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81.
82.
Baldridge BR Burgess DE Zimmerman EE Carroll JJ Sprinkle AG Speakman RO Li SG Brown DR Taylor RF Dworkin S Randall DC 《American journal of physiology. Regulatory, integrative and comparative physiology》2002,283(3):R748-R756
This experiment quantified the initial disruption and subsequent adaptation of the blood pressure (BP)-heart rate (HR) relationship after spinal cord transection (SCT). BP and HR were recorded for 4 h via an implanted catheter in neurally intact, unanesthetized rats. The animals were then anesthetized, and their spinal cords were severed at T(1)-T(2) (n = 5) or T(4)-T(5) (n = 6) or sham lesioned (n = 4). BP was recorded for 4 h daily over the ensuing 6 days. The neurally intact rat showed a positive cross correlation, with HR leading BP at the peak by 1.8 +/- 0.8 (SD) s. The cross correlation in unanesthetized rats (n = 2) under neuromuscular blockade was also positive, with HR leading. After SCT at T(1)-T(2), the cross correlation became negative, with BP leading HR, and did not change during the next 6 days. The cross correlation also became negative 1-3 days after SCT at T(4)-T(5), but in four rats by day 6 and thereafter the cross correlation progressively reverted to a positive value. We propose that the positive cross correlation with HR leading BP in the intact rat results from an open-loop control that depends on intact supraspinal input to sympathetic preganglionic neurons in the spinal cord. After descending sympathetic pathways were severed at T(1)-T(2), the intact vagal pathway to the sinoatrial node dominated BP regulation via the baroreflex. We suggest that reestablishment of the positive correlation after SCT at T(4)-T(5) was attributable to the surviving sympathetic outflow to the heart and upper vasculature reasserting some effective function, perhaps in association with decreased spinal sympathetic hyperreflexia. The HR-BP cross correlation may index progression of sympathetic dysfunction in pathological processes. 相似文献
83.
84.
Albertine KH Wang L Watanabe S Marathe GK Zimmerman GA McIntyre TM 《American journal of physiology. Lung cellular and molecular physiology》2002,283(1):L219-L233
Airway hyperresponsiveness, airway inflammation, and reversible airway obstruction are physiological hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole body plethysmography to noninvasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indexes of airway hyperresponsiveness measured by invasive means. Furthermore, correlation with quantitative histological data for tissue infiltration by inflammatory and immune cells, particularly in the wall of airways, during daily airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice that were immunized with ovalbumin or vehicle (saline) and sensitized to aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed to aerosolized ovalbumin or vehicle, respectively, on days 14-22. We assessed airway hyperresponsiveness to methacholine noninvasively on days 14, 15, 18, or 22; we studied the same mice 24 h later while they were anesthetized for invasive analyses of airway hyperresponsiveness. Plasma total IgE concentration was significantly higher in the ovalbumin-treated mice compared with the vehicle-treated mice, but this did not correlate with eosinophil number. Peak airway hyperresponsiveness measured by either approach correlated early during daily antigen challenge (days 14 and 15), but this correlation was lost later during subsequent daily antigen challenges (days 18 and 22). On days 14 and 15, peak airway hyperresponsiveness correlated with transmigration of neutrophils and macrophages, but not lymphocytes, in the peribronchovascular connective tissue sheaths. This extravascular accumulation was found to be focal by three-dimensional microscopy. We conclude that, although ovalbumin treatment changed lung function in mice, correlation between noninvasive and invasive measures of peak airway hyperresponsiveness was inconsistent. 相似文献
85.
Zimmerman SB 《Journal of structural biology》2002,138(3):4180-206
The DNA of growing cells of Escherichia coli occurs in one or a few lobular bodies known as nucleoids. Upon exposure to chloramphenicol, the nucleoids assume compact, rounded forms ("cm-nucleoids") that have been described as ring- or sphere-shaped. Multiple views of single cells or spheroplasts, however, support a different, curved toroid shape for cm-nucleoids. The multiple views were obtained either by DNA fluorescence imaging as the cells or spheroplasts reoriented in liquid medium or by optical sectioning using phase-contrast or fluorescence imaging of immobilized cells. The curved toroid shape is consistent with electron microscope images of thin sections of chloramphenicol-treated cells. The relationship of this structure to active and inactive nucleoids and to the smaller toroidal forms made by in vitro DNA condensation is discussed. 相似文献
86.
Savage-Dunn C Maduzia LL Zimmerman CM Roberts AF Cohen S Tokarz R Padgett RW 《Genesis (New York, N.Y. : 2000)》2003,35(4):239-247
In the nematode Caenorhabditis elegans, a TGFbeta-related signaling pathway regulates body size and male tail morphogenesis. We sought to identify genes encoding components or modifiers of this pathway in a large-scale genetic screen. Remarkably, this screen was able to identify essentially all core components of the TGFbeta signaling pathway. Among 34 Small mutants, many mutations disrupt genes encoding recognizable components of the TGFbeta pathway: DBL-1 ligand, DAF-4 type II receptor, SMA-6 type I receptor, and SMA-2, SMA-3, and SMA-4 Smads. Moreover, we find that at least 11 additional complementation groups can mutate to the Small phenotype. Four of these 11 genes, sma-9, sma-14, sma-16, and sma-20 affect male tail morphogenesis as well as body size. Two genes, sma-11 and sma-20, also influence regulation of the developmentally arrested dauer larval stage, suggesting a role in a second characterized TGFbeta pathway in C. elegans. Other genes may represent tissue-specific factors or parallel pathways for body size control. Because of the conservation of TGFbeta signaling pathways, homologs of these genes may be involved in tissue specificity and/or crosstalk of TGFbeta pathways in other animals. 相似文献
87.
Vinores SA Xiao WH Zimmerman R Whitcup SM Wawrousek EF 《Histology and histopathology》2003,18(3):797-810
IL-1beta is a pro-inflammatory agent associated with angiogenesis and increased vascular permeability. To determine whether IL-1beta elicits these responses through an upregulation of VEGF, transgenic mice that overexpress IL-1beta in the lens were evaluated at various time points for the localization of VEGF, the location and extent of blood-retinal barrier (BRB) breakdown, and the origin and extent of neovascularization (NV). In homozygous and heterozygous transgenic mice, but not controls, intense VEGF immunoreactivity was scattered throughout the retina at postnatal days 5-7 (P5-7), just after the onset of inflammatory cell infiltration. VEGF staining in the retina remained widespread, but weak from P9-15. Beginning at P15, the intensity of VEGF immunoreactivity achieved a second peak, which it maintained through adulthood. This peak coincided with significant retinal destruction due to massive inflammation. The onset of BRB breakdown coincided with the upregulation of VEGF (P5-7) and widespread BRB breakdown was demonstrated from about P9. From P9-12, aggregates of cells positive for Griffonia simplicifolia isolectin-B4, a marker for vascular endothelial cells, formed on the retinal surface. These cells migrated into the retina at P12-15 with the more superficial cells forming a network of vessels and the deeper cells remaining in small clusters, thus demonstrating that NV occurs much later than BRB breakdown. Non-transgenic FVB/N mice, which undergo retinal degeneration beginning at about P9, also demonstrate the latter peak of VEGF upregulation and the accompanying BRB breakdown, but not the early upregulation. VEGF immunostaining of transgenic and non-transgenic mouse retinas was eliminated by pre-incubation of the VEGF antibodies with VEGF peptide. The data suggest that the early peak of VEGF upregulation (P5-7) and its accompanying BRB breakdown is due to IL-1beta expression and is likely to be dependent on inflammatory cell infiltration. The latter peak appears to be related to retinal destruction. 相似文献
88.
89.
Jochem FJ Smith GJ Gao Y Zimmerman RC Cabello-Pasini A Kohrs DG Alberte RS 《Cytometry》2000,39(3):173-178
BACKGROUND: The uptake of nitrate by phytoplankton is a central issue in biological oceanography due to its importance to primary production and vertical flux of biogenic carbon. Nitrate reductase catalyzes the first step of nitrate assimilation, the reduction of NO(3) to NO(2). A cytometric protocol to detect and quantify relative changes in nitrate reductase (NR) protein content of the marine centric diatom Skeletonema costatum is presented. METHODS: Immunolabeling of NR protein was achieved with polyclonal antibodies raised against S.costatum NR. Antisera specific to a NR protein subunit and to a NR polypeptide sequence were compared, and cytometric results of NR protein abundance were related to Western analyses. Changes in cellular NR abundance and activity were followed during an upwelling simulation experiment in which S. costatum was exposed to a shift from ammonia to nitrate as major nitrogen source. RESULTS: NR protein could be detected in NO(3)-grown cells and at extremely low levels hardly discernible by Western Blot densiometry in NH(4)-grown cells. The protocol allowed observation of early stages of NR induction during an upwelling simulation. NR abundance increased after the nutrient shift to reach a new physiological "steady-state" 96 hrs later. NR activity exhibited diel variation with maxima at mid-day. NR abundance as estimated by both flow cytometry and Western analysis exhibited a hyperbolic relationship to NR activity. This pattern suggests post-translational activation of NR protein. CONCLUSIONS: The presented protocol allows the differentiation of NH(4)- versus NO(3)-grown algae as well as the monitoring of early stages in the induction of nitrate assimilatory capacities. 相似文献
90.
Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions 总被引:8,自引:0,他引:8
Fatty acid binding proteins (FABP) form a family of proteins displaying tissue-specific expression. These proteins are involved in fatty acid (FA) transport and metabolism by mechanisms that also appear to be tissue-specific. Cellular retinoid binding proteins are related proteins with unknown roles in FA transport and metabolism. To better understand the origin of these tissue-specific differences we report new measurements, using the acrylodated intestinal fatty acid binding protein (ADIFAB) method, of the binding of fatty acids (FA) to human fatty acid binding proteins (FABP) from brain, heart, intestine, liver, and myelin. We also measured binding of FA to a retinoic acid (CRABP-I) and a retinol (CRBP-II) binding protein and we have extended to 19 different FA our characterization of the FA-ADIFAB and FA-rat intestinal FABP interactions. These studies extend our previous analyses of human FABP from adipocyte and rat FABPs from heart, intestine, and liver. Binding affinities varied according to the order brain approximately myelin approximately heart > liver > intestine > CRABP > CRBP. In contrast to previous studies, no protein revealed a high degree of selectivity for particular FA. The results indicate that FA solubility (hydrophobicity) plays a major role in governing binding affinities; affinities tend to increase with increasing hydrophobicity (decreasing solubility) of the FA. However, our results also reveal that, with the exception of the intestinal protein, FABPs exhibit an additional attractive interaction for unsaturated FA that partially compensates for their trend toward lower affinities due to their higher aqueous solubilities. Thermodynamic potentials were determined for oleate and arachidonate binding to a subset of the FABP and retinoid binding proteins. FA binding to all FABPs was enthalpically driven. The DeltaH degrees values for paralogous FABPs, proteins from the same species but different tissues, reveal an exceptionally wide range of values, from -22 kcal/mol (myelin) to -7 kcal/mol (adipocyte). For orthologous FABPs from the same tissue but different species, DeltaH degrees values were similar. In contrast to the enthalpic dominance of FA binding to FABP, binding of FA to CRABP-I was entropically driven. This is consistent with the notion that FA specificity for FABP is determined by the enthalpy of binding. Proteins from different tissues also revealed considerable heterogeneity in heat capacity changes upon FA binding, DeltaC(p) values ranged between 0 and -1.3 kcal mol(-1) K(-1). The results demonstrate that thermodynamic parameters are quite different for paralogous but are quite similar for orthologous FABP, suggesting tissue-specific differences in FABP function that may be conserved across species. 相似文献