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43 records · Page 3Linked to original sources
PubMed2006

Cytotoxic and biochemical effects of 3,3',4,4',5,5'-hexahydroxystilbene, a novel resveratrol analog in HL-60 human promyelocytic leukemia cells.

OBJECTIVE: Resveratrol (3,4',5,-trihydroxystilbene, RV), an ingredient of wine, is an inhibitor of the proliferation-linked enzyme ribonucleotide reductase (RR) and shows a broad spectrum of cytotoxic effects against human cancer cells. In order to enhance these effects, we introduced additional hydroxyl moieties into the molecule. In the present study, the activity of a novel RV analog, 3,3',4,4',5,5'-hexahydroxystilbene (M8), was investigated in HL-60 human promyelocytic leukemia cells. METHODS: Cytotoxicity of M8 alone or in combination with Ara-C was assessed employing growth inhibition assays. Effects of M8 on nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) were examined by HPLC. The apoptotic potential of M8 and RV was compared using a specific double-staining method and inhibition of TNF-alpha-induced activation of NF-kappaB was studied. Cell-cycle distribution was analyzed by FACS. RESULTS: Addition of ascorbic acid decreased the IC(50) value of M8 from 6.25 microM to 2 microM. M8 depleted dATP and dTTP pools to 41% and 21% of control values, whereas dCTP pools increased to 199% of untreated controls. In addition, TTP, ATP, CTP, and GTP concentrations were decreased while UTP concentrations increased. M8 induced apoptosis at concentrations significantly lower than RV and could remarkably inhibit the activation of NF-kappaB. M8 arrested cells in the S phase of the cell cycle while depleting cells in the G2-M phase and exhibited synergistic combination effects when applied simultaneously with Ara-C. CONCLUSION: Due to these promising results, this novel polyhydroxylated stilbene derivative might become an additional option for the treatment of leukemia and therefore deserves further preclinical and in vivo testing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Atrial and ventricular septal defects can safely be closed by percutaneous intervention.

Various transcatheter devices and methods to close congenital heart defects are currently available. Devices have been designed specifically for atrial septal defect (ASD), patent foramen ovale (PFO), and ventricular septal defect (VSD) closure. The trend in interventional treatment of intracardiac shunts shows toward defect-specific systems. The PFO is a tunnel defect requiring occluders that adapt to its length while common ASD strongly vary in their diameter, making a large scale of device sizes indispensable. VSDs are predominantly sealed by coils or tissue-adapted devices like muscular or perimembranous occluders. Since VSDs may occur with an aneurysm (VSA), a multi-perforated septum, an instable myocardial situation (postinfarction) or a high interventricular pressure gradient, closure of these defects is regarded sometimes as complicated. But during the last 30 years (since King and Mills implanted the first double-umbrella occluding system) several studies have proven procedure efficacy and safety of both ASD and VSD closure. This article reviews a large scale of studies and includes our single center data on 1,609 PFO, ASD, and VSD patients.

Cardiac Catheterization↗
PubMed2004

Effect of task conditions on brain responses to threatening faces in social phobics: an event-related functional magnetic resonance imaging study.

BACKGROUND: The aim of this study was to identify brain activation to socially threatening stimuli in social phobic subjects during different experimental conditions. METHODS: With event-related functional magnetic resonance imaging, brain activation to photographs and schematic pictures depicting angry or neutral facial expressions was measured in social phobic subjects and healthy control subjects, while subjects assessed either emotional expression (angry vs. neutral; explicit task) or picture type (photographic vs. schematic; implicit task). RESULTS: Compared with control subjects, phobics showed greater responses to angry than to neutral photographic faces in the insula regardless of task, whereas amygdala, parahippocampal gyrus, and extrastriate visual cortex were more strongly activated only during the implicit task. Phobics, in contrast to control subjects, showed similar activation patterns during both tasks. For schematic angry versus neutral faces, activation of insula and extrastriate visual cortex was found in phobics, but not in control subjects, during both tasks. CONCLUSIONS: Differences between social phobics and control subjects in brain responses to socially threatening faces are most pronounced when facial expression is task-irrelevant. Phobics intensively process angry (photographic as well as schematic) facial expressions, regardless of whether this is required. The insula plays a unique role in the processing of threat signals by social phobics.

Adult↗
PubMed2004

Gene expression analysis in platelets from a single donor: evaluation of a PCR-based amplification technique.

BACKGROUND: Genetic analysis of platelet mRNA may facilitate the diagnosis of disorders affecting the megakaryocytic-platelet lineage. Its use, however, is limited by the exceptionally small yield of platelet mRNA and the risk of leukocyte contamination during platelet preparation. METHODS: We depleted platelet suspensions of leukocytes by filtration and used a PCR-based RNA amplification step [switching mechanism at the 5' end of RNA templates (SMART)]. We tested the reliability and precision of the RNA amplification procedure by use of real-time PCR to measure quantities of specific transcripts: von Willebrand factor (vWF), A-subunit of coagulation factor XIII (F13A), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Microarray analysis was performed on platelet RNA with and without amplification. RESULTS: Microgram quantities of platelet-specific cDNAs were produced from as little as 50 ng of total platelet RNA or 40 mL of whole blood. At cycle numbers <16, amplification of all transcripts tested was exponential with slightly more efficient amplification of low-abundance transcripts. Expression profiling of 9850 genes gave identical results for 9815 genes (1576 positive/8239 negative). Eight transcripts failed to be amplified by the SMART procedure. Expression of vWF, F13A, and GAPDH transcripts showed only minor day-to-day variations in three healthy individuals. CONCLUSION: The proposed protocol makes extremely small amounts of platelet RNA available for gene expression analysis in single patients.

Blood Platelets↗
PubMed2005

Induction of anti-proliferative mechanisms in hepatitis B virus producing cells.

BACKGROUND/AIMS: Hepatitis B virus (HBV) preferentially replicates in quiescent cells. It was analyzed whether HBV affects cell cycle control. METHODS: The amount of EGF-receptor (EGFR) and the binding capacity for 125I-EGF was determined. Expression of mdm2 and p21 and relevance of p53 for it were analyzed by reporter gene assays and western blotting. Cyclin A/E associated cdk2 activities were determined by immunocomplex assays. Cell proliferation was quantified by measurement of BrdU incorporation. RESULTS: In HBV producing cells a significant reduction of EGFR expression, diminished 125I-EGF-binding capacity and insensitivity to EGF-stimulation were observed as compared to the control. Moreover, c-Raf-1-dependent induction of mdm2-P2 and p21cip1/waf1-promoter and elevated amounts of the respective proteins were observed in HBV producing cells. Whereas activation of mdm2-P2-promoter requires p53, activation of p21cip1/waf1-promoter is mediated partially by a p53-independent process. Induction of p21cip1/waf1 is reflected by a reduction of cyclin A associated cdk2 activity and an increase of cyclin E associated cdk2 activity. In accordance with this proliferation rate of HBV-producing hepatocytes is reduced as compared to control cells. CONCLUSIONS: These results describe novel cell-cycle inhibitory functions of HBV that correlate well with the general concept of enhanced HBV replication in quiescent cells.

Carcinoma, Hepatocellular↗
PubMed2005

Is heparin treatment the optimal management for cerebral venous thrombosis? Effect of abciximab, recombinant tissue plasminogen activator, and enoxaparin in experimentally induced superior sagittal sinus thrombosis.

BACKGROUND: Based on a newly developed model of reversible superior sagittal sinus (SSS) thrombosis in the rat, we investigated the effect of thrombolytic and anticoagulant treatment on recanalization, brain parenchymal changes, and motor deficits. METHODS: Thrombosis of the SSS was induced by topical application of ferric chloride. Occlusion was confirmed by magnetic resonance angiography (MRA). Six hours after operation, single treatment with 10 mg recombinant tissue plasminogen activator (rtPA)/kg and 6 mg abciximab/kg or subcutaneous injection of 450 IU/kg enoxaparin twice daily was started, each group containing 10 rats. Follow-up MRI with T2- and diffusion-weighted images was performed on the first, second, and seventh postoperative day. RESULTS: Control and enoxaparin-treated animals developed diffuse brain edema without infarction or intracerebral bleeding. This was indicated by an increase of T2 relaxation time and a decrease of the apparent diffusion coefficient in the parasagittal and lateral cortex. In these groups, the degree of recanalization after 7 days was comparable (48% versus 52%). Enoxaparin-treated animals showed significant amelioration of functional deficits. Clinical outcome was best in the abciximab-treated group, with a residual sinus occlusion of 36% after 1 week. Highest recanalization was achieved by lysis with rtPA (85%). CONCLUSIONS: Enoxaparin treatment in rats with cerebral venous thrombosis significantly influences clinical outcome. However, it has no effect on recanalization. GPIIb/IIIa antagonists and rtPA accelerate thrombolysis. They may represent an alternative in treatment of cerebral venous thrombosis.

Abciximab↗
PubMed2005

A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells.

BACKGROUND & AIMS: Although Helicobacter pylori is recognized by the human immune system, the bacteria are not eliminated and lead to a chronic inflammation of the gastric mucosa. METHODS: We investigated the interaction of H. pylori with human lymphocytes. T and B lymphocytes were isolated from H. pylori-infected patients and stimulated with anti-CD3/CD28 or interleukin-6. RESULTS: Proliferation of lymphocytes was abolished on co-incubation with different H. pylori strains (1-5 bacteria/cell) or with protein extracts of culture supernatants. Inhibition of proliferation was independent of known virulence factors. The factor is a protein or protein complex with an apparent molecular weight between 30 and 60 kilodaltons, clearly distinct from VacA. Although antigen-specific activation of T cells (as shown by nuclear factor of activated T cells [NFAT]-activation, interferon-gamma production, and CD25 or CD69 up-regulation) remained intact, cell-cycle analysis showed that S-phase entry of T cells was inhibited completely by H. pylori. Consequently, stimulated T cells arrested in the G1 phase of the cell cycle. Western blot analysis showed markedly reduced phosphorylation of the retinoblastoma protein (pRb), suggesting inhibition of G1 cyclin-dependent kinase activity. In line with this, activities of cyclin D3 and cyclin E were down-regulated, and levels of the cyclin-dependent kinase inhibitor p27Kip1 were increased. Mouse embryonic fibroblasts deficient in p27 showed a decrease in H. pylori-induced inhibition of cell proliferation, suggesting a central role for p27 in mediating H. pylori-induced G1 arrest. CONCLUSIONS: Induction of cell-cycle arrest in lymphocytes may be of major significance for the chronic persistence of bacteria in the human stomach.

Antigens, CD19↗