Protein kinase C agonist and antagonist effects in normal human epidermal keratinocytes

Abstract Several lines of evidence implicate protein kinase C (PKC) in the development of basal cell and squamous cell carcinomas, tumors which originate from epidermal keratinocytes. To examine PKC in a model relevant to human skin, we exposed normal human epidermal keratinocytes (NHEK) in serum-free media to a variety of PKC agonists and antagonists. NHEK PKC activity increased up to 10-fold within the 1st hour of exposure to tetradecanoyl phorbol acetate (TPA), and gradually returned to control values within 72 h. TPA-induced PKC activity was enhanced by pretreatment of cultures with protein and RNA synthesis inhibitors. TPA-induced growth arrest and differentiation was antagonized by staurosporine. Down-regulation by bryostatin pretreatment blocked TPA-stimulated differentiation. Our overall conclusion is that activation of PKC in cultured human keratinocytes is required for differentiation. These results are crucial to the analysis of compounds suspected of promoting or inhibiting epidermal tumors.     

The updated electrostatic potential for cytosine completes the qualitative explanations of base alkylation regiochemistry

The relationship between the structures of different alkylatingagents and the relative extents to which they modify the oxygenand nitrogen centers of nucleic acid bases has been discussedin the literature from several points of view, although eacheffectively attributes the increasing preference for oxygenalkylation to the increasing importance of electrostatic interactionsbetween the reacting moieties. This is in direct contradictionto the published electrostatic potential data for cytosine whichindicate the most attractive potential to lie in the vicinityof the 3-nitrogen. However, we have discovered the latter tobe an artefact of the use of inadequate levels of theory. Whenthe electrostatic potentials of cytosine are computed usingmore sophisticated ab initio Hartree-Fock/6–31G^* calculationsthe global minimum does indeed lie in the vicinity of the O²-positionas required by the various rationalizations of the alkylationdata.     

外周血及移植肾内嗜酸性粒细胞变化的临床意义

为了解移植肾在急性排斥时外周血和移植肾内嗜酸性粒细胞（ＥＯ）变化的意义，动态观察３１例同种异体肾脏移植病人的外周血和移植肾内ＥＯ的变化。结果发现在急性排斥反应时，移植肾内ＥＯ数＞２％者占８０．９％，明显高于肾功能稳定时，Ｐ＜０．０１；重度排斥中血ＥＯ数＞４％者占８２．６％，明显高于肾功能稳定时和中度以下排斥者，Ｐ＜０．０１。结果认为，测定移植肾内的ＥＯ变化可以做为监测急性排斥反应的可靠指标，外周血中的ＥＯ明显增多常提示排斥反应较为严重。     

Blood flow variation and energy metabolism in the gastric mucosa following 7．5％ hypertonic saline resuscitation

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药物浓度和病因对三磷酸腺苷治疗阵发性室上性心动过速的影响

本文报告23例次ATP治疗PSVT的效果,总有效率56.5％,9例次高浓度快速注射者8例转复。器质性心脏病者副作用较多,1例冠心速注高浓度ATP后,发生心室颤动和阿-斯氏综合征。这一结果提示:药物浓度和注射速度是影响疗效的主要因素,PSVT伴AVB者疗效也很低;病因和药物浓度是决定副作用的因素。因此,对于器质性心脏病者,尤其冠心病人,应避免高浓度快速静脉注射ATP。     

Alterations of G-protein Coupling Function in Phosphoinositide Signalling Pathways of Rat Hippocampus by Ischaemic Brain Injury

The activation of membrane-associated phospholipase C is rapidly and transiently induced in the central nervous system by a variety of stimuli. Ischaemic brain injury is one of the situations that leads to a dramatic increase in polyphosphoinositide (PPI) turnover. In this study, stimulation of PPI hydrolysis by glutamate (500 μM) was measured in hippocampal slices from rats up to 21 days after an ischaemic insult of 30 min. Ischaemia was induced using the four-vessel occlusion method. PPI hydrolysis elicited by glutamate was significantly increased in the slices prepared from ischaemic rats 24 h after reperfusion, the accumulation of inositol phosphates (InsP_s) and inositol 1,4,5-trisphosphate (InsP₃) was 614±74% ( n = 8) and 182±11% ( n = 9) of the basal level respectively. This potentiation was also observed 21 days after ischaemia. Hyper-responsiveness to glutamate was also accompanied by an increase in AIF⁻₄-stimulated formation of [³H]inositol phosphates. In addition, global ischaemia did not change either high-affinity [³H]glutamate binding in hippocampal membranes or the stimulation of PPI hydrolysis by carbachol or noradrenaline in hippocampal slices. The present results suggest that the increased responsiveness to glutamate is the result, at least in part, of functional changes at the G-protein level, and may contribute to the pathophysiology of ischaemic brain injury or to the regenerative phenomena that accompany ischaemic damage.