bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction
Authors: Magga Jarkko , Puhakka Mikko , Hietakorpi Seppo , Punnonen Kari , Uusimaa Paavo , Risteli Juha , Vuolteenaho Olli , Ruskoaho Heikki , Peuhkurinen Keijo
Published: March 2004

Experimental data suggest that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) act locally as antifibrotic factors in heart. We investigated the interrelationships of natriuretic peptides and collagen markers in 93 patients receiving thrombolytic treatment for their first acute myocardial infarction (AMI). Collagen formation following AMI, evaluated as serum levels of amino terminal propeptide of type III procollagen, correlated with NH2-terminal proANP ( r = 0.45, P < 0.001), BNP ( r = 0.55, P < 0.001) and NH2-terminal proBNP ( r = 0.50, P < 0.01) on day 4 after thrombolysis. Levels of intact amino terminal propeptide of type I procollagen decreased by 34% ( P < 0.001), and levels of carboxy terminal cross-linked telopeptide of type I collagen (ICTP) increased by 65% ( P < 0.001). ICTP levels correlated with NH2-terminal proBNP ( r = 0.25, P < 0.05) and BNP ( r = 0.28, P < 0.05) on day 4. Our results suggest that ANP and BNP may act as regulators of collagen scar formation and left ventricular remodeling after AMI in humans. Furthermore, degradation of type I collagen is increased after AMI and may be regulated by BNP.
Intramuscular pressure and EMG relate during static contractions but dissociate with movement and fatigue
Authors: Sjøgaard Gisela , Jensen Bente R. , Hargens Alan R. , Søgaard Karen
Published: March 2004

Intramuscular pressure (IMP) and electromyography (EMG) mirror muscle force in the nonfatigued muscle during static contractions. The present study explores whether the constant IMP-EMG relationship with increased force may be extended to dynamic contractions and to fatigued muscle. IMP and EMG were recorded from shoulder muscles in three sessions: 1) brief static arm abductions at angles from 0 to 90°, with and without 1 kg in the hands; 2) dynamic arm abductions at angular velocities from 9 to 90°/s, with and without 1 kg in the hands; and 3) prolonged static arm abduction at 30° for 30 min followed by recovery. IMP and EMG increased in parallel with increasing shoulder torque during brief static tasks. During dynamic contractions, peak IMP and EMG increased to values higher than those during static contractions, and EMG, but not IMP, increased significantly with speed of abduction. In the nonfatigued supraspinatus muscle, a linear relationship was found between IMP and EMG; in contrast, during fatigue and recovery, significant timewise changes of the IMP-to-EMG ratio occurred. The results indicate that IMP should be included along with EMG when mechanical load sharing between muscles is evaluated during dynamic and fatiguing contractions.
Exercise training-induced adaptations of immune response are mediated by β-adrenergic receptors in aged but not young mice
Authors: Kohut Marian L. , Thompson James R. , Lee Wanglok , Cunnick Joan E.
Published: March 2004

β-Adrenergic blockade was used to determine whether the exercise training-induced adaptations of immune response to viral infection were mediated by catecholamines in young and old mice. Young (2 mo) and older (16 mo) male BALB/c mice were randomly assigned to an exercise or control group, and half of the mice in each group received the β-adrenergic receptor antagonist nadolol. After 8 wk of moderate exercise training, mice were challenged with herpes simplex virus (HSV) 24 h postexercise. The results showed that exercise treatment increased anti-HSV IgM antibody, enhanced IL-10, and altered the kinetics of IFN-γ and IL-2 production in young and old mice. Unique to older mice, exercise decreased mitogen-induced proliferation, increased splenocytes, and tended to decrease memory cells (CD44hi+). In contrast, exercise increased mitogen-induced proliferation but decreased the number of splenic lymphocyte and CD4+ cells in young mice. β-Adrenergic blockade blunted the exercise-induced changes in anti-HSV IgM, IL-2, IFNγ, and mitogen-induced proliferation in old but not young mice. The findings suggest that some of the immunomodulatory effects of chronic exercise are mediated via β-adrenergic receptors and that the role of β-adrenergic receptors is age dependent.
Influences of head positions and bite opening on collapsibility of the passive pharynx
Authors: Isono Shiroh , Tanaka Atsuko , Tagaito Yugo , Ishikawa Teruhiko , Nishino Takashi
Published: March 2004

A collapsible tube surrounded by soft material within a rigid box was proposed as a two-dimensional mechanical model for the pharyngeal airway. This model predicts that changes in the box size (pharyngeal bony enclosure size anatomically defined as cross-sectional area bounded by the inside edge of bony structures such as the mandible, maxilla, and spine, and being perpendicular to the airway) influence patency of the tube. We examined whether changes in the bony enclosure size either with head positioning or bite opening influence collapsibility of the pharyngeal airway. Static mechanical properties of the passive pharynx were evaluated in anesthetized, paralyzed patients with sleep-disordered breathing before and during neck extension with bite closure ( n = 11), neck flexion with bite closure ( n = 9), and neutral neck position with bite opening ( n = 11). Neck extension significantly increased maximum oropharyngeal airway size and decreased closing pressures of the velopharynx and oropharynx. Notably, neck extension significantly decreased compliance of the oropharyngeal airway wall. Neck flexion and bite opening decreased maximum oropharyngeal airway size and increased closing pressure of the velopharynx and oropharynx. Our results indicate the importance of neck and mandibular position for determining patency and collapsibility of the passive pharynx.
Loss of exercise-induced cardioprotection after cessation of exercise
Authors: Lennon Shannon L. , Quindry John , Hamilton Karyn L. , French Joel , Staib Jessica , Mehta Jawahar L. , Powers Scott K.
Published: March 2004

Endurance exercise provides cardioprotection against ischemia-reperfusion (I/R) injury. Exercise-induced cardioprotection is associated with increases in cytoprotective proteins, including heat shock protein 72 (HSP72) and increases in antioxidant enzyme activity. On the basis of the reported half-life of these putative cardioprotective proteins, we hypothesized that exercise-induced cardioprotection against I/R injury would be lost within days after cessation of exercise. To test this, male rats (4 mo) were randomly assigned to one of five experimental groups: 1) sedentary control, 2) exercise followed by 1 day of rest, 3) exercise followed by 3 days of rest, 4) exercise followed by 9 days of rest, and 5) exercise followed by 18 days of rest. Exercise-induced increases ( P < 0.05) in left ventricular catalase activity and HSP72 were evident at 1 and 3 days postexercise. However, at 9 days postexercise, myocardial HSP72 and catalase levels declined to sedentary control values. To evaluate cardioprotection during recovery from I/R, hearts were isolated, placed in working heart mode, and subjected to 20.5 min of global ischemia followed by 30 min of reperfusion. Compared with sedentary controls, exercised animals sustained less I/R injury as evidenced by maintenance of a higher ( P < 0.05) percentage of preischemia cardiac work during reperfusion at 1, 3, and 9 days postexercise. The exercise-induced cardioprotection vanished by 18 days after exercise cessation. On the basis of the time course of the loss of cardioprotection and the return of HSP72 and catalase to preexercise levels, we conclude that HSP72 and catalase are not essential for exercise-induced protection during myocardial stunning. Therefore, other cytoprotective molecules are responsible for providing protection during I/R.
Oxidation of combined ingestion of glucose and fructose during exercise
Authors: Jentjens Roy L. P. G. , Moseley Luke , Waring Rosemary H. , Harding Leslie K. , Jeukendrup Asker E.
Published: March 2004

The purpose of the present study was to examine whether combined ingestion of a large amount of fructose and glucose during cycling exercise would lead to exogenous carbohydrate oxidation rates >1 g/min. Eight trained cyclists (maximal O2consumption: 62 ± 3 ml·kg-1·min-1) performed four exercise trials in random order. Each trial consisted of 120 min of cycling at 50% maximum power output (63 ± 2% maximal O2consumption), while subjects received a solution providing either 1.2 g/min of glucose (Med-Glu), 1.8 g/min of glucose (High-Glu), 0.6 g/min of fructose + 1.2 g/min of glucose (Fruc+Glu), or water. The ingested fructose was labeled with [U-13C]fructose, and the ingested glucose was labeled with [U-14C]glucose. Peak exogenous carbohydrate oxidation rates were ∼55% higher ( P < 0.001) in Fruc+Glu (1.26 ± 0.07 g/min) compared with Med-Glu and High-Glu (0.80 ± 0.04 and 0.83 ± 0.05 g/min, respectively). Furthermore, the average exogenous carbohydrate oxidation rates over the 60- to 120-min exercise period were higher ( P < 0.001) in Fruc+Glu compared with Med-Glu and High-Glu (1.16 ± 0.06, 0.75 ± 0.04, and 0.75 ± 0.04 g/min, respectively). There was a trend toward a lower endogenous carbohydrate oxidation in Fruc+Glu compared with the other two carbohydrate trials, but this failed to reach statistical significance ( P = 0.075). The present results demonstrate that, when fructose and glucose are ingested simultaneously at high rates during cycling exercise, exogenous carbohydrate oxidation rates can reach peak values of ∼1.3 g/min.
A bronchial epithelium-derived factor reduces pulmonary vascular tone in the newborn rat
Authors: Belik J. , Pan J. , Jankov R. P. , Tanswell A. K.
Published: March 2004

The factors accounting for the maintenance of a low pulmonary vascular resistance postnatally are not completely understood. The aim of this study was to test the hypothesis that bronchial epithelium produces a factor capable of relaxing adjacent pulmonary arterial smooth muscle. We studied fourth-generation intralobar pulmonary arteries and bronchi of 4- to 8-day-old rats. Arteries were mounted on a wire myograph, alone or with the adjacent bronchus. The presence of the attached bronchus significantly reduced pulmonary artery force generation induced by the thromboxane analog (U-46619) or KCl whether the endothelium was present or absent ( P < 0.01). The converse was not true in that bronchial force generation was not affected when studied with the adjacent pulmonary artery. Mechanical removal of the bronchial epithelium or addition of the nitric oxide (NO) synthase (NOS) nonspecific ( NG-monomethyl-l-arginine) or the specific neuronal NOS (7-nitroindazole) inhibitors increased arterial force generation to levels comparable to the isolated artery preparation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, significantly decreased ( P < 0.01) NO release of pulmonary arteries only when the adjacent bronchus was present. We conclude that bronchial epithelium in the newborn rat produces a factor capable of lowering pulmonary vascular muscle tone. This relaxant effect can be suppressed by NOS and phosphatidylinositol 3-kinase kinase inhibition, suggesting an action via NOS phosphorylation and NO release. We speculate that such a mechanism may be operative in vivo and plays an important role in control of pulmonary vascular resistance in the early postnatal period.
Relative contributions of eyelid and eye-retraction motor systems to reflex and classically conditioned blink responses in the rabbit
Authors: Leal-Campanario Rocío , Barradas-Bribiescas José Alberto , Delgado-García José M. , Gruart Agnès
Published: March 2004

Early compensatory mechanisms between eyelid and eye-retraction motor systems following selective nerve and/or muscle lesions were studied in behaving rabbits. Reflex and conditioned eyelid responses were recorded in 1) controls and following 2) facial nerve section, 3) retractor bulbi muscle removal, and 4) facial nerve section and retractor bulbi muscle removal. Animals were classically conditioned with a delay paradigm by using a tone (350 ms, 600 Hz, 90 dB) as conditioned stimulus, followed 250 ms later by an air puff (100 ms, 3 kg/cm2) as unconditioned stimulus. Conditioned eyelid responses generated in the absence of the facial motor system (i.e., by the almost sole action of the retractor bulbi motor system) presented a wavy profile, due to the succession of eye-retraction movements. Learned eyelid responses generated in the absence of the eye-retraction motor system (i.e., by the almost exclusive action of the facial motor system) were similar to those of controls, but were reduced in amplitude and peak velocity. Finally, the isolated action of the extraocular recti muscle produced very small eyelid movements during both reflex and learned eyelid responses. Although each of these motor systems could act independently of the others, the motor result of their joint action did not coincide with the simple addition of their separate actions. Both facial and eye-retraction motor systems appear to be necessary for normal eyelid closure during blinking in rabbits. Central reorganization to compensate for loss of either of these systems may explain why the response of each system in isolation cannot be added linearly to obtain normal blink response magnitudes and profiles.
Effects of ventilation on the collection of exhaled breath in humans
Authors: Cope Keary A. , Watson Michael T. , Foster W. Michael , Sehnert Shelley S. , Risby Terence H.
Published: March 2004

A computerized system has been developed to monitor tidal volume, respiration rate, mouth pressure, and carbon dioxide during breath collection. This system was used to investigate variability in the production of breath biomarkers over an 8-h period. Hyperventilation occurred when breath was collected from spontaneously breathing study subjects ( n = 8). Therefore, breath samples were collected from study subjects whose breathing were paced at a respiration rate of 10 breaths/min and whose tidal volumes were gauged according to body mass. In this “paced breathing” group ( n = 16), end-tidal concentrations of isoprene and ethane correlated with end-tidal carbon dioxide levels [Spearman's rank correlation test ( rs) = 0.64, P = 0.008 and rs= 0.50, P = 0.05, respectively]. Ethane also correlated with heart rate ( rs= 0.52, P < 0.05). There was an inverse correlation between transcutaneous pulse oximetry and exhaled carbon monoxide ( rs= -0.64, P = 0.008). Significant differences were identified between men ( n = 8) and women ( n = 8) in the concentrations of carbon monoxide (4 parts per million in men vs. 3 parts per million in women; P = 0.01) and volatile sulfur-containing compounds (134 parts per billion in men vs. 95 parts per billion in women; P = 0.016). There was a peak in ethanol concentration directly after food consumption and a significant decrease in ethanol concentration 2 h later ( P = 0.01; n = 16). Sulfur-containing molecules increased linearly throughout the study period (β = 7.4, P < 0.003). Ventilation patterns strongly influence quantification of volatile analytes in exhaled breath and thus, accordingly, the breathing pattern should be controlled to ensure representative analyses.
Regulation of gastric motility at simulated high altitude in conscious rats
Authors: Yoshimoto Misa , Sasaki Mitsuko , Naraki Nobuo , Mohri Motohiko , Miki Kenju
Published: March 2004

The aim of the present study was to examine the effects of acute exposure to hypobaric hypoxia on gastric and colonic motilities. Wistar rats, which were instrumented chronically with strain gauge force transducer to measure gastric and colonic motilities, were exposed acutely to hypobaric hypoxia [0.5 atmosphere absolute (ATA, 380 Torr)] over 1 h. In a separate group, the gastric branches of the vagal nerves were cut and underwent the same experimental protocol. Each contraction wave of the stomach and colon was analyzed into frequency and area under the curves, which were then averaged every 10 min. Acute exposure to 0.5 ATA resulted in significant ( P < 0.05) decreases in frequency and area of gastric contraction wave by 0.5 ± 0.1 cycles/min and 64.6 ± 4.0%, respectively. Gastric vagotomy abolished completely the suppression in the area observed in the intact rats during the 0.5-ATA exposures. Colonic motility increased significantly only at the start and end of exposure to 0.5 ATA and sham exposure [1 ATA (760 Torr), time control] in both intact and vagotomized rats. These data suggest that the acute suppression of the area of the gastric contraction wave that occurred during 0.5-ATA exposure is likely to be mediated by the vagal nerve.
Alterations in PKC signaling underlie enhanced myogenic tone in exercise-trained porcine coronary resistance arteries
Authors: Korzick D. H. , Laughlin M. H. , Bowles D. K.
Published: March 2004

The intracellular mechanisms underlying enhanced myogenic contraction (MC) in coronary resistance arteries (CRAs) from exercise-trained (EX) pigs have not been established. The purpose of this study was to test the hypothesis that exercise-induced alterations in protein kinase C (PKC) signaling underlie enhanced MC. Furthermore, we sought to determine whether modulation of intracellular Ca2+signaling by PKC underlies enhanced MC in EX animals. Male Yucatan miniature swine were treadmill trained ( n = 7) at ∼75% of maximal O2uptake for 16 wk (6 miles/h, 60 min) or remained sedentary (SED, n = 6). Diameter measurements in response to intraluminal pressure (60, 75, and 90 cmH2O) or 60 mM KCl were determined in single, cannulated CRAs (∼100 μm ID) with and without the PKC inhibitor chelerythrine (CE, 1 μM). Confocal imaging of Ca2+signaling [myogenic Ca2+(Cam)] was also performed in CRAs of similar internal diameter after abluminal loading of the Ca2+indicator dye fluo 4 (1 μM, 37°C, 30 min). We observed significantly greater MC in CRAs isolated from EX than from SED animals at 90 cmH2O, as well as greater reductions in MC after CE at all pressures studied. At intraluminal pressures of 75 and 90 cmH2O, CE produced greater decreases in Camin CRAs from EX than from SED animals (64% vs. 25%, P < 0.05). Inhibition of KCl constriction and Camby CE was also greater in EX animals ( P < 0.05). Western blotting revealed significant increases in Ca2+-dependent PKC-α (∼50%) but not Ca2+-independent PKC-ϵ levels in CRAs isolated from EX animals ( P < 0.05). We also observed significant group differences in phosphorylated PKC-α levels. Finally, voltage-gated Ca2+current (VGCC) was effectively blocked by CE, bisindolylmaleimide, and staurosporine in isolated smooth muscle cells from CRAs, providing evidence for a mechanistic link between VGCCs and PKC in our experimental paradigm. These results suggest that enhanced MC in CRAs from EX animals involves PKC-dependent modulation of intracellular Ca2+, including regulation of VGCCs.
NaHCO3 does not affect arterial O2 tension but attenuates desaturation of hemoglobin in maximally exercising Thoroughbreds
Authors: Manohar Murli , Goetz Thomas E. , Hassan Aslam S.
Published: March 2004

The objective of the present study was to examine the effects of preexercise NaHCO3 administration to induce metabolic alkalosis on the arterial oxygenation in racehorses performing maximal exercise. Two sets of experiments, intravenous physiological saline and NaHCO3 (250 mg/kg iv), were carried out on 13 healthy, sound Thoroughbred horses in random order, 7 days apart. Blood-gas variables were examined at rest and during incremental exercise, leading to 120 s of galloping at 14 m/s on a 3.5% uphill grade, which elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. NaHCO3 administration caused alkalosis and hemodilution in standing horses, but arterial O2 tension and hemoglobin-O2 saturation were unaffected. Thus NaHCO3 administration caused a reduction in arterial O2 content at rest, although the arterial-to-mixed venous blood O2 content gradient was unaffected. During maximal exercise in both treatments, arterial hypoxemia, desaturation, hypercapnia, acidosis, hyperthermia, and hemoconcentration developed. Although the extent of exercise-induced arterial hypoxemia was similar, there was an attenuation of the desaturation of arterial hemoglobin in the NaHCO3-treated horses, which had higher arterial pH. Despite these observations, the arterial blood O2 content of exercising horses was less in the NaHCO3 experiments because of the hemodilution, and an attenuation of the exercise-induced expansion of the arterial-to-mixed venous blood O2 content gradient was observed. It was concluded that preexercise NaHCO3 administration does not affect the development and/or severity of arterial hypoxemia in Thoroughbreds performing short-term, high-intensity exercise.
Influence of fingertip contact on illusory arm movements
Authors: Rabin Ely , Gordon Andrew M.
Published: March 2004

Recent evidence suggests that reaching movements are more accurate when end point contact occurs, suggesting that fingertip contact contributes to a final estimation of arm position. In the present study we tested two hypotheses: 1) that fingertip contact influences illusions of arm movement produced by muscle vibration and 2) that this influence depends on the a priori context of the stability of the contact surface. Subjects sat with their elbows on a table and eyes closed. They demonstrated the perceived orientation of the left (cue) arm by mirroring the location with the right (report) arm. We manipulated deep proprioceptive cues by vibrating the left biceps brachia, causing illusions of elbow extension, and tested whether these illusions were altered when the fingertip remained in contact with a stable external surface. The context at this point represents a prior assumption that the external contact surface is stable. Midway through the experiment, the context was changed by challenging the prior assumption that the contact surface was stable by demonstrating that it could move. Unbeknownst to the subject, the external contact surface remained stable during data collection throughout the experiment. As expected, without tactile cues, biceps vibration caused illusory elbow extension. Conditions with fingertip contact and biceps vibration in the stable context demonstrated that contact largely eliminated the overestimation of cue arm elbow angle. However, in the context of a possibly unstable (movable) contact surface, the reports of elbow extension returned. Thus a priori notions about the stability context of an external contact surface influence how this tactile cue is integrated with proprioceptive sensory modalities to generate an estimate of arm location in space. These findings support the notion that tactile cues are used to calibrate proprioception against external spatial frameworks.
Depression of diaphragm motor cortex excitability during mechanical ventilation
Authors: Sharshar Tarek , Ross Ewen T. , Hopkinson Nicholas S. , Porcher Raphael , Nickol Annabel H. , Jonville Sophie , Dayer Mark J. , Hart Nicholas , Moxham John , Lofaso Frédéric , Polkey Michael I.
Published: March 2004

The effect of mechanical ventilation on the diaphragm motor cortex remains unknown. We assessed the effect of mechanical ventilation on diaphragm motor cortex excitability by measuring the costal and crural diaphragm motor-evoked potential (MEP) elicited by single and paired transcranial magnetic stimulation. In six healthy subjects, MEP recruitment curves of the costal and crural diaphragms were assessed at relaxed end expiration during spontaneous breathing [baseline tidal volume (Vtbaseline)] and isocapnic volume cycled ventilation delivered noninvasively (NIV) at three different levels of tidal volume (Vtbaseline, Vtbaseline + 5 ml/kg liters, and Vtbaseline + 10 ml/kg liters). The costal and crural diaphragm response to peripheral stimulation of the right phrenic nerve was not reduced by NIV. NIV reduced the costal and crural MEP amplitude during NIV ( P < 0.0001) with the maximal reduction at Vtbaseline + 5 ml/kg. Response to paired TMS showed that NIV (Vtbaseline + 5 ml/kg) significantly increased the sensitivity of the cortical motoneurons to facilitatory (>9 ms) interstimulus intervals ( P = 0.002), suggesting that the diaphragm MEP amplitude depression during NIV is related to neuromechanical inhibition at the level of motor cortex. Our results demonstrate that mechanical ventilation directly inhibits central projections to the diaphragm.
Dependence of lung injury on inflation rate during low-volume ventilation in normal open-chest rabbits
Authors: D'Angelo Edgardo , Pecchiari Matteo , Saetta Marina , Balestro Elisabetta , Milic-Emili Joseph
Published: March 2004

Lung mechanics and morphometry were assessed in two groups of nine normal open-chest rabbits mechanically ventilated (MV) for 3–4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (Vt; 11 ml/kg) and high ( group A) or low ( group B) inflation flow (44 and 6.1 ml·kg−1·s−1, respectively). Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH2O), MV on ZEEP increased quasi-static elastance and airway and viscoelastic resistance more in group A (+251, +393, and +225%, respectively) than in group B (+180, +247, and +183%, respectively), with no change in viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control, whereas airway resistance, still relative to initial values, remained elevated more in group A (+86%) than in group B (+33%). In contrast, prolonged high-flow MV on PEEP had no effect on lung mechanics of seven open-chest rabbits ( group C). Gas exchange on PEEP was equally preserved in all groups, and the lung wet-to-dry ratios were normal. Relative to group C, both groups A and B had an increased percentage of abnormal alveolar-bronchiolar attachments and number of polymorphonuclear leukocytes in alveolar septa, the latter being significantly larger in group A than in group B. Thus prolonged MV on ZEEP with cyclic opening-closing of peripheral airways causes alveolar-bronchiolar uncoupling and parenchymal inflammation with concurrent, persistent increase in airway resistance, which are worsened by high-inflation flow.
Role of nitric oxide in exercise sympatholysis
Authors: Buckwalter John B. , Taylor Jessica C. , Hamann Jason J. , Clifford Philip S.
Published: March 2004

The production of nitric oxide is the putative mechanism for the attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during exercise. We hypothesized that nitric oxide synthase blockade would eliminate the reduction in α-adrenergic-receptor responsiveness in exercising skeletal muscle. Ten mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective α1-adrenergic agonist (phenylephrine) or the selective α2-adrenergic agonist (clonidine) was infused as a bolus into the femoral artery catheter at rest and during mild and heavy exercise. Before nitric oxide synthase inhibition with NG-nitro-l-arginine methyl ester (l-NAME), intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of −91 ± 3, −80 ± 5, and −75 ± 6% (means ± SE) at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by −65 ± 6, −39 ± 4, and −30 ± 3%. After l-NAME, intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of −85 ± 5, −85 ± 5, and −84 ± 5%, whereas clonidine reduced vascular conductance by −67 ± 5, −45 ± 3, and −35 ± 3%, at rest, 3 miles/h, and 6 miles/h and 10% grade. α1-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, α2-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity. Whereas the inhibition of nitric oxide production eliminated the exercise-induced attenuation of α1-adrenergic-receptor responsiveness, the attenuation of α2-adrenergic-receptor responsiveness was unaffected. These results suggest that the mechanism of exercise sympatholysis is not entirely mediated by the production of nitric oxide.
Exercise delays allogeneic tumor growth and reduces intratumoral inflammation and vascularization
Authors: Zielinski Mark R. , Muenchow Melissa , Wallig Matthew A. , Horn Peggy L. , Woods Jeffrey A.
Published: March 2004

This investigation determined whether daily strenuous exercise would alter the progression and regression of an allogeneic lymphoid tumor in mice. We also determined whether exercise would alter the cellular composition and vascularity of the tumor. Female BALB/c mice (age 6–8 wk) were randomly assigned to sedentary control (Con) or daily exercised groups (EXH). EXH mice ran on a treadmill at incremental speeds (20–40 m/min) for 3 h or until fatigue. Each mouse was subcutaneously injected with 20 × 106 EL-4 lymphoma cells immediately after the first exercise bout ( day 1) and run daily. Tumor volume was measured daily with calipers. In some experiments, mice were euthanized on days 5–10, 12, and 14. Tumors were excised and stained with hematoxylin and eosin or for Factor VIII-associated antigen using immunohistochemistry and analyzed in a blinded fashion under a light microscope. There was no significant treatment main effect found for tumor volumes. Interestingly, a significant treatment × time interaction was found, such that there was a 2-day delay in peak tumor volume and a more rapid tumor regression in EXH. Tumors isolated from Con exhibited significantly higher numbers of apoptotic bodies, blood vessels, macrophages, and neutrophils when compared with EXH. Intratumoral lymphocytes were higher in Con early in tumor growth but higher in EXH at peak tumor size. These data indicate that daily strenuous exercise may influence tumor growth by affecting the microenvironment of the tumor, resulting in a delay in tumor growth and a more rapid regression.
Reducing the time period of steady state does not affect the accuracy of energy expenditure measurements by indirect calorimetry
Authors: Reeves Marina M. , Davies Peter S. W. , Bauer Judith , Battistutta Diana
Published: March 2004

Achievement of steady state during indirect calorimetry measurements of resting energy expenditure (REE) is necessary to reduce error and ensure accuracy in the measurement. Steady state is often defined as 5 consecutive min (5-min SS) during which oxygen consumption and carbon dioxide production vary by ±10%. These criteria, however, are stringent and often difficult to satisfy. This study aimed to assess whether reducing the time period for steady state (4-min SS or 3-min SS) produced measurements of REE that were significantly different from 5-min SS. REE was measured with the use of open-circuit indirect calorimetry in 39 subjects, of whom only 21 (54%) met the 5-min SS criteria. In these 21 subjects, median biases in REE between 5-min SS and 4-min SS and between 5-min SS and 3-min SS were 0.1 and 0.01%, respectively. For individuals, 4-min SS measured REE within a clinically acceptable range of ±2% of 5-min SS, whereas 3-min SS measured REE within a range of −2–3% of 5-min SS. Harris-Benedict prediction equations estimated REE for individuals within ±20–30% of 5-min SS. Reducing the time period of steady state to 4 min produced measurements of REE for individuals that were within clinically acceptable, predetermined limits. The limits of agreement for 3-min SS fell outside the predefined limits of ±2%; however, both 4-min SS and 3-min SS criteria greatly increased the proportion of subjects who satisfied steady state within smaller limits than would be achieved if relying on prediction equations.
Expression of nitric oxide synthase-2 in the lungs decreases airway resistance and responsiveness
Authors: Hjoberg Josephine , Shore Stephanie , Kobzik Lester , Okinaga Shoji , Hallock Arlene , Vallone Joseph , Subramaniam Venkat , De Sanctis George T. , Elias Jack A. , Drazen Jeffrey M. , Silverman Eric S.
Published: March 2004

Individuals with asthma have increased levels of nitric oxide in their exhaled air. To explore its role, we have developed a regulatable transgenic mouse capable of overexpressing inducible nitric oxide synthase in a lung-specific fashion. The CC10-rtTA-NOS-2 mouse contains two transgenes, a reverse tetracycline transactivator under the control of the Clara cell protein promoter and the mouse nitric oxide synthase-2 (NOS-2) coding region under control of a tetracycline operator. Addition of doxycycline to the drinking water of CC10-rtTA-NOS-2 mice causes an increase in nitric oxide synthase-2 that is largely confined to the airway epithelium. The fraction of expired nitric oxide increases over the first 24 h from ∼10 parts per billion to a plateau of ∼20 parts per billion. There were no obvious differences between CC10-rtTA-NOS-2 mice, with or without doxycycline, and wild-type mice in lung histology, bronchoalveolar protein, total cell count, or count differentials. However, airway resistance was lower in CC10-rtTA-NOS-2 mice with doxycycline than in CC10-rtTA-NOS-2 mice without doxycycline or wild-type mice with doxycycline. Moreover, doxycycline-treated CC10-rtTA-NOS-2 mice were hyporesponsive to methacholine compared with other groups. These data suggest that increased nitric oxide in the airways has no proinflammatory effects per se and may have beneficial effects on pulmonary function.
Environmental Enrichment Improves Response Strength, Threshold, Selectivity, and Latency of Auditory Cortex Neurons
Authors: Engineer Navzer D. , Percaccio Cherie R. , Pandya Pritesh K. , Moucha Raluca , Rathbun Daniel L. , Kilgard Michael P.
Published: March 2004

Over the last 50 yr, environmental enrichment has been shown to generate more than a dozen changes in brain anatomy. The consequences of these physical changes on information processing have not been well studied. In this study, rats were housed in enriched or standard conditions either prior to or after reaching sexual maturity. Evoked potentials from awake rats and extracellular recordings from anesthetized rats were used to document responses of auditory cortex neurons. This report details several significant, new findings about the influence of housing conditions on the responses of rat auditory cortex neurons. First, enrichment dramatically increases the strength of auditory cortex responses. Tone-evoked potentials of enriched rats, for example, were more than twice the amplitude of rats raised in standard laboratory conditions. Second, cortical responses of both young and adult animals benefit from exposure to an enriched environment and are degraded by exposure to an impoverished environment. Third, housing condition resulted in rapid remodeling of cortical responses in <2 wk. Fourth, recordings made under anesthesia indicate that enrichment increases the number of neurons activated by any sound. This finding shows that the evoked potential plasticity documented in awake rats was not due to differences in behavioral state. Finally, enrichment made primary auditory cortex (A1) neurons more sensitive to quiet sounds, more selective for tone frequency, and altered their response latencies. These experiments provide the first evidence of physiologic changes in auditory cortex processing resulting from generalized environmental enrichment.
Motor Outputs From the Primate Reticular Formation to Shoulder Muscles as Revealed by Stimulus-Triggered Averaging
Authors: Davidson Adam G. , Buford John A.
Published: March 2004

The motor output of the medial pontomedullary reticular formation (mPMRF) was investigated using stimulus-triggered averaging (StimulusTA) of EMG responses from proximal arm and shoulder muscles in awake, behaving monkeys ( M. fascicularis). Muscles studied on the side ipsilateral (i) to stimulation were biceps (iBic), triceps (iTri), anterior deltoid (iADlt), posterior deltoid (iPDlt), and latissimus dorsi (iLat). The upper and middle trapezius were studied on the ipsilateral and contralateral (c) side (iUTr, cUTr, iMTr, cMTr). Of 133 sites tested, 97 (73%) produced a poststimulus effect (PStE) in one or more muscles; on average, 38% of the sampled muscles responded per effective site. For responses that were observed in the arm and shoulder, poststimulus facilitation (PStF) was prevalent for the flexors, iBic (8 responses, 100% PStF) and iADlt (13 responses, 77% PStF), and poststimulus suppression (PStS) was prevalent for the extensors, iTri (22 responses, 96% PStS) and iLat (16 responses, 81% PStS). For trapezius muscles, PStS of upper trapezius (iUTr, 49 responses, 73% PStS) and PStF of middle trapezius (iMTr, 22 responses, 64% PStF) were prevalent ipsilaterally, and PStS of middle trapezius (cMTr, 6 responses, 67% PStS) and PStF of upper trapezius (cUTr, 46 responses, 83% PStS) were prevalent contralaterally. Onset latencies were significantly earlier for PStF (7.0 ± 2.2 ms) than for PStS (8.6 ± 2.0 ms). At several sites, extremely strong PStF was evoked in iUTr, even though PStS was most common for this muscle. The anatomical antagonists iBic/iTri were affected reciprocally when both responded. The bilateral muscle pair iUTr/cUTr demonstrated various combinations of effects, but cUTr PStF with iUTr PStS was prevalent. Overall, the results are consistent with data from the cat and show that outputs from the mPMRF can facilitate or suppress activity in muscles involved in reaching; responses that would contribute to flexion of the ipsilateral arm were prevalent.
Calcium Influx Through HCN Channels Does Not Contribute to cAMP-Enhanced Transmission
Authors: Zhong Ning , Beaumont Vahri , Zucker Robert S.
Published: March 2004

Serotonin is a native neuromodulator of synaptic transmission at glutamatergic neuromuscular junctions of crayfish limb muscles. During times of stress, serotonin binds to presynaptic receptors, which activate adenylyl cyclase to elevate presynaptic levels of cAMP. cAMP binds to two presynaptic target proteins, hyperpolarization and cyclic nucleotide-activated (HCN) ion channels and an exchange protein activated by cAMP (Epac), and activation of these effectors results in enhancement of transmitter release to action potentials. cAMP elevation also results in a small preterminal rise in [Ca2+]i, which we show here to result from Ca2+ influx through the presynaptic HCN channels opened by cAMP. Little or no Ca2+ influx occurs through voltage-dependent Ca2+ channels, despite the small presynaptic depolarization caused by current through the HCN channels. Loading terminals with BAPTA delays the rise in preterminal [Ca2+]i without affecting the enhancement of transmission to cAMP elevation. This dissociation of the dynamics of the [Ca2+]i rise and synaptic enhancement, plus the small magnitude and location of [Ca2+]i elevation distant from release sites, seems to preclude any direct role for this [Ca2+]i elevation in cAMP-dependent enhancement of transmission.
Subthreshold Resonance Explains the Frequency-Dependent Integration of Periodic as Well as Random Stimuli in the Entorhinal Cortex
Authors: Schreiber Susanne , Erchova Irina , Heinemann Uwe , Herz Andreas V. M.
Published: March 2004

Neurons integrate subthreshold inputs in a frequency-dependent manner. For sinusoidal stimuli, response amplitudes thus vary with stimulus frequency. Neurons in entorhinal cortex show two types of such resonance behavior: stellate cells in layer II exhibit a prominent peak in the resonance profile at stimulus frequencies of 5–16 Hz. Pyramidal cells in layer III show only a small impedance peak at low frequencies (1–5 Hz) or a maximum at 0 Hz followed by a monotonic decrease of the impedance. Whether the specific frequency selectivity for periodic stimuli also governs the integration of non-periodic stimuli has been questioned recently. Using frozen-noise stimuli with different distributions of power over frequencies, we provide experimental evidence that the integration of non-periodic subthreshold stimuli is determined by the same subthreshold frequency selectivity as that of periodic stimuli. Differences between the integration of noise stimuli in stellate and pyramidal cells can be fully explained by the resonance properties of each cell type. Response power thus reflects stimulus power in a frequency-selective way. Theoretical predictions based on linear system's theory as well as on conductance-based model neurons support this finding. We also show that the frequency selectivity in the subthreshold range extends to suprathreshold responses in terms of firing rate. Cells in entorhinal cortex are representative examples of cells with resonant or low-pass filter impedance profiles. It is therefore likely that neurons with similar frequency selectivity will process input signals according to the same simple principles.
Local GABA Receptor Blockade Reveals Hindlimb Responses in the SI Forelimb-Stump Representation of Neonatally Amputated Rats
Authors: Pluto Charles P. , Lane Richard D. , Rhoades Robert W.
Published: March 2004

In adult rats that sustained forelimb amputation on the day of birth, there are numerous multi-unit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) that also respond to cutaneous stimulation of the hindlimb when cortical receptors for GABA are blocked. These normally suppressed hindlimb inputs originate in the SI hindlimb representation and synapse in the dysgranular cortex before exciting SI forelimb-stump neurons. In our previous studies, GABA (A + B) receptor blockade was achieved by topically applying a bicuculline methiodide/saclofen solution (BMI/SAC) to the cortical surface. This treatment blocks receptors throughout SI and does not allow determination of where along the above circuit the GABA-mediated suppression of hindlimb information occurs. In this study, focal injections of BMI/SAC were delivered to three distinct cortical regions that are involved in the hindlimb-to-forelimb-stump pathway. Blocking GABA receptors in the SI hindlimb representation and in the dysgranular cortex was largely ineffective in revealing hindlimb inputs (∼10% of hindlimb inputs were revealed in both cases). In contrast, when the blockade was targeted at forelimb-stump recording sites, >80% of hindlimb inputs were revealed. Thus GABAergic interneurons within the forelimb-stump representation suppress the expression of reorganized hindlimb inputs to the region. A circuit model incorporating these and previous observations is presented and discussed.
Modular Functional Organization of Cat Anterior Auditory Field
Authors: Imaizumi Kazuo , Priebe Nicholas J. , Crum Poppy A. C. , Bedenbaugh Purvis H. , Cheung Steven W. , Schreiner Christoph E.
Published: March 2004

Two tonotopic areas, the primary auditory cortex (AI) and the anterior auditory field (AAF), are the primary cortical fields in the cat auditory system. They receive largely independent, concurrent thalamocortical projections from the different thalamic divisions despite their hierarchical equivalency. The parallel streams of thalamic inputs to AAF and AI suggest that AAF neurons may differ from AI neurons in physiological properties. Although a modular functional organization in cat AI has been well documented, little is known about the internal organization of AAF beyond tonotopy. We studied how basic receptive field parameters (RFPs) are spatially organized in AAF with single- and multiunit recording techniques. A distorted tonotopicity with an underrepresentation in midfrequencies (1 and 5 kHz) and an overrepresentation in the high-frequency range was found. Spectral bandwidth (Q-values) and response threshold were significantly correlated with characteristic frequency (CF). To understand whether AAF has a modular organization of RFPs, CF dependencies were eliminated by a nonparametric, local regression model, and the residuals (difference between the model and observed values) were evaluated. In a given isofrequency domain, clusters of low or high residual RFP values were interleaved for threshold, spectral bandwidth, and latency, suggesting a modular organization. However, RFP modules in AAF were not expressed as robustly as in AI. A comparison of RFPs between AAF and AI shows that AAF neurons were more broadly tuned and had shorter latencies than AI neurons. These physiological field differences are consistent with anatomical evidence of largely independent, concurrent thalamocortical projections in AI and AAF, which strongly suggest field-specific processing.
Supplementary Eye Fields Stimulation Facilitates Anticipatory Pursuit
Authors: Missal M. , Heinen S. J.
Published: March 2004

Anticipatory movements are motor responses occurring before likely sensory events in contrast to reflexive actions. Anticipatory movements are necessary to compensate for delays present in sensory and motor systems. Smooth pursuit eye movements are often used as a paradigmatic example for the study of anticipation. However, the neural control of anticipatory pursuit is unknown. A previous study suggested that the supplementary eye fields (SEFs) could play a role in the guidance of smooth pursuit to predictable target motion. In this study, we favored anticipatory responses in monkeys by making the parameters of target motion highly predictable and electrically stimulated the SEF before and during this behavior. Stimulation sites were restricted to regions of the SEF where saccades could not be evoked at the same low currents. We found that electrical microstimulation in the SEF increased the velocity of anticipatory pursuit movements and decreased their latency. These effects will be referred to as anticipatory pursuit facilitation. The degree of facilitation was the largest if the stimulation train was delivered near the end of the fixation period, before the moment when anticipatory pursuit usually begins. No anticipatory smooth eye movements could be evoked during fixation without an expectation of target motion. These results suggest that the SEF pursuit area might be involved in the process of guiding anticipatory pursuit.
The mouse muscle creatine kinase promoter faithfully drives reporter gene expression in transgenicXenopus laevis
Authors: Lim Wayland , Neff Eric S. , Furlow J. David
Published: March 2004

Developing Xenopus laevis experience two periods of muscle differentiation, once during embryogenesis and again at metamorphosis. During metamorphosis, thyroid hormone induces both muscle growth in the limbs and muscle death in the tail. In mammals, the muscle creatine kinase (MCK) gene is activated during the differentiation from myoblasts to myocytes and has served as both a marker for muscle development and to drive transgene expression in transgenic mice. Transcriptional control elements are generally highly conserved throughout evolution, potentially allowing mouse promoter use in transgenic X. laevis. This paper compares endogenous X. laevis MCK gene expression and the mouse MCK (mMCK) promoter driving a green fluorescent protein reporter in transgenic X. laevis. The mMCK promoter demonstrated strong skeletal muscle-specific transgene expression in both the juvenile tadpole and adult frog. Therefore, our results clearly demonstrate the functional conservation of regulatory sequences in vertebrate muscle gene promoters and illustrate the utility of using X. laevis transgenesis for detailed comparative study of mammalian promoter activity in vivo.