The endocannabinoid 2-AG controls skeletal muscle cell differentiation via CB1 receptor-dependent inhibition of Kv7 channels.

Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C2C12 myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation.

Retinoids produced by macrophages engulfing apoptotic cells contribute to the appearance of transglutaminase 2 in apoptotic thymocytes.

Transglutaminase 2 (TG2) has been known for a long time to be associated with the in vivo apoptosis program of various cell types including T cells. Though the expression of the enzyme was strongly induced in mouse thymocytes following apoptosis induction in vivo, no significant induction of TG2 could be detected, when thymocytes were induced to die by the same stimuli in vitro indicating that signals arriving from the tissue environment are required for the in vivo induction of the enzyme in apoptotic thymocytes. Previous studies have shown that one of these signals is transforming growth factor-β (TGF-β) which is released by macrophages engulfing apoptotic cells.

Recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.

Objective: We report an extremely rare case of recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis.

Method: Case report presenting a 15-year-old girl referred with hoarseness and soft voice.

Results: Right-sided recurrent laryngeal nerve paralysis was observed using videolaryngoscopy.

Histopathology of nonotosclerotic stapes fixations.

Hypothesis: Different diseases without exact histopathologic classification can cause stapes ankylosis.

Background: Otosclerosis is a complex bone remodeling disorder of the otic capsule due to persisting measles virus infection and consecutive inflammatory reaction. In fact, clinical and demographic features of otosclerosis have reference to stapes ankylosis.

Principles of resonance energy transfer.

This unit describes the basic principles of the fluorescence resonance energy (FRET) process. In addition, it characterizes available parameters and instruments for FRET measurements, discusses limitations, and shows a few examples of the application of FRET.

Disease-associated novel CD46 splicing variants and pathologic bone remodeling in otosclerosis.

Objective/hypothesis: Otosclerotic bone is supposed to show unique CD46 expression pattern because otosclerosis is an organ-specific disease with viral etiology.

Study Design: Otosclerosis is a complex bone remodeling disorder of the human otic capsule, which is associated with persisting measles virus infection. The general cellular receptor of measles virus is the CD46, which has 14-known splicing isoforms.

Some lessons from the tissue transglutaminase knockout mouse.

Transglutaminase 2 (TG2) is an inducible transamidating acyltransferase that catalyzes Ca(2+)-dependent protein modifications. It acts as a G protein in transmembrane signaling and as a cell surface adhesion mediator, this distinguishes it from other members of the transglutaminase family. The sequence motifs and domains revealed in the TG2 structure, can each be assigned distinct cellular functions, including the regulation of cytoskeleton, cell adhesion, and cell death.

Novel antiarrhythmic agents with combined mode of action.

In spite of the accelerated evolution in antiarrhythmic drug research and design, the ideal antiarrhythmic compound has not yet emerged. Pure class III agents have not been clinically successful, mainly due to their torsadogenic side-effects. Combination of class III effect with class I, II or IV effects has given better therapeutic results, whilst combination of the various antiarrhythmic mechanisms within one molecule, rather than combination of drugs, seems to be an even more promising strategy.

Cardiac manifestations in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease associated with arterial and venous thrombotic events and recurrent fetal loss. Cardiac manifestations in APS primarily include accelerated atherosclerosis leading to cardiovascular disease. There is increased cardiovascular mortality in APS.

Expression of measles virus receptors in otosclerotic, non-otosclerotic and in normal stapes footplates.

Otosclerosis is a bone remodeling disorder of complex etiology. Persistent measles virus infection of the otic capsule could increase the expression level of measles virus receptors (CD46) on the osteoclasts and endothelial cells of the otosclerotic foci. Presence of measles virus RNA was demonstrated in the footplates of histologically diagnosed otosclerotic patients by RT-PCR; however, no reports were available about the CD46 expression pattern and level in otosclerosis.

Measles virus prevalence in otosclerotic foci.

The etiology of otosclerosis is still unknown. Persistent measles virus infection of the otic capsule is supposed to be one of the etiologic factors in otosclerosis. The presence of measles virus was shown in otosclerotic patients by RT-PCR amplification of the viral RNA, detecting the viral proteins by immunohistochemistry and antimeasles immunoglobulin G in the perilymph samples.

Chip-on-beads: flow-cytometric evaluation of chromatin immunoprecipitation.

Background: Chromatin immunoprecipitation (ChIP) is a widely used technique for the detection of in vivo DNA-protein interactions underlying epigenetic regulation. The standard readout of ChIP is based on semi-quantitative or quantitative PCR measurements; however, the development of alternative platforms with high throughput potentialities is expected to facilitate the introduction of this method into routine diagnostics.

Methods: We have established a flow-cytometry-based alternative for the evaluation of ChIP data.

Activated osteoclasts with CD51/61 expression in otosclerosis.

Hypothesis: Stapes ankylosis is supposed to be a disease with variable histopathology caused by otosclerosis or pseudo-otosclerosis. Persistent measles virus infection of the otic capsule could induce reactivation of quiescent embryonic osteoclasts in otosclerosis.

Background: Presence of measles virus RNA was demonstrated in the footplates of otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR).

Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic Stapes footplates in connection with measles virus positivity.

Hypothesis: Otosclerosis is a bone remodeling disorder of the otic capsule causing conductive and sensorineural hearing loss. Persistent measles virus infection of the temporal bone with increased tumor necrosis factor (TNF)-alpha and decreased osteoprotegerin mRNA expression is supposed to be the main etiologic factor in otosclerosis.

Background: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis.

Superoxide anion production of granulocytes in patients with endometrial cancer at presentation and after treatment.

Background: In current medical science the reactive oxygen intermediates play an ever more important role.

Methods: The authors analysed superoxide anion production of polymorphonuclear leukocytes (PMNLs) in 30 blood samples from endometrial carcinoma patients. They measured it before the complex treatment and in nine cases at least 1 year after finishing the treatment.

Antimeasles immunoglobulin g for serologic diagnosis of otosclerotic hearing loss.

Hypothesis: Persistent measles virus infection of the otic capsule is suggested to be an etiologic factor in otosclerosis. Otosclerosis is a disease of complex unknown etiology causing progressive conductive and/or sensorineural hearing loss (HL).

Background: Diagnostic methods of otosclerosis are sensitive to ossicular chain fixation with low specificity for otosclerotic stapes ankylosis.

Two subgroups of stapes fixation: otosclerosis and pseudo-otosclerosis.

Hypothesis: Stapes ankylosis is a disease with variable histopathology and can be caused by otosclerosis or pseudo-otosclerosis. Viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplate and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the viral RNA.

Background: Presence of the RNA genome of measles virus was demonstrated in the footplates of clinically otosclerotic patients by RT-PCR, and also viral proteins were detected by immunohistochemistry.

Histologic otosclerosis is associated with the presence of measles virus in the stapes footplate.

Hypothesis: Persistent measles virus infection of the otic capsule is presumed to be one of the etiologic factors in otosclerosis. The viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplates and reverse-transcriptase polymerase chain reaction amplification of the viral RNA. At present, histologic analysis of the removed stapes footplates is the only appropriate method of distinguishing otosclerotic and nonotosclerotic stapes fixations.

High prevalence of oesophageal involvement in patients with undifferentiated connective tissue disease using radionuclide oesophageal transit scintigraphy.

Aim: To look for the frequency of oesophageal dysfunction using radionuclide oesophageal transit scintigraphy in 145 patients with undifferentiated connective tissue disease (UCTD); to seek the correlation between the clinical/laboratory data and scintigraphic alterations; and to determine predictive value of radionuclide oesophageal transit scintigraphy for evolution to established connective tissue disease (CTD).

Method: One hundred and forty-five patients with UCTD were examined by 99mTc-DTPA oesophageal transit scintigraphy. The intraoesophageal transport of the radiopharmaceutical was followed and imaged by a gamma camera, a series of 128 x 128 images were stored and evaluated.

Marked phenotypic variation in a family with a new myelin protein zero mutation.

Myelin protein zero (MPZ) is a member of the immunoglobulin gene superfamily, which has a role in myelin compaction. MPZ gene mutations cause mostly demyelinating neuropathies of the Charcot-Marie-Tooth 1B type (CMT1B), but axonal CMT have been described as well. There is a broad spectrum of phenotypic manifestation of neuropathies caused by MPZ mutations.

Nick-forming sequences may be involved in the organization of eukaryotic chromatin into approximately 50 kbp loops.

Phenomena involving the disassembly of chromosomes to approximately 50 kbp double-stranded fragments upon protein denaturing treatments of normal and apoptotic mammalian nuclei as well as yeast protoplasts may be an indication of special, hypersensitive regions positioned regularly at loop-size intervals in the eukaryotic chromatin. Here we show evidence in yeast cell systems that loop-size fragmentation can occur in any phase of the cell cycle and that the plating efficiency of these cells is approximately 100%. The possibility of sequence specificity was investigated within the breakpoint cluster region (bcr) of the human MLL gene, frequently rearranged in certain leukemias.

Effects of SEA0400 and KB-R7943 on Na+/Ca2+ exchange current and L-type Ca2+ current in canine ventricular cardiomyocytes.

SEA0400 and KB-R7943 are compounds synthesised to block transsarcolemmal Na+/Ca2+ exchange current (I(Na/Ca)); however, they have also been shown to inhibit L-type Ca2+ current (I(Ca)). The potential value of these compounds depends critically on their relative selectivity for I(Na/Ca) over I(Ca). In the present work, therefore, the concentration-dependent effects of SEA0400 and KB-R7943 on I(Na/Ca) and I(Ca) were studied and compared in canine ventricular cardiomyocytes using the whole-cell configuration of the patch clamp technique.

Codetection of measles virus and tumor necrosis factor-alpha mRNA in otosclerotic stapes footplates.

Hypothesis: Otosclerosis is a disease of unknown etiology causing conductive or sensorineural hearing loss. Persistent measles virus infection of the otic capsule is considered to be one of the etiologic factors in otosclerosis.

Background: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis.

Ligation of RARgamma inhibits proliferation of phytohaemagglutinin-stimulated T-cells via down-regulating JAK3 protein levels.

The mechanisms whereby Vitamin A regulates the immune system are poorly understood. We have shown previously that retinoic acids, the Vitamin A derivatives, promote both apoptosis of neglected thymocytes and the activation-induced cell death of peripheral T-cells via ligating the nuclear retinoid receptor (RAR) gamma. In the present study, we found that human peripheral T-cells express RARalpha and gamma, but not RARbeta.

Plasmin promotes keratinocyte migration and phagocytic-killing accompanied by suppression of cell proliferation which may facilitate re-epithelialization of wound beds.

Keratinocytes were shown to induce the activation of plasminogen activator resulting in the formation of plasmin and the initiation of proteolysis in vitro. Activation of surface bound plasminogen may localize protease activity in the pericellular microenvironment and play a role in inducing both a conformational change and cell locomotion. Plasmin, however, can induce non-proteolytic effects on certain cell functions in a variety of cell lineages.