip force during loading. Both the loading and the unloading events activated the cingulate motor area and the medial cerebellum. We suggest that these regions could participate in the updating of the sensorimotor representations of the fingertip forces. Finally, the supplementary somatosensory area located on the medial wall of the parietal lobe showed an increase in activity only during unloading, indicating that this area is involved in the sensorimotor processing generating the unloading response. Taken together, our findings suggest different central mechanisms for the grip-force responses during loading and unloading.