Trunk muscle fatigue and associated EMG changes during a dynamic iso-inertial test

This study was designed to investigate the relationship between trunk muscle fatigue and associated changes in the electromyographic (EMG) signals during a dynamic iso-inertial test. Eleven subjects performed dynamic trunk flexion/extension movements against 40% maximum voluntary contraction (MVC) torque until exhaustion in a tri-axial trunk dynamometer. EMG parameters in the time and frequency domain were studied by analysing changes of the signal amplitudes and the spectral density (using the zero-crossing-rate and the median frequency). The kinematics of the movement were analysed according to the movement velocities and the deviations from the required movement plane. The flexion and extension velocities decreased from the beginning to the end of the test. Movement deviations from the sagittal plane into the frontal and transverse plane increased with increasing test duration, as did the EMG amplitude. The median frequency during periods with maximum muscle activity decreased, as did the zero-crossing-rate. The increase in amplitude and decrease in median frequency were more pronounced in the trunk flexors than in the trunk extensors. The parameters of median frequency, zero-crossing-rate and amplitude seem to be sensitive identifiers of muscle fatigue during well-controlled dynamic contractions. While the kinematic data did not yield any information on the mechanisms of the fatigue, changes in the EMG parameters demonstrated that the duration of the test was limited by the fatigue of the trunk flexors.     

Effect of exercise,hypoxia, and epinephrine on lysosomes and plasma enzymes

In order to study the possible relation of hepatic lysosomal stability and enzyme release from the liver during stress, rats were sacrificed after swimming exercise, hypoxia, and epinephrine injections. Each of the stresses caused a decrease in hepatic lysosomal stability, an increase in plasma ornithine carbamoyltransferase (OCT), a liver specific enzyme, and increases in plasma creatine phosphokinase (CPK) and aspartate aminotransferase (AAT). With exercise, the decrease in lysosomal stability and the increase in OCT were first seen at one hour. The OCT increase preceded the lysosomal changes after hypoxia and followed the lysosomal changes after epinephrine injection. Prednisolone reduced the lysosomal and CPK (but not the OCT and AAT) changes with exercise, but had no effect with hypoxia or epinephrine injections. Adrenalectomy delayed the lysosomal changes and eliminated the increase in OCT after hypoxia and epinephrine. The varying time sequence of hepatic lysosomal changes and enzyme release with these stresses suggests that these two phenomena are not causally related.     

The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis

Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease, for which until now no effective therapy is available. The biochemical hallmark of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which results in elevated sulfite and diminished sulfate levels throughout the organism. In humans, Moco-deficiency results in neurological damage, which is apparent in untreatable seizures and various brain dysmorphisms. We have recently described a murine model for Moco-deficiency, which reflects all enzyme and metabolite changes observed in the patients, and an efficient therapy using a biosynthetic precursor of Moco has been established in this animal model. We now analyzed these mice in detail and excluded morphological brain damage, while expression analysis with microarrays indicates a massive cell death program. This neuronal damage appears to be triggered by elevated sulfite levels and is ameliorated in affected embryos by maternal clearance.     

Heat shock proteins as "danger signals": eukaryotic Hsp60 enhances and accelerates antigen-specific IFN-gamma production in T cells.

The heat shock proteins (HSP) gp96, Hsp70 and Hsp60 activate professional antigen-presenting cells (APC) to secrete proinflammatory cytokines and to express costimulatory molecules. Here, we analyze the impact of Hsp60 as a hypothetical danger signal on the antigen-specific activation of T cells derived from DO11.10 TCR-transgenic mice. The release of IFN-gamma, induced by the antigenic OVA(323-339)-peptide, is increased and accelerated dramatically by the addition of Hsp60 to ex vivo purified populations of T cells and peritoneal macrophages (PEC), while the antigen-specific IL-2 production or proliferation of the T cells remain unchanged. In contrast, "effector" T cells, undergoing secondary stimulation, displayed almost unchanged activation kinetics in the presence of Hsp60. The presence of Hsp60 induces IFN-gamma and up-regulation of CD69 in T cell/PEC cocultures even in the absence of antigenic peptide and this induction of IFN-gamma is strictly dependent on the ability of the macrophages to produce IL-12. Taken together, our data strongly suggest that the presence of eukaryotic mitochondrial Hsp60 allows antigen-specific IFN-gamma secretion under conditions when an antigenic stimulus alone is not sufficient to activate T cells.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Molecular analysis of CD26-mediated signal transduction in T cells

CD26 or dipeptidylpeptidase IV (DPP IV) is a cell surface protease involved in T cell activation. It is a type II transmembrane glycoprotein consisting of a large extracellular part, a single transmembrane region and a short cytoplasmic tail without any common signalling motifs. To eluciate the mechanisms involved in CD26-mediated signalling we have constructed C-terminal deletion mutants of the human CD26 molecule and transfected them into murine T cell hybridomas. Stimulation experiments show that most of the extracellular part of CD26 can be deleted without affecting its costimulatory activity. The membrane proximal glycosylation rich region of CD26 is sufficient to transduce costimulatory signals. Activation of T cells via CD26, however, is not mediated by the important T cell receptor associated adaptor proteins LAT and TRIM as shown in colocalization assays.     

Arthus phenomenon like skin reaction and antibody pattern in rabbits immunized with various myxovirus fractions

Summary Rabbits immunized with measles- and mumps viruses grown in monkey kidney cells and chick embryo fibroblasts and with their water- and organic solvent fractions obtained by Tween-ether treatment developed immediate type skin hyperreactivity (Arthus phenomenon-like) to challenge with the complete viruses and calf serum, but not to challenge with tissue antigens prepared in the absence of calf serum. The skin reaction in animals immunized with ether fractions was stronger than in animals immunized with water fractions or complete virus, respectively. The intensity of individual skin reactions in each animal was better correlated to the presence of precipitating antibody against calf serum or a component thereof than to the HI titer against the viruses used for immunization.The seriological tests for measles and mumps were supported by the Bundesminister für Jugend, Familie und Gesundheit, Bonn, BRD.     

Natural variants of the Sabin type 1 vaccine strain of poliovirus and correlation with a poliovirus neutralization site

Independent substitution mutations have been detected in capsid polypeptide VP1 of the type 1 oral poliovirus vaccine isolated from normal infant vaccine recipients. These mutations map at amino acid residues 142 and 147 of VP1, a region only minimally hydrophilic. A synthetic peptide, corresponding to residues 141 to 147 of VP1 was synthesized, conjugated to a carrier polypeptide of bovine serum albumin. The conjugate was found to elicit a weak poliovirus neutralizing antibody response. It was also capable of priming the immune system for the production of IgG-type antibodies able to neutralize greater than 99.999% of infectious type 1 virus. It is suggested that region 141 to 147 of VP1 may be involved in neutralization of the virus and that the mutants may have accumulated by antibody selection.     

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.