Anticipatory postural adjustments during self-paced and reaction-time movements

We studied the changes in the anticipatory postural adjustments (APAs), associated with dropping a load from extended arms and during fast bilateral shoulder flexion movements, when movements were performed in a self-paced manner and under a simple reaction-time instruction. The latter instruction applied time pressure and did not allow the regular pattern of APAs to be used. In particular, the following questions were asked: (1) are there changes in the relative timing of APAs under the reaction time condition; (2) are changes in the relative timing of APAs associated with changes in APAs themselves; (3) can different postural strategies be used to maintain stability under self-paced and reaction time conditions; and (4) are changes in APAs related to actual reaction time or to a change in the instruction? In particular, under reaction-time conditions, APAs occurred later in time, typically simultaneously with the initiation of the focal movement. Additional changes in electromyographic (EMG) patterns in postural muscles included an increase in the amplitude of EMG bursts and “speeding-up” some of the tri-phasic patterns in postural dorsal-ventral muscle pairs. This was accompanied by a smaller early shift of the center of pressure followed by its more rapid delayed displacement. There was considerable variability in the changes of EMG and dynamic characteristics across subjects. Some of the changes in the EMG patterns in postural muscles depended on actual reaction time, while others were related to a change in the instruction and occurred even if actual reaction times were long enough to allow for the typical self-paced APA patterns to occur. These findings can be interpreted as supporting the parallel control hypothesis for the focal movement and postural adjustments. Alternatively, they can be interpreted within a framework that implies the generation of a single control function, which is transformed into two components, one directed at the focal muscles/joints and the other directed at postural muscles/joints.     

Mice lacking the transcription factor RelB develop T cell-dependent skin lesions similar to human atopic dermatitis

Mice with a targeted disruption of the Rel / NF-kappaB family member RelB develop a complex inflammatory phenotype and hematopoietic abnormalities. RelB-deficient (relB(- / -)) mice were clinically normal until 4 - 10 weeks after birth when thickening of the skin and hair loss developed. Histological and immunohistochemical evaluation of relB(- / -) skin lesions revealed hyperkeratosis and marked epidermal hyperplasia. Many CD4(+) T cells and eosinophils mixed with lesser numbers of CD8(+) T cells and neutrophils were present in the dermis. There was a moderate increase of MHC class II-positive dermal dendritic cells and dermal mast cells. Increased expression of Th2 cytokines correlated with increased mRNA levels of eotaxin and CCR3 in relB(- / -) skin. The dermatitis did not develop in the offspring of relB(- / -) mice crossed with transgenic mice that lack peripheral T cells, demonstrating that the skin lesions were T cell dependent. The dermatitis observed in RelB-deficient mice had many similarities with atopic dermatitis in human patients including infiltrating CD4(+) T cells and eosinophils in the skin, increased number of eosinophils in the blood and increased serum IgE. Thus, the relB(- / -) mouse should be a useful model to study the pathogenesis of this common allergic human disease.     

Transforming growth factor-beta1 increases CXCR4 expression, stromal-derived factor-1alpha-stimulated signalling and human immunodeficiency virus-1 entry in human monocyte-derived macrophages

Stromal-derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 play crucial roles in leukocyte migration and activation, as well as embryogenesis, angiogenesis, cancer and viral pathogenesis. CXCR4 is one of the major human immunodeficiency virus-1 (HIV-1) coreceptors on macrophages. In many tissues macrophages are one of the predominant cell types infected by HIV-1 and act as a reservoir for persistent infection and viral dissemination. In patients infected by HIV-1, blood and tissue levels of transforming growth factor-beta1 (TGF-beta1) are increased. The purpose of this study was to evaluate the effects of TGF-beta1 on CXCR4 expression and function in primary human monocyte-derived macrophages (MDMs) and rat microglia. TGF-beta1 up-regulated CXCR4 and enhanced SDF-1alpha-stimulated ERK1,2 phosphorylation in these cells. The increased CXCR4 expression in human MDMs resulted in increased susceptibility of the cells to entry by dual-tropic CXCR4-using HIV-1 (D-X4). In contrast, TGF-beta1 failed to increase CCR5 expression or infection by a CCR5-using virus in MDMs. Our data demonstrate that TGF-beta1 enhances macrophage responsiveness to SDF-1alpha stimulation and susceptibility to HIV-1 by selectively increasing expression of CXCR4. The results suggest that increased expression of CXCR4 on macrophages may contribute to the emergence of dual-tropic X4 viral variants at later stages of HIV-1 infection.     

Assessment of Antibody Response Elicited by a 7-valent Pneumococcal Conjugate Vaccine in Pediatric Human Immunodeficiency Virus Infection

We investigated antibody responses against pneumococci of serotypes 6B, 14, and 23F in 56 children and adolescents with perinatal human immunodeficiency virus (HIV) infection who were vaccinated with 7-valent pneumococcal conjugate vaccine. Overall immune responses differed greatly between serotypes. Correlation coefficients between immunoglobulin G (IgG) measured by enzyme-linked immunosorbent assay (ELISA) and functional antibodies measured by a flow cytometry opsonophagocytosis assay (OPA) varied with serotype and time points studied. After 3 months of administering a second PCV7 dose we got the highest correlation (with significant r values of 0.754, 0.414, and 0.593 for serotypes 6B, 14, and 23F, respectively) but no significant increase in IgG concentration and OPA titers compared to the first dose. We defined a responder to a serotype included in the vaccine with two criteria: frequency of at least twofold OPA and ELISA increases for each serotype and frequency of conversion from negative to positive OPA levels. Responders varied from 43.9% to 46.3%, 28.5% to 50.0%, and 38.0% to 50.0% for serotypes 6B, 14, and 23F, respectively, depending on the response criterion. The present research highlights the importance of demonstrating vaccine immunogenicity with suitable immunological endpoints in immunocompromised patients and also the need to define how much antibody is required for protection from different serotypes, since immunogenicity differed significantly between serotypes.     

Triploidy syndrome: A report on two live-born (69, XXY) and one still-born (69, XXX) infants

Two live-born cases, 69,XXY and one stillbirth, 69,XXX are reported. Further evidence is presented to delineate the triploidy syndrome. Common external and internal features which characterize the triploidy syndrome are low-set ears, hypertelorism, colobomata, syndactyly, simian creases, microphallus, undescended testes, scrotal aplasia, anomalous heart and hypoplasia of kidneys and adrenals. The triploidy syndrome encompasses features found in trisomies 13, 18 and 21. We suggest that the abnormal development of the triploidy infants is the result of the mentioned trisomies and their subsequent effect on the remaining genome.     

Disseminated infection with Nattrassia mangiferae in an immunosuppressed patient

Disseminated infection with the coelomycetous fungus Nattrassia mangiferae is a very rare disease affecting only the immunocompromised host. We report the first case of a disseminated infection with spondylodiscitis and granular skin lesions due to N. mangiferae in a renal transplant patient.     

Endocrine-metabolic response to abdominal aortic surgery: A randomized trial of general anesthesia versus general plus epidural anesthesia

The influence of epidural anesthesia on the endocrine-metabolic response following abdominal aortic reconstruction was studied in a prospective randomized trial. Cortisol and catecholamine responses and nitrogen balance were measured in two groups of five patients receiving general anesthesia only (group 1) or general anesthesia combined with epidural bupivacaine (group 2). The study lasted from preoperatively until the first postoperative day. At 2100 hours on the day of surgery serum cortisol concentrations were higher in group 1 than in group 2 (1.41 versus 0.82 mol/L; p<0.01). Likewise the total perioperative hypercortisolemia, expressed as the area under the curve, was significantly higher in group 1 (11.7 versus 5.7 mol/L/hr, p<0.01). Intraoperative urinary excretion of epinephrine and postoperative norepinephrine excretion were significantly higher in group 1 than in group 2. Urinary excretion of free cortisol and cumulative nitrogen balance were not different between the groups. Although the number of patients was limited and the sensory nerve block level was not measured perioperatively, this study suggests that epidural anesthesia attenuates the stress response to aortic surgery.

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Resumen Se diseñó un ensayo clínico prospectivo y randomizado con el fin de estudiar el efecto de la anestesia epidural sobre la respuesta endocrino-metabolica luego de una reconstrucción aórtica abdominal. Se determinaron la respuesta de cortisol y catecolaminas y el balance de nitrógeno en dos grupos de 5 pacientes que recibieron anestesia general solamente (Grupo 1) o anestesia general combinada con bupivacaína epidural (Grupo 2). El estudio se realizó en el periodo comprendido entre la fase preoperatoria hasta el primer día postoperatorio. A las 21:00 horas del mismo día de la cirugía las concentraciones séricas de cortisol resultaron más altas en el Grupo 1 que en el Grupo 2 (1.41 versus 0.82 micromol/l, p<0.01). Igualmente, la hipercortisolemia total perioperatoria apareció más alta en el Grupo 1 (11.7 versus 5.7 micromol/l^* hora, p<0.01). La excreción urinaria intraoperatoria de epinefrina y la excreción postoperatoria de norepinefrina aparecieron significativamente más altas en el Grupo 1 que en el Grupo 2. No se registraron diferencias en la excreción urinaria de cortisol libre ni en el balance acumulado de nitrógeno. Aunque el número de pacientes fue limitado y el nivel del bloqueo sensorial no fue determinado perioperatoriamente, el presente estudio sugiere que la anestesia epidural atenúa la respuesta de estrés en la cirugia aórtica.

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Résumé Dans une étude prospective et randomisée, l'influence de l'anesthésie péridurale sur la résponse métabolique endocrinienne a été étudiée dans la période préopératoire immédiate jusqu'au premier jour postopératoire après la chirurgie de l'aorte abdominale. On a mesuré les résponses en catécholamines et l'équilibre azoté chez cinq patients ayant eu une anesthésie générale seule (groupe 1) et cinq patients ayant une anesthésie générale combinée avec une anesthésie péridurale par la bupivacaïne (groupe 2). A 21H00 le jour de l'intervention,. la concentration en cortisol était plus haute dans le groupe 1 par rapport au groupe 2 (1.41 vs 0.82 micromol/l, p<0.01). De même, l'hypercortisolémie périopératoire totale, exprimée par la surface sous la courbe, était significativement plus élevée dans le groupe 1 (11.7 vs 5.7 micromol/l heure, p<0.01). L'excrétion urinaire peropératoire d'épinéphrine et l'excrétion postopératoire de la norépinéphrine étaient significativement plus élevées dans le groupe 1 par rapport au groupe 2. L'excrétion urinaire du cortisol libre et l'équilibre azoté tout au long de l'étude n'étaient pas très différents. Bien que le nombre de patients était limité et que le niveau supérieur de l'anesthésie n'ait pas été mesuré en périopératoire, les résultats de cette étude suggèrent que l'anesthésie péridurale atténue la réponse au stress dans la chirurgie de l'aorte abdominale.