Adenovirus-mediated inducible gene expression in vivo by a hybrid ecdysone receptor.

Precise control of transgene expression would markedly facilitate certain applications of gene therapy. To regulate expression of a transferred gene in response to an exogenous compound in vivo, we modified the ecdysone-responsive system. We combined the advantages of the Drosophila (DmEcR) and the Bombyx ecdysone receptor (BmEcR) by creating a chimeric Drosophila/Bombyx ecdysone receptor (DB-EcR) that preserved the ability to bind to the modified ecdysone promoter without exogenous retinoid X receptor (RXR).

Viral gene transfer of dominant-negative Kv4 construct suppresses an O2-sensitive K+ current in chemoreceptor cells.

Hypoxia initiates the neurosecretory response of the carotid body (CB) by inhibiting one or more potassium channels in the chemoreceptor cells. Oxygen-sensitive K(+) channels were first described in rabbit CB chemoreceptor cells, in which a transient outward K(+) current was reported to be reversibly inhibited by hypoxia. Although progress has been made to characterize this current with electrophysiological and pharmacological tools, no attempts have been made to identify which Kv channel proteins are expressed in rabbit CB chemoreceptor cells and to determine their contribution to the native O(2)-sensitive K(+) current.

Infarct related artery patency: relation to serial electropharmacological studies and outcome in patients with previous myocardial infarction and ventricular tachyarrhythmias.

Evidence suggests that infarct related artery (IRA) patency may improve survival after acute myocardial infarction, which is thought to be partially due to a lower incidence of malignant ventricular tachyarrhythmias. However, little is known about the effect of IRA patency on antiarrhythmic drug response and long-term outcome in patients with previous infarction who already experienced sustained ventricular tachyarrhythmias. A total of 152 patients with remote myocardial infarction and documented ventricular tachycardia (VT) or ventricular fibrillation (VF) underwent coronary angiography and programmed ventricular stimulation before and after oral administration of d,l-sotalol (240-640 mg/day).

Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer.

Heart failure leads to marked suppression of the Ca(2+)-independent transient outward current (I(to1)), but it is not clear whether I(to1) downregulation suffices to explain the concomitant action potential prolongation. To investigate the role of I(to1) in cardiac repolarization while circumventing culture-related action potential alterations, we injected adenovirus vectors in vivo to overexpress or to suppress I(to1) in guinea pigs and rats, respectively. Myocytes were isolated 72 hours after intramyocardial injection and stimulation of the ecdysone-inducible vectors with intraperitoneal injection of an ecdysone analog.

Surgical repair of right-atrial aneurysm.

Atrial fibrillation and embolic events are the most common clinical symptoms of congenital right- or left-atrial aneurysms. We report an a case of righ-atrial aneurysm, in a patient with typical history of atrial fibrillation and history of stroke. The aneurysm was resected, but the patient suffered from acute embolic occlusion of the left anterior descending coronary artery on the fourth postoperative day despite of systemic heparinization with 300 IU/kg bw per 24 hours.

[Outcome of hyperbaric oxygen therapy in therapy refractory tinnitus].

Although many studies are available concerning the treatment of sudden deafness using hyperbaric oxygenation, only a few of these deal with tinnitus. The aim of the present study was to evaluate the therapeutic use of hyperbaric oxygenation in cases of tinnitus. A total of 193 patients, having undergone primary intravenous hemorheologic therapy, were treated with hyperbaric oxygenation.

Two ceramide subfractions detectable in Cer(AS) position by HPTLC in skin surface lipids of non-lesional skin of atopic eczema.

The non-involved skin of atopic eczema (NEAE) is characterized by severe dryness and an impaired barrier function of the stratum corneum as indicated by an increased transepidermal water loss. Previous studies have demonstrated that this barrier impairment coincides with marked alterations in the amount and composition of stratum corneum ceramides. The aim of this study was to identify specific alterations in NEAE that may be used in the diagnosis of the atopic eczema.

Effect of gentian violet, corticosteroid and tar preparations in Staphylococcus-aureus-colonized atopic eczema.

Background: In atopic eczema (AE), skin colonization with Staphylococcus aureus plays a possible role in the pathophysiology of the disease.

Methods: Thirty-eight patients with AE were screened for their cutaneous colonization with S. aureus.

Coenzyme Q10, a cutaneous antioxidant and energizer.

The processes of aging and photoaging are associated with an increase in cellular oxidation. This may be in part due to a decline in the levels of the endogenous cellular antioxidant coenzyme Q10 (ubiquinone, CoQ10). Therefore, we have investigated whether topical application of CoQ10 has the beneficial effect of preventing photoaging.

[Modulation of oxidative stresses in human aging skin].

Oxidative stress (UV irradiation, free radicals) plays a significant role in aging. Coenzyme Q10 (CoQ10) and exogenously applied antioxidants can significantly reduce the formation of oxidative stress with increasing age. In our in vitro and in vivo experiments concerning the parameters of ultraweak photon emission (UPE), intracellular thiol status, mitochondrial membrane potential and cell vitality, we demonstrated a diminished resistance in keratinocytes of old donors against UV irradiation.

Determination of acute noise effects using distortion product otoacoustic emissions.

Because distortion product otoacoustic emissions (DPOAE) are the product of the effect of two sinus tones on the cochlea, a multitude of combinations regarding the amplitude and the frequency ratio of the primary tones exists. The goal of the present study was to directly compare different stimulus combinations described in the literature in the detection of acute noise trauma using DPOAE. In the present study, 13 volunteers were exposed for 1 h to noise that was equivalent to sound levels in a discotheque.

Manipulation of cellular excitability by cell fusion: effects of rapid introduction of transient outward K+ current on the guinea pig action potential.

To investigate the still-undetermined role of the Ca2+-independent transient outward current (Ito1) on repolarization of the cardiac action potential, we used cell fusion to introduce Ito1 into guinea pig cardiomyocytes, which normally lack this current. This technique enables the rapid delivery of premade functional ion channels to cardiomyocytes within hours of isolation, thus eliminating the action potential alterations that complicate prolonged cell culture. Chinese hamster ovary (CHO) cells stably expressing Kv4.

Semiquantitative chemiluminescent detection of UV-B-induced point mutations in the p53 tumor-suppressor gene.

The technique of allele-specific PCR (AS-PCR) enables the detection of a small number of mutant alleles in a large number of wild-type (WT) alleles. We used the AS-PCR technique and Southern blotting, using a nonradioactive labeled probe to analyze the formation of point mutations in the tumor-suppressor gene p53 of primary keratinocytes after UV-B irradiation. These permanent mutations resulting from CC dimers occur at distinct "hot-spots", one of which is affected in the human keratinocyte cell line HaCaT.

[Auditory speech-evoked cerebral cortex potentials in patients with stuttering syndromes].

Background: The cause of stuttering is unknown. For clinical purposes it proved to be useful to assume a multifactorial genesis with organic psychological and social aspects. A longstanding organic theory focussed on the failure to develop left-hemispheric dominance for speech, whereas others favoured deficits of the speech motor system.

Modulation of the hyperpolarization-activated inward current (If) by antiarrhythmic agents in isolated human atrial myocytes.

The hyperpolarization-activated inward current (If) has been discussed to contribute to arrhythmias in human atrial myocardium. If was found to be increased by beta-adrenergic stimulation. In the present study, we evaluate the modulation of If by carbachol, adenosine and by class Ic, III and IV antiarrhythmic drugs in isolated human atrial myocytes.

[Johanson-Blizzard syndrome. A complex dysplasia syndrome with aplasia of the nasal alae and inner ear deafness].

Background: The Johanson-Blizzard syndrome is a rare autosomal recessive syndrome with ectodermal dysplasia. ENT findings in the syndrome include profound bilateral hearing loss, aplasia of the alae nasi and dental malformations. To date approximately 30 cases have been described.

Butyrylcholinesterase antisense transfection increases apoptosis in differentiating retinal reaggregates of the chick embryo.

To investigate the roles of the enzymes butyryl- and acetylcholinesterase (BChE and AChE) in retinal proliferation and differentiation, we use reaggregated spheres from retinal cells of the 6-day-old chick embryo, forming cellular and fibrous areas homologous to all layers of a normal retina. Recently, we could suppress BChE expression by transfecting these so-called retinospheroids during their proliferation period with a pSVK3 expression vector containing a 5' fragment of the rabbit BChE gene in antisense orientation. Along with morphological changes, proliferation was significantly decreased.

Characterization of the hyperpolarization-activated inward current in isolated human atrial myocytes.

Objective: The hyperpolarization-activated inward current (I(f)) has been discussed to contribute to arrhythmias in rat hypertrophied and human failing ventricular myocardium. Cat atrial myocytes were found to exhibit variable size of I(f). In the present study, we evaluate characteristics of I(f) in human atrial myocardium and investigate if human atria might exhibit any electrophysiological heterogeneity in the diastolic voltage range.

Late-onset sensorineural hearing loss in Coffin-Lowry syndrome.

The Coffin-Lowry syndrome (CLS) is a rare clinical entity where patients present with a characteristic facies, mental retardation and bone abnormalities. So far about 60 cases have been reported. Sensorineural hearing loss is not a characteristic symptom and a late-onset hearing loss has not been reported so far.

Kinetics of DNA strand breaks and protection by antioxidants in UVA- or UVB-irradiated HaCaT keratinocytes using the single cell gel electrophoresis assay.

The aim of this study was to characterize the genotoxic action of UVA and UVB in human keratinocytes by application of the single cell gel electrophoresis assay (SCGE assay). Dose dependence of DNA damage, the time course of its repair, and the influence of cellular antioxidant status were assessed. Irradiation with UVA or UVB both resulted in a dose-dependent increase in the level of DNA damage.

[Chronic tinnitus in children and adolescents].

Background: The problem of tinnitus in adults is reviewed systematically in nearly all standard otolaryngology reference works, whereas textbooks and monographs that focus on pediatric otorhinolaryngology or audiology and hearing in children and adolescents provide only little information concerning the epidemiology, etiology and therapy of tinnitus. The purpose of this study was to evaluate the psychosomatic aspects of chronic tinnitus in this younger age group. A rational diagnostic approach is discussed as to which diagnostic measures are necessary in the pediatric group for deciding which therapeutic option to chose.

Regulation of cholinesterase gene expression affects neuronal differentiation as revealed by transfection studies on reaggregating embryonic chicken retinal cells.

In the embryonic chicken neuroepithelium, butyrylcholinesterase (BChE) as a proliferation marker and then acetylcholinesterase (AChE) as a differentiation marker are expressed in a mutually exclusive manner. These and other data indicate a coregulation of cholinesterase expression, and also possible roles of cholinesterases during neurogenesis. Here, both aspects are investigated by two independent transfection protocols of dissociated retina cells of the 6-day-old chick embryo in reaggregation culture, both protocols leading to efficient overexpression of AChE protein.