脉络膜黑色素瘤的三种影像学检查对比分析

目的通过对比超声、磁共振成像及眼底血管造影三种影像学检查方法对脉络膜黑色素瘤的诊断结果与病理诊断的一致性，探讨脉络膜黑色素瘤影像学检查的合理应用方法，提高脉络膜黑色素瘤的确诊率。设计回顾性病例系列。研究对象疑诊为脉络膜黑色素瘤的26例（28眼）患者。方法对26例（28眼）疑诊为脉络膜黑色素瘤患者术前进行眼B超和（或）彩色超声多普勒血流成像（CDFI）、磁共振成像（MRI）、荧光素眼底血管造影（FFA）和（或）吲哚青绿血管造影（ICGA）检查，结合病理诊断，应用SPSS12．0软件对影像学检查结果与病理诊断的一致性进行统计学分析。主要指标眼部超声、MRI、眼底血管造影的表现及肿瘤病理诊断。结果三种影像学检查结果与病理诊断的一致性由好到差依次为：MRI（r=0．494，P=0．010）、超声检查（k=0．348，P=0．050）、眼底血管造影（k=0．140，P=0．463）；超声检查对脉络膜黑色素瘤诊断的敏感度和特异度分别为95．2％和33．3％，MRI的敏感度和特异度分别为85．7％和66．7％，眼底血管造影的敏感度和特异度分别为76．2％和40．0％。联合MRI和眼底血管造影或三种影像学检查的诊断结果与病理诊断的一致性最好（k=0．886，P=0．000），其对脉络膜黑色素瘤诊断的敏感度和特异度分别为100％和83．3％。结论三种影像学检查联合是目前除病理外敏感性和特异性最佳的诊断方法，优于单独应用以及其他两两组合。     

Characterization of altered calcium signalling in T lymphocytes from patients with rheumatoid arthritis (RA)

Abnormal function of peripheral blood T lymphocytes is characteristic of RA; diminished proliferation and secretion of cytokines following in vitro mitogen stimulation are observed. We have investigated the calcium flux initiating T cell activation in rheumatoid peripheral blood mononuclear cells (PBMC) to determine whether abnormalities in signalling are also present. We have found that both phytohaemagglutinin (PHA-P)- and anti-CD3-stimulated calcium fluxes were much reduced in the patients’ PBMC compared with controls, with a mean six-fold difference (P < 0·01) in rate of Ca²⁺ flux with PHA-P stimulation. When purified T cells were examined with PHA and CD3 stimulation, a reduction in the peak and plateau [Ca²⁺]_i was observed in RA T cells, but the rate of rise of [Ca²⁺]_i was only reduced in those cells stimulated with PHA. These results suggest that alterations in the initiating signal may underlie the functional T cell abnormalities associated with RA, and that there may be an additional extrinsic influence from non-T cells in the PBMC population.     

Effects of β-Adrenergic Receptor Activation on Intracellular Calcium and Membrane Potential in Adult Cardiac Myocytes

β-Adrenergic Receptor Activation and Intracellular Ca²⁺. Introduction:β-Adrenergic receptor agonists have been shown to increase the voltage-dependent Ca²⁺ current in cardiac myocytes. Additionally, adrenergic receptor activation has been shown to increase intracellular Ca²⁺, to increase systolic Ca²⁺ transients and to enhance Ca²⁺ uptake into the sarcoplasmic reticulum, thereby accelerating relaxation. The present study was designed first to characterize the influences of β-adrenergic receptor activation on intracellular Ca²⁺ activity as well as membrane potential in ventricular myocytes characterized as normal based on rigorous morphologic and electrophysiologic criteria. The second objective was to assess whether the increase in intracellular Ca²⁺ activity elicited by β-adrenergic receptor activation could elicit afterdepolarizations and triggered activity. Methods and Results: Intracellular Ca²⁺ and whole-cell voltage recordings were measured in cells in which indo-1 free acid was delivered intracellularly through the recording pipette. Isoproterenol produced complex Ca²⁺ transients underlying both early and delayed afterdepolarizations during pacing as well as aftertransients underlying triggered action potentials and delayed afterdepolarizations in the absence of pacing. The coupling interval of Ca²⁺_i aftertransients was frequency dependent and followed that of the delayed afterdepolarizations. Ca²⁺_i after transient amplitudes, however, exhibited a biphasic response with frequency revealing that factors other than pacing frequency alone contribute to control of the amplitude of the aftertransients. Inhibition of sarcoplasmic reticular release of Ca²⁺ by ryanodine abolished Ca²⁺_i aftertransients and afterdepolarizations otherwise elicited by isoproterenol. Conclusion: These data demonstrate that normal cells stimulated by β-adrenergic agonists exhibit marked changes in intracellular Ca²⁺ homeostasis that may serve as the substrate for abnormal ion fluxes that ultimately contribute to electrophysiologic derangements underlying arrhythmogenesis in the intact heart. (J Cardiovasc Electrophysiol, Vol. 3, pp. 209–224, June 1992)     

Analysis of Pb2+ Entry into Cultured Astroglia

Astroglia serve as a presumptive lead (Pb) sink in the brain;therefore, this study examined Pb entry into cultured rat astrogliautilizing the Ca²⁺ fluorophore indo-1 as a tool for detectingPb²⁺ entry during acute exposure. The interactions of Pb²⁺ withindo-1 were analyzed by fluorescence spectrophotometry in acell-free system. The emission spectrum of Pb²⁺/indo-1 was substantiallydifferent from that of Ca²⁺/indo-1 due to suppression of indo-1fluorescence emission intensity. Next, we established the presenceof L-type Ca²⁺ channels in astroglial cultures and demonstratedthat Pb accumulation is enhanced under serum-free conditionsand by the application of Bay-K 8644. Because acute exposureis of less toxicologic relevance than repeated low-level exposure,we then examined Pb uptake in cultures treated for up to 1 weekwith Pb. AAS revealed that Pb accumulation was accompanied byan increase in total cellular [Ca]. In addition, differencesin basal indo-1 fluorescence levels and differences in responsivenessto ionomycin were observed. Ionomycin induced an increase inthe fluorescence ratio in untreated cells but cells treatedfor 1 day with Pb showed no response to ionomycin. However,cells treated for 3 and 7 days showed a partial response toionomycin. TPEN was used to evaluate the interactions of Pb²⁺with indo-1 and only cells treated for 7 days showed a responseto TPEN. Thus, the present study characterizes Pb²⁺ entry intoastroglia via L-type Ca²⁺ channels and presents the possibilityof using indo-1 for analysis of Pb²⁺ uptake and the subsequentneurotoxic events in astroglia.     

脑室注射催产素对大鼠胃和十二指肠溃疡的作用

INTRODUCTION Central neurons that synthesize oxytocin are locatedin the supraoptic(SON) and paraventricular nuclei(PVN) of the hypothalamus. Magnocellular neurons inboth nuclei project to the posterior pituitary gland,     

Neuroprotective compounds inhibit depolarisation-evoked calcium transients in granule cells

The effects of several neuroprotective or anticonvulsant compounds on depolarisation-evoked calcium mobilisation in cultured rat cerebellar granule cells were compared using a calcium imaging method. Calcium transients were evoked by brief stimulations with N-methyl-D -aspartate (NMDA), veratridine, or potassium chloride. The compounds tested were aptiganel, felbamate, gabapentin, lamotrigine, lubeluzole, riluzole, RP 66055A, sipatrigine, and SR 57746A. Aptiganel and riluzole inhibited calcium transients evoked both by NMDA and by veratridine. On the other hand, none of the other potential neuroprotective compounds studied shared this dual mechanism of action. Lamotrigine, lubeluzole, RP 66055A, sipatrigine, and SR 57746A only blocked responses to veratridine, whereas felbamate only (and partially) inhibited responses mediated by means of the NMDA receptor. SR 57746A also blocked responses to potassium chloride, suggesting that this compound may act at the level of the voltage-dependent calcium channel. Aptiganel, lubeluzole, and RP 66055 also blocked responses to potassium chloride, but only at concentrations considerably higher than those needed to block responses to veratridine. Gabapentin was unable to inhibit calcium transients evoked by any of the three depolarising agents. The effects of these various compounds on intracellular calcium homeostasis described here may be relevant to their therapeutic efficacy in the treatment of epilepsy and neurodegenerative disorders. Drug Dev. Res. 45:74–82, 1998. © 1998 Wiley-Liss, Inc.     

Overexpression of diacylglycerol kinase zeta inhibits endothelin-1-induced decreases in Ca2+ transients and cell shortening in mouse ventricular myocytes

Endothelin-1 (ET-1) is released in various cardiovascular disorders including congestive heart failure, and may modulate significantly the disease process by its potent action on vascular and cardiac muscle cell function and gene regulation. In adult mouse ventricular cardiomyocytes loaded with indo-1, ET-1 induced a sustained negative inotropic effect (NIE) in association with decreases in Ca²⁺ transients. The ET-1-induced effects on Ca²⁺ transients and cell shortening were abolished in diacylglycerol (DAG) kinase ζ-overexpressing mouse ventricular myocytes. A nonselective protein kinase C (PKC) inhibitor, GF109203X, inhibited the ET-1-induced decreases in Ca²⁺ transients and cell shortening in concentration-dependent manners, whereas a selective Ca²⁺-dependent PKC inhibitor, Gö6976, did not affect the ET-1-induced effects. A phospholipase Cβ inhibitor, U73122, and an inhibitor of phospholipase D, C₂-ceramide, partially, but significantly, attenuated the ET-1-induced effects. Derivatives of the respective inhibitors with no specific effects, U73343 and dihydro-C₂-ceramide, did not affect the ET-1-induced effects. Taken together, these results indicate that activation of a Ca²⁺-independent PKC isozyme by 1,2-DAG, which is generated by phospholipase Cβ and phospholipase D activation and inactivated by phosphorylation via DAG kinase, is responsible for the ET-1-induced decreases in Ca²⁺ transients and cell shortening in mouse ventricular cardiomyocytes.     

Heterogeneity and underlying mechanism for inotropic action of endothelin-1 in rat ventricular myocytes

1. To clarify the mechanisms underlying the positive inotropic action of endothelin-1 (ET-1), we investigated the effect of ET-1 on twitch cell shortening and the Ca²⁺ transient in rat isolated ventricular myocytes loaded with a fluorescent Ca²⁺ indicator indo-1.
2. There was a cell-to-cell heterogeneity in response to ET-1. ET-1 (100 nM) increased twitch cell shortening in only 6 of 14 cells (44 %) and the increase in twitch cell shortening was always accompanied by an increase in the amplitude of the Ca²⁺ transient.
3. The ET_A- and ET_B-receptors antagonist TAK-044 (100 nM) almost reversed both the ET-1-induced increases in twitch cell shortening and in the Ca²⁺ transient. In the ET-1 non-responding cells, the amplitude of the Ca²⁺ transient never increased.
4. Intracellular pH slightly increased (∼0.08 unit) after 30 min perfusion of ET-1 in rat ventricular myocytes. However, ET-1 did not change the myofilament responsiveness to Ca²⁺, which was assessed by (1) the relationship between the Ca²⁺ transient amplitude and twitch cell shortening, and by (2) the Ca²⁺ transient-cell shortening phase plane diagram during negative staircase.
5. We concluded that there was a cell-to-cell heterogeneity in the positive inotropic effect of ET-1, and that the ET-receptor-mediated positive inotropic effect was mainly due to an increase in the Ca²⁺ transient amplitude rather than to an increase in myofilament responsiveness to Ca²⁺.

     

Effect of Angiotensin II on Calcium Release Phenomena in Normal and Hypertrophied Single Cardiac Myocytes

The effects of angiotensin II (Ang II) (10^-9 M to 10^-7 M) on calcium releases were established in ventricular myocytes from normal and renal hypertensive adult rats. From each peak systolic indo-1 ratio (405 nm/480 nm), amplitude variation, duration (rise time and fall time), and frequency of spontaneous calcium releases were investigated on freshly isolated cardiomyocytes at rest or under electrical stimulation. The following changes were observed: (1) in spontaneous contracting myocytes, an increase in frequency of calcium transients at 10^-7 M in normal cells (+157%, P < 0.05) and at whatever angiotensin II concentration in hypertrophied cells (10^-9 M: +79%, P < 0.05; 10^-8 M +82%, P < 0.01; 10^-7 M: +285%, P < 0.01) with a greater sensitivity of hypertrophied cells to Ang II (P < 0.05 at 10^-9 M, P <0.01 at 10^-8 M). (2) In stimulated myocytes, a prolongation of the duration of calcium atransients at 10^-7 M in normal cells (+68%, P < 0.01) and at 10^-9 M, 10^-8 M, 10^-7 M in hypertrophied cells: (+36%, P < 0.05; +39%, P < 0.01; +77%, P < 0.01) with a greater sensitivity of hypertrophied myocytes (P < 0.05 at 10^-9 M and 10^-8 M). An increase in duration may be explained by the occurrence of calcium releases during the fall time of calcium transients. Thus, both in normal and hypertrophied myocytes, Ang II induced the occurrence of calcium releases with increased sensitivity of hypertrophied cells to Ang II. Such calcium releases are known to be a possible cause of arrhythmias termed "triggered activity".