Cross education of muscular strength during unilateral resistance training and detraining

Abstract. The purpose of the present study was to examine the changes in maximum voluntary isometric contraction (MVC) in the contralateral untrained limb during unilateral resistance training and detraining, and to examine the factors inducing these changes by means of electrophysiological techniques. Nine healthy males trained their plantar flexor muscles unilaterally 4 days·week^–1 for 6 weeks using 3 sets of 10–12 repetitions at 70–75% of one-repetition maximum a day, and detrained for 6 weeks. Progressive unilateral resistance training significantly (P<0.05) increased MVC, integrated electromyogram (iEMG), and voluntary activation in the trained and contralateral untrained limbs. The changes in MVC after training were significantly correlated with the changes in iEMG in both limbs. No significant changes occurred in MVC, voluntary activation, and iEMG in the contralateral limb after detraining. The changes in MVC after detraining did not correlate with the changes in voluntary activation or iEMG in either limb. Training and detraining did not alter twitch and tetanic peak torques in either limb. These results suggest that the mechanisms underlying cross education of muscular strength may be explained by central neural factors during training, but not solely so during detraining. Electronic Publication     

Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD

Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrP(C)) converts into its pathogenic isoform (PrP(Sc)). While PrP(C) conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrP(Sc) with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrP(Sc) of fCJD(R148H) were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrP(Sc) had similar characteristics. Furthermore, comparison of fCJD(R148H) with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrP(Sc) features of fCJD(R148H).     

结核分枝杆菌Ag85B基因疫苗免疫保护作用的初步研究

目的:研究编码结核分枝杆菌分泌蛋白Ag85B的基因疫苗pTB30m和pTB30s对免疫动物的保护作用。方法:以基因疫苗pTB30m和pTB30s肌注免疫BALB/c小鼠。免疫完成6 wk后,用5×105 CFU的MTB H37Rv毒株经小鼠尾静脉攻击感染。同时用尼龙毛柱分离基因免疫BALB/c小鼠的T细胞,并以5×106 T细胞/只小鼠过继免疫正常BALB/c小鼠,立即用105 CFU的MTB毒株经小鼠尾静脉攻击感染。4 wk后分别计数脾脏中的细菌负荷。结果:与生理盐水对照组相比较,pTB30m及pTB30s质粒免疫组BALB/c小鼠脾脏中的细菌负荷均减少,分别为0.645(log10 CFU,P<0.01)和0.839(log10CFU,P<0.001);而空质粒对照组小鼠脾脏中的细菌负荷减少较少。经质粒pTB30m和pTB30s免疫的BALB/c小鼠的T细胞,过继免疫的正常BALB/c小鼠,对攻击感染的MTB H37Rv毒株在脾脏中的增殖具有部分抑制作用。结论:pTB30s免疫的BALB/c小鼠,对MTB H37 Rv毒株攻击的保护作用优于pTB30m质粒免疫,有望进一步用于结核病的防治研究。     

Monoclonal antibodies define genus-specific, species-specific, and cross-reactive epitopes of the chlamydial 60-kilodalton heat shock protein (hsp60): specific immunodetection and purification of chlamydial hsp60.

Ocular and urogenital tract infections with Chlamydia trachomatis can progress to chronic inflammatory diseases that produce blindness and tubal infertility. The pathophysiology of these chronic disease conditions is thought to be immunologically mediated, and the chlamydial 60-kDa heat shock protein (hsp60) has been implicated as a major target antigen that stimulates the immunopathological response. The lack of chlamydial hsp60 antibodies and purified hsp60 has severely restricted studies to define more thoroughly the role of this protein in the immunopathogenesis of chlamydial disease. We produced a panel of antichlamydial hsp60 monoclonal antibodies (MAbs) and defined their specificities by immunoblotting against lysates of C. trachomatis, C. psittaci, and six other genera of bacteria. Three patterns of anti-hsp60 immunoreactivity were observed: chlamydial species specific, chlamydial genus specific, and cross-reactive. The epitopes recognized by these MAbs were localized within the primary amino acid sequence of hsp60 by immunoblotting against recombinant amino-terminal truncated hsp60 fusion polypeptides and then precisely mapped by use of overlapping synthetic peptides. The majority of the MAbs mapped to either the amino or the carboxyl termini of hsp60. Epitopes defining all three MAb reactivities mapped within amino-terminal residues 6 to 16. Genus-specific hsp60 MAbs mapped to epitopes located within this region and to residues 17 to 28 and 177 to 189. Antichlamydial hsp60 MAbs stained inclusions as effectively as MAbs specific for the major outer membrane protein. Homogeneous preparations of full-length recombinant chlamydial hsp60 and amino-terminal truncated recombinant hsp60 polypeptides were obtained by immunoabsorption chromatography with an hsp60 MAb reactive to the carboxyl terminus of the protein. Thus, the antichlamydial MAbs described here should be extremely useful for the specific immunodetection of hsp60 in tissues from individuals having different disease manifestations and for the purification of hsp60 or truncated hsp60 polypeptides for use in serologic and lymphocyte proliferation assays. The availability of these MAbs will facilitate studies to define more precisely the role of hsp60 in the immunopathogenesis of chlamydial disease.     

3D MRI-Based Multicomponent FSI Models for Atherosclerotic Plaques

A three-dimensional (3D) MRI-based computational model with multicomponent plaque structure and fluid-structure interactions (FSI) is introduced to perform mechanical analysis for human atherosclerotic plaques and identify critical flow and stress/strain conditions which may be related to plaque rupture. Three-dimensional geometry of a human carotid plaque was reconstructed from 3D MR images and computational mesh was generated using Visualization Toolkit. Both the artery wall and the plaque components were assumed to be hyperelastic, isotropic, incompressible, and homogeneous. The flow was assumed to be laminar, Newtonian, viscous, and incompressible. The fully coupled fluid and structure models were solved by ADINA, a well-tested finite element package. Results from two-dimensional (2D) and 3D models, based on ex vivo MRI and histological images (HI), with different component sizes and plaque cap thickness, under different pressure and axial stretch conditions, were obtained and compared. Our results indicate that large lipid pools and thin plaque caps are associated with both extreme maximum (stretch) and minimum (compression when negative) stress/strain levels. Large cyclic stress/strain variations in the plaque under pulsating pressure were observed which may lead to artery fatigue and possible plaque rupture. Large-scale patient studies are needed to validate the computational findings for possible plaque vulnerability assessment and rupture predictions.     

Specific immunoglobulin g antibody detected in umbilical blood and amniotic fluid from a pregnant woman infected by the coronavirus associated with severe acute respiratory syndrome

Specific immunoglobulin G antibody for severe acute respiratory syndrome (SARS) coronavirus was detected in maternal blood, umbilical blood, and amniotic fluid from a pregnant SARS patient. Potential protection of fetus from infection was suggested.     

Oral DNA vaccination with a plasmid encoding soluble ICAM-1 modulates cytokine expression profiles in nonobese diabetic mice

Adhesion molecules are important for leukocyte extravasation and for the delivery of costimulatory signals in T cell activation. We therefore interfered in the immune process leading to islet inflammation in diabetes prone NOD mice by oral vaccination with plasmid DNA encoding soluble ICAM-1. Female NOD mice were treated orally with ICAM-1, TGF-beta, or control plasmid DNA and received a single injection of cyclophosphamide for synchronization and acceleration of the disease process in the pancreas. Quantitative RT-PCR analysis of pancreatic mRNA showed that cyclophosphamide induced the expression of Th1 cytokines (IFN-gamma and IL-12p40) in vehicle- or control plasmid-treated mice. Treatment with ICAM-1 and TGF-beta DNA resulted in increased levels of IL-10 mRNA in the pancreas, indicating an anti-inflammatory regulatory immune response. Histological analysis of pancreatic islets showed that the DNA treatment did not alter islet infiltration in response to cyclophosphamide. Hence vaccination with the ICAM-1 plasmid had not suppressed leukocyte migration but rather modulated lymphocyte activity, similarly as seen for the TGF-beta-encoding plasmid. Neither of the three plasmids caused recognizable changes in cytokine expression in the small intestine, Peyer's patches, or mesenteric lymph nodes. We conclude that oral vaccination with DNA encoding immunoregulatory molecules such as ICAM-1 and TGF-beta represents an approach for modulating the ongoing inflammatory process in the pancreas of diabetes prone NOD mice.     

SGK1, a potential regulator of <Emphasis Type="Italic">c-fms</Emphasis> related breast cancer aggressiveness

The aggressive behavior of breast cancer cells can at times be modulated by hormonal mechanisms. Exposure to glucocorticoids (GC) has been shown to stimulate the invasiveness, motility and adhesiveness of breast cancer cells containing the glucocorticoid receptor. This is largely explained by GC-associated overexpression of the c-fms proto-oncogene, which encodes the receptor for the colony stimulating factor-1 (CSF-1). Our objective is to investigate additional GC-associated genetic alterations that could modulate c-fms related malignant behavior in breast cancer cells. A microarray technique using an oligonucleotide array representing 16,700 known expressed human genes was used to analyze the gene expression profile of breast cancer cells exposed to dexamethasone (Dex) or vehicle. Results were confirmed by western blot analysis. Six genes were found to be consistently differentially overexpressed in the Dex-exposed cells compared to control. We focused on serum-glucose kinase 1 (SGK1), a serine-threonine kinase known to be involved in intracellular signal transduction pathways and induced by GC and serum. An adhesion assay was performed on extracellular matrix after exposing the breast cancer cells to Dex, CSF-1 or to Dex or CSF-1 plus LY294002, a functional inhibitor of SGK1 action. Exposure to LY294002 significantly decreased both CSF-1 and Dex-induced adhesiveness to the level of control cells. SGK1 may act as a downstream intracellular regulator of c-fms, particularly of c-fms-induced adhesiveness of breast cancer cells after exposure to GC or CSF-1. This finding may have implications for potential therapeutic interventions aimed at decreasing the aggressiveness of breast cancer cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Phylogenomics of the dog and fox family (Canidae,Carnivora) revealed by chromosome painting

Canid species (dogs and foxes) have highly rearranged karyotypes and thus represent a challenge for conventional comparative cytogenetic studies. Among them, the domestic dog is one of the best-mapped species in mammals, constituting an ideal reference genome for comparative genomic study. Here we report the results of genome-wide comparative mapping of dog chromosome-specific probes onto chromosomes of the dhole, fennec fox, and gray fox, as well as the mapping of red fox chromosome-specific probes onto chromosomes of the corsac fox. We also present an integrated comparative chromosome map between the species studied here and all canids studied previously. The integrated map demonstrates an extensive conservation of whole chromosome arms across different canid species. In addition, we have generated a comprehensive genome phylogeny for the Canidae on the basis of the chromosome rearrangements revealed by comparative painting. This genome phylogeny has provided new insights into the karyotypic relationships among the canids. Our results, together with published data, allow the formulation of a likely Canidae ancestral karyotype (CAK, 2n = 82), and reveal that at least 6–24 chromosomal fission/fusion events are needed to convert the CAK karyotype to that of the modern canids. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.