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751.
Muth H Kreis I Zimmermann R Tillmanns H Hölschermann H 《Thrombosis and haemostasis》2005,94(5):1028-1034
Factor VIIa/tissue factor (FVIIa/TF) interaction has been reported to induce intracellular signalling in cells constitutively expressing TF, independently of downstream activation of the coagulation cascade. It is unknown, however, whether binding of FVII to its cofactor TF alters the gene expression profile in cells which inducible express TF under inflammatory conditions. To address this issue, gene expression patterns in cultured LPS-stimulated monocyte-derived macrophages with or without exposure to FVIIa were compared by cDNA macro-array analysis. Of the 1176 genes examined on the array, a small set of six genes (IL-6, IL-8,TNF-a, GRO-beta alpha-thymosin, cathepsin H) were consistently up-regulated and one gene suppressed (alpha-antitrypsin) in response to FVIIa in activated monocyte-derived macrophages. Among the seven genes identified by array analysis, five genes were finally confirmed by real-time RT-PCR. Interestingly, all of these genes differentially regulated in response to FVIIa (GRO-beta, IL-6, IL-8, TNF-alpha and alpha-antitrypsin) are critical in inflammation. The changes in gene expression were reflected by corresponding changes in the protein concentrations of IL-6 and IL-8 as demonstrated by ELISA. Active site-inhibited FVIIa had no effect on gene expression indicating that FVIIa-induced gene alteration is dependent on the proteolytic activity of FVIIa. The FVIIa-induced alterations in gene expression were found to be TF-dependent but independent of downstream coagulation proteins like thrombin and FXa. In summary, this study demonstrates that binding of FVIIa to its cofactor TF enhances restricted pro-inflammatory genes in activated monocyte-derived macrophages. By up-regulation of chemokines critical for leukocyte recruitment, FVIIa/TF interaction on activated monocyte-derived macrophages could be relevant to prepare monocytes/macrophages for extravasation and may represent a novel amplification loop of leukocyte recruitment. 相似文献
752.
Müller-Vahl KR Schneider U Prevedel H Theloe K Kolbe H Daldrup T Emrich HM 《The Journal of clinical psychiatry》2003,64(4):459-465
BACKGROUND: Preliminary studies suggested that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa L., might be effective in the treatment of Tourette syndrome (TS). This study was performed to investigate for the first time under controlled conditions, over a longer-term treatment period, whether THC is effective and safe in reducing tics in TS. METHOD: In this randomized, double-blind, placebo-controlled study, 24 patients with TS, according to DSM-III-R criteria, were treated over a 6-week period with up to 10 mg/day of THC. Tics were rated at 6 visits (visit 1, baseline; visits 2-4, during treatment period; visits 5-6, after withdrawal of medication) using the Tourette Syndrome Clinical Global Impressions scale (TS-CGI), the Shapiro Tourette-Syndrome Severity Scale (STSSS), the Yale Global Tic Severity Scale (YGTSS), the self-rated Tourette Syndrome Symptom List (TSSL), and a videotape-based rating scale. RESULTS: Seven patients dropped out of the study or had to be excluded, but only 1 due to side effects. Using the TS-CGI, STSSS, YGTSS, and video rating scale, we found a significant difference (p <.05) or a trend toward a significant difference (p <.10) between THC and placebo groups at visits 2, 3, and/or 4. Using the TSSL at 10 treatment days (between days 16 and 41) there was a significant difference (p <.05) between both groups. ANOVA as well demonstrated a significant difference (p =.037). No serious adverse effects occurred. CONCLUSION: Our results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology. 相似文献
753.
Psychophysiological course studies are still the exception in AP hospitalized for psychotherapy. The aim of this study was to perform a more precise psychophysiological analysis of anxiety patients (AP) before and after hospital treatment. From a sample of 28 AP, 13 were psychophysiologically and psychodiagnostically examined and compared to controls (CG) at the beginning and end of in-patient psychotherapy and 4 months later. APs showed higher heart rate (HR) and electrodermal spontaneous fluctuation (SF) than control patients but did not differ in their resting systolic (SBP) and diastolic blood pressure (DBP). Under cognitive stress, the controls had a significantly stronger HR and SBP reaction, while the AP showed more SF during the tone sequence and while being asked about their subjectively experienced anxiety. Following inpatient psychotherapy, the two groups showed correlation in their vegetative reaction patterns. The study clearly demonstrates the effectiveness of the applied depth psychology-oriented multimodal therapy from a psychophysiological standpoint. 相似文献
754.
Pharmacoresistance and expression of multidrug transporter P-glycoprotein in kindled rats 总被引:6,自引:0,他引:6
Multidrug transporter over-expression is considered to limit access of antiepileptic drugs to the epileptic focus region and to be one cause of intractable epilepsy. To reach further proof for this multidrug transporter hypothesis, we compared P-glycoprotein expression rates in subgroups of Wistar rats which are sensitive or resistant to the anticonvulsant effect of the antiepileptic drug phenytoin in the amygdala-kindling model of temporal lobe epilepsy. In the electrode-implanted amygdala of phenytoin-resistant rats, the area labelled for P-glycoprotein was more than twice as large than that in phenytoin-sensitive rats. The data indicate that P-glycoprotein expression levels in the kindled focus have a critical impact on the anticonvulsant response to antiepileptic drugs. 相似文献
755.
Antje Will Christine Blank Martin Rllinghoff Heidrun Moll 《European journal of immunology》1992,22(6):1341-1347
Cutaneous leishmaniasis is initiated by the bite of an infected sandfly and inoculation of Leishmania major parasites into the mammalian skin. Macrophages are known to play a central role in the course of infection because they are the prime host cells and function as antigen-presenting cells (APC) for induction of the cell-mediated immune response. However, in addition to macrophages in the dermis, the skin contains epidermal Langerhans cells (LC) which can present antigen (Ag) to T cells. Therefore, using a murine model of cutaneous leishmaniasis, we analyzed the ability of epidermal cells to induce a T cell response to L.major. The results demonstrated that freshly isolated LC, but not cultured LC, are highly active in presenting L.major Ag in vitro to T cells from primed mice and to a L.major-specific T cell clone. Furthermore, freshly isolated LC had the ability to retain L.major Ag in immunogenic form for at least 2 days. Their efficiency was much greater than that of irradiated spleen cells, a standard population of APC. LC stimulated both T cell proliferation and production of the lymphokines interleukin (IL)-2 and IL-4. The response was Ag specific and could be induced by lysate of L.major parasites and by live organisms. The data suggest that epidermal LC are important APC in cutaneous leishmaniasis. They may perform a critical function by capturing L.major Ag in the skin and presenting it either to quiescent T cells circulating through the draining lymph node or locally to T effector cells infiltrating the cutaneous lesion. 相似文献
756.
757.
Meron G Kürkciyan I Sterz F Tobler K Losert H Sedivy R Laggner AN Domanovits H 《Resuscitation》2004,60(2):143-150
OBJECTIVE: To evaluate the frequency, presentation and outcome of non-traumatic aortic dissection/rupture as a cause of cardiac arrest. DESIGN: Retrospective analysis of a cardiac arrest registry in a tertiary care hospital emergency department. RESULTS: Over 11.5 years, aortic dissection/rupture was identified as the immediate cause of cardiac arrest in 46 (2,3%) out of 1990 patients with sudden cardiac arrest, primarily affecting the abdominal aorta in 25 and the thoracic aorta in 21 cases. The characteristics of the 46 patients were as follows: male gender (74%), median age 71 years (IQR 59-76), high co-morbidity (89%), previously known aortic aneurysm (33%), pulseless electric activity (70%) as initial cardiac rhythm. When performed, bedside abdominal sonography or echocardiography was almost always diagnostic. Patients with abdominal aortic dissection/rupture had abdominal (52%) and/or flank pain (32%). Patients with thoracic aortic dissection/rupture complained of chest pain (48%) or dyspnoea (19%). Return of spontaneous circulation occurred in 12 (26%) of 46 patients, emergency surgery was performed in eight of these patients, 2 (4%) survived to discharge in good neurological condition. CONCLUSIONS: Cardiac arrest caused by aortic dissection/rupture is rare, and mortality remains very high, even when circulation can be restored initially. Common features such as previously known aortic aneurysm, old age, male gender and pulseless electrical activity as initial cardiac rhythm should increase suspicion of the condition. 相似文献
758.
759.
A new neurophysiological/neuropathological ex vivo model localizes the origin of glioma-associated epileptogenesis in the invasion area 总被引:1,自引:0,他引:1
Senner V Köhling R Püttmann-Cyrus S Straub H Paulus W Speckmann EJ 《Acta neuropathologica》2004,107(1):1-7
Seizures commonly occur in glioma patients, but their pathogenesis is poorly understood, in part due to a lack of valid and versatile experimental models. We have established a new model that enables comprehensive neuropathological and neurophysiological analysis on identical tissue preparations. Rat C6 glioma cells stably transfected with a green fluorescence protein (GFP) gene are transplanted into rat neocortex, giving rise to diffusely invading gliomas histologically resembling human glioblastomas. After 2 weeks, 500-µm-thick cerebral slices are prepared, stained with the voltage-sensitive dye RH795, and fluorescence changes associated with origin and spread of abnormal bioelectric activity upon washout of Mg2+ are detected by a 464-element photodiode array at a rate of 785 frames/s. GFP fluorescence promotes identification of tumor cells during electrophysiological experiments and in neuropathological analyses using frozen and paraffin-embedded tissue sections. By performing subsequent histological analysis of the slices examined neurophysiologically, origin and spread of abnormal activity can be correlated with structural and molecular (immunohistochemical) features. Specifically, we found that ictaform activity was initiated in cortical areas diffusely invaded by single tumor cells. This model is useful for further elucidating the electrophysiological, molecular and structural basis of glioma-associated epileptogenesis.V.S. and R.K. contributed equally to this study 相似文献
760.
Kusserow H Davies B Hörtnagl H Voigt I Stroh T Bert B Deng DR Fink H Veh RW Theuring F 《Brain research. Molecular brain research》2004,129(1-2):104-116
Serotonergic neurons play a major role in the modulation of emotion and behaviour. Especially knockout studies have revealed a role for the serotonin(1A) (5-HT(1A)) receptor in anxiety related behaviour. Mutant animals exhibit enhanced anxiety-like responses, possibly resulting from impaired autoinhibitory control of midbrain serotonergic neurons. To further elucidate the role of the 5-HT(1A) receptors in affective behaviour, a complementary approach has been used and transgenic mice overexpressing this receptor subtype have been generated. The expression of the active 5-HT(1A) receptor protein as indicated by autoradiography was transiently increased during early postnatal development (P1.5) as compared to wild-type mice. Within the next 2 weeks, the increase in receptor binding vanished and was also not apparent in adult animals indicating adaptive changes in the regulation of 5-HT(1A) receptor expression. Although no evidence for increased receptor binding in the brains of adult homozygous mice was found by autoradiography, typical phenotypic changes indicative of 5-HT(1A) receptor overactivity were apparent. Transgenic mice revealed a reduced molar ratio of 5-hydroxyindoleacetic acid to serotonin in several brain areas and elevated serotonin values in the hippocampus and striatum. Moreover, anxiety-like behaviour was decreased in male and female transgenic mice and body temperature was lowered in male transgenic mice in comparison with heterozygous and wild-type mice. These findings further underline the pivotal role of 5-HT(1A) receptors in the homeostasis of anxiety-like behaviour and the crucial importance of stimulation of the 5-HT(1A) receptor during the early postnatal development for normal anxiety-like behaviour throughout life. 相似文献