Quantification of the Cannabinoid Type 1 Receptor Availability in the Mouse Brain.

: The endocannabinoid system is involved in several diseases such as addictive disorders, schizophrenia, post-traumatic stress disorder, and eating disorders. As often mice are used as the preferred animal model in translational research, in particular when using genetically modified mice, this study aimed to provide a systematic analysis of cannabinoid type 1 (CB1) receptor ligand-binding capacity using positron emission tomography (PET) using the ligand [F]MK-9470. We then compared the PET results with literature data from immunohistochemistry (IHC) to review the consistency between protein expression and ligand binding.

A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer.

CV9201 is an RNActive-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400-1600 µg of mRNA). The primary objective of the trial was to assess safety.

Analysing the opinions of UK veterinarians on practice-based research using corpus linguistic and mathematical methods.

The use of corpus linguistic techniques and other related mathematical analyses have rarely, if ever, been applied to qualitative data collected from the veterinary field. The aim of this study was to explore the use of a combination of corpus linguistic analyses and mathematical methods to investigate a free-text questionnaire dataset collected from 3796 UK veterinarians on evidence-based veterinary medicine, specifically, attitudes towards practice-based research (PBR) and improving the veterinary knowledge base. The corpus methods of key word, concordance and collocate analyses were used to identify patterns of meanings within the free text responses.

Distinct transcriptional changes in non-small cell lung cancer patients associated with multi-antigenic RNActive® CV9201 immunotherapy.

We recently completed a phase I/IIa trial of RNActive® CV9201, a novel mRNA-based therapeutic vaccine targeting five tumor-associated antigens in non-small cell lung cancer (NSCLC) patients. The aim of the study presented here was to comprehensively analyze changes in peripheral blood during the vaccination period and to generate hypotheses facilitating the identification of potential biomarkers correlating with differential clinical outcomes post RNActive® immunotherapy. We performed whole-genome expression profiling in a subgroup of 22 stage IV NSCLC patients before and after initiation of treatment with CV9201.

Specification of the cholesterol interaction with the oxytocin receptor using a chimeric receptor approach.

The oxytocin receptor specifically requires cholesterol to maintain and stabilize its high-affinity agonist binding. Here, we applied a receptor chimeric approach to coarsely localize the cholesterol binding domain of the oxytocin receptor. During these studies, we identified the specific dependence on cholesterol as a common property of the oxytocin-vasopressin receptor family.

Transport of plasma membrane-derived cholesterol and the function of Niemann-Pick C1 Protein.

To visualize the intracellular transport of plasma membrane-derived cholesterol under physiological and pathophysiological conditions, a novel fluorescent cholesterol analog, 6-dansyl cholestanol (DChol), has been synthesized. We present several lines of evidence that DChol mimics cholesterol. The cholesterol probe could be efficiently incorporated into the plasma membrane via cyclodextrin-donor complexes.

Cholesterol and steroid hormones: modulators of oxytocin receptor function.

The function and physiological regulation of the oxytocin-receptor system is strongly steroid-dependent. This is, unexpectedly, only partially reflected by the promoter sequences in the oxytocin receptor and favors the idea that posttranscriptional mechanisms may also play a significant role for the physiological regulation of the oxytocin-receptor system. Our data indicate that cholesterol acts as an allosteric modulator of the oxytocin receptor and stabilizes both membrane-associated and solubilized OT receptors in a high-affinity state for agonists and antagonists.

Molecular modelling study of the role of cholesterol in the stimulation of the oxytocin receptor.

Cholesterol, an integral component of membranes in Eucaryota, is a modifier of membrane properties. In vivo studies have demonstrated that cholesterol can also modulate activities of some G protein-coupled receptors (GPCRs), which are integral membrane proteins. This can result either from an effect of cholesterol on the membrane fluidity or from specific interactions of the membrane cholesterol with the receptor, as recently demonstrated for the cholecystokinin type beta (CCKRbeta) or the oxytocin receptor (OTR).

Proliferative response of human and minipig smooth muscle cells after coronary angioplasty to growth factors and platelets.

Objectives: Platelets aggregating at the site of angioplasty, shown to be a potent proliferative stimulus for cultured smooth muscle cells (SMC), could contribute to proliferation after angioplasty.

Methods: SMC were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty coronary artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation.

Recoil following Wiktor stent implantation for restenotic lesions of coronary arteries.

The purpose of this study was to determine acute recoil of the vessel wall immediately after Wiktor stent implantation in native coronary arteries of 77 consecutive patients and to assess whether there was compression or "late recoil" of the stent itself at long-term follow-up. Furthermore, the relationship between recoil and a number of clinical, angiographic, and procedural variables was studied in addition to the relation between acute recoil renarrowing or restenosis was assessed. All angiograms were analyzed with the Cardiovascular Angiography Analysis System using automated edge detection.

Autofluorescence spectroscopy using a XeCl excimer laser system for simultaneous plaque ablation and fluorescence excitation.

Laser-induced fluorescence may be used to guide laser ablation of atherosclerotic lesions. This study was performed to evaluate arterial autofluorescence spectroscopy in vitro using a single XeCl excimer laser (308 nm) for simultaneous tissue ablation and fluorescence excitation. The laser beam was coupled to a 600-microns silica fiber transmitting 40-50 mJ/mm2 per pulse.

Cutting balloon coronary angioplasty--initial clinical experience.

The success of percutaneous transluminal coronary angioplasty is limited by acute occlusion and late restenosis. In 25 patients (20 men, 5 women, age range 36-81 years) coronary angioplasty was performed using a new cutting balloon into which 3-4 longitudinally orientated blades are incorporated so as to reduce the rate of severe dissections. In 12 patients stenoses were reduced from 83.

Angiographic predictors of recurrence of restenosis after Wiktor stent implantation in native coronary arteries.

Intracoronary stenting has been proposed as an adjunct to balloon angioplasty to improve the immediate and long-term results. However, late luminal narrowing has been reported following the implantation of a variety of stents. One of the studies conducted with the Wiktor stent is a prospective registry designed to evaluate the feasibility, safety and efficacy of elective stent implantation in patients with documented restenosis of a native coronary artery.

[Coronary angioplasty with controlled longitudinal dissection. Initial clinical results using a new cutting balloon].

A recently developed cutting balloon was used for coronary angioplasty in 21 patients (4 women, 17 men; mean age 57.6 [36-81] years) with coronary heart disease (angioplasty of the right coronary artery in 4, of the circumflex branch in 4, and of the anterior interventricular branch in 13 patients). The balloon contains 3-4 longitudinally arranged metal cutters to prevent uncontrolled vessel tears.

Immune thrombocytopenia associated with hemorrhagic diathesis due to ibuprofen administration.

Acute thrombocytopenic purpura temporally related to the oral administration of ibuprofen developed in a patient with ankylosing spondylitis. Clinical manifestations, with sudden onset occurring within 12 h of drug ingestion and rapid increase of platelet counts following discontinuation of the drug, were characteristic of an antibody-mediated immune pathomechanism. Immunological studies demonstrated IgM and IgG antibodies in the patient's serum that were capable of binding to allogenic platelets in the presence of a metabolite preparation.

Stent wire cutting during coronary directional atherectomy.

Directional atherectomy represents one potential approach for the treatment of restenosis in stented coronary arteries. In this case report we demonstrate an important pitfall of this angioplasty technique for stent restenosis--inadvertent entanglement of the stent wire in the device. While cutting and removal of part of the wire was achieved in the case presented, this potential adverse event limits the applicability of directional atherectomy for restenosis in coronary stents.

Fractured strut of Björk-Shiley 70 degrees convexo-concave mitral valve prosthesis found in left coronary artery. Use of a portable transcutaneous cardiopulmonary bypass system for successful valve replacement.

Strut fractures followed by disk escape of Björk-Shiley convexo-concave valve prostheses are a well-known problem. This article discusses the case of a successfully treated patient who was admitted to our institution with extreme and prolonged cardiogenic shock. The strut was dislodged into the main stem of the left coronary artery and the disk into the iuxtarenal abdominal aorta.

Aorto-coronary artery to coronary vein fistula with the potential of coronary steal as complication of saphenous vein jump bypass graft.

We report the first documented case of an iatrogenic aorto-coronary artery to coronary vein fistula secondary to an aortocoronary saphenous vein jump bypass graft inadvertently anastomosed to a coronary vein. Angiographic and oximetric results of left and right cardiac catheterization--including direct catheterization of the anastomosed coronary vein--as well as clinical data with a four-year follow-up are presented. The role of surgery, percutaneous transcatheter embolization, and conservative treatment is discussed in this unique case with the potential of a coronary steal phenomenon.

Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.

Objectives: The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting.

Background: Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices.

Methods: In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents.

[Vital recognition of complete occlusion of the left main coronary artery].

Left main coronary artery occlusion is found in about 0.05% of all coronary arteriograms. In this case report left main occlusion was associated with a dominant right coronary artery and good collaterals to the circumflex and left anterior descending coronary arteries, which seems to be essential for survival in this lesion.

Antiproliferative effects of a c-myc antisense oligonucleotide on human arterial smooth muscle cells.

The effects of a c-myc antisense phosphorothioate DNA oligonucleotide were assessed on the proliferation rate of human arterial smooth muscle cells (HSMCs). Compared to a control oligonucleotide the antisense oligonucleotide suppressed the proliferation of HSMCs in a concentration-dependent manner without a major cytotoxic effect. Outgrowth of HSMCs from media explants was significantly inhibited as well.

Coronary angioplasty in patients with previous coronary artery bypass grafting.

Between 1982 and 1990, in 134 patients with prior coronary artery bypass grafting and recurrent angina, repeat coronary angiography and balloon angioplasty of stenoses in grafts or native arteries were attempted. Mean age of grafts was 45.6 months, range three days to twelve years.