Median frequency of the myoelectric signal

Summary A study was performed to investigate the changes that occur in the median frequency of the myoelectric signal during local ischemia or reduction of intramuscular temperature produced by surface cooling. Data was obtained from experiments which involved the first dorsal interosseous muscle of 10 female and 16 male subjects. These subjects were asked to perform isometric constant-force abduction contractions of the index finger at 20% and 80% of maximal voluntary contraction level. The initial median frequency (IMF) of the myoelectric signal during the first 0.5 s of contraction was calculated. Results showed a significant reduction of the IMF in contractions performed under ischemic conditions; upon release, the IMF recovered quickly. At 80% maximal voluntary level of contraction, a greater decrease of the IMF was recorded. Similar results were demonstrated during reduction of intramuscular temperature with gradual recovery of the IMF after cooling. These results demonstrate that the median frequency of the myoelectric signal displays behavior similar to that reported for conduction velocity and this is consistent with the notion that accumulation of metabolic byproducts in muscle tissue causes a decrease in the conduction velocity of the muscle fibers.Dr. R. Merletti was on a leave of absence from the Institute of Electrical Engineering, Politecnico di Torino, Italy     

Human immunodeficiency virus-associated changes in signal transduction

It is well established that the activation of T lymphocytes by mitogen/antigen is accompanied by a rise in intracellular free calcium ([Ca²⁺]_i), changes in membrane potential, metabolism of inositol phospholipid, and activation of protein kinase C. Theseearly events of signal transduction culminate inlate events of lymphocyte activation, namely, DNA synthesis, lymphokine production, and cellular proliferation. In this study we examined the effect of human immunodeficiency virus (HIV) on changes in membrane potential and [Ca²⁺]_i levels. The membrane potentials were markedly decreased (depolarized) in T cell lines infected with HIV (H9/HTLV IIIb) and did not respond normally to phytohemagglutinin (PHA) or anti-T3 (anti-CD3) monoclonal antibody compared to uninfected H9 cell line. The basal [Ca²⁺]_i levels in H9/HTLV IIIb cells were increased in comparison to those in H9 cells; however, there was very little further increase in [Ca²⁺]_i in H9/HTLV IIIb cells following activation with PHA or anti-T3 monoclonal antibody. This is in contrast to a significant rise in [Ca²⁺]_i in H9 cells following similar stimulation. These data demonstrate abnormalities in the plasma membrane potential and [Ca²⁺]_i levels in chronically infected T cells with HIV. These abnormalities in signal transduction of the T-cell activation pathway could be responsible for T-cell dysfunction in patients with HIV infection.     

Improvement in Doppler ultrasound human foetal heart rate records by signal correlation

An improved method for the determination of foetal heart rate from Doppler ultrasound signals is described and evaluated. It determines the most probable pulse interval from the recurrence times of multiple echoes generated by each cardiac pulse. The method, when optimised, is shown to offer an improvement over current systems, especially in reduced signal loss.     

Extra- and intracellular free iron and the carotid body responses

The hypothesis that chelation of free iron, by decreasing reactive oxygen species (ROS), might mimic hypoxia and stimulate the carotid body was tested. We used the iron chelators, desferrioxamine (DFO, 200-400 microM) initially, and later ciclopirox olamine (CPX, 2.5-5.0 microM), on rat carotid body in vitro and measured chemosensory activity and [Ca2+]i in isolated cultured glomus cell clusters during normoxia and hypoxia. Although acute treatment of DFO might not penetrate the cell, and extracellular DFO would not influence these activities whereas CPX significantly increased chemosensory activities as well as increased [Ca2+]i in normoxia. We concluded that chelation of extracellular free iron did not alter ROS formation and oxygen sensing. Chelation of intracellular free iron and, therefore, a decrease in intracellular ROS appears to influence oxygen sensing in the carotid body.     

Frequency-domain analysis of cerebral autoregulation from spontaneous fluctuations in arterial blood pressure

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in crebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n=23) or impaired (group B, n=21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables in demonstrated by mean values of squared coherence >0.50 for both groups in the frequency range 0.02–0.50 Hz. However, group A has significanlty smaller coherences than group B in the frequency ranges 0.02–0.10 Hz and 0.33–0.49 Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.3±1.05 and 1.80±1.2 rad Hz⁻¹, respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25–0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.     

A model for antigen-induced T cell unresponsiveness based on autophosphorylative protein tyrosine kinase activity

Helper T cell signaling is initiated by the aggregation of TCRwith the induction of tyrosine kinase activity as one of theearliest consequences. Here, a theoretical model for antigen-inducedunresponsiveness is presented that relies on a cascade of tyrosinephosphorylation- dephoshorylation cycles. A mechanism is describedfor both desensitization in the presence of antigen and persistentlowering of cell responsiveness after stimulus removal. An importantcomponent of the model, leading to bistability, is the presenceof autophosphorylating protein tyrosine kinases in the earlysteps of TCR signaling. One of its predictions is that, followingstimulation, the net phosphorylative activity of these receptor-associatedtyrosine kinases will remain above background level after removalof the antigen. It is proposed that this residual tyrosine kinaseactivity is linked to a deficient signal transduction capacityof the TCR system that leads to a state of prolonged unresponsiveness.In addition, the present analysis defines the notion of a signalingthreshold for hyporesponsiveness induction, associated witha durable switch and amplification of the net tyrosine kinaseactivity. This approach emphasizes the role of tyrosine kinasesin the down-regulation of cellular competence.     

Cell biology and pathology of liver sinusoidal endothelial cells

Growing evidence revealed that liver sinusoidal endothelial cells (SEC) play several important roles in physiology and pathology of the liver. It has been well understood that their structural characteristics, such as the membrane sieve and lack of basement membrane, facilitate direct contact of soluble and insoluble serum substances with hepatic parenchymal cells, resulting in enhancement of hepatic metabolic activity. In addition, SEC is now regarded as a member of the scavenger endothelial cells, which have potential to eliminate a variety of macromolecules from the blood circulation by receptor-mediated endocytosis. It is reported that molecules preferentially eliminated by SEC are denatured or modified proteins such as advanced glycation end products, extracellular matrix components including hyaluronic acid, and some lipoproteins. The nature of the scavenger receptors corresponding to these molecules remains to be clarified. Recently, it was noted that SEC has an antigen-presenting function similar to dendritic cells. Taken together, it is suggested that SEC, cooperating with Kupffer cells and hepatic dendritic cells, may partake of immunoregulatory functions in the liver. SEC also plays a pivotal role in the pathological process of ischemia-reperfusion injury following liver surgery and liver transplantation. Thus, it is of importance to elucidate the mechanisms of apoptosis and proliferation of SEC. Recent results on the regulation of growth and apoptotic signaling of SEC are discussed.     

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.