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Biomedical subjects

Vincent J Caiozzo

Publications and source records attributed to Vincent J Caiozzo.

At least 19 recordsLinked to original sources
PubMed2006

Maintenance of slow type I myosin protein and mRNA expression in overwintering prairie dogs (Cynomys leucurus and ludovicianus) and black bears (Ursus americanus).

Hibernating mammals have the remarkable ability to withstand long periods of fasting and reduced activity with dramatic maintenance of skeletal muscle function and protein composition. We investigated several hindlimb muscles of white-tailed prairie dogs (Cynomys leucurus) and black bears (Ursus americanus), two very different hibernators who are dormant and fasting during winter. The black-tailed prairie dog (C. ludovicianus) remains active during winter, but suffers minor skeletal muscle atrophy; nevertheless, they also demonstrate apparent skeletal muscle adaptations. Using SDS-PAGE, we measured myosin protein isoform profiles before and after the hibernation season. All species maintained or increased levels of slow myosin, despite the collective physiological challenges of hypophagia and reduced activity. This contrasts markedly with standard mammalian models of skeletal muscle inactivity and atrophy predicting significant loss of slow myosin. A mechanism for changes in myosin isoforms was investigated using reverse-transcription PCR, following partial sequencing of the adult MHC isoforms in C. leucurus and U. americanus. However, mRNA expression was not well correlated with changes in MHC protein isoforms, and other synthesis and degradation pathways may be involved besides transcriptional control. The muscles of hibernating mammals demonstrate surprising and varied physiological responses to inactivity and atrophy with respect to slow MHC expression.

Animals↗
PubMed2006

Maximal oxygen uptake at the same fat-free mass is greater in men than women.

Maximal oxygen uptake (VO(2max)) is commonly divided by body mass or fat-free mass (body mass minus fat mass) in order to make it size independent so that comparisons among persons of different size can be made. However, numerous studies have shown that the ratio created is not size-independent. Analysis of covariance (ANCOVA) allows a dependent variable to be compared between groups at a common value of a covariate. The purpose of this study was to compare VO(2max) at the same fat-free mass (FFM) in 230 sedentary subjects (half men) who ranged in age from 20 to 70 years. The subjects underwent maximal cardiopulmonary exercise testing on a cycle ergometer as ventilation and the expired gas fractions were being measured. Two ANCOVA models were evaluated. The dependent variable, fixed factor and covariate(s) in the linear model were VO(2max), sex and FFM, respectively. The corresponding terms in the log-linear model were ln VO(2max), sex, and ln FFM and age. Sex made a significant contribution to both models. In the linear model, the mean VO(2max) at the same FFM was 27% higher in men (2,444 versus 1,929 ml min(-1); P<0.001). In the log-linear model, the corresponding value at the same FFM and age was 32% higher in men (2,368 versus 1,794 ml min(-1); P<0.001). The goodness of fit indices of squared multiple correlation coefficient and standard error of estimate were significantly better for the log-linear model. We conclude that VO(2max) at the same FFM is considerably higher in men than in women who have a sedentary lifestyle.

Adult↗
PubMed2005

Pathogenic accumulation of APP in fast twitch muscle of IBM patients and a transgenic model.

Inclusion body myositis (IBM) is the most common age-related degenerative skeletal muscle disorder. The aberrant intracellular accumulation of the beta-amyloid (Abeta) peptide within skeletal muscle is a pathological hallmark of IBM. Skeletal muscle is comprised of both slow and fast twitch fibers, which are present in different proportions in various muscles. It remains unclear if fast and/or slow twitch fibers are differentially involved in IBM pathogenesis. To better understand the molecular pathogenesis of IBM, we analyzed human IBM muscle biopsies and muscle from a transgenic mouse model of IBM (MCK-betaAPP). Here we report that the majority of histopathologically-affected fibers in human IBM biopsies were type II fast fibers. Skeletal muscle from MCK-betaAPP mice exhibited higher transgene expression and steady-state levels of human betaAPP in fast type IIB fibers compared to slow type I fibers. These findings indicate that fast twitch fibers may selectively accumulate and be more vulnerable to betaAPP- and Abeta-mediated damage in IBM. These findings also highlight parallels between the MCK-betaAPP mice and the human IBM condition.

Aged↗
PubMed2005

Early effects of mechanical ventilation on isotonic contractile properties and MAF-box gene expression in the diaphragm.

This study aimed to determine the time-dependent effects of diaphragmatic inactivity on its maximum shortening velocity (V(max)) and the muscle atrophy F-box (MAF-box, atrogin-1) gene expression during controlled mechanical ventilation (CMV). Twenty-four New Zealand White rabbits were grouped into 1 day, 2 days, and 3 days of CMV and controls in equal numbers. The in vitro isotonic contractile properties of the diaphragm were determined. In addition, myosin heavy chain protein and mRNA, myosin light chain, MAF-box mRNA, and volume density of abnormal myofibrils were measured. Tetanic force decreased, and V(max) increased from control of 6.4 to 6.6, 7.7, and 8.1 muscle lengths per second after 1, 2, and 3 days of CMV, respectively (P < 0.02). The increased V(max) compensated for the decreased tetanic force; consequently, compared with the controls, maximum power output was unchanged after 3 days of CMV. V(max) correlated with the volume density of abnormal myofibrils [y = 0.1x + 5.7 (r = 0.87, P < 0.01)]. In the diaphragm, MAF-box was overexpressed (355% of control) after 1 day of CMV, before the evidence of structural myofibril disarray. In conclusion, CMV produced a time-dependent increase in V(max) that was associated with the degree of myofibrillar disarray and independent of changes in myosin isoform expression. Furthermore, CMV produced an increase in MAF-box mRNA levels that may be partially or completely responsible for the degree of myofibrillar disarray resulting from CMV.

Animals↗
PubMed2005

Physiology: postprandial cardiac hypertrophy in pythons.

Oxygen consumption by carnivorous reptiles increases enormously after they have eaten a large meal in order to meet metabolic demands, and this places an extra load on the cardiovascular system. Here we show that there is an extraordinarily rapid 40% increase in ventricular muscle mass in Burmese pythons (Python molurus) a mere 48 hours after feeding, which results from increased gene expression of muscle-contractile proteins. As this fully reversible hypertrophy occurs naturally, it could provide a useful model for investigating the mechanisms that lead to cardiac growth in other animals.

Adaptation, Physiological↗
PubMed2004

Cloning and sequencing of myosin heavy chain isoform cDNAs in golden-mantled ground squirrels: effects of hibernation on mRNA expression.

The golden-mantled ground squirrel is a small rodent hibernator that demonstrates unusual myosin heavy chain (MHC) isoform plasticity during several months of torpor, punctuated by bouts of rewarming and shivering thermogenesis. We measured MHC mRNA levels to determine whether pretranslational control mechanisms were responsible for differences in MHC2x protein expression, as we previously observed between active and hibernating ground squirrels. We first cloned cDNA using the 3' rapid amplification of cDNA ends (3' RACE) technique and identified three sequences corresponding to MHC1, MHC2x, and MHC2b. A DNA control fragment was developed to be used in conjunction with a coupled RT-PCR reaction to simultaneously measure MHC mRNA levels for each isoform in the skeletal muscle of ground squirrels. MHC mRNA and protein expression were strongly correlated, and type IIx and IIb mRNA levels were significantly different between active and hibernating ground squirrels. Pretranslational control of MHC protein is apparently an important process during hibernation, although the exact stimulus is not known. The techniques presented can be used to obtain MHC cDNA sequences and to measure mRNA expression in many vertebrate groups.

Animals↗
PubMed2004

Assist-control mechanical ventilation attenuates ventilator-induced diaphragmatic dysfunction.

Controlled mechanical ventilation induced a profound diaphragm muscle dysfunction and atrophy. The effects of diaphragmatic contractions with assisted mechanical ventilation on diaphragmatic isometric, isotonic contractile properties, or the expression of muscle atrophy factor-box (MAF-box), the gene responsible for muscle atrophy, are unknown. We hypothesize that assisted mechanical ventilation will preserve diaphragmatic force and prevent overexpression of MAF-box. Studying sedated rabbits randomized equally into control animals, those with 3 days of assisted ventilation, and those with controlled ventilation, we assessed in vitro diaphragmatic isometric and isotonic contractile function. The concentrations of contractile proteins, myosin heavy chain isoform, and MAF-box mRNA were measured. Tetanic force decreased by 14% with assisted ventilation and 48% with controlled ventilation. Maximum shortening velocity tended to increase with controlled compared with assisted ventilation and control. Peak power output decreased 20% with assisted ventilation and 41% with controlled ventilation. Contractile proteins were unchanged with either modes of ventilation; myosin heavy chain 2X mRNA tended to increase and that of 2A to decrease with controlled ventilation. MAF-box gene was overexpressed with controlled ventilation. We conclude that preserving diaphragmatic contractions during mechanical ventilation attenuates the force loss induced by complete inactivity and maintains MAF-box gene expression in control.

Actins↗
PubMed2004

Effects of exercise on gene expression in human peripheral blood mononuclear cells.

Exercise leads to increases in circulating levels of peripheral blood mononuclear cells (PBMCs) and to a simultaneous, seemingly paradoxical increase in both pro- and anti-inflammatory mediators. Whether this is paralleled by changes in gene expression within the circulating population of PBMCs is not fully understood. Fifteen healthy men (18-30 yr old) performed 30 min of constant work rate cycle ergometry (approximately 80% peak O2 uptake). Blood samples were obtained preexercise (Pre), end-exercise (End-Ex), and 60 min into recovery (Recovery), and gene expression was measured using microarray analysis (Affymetrix GeneChips). Significant differential gene expression was defined with a posterior probability of differential expression of 0.99 and a Bayesian P value of 0.005. Significant changes were observed from Pre to End-Ex in 311 genes, from End-Ex to Recovery in 552 genes, and from Pre to Recovery in 293 genes. Pre to End-Ex upregulation of PBMC genes related to stress and inflammation [e.g., heat shock protein 70 (3.70-fold) and dual-specificity phosphatase-1 (4.45-fold)] was followed by a return of these genes to baseline by Recovery. The gene for interleukin-1 receptor antagonist (an anti-inflammatory mediator) increased between End-Ex and Recovery (1.52-fold). Chemokine genes associated with inflammatory diseases [macrophage inflammatory protein-1alpha (1.84-fold) and -1beta (2.88-fold), and regulation-on-activation, normal T cell expressed and secreted (1.34-fold)] were upregulated but returned to baseline by Recovery. Exercise also upregulated growth and repair genes such as epiregulin (3.50-fold), platelet-derived growth factor (1.55-fold), and hypoxia-inducible factor-I (2.40-fold). A single bout of heavy exercise substantially alters PBMC gene expression characterized in many cases by a brisk activation and deactivation of genes associated with stress, inflammation, and tissue repair.

Adolescent↗
PubMed2004

Effects of denervation on cell cycle control in laryngeal muscle.

Denervation of skeletal muscle is thought to lead to an accelerated proliferation of myogenic stem cells known as satellite cells. The transition of these cells from a quiescent to a proliferative state is thought to require satellite cells to enter the cell cycle and replicate. Little is known about the expression of genes associated with cell cycle control, and so the objective of this study was to examine the effects of denervation and reinnervation of the posterior cricoarytenoid (PCA) muscle on key cell cycle genes. Female Sprague-Dawley rats were assigned to control, denervated, or reinnervated groups. Animals were killed at 7, 14, and 30 days after ligation of the recurrent laryngeal nerve. The PCA muscle was then analyzed for changes in the messenger RNA levels of key genes associated with cell cycle control, differentiation, and proliferation. Cyclin D1 is a key gene responsible for initiating progression of the cell cycle from G1 to S phase. Interestingly, neither denervation nor reinnervation affected the expression of this gene. In contrast, we found large increases in key cell cycle inhibitors (p21 and the growth arrest and DNA destruction 45 [GADD45] gene) in both the denervated and reinnervated groups. We interpret the increases in these cell cycle inhibitors to reflect (1) an inhibition of satellite cell proliferation and/or (2) a special form of apoptosis that results in the loss of myonuclei known to occur under atrophic conditions. To our knowledge, this is the first study to examine the effects of denervation on cell cycle regulation.

Analysis of Variance↗
PubMed2004

The plasticity of denervated and reinnervated laryngeal muscle: focus on single-fiber myosin heavy-chain isoform expression.

No studies have examined the effects of denervation on the single-fiber distribution of myosin heavy-chain (MyHC) isoforms in laryngeal muscle. The fast type IIB MyHC isoform represents the largest proportion of the myosin pool in the posterior cricoarytenoid (PCA) and the thyroarytenoid (TA) muscles. However, the fast type IIB MyHC isoform is distributed differently at the single-fiber level. Hence, we hypothesized that denervation would result in markedly different patterns of MyHC isoform expression at the single-fiber level. To test this hypothesis, we assigned animals to the following 3 groups: (1) control group; (2) denervation group; or (3) reinnervation group. Animals were killed 7, 14, 30, 90, and 180 days after denervation or reinnervation. Subsequently, the distribution of MyHC isoforms were electrophoretically determined in approximately 7200 single fibers. There were 4 key findings to emerge from this study: (1) The MyHC isoform profile of the PCA muscle, at both the whole-muscle and single-fiber level, is more malleable than that of the TA muscle. (2) In the PCA and TA muscles, denervation produced some similar changes, resulting in a large increase in the pool of fibers coexpressing fast type IIX and IIB MyHC isoforms. (3) Reinnervation of the TA muscle produced significant alterations in the single-fiber distribution of MyHC isoforms while having little effect on the whole-muscle MyHC isoform composition. (4) Since the transitions in MyHC isoform expression associated with denervation were limited primarily to fast type IIB to fast type IIX, we postulate that only minor reductions in muscle function would result (as defined by maximum shortening velocity and the force-velocity relationship).

Analysis of Variance↗
PubMed2004

Hemodynamic and metabolic responses to hypergravity on a human-powered centrifuge.

INTRODUCTION: Microgravity causes the deconditioning of many physiological systems, and there is great interest in developing effective countermeasures. We recently developed a short-arm human-powered centrifuge, and the primary objective of this study was to assess the hemodynamic and metabolic responses to exercise under hypergravity conditions. METHODS: Phase I compared the hemodynamic and metabolic responses to 1 Gz (upright cycle ergometry) and 2 Gz conditions (Space Cycle) at the same work rate. Phase II contrasted the hemodynamic and metabolic responses at 2 and 3 Gz and at the same work rate. Phase III examined the BP and heart rate (HR) responses during passive and active centrifugation. Phase IV examined the relationship between work rate and oxygen uptake. RESULTS: In Phase I, the HR and BP responses were very similar between the two Gz conditions, with the exception that 2 Gz produced a lower diastolic BP in female subjects. In Phase II, both systolic and diastolic BPs were similar under the two different Gz conditions. However, there was a significant increase in HR at 3 Gz. In Phase III, the slope of the HR/Gz relationship was greater for passive conditions, suggesting that venous return is facilitated by the skeletal muscle pump. In Phase IV, it was found that there was a highly linear relationship between work rate and oxygen uptake. CONCLUSION: The results of this study demonstrate that exercise under low hypergravity conditions on the Space Cycle is well tolerated from a hemodynamic perspective.

Adult↗
PubMed2003

Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?

Previous studies have reported the existence of skeletal muscle fibers that coexpress multiple myosin heavy chain isoforms. These surveys have usually been limited to studying the polymorphic profiles of skeletal muscle fibers from a limited number of muscles (i.e., usually <4). Additionally, few studies have considered the functional implications of polymorphism. Hence, the primary objective of this study was to survey a relatively large number of rat skeletal muscle/muscle regions and muscle fibers (n approximately 5,000) to test the hypothesis that polymorphic fibers represent a larger fraction of the total pool of fibers than do so-called monomorphic fibers, which express only one myosin heavy chain isoform. Additionally, we used Hill's statistical model of the force-velocity relationship to differentiate the functional consequences of single-fiber myosin heavy chain isoform distributions found in these muscles. The results demonstrate that most muscles and regions of rodent skeletal muscles contain large proportions of polymorphic fibers, with the exception of muscles such as the slow soleus muscle and white regions of fast muscles. Several muscles were also found to have polymorphic profiles that are not consistent with the I<-->IIA<-->IIX<-->IIB scheme of muscle plasticity. For instance, it was found that the diaphragm muscle normally contains I/IIX fibers. Functionally, the high degree of polymorphism may 1) represent a strategy for producing a spectrum of contractile properties that far exceeds that simply defined by the presence of four myosin heavy chain isoforms and 2) result in relatively small differences in function as defined by the force-velocity relationship.

Animals↗
PubMed2003

Skeletal muscle unweighting: spaceflight and ground-based models.

Long-term manned spaceflight requires that flight crews be exposed to extended periods of unweighting of antigravity skeletal muscles. This exposure will result in adaptations in these muscles that have the potential to debilitate crew members on return to increased gravity environments. Therefore, the development of countermeasures to prevent these unwanted adaptations is an important requirement. The limited access to microgravity environments for the purpose of studying muscle adaptation and evaluating countermeasure programs has necessitated the use of ground-based models to conduct both basic and applied muscle physiology research. In this review, the published results from ground-based models of muscle unweighting are presented and compared with the results from related spaceflight research. The models of skeletal muscle unweighting with a sufficient body of literature included bed rest, cast immobilization, and unilateral lower limb suspension. Comparisons of changes in muscle strength and size between these models in the context of the limited results available from spaceflight suggest that each model may be useful for the investigation of certain aspects of the skeletal muscle unweighting that occur in microgravity.

Animals↗
PubMed2002

Plasticity of skeletal muscle phenotype: mechanical consequences.

Muscles are complex biological machines that perform a wide variety of mechanical activities. Over the past 30 to 40 years, a large amount of effort has been devoted to understanding cellular/molecular responses of skeletal muscle to various altered physiological states (e.g., altered loading state induced via immobilization/spaceflight, resistance training). Many cellular/molecular adaptations brought about by such interventions act on underlying processes that regulate activation, force and velocity of shortening/lengthening, and relaxation. In this context, measurements of mechanical properties (e.g., force-velocity relationship) are important, because they can provide insight into the physiological consequences of such adaptations. During the course of the past 10 to 15 years, a number of investigators have employed the work-loop technique to provide a more realistic approach toward understanding muscle function. Additionally, the work-loop technique provides a unique conceptual perspective that integrates: (1) the length-tension relationship, (2) activation kinetics, (3) the force-velocity relationship in the shortening domain, (4) relaxation kinetics, (5) the force-velocity relationship in the lengthening domain, and (6) the compliance of the passive elastic elements. A discussion of those factors (i.e., factors 2-5) that appear to be highly malleable forms the basis of this paper.

Animals↗
PubMed2002

Lower reference limit for maximal oxygen uptake in men and women.

Maximal oxygen uptake (VO2max) is an important measure of exercise tolerance and low values may have clinical significance. Our purpose was to develop the necessary statistics--prediction equations and standard errors of estimate (SEE)--so that the lower reference limit for VO2max can be predicted for men and women. The subjects were healthy, non-smoking, sedentary men (n = 115) and women (n = 115) aged 20-70 years who performed 15 W min-1 cycle ergometer exercise tests. Three equations were developed for each gender using multiple linear regression with the non-exercise predictor variables of age and height, age and mass, and age and fat-free mass (FFM). The assumptions of regression analysis were examined and the predicted residual sum of squares (PRESS) method was used to cross-validate each equation. Healthy and diseased individual subject data from the literature were used to externally validate our lower reference limit statistics. The equations developed meet the assumptions of regression analysis and have an accuracy similar to the non-exercise prediction equations in the literature with R2 values of approximately 0.581. The PRESS method revealed that the equations are generalizable, i.e. may be used in future studies without a significant loss of accuracy. The lower reference limit predictions for the healthy and diseased individual subject data from the literature produced few miscategorizations unless the subjects were obese and mass was used as a predictor variable. In conclusion, the equations and SEE generated in this study can be used to predict an accurate and valid VO2max lower reference limit for a given subject.

Adult↗