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Biomedical subjects

D Hof

Publications and source records attributed to D Hof.

9 recordsLinked to original sources

Apoptotic modifications affect the autoreactivity of the U1 snRNP autoantigen.

A hallmark of systemic autoimmune diseases is the presence of high titers of serum autoantibodies targeting a diversity of autoantigens. Most components of the U1 snRNP complex are autoantigenic in systemic lupus erythematosus (SLE) and SLE overlap syndrome, which is also called mixed connective tissue disease (MCTD). It is hypothesized that posttranslational modifications, in particular cell death-associated modifications, play an important role in breaking tolerance to self-antigens. Recently, it became clear that the U1 snRNP particle, more specifically its U1-70K protein component, displays a new epitope during apoptosis. This review intends to give an overview of the modifications that occur on the U1 snRNP autoantigens, especially those arising during cell death, to summarize recent data describing autoantibody reactivities with apoptosis-specific epitopes on the U1 snRNP complex, and to provide some insight into the mechanisms that might underlie the immune response to self-antigens.

Animals↗

Epidemiology of apparent life threatening events.

AIMS: To investigate the epidemiology and risk factors of apparent life threatening events (ALTE). METHODS: A prospective study enrolled all live-born infants in the Tyrol (1993-2001). Information on pregnancy, sociodemographic characteristics, child care practices, and infant's behaviour in the first four to six weeks of life was collected with a standardised questionnaire, and was available for 44,184 infants. ALTE was identified from hospital admission records. RESULTS: During the study period 164 ALTE cases were identified, corresponding to an incidence of 2.46/1000 live births. In 73 of these infants no cause for the event and no comorbidity could be found (idiopathic ALTE). On average ALTE manifested ten weeks earlier than SIDS. Of various SIDS risk factors in the survey area, the prone sleeping position, smoking during pregnancy, low gestational age, profuse night sweating, and family history of infant death showed a moderate relation to the risk of overall ALTE, but only smoking maintained significance in the multivariate risk model. None of these variables was associated with idiopathic ALTE. In contrast to SIDS the frequency of ALTE did not change during the study period. None of the ALTE infants experienced SIDS later in life. Behavioural abnormalities such as feeding difficulties, episodes of pallor, cyanotic episodes, and repeated apnoea episodes were strongly associated with an increased risk of overall and idiopathic ALTE. CONCLUSIONS: Although there are some similarities in the clinical presentation and epidemiology of SIDS and ALTE, differences clearly predominate. Accordingly, ALTE and SIDS should not be considered different manifestations of the same disease process.

Austria↗

The flaginserter: a simple device for automatically marking events in video recordings.

Dynamic imaging of cellular responses often involves the use of standard video components. While these components (cameras, monitors, etc.) are relatively inexpensive and easily available, there is the difficulty of integrating them into experimental set-ups. Especially for video recordings of fast signals that occur in neurobiological preparations (e.g. synaptic responses), there is a critical need for accurate synchronisation of video images with external events, such as extracellular stimulation or intracellular depolarising voltage steps. We developed a circuit that allows such events within the video sequence to be marked by means of a white flag that is inserted into the video image. Depending on the mode of insertion, the time resolution is better than 17 ms or better than 65 micros (i.e. a single video field or video line, respectively). The circuit has been shown to work reliable in combination with video-rate confocal imaging and patch-clamp recordings.

Animals↗

The dual effect of internal tetramethylammonium ions on the open states of the sodium channel in the squid giant axon.

Voltage-clamp recordings of INa in squid axons dialysed with Cs or TMA, and bathed in low Na choline seawater, showed that, except close to threshold, the initial peak of fast-inactivating current was invariably decreased by TMA, whereas the non-inactivating current in the steady state was simultaneously increased. The results suggest that although TMA does not act directly on the movements of the voltage sensors that activate the sodium system, it blocks single-channel conductance in a voltage-dependent fashion in both the open states of the Na channel, while it has an entirely different type of action by increasing the probability of late openings in the steady state. Another difference between the two open states was that the sodium permeability coefficient had a Q10 of 1.8 in the initial open state, whereas in the steady state the effect of temperature was much smaller or even negative.

Animals↗

A pulse generating and data recording system based on the microcomputer PDP 11/23.

A widely applicable measuring system, especially suited for all types of 'voltage-clamp' (including 'patch-clamp') experiments, is presented. It is mainly based on commercially available hardware and software components. All interfacing with the analog world takes place on the front panel of the microcomputer box. Synchronization of pulse generation with data acquisition and other control actions take advantage of the four upper bits not used by the digital-to-analog converter during direct memory access transfer.

Computer Systems↗

Modification of ultraviolet radiation effects on the membrane of myelinated nerve fibers by sulfhydryl compounds.

The modification of the ultraviolet blocking of sodium channels and of the ultraviolet-induced potential shift of the gating parameters by means of the sulfhydryl compounds l-cysteine and 2-mercaptoethanol was investigated in the node of Ranvier under voltage-clamp conditions. The UV wavelength was 280 nm. The radiation-induced potential shift of the voltage-dependent gating parameters was prevented or even reversed by the action of the sulfhydryl compounds (internal application), while the blocking effect was not affected. It is concluded that the two radiation effects are caused by two separate photoreactions. Internally applied N-ethylmaleimide, binding specifically to protein-SH groups, exhibits an effect similar to the ultraviolet-induced potential shift, without affecting the maximum sodium permeability. Therefore, the ultraviolet-induced potential shift might be caused by a photocatalyzed oxidation of -SH groups of membrane proteins changing the surface charge density at the inner side of the nodal membrane.

Animals↗

Single Na channels in mouse neuroblastoma cell membrane. Indications for two open states.

Single sodium channel currents were studied in mouse neuroblastoma cells. Channel conductance (gamma) was 11.6 +/- 3.4 pS at 6-8 degrees C. Unitary current amplitudes and channel activity increased with increasing temperature. The Arrhenius plot of the conductance was linear between 5 and 35 degrees C with an activation enthalpy of 27.1 kJ/mole (Q10 = 1.28). Amplitude distributions were fitted by the sum of two Gaussian functions indicating the presence of two different single channel amplitudes: smaller i1 and larger i2. The relative probability of appearance of i1, which has a shorter mean open time, was higher during the early phase of depolarization (t less than 16 ms). The open time histograms, inactivating phase of macroscopic currents and delay time histograms were fitted by the sum of two exponentials. The distinct kinetic and steady-state parameters reflect two open states of sodium channels.

Animals↗

Changes of ultraviolet sensitivity of voltage-clamped sodium channels during their potential-induced conductance cycle.

The effects of ultraviolet (UV) radiation at various intermediate states of excitation of the frog nerve membrane were measured under voltage-clamp conditions. By synchronizing a UV flash source (flash duration: 10 microseconds) with the stimulating voltage-clamp pulses it was possible to irradiate the membrane at any state of excitation. The resulting UV sensitivities gamma Na and gamma h of gNa and h infinity (V = 0) were compared with those found at the end of a hyperpolarizing prepulse (m = 0, h = 1). The irradiation always induced a decrease of both parameters, gNa and h infinity (V = 0), and the more "h-gates" there were in the closed position at the moment of irradiation, the more pronounced were the effects. The normalized sensitivity of both parameters can be described fairly well by linear relations of the form: gamma x(m,h)/ gamma x(0, 1) = 1 + Px(1 - h) + Qxm2h (x = Na or h). The coefficients P and Q depend on wavelength. The results suggest a conformational change of the nodal membrane during excitation and an interdependence of m and h to some extent.

Animals↗