Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.     

Effects of caffeine on the metabolic and catecholamine responses to exercise in 5 and 28 degrees C

A controversy presently exists concerning the ability of albumin to inhibit the tubular reabsorption of low-molecular-weight (M(r)) proteins in experimental renal diseases leading to massive proteinuria. We have examined the urinary excretion of albumin and of 2 low-M(r) proteins, beta 2-microglobulin and cystatin C, in rats treated with toxins affecting primarily the glomerulus (puromycin amino-nucleoside and Adriamycin) or the tubule (mercuric chloride and maleic acid). Above a threshold of 100 mg/24 h, albuminuria induced by puromycin aminonucleoside (50 mg/kg) and Adriamycin (5 mg/kg) was associated with a marked increase in the urinary excretion of beta 2-microglobulin and cystatin C peaking at more than 100-fold the baseline levels. These glomerulotoxins did not affect the urinary excretion of the tubular enzyme N-acetyl-beta-D-glucosaminidase. This pattern of effects was completely different from that induced by mercuric chloride (2 mg/kg) and maleic acid (400 mg/kg) which increased the excretion of both N-acetyl-beta-D-glucosaminidase and low-M(r) proteins in rats with albuminuria values below 100 mg/24 h. These results strongly support the hypothesis that at high filtered loads, albumin decreases the tubular uptake of low-M(r) proteins most likely by competition for a common transport mechanism.     

Effects of CO2 on pulmonary air flow resistance in the duck

Effects of CO2 on pulmonary smooth muscle were assessed by measuring the air flow resistance of secondary bronchi and parabronchi in ducks unidirectionally ventilated with a constant gas flow through the parabronchial lung, the bypass of the primary bronchus being occluded by a blocking catheter. Pressure differences across the blocking balloon (deltaP), corresponding to the pressure drop in the gas flowing through the mediodorsal and medioventral secondary bronchi (MD and MV) and parabronchi, were measured at flow rates (V) varied from 0.5 to 3 L-min-1 and at CO2 concentrations of ventilating gas (FICO2) varied from 0 to 10%. 1) deltaP increased more than linearly with V. The resulting flow resistance R(= deltaP/V) averaged 43 and 95 cm H2O-L-1-sec at V = 0.5 and 3 L-min-1, respectively. 2) Step changes in FICO2 at constant V were followed within 0.5 to 5 sec by changes in R. 3) Lowering FICO2 from 5% resulted in marked increases in R, the value at FICO2 = 0% being more than twice the average value at 5%. Raising FICO2 from 5% up to 10% was followed by only slight changes in R. 4) Vagotomy did not consistently change R at any level of CO2; it did, however, slightly increase the delay time for changes in R on step changes of FICO2. 5)The medioventral secondary bronchi and their orifices into the primary bronchus appeared to be mainly responsible for the resistance measured and its changes with CO2. The resistance offered by the parabronchi appeared to be much smaller and much less dependent on CO2. The results suggest importance of lung gas CO2 in aerodynamic valving of respiratory flow in avian lungs during normal breathing and particularly during thermal panting to prevent alkalosis.     

Electron tomography of insect flight muscle in rigor and AMPPNP at 23 degrees C

Treatment of rigor fibers of insect flight muscle (IFM) with AMPPNP at 23 degrees C causes a 70% drop in tension with little change in stiffness. In order to visualize the changes in crossbridge conformation and distribution that give rise to the mechanical response, we have produced three-dimensional reconstructions by tomography of both rigor and AMPPNP-treated muscle that do not average the repeating motifs of crossbridges, and thereby retain information on variability of crossbridge structure and distribution. Tomograms can be averaged when display of only the regular features is wanted. Tomograms of rigor IFM show double-headed lead and single-headed rear crossbridges. Tomograms of IFM treated with AMPPNP at 23 degrees C reveal many double-headed and some single-headed "lead" bridges but few crossbridges corresponding to the rear bridges of rigor. Instead, new non-rigor forms of variably angled crossbridges are found bound to actin sites not labeled with myosin heads in rigor. This indicates that the rear bridges of rigor have redistributed during the transition from rigor to the AMPPNP state, which could explain the maintenance of rigor stiffness despite the loss of tension. Comparison of in situ crossbridges in tomograms of rigor with atomic model of acto-S1, the complex formed by myosin subfragment 1 and actin, reveals that the regulatory domain of S1 would require significant bending and realignment to fit into both types of rigor crossbridges. The modifications are particularly significant for the rear bridges and suggest that differential strain in the regulatory domain of rear bridges may be the basis for their detachment and redistribution upon binding AMPPNP. Similar comparison using lead-type crossbridges in AMPPNP reveals departures from the rigor acto-S1 atomic model that include azimuthal straightening and a slight M-ward bending in the regulatory domain. Both the motor and regulatory domains of the new non-rigor crossbridges differ from those in the atomic model of acto-S1. A new crossbridge motif identified in AMPPNP-treated muscle consists of paired rigor-like and non-rigor crossbridges and suggests possible transitions in the myosin working stroke.     

On the reactions 2 C + O2 and C + CO2 at very low pressure

In an ultra high vacuum heterogeneous gas reactions such as 2 C + O₂^G → 2 CO^G and C + CO₂^G → 2 CO^G often show a less complicated reaction path than under normal pressure. In the present study the graphite sample is a commercial light‐bulb filament, which is extremely resistant against oxidation. Under low pressure the combustion reaction is of first order with a continuous transition to zero order at temperatures between 900 and 1300 K depending on the oxygen pressure. The Boudouard reaction behaves similarly but obeys zero order only around 2000 K and for CO₂ pressures around 1 bar. The measured and the statistically calculated reaction rates agree well. An insight of the details of the reaction and chemisorption is determined by the evaluation of experiments carried out in an ultra high vacuum using isotopes such as ¹³CO₂^G. The Boudouard equilibrium for graphite can be reached only catalytically, e.g., with sponge iron in statu nascendi.     

Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers

Clenbuterol, a beta 2-adrenoceptor agonist, has therapeutic potential for the treatment of muscle-wasting diseases, yet its effects, especially at the single-fiber level, have not been fully characterized. Male C57BL/10 mice were allocated to three groups: Control-Treated mice were administered clenbuterol (2 mg.kg-1. day-1) via their drinking water for 15 wk; Trained-Treated mice underwent low-intensity training (unweighted swimming, 5 days/wk, 1 h/day) in addition to receiving clenbuterol; and Control mice were sedentary and untreated. Contractile characteristics were determined on membrane-permeabilized fibers from the extensor digitorum longus (EDL) and soleus muscles. Fast fibers from the EDL and soleus muscles of Treated mice exhibited decreases in Ca2+ sensitivity. Endurance exercise offset clenbuterol's effects, demonstrated by similar Ca2+ sensitivities in the Trained-Treated and Control groups. Long-term clenbuterol treatment did not affect the normalized maximal tension of fast or slow fibers but increased the proportion of fast fibers in the soleus muscle. Training increased the proportion of fibers with high and intermediate succinate dehydrogenase activity in the EDL and soleus muscles, respectively. If clenbuterol is to be used for treating muscle-wasting disorders, some form of low-intensity exercise might be encouraged such that potentially deleterious slow-to-fast fiber type transformations are minimized. Indeed, in the mouse, low-intensity exercise appears to prevent these effects.     

Capillaries with fenestrations around regenerating muscle fibers in the soleus muscle of the dystrophic (dy) mouse

A 65-year-old woman developed nephrotic syndrome 7 years after receiving a cadaveric renal allograft. Renal biopsy and clinical laboratory evaluation revealed the underlying disease process to be AL amyloidosis. To our knowledge, this is the first reported case of de novo AL amyloid occurring in a renal allograft.     

The effect of CO2 on the blocking of excitation conduction by local anesthetics in feline A-delta and C fibers]

The data obtained showed that the CO2 potentiated the conduction blockade of the saphenous nerve with tertiary amine trimecaine in anesthetised cats. The data suggests that acidification of cytoplasm with increased CO2 increases the concentration of active cationic protonated forms of a local anesthetic agent.     

Effects of human and experimental cancer on the conversion of 14C tripalmitin to 14CO2

14C Tripalmitin was administered intraperitoneally to control mice and to mice bearing subcutaneous Krebs-2 carcinoma. The rate of excretion of 14CO2 was studied. The presence of a tumor induced a greater than 80% suppression of the formation of 14CO2 within 24 hours from the implantation of the tumor, thus allowing unambiguous identification of the tumor-bearing mice. When cancer patients were studied, along with normal volunteers and patients with non-neoplastic diseases, 14CO2 excretion data could be used to identify the cancer patients with an overall accuracy of 84%.     

Size and myosin heavy chain profiles of rat hindlimb extensor muscle fibers after 2 weeks at 2G

METHOD: The effects of 14 d of continuous centrifugation at approximately 2G on the hindlimb extensor musculature of male rats were studied. RESULTS: The mean body mass of centrifuged rats was 17% smaller than age-matched controls. In centrifuged rats, the mean absolute masses of the soleus and medial gastrocnemius (MG) were similar to control, while the mean relative masses (expressed as milligram muscle mass/gram of body mass) were larger than control. Based on a battery of monoclonal antibodies for specific myosin heavy chains (MHC), the soleus of centrifuged rats had a lower percentage (68 vs. 74%) of fibers expressing type I MHC only and a higher percentage (15 vs. 10%) that co-expressed type I and IIa MHC's. The MHC composition of fibers from the deep portion of the MG was unaffected by centrifugation. The MHC compositions based on SDS-PAGE gel electrophoresis for each muscle were similar in the two groups. Mean fiber size of each fiber type in the soleus was unaffected by centrifugation. In the MG, the fibers, expressing only type IIb MHC were smaller in the centrifuge compared to control rats. CONCLUSION: Although 2 weeks of chronic centrifugation at 2G resulted in a cessation of body growth, there was essentially no effect on the muscle masses or fiber size in either a slow or fast extensor muscle. These data suggest that periods of centrifugation may be beneficial in maintaining extensor muscle mass in an animal that is not growing at a normal rate e.g., during chronic unloading.     

活性炭表面性质对Pd/C常温氧化CO的影响

采用等体积浸渍法制备了活性炭负载Pd催化剂(Pd/C),通过正交实验研究了活性炭的种类、催化剂的制备条件等对活性炭负载钯催化剂上CO氧化性能的影响,得到了最优的制备条件。并通过N2吸附、程序升温脱附(TPD)、程序升温还原(H2-TPR)和透射电镜(TEM)等对催化剂进行了表征。正交实验极差分析表明制备各因素对催化剂氧化CO活性影响的次序为:还原剂>活性炭>还原剂用量>还原温度>还原溶pH值。催化剂表征结果表明活性炭的比表面积和孔径分布不是决定Pd/C催化剂性能的关键因素,活性炭的种类、表面组成和性质对催化剂的性能有显著的影响。其中椰壳炭(AC1)表面羧基的活性较高,同时具有较强的表面碱性,有利于活性金属Pd在载体表面的分散,并提高了Pd与载体之间的相互作用,从而使催化剂具有较高的CO氧化性能。提高Pd的担载量,可显著提高催化剂稳定性。以乙二醇作为还原剂,在pH=10,还原温度为60℃的条件下所制备的0.5%Pd/AC催化剂,在反应温度20℃时连续反应120 h仍可保持CO的全转化。     

Iodination of mouse EGF with chloramine T at 4 degrees C: characterization of the iodinated peptide and comparison with other labelling methods

The BP-1/6C3 molecule expressed by early B lineage cells and some stromal cells has been identified as aminopeptidase A (APA). We have previously demonstrated that IL-7 selectively induces BP-1/APA expression by pre-B cells coincident with their growth. Here we directly demonstrate that BP-1 is preferentially expressed by the proliferating subpopulation of normal B cell progenitors. Furthermore, when non-adherent BALB/c bone marrow cells were incubated with IL-7 in the presence of purified BP-1 antibody, B cell precursor proliferation was markedly inhibited. Modulation of the BP-1/6C3 antigen did not occur in the presence of the BP-1 antibody, but APA enzymatic activity was significantly inhibited. The 6C3 antibody, which recognizes a different epitope on the APA molecule, had no effect on either B cell precursor proliferation or APA enzyme activity. We hypothesized that neutralization of APA by the BP-1 antibody results in inhibition of IL-7 driven B cell precursor proliferation. However, when isolated 14.8+ bone marrow cells were cultured with IL-7 in the presence of the BP-1 antibody, no inhibition of proliferation occurred. This data suggested that the effect of the BP-1 antibody might be related to the action of APA on peptides in the marrow microenvironment which are not present in cultures of isolated B cell precursors. The addition of irradiated non-adherent bone marrow cells to the 14.8+ cell cultures restored the inhibitory effect of the BP-1 antibody. Based on these observations, we propose that APA cleaves a small peptide which serves as a natural inhibitor of B cell precursor proliferation.     

The micromechanics of fatigue crack growth at 25 °C in Ti-6Al-4V reinforced with SCS-6 fibers

Micromechanics parameters for fatigue cracks growing perpendicular to fibers were measured for the center-notched specimen geometry. Fiber displacements, measured through small port holes in the matrix made by electropolishing, were used to determine fiber stresses, which ranged from 1.1 to 4 GPa. Crack opening displacements at maximum load and residual crack opening displacements at minimum load were measured. Matrix was removed along the crack flanks after completion of the tests to reveal the extent and nature of the fiber damage. Analyses were made of these parameters, and it was found possible to link the extent of fiber debonding to residual COD and the shear stress for fiber sliding to COD. Measured experimental parameters were used to compute crack growth rates using a well-known fracture mechanics model for fiber bridging tailored to these experiments.     

Effects of a single administration of clozapine on mouse brain catecholamines

In acute experiments on cats anesthetized with nembutal and chloralose the projections of different parts of orbito-frontal cortex, basal temporal cortex and hippocampus to hypothalamic nuclei were studied by focal potential recording. It was found that the proreal gyrus has local projections into the latero-dorsal parts of the preoptical region, rostral parts of the forebrain medial bundle, lateral and posterior hypothalamus with mammilary bodies. The orbital gyrus is projected mainly into latero-dorsal parts of the forebrain medial bundle, latero-ventral part of the preoptical region, and the region of lateral and latero-dorsal hypothalamic nuclei. Projections from the orbital gyrus are of a relatively diffuse character. The basal temporal cortex has diffuse projections into the central part of the preoptical region, latero-ventral part of the forebrain medial bundle and lateral mammilary body. No pronounced foci were observed in the hypothalamic structures during stimulation of the hyppocampus, but diffuse projections were found into ventral parts of the preoptical region and ventral regions of the forebrain medial bundle as well as into lateral hypothalamus and lateral mammilary nucleus.     

Effects of adrenalectomy or RU-486 on rat muscle fibers during hindlimb suspension

The purpose of this study was to investigate the effects of a glucocorticoid antagonist, RU-486, and of adrenalectomy (ADX) on rat skeletal muscle structural properties after 3, 7, and 14 days of hindlimb suspension (H). After H, a significant loss in muscle weight was observed as early as 3 days in soleus (SOL; -10%) and adductor longus (AL; -14%) muscles. In SOL, after only 7 days, a reduction (-14%) in type I fiber percent distribution occurred, accompanied by an increase (+129%) in intermediate type I fibers. Fiber type changes increased depending on the duration of H. In AL muscle, no change occurred after H in the fiber type composition despite a similar degree of muscle atrophy. Treatment with RU-486 or ADX significantly reduced the loss of SOL weight observed after 14 days (-42 and -44%, respectively, vs. -50% for H rats), delayed the SOL atrophy (from 3 to 7 days), and normalized the shift in fiber type distribution induced by H. In SOL, administration of RU-486 (but not ADX) partly prevented the reduction in size induced by H of all the fibers. In AL, neither treatment affected the extent of muscle atrophy, even though the reduction in type IIa fiber size was prevented by RU-486 but not by ADX after 14 days of suspension. ADX or RU-486 administration did not prevent the extensor digitorum longus weight loss observed after 14 days of suspension but allowed a recovery of its normal fiber type composition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Three-dimensional structure of nucleotide-bearing crossbridges in situ: oblique section reconstruction of insect flight muscle in AMPPNP at 23 degrees C

We have explored the three-dimensional structure of myosin crossbridges in situ in order to define the structural changes that occur when nucleotide binds to the myosin motor. When AMPPNP binds to rigor insect flight muscle, each half sarcomere lengthens by approximately 2.0 nm and tension is reduced by approximately 70% without a reduction in stiffness, suggesting partial reversal of the power stroke. We have obtained averaged oblique section three-dimensional reconstructions of mechanically monitored insect flight muscle in AMPPNP that permit simultaneous examination of all myosin crossbridges within the unit cell and direct comparison of calculated transforms with X-ray diagrams of the native fibers. Transforms calculated from the oblique section reconstruction of AMPPNP insect flight muscle at 23 degrees C show good agreement with native X-ray diagrams, suggesting that the average crossbridge forms in the reconstruction reflect the native structure. In contrast to the rigor lead and rear crossbridges in the double chevrons, the averaged reconstruction of AMPPNP fibers show only one crossbridge class, in the position of the rigor lead bridge. The portion of the crossbridge close to the thick filament appears broader than in rigor, and shows a small 0.5 to 1.0 nm M-ward shift of the regulatory domain region of myosin. In transverse view, AMPPNP "lead" crossbridges are less azimuthally bent than rigor. Fitting the atomic model of actomyosin subfragment 1 to the averaged crossbridges shows that the detectable differences between rigor bridges and between rigor and AMPPNP bridges occur in the alignment and angles of the regulatory domains and suggests that rear bridges are more strained than lead crossbridges. The apparent absence of rear bridges in AMPPNP in averaged reconstructions indicates detachment of a number of force-bearing bridges, which conflicts with the maintained stiffness of the fibers used for the reconstruction. This conflict may be explained if rigor rear bridges become distributed irregularly over more actin sites in AMPPNP, so that their average density is too low to appear in the averaged reconstructions. The reconstructions indicate that in insect flight muscle the response of in situ rigor crossbridges to AMPPNP binding is not uniform. Lead bridges persist but have altered structure in the light chain domain, whereas rear bridges detach and possibly redistribute. Shape changes in attached myosin heads within the myofibrillar lattice are in the appropriate direction and of the appropriate magnitude needed to explain the sarcomere lengthening. This could be a direct response to nucleotide binding, a passive response to rear bridge detachment, or a combination of both.