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1.
S W Rogers T E Hughes M Hollmann G P Gasic E S Deneris S Heinemann 《The Journal of neuroscience》1991,11(9):2713-2724
The cloning of cDNAs that encode functional glutamate receptors makes it possible to produce antibodies that can be used as high-affinity probes for the localization and characterization of these receptors in the mammalian brain. We have made antibodies to different regions of the first cloned member of this family, GluR1, using bacterially overproduced antigen. On Western blots, these antisera detect glycoprotein(s) of 105 kDa present in crude membranes of the hippocampus and cerebellum. The 105-kDa band is associated with postsynaptic densities, and it is observed in cultured cells upon transfection with the GluR1 cDNA. Although glutamate receptors are thought to be the most prevalent excitatory ligand-gated ion channel in the mammalian brain, immunohistochemistry reveals that the receptors recognized by these antisera are localized predominantly in neurons of the cerebellum and some structures of the limbic system, including the hippocampus, the central nucleus of the amygdala, and portions of the septum. This pattern of expression is, in general, consistent with the distribution of GluR1 mRNA as determined by in situ hybridization histochemistry. Our results suggest that glutamate excitatory circuits recognized by these antisera are predominantly found in regions of the limbic system that are reciprocally interconnected. 相似文献
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3.
Picrotoxin-induced epileptiform activity was examined in neocortical slices prepared from 8- to 15-day-old rats. This activity consisted of spontaneous bursts of 3-5 discharges that resembled interictal spikes and were interspersed with ictal-like paroxysms lasting 10-30 s. Measurements of extracellular potassium ([K+]o) and calcium ([Ca2+]o) were made during these spontaneous epileptiform events, using ion-sensitive electrodes. Individual interictal spikes were associated with [Ca2+]o decreases of 0.1-0.2 mM, whereas sustained ictal-like discharges were accompanied by decreases of 0.3-0.4 mM. Measurement of [K+]o showed that individual interictal spikes were associated with increases in [K+]o up to 12 mM, whereas increases to more than 20 mM accompanied long-lasting ictal-like discharges. Maximum increases in [K+]o were observed ca. 600 microns below the pial surface. [K+]o increases were followed by undershoots of the resting [K+]o level. The unusually high [K+]o levels associated with epileptiform discharges in the immature neocortex suggest that disturbances in [K+]o regulation may contribute to the generation of the picrotoxin-induced, spontaneous, prolonged ictal-like discharges observed in the 8- to 15-day age group. 相似文献
4.
Practical management of patients with non-small-cell lung cancer treated with gefitinib. 总被引:7,自引:0,他引:7
Neelam T Shah Mark G Kris William Pao Leslie B Tyson Barbara M Pizzo Murk-Hein Heinemann Leah Ben-Porat Dana L Sachs Robert T Heelan Vincent A Miller 《Journal of clinical oncology》2005,23(1):165-174
PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib. 相似文献
5.
Using the whole-cell configuration of the patch clamp technique, calcium-activated potassium currents (IK,Ca) were investigated in ramified murine brain macrophages. In order to induce IK,Ca the intracellular concentration of nominal free Ca2+ was adjusted to 1μM. The Ca2+-activated K+ current of brain macrophages did not show any voltage dependence at test potentials between –120 and +30mV. A tenfold change
in extracellular K+ concentration shifted the reversal potential of IK,Ca by 51mV. The bee venom toxin apamin applied at concentrations of up to 1μM did not affect IK,Ca. Ca2+-activated K+ currents of ramified brain macrophages were highly sensitive to extracellularly applied charybdotoxin (CTX). The half-maximal
effective concentration of CTX was calculated to be 4.3nM. In contrast to CTX, the scorpion toxin kaliotoxin did not inhibit
IK,Ca at concentrations between 1 and 50nM. Tetraethylammonium (TEA) blocked 8.0% of IK,Ca at a concentration of 1mM, whereas 31.4% of current was blocked by 10mM TEA. Several inorganic polyvalent cations were tested
at a concentration of 2mM for their ability to block IK,Ca. La3+ reduced IK,Ca by 72.8%, whereas Cd2+ decreased IK,Ca by 17.4%; in contrast, Ni2+ did not have any effect on IK,Ca. Ba2+ applied at a concentration of 1mM reduced IK,Ca voltage-dependently at hyperpolarizing potentials.
Received: 17 January / Accepted: 5 May 1997 相似文献
6.
神经生长因子对小鼠突触体内Ca^2+水平的调节作用 总被引:4,自引:1,他引:3
观察了多次海马内微注射NGF对小鼠突触体内游离钙水平的影响,并在离体情况下观察NGF对EGTA和CaCl2分别造成突触体内低钙和高钙状态的调节作用。结果如下:(1)在体实验表明,一定剂量的NGF可显著降低老年小鼠海马突触体内游离钙水平(P<005);(2)离体实验表明,当突触体游离钙水平降低时,适当剂量的NGF具有升高游离钙水平的作用;而突触体内游离钙水平升高时,则NGF有降低游离钙水平的作用。提示NGF对游离钙水平的双向调节作用可能是NGF改善老年性记忆衰退的作用机制。 相似文献
7.
Volker Heinemann 《Breast cancer research and treatment》2003,81(1):43-48
Single-agent chemotherapy of metastatic breast cancer is the treatment of choice in patients with slow tumor progression and asymptomatic disease. In this patient group, the choice of drugs is based more on good tolerability than on efficacy. By contrast, symptomatic or rapidly progressing disease requires the use of highly active regimens where more weight is put on reliable antitumor activity. While anthraycline-based combination regimens have set the standard of effective treatment, the addition of docetaxel (and to a lesser extent paclitaxel) has improved tumor response, but failed to induce a consistent prolongation of survival. Based on retrospective analyses, it is hypothesised that the combined use of anthracyclines and taxanes in first-line therapy may be most beneficial in defined subgroups: after adjuvant chemotherapy, in patients with HER-2 gene amplification, possibly also in patients with rapidly progressing visceral disease. 相似文献
8.
S. M. Fuchs C. Heinemann S. Schliemann-Willers H. Härtl J. W. Fluhr P. Elsner 《Skin research and technology》2006,12(4):223-227
OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti-irritative effect of PoCo was evaluated with a visual score and quantified by non-invasive bioengineering methods, namely chromametry and transepidermal water loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient; German pharmacopoeia) were tested in a 4-day repetitive irritation test using SLS. RESULTS: A statistically significant anti-inflammatory activity was observed for PoCo by all three methods when applied in parallel to the induction period of ICD. Application of PoCo after induction of ICD once a day for 5 days, starting just at the end of 4 days, was without any effect. CONCLUSION: An anti-inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by repeated SLS test could be observed and quantified by three independent, non-invasive biophysical assessment parameters. This effect can be explained by its influence on pro-inflammatory enzymes, namely phospholipase A2. 相似文献
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10.
Monoclonal Antibody Specific for TIRC7 Induces Donor-specific Anergy and Prevents Rejection of Cardiac Allografts in Mice 总被引:1,自引:0,他引:1
Yusuke Kumamoto Antje Tomschegg Fatima Bennai-Sanfourche Anke Boerner Arthur Kaser Isabella Schmidt-Knosalla Thomas Heinemann Mirko Schlawinsky Richard S. Blumberg Hans-Dieter Volk Nalan Utku 《American journal of transplantation》2004,4(4):505-514
T cell immune response c-DNA (TIRC7) is up-regulated during the early stages of T-cell activation in response to alloantigens. In this study, we analyzed the effects of newly developed monoclonal antibodies (mAb) against TIRC7 in acute cardiac allograft rejection. Fully vascularized heterotopic allogeneic heart transplantation was performed in mice across a full-mismatch barrier (C57Bl/10 into CBA). Recipients received seven injections (day 0-7) of a novel anti-TIRC7 mAb or remained untreated. Graft survival, histology and ex vivo lymphocyte functions were tested. Targeting of TIRC7 with an anti-TIRC7 mAb diminishes lymphocyte infiltration into grafts resulting in delay of morphological graft damage and prolongation of allograft survival. The lymphocytes from anti-TIRC7 mAb-treated animals exhibit hypo-responsiveness without evidence of lymphocyte depletion against the donor allo-antigens. Proliferation and expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were down-regulated while interleukin-4 (IL-4) and IL-10 expression were spared. Moreover, anti-TIRC7 mAb enhanced up-regulation of CTLA-4 expression but suppressed up-regulation of CD25 on stimulated lymphocytes in vitro and in vivo. Ligation of TIRC7 has important effects on the regulation of co-stimulatory signaling pathways associated with suppressing of T-cell activation. Targeting of TIRC7 may therefore provide a novel therapeutic approach for modulating T cell immune responses during organ transplantation. 相似文献