Adaptive spatial filtering of multichannel surface electromyogram signals

Spatial filtering of surface electromyography (EMG) signal can be used to enhance single motor unit action potentials (MUAPs). Traditional spatial filters for surface EMG do not take into consideration that some electrodes could have poor skin contact. In contrast to the traditional a priori defined filters, this study introduces an adaptive spatial filtering method that adapts to the signal characteristics. The adaptive filter, the maximum kurtosis filter (MKF), was obtained by using the linear combination of surrounding channels that maximises kurtosis. The MKF and conventional filters were applied to simulated EMG signals and to real EMG signals recorded with an electrode grid to evaluate their performance in detecting single motor units. The MKF was compared with conventional spatial filtering methods. Simulated signals, with different levels of spatially correlated noise, were used for comparison. The influence of one electrode with poor skin contact was also investigated. The MKF was found to be considerably better at enhancing a single MUAP than conventional methods for all levels of spatial correlation of the noise. For a spatial correlation of 0.97 of the noise, the improvement in the signal-to-noise ratio, where a MUAP could be detected, was at least 6 dB. With a simulated poor skin contact for one electrode, the improvement over the other methods was at least 19 dB.     

Bone marrow mast cell reaction in preleukaemic myelodysplasia and in aplastic anaemia

Summary The relationship of bone marrow mast cell counts to prognosis was investigated in 48 patients with preleukaemic myelodysplasia, in 59 patients with aplastic anemia and in a DMBA induced myelodysplasia/leukaemia rat model. In patients with myelodysplasia terminating in overt leukaemia the number of mast cells per square millimeter was not correlated to duration of the preleukaemic course. Leukaemia development probabilities of patients at risk were not different for low and elevated mast cell counts. In aplastic anaemia, however, a lower bone marrow mast cell count was related to a higher survival probability and longer survival time. In the animal model no significant differences could be found between myelodysplastic, leukaemic, and control animals.     

Bam32 links the B cell receptor to ERK and JNK and mediates B cell proliferation but not survival

Bam32 is an adaptor protein recruited to the plasma membrane upon B cell receptor (BCR) crosslinking in a phosphoinositol 3-kinase (PI3K)-dependent manner; however, its physiologic function is unclear. To determine its physiologic function, we produced Bam32-deficient mice. Bam32(-/-) B cells develop normally but have impaired T-independent antibody responses in vivo and diminished responses to BCR crosslinking in vitro. Biochemical analysis revealed that Bam32 acts in a novel pathway leading from the BCR to MAPK/ERK Kinases (MEK1/2), MAPK/ERK Kinase Kinase-1 (MEKK1), extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (p38). This pathway appears to be initiated by hematopoietic progenitor kinase-1 (HPK1), which interacts directly with Bam32, and differs from all previously characterized BCR signaling pathways in that it is required for normal BCR-mediated proliferation but not for B cell survival.     

Novel OCTN2 mutations: No genotype–phenotype correlations: Early carnitine therapy prevents cardiomyopathy

Primary systemic carnitine deficiency or carnitine uptake defect (OMIM 212140) is a potentially lethal, autosomal recessive disorder characterized by progressive infantile‐onset cardiomyopathy, weakness, and recurrent hypoglycemic hypoketotic encephalopathy, which is highly responsive to L ‐carnitine therapy. Molecular analysis of the SLC22A5 (OCTN2) gene, encoding the high‐affinity carnitine transporter, was done in 11 affected individuals by direct nucleotide sequencing of polymerase chain reaction products from all 10 exons. Carnitine uptake (at Km of 5 μM) in cultured skin fibroblasts ranged from 1% to 20% of normal controls. Eleven mutations (delF23, N32S, and one 11‐bp duplication in exon 1; R169W in exon 3; a donor splice mutation [IVS3+1 G > A] in intron 3; frameshift mutations in exons 5 and 6; Y401X in exon 7; T440M, T468R and S470F in exon 8) are described. There was no correlation between residual uptake and severity of clinical presentation, suggesting that the wide phenotypic variability is likely related to exogenous stressors exacerbating carnitine deficiency. Most importantly, strict compliance with carnitine from birth appears to prevent the phenotype. © 2002 Wiley‐Liss, Inc.     

Established beta-adrenergic receptor blocking therapy and acute myocardial infarction. A clinical study of risks and benefits

In order to evaluate the risks and benefits of continuing established therapy with beta-adrenergic receptor blocking drugs during acute myocardial infarction (AMI), 183 consecutive patients, 63 with (beta-blocker group) and 120 without (control group) this therapy, were studied. Detailed information on previous diseases, present symptoms, established medication, clinical and laboratory findings on admission and during the first 12 hours in the CCU was collected. The incidences of congestive heart failure, hypotension, AV blocks and ventricular arrhythmias were not significantly more common in the control group (8 vs. 28%, p less than 0.01). Thus, continuation of established therapy with beta-adrenergic receptor blocking drugs does not seem to increase the risk of complications after hospital admission for AMI. The reason for the low incidence of inferior wall infarction in the beta-blocker group is not clear but it cannot be excluded that when patients on beta-adrenergic receptor blocking therapy develop an inferior AMI, they may run a greater risk of sudden death.     

Estimation of surface electromyogram spectral alteration using reduced-order autoregressive model

A new method is proposed, based on the pole phase angle (PPA) of a second-order autoregressive (AR) model, to track spectral alteration during localised muscle fatigue when analysing surface myo-electric (ME) signals. Both stationary and non-stationary, simulated and real ME signals are used to investigate different methods to track spectral changes. The real ME signals are obtained from three muscles (the right vastus lateralis, rectus femoris and vastus medialis) of six healthy male volunteers, and the simulated signals are generated by passing Gaussian white-noise sequences through digital filters with spectral properties that mimic the real ME signals. The PPA method is compared, not only with spectra-based methods, such as Fourier and AR, but also with zero crossings (ZCs) and the first AR coefficient that have been proposed in the literature as computer efficient methods. By comparing the deviation (dev), in percent, between the linear regression of the theoretical and estimated mean frequencies of the power spectra for simulated stationary (s) and non-stationary (ns) signals, in general, it is found that the PPA method (dev_s=4.29; dev_ns=1.94) gives a superior performance to ZCs (dv_s=8.25) and the first AR coefficient (4.18<dev_s<21.8; 0.98<dev_ns<4.36) but performs slightly worse than spectra-based methods (0.33<dev_s<0.79; 0.41<dev_ns<1.07). However, the PPA method has the advantage that it estimates spectral alteration without calculating the spectra and therefore allows very efficient computation.     

Factors affecting the determination of threshold doses for allergenic foods: how much is too much?

BACKGROUND: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. OBJECTIVE: We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. METHODS: In September 1999, 12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. RESULTS: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows' milk, and egg; limited data were available for other foods, such as fish and mustard. CONCLUSIONS: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed.     

An established immune response against ovalbumin is suppressed by a transferable serum factor produced after ovalbumin feeding: a role of CD25+ regulatory cells

We have previously demonstrated that rats fed ovalbumin (OVA) develop a tolerogenic activity in serum, which upon transfer induces tolerance to OVA and suppression of the immune response to a bystander antigen. Here, we have extended these studies and analysed if the tolerogenic activity in serum could suppress an established immune response in the recipients. Rats were immunized with OVA, 4 and 1 week prior to the transfer of serum from either OVA-fed or control animals. Rats that received serum from OVA-fed donors had significantly lower delayed-type hypersensitivity (DTH) reaction against OVA 1 week after the serum transfer compared with the controls, and the levels of immunoglobulin (IgG) anti-OVA antibodies were significantly lower 2 and 4 weeks after serum transfer. Monomeric OVA in amounts corresponding to the OVA transferred with serum did not induce the reduction of DTH response or IgG anti-OVA antibody levels. In vitro, the proliferation of OVA-stimulated spleen cells, taken from recipients of tolerogenic serum, was significantly lower compared with spleen cells from the controls. The in vitro suppression seemed to be mediated by a population of CD25+ cells, because the removal of such cells from OVA-stimulated spleen cell suspensions resulted in increased proliferation in cultures from rats receiving tolerogenic serum. Our results showed that the tolerogenic serum factor can suppress an established immune response in recipient animals, possibly through induction of regulatory CD25+ cells. Whether this capacity might be used to influence chronic inflammatory conditions needs to be investigated.     

The Cbl family of ubiquitin ligases: critical negative regulators of tyrosine kinase signaling in the immune system

The Cbl family of proteins are evolutionarily conserved negative regulators of activated tyrosine kinase-coupled receptors. Antigen receptors are prominent targets of negative regulation by the Cbl family members, Cbl and Cbl-b, which proteins function as ubiquitin ligases. Cbl and Cbl-b contain substrate recognition domains that interact specifically with activated protein tyrosine kinases of the Src and Syk/ZAP-70 families. Cbl-mediated ubiquitination of these kinases leads to their degradation, resulting in attenuation of receptor signals. Cbl may also control activation-induced monoubiquitination of antigen receptors, thus facilitating their delivery to lysosomes for subsequent degradation. Finally, the interactions of Cbl proteins with downstream targets of tyrosine kinases, such as PI-3-kinase and Vav, could provide an additional mechanism to attenuate receptor signaling. By targeting multiple components of antigen receptor signaling for degradation, the Cbl protein family provides a critical mechanism to ensure an appropriate immune response. The hyperresponsiveness of Cbl(-/-) and Cbl-b(-/-) lymphocytes and the autoimmune phenotype of Cbl-b(-/-) mice lend strong support for this proposal. The ability to control early receptor signals through regulated protein degradation provides a novel paradigm of immunoregulation.