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121.
Mechanical impedance as determinant of inspiratory neural drive during exercise in humans 总被引:1,自引:0,他引:1
Five healthy males exercised progressively with small 2-min increments in work load. We measured inspiratory drive (occlusion pressure, P0.1), pulmonary resistance (RL), dynamic pulmonary compliance (Cdyn), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi). Minute ventilation (VE), mean inspiratory flow rate (VT/TI), and P0.1 all increased exponentially with increased work load, but P0.1 increased at a faster rate than did VT/TI or VE. Thus effective impedance (P0.1/VT/TI) rose throughout exercise. The increasing P0.1 was mostly due to augmented Pdi and coincided with increased EMGdi during this initial portion of inspiration. We found no consistent change in RL or Cdyn throughout exercise. With He breathing (80% He-20% O2), RL was reduced at all work loads; P0.1 fell in comparison with air-breathing values and VE, VT, and VT/TI rose in moderate and heavy work; and P0.1/VT/TI was unchanged with increasing exercise loads. Step reductions in gas density at a constant work load of any intensity showed an immediate reduction in the rate of rise of EMGdi and Pdi followed by increased VT/TI, breathing frequency, and hypocapnia. These changes were maintained during prolonged periods of unloading and were immediately reversible on return to air breathing. These data are consistent with the existence of a reflex effect on the magnitude of inspiratory neural drive during exercise that is sensitive to the load presented by the normal mechanical time constant of the respiratory system. This "load" is a significant determinant of the hyperpneic response and thus of the maintenance of normocapnia during exercise. 相似文献
122.
The effect of non-rapid-eye-movement (NREM) sleep on total pulmonary resistance (RL) and respiratory muscle function was determined in four snorers and four nonsnorers. RL at peak flow increased progressively from wakefulness through the stages of NREM sleep in all snorers (3.7 +/- 0.4 vs. 13.0 +/- 4.0 cmH2O X 0.1(-1) X s) and nonsnorers (4.8 +/- 0.4 vs. 7.5 +/- 1.1 cmH2O X 1(-1) X s). Snorers developed inspiratory flow limitation and progressive increase in RL within a breath. The increased RL placed an increased resistive load on the inspiratory muscles, increasing the pressure-time product for the diaphragm between wakefulness and NREM sleep. Tidal volume and minute ventilation decreased in all subjects. The three snorers who showed the greatest increase in within-breath RL demonstrated an increase in the contribution of the lateral rib cage to tidal volume, a contraction of the abdominal muscles during a substantial part of expiration, and an abrupt relaxation of abdominal muscles at the onset of inspiration. We concluded that the magnitude of increase in RL leads to dynamic compression of the upper airway during inspiration, marked distortion of the rib cage, recruitment of the intercostal muscles, and an increased contribution of expiratory muscles to inspiration. This increased RL acts as an internal resistive load that probably contributes to hypoventilation and CO2 retention in NREM sleep. 相似文献
123.
David A. Schaer Richard P. Beckmann Jack A. Dempsey Lysiane Huber Amelie Forest Nelusha Amaladas Yanxia Li Ying Cindy Wang Erik R. Rasmussen Darin Chin Andrew Capen Carmine Carpenito Kirk A. Staschke Linda A. Chung Lacey M. Litchfield Farhana F. Merzoug Xueqian Gong Philip W. Iversen Michael Kalos 《Cell reports》2018,22(11):2978-2994
124.
Apical Enrichment of Human EGF Precursor in Madin-Darby Canine Kidney Cells Involves Preferential Basolateral Ectodomain Cleavage Sensitive to a Metalloprotease Inhibitor 总被引:2,自引:0,他引:2
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Peter J. Dempsey Katherine S. Meise Yoshino Yoshitake Katsuzo Nishikawa Robert J. Coffey 《The Journal of cell biology》1997,138(4):747-758
EGF precursor (proEGF) is a member of the family of membrane-anchored EGF-like growth factors that bind with high affinity to the epidermal growth factor receptor (EGFR). In contrast to human transforming growth factor-α precursor (proTGFα), which is sorted basolaterally in Madin-Darby canine kidney (MDCK) cells (Dempsey, P., and R. Coffey, 1994. J. Biol. Chem. 269:16878–16889), we now demonstrate that human proEGF overexpressed in MDCK cells is found predominantly at the apical membrane domain under steady-state conditions. Nascent proEGF (185 kD) is not sorted but is delivered equally to the apical and basolateral membranes, where it is proteolytically cleaved within its ectodomain to release a soluble 170-kD EGF form into the medium. Unlike the fate of TGFα in MDCK cells, the soluble 170-kD EGF species accumulates in the medium, does not interact with the EGFR, and is not processed to the mature 6-kD peptide. We show that the rate of ectodomain cleavage of 185-kD proEGF is fourfold greater at the basolateral surface than at the apical surface and is sensitive to a metalloprotease inhibitor, batimastat. Batimastat dramatically inhibited the release of soluble 170-kD EGF into the apical and basal medium by 7 and 60%, respectively, and caused a concordant increase in the expression of 185-kD proEGF at the apical and basolateral cell surfaces of 150 and 280%, respectively. We propose that preferential ectodomain cleavage at the basolateral surface contributes to apical domain localization of 185-kD proEGF in MDCK cells, and this provides a novel mechanism to achieve a polarized distribution of cell surface membrane proteins under steady-state conditions. In addition, differences in disposition of EGF and TGFα in polarized epithelial cells offer a new conceptual framework to consider the actions of these polypeptide growth factors. 相似文献
125.
Babcock Mark A.; Pegelow David F.; Johnson Bruce D.; Dempsey Jerome A. 《Journal of applied physiology》1996,81(5):2156-2164
Babcock, Mark A., David F. Pegelow, Bruce D. Johnson, andJerome A. Dempsey. Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue. J. Appl.Physiol. 81(5): 2156-2164, 1996.We usedbilateral phrenic nerve stimulation (BPNS; at 1, 10, and 20 Hz atfunctional residual capacity) to compare the amount of exercise-induceddiaphragm fatigue between two groups of healthy subjects, a high-fitgroup [maximal O2consumption (O2 max) = 69.0 ± 1.8 ml · kg1 · min1,n = 11] and a fit group(O2 max = 50.4 ± 1.7 ml · kg1 · min1,n = 13). Both groups exercised at88-92% O2 maxfor about the same duration (15.2 ± 1.7 and 17.9 ± 2.6 min forhigh-fit and fit subjects, respectively,P > 0.05). The supramaximal BPNS test showed a significant reduction (P < 0.01) in the BPNS transdiaphragmatic pressure (Pdi) immediatelyafter exercise of 23.1 ± 3.1% for the high-fit group and23.1 ± 3.8% (P > 0.05)for the fit group. Recovery of the BPNS Pdi took 60 min in both groups.The high-fit group exercised at a higher absolute workload, whichresulted in a higher CO2production (+26%), a greater ventilatory demand (+16%) throughout theexercise, and an increased diaphragm force output (+28%) over theinitial 60% of the exercise period. Thereafter, diaphragm force outputdeclined, despite a rising minute ventilation, and it was not differentbetween most of the high-fit and fit subjects. In summary, the high-fitsubjects showed diaphragm fatigue as a result of heavy enduranceexercise but were also partially protected from excessive fatigue,despite high ventilatory requirements, because their hyperventilatoryresponse to endurance exercise was reduced, their diaphragm wasutilized less in providing the total ventilatory response, and possiblytheir diaphragm aerobic capacity was greater. 相似文献
126.
Thomas GH; Newbern EC; Korte CC; Bales MA; Muse SV; Clark AG; Kiehart DP 《Molecular biology and evolution》1997,14(12):1285-1295
Many structural, signaling, and adhesion molecules contain tandemly
repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin
superfamily of F-actin-crosslinking proteins contains an array of triple
alpha-helical motifs (spectrin repeats). We present here the complete
sequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H).
The sequence of beta H supports the origin of alpha- and beta-spectrins
from a common ancestor, and we present a novel model for the origin of the
spectrins from a homodimeric actin-crosslinking precursor. The pattern of
similarity between the spectrin repeat units indicates that they have
evolved by a series of nested, nonuniform duplications. Furthermore, the
spectrins and dystrophins clearly have common ancestry, yet the repeat unit
is of a different length in each family. Together, these observations
suggest a dynamic period of increase in repeat number accompanied by
homogenization within each array by concerted evolution. However, today,
there is greater similarity of homologous repeats between species than
there is across repeats within species, suggesting that concerted evolution
ceased some time before the arthropod/vertebrate split. We propose a
two-phase model for the evolution of the spectrin repeat arrays in which an
initial phase of concerted evolution is subsequently retarded as each new
protein becomes constrained to a specific length and the repeats diverge at
the DNA level. This evolutionary model has general applicability to the
origins of the many other proteins that have tandemly repeated motifs.
相似文献
127.
Identification of an Arabidopsis locus required for resistance to turnip crinkle virus 总被引:8,自引:1,他引:7
D'Maris Amick Dempsey M. Sudam Pathirana Kristin K. Wobbe Daniel F. Klessig 《The Plant journal : for cell and molecular biology》1997,11(2):301-311
Inoculation of turnip crinkle virus (TCV) into a (TCV)-resistant line of Arabidopsis thaliana , Di-17, results in the development of a hypersensitive response (HR) on the inoculated leaves. In contrast, an HR does not occur when leaves of the TCV-susceptible Di-3 line or the susceptible ecotypes Columbia (Col-0), or Landsberg erecta ( Ler ) are inoculated. Genetic analysis of progeny from crosses between Di-17 and either Di-3, Col-0 or Ler demonstrates that the development of an HR is regulated by a single dominant nuclear locus, herein designated HRT . Using progeny from a Di-17 X Col-0 cross, HRT was mapped to chromosome 5, where it is tightly linked to the DFR locus. We also demonstrate that a variety of resistance-associated phenomena, including the TCV-induced accumulation of salicylic acid, camalexin and autofluorescent cell-wall material, correlate with the HR, suggesting the possibility that HRT is required for their activation. 相似文献
128.
W B Dempsey 《Journal of bacteriology》1973,116(1):373-377
Pyridoxineless mutants of Escherichia coli are lysed in a few hours when starved for pyridoxine in a glucose minimal medium containing glycine at 10 mM. The lysis is prevented equally well by l-alanine and by d-alanine when either is present at 0.1 mM. The lysis is potentiated by 0.5 mM l-methionine. The peculiar susceptibility of E. coli B to glycine-mediated lysis during starvation for pyridoxine suggests that the starvation reduces the availability of some normal antagonist of glycine, presumably alanine. 相似文献
129.
130.
W B Dempsey 《Journal of bacteriology》1971,108(1):415-421
Pyridoxineless mutants of Escherichia coli B which specifically require pyridoxal or pyridoxamine for growth can be divided into classes according to their growth responses in enriched media. Members of the slowest growing class synthesize vitamin B(6) at the fastest rates when starved for pyridoxal in glycerol minimal medium. After 80 min of synthesis at 4 x 10(-10) moles of vitamin B(6) per mg of cells per hr, the rate increases four- to fivefold and continues at the new rate for several hours. The shift to the new rate is prevented by chloramphenicol, thus suggesting that a derepression mechanism exists to control vitamin B(6) synthesis in addition to the previously discovered feedback control. 相似文献