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T W Beck

Publications and source records attributed to T W Beck.

At least 19 recordsLinked to original sources
PubMed2006

Is fatigue all in your head? A critical review of the central governor model.

The central governor model has recently been proposed as a general model to explain the phenomenon of fatigue. It proposes that the subconscious brain regulates power output (pacing strategy) by modulating motor unit recruitment to preserve whole body homoeostasis and prevent catastrophic physiological failure such as rigor. In this model, the word fatigue is redefined from a term that describes an exercise decline in the ability to produce force and power to one of sensation or emotion. The underpinnings of the central governor model are the refutation of what is described variously as peripheral fatigue, limitations models, and the cardiovascular/anaerobic/catastrophe model. This argument centres on the inability of lactic acid models of fatigue to adequately explain fatigue. In this review, it is argued that a variety of peripheral factors other than lactic acid are known to compromise muscle force and power and that these effects may protect against "catastrophe". Further, it is shown that a variety of studies indicate that fatigue induced decreases in performance cannot be adequately explained by the central governor model. Instead, it is suggested that the concept of task dependency, in which the mechanisms of fatigue vary depending on the specific exercise stressor, is a more comprehensive and defensible model of fatigue. This model includes aspects of both central and peripheral contributions to fatigue, and the relative importance of each probably varies with the type of exercise.

Energy Metabolism↗
PubMed2005

Comparison of Fourier and wavelet transform procedures for examining mechanomyographic and electromyographic frequency versus isokinetic torque relationships.

The purpose of this study was to compare the isokinetic torque-related patterns for mechanomyographic (MMG) and electromyographic (EMG) center frequency [wavelet center frequency (CF), mean power frequency (MPF), and median frequency (MDF)] determined by the fast Fourier transform (FFT) and discrete wavelet transform (DWT). Ten adults [mean +/- SD age = 22.0 +/- 3.4 yrs] performed submaximal to maximal, isokinetic muscle actions of the biceps brachii on a Cybex II dynamometer. For both MMG and EMG, the CF, MPF, and MDF values were intercorrelated at (r = 0.91-0.98). Quadratic models provided the best fit for the absolute and normalized CF, MPF, and MDF versus isokinetic torque relationships for MMG (R2 = 0.67-0.83) and EMG (R2 = 0.72-0.90). The similarities among the CF, MPF, and MDF patterns suggested that Fourier or wavelet transform procedures can be used to examine the patterns of MMG and EMG responses during dynamic muscle actions.

Adult↗
PubMed2004

The acute effects of static stretching on peak torque, mean power output, electromyography, and mechanomyography.

The purpose of this study was to examine the acute effects of static stretching on peak torque (PT), the joint angle at PT, mean power output (MP), electromyographic (EMG) amplitude, and mechanomyographic (MMG) amplitude of the vastus lateralis (VL) and rectus femoris (RF) muscles during maximal, voluntary concentric isokinetic leg extensions at 60 and 240 degrees x s(-1) of the stretched and unstretched limbs. Twenty-one volunteers [mean age (SD) 21.5 (1.3) years] performed maximal, voluntary concentric isokinetic leg extensions for the dominant and non-dominant limbs at 60 and 240 degrees x s(-1). Surface EMG (muVrms) and MMG (mVrms) signals were recorded from the VL and RF muscles during the isokinetic tests. PT (Nm), the joint angle at PT, and MP (W) were calculated by a dynamometer. Following the initial isokinetic tests, the dominant leg extensors were stretched using four static stretching exercises. After the stretching, the isokinetic tests were repeated. PT decreased (P< or =0.05) from pre- to post-stretching for the stretched limb at 60 and 240 degrees x s(-1) and for the unstretched limb at 60 degrees x s(-1). EMG amplitude of the VL and RF also decreased (P< or =0.05) from pre- to post-stretching for the stretched and unstretched limbs. There were no stretching-induced changes (P>0.05) for the joint angle at PT, MP, or MMG amplitude. These findings indicated stretching-induced decreases in force production and muscle activation. The decreases in PT and EMG amplitude for the unstretched limb suggested that the stretching-induced decreases may be due to a central nervous system inhibitory mechanism.

Adult↗
PubMed2004

Mechanomyographic time and frequency domain responses of the vastus medialis muscle during submaximal to maximal isometric and isokinetic muscle actions.

The purpose of this study was to examine the patterns for the mechanomyographic (MMG) amplitude and mean power frequency (MPF) versus torque relationships during isometric and isokinetic muscle actions. Ten adults (mean age +/- SD = 22 +/- 1 y) volunteered to perform isometric and isokinetic leg extension muscle actions at 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100% of peak torque on a Cybex II dynamometer. A piezoelectric crystal contact sensor was placed on the vastus medialis to detect the MMG signal. Regression analyses indicated that for the isometric muscle actions, the relationships for MMG amplitude (R2 = 0.998) and MPF (R2 = 0.987) versus torque were cubic. For the isokinetic muscle actions, the relationships for MMG amplitude (r2 = 0.927) and MPF (r2 = 0.769) versus torque were linear. The different patterns for MMG amplitude and frequency may reflect differences in the motor control strategies that modulate torque production for isometric versus dynamic muscle actions.

Adult↗
PubMed2001

Comparative feline genomics: a BAC/PAC contig map of the major histocompatibility complex class II region.

The genome organization of the human major histocompatibility complex (MHC) will be best understood in a comparative evolutionary context. We describe here the construction of a physical map for the feline MHC. A large-insert domestic cat genomic DNA library was developed using a P1 artificial chromosome (PAC) with a genomic representation of 2.5x and an average insert size of 80 kb. A sequence-ready 660-kb bacterial artificial chromosome/PAC contig map of the domestic cat MHC class II region was constructed with a gene order similar to, but distinct from, that of human and mice: DPB/DPA, Ring3, DMB, TAP1, DOB, DRB2, DRA3, DRB1, DRA2, and DRA1. Fluorescence in situ hybridization analyses of selected class II PAC clones confirmed that the class II region lies in the pericentromeric region of cat chromosome B2. However, apparently unlike the human and mouse MHCs, the domestic cat DRA and DRB genes have undergone multiple duplications and the DQ region has been deleted.

Animals↗
PubMed2000

Post-exposure chemoprophylaxis (PECP) against SIV infection of macaques as a model for protection from HIV infection.

We report that simian immunodeficiency virus (SIV) infection in macaques is a valuable animal model for studying post-exposure chemoprophylaxis (PECP). PECP with the acyclic nucleoside reverse transcriptase inhibitors 9-(2-phosphonylmetho-xyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) at early viral infection can provide long-term protection against subsequent heterologous SIV challenge. Eight macaques previously treated with PECP (called PECP macaques) and four naive controls were challenged intravenously with the most virulent form of SIV, SIV(PBj14). All controls showed signs of SIV(PBj14)-induced acute disease syndrome on days 6 and 7 post-inoculation (PI). One had a fatal viral infection and two surviving controls had persistent infection and decreased CD4+ cell count. Virologic studies of the three surviving controls revealed SIV in multiple lymphoid tissues and peripheral blood mononuclear cells (PBMCs) at necropsy. In contrast, the PECP macaques showed none to mild signs of acute disease syndrome at day 9 PI and exhibited only transient SIV infection in PBMCs between weeks 1 and 8 PI. In virologic studies of five PECP macaques necropsied, two macaques were SIV-negative and the other three were SIV-positive only in either lymph node or bone marrow. Three SIV(PBj14)-challenged PECP macaques, that were randomly reserved for a follow-up study for > 4.0 years PI showed extremely low to undetectable levels of PBMC-associated viremia and normal to increased levels of CD4 + and CD8 + cell counts throughout the study. Our results indicate that early PECP could activate immune responses to protect against subsequent infection with heterologous challenge virus.

Adenine↗
PubMed1998

Craf-1 protein kinase is essential for mouse development.

The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from a variety of cell surface receptors to the nucleus. We report here that Craf-1 is essential for mouse development, as its mutation results in embryonic lethality. Developmental defects are found in mutant placentas as well as in the skin and in the lungs of mutant embryos. Craf-1 mutants also display a generalized growth retardation which is consistent with the ubiquitous expression of Craf-1 and which could be due to the reduced proliferation of mutant cells. Interestingly, the time-point of embryonal death varies depending on the genetic background. This suggests that Craf-1-mediated signaling is affected by genetic background-specific alleles of other genes.

Abnormalities, Multiple↗
PubMed1998

Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment.

(R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA), an acyclic nucleoside phosphonate analog, is one of a new class of potent antiretroviral agents. Previously, we showed that PMPA treatment for 28 days prevented establishment of persistent simian immunodeficiency virus (SIV) infection in macaques even when therapy was initiated 24 h after intravenous virus inoculation. In the present study, we tested regimens involving different intervals between intravenous inoculation with SIV and initiation of PMPA treatment, as well as different durations of treatment, for the ability to prevent establishment of persistent infection. Twenty-four cynomolgus macaques (Macaca fascicularis) were studied for 46 weeks after inoculation with SIV. All mock-treated control macaques showed evidence of productive infection within 2 weeks postinoculation (p.i.). All macaques that were treated with PMPA for 28 days beginning 24 h p.i. showed no evidence of viral replication following discontinuation of PMPA treatment. However, extending the time to initiation of treatment from 24 to 48 or 72 h p.i. or decreasing the duration of treatment reduced effectiveness in preventing establishment of persistent infection. Only half of the macaques treated for 10 days, and none of those treated for 3 days, were completely protected when treatment was initiated at 24 h. Despite the reduced efficacy of delayed and shortened treatment, all PMPA-treated macaques that were not protected showed delays in the onset of cell-associated and plasma viremia and antibody responses compared with mock controls. These results clearly show that both the time between virus exposure and initiation of PMPA treatment as well as the duration of treatment are crucial factors for prevention of acute SIV infection in the macaque model.

Adenine↗
PubMed1997

Effects of (R)-9-(2-phosphonylmethoxypropyl)adenine monotherapy on chronic SIV infection in macaques.

(R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA) acts as a reverse transcriptase inhibitor of retroviruses and has been shown to be effective against acute simian immunodeficiency virus (SIV) infection in macaques. To study its efficacy at different stages of infection, we tested PMPA in cynomolgus macaques (Macaca fascicularis) that had been chronically infected with SIVMne for at least 19 weeks before treatment was begun. PMPA was administered subcutaneously in a single daily dose of either 30 or 75 mg/kg body weight for 28 days. Within < or = 2 weeks of treatment, PMPA in both dosing regimens reduced SIV levels by >99% in the plasma or peripheral blood mononuclear cells; in some macaques SIV levels were reduced to below the lower quantitation limit. At a dose of 30 mg/kg/day PMPA was well tolerated, causing no side effects while increasing the mean CD4+ cell counts in animals that received this dose. Thus PMPA seems to be a promising agent for use against retroviral infections.

Adenine↗
PubMed1997

Endothelial apoptosis in Braf-deficient mice.

Tyrosine kinase growth factor receptors and Ras/Raf/MEK/MAPK signalling have been implicated in the suppression as well as augmentation of programmed cell death. In addition, a Ras-independent role for Raf as a suppressor of programmed cell death has been suggested by the recent finding that Craf1 interacts with members of the Bcl-2 family at mitochondrial membranes. However, genetic studies of C. elegans and Drosophila, as well as the targeted mutagenesis of the murine Araf gene, have failed to support such a role. Here we show that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation. Braf -/- embryos, unlike Araf -/- or Craf1 -/- embryos (L.W. et al., unpublished), show an increased number of endothelial precursor cells, dramatically enlarged blood vessels and apoptotic death of differentiated endothelial cells. These results establish Braf as a critical signalling factor in the formation of the vascular system and provide the first genetic evidence for an essential role of Raf gene in the regulation of programmed cell death.

Animals↗
PubMed1996

Regulation of A-raf expression.

The Raf family proto-oncogenes encode cytoplasmic protein serine/threonine kinases which play a critical role in cell growth and development. A-raf shares several functional properties with Raf-1 including transforming activity, stimulation of the Raf/MAPK pathway and the ability of dominant negative versions to functionally block Ras signalling. A-raf transcripts are predominantly expressed in the mouse urogenital tissues. Interestingly, the human A-raf promoter region contains three potential glucocorticoid response elements GRE-1, GRE-2 and GRE-3, at positions -17, -34 and -168 respectively from the transcriptional start site. DNA sequence analysis of the mouse A-raf promoter region demonstrated that GRE-1 and -2 were conserved evolutionarily. To determine whether the human A-raf GREs represent functional motifs, an expression vector for the glucocorticoid receptor was cotransfected with A-raf promoter/reporter constructs into HeLa cells. A fivefold dexamethasone-dependent induction of A-raf promoter activity was observed using constructs containing all three GRE motifs whereas point mutations in the GREs either diminished or abolished dexamethasone induction. Electrophoretic mobility shift assays (EMSAs) using purified glucocorticoid receptor DNA binding domain (DBD) demonstrated that both GRE-2 and -3 motifs interact with DBD and oligonucleotide competition experiments established that these have different affinities for DBD. Using nuclear extracts from human and rodent cell lines in EMSAs, a specific protein-DNA complex was observed with GRE-1 which displayed binding properties unlike that of glucocorticoid receptor. These results demonstrate that the A-raf promoter is regulated in part by members of the glucocorticoid family of steroid hormone receptors and suggest a model for the regulation of A-raf expression in urogenital tissues.

Animals↗
PubMed1996

Effect of intracellular pH on force development depends on temperature in intact skeletal muscle from mouse.

The cellular mechanism of muscle fatigue is still in debate. Opposite conclusions regarding the role of intracellular pH (pHi) in fatigue have been drawn from skinned fiber vs. isolated perfused muscle studies. Because these experiments are typically performed at different temperatures, we tested the hypothesis that temperature alters the effects of pH on force. Tetanic force of isolated mouse extensor digitorum longus was measured at temperatures between 13 and 25 degrees C in either normocapnia (5% CO2) or hypercapnia (25% CO2). Hypercapnia decreased pHi (monitored by 31P nuclear magnetic resonance spectroscopy) by the same amount at both 15 and 25 degrees C. However, inhibition of force by hypercapnia was greater at the lower temperature. A similar pattern of temperature-dependent inhibition of force by pH was observed in glycerinated fibers from rabbit psoas at maximum Ca2+ activation. We conclude that temperature differences are responsible for disparate conclusions on the role of pHi in muscle fatigue. Based on our results, we suggest that changes in pHi may have little or no role in the loss in force production associated with muscular fatigue at physiological temperatures.

Animals↗
PubMed1995

Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine.

The efficacy of pre- and postexposure treatment with the antiviral compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian immunodeficiency virus (SIV) in macaques as a model for human immunodeficiency virus (HIV). PMPA was administered subcutaneously once daily beginning either 48 hours before, 4 hours after, or 24 hours after virus inoculation. Treatment continued for 4 weeks and the virologic, immunologic, and clinical status of the macaques was monitored for up to 56 weeks. PMPA prevented SIV infection in all macaques without toxicity, whereas all control macaques became infected. These results suggest a potential role for PMPA prophylaxis against early HIV infection in cases of known exposure.

Adenine↗
PubMed1994

NADPH cytochrome P-450 oxidoreductase gene: identification and characterization of the promoter region.

The untranslated first exon and the 5'-flanking region for the rat liver NADPH-cytochrome P450 oxidoreductase gene has been isolated from a Wistar-Furth genomic library. The remainder of the gene is composed of 15 exons which code for the mature protein and a 3'-nontranslated segment (T. D. Porter et al. Biochemistry, 1990, 29, 9814-9818). The 56-bp first exon resides 30.5 kb upstream from exon two, making the total gene length approximately 50 kb. While the region surrounding the start site (TCAGAGAC) was found to be homologous to a eukaryotic cap signal, the 5' flanking region possesses neither a TATA nor a CCAAT box. Instead it contains five GC-rich hexanucleotide consensus sequences for the transcription factor Sp1. These features clearly distinguish it from genes encoding other members of the mixed-function oxidase system, the cytochromes P450. Primer extension analysis and S1 nuclease mapping identified multiple transcriptional start sites. In many respects, the TATA-less oxidoreductase promoter resembles the promoter regions of dihydrofolate reductase and other housekeeping genes. Northern blot analysis demonstrates that this promoter is modulated by phenobarbital and trans-stilbene oxide, known inducers of oxidoreductase.

Animals↗
PubMed1994

The complete sequence and promoter activity of the human A-raf-1 gene (ARAF1).

The raf proto-oncogenes encode cytoplasmic protein serine/threonine kinases, which play a critical role in cell growth and development. One of these, A-raf-1 (human gene symbol, ARAF1), which is predominantly expressed in mouse urogenital tissues, has been mapped to an evolutionarily conserved linkage group composed of ARAF1, SYN1, TIMP, and properdin located at human chromosome Xp11.2. We have isolated human genomic DNA clones containing the expressed gene (ARAF1) on the X chromosome and a pseudogene (ARAF2) on chromosome 7p12-q11.21. Analysis of the nucleotide sequence from the ARAF1 genomic clones demonstrated that it consists of 16 exons encoded by minimally 10,776 nucleotides. The major transcriptional start site (+1) was determined by RNase protection and primer extension assays. Promoter activity was confirmed by functional assays using DNA fragments fused to a CAT reporter gene. The ARAF1 minimal promoter, located between nucleotides -59 and +93, has a low G + C content and lacks consensus TATA and Inr sequences but shows sequence similarity at position -1 to the E box that is known to interact with USF and TFII-I transcription factors.

3T3 Cells↗
PubMed1991

Molecular charge dominates the inhibition of actomyosin in skinned muscle fibers by SH1 peptides.

It is not definitively known whether the highly conserved region of myosin heavy chain around SH1 (Cys 707) is part of the actin-binding site. We tested this possibility by assaying for competitive inhibition of maximum Ca-activated force production of skinned muscle fibers by synthetic peptides which had sequences derived from the SH1 region of myosin. Force was inhibited by a heptapeptide (IRICRKG) with an apparent K0.5 of about 4 mM. Unloaded shortening velocity of fibers, determined by the slack test, and maximum Ca-activated myofibrillar MgATPase activity were also inhibited by this peptide, but both required higher concentrations. We found that other cationic peptides also inhibited force in a manner that depended on the charge of the peptide; increasing the net positive charge of the peptide increased its efficacy. The inhibition was not significantly affected by altering solution ionic strength (100-200 mM). Disulfide bond formation was not involved in the inhibitory mechanism because a peptide with Thr substituted for Cys was inhibitory in the presence or absence of DTT. Our data demonstrate that the net charge was the predominant molecular characteristic correlated with the ability of peptides from this region of myosin heavy chain to inhibit force production. Thus, the hypothesis that the SH1 region of myosin is an essential part of the force-producing interaction with actin during the cross-bridge cycle (Eto, M., R. Suzuki, F. Morita, H. Kuwayama, N. Nishi, and S. Tokura., 1990, J. Biochem. 108:499-504; Keane et al., 1990, Nature (Lond.). 344:265-268) is not supported.

Actomyosin↗
PubMed1990

NADPH-cytochrome P-450 oxidoreductase gene organization correlates with structural domains of the protein.

cDNA clones to rat liver NADPH-cytochrome P-450 oxidoreductase were used to isolate genomic clones from a Wistar-Furth inbred rat genomic DNA library. Fifteen exons containing the coding region and 3'-nontranslated segment of the P-450 reductase gene were identified, spanning 20 kilobases of DNA contained in 3 lambda-Charon 35 clones. The organization of this single copy gene reveals a general correspondence between exons and structural domains of the protein, with the segment responsible for anchoring the reductase to the microsomal membrane and several segments involved in FMN, FAD, and NADPH binding encoded by discrete exons.

Amino Acid Sequence↗