Electromyographic Responses from the Vastus Medialis during Isometric Muscle Actions.

This study examined the electromyographic (EMG) responses from the vastus medialis (VM) for electrodes placed over and away from the innervation zone (IZ) during a maximal voluntary isometric contraction (MVIC) and sustained, submaximal isometric muscle action. A linear electrode array was placed on the VM to identify the IZ and muscle fiber pennation angle during an MVIC and sustained isometric muscle action at 50% MVIC. EMG amplitude and frequency parameters were determined from 7 bipolar channels of the electrode array, including over the IZ, as well as 10 mm, 20 mm and 30 mm proximal and distal to the IZ. There were no differences between the channels for the patterns of responses for EMG amplitude or mean power frequency during the sustained, submaximal isometric muscle action; however, there were differences between channels during the MVIC. The results of the present study supported the need to standardize the placement of electrodes on the VM for the assessment of EMG amplitude and mean power frequency. Based on the current findings, it is recommended that electrode placements be distal to the IZ and aligned with the muscle fiber pennation angle during MVICs, as well as sustained, submaximal isometric muscle actions.

Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells.

Exposure of BALB/c mice to mosquitoes infected with irradiated Plasmodium berghei confers protective immunity against subsequent sporozoite challenge. Immunized mice challenged with viable sporozoites develop parasitemia when treated orally with substrate inhibitors of nitric oxide synthase (NOS). This suggests that the production of nitric oxide (NO) prevents the development of exoerythrocytic stages of malaria in liver. Liver tissue from immunized mice expressed maximal levels of mRNA for inducible NOS (iNOS) between 12 and 24 h after challenge with sporozoites. Intraperitoneal injection of neutralizing monoclonal antibody against interferon gamma (IFN-gamma) or in vivo depletion of CD8+ T cells, but not CD4+ T cells, at the time of challenge blocked expression of iNOS mRNA and ablated protection in immunized mice. These results show that both CD8+ T cells and IFN-gamma are important components in the regulation of iNOS in liver which contributes to the protective response of mice immunized with irradiated malaria sporozoites. IFN-gamma, likely provided by malaria-specific CD8+ T cells, induces liver cells, hepatocytes and/or Kupffer cells, to produce NO for the destruction of infected hepatocytes or the parasite within these cells.

Wavelet-based analysis of surface mechanomyographic signals from subjects with differences in myosin heavy chain isoform content.

The purpose of this study was to use a wavelet analysis designed specifically for surface mechanomyographic (MMG) signals to determine if the % myosin heavy chain (MHC) isoform content affected the shape of the MMG frequency spectrum during isometric muscle actions. Five resistance-trained (mean +/- SD age = 23.2 +/-3.7 yrs), five aerobically-trained (mean +/- SD age = 32.6 +/- 5.2 yrs), and five sedentary (mean +/- SD age = 23.4 +/- 4.1 yrs) men performed isometric muscle actions of the dominant leg extensors at 20%, 40%, 60%, 80%, and 100% of the maximum voluntary contraction (MVC). Surface MMG signals were detected from the vastus lateralis during each muscle action and processed with the MMG wavelet analysis. In addition, muscle biopsies were taken from the vastus lateralis and analyzed for % MHC isoform content. The results showed that there were distinct differences among the three groups of subjects for % MHC isoform content. These differences were not manifested, however, in the isometric force-related changes in the total intensity of the MMG signal in each wavelet band. It is possible that factors such as the thicknesses of the subcutaneous adipose tissue and/or iliotibial band reduced the potential influence of differences in % MHC isoform content on the MMG signal.

Sex-related differences in muscle size explained by amplitudes of higher-threshold motor unit action potentials and muscle fibre typing.

AIM: To investigate the relationships between motor unit action potential amplitudes (MUAPAMP ), muscle cross-sectional area (mCSA) and composition (mEI), per cent myosin heavy chain (%MHC) areas and sex in the vastus lateralis (VL). METHODS: Ten males and 10 females performed a submaximal isometric trapezoid muscle action that included a linearly increasing, steady torque at 40% maximal voluntary contraction, and linearly decreasing segments. Surface electromyographic decomposition techniques were utilized to determine MUAPAMPS in relation to recruitment thresholds (RT). Ultrasound images were taken to quantify muscle mCSA and mEI. Muscle biopsies were collected to calculate %MHC areas. Y-intercepts and slopes were calculated for the MUAPAMP vs RT relationships for each subject. Independent-samples t tests and ANOVA models examined sex-related differences in mCSA, mEI, slopes and y-intercepts for the MUAPAMP vs RT relationships and %MHC areas. Correlations were performed among type IIA and total type II %MHC area, mCSA and the slopes and y-intercepts for the MUAPAMP vs RT relationships. RESULTS: Males exhibited greater slopes for the MUAPAMP vs RT relationships (P = .003), mCSA (P < .001) and type IIA %MHC (P = .011), whereas females had greater type I %MHC area (P = .010) and mEI (P = .024). The mCSA, type IIA and total II %MHC area variables were correlated (P < .001-.015, r = .596-.836) with the slopes from the MUAPAMP vs RT relationships. CONCLUSION: Sex-related differences in mCSA and MUAPAMPS of the higher-threshold MUs were likely the result of larger muscle fibres expressing type II characteristics for males.

The effect of pedaling cadence and power output on mechanomyographic amplitude and mean power frequency during submaximal cycle ergometry.

The purpose of this study was to examine the effects of power output and pedaling cadence on the amplitude and mean power frequency (MPF) of the mechanomyographic (MMG) signal during submaximal cycle ergometry. Nine adults (mean age +/- SD = 22.7 +/- 2.1 yrs) performed an incremental (25 W increase every min) test to exhaustion on an electronically braked cycle ergometer to determine VO2Peak and Wpeak. The subjects also performed three, 8 min continuous, constant power output rides (randomly ordered) at 35%, 50%, and 65% Wpeak. The continuous 8 min workbouts were divided into 4 min epochs. The subjects pedaled at either 50 or 70 rev x min(-1) (randomized) during the first 4 min epoch, then changed to the alternate cadence during the second 4 min epoch. The MMG signal was recorded from the vastus lateralis during the final 10 s of each minute. Two separate two-way [cadence (50 and 70 rev x min(-1)) x %Wpeak (35, 50, and 65)] repeated measures ANOVAs indicated that MMG amplitude followed power output, but not pedaling cadence, whereas MMG MPF was not consistently affected by power output or pedaling cadence. Furthermore, these findings suggested that power output was modulated by motor unit recruitment and not rate coding.

The influence of muscle fiber type composition on the patterns of responses for electromyographic and mechanomyographic amplitude and mean power frequency during a fatiguing submaximal isometric muscle action.

The purpose of this investigation was to examine the influence of muscle fiber type composition on the patterns of responses for electromyographic (EMG) and mechanomyographic (MMG) amplitude and mean power frequency (MPF) during a fatiguing submaximal isometric muscle action. Five resistance-trained (mean +/- SD age = 23.2 +/- 3.7 yrs) and five aerobically-trained (mean +/- SD age = 32.6 +/- 5.2 yrs) men volunteered to perform a fatiguing, 30-sec submaximal isometric muscle action of the leg extensors at 50% of the maximum voluntary contraction (MVC). Muscle biopsies from the vastus lateralis revealed that the myosin heavy chain (MHC) composition for the resistance-trained subjects was 59.0 +/- 4.2% Type IIa, 0.1 +/- 0.1% Type IIx, and 40.9 +/- 4.3% Type I. The aerobically-trained subjects had 27.4 +/- 7.8% Type IIa, 0.0 +/- 0.0% Type IIx, and 72.6 +/- 7.8% Type I MHC. The patterns of responses and mean values for absolute and normalized EMG amplitude and MPF during the fatiguing muscle action were similar for the resistance-trained and aerobically-trained subjects. The resistance-trained subjects demonstrated relatively stable levels for absolute and normalized MMG amplitude and MPF across time, but the aerobically-trained subjects showed increases in MMG amplitude and decreases in MMG MPE The absolute MMG amplitude and MPF values for the resistance-trained subjects were also greater than those for the aerobi-cally-trained subjects. These findings suggested that unlike surface EMG, MMG may be a useful noninvasive technique for examining fatigue-related differences in muscle fiber type composition.

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.

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.

Herpesvirus vector-mediated gene delivery to human monocytes.

In vitro delivery of interferon-alpha (IFN-alpha) to cultured human monocytes by means of a replication-incompetent herpesvirus vector inhibits human immunodeficiency virus (HIV) replication. To explore the possibility of IFN-alpha gene delivery by vector-infected human monocytes, monocytes were isolated and the culture conditions necessary for efficient vector infection and gene expression were examined. Monocytes were efficiently infected between 1 and 7 days after isolation. Expression of IFN-alpha was greater in cells infected 7 days after isolation compared to 1 day after isolation, but the levels of expression were equivalent regardless of whether cells were maintained in suspension or monolayer culture. When suspension-cultured monocytes were treated with vd120/IFN-alpha and added to monolayer cultures of HIV-infected monocytes, IFN-alpha was expressed and replication of HIV was inhibited. HIV replication was arrested even when HIV had spread through much of the monolayer. The persistence of the viral vector in infected cells was examined by a superinfection rescue assay using a second replication-incompetent herpes simplex virus, 5dl1.2. The initial replication-incompetent vector remained in a recoverable form for at least 7 days after delivery, even though foreign gene expression was transient.

In vivo delivery of interleukin-4 by a recombinant vaccinia virus prevents tumor development in mice.

To study the immunotherapeutic potential of interleukin-4 (IL-4) delivered in vivo via a recombinant vaccinia virus, a thymidine kinase-negative (TK-) vaccinia virus that expressed the murine IL-4 gene (VV1/IL-4) was constructed. When mice were inoculated with 10(7) plaque-forming units (pfu) of VV1/IL-4 subcutaneously (s.c.), 10(5) pfu/cm2 were found in skin, and smaller numbers in liver and kidney between 1 and 7 days after infection; few viral pfu were found in spleen and lung, or in any organ after intravenous infection. This suggested that recombinant vaccinia viruses might be most efficient at delivery of cytokine genes to the skin. Because IL-4 has recently been found to have potent anti-tumor activity, the effect of recombinant virus infection on the development of s.c. tumors was studied. A single s.c. inoculation with VV1/IL-4 delayed the development of NCTC 2472 tumors, but when VV1/IL-4 was inoculated s.c. weekly for 8 weeks, tumor development was completely prevented in 93% of mice. Similarly, the development of M-3 melanoma tumors was also prevented by weekly s.c. inoculations of VV1/IL-4. About 40% of mice treated with control VV2/beta gal by the same regimen also failed to develop tumors. Weekly virus treatment did not prevent NCTC 2472 tumor development in athymic nu/nu mice, suggesting that mature T cells are required for expression of VV1/IL-4 induced antitumor activity. Thus, recombinant vaccinia viruses may be especially well suited for convenient therapeutic delivery of immunomodulator genes to skin-related sites.

Regulation of herpes simplex virus gene expression.

Expression of the more than 80 individual genes of herpes simplex virus 1 (HSV-1) takes place in a tightly regulated sequential manner that was first described over 20 years ago. Investigations since that time have focused on understanding the mechanisms that regulate this orderly and efficient expression of viral genes. This review examines recent findings that have shed light on how this process is regulated during productive infection of the cell. Although the story is still not complete, several aspects of HSV gene expression are now clearer as a result of these findings. In particular, several new functions have recently been ascribed to some of the known viral regulatory proteins. The results indicate that the viral gene expression is regulated through transcriptional as well as post-transcriptional mechanisms. In addition, it has become increasingly clear that the virus has evolved specific functions to interact with the host cell in order to divert and redirect critical host functions for its own needs. Understanding the interactions of HSV and the host cell during infection will be essential for a complete understanding of how viral gene expression is regulated. Future challenges in the field will be to develop a complete understanding of the mechanisms that temporally regulate virus gene expression, and to identify and characterize the relevant interactions between the virus and the distinctive cell types normally infected by the virus.

Plasmid insertion vectors that facilitate construction of herpes simplex virus gene delivery vectors.

Plasmid insertion vectors were designed for the expression of foreign genes in recombinant herpes simplex virus (HSV) vectors. One vector, pGal9, was designed for the insertion of foreign genes with their own promoter; a second vector, pGal10, was designed for the insertion of coding sequences downstream from the HSV immediate-early 110K promoter. The 110K promoter directed efficient expression of foreign genes, particularly in replication-incompetent virus recombinants, as shown by the expression of the lacZ and IFN alpha genes. These vectors should be useful for the characterization of various promoters for gene delivery, and for the efficient expression of foreign genes in a variety of cell types.

An insertion vector for the analysis of gene expression during herpes simplex virus infection.

A herpes simplex virus type 1 (HSV-1) insertion vector, pGal8, was designed for analysis of herpesvirus promoters during virus infection. This vector contains a multiple cloning site (MCS) positioned at the 5' end of the lacZ gene for the insertion of promoter sequences. The MCS and lacZ are flanked by sequences from the HSV-1 thymidine kinase encoding gene (tk) to direct homologous recombination into the tk locus of the viral genome. The utility of this vector is demonstrated by construction and comparison of recombinant viruses that express lacZ from the promoters of the genes encoding glycoprotein C, glycoprotein H and glycoprotein E.

The relative stability of selected herpes simplex virus type 1 mRNAs.

The relative stability of herpes simplex virus type 1 mRNAs was investigated by examination of the decay rates of selected viral transcripts. The synthesis of mRNA was inhibited by the addition of dactinomycin to HSV-1 infected cells, and the abundance of individual transcripts was determined at subsequent times by RNA blot hybridization. For two immediate-early mRNAs, those encoding the 110 and 63 kilodalton immediate-early proteins, RNA synthesis was inhibited at 3 h post-infection and mRNA half-lives of 5-7 h were found. Examination at 5 h post-infection of the early mRNA encoding thymidine kinase as well as the late mRNA encoding glycoprotein H revealed half-lives of 8-11 h. In contrast, at 12 h post-infection, the late mRNAs encoding the glycoproteins C, E, as well as H were found to have half-lives of 14-29 h. These findings suggest that the relative stability of viral mRNA increases late in infection and is dependent upon the time after infection rather than being strictly a property of the mRNA itself.

Expression of the human immunodeficiency virus gag gene products by a replication-incompetent herpes simplex virus vector.

A recombinant replication-incompetent herpes simplex virus vector (vd120/Gag) that expressed the human immunodeficiency virus 1 gag gene and part of the pol gene that encodes the HIV-1 protease was constructed. Examination of cells infected with vd120/Gag revealed the presence of the Gag polyprotein Pr55gag by 12 h post-infection, as well as abundant levels of the proteolytically processed 24-kDa capsid protein. Analysis of vector-infected cells and culture supernatant indicated that the majority of the 24-kDa protein remained cell-associated. Although the HIV-1 Gag polyprotein was produced in vd120/Gag-infected cells, there was no evidence of HIV virus-like particle production upon examination of vector-infected cells by transmission electron microscopy.

The proportion of herpes simplex virus-specific cytotoxic T lymphocytes (Tc) that recognize glycoprotein C varies between individual mice and is dependent on the form of immunization.

In mice the immune response to HSV-1 includes a brisk Tc response that is intimately associated with the control of infection. This report evaluated the Tc response to gC, one of the envelope glycoproteins of HSV-1. This protein was recognized as a target antigen for Tc from HSV-1 immune mice only if they expressed the H-2Kb MHC allele. However, even within these "responder" strains of mice the proportion of gC specific Tc was highly variable. The failure of HSV-induced Tc to recognize gC in the context of other class 1 MHC haplotypes (H-2d and H-2k) was demonstrable at the clonal level and could not be attributed to peculiarities of the recombinant constructs. Surprisingly, despite the inability of H-2k-restricted, HSV-1-induced Tc to recognize gC, when a vaccinia gC virus construct was used to immunize H-2k strains of mice it showed a variable ability to induce memory Tc populations capable of lysing HSV-1-infected autologous cells. Of added importance was the correlation of this induced Tc response with optimum protection against subsequent challenge with HSV-1. This demonstrated that despite the presence of suitable epitopes, the context of the immunogen would also influence its ability to induce Tc. Consequently, the potential repertoire of available HSV-1-specific Tc specificities is larger than indicated by studying animals immunized with HSV.

Role of coexpression of IL-2 and herpes simplex virus proteins in recombinant vaccinia virus vectors on levels of induced immunity.

Vaccinia virus recombinants co-expressing the genes for IL-2 and HSV-1 gC or gD were used to study the potential adjuvant effects of IL-2 on immunity to HSV-1. In addition, constructs were produced which, while expressing IL-2, encoded for reduced levels of HSV-1 gC. Studies with mice revealed that gC and gD could stimulate HSV-1 immunity as measured by neutralizing antibody (NA), lymphoproliferation and viral clearance. IL-2 enhancement of NA and lymphoproliferation was observed only in those groups of mice immunized with the sub-optimal gC construct which co-expressed IL-2. In no instance did the presence of IL-2 augment the ability of mice to clear an epithelial challenge of HSV-1.

Electromyographic evaluation of joint angle specificity and cross-training after isometric training.

The purpose of this study was to examine the effects of unilateral strength training on the strength and integrated electromyogram (IEMG) of the trained and untrained limbs at several joint angles. A training group [TRN; 4 females and 3 males, age 22 +/- 4 yr (SD)] exercised for 6 wk with isometric leg extensions at 80% of maximal isometric torque. A control group (3 females and 3 males, age 24 +/- 4 yr) did not exercise. The training was performed three times per week at 0.79 rad below the horizontal plane. The subjects were tested at joint angles of 0.00, 0.26, 0.79, 1.31, and 1.57 rad. Bipolar surface electrodes were used to record the IEMG of the vastus lateralis. The results indicated a cross-training effect and joint angle specificity for isometric torque in TRN only, with significant (P < 0.0005) increases in torque (collapsed across limb) at 0.26 (23.3%) and 0.79 (22.3%) rad. There was a dissociation, however, between changes in torque and IEMG with an increase (P < 0.05) in IEMG (collapsed across limb and angle) for TRN. The dissociation between the IEMG and strength changes was possibly due to differential responses to training in the four muscles of the quadriceps femoris.

Acute effects of different intensities of weight lifting on serum testosterone.

The purpose of this investigation was to determine the effect of moderate weight lifting (MWL) and light weight lifting (LWL) on concentrations of serum testosterone in males. Baseline testosterone concentrations were determined via an indwelling catheter in the median cubital vein. An initial sample of blood was followed 7 min later by five samples taken at 4-min intervals. A final sample was taken 10 min after the last 4-min blood draw. Blood samples were obtained at similar times and intervals on the weight lifting days. The MWL consisted of four sets of six squats at 90-95% of a six-repetition maximum (RM), while the LWL consisted of four sets of 9 or 10 repetitions at 60-65% of the weight used for the sets during MWL. There was a significant increase in serum testosterone concentrations following the fourth set for both MWL and LWL when compared with baseline concentrations and both MWL and LWL testosterone concentrations returned to baseline levels at 10 min postexercise. These results indicate that MWL and LWL caused increases in serum testosterone that were greater than those associated with baseline levels. Postexercise responses for the MWL and LWL were similar.

Anthropometric estimation of thigh muscle cross-sectional area.

The purpose of this investigation was to derive and validate circumference and skinfold equations for estimating the anatomical cross-sectional area (CSA) of the quadriceps, hamstrings, and total thigh muscles. Forty-three adult male (mean age +/- SD = 25 +/- 5 yr) volunteers underwent magnetic resonance imaging (MRI) to determine the CSA of the thigh muscles at the midfemur level as well as midthigh circumference and anterior thigh skinfold assessment. Multiple regression analyses were used to derive equations for predicting quadriceps, hamstrings, and total thigh muscle CSA of the dominant limb from the anthropometric dimensions on a random sample of 30 of the subjects. Cross-validation (CV) analyses were performed for each equation on: (a) the nondominant thigh of the derivation group (N = 30); (b) the dominant thigh of the CV group (N = 13); and (c) the nondominant thigh of the CV group (N = 13). The CV total error values for the quadriceps, hamstrings, and total thigh muscle CSA ranged from 5.4 to 14.4, 3.3 to 5.5, and 10.0 to 25.4 cm2, respectively. The anthropometric equations are recommended for one-time estimates of muscle CSA values in healthy, well-nourished young adult males when more sophisticated procedures are not available.