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1.
An perfusion system was used to assess the effects of chloride channel blockers, dopamine (DA) receptor agonists and antagonists, and GABA receptor agonists and antagonists on prolactin release from the mouse anterior pituitary. Dopamine and muscimol inhibited prolactin release ( respectively). The GABA receptor antagonist bicuculline blocked the inhibition of prolactin release by muscimol but not dopamine. The dopamine receptor antagonist chlorpromazine blocked the dopamine- but not muscimol-induced inhibition of prolactin release. Haloperidol, however, reversed both the muscimol and dopamine induced inhibition of prolactin release. Furthermore, the chloride channel blocker picrotoxinin blocked the inhibition of prolactin release elicited by both dopamine and muscimol. These later results suggest that the anterior pituitary dopamine receptor which mediates the inhibition of prolactin release may be coupled to a picrotoxinin sensitive chloride ionophore and that haloperidol may affect the function of both DA and GABA receptors in the anterior pituitary. 相似文献
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Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), and tumorigenesis have been increasing over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that in response to increased transforming growth factor - beta (TGFβ) signaling, the alveolar type II (ATII) epithelial cell undergoes phenotypic changes that may contribute to the complex pathobiology of PF. We have previously demonstrated that increased tissue stiffness associated with PF is a potent extracellular matrix (ECM) signal for epithelial cell activation of TGFβ. The work reported here explores the relationship between tissue stiffness and exposure to environmental stimuli in the activation of TGFβ. We hypothesized that exposure of ATII cells to fine particulate matter (PM2.5) will result in enhanced cell contractility, TGFβ activation, and subsequent changes to ATII cell phenotype. ATII cells were cultured on increasingly stiff substrates with or without addition of PM2.5. Exposure to PM2.5 resulted in increased activation of TGFβ, increased cell contractility, and elongation of ATII cells. Most notably, on 8 kPa substrates, a stiffness greater than normal but less than established fibrotic lung, addition of PM2.5 resulted in increased cortical cell stiffness, enhanced actin staining and cell elongation; a result not seen in the absence of PM2.5. Our work suggests that PM2.5 exposure additionally enhances the existing interaction between ECM stiffness and TGFβ that has been previously reported. Furthermore, we show that this additional enhancement is likely a consequence of intracellular reactive oxygen species (ROS) leading to increased TGFβ signaling events. These results highlight the importance of both the micromechanical and biochemical environment in lung disease initiation and suggest that individuals in early stages of lung remodeling during fibrosis may be more susceptible than healthy individuals when exposed to environmental injury adjuvants. 相似文献
4.
Cataract is the major reason for human blindness worldwide. α-Crystallin, as a key chaperone of eye lenses, keeps the lenticular tissues in its transparent state over time. In this study, cataract-causing familial mutations, P20R and A171T, were introduced in CRYАB gene. After successful expression in Escherichia coli and subsequent purification, the recombinant proteins were subjected to extensive structural and functional analyses using various spectroscopic techniques, gel electrophoresis, and electron microscopy. The results of fluorescence and Raman assessments suggest important but discreet conformational changes in human αB-Cry upon these cataractogenic mutations. Furthermore, the mutant proteins exhibited significant secondary structural alteration as revealed by FTIR and Raman spectroscopy. An increase in conformational stability was seen in the human αB-Cry bearing these congenital cataractogenic mutations. The oligomeric size distribution and chaperone-like activity of human αB-Cry were significantly altered by these mutations. The P20R mutant protein was observed to loose most of the chaperone-like activity. Finally, these cataractogenic mutant proteins exhibited an increased propensity to form the amyloid fibrils when incubated under environmental stress. Overall, the structural and functional changes in mutated human αB-Cry proteins can shed light on the pathogenic development of congenital cataracts. 相似文献
5.
Time-resolved x-ray diffraction and calorimetric studies at low scan rates: I. Fully hydrated dipalmitoylphosphatidylcholine (DPPC) and DPPC/water/ethanol phases 总被引:4,自引:4,他引:0
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The phase transitions in fully hydrated dipalmitoylphosphatidylcholine (DPPC) and DPPC/water/ethanol phases have been studied by lowangle time-resolved x-ray diffraction under conditions similar to those employed in calorimetry (scan rates 0.05-0.5°C/min and uniform temperature throughout the samples). This approach provides more adequate characterization of the equilibrium transition pathways and allows for close correlations between structural and thermodynamic data. No coexistence of the rippled gel (Pβ') and liquid-crystalline (Lα) phases was found in the main transition of DPPC; rather, a loss of correlation in the lamellar structure, observed as broadening of the lamellar reflections, takes place in a narrow temperature range of ~100 mK at the transition midpoint. Formation of a long-living metastable phase, denoted by Pβ'(mst), differing from the initial Pβ' was observed in cooling direction by both x-ray diffraction and calorimetry. No direct conversion of Pβ'(mst) into Pβ' occurs for over 24 h but only by way of the phase sequence Pβ'(mst) → Lβ' → Pβ'. According to differential scanning calorimetry (DSC), the enthalpy of the Pβ'(mst)-Lα transition is by ~5% lower than that of the Pβ'-Lα transition. The effects of ethanol (Rowe, E. S. 1983. Biochemistry. 22:3299-3305; Simon, S. A., and T. J. McIntosh. 1984. Biochim. Biophys. Acta 773:169-172) on the mechanism and reversibility of the DPPC main transition were clearly visualized. At ethanol concentrations inducing formation of interdigitated gel phase, the main transition proceeds through a coexistence of the initial and final phases over a finite temperature range. During the subtransition in DPPC recorded at scan rate 0.3°C/min, a smooth monotonic increase of the lamellar spacing from its subgel (Lc) to its gel (Lβ') phase value takes place. The width of the lamellar reflections remains unchanged during this transformation. This provides grounds to propose a “sequential” relaxation mechanism for the subgel-gel transition which is not accompanied by growth of domains of the final phase within the initial one. 相似文献
6.
Phylogenetic analysis and identification of different serovars of Mycobacterium intracellulare at the molecular level 总被引:17,自引:0,他引:17
Boris Böddinghaus Jörn Wolters Wiepke Heikens Erik C. Böttger 《FEMS microbiology letters》1990,70(2):197-204
Comparative 16S rRNA sequencing was used to infer the phylogenetic relationship among different serovars of the Mycobacterium avium-M. intracellulare complex as well as to define signature nucleotides characteristic for different serovars. In general, the groups defined by rRNA sequencing reflect the classification obtained with sensitin tests and pathogenicity examinations in chickens. Unique 16S rRNA sequence patterns could be defined for (1) M. avium, (2) M. intracellulare serovars 4, 5, 6, 8, 9, 10 and 11, (3) M. intracellulare serovars 12, 13, 14, 15, 17, 19 and 20, (4) M. intracellulare serovar 7 and (5) M. intracellulare serovar 18. Phylogenetically, groups 1 and 2 on one hand and groups 3, 4 and 5 on the other hand each share a common ancestor. M. paratuberculosis was indistinguishable from M. intracellulare serovars 4, 5, 6, 8, 9, 10 and 11 by this kind of analysis. 相似文献
7.
volker mosbrugger Bonn 《Pal?ontologische Zeitschrift》1985,59(3-4):183-199
In the last decade numerous evolutionary models have been proposed and intensively discussed. Surprisingly, the logical analysis of these different hypotheses is not of great importance in this debate. As a matter of fact, Neodarwinism is a consistent deductive system which is based on few but wellconfirmed axioms. Hence, very often, precise statements and definitions of standpoint can be made. This is exemplified by some repeatedly discussed models concerning the problems of Darwinian »adaptation« and »natural selection« 1. Following the logic of the Neodarwinian theory, extinction can only be the result of overspecialization if some very unusual assumptions are made. 2. The hypothesis of »punctuated equilibrium« GOULD 1982), the »effect hypothesis« (VRBA 1983) and the stochastic evolutionary model SCHOPF 1979) include elements which are logically inconsistent with the »modern synthesis«; they could be »true« only if at least one of the neodarwinian axioms (so far not disproved) is negated. 相似文献
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9.
Athanas I. Boyanov Boris G. Tenchov Rumiana D. Koynova Kamen S. Koumanov 《生物化学与生物物理学报:生物膜》1983,732(3):711-713
dl-Dipalmitoylphosphatidylcholine multilamellar vesicle suspensions were examined by the method of differential scanning calorimetry. A lack of the subtransition at 18°C was established. Such a subtransition is characteristic for l-dipalmitoylphosphatidylcholine suspensions. This lack is supposed to be the result of the impossibility of the racemic phospholipid mixture to form the low-temperature crystal structure Lc. 相似文献
10.
A survey of toxicity of cyanobacterial blooms in Lake Ladoga and adjacent water bodies 总被引:3,自引:1,他引:2
Boris V. Gromov Alexey A. Vepritsky Kira A. Mamkaeva Lyudmila N. Voloshko 《Hydrobiologia》1996,322(1-3):149-151
Twentyfive cyanobacterial blooms in Lake Ladoga and adjacent water bodies were studied in the summer of 1990–1992. Toxicity of the water bloom material for mice was detected in 9 cases. The maximal tolerable doses (MTD) of the material extracted from biomass varied within 3–30 mg kg–1 mouse body weight; 50% lethal doses (LD50) were within 45–125 mg kg–1. Toxic water blooms were registered in Karelian lakes and in the Neva Bay, Gulf of Finland. Cyanobacterial samples collected on the eastern coast of Lake Ladoga proved to be non-toxic. The species identified in toxic bloom material included Anabaena circinalis, A. flos-aquae, A. lemmermannii, Anabaena sp., Aphanizomenonflos-aquae, Gloeotrichia echinulata, G. pisum, Microcystis aeruginosa and Oscillatoria sp. These data suggest that toxic forms of cyanobacteria are widespread in Karelian lakes belonging to the drainage basin of Lake Ladoga. 相似文献