Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity.

Estrogens are known to cause hepatotoxicity such as intrahepatic cholestasis in susceptible women during pregnancy, after administration of oral contraceptives, or during postmenopausal replacement therapy. Enterohepatic nuclear receptors including farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive active/androstane receptor (CAR) are important in maintaining bile acid homeostasis and protecting the liver from bile acid toxicity. However, no nuclear receptor has been implicated in the mechanism for estrogen-induced hepatotoxicity.

Dispersion in active transport by kinesin-powered molecular shuttles.

Active transport driven by molecular motors is a key technology for the continued miniaturization of lab-on-a-chip devices, because it is expected to enable nanofluidic devices with channel diameters of less than 1 microm and total channel lengths on the order of 1 mm. An important metric for a transport mechanism employed in an analytic device is dispersion, because it critically affects the sensitivity and resolution. Here, we investigate the mechanisms responsible for the dispersion of a swarm of "molecular shuttles", consisting of functionalized microtubules propelled by surface-adhered kinesin motor proteins.

"Safe" Coulomb excitation of 30Mg.

We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient gamma spectrometer MINIBALL. Using 30Mg ions accelerated to an energy of 2.25 MeV/u together with a thin (nat)Ni target, Coulomb excitation of the first excited 2+ states of the projectile and target nuclei well below the Coulomb barrier was observed.

Caenorhabditus elegans arrestin regulates neural G protein signaling and olfactory adaptation and recovery.

Although regulation of G protein-coupled receptor signaling by receptor kinases and arrestins is a well established biochemical process, the physiological significance of such regulation remains poorly understood. To better understand the in vivo consequences of arrestin function, we have examined the function of the sole arrestin in Caenorhabditis elegans (ARR-1). ARR-1 is primarily expressed in the nervous system, including the HSN neuron and various chemosensory neurons involved in detecting soluble and volatile odorants.

The right hand knows what the left hand is feeling.

The mislocalization profile, describing incorrect localization of faint tactile stimuli to different regions of the body, has been shown to provide insight into the processing of tactile stimuli. Interhemispheric somatosensory processing was examined in 15 subjects by studying the interference of left-hand stimulation on right-hand perception. In different conditions supra-threshold interference stimuli were applied to the left thumb or little finger either 200 or 500 ms prior to the application of a test stimulus on the right hand.

Molecular self-assembly of "nanowires"and "nanospools" using active transport.

Mastering supramolecular self-assembly to a similar degree as nature has achieved on a subcellular scale is critical for the efficient fabrication of complex nanoscopic and mesoscopic structures. We demonstrate that active, molecular-scale transport powered by biomolecular motors can be utilized to drive the self-assembly of mesoscopic structures that would not form in the absence of active transport. In the presented example, functionalized microtubules transported by surface-immobilized kinesin motors cross-link via biotin/streptavidin bonds and form extended linear and circular mesoscopic structures, which move in the presence of ATP.

RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans.

Heterotrimeric G proteins promote microtubule forces that position mitotic spindles during asymmetric cell division in C. elegans embryos. While all previously studied G protein functions require activation by seven-transmembrane receptors, this function appears to be receptor independent.

Control of exercise-stimulated muscle glucose uptake by GLUT4 is dependent on glucose phosphorylation capacity in the conscious mouse.

Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during exercise because GLUT4 overexpression does not increase exercise-stimulated MGU. Instead of glucose transport, glucose phosphorylation is a primary limitation of exercise-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair exercise-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity was increased.

Regulation of insulin-stimulated muscle glucose uptake in the conscious mouse: role of glucose transport is dependent on glucose phosphorylation capacity.

Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during hyperinsulinemia, because glucose phosphorylation is the more formidable barrier to insulin-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair insulin-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity is increased. Thus, chow-fed C57BL/6J mice with a GLUT4 partial knockout (GLUT4(+/-)), hexokinase II overexpression (HK(Tg)), or both (HK(Tg) + GLUT4(+/-)) and wild-type littermates were studied.

Effects of Sapindus saponaria fruits on ruminal fermentation and duodenal nitrogen flow of sheep fed a tropical grass diet with and without legume.

Six adult African-type hair sheep (BW = 40.3 +/- 6.3 kg) fitted with ruminal and duodenal cannulas were subjected to four treatments.

Powering nanodevices with biomolecular motors.

Biomolecular motors, in particular motor proteins, are ideally suited to introduce chemically powered movement of selected components into devices engineered at the micro- and nanoscale level. The design of such hybrid "bio/nano"-devices requires suitable synthetic environments, and the identification of unique applications. We discuss current approaches to utilize active transport and actuation on a molecular scale, and we give an outlook to the future.

Motor-protein "roundabouts": microtubules moving on kinesin-coated tracks through engineered networks.

Nanotechnology promises to enhance the functionality and sensitivity of miniaturized analytical systems. For example, nanoscale transport systems, which are driven by molecular motors, permit the controlled movement of select cargo along predetermined paths. Such shuttle systems may enhance the detection efficiency of an analytical system or facilitate the controlled assembly of sophisticated nanostructures if transport can be coordinated through complex track networks.

[Injuries and chronic damages in classic ballet].

From 1994 till 1996 there were examined 219 dancers (male and female) at 8 theatres because of typical injuries and damages. It was elevated an exactly anamnese and physical examination with regard to orthopedic peculiarity. The determined dates were documented on a standardized form and analyzed separately to the respective part of the body.

Molecular shuttles based on motor proteins: active transport in synthetic environments.

Active transport in cells, utilizing molecular motors like kinesin and myosin, provides the inspiration for the integration of active transport into synthetic devices. Hybrid devices, employing motor proteins in a synthetic environment, are the first prototypes of molecular shuttles. Here the basic characteristics of motor proteins are discussed from an engineering point of view, and the experiments aimed at incorporating motor proteins, such as myosins and kinesins, into devices are reviewed.

Absence of clinically relevant drug interactions following simultaneous administration of didanosine-encapsulated, enteric-coated bead formulation with either itraconazole or fluconazole.

This open-label, two-way crossover study was undertaken to determine whether the enteric formulation of didanosine influences the pharmacokinetics of itraconazole or fluconazole, two agents frequently used to treat fungal infections that occur with HIV infection, and whose bioavailability may be influenced by changes in gastric pH. Healthy subjects were randomized to Treatment A (200-mg itraconazole or 200-mg fluconazole) or Treatment B (same dose of itraconazole or fluconazole with 400 mg of didanosine as an encapsulated, enteric-coated bead formulation). In the itraconazole study, a lack of interaction was concluded if the 90% confidence interval (CI) of the ratio of the geometric means of log-transformed C(max) and AUC(0-T) values of itraconazole and hydroxyitraconazole, the active metabolite of itraconazole, were contained entirely between 0.

Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoropopliteal occlusions: a prospective, randomized multicenter trial.

Purpose: To report the outcome of a prospective, randomized, open multicenter trial comparing (1) the effects of local thrombolysis with recombinant tissue plasminogen activator (rtPA) or urokinase (UK) and (2) 2 administration techniques.

Methods: Two hundred thirty-four patients with thromboembolic occlusions in 223 native femoral or popliteal arteries (95%) and 11 bypass grafts (5%) were randomized to rtPA (n = 124) or UK (n = 110) administered either through an endhole catheter (Hess technique) in 81 patients or a microporous balloon catheter (Schneider technique) in 153 patients. When lysis was incomplete, additional catheter interventions were applied to achieve patency.

Modem remote support of pulmonary-function testing and quality control systems.

The data coordinating center (DCC) of the Asthma Clinical Research Network (ACRN) is responsible for the support of 11 pulmonary-function testing systems and two quality control systems. Pulmonary-function data from these systems are used as outcome indicators in studies conducted by the ACRN. Each of these systems is composed of a spirometer, a personal computer for data acquisition from the spirometer, a modem, and a printer.

Null mutations in the lin-31 gene indicate two functions during Caenorhabditis elegans vulval development.

The lin-31 gene is required for the proper specification of vulval cell fates in the nematode Caenorhabditis elegans and encodes a member of the winged-helix family of transcription factors. Members of this important family have been identified in many organisms and are known to bind specific DNA targets involved in a variety of developmental processes. DNA sequencing of 13 lin-31 alleles revealed six nonsense mutations and two missense mutations within the DNA-binding domain, plus three deletions, one transposon insertion, and one frameshift mutation that all cause large-scale disruptions in the gene.

Extracardiac conduit fontan procedure: early and intermediate results.

Objective: The extracardiac Fontan procedure, as compared with classic atriopulmonary connections, may have the potential for optimizing ventricular and pulmonary vascular function by maximizing the laminar flow principle, by the avoidance of intra-atrial suture lines and cardiac manipulation, and by minimizing cardiopulmonary bypass time. In this study the clinical results of this procedure are assessed.

Methods: From January 1990 until January 1997, 45 patients (33 males and 12 females) with a median age of 4.

Imaging of localized electronic states in the quantum Hall regime.

The concept of electron localization has long been accepted to be essential to the physics of the quantum Hall effect in a two-dimensional electron gas. The exact quantization of the Hall resistance and the zero of the diagonal resistance over a range of filling factors close to integral are attributed to the localization of electronic states at the Fermi level in the interior of the gas. As the electron density is changed, charging of the individual localized states may occur by single-electron jumps, causing associated oscillations in the local electrostatic potential.

Excision of coronary artery fistula and coronary artery reconstruction without cardiopulmonary bypass.

In three patients, coronary artery fistulas originating from a conal branch of the mid-segment of the left anterior descending coronary artery (n = 2) and right coronary artery (n = 1) with drainage into the right atrium (n = 2) and right ventricle (n = 1) were successfully closed without the use of cardiopulmonary bypass. The use of a coronary artery stabilizer greatly facilitated the operation by immobilization of the fistula, its supplying coronary artery, and the regional myocardium. In selected patients, this technique allows secure closure of the fistula and meticulous reconstruction of the coronary artery without the use of cardiopulmonary bypass.

Early repair of coarctation of the aorta.

Background: Repair of coarctation of the aorta with hypoplasia and elongation of the proximal aortic arch is a technically demanding procedure with a substantial rate of recurrent stenosis at the coarctation repair site. In addition, a high incidence of hypertension has been reported in patients who underwent repair beyond infancy.

Patients And Methods: Between January 1991 and June 1997, 52 patients (34 neonates and 18 infants with a median age of 37 days; range 2 days to 8 months) with a mean peak systolic upper to lower extremity resting gradient of 33.

Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation.

We have compared the efficiency of central nervous system and peripheral antigen-presenting cells (APC) in T cell priming and restimulation. OVA peptide 323 - 339-dependent activation of DO11.10 TCR-transgenic naive CD4+ and polarized Th1 or Th2 cells was assessed in the presence of microglia and astrocytes from the neonatal mouse brain as well as dendritic cells (DC) and B cells purified from adult mouse lymph nodes.