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V J Caiozzo

Publications and source records attributed to V J Caiozzo.

At least 37 records · Page 2Linked to original sources
PubMed1996

Microgravity-induced transformations of myosin isoforms and contractile properties of skeletal muscle.

This study examined the effects of microgravity (14 days) on 1) the contractile properties of the soleus (Sol), an antigravity skeletal muscle; and 2) the myosin heavy chain (MHC) protein and mRNA isoform content of the Sol, vastus intermedius (VI), plantaris (Plan), and tibialis anterior (TA) muscles. The force-velocity relationships of the flight Sol muscles had a significant reduction in maximal isometric tension (-37%) and a corresponding increase in maximal shortening velocity (+20%). Additionally, the force-frequency relationship of the flight Sol muscles was shifted to the right of the ground-based control group. Microgravity had the greatest effect on muscle fiber composition in the Sol muscle, with a reduction in slow muscle fibers and a corresponding increase in muscle fibers categorized as hybrid fibers. The estimated absolute MHC isoform content was altered to the greatest extent in the Sol and VI muscles, with significant decreases and elevations in the slow type I and fast type IIX MHC protein isoforms, respectively. Consistent with the protein data, both the flight Sol and VI muscles exhibited significant elevations in the fast type IIX MHC mRNA isoform. In contrast, however, the flight Plan and TA groups had significant increases in the fast type IIB MHC mRNA isoform content without corresponding changes at the protein level. The results of this study suggest that spaceflight of even short duration produces important changes in the contractile properties of antigravity skeletal muscle. These changes are mediated by alterations in MHC phenotype and reductions in muscle mass. In some instances, the alterations in MHC mRNA isoform content seemed to be uncoupled from those occurring at the protein level. This apparent uncoupling between mRNA and protein expression demonstrates that the effects of microgravity must be better understood at the transcriptional, translational, and post-translational levels.

Animals↗
PubMed1995

Functional and cellular adaptations of rodent skeletal muscle to weightlessness.

Microgravity perturbs a wide variety of physiological systems. Specifically, skeletal muscle has been shown to undergo dramatic changes even during spaceflights of short durations. Despite a growing body of knowledge, many critical issues related to sarcomeric gene expression and the translation of this information into muscle function remain relatively unexplored. Ultimately, the types and quantities of contractile proteins present in skeletal muscle fibers determine muscle function. As shown in Figure 1, the pool of contractile proteins is determined by 4 important processes: i) transcription of sarcomeric genes; ii) translation of sarcomeric mRNA transcripts; iii) myofibrillar assembly; and iv) myofibrillar disassembly (i.e., protein degradation). Any factor(s) affecting one or more of these systems will ultimately impact skeletal muscle function. With respect to Figure 1, the objective of this paper is to provide a focused summary of the affects of short duration spaceflights on myosin composition of the soleus (SOL) muscle. This will be achieved by describing the affects of spaceflight upon: i) mechanical properties of skeletal muscle that are determined by the types and quantity of myosin; ii) myosin heavy chain (MHC) protein isoform composition; and ii) MHC mRNA isoform content. Data reported in this paper are from spaceflight missions having durations of 6 (PARE-02;2) and 14 days (SLS-2).

Animals↗
PubMed1994

Effect of spaceflight on skeletal muscle: mechanical properties and myosin isoform content of a slow muscle.

This study examined changes in contractile, biochemical, and histochemical properties of slow antigravity skeletal muscle after a 6-day spaceflight mission. Twelve male Sprague-Dawley rats were randomly divided into two groups: flight and ground-based control. Approximately 3 h after the landing, in situ contractile measurements were made on the soleus muscles of the flight animals. The control animals were studied 24 h later. The contractile measurements included force-velocity relationship, force-frequency relationship, and fatigability. Biochemical measurements focused on the myosin heavy chain (MHC) and myosin light chain profiles. Adenosine-triphosphatase histochemistry was performed to identify cross-sectional area of slow and fast muscle fibers and to determine the percent fiber type distribution. The force-velocity relationships of the flight muscles were altered such that maximal isometric tension (Po) was decreased by 24% and maximal shortening velocity was increased by 14% (P < 0.05). The force-frequency relationship of the flight muscles was shifted to the right of the control muscles. At the end of the 2-min fatigue test, the flight muscles generated only 34% of Po, whereas the control muscles generated 64% of Po. The flight muscles exhibited de novo expression of the type IIx MHC isoform as well as a slight decrease in the slow type I and fast type IIa MHC isoforms. Histochemical analyses of flight muscles demonstrated a small increase in the percentage of fast type II fibers and a greater atrophy of the slow type I fibers. The results demonstrate that contractile properties of slow antigravity skeletal muscle are sensitive to the microgravity environment and that changes begin to occur within the 1st wk. These changes were at least, in part, associated with changes in the amount and type of contractile protein expressed.

Adenosine Triphosphatases↗
PubMed1994

Interaction of thyroid hormone and functional overload on skeletal muscle isomyosin expression.

This study examined the interaction of exogenous thyroid hormone 3,5,3'-triiodothyronine (T3) and functional overload on skeletal muscle myosin heavy chain (MHC) expression, studied at both the protein and mRNA level of analysis. Animals were allocated to the following groups: 1) normal control, 2) overload control, 3) hyperthyroid control, and 4) hyperthyroid+overload. Overload of the rat plantaris was accomplished by surgical removal of its synergists (soleus and gastrocnemius), and the animals were made hyperthyroid by injections of T3 (350 micrograms/kg every other day). After overload of 8 wk, muscle enlargement occurred by 53% for both overload groups (P < 0.05). This was accompanied by a 330 and 82% increase in the relative content of type I and IIa MHC, respectively, and a corresponding decrease by 16 and 44% in type IIx and IIb MHC, respectively, in the overload control group (P < 0.05 vs. normal control). Changes in the relative and absolute content of mRNA for these MHCs paralleled the protein response. Exogenous T3 completely reversed the upregulation of type I MHC and the downregulation of type IIx associated with overload at both the protein and mRNA level (P < 0.05). However, T3 was only partially effective in blunting the downregulation of IIb MHC and the upregulation of IIa MHC (protein and mRNA) accompanying the overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning.

Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

Aging↗
PubMed1993

A functional in vitro model for studying the cellular and molecular basis of spinal cord injury.

Very little is understood about how spinal cord injury affects the molecular mechanisms responsible for generating locomotion. Recently, it has been shown in the spinal cord that the N-methyl-D-aspartate receptor, a specific class of excitatory amino acid receptors, plays a major role in the neurogenesis of locomotion. Paradoxically, studies of the brain and the spinal cord have shown that overeactivation of this receptor can cause excitotoxicity and subsequent cell death. The ultimate goal of these experiments was to develop an isolated brain stem/spinal cord/hind limb preparation that would allow study of issues related to excitotoxicity and the neurogenesis of locomotion. Findings indicate that: 1) exposure of the spinal cord to the excitatory amino acids produced an alternating gate of the hind limbs; 2) application of N-methyl-D-aspartate inhibitors were effective in preventing hind limb movement initiated by exposure to N-methyl-D-aspartate; 3) sensorimotor stimulation of the tail produced hind limb movement that could be evoked for periods up to 8 hours; and 4) an excitotoxic event produced substantial loss of protein and possible osmotic changes. This study represents the first step in developing a powerful model for examining the effect of spinal cord injury on molecular mechanisms responsible for the neurogenesis of locomotion both at the brain stem, spinal motor generator, or sensorimotor level. The opportunity of observing hind limb movement in this preparation represents a powerful functional bioassay for evaluating the extent of spinal cord injury.

Animals↗
PubMed1993

Single fiber analyses of type IIA myosin heavy chain distribution in hyper- and hypothyroid soleus.

The objectives of this study were to 1) examine the effect of hypo- and hyperthyroidism (triiodothyronine treatment) on the distribution of type IIA myosin heavy chain (MHC) in the soleus at the single fiber level and 2) correlate changes in the single fiber distribution of type IIA MHC with the maximal shortening velocity of whole skeletal muscle. The presence of the type IIA MHC in single fibers was determined using a monoclonal antibody reactive to the type IIA MHC and quantified with a Meridian ACAS 570 interactive laser cytometer. The findings of this study demonstrate that 1) hyperthyroidism significantly increases the relative number of muscle fibers that express type IIA MHC, 2) not all type I fibers are capable of expressing fast type IIA MHC under hyperthyroid conditions, and 3) there is a high correlation between maximal shortening velocity and the relative number of type IIA fibers. This latter observation suggests that the maximal shortening velocity of whole skeletal muscle may not be solely determined by its fastest fiber(s) but rather by the relative proportion of fibers expressing fast type IIA MHC.

Animals↗
PubMed1993

Activity-induced regulation of myosin isoform distribution: comparison of two contractile activity programs.

This study examined the role of specific types of contractile activity in regulating myosin heavy chain (MHC) isoform expression in rodent soleus. A combination of hindlimb suspension (SN) and two programmed contractile training activity paradigms, either isometric contractile activity (ST-IM) or high-load slowly shortening isovelocity activity, were utilized. Both training paradigms increased muscle mass compared with SN alone. However, only ST-IM resulted in a partial prevention of the suspension-induced decrease in type I MHC. With the use of a fluorescently labeled antibody to type IIa MHC, the distribution of MHCs among fibers was examined immunohistochemically. In SN, the percentage of cells staining positive for type IIa MHC was increased but the staining intensity of the positively staining cells was unchanged compared with control cells. In the ST-IM soleus, the percentage of positively staining fibers was unchanged but the intensity of the positively staining cells was decreased compared with SN values. These results suggest that: 1) isometric contractile activity is more effective than isovelocity activity in preventing suspension-induced shifts in soleus MHC distribution and 2) changes associated with both suspension and training occur in only a small number of fibers, with the majority of fibers apparently unresponsive to these interventions.

Animals↗
PubMed1992

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms.

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Adenosine Triphosphatases↗
PubMed1992

A new animal model for modulating myosin isoform expression by altered mechanical activity.

The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated.

Adenosine Triphosphatases↗
PubMed1992

Alterations in the in vivo torque-velocity relationship after Achilles tendon rupture. Further evidence of speed-specific impairment.

The torque-velocity relationship of the ankle plantar flexors was determined in 31 patients recovering from Achilles tendon rupture. Isokinetic torque measurements were made at speeds of 0 to 240 degrees.s-1 at 24 degrees.s-1 intervals. Measurements of instantaneous torque were made at joint angles corresponding to neutral and 10 degrees plantar flexion. In 17 patients treated surgically, there was little difference between the injured and the uninjured leg. In contrast, patients who were treated by casting exhibited major differences between the injured and uninjured legs. This difference became amplified when torque values at 10 degrees plantar flexion were compared. Additionally, the differences between the injured and uninjured legs were not uniform. The differences in torque were greatest at slow test speeds and least at fast test speeds. Comparisons of the injured surgical and injured nonsurgical legs demonstrated that the surgical group had significantly greater torque. This difference was also speed specific. These findings demonstrate that both groups exhibited speed-specific impairment with the loss of muscle strength being greatest at slow speeds. Also, the degree of impairment was dependent on the ankle position at which torque was measured. Surgical treatment provides better functional results as observed by the torque-velocity relationship.

Achilles Tendon↗
PubMed1991

Contractile and biochemical properties of rat soleus and plantaris after hindlimb suspension.

This study examined the relationship between contractile and isomyosin changes occurring in rat soleus (SOL) and plantaris (PLAN) muscles after 28 days of hindlimb suspension. SOL muscles from suspended animals exhibited a 45% decline in muscle weight compared with controls (P less than 0.05) accompanied by a 49% decrease in peak twitch tension (Pt) and a 59% reduction in peak tetanic tension (Po). Smaller reductions were observed in muscle weight, Pt, and Po (12, 43, and 24%, respectively) for the suspended PLAN. Maximal shortening velocity (Vmax) of the suspended SOL and the velocity of unloaded shortening were increased by 36 and 35%, respectively, but there was no suspension-induced change in PLAN Vmax. Suspension induced a 22% increase in SOL myosin adenosinetriphosphatase (ATPase) activity that was accompanied by a shift in the native myosin isoform distribution characterized by an increase in the relative amounts of intermediate and fast myosin. The more modest changes in the contractile function of suspended PLAN were accompanied by a small (7%) increase in myosin ATPase activity but no significant changes in myosin isoform distribution. The results of this study confirm that hindlimb suspension results in significant speeding of SOL contractile properties and suggest that the shift toward faster myosin isoforms with a higher myosin ATPase activity likely accounts for these mechanical changes.

Animals↗
PubMed1991

Influence of hyperthyroidism on maximal shortening velocity and myosin isoform distribution in skeletal muscles.

The objectives of this study were 1) to examine the effects of hyperthyroidism on the myosin isoform distribution in slow and fast skeletal muscle, 2) to explore how these effects were manifested with respect to the force-velocity relationship and maximal shortening velocity, and 3) to contrast two different techniques of measuring maximal shortening velocity under normal and hyperthyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 8) or hyperthyroid (n = 8). Hyperthyroidism was induced by injections of 3,3',5-triiodo-L-thyronine every other day for 20 wk. We found that hyperthyroidism produced a significant shift in the myosin isoform distribution of the soleus but not the plantaris. The relative amount of the slow myosin isoform was reduced from a control value of 93 to 69% in the hyperthyroid condition. In contrast, both the intermediate and fast myosin-3 isoform pools were substantially increased (P less than 0.001) by approximately fourfold. Hyperthyroidism produced an increase in the maximal shortening velocity of the soleus as measured either by the slack test (+57%; P less than 0.001) or by extrapolation of force-velocity data (+33%; P less than 0.001). The hyperthyroid condition did not, however, affect the mechanical properties of the plantaris.

Adenosine Triphosphate↗
PubMed1990

Excitotoxins can produce protein degradation in the spinal cord.

Overdistraction and derotation of the scoliotic spine during surgery represent potential complications that could lead to spinal cord dysfunction and paralysis. Neuronal loss and, consequently, the inability to regain function may be attributable to primary damage (eg, mechanical), secondary cell death (eg, such as that produced by ischemia) or a combination of both. Beyond intraoperative recognition and removal of the rods, effective strategies to prevent this neuronal loss have yet to be developed. This emphasizes the need for a clearer understanding of the molecular events that contribute to neuronal injury in the central nervous system. Considerable evidence has indicated that the excitatory transmitter L-glutamate and the N-methyl-D-aspartate (NMDA) excitatory amino acid receptor may contribute to the secondary neuronal death observed in a wide variety of neurological insults, including ischemia. The current investigation was undertaken to elucidate the potential role of the NMDA receptor in spinal cord pathology. Isolated rat spinal cords were exposed to anoxic physiologic solutions in the presence and absence of Ca++, NMDA receptor agonists, and a noncompetitive NMDA receptor antagonist. The extent of neuronal damage was assessed by quantitating the degradation of the cytoskeletal neurofilament protein. A substantial increase in the loss of neurofilament protein was observed in spinal cords exposed to anoxic conditions in the presence of Ca++ as compared with the absence of Ca++. Exposure to excitatory amino acid agonists (L-glutamate or NMDA) further potentiated the degradation of the neurofilament protein; an effect that was reversed by a noncompetitive NMDA receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Accurate prediction of VO2max in cycle ergometry.

Numerous equations exist for predicting VO2max from the duration (an analog of maximal work rate, Wmax) of a treadmill graded exercise test (GXT). Since a similar equation for cycle ergometry (CE) was not available, we saw the need to develop such an equation, hypothesizing that CE VO2max could be accurately predicted due to its more direct relationship with W. Thus, healthy, sedentary males (N = 115) and females (N = 116), aged 20-70 yr, were given a 15 W.min-1 CE GXT. The following multiple linear regression equations which predict VO2max (ml.min-1) from the independent variables of Wmax (W), body weight (kg), and age (yr) were derived from our subjects: Males: Y = 10.51 (W) + 6.35 (kg) - 10.49 (yr) + 519.3 ml.min-1; R = 0.939, SEE = 212 ml.min-1. Females: Y = 9.39 (W) + 7.7 (kg) - 5.88 (yr) + 136.7 ml.min-1; R = 0.932, SEE = 147 ml.min-1 Using the 95% confidence limits as examples of worst case errors, our equations predict VO2max to within 10% of its true value. Internal (double cross-validation) and external cross-validation analyses yielded r values ranging between 0.920 and 0.950 for the male and female regression equations. These results indicate that use of the equations generated in this study for a 15 W.min-1 CE GXT provides accurate estimates of VO2max.

Adult↗
PubMed1989

Histochemical properties of muscle allografts enhanced via cyclosporine.

Until recently, the transplantation of skeletal muscle across a major histocompatibility barrier has proved difficult. However, with the advent of cyclosporine (CsA), it has become possible to achieve extended survival across such histocompatibility barriers. To date, very little is known about the histochemical, biochemical, immunological or contractile properties of long-term-surviving muscle allografts. Consequently, it was the focus of this study to histochemically examine muscle allografts prolonged with CsA and determine the cross-sectional area of fast glycolytic muscle fibers. Measurements of cross-sectional area were made because they are an important correlate to the amount of tension a muscle can generate. Animals were assigned randomly to one of three groups: control (normal) (n = 5), syngeneic (n = 4), and allogeneic (n = 4). Muscle allografts were performed by transplanting the gastrocnemius of an ACI rat (RT1a) hindlimb into the hindlimb of a Lewis rat (LEW;RT1(1]. The syngeneic model consisted of an ACI-to-ACI transplant. Animals in the allograft group were given CsA (8 mg/kg/day) until the time of sacrifice. At approximately 100 days following transplantation, both syngeneic and allogeneic muscles were removed from the recipient, and quickly frozen in isopentane cooled by liquid nitrogen. Muscle fibers were classified as slow-oxidative (SO), fast-oxidative-glycolytic (FOG), or fast-glycolytic (FG) based upon their staining for myofibrillar ATPase and NADH-dehydrogenase. From each muscle, the cross-sectional area of approximately 175 FG muscle fibers was determined. The fast-glycolytic muscle fibers of both the syngeneic and allogeneic grafts demonstrated a substantial decrease in cross-sectional area. The mean value (+/- SD) for the fibers of the allografted muscle was 1165 +/- 533 microns 2. The mean (+/- SD) fiber cross-sectional area for the fibers of the syngeneic muscle was 973 +/- 421 microns 2. These values contrast with a mean (+/- SD) value of 3552 +/- 601 microns 2 for fibers from age-matched control animals. The differences between the syngeneic and allogeneic muscles were not significant (P greater than 0.05). However, both exhibited significant (P less than 0.01) atrophy compared with the control muscle.

Animals↗