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Biomedical subjects

S Witte

Publications and source records attributed to S Witte.

At least 37 records · Page 2Linked to original sources
PubMed1997

Specific interactions of the autoantigen L7 with multi-zinc finger protein ZNF7 and ribosomal protein S7.

The eucaryotic protein L7, which associates with the large subunit of ribosomes, has been shown to be a major autoantigen in systemic autoimmune arthritis. The N terminus carries a sequence motif that is similar to the leucine zipper domain of eucaryotic transcription factors. This domain promotes the homodimerization of protein L7 through alpha-helical coiled-coil formation and binds to distinct mRNAs, thereby inhibiting their cell-free translation. Using a yeast two-hybrid selection, we have identified from a Jurkat T lymphoma cDNA library ribosomal protein S7 and the multi-zinc finger protein ZNF7 as proteins that interact with protein L7. A fragment of L7 carrying the leucine zipper-like domain is fully sufficient to mediate these interactions. Their potential biological significance is indicated by low apparent dissociation constants of S7-L7 (15 x 10(-9) M) and, respectively, ZNF7-L7 (2 x 10(-9) M) complexes and co-immunoprecipitation of proteins S7, ZNF7, and L7 from a cell lysate with an anti-L7 antibody. We also show that ZNF7-like L7 and S7 can exist in a ribosome-bound form. This study provides further evidence suggesting that L7 is involved in translational regulation through interactions with components of the translational apparatus.

DNA-Binding Proteins↗
PubMed1996

Low lead levels stunt neuronal growth in a reversible manner.

The developing brain is particularly susceptible to lead toxicity; however, the cellular effects of lead on neuronal development are not well understood. The effect of exposure to nanomolar concentrations of lead on several parameters of the developing retinotectal system of frog tadpoles was tested. Lead severely reduced the area and branchtip number of retinal ganglion cell axon arborizations within the optic tectum at submicromolar concentrations. These effects of lead on neuronal growth are more dramatic and occur at lower exposure levels than previously reported. Lead exposure did not interfere with the development of retinotectal topography. The deficient neuronal growth does not appear to be secondary to impaired synaptic transmission, because concentrations of lead that stunted neuronal growth were lower than those required to block synaptic transmission. Subsequent treatment of lead-exposed animals with the chelating agent 2,3-dimercaptosuccinic acid completely reversed the effect of lead on neuronal growth. These studies indicate that impaired neuronal growth may be responsible in part for lead-induced cognitive deficits and that chelator treatment counteracts this effect.

Animals↗
PubMed1996

Mass spectrometric identification of leucine zipper-like homodimer complexes of the autoantigen L7.

The eucaryotic protein L7 has been shown to associate in the cytoplasm with the large subunit of ribosomes and to interact specifically with as yet unknown cognate sites of mRNA, thereby inhibiting cell-free translation (Neumann, F., Hemmerich, P., von Mikecz, A., Peter, H. H., and Krawinkel, U.(1995) Nucleic Acids Res. 23, 195-202). The N-terminal region of protein L7 contains a sequence motif similar to the leucine zipper domain of eucaryotic transcription factors, which promotes dimerization through alpha-helical coiled coil formation. Using electrospray-ionization mass spectrometry as a method of molecular specificity, we have directly identified the dimeric complexes comprising the leucine zipper-like region of protein L7 and have determined the dissociation constant of L7 homodimers in an affinity binding assay. We also demonstrate the high content of alpha-helicity of the dimer by circular dichroism spectra and computer-based structure simulation and show that the leucine zipper region of protein L7 is fully sufficient to mediate the inhibition of cell-free mRNA translation. A structural basis for the function of L7 to regulate translation is discussed. From the present results we conclude that L7 interacts with double stranded mRNA in a similar fashion as leucine zipper proteins with specific cognate sites on double stranded DNA.

Amino Acid Sequence↗
PubMed1996

In vivo observations of timecourse and distribution of morphological dynamics in Xenopus retinotectal axon arbors.

Changes in neuronal structure can contribute to the plasticity of neuronal connections in the developing and mature nervous system. However, the expectation that they would occur slowly precluded many from considering structural changes as a mechanism underlying synaptic plasticity that occurs over a period of minutes to hours. We took time-lapse confocal images of retinotectal axon arbors to determine the timecourse, magnitude, and distribution of changes in axon arbor structure within living Xenopus tadpoles. Images of axons were collected at intervals of 3 min, 30 min, and 2 h over total observation periods up to 8 h. Branch additions and retractions in arbors imaged at 3 or 30 min intervals were confined to shorter branches. Sites of additions and retractions were distributed throughout the arbor. The average lifetime of branches was about 10 min. Branches of up to 10 microns could be added to the arbor within a single 3 min observation interval. Observations of arbors at 3 min intervals showed rapid changes in the structure of branchtips, including transitions from lamellar growth cones to more streamlined tips, growth cone collaps, and re-extension. Simple branchtips were motile and appeared capable of exploratory behavior when viewed in time-lapse movies. In arbors imaged at 2-h intervals over a total of 8 h, morphological changes included longer branches, tens of microns in length. An average of 50% of the total branch length in the arbor was remodeled within 8 h. The data indicate that the elaboration of the arbor occurs by the random addition of branches throughout the arbor, followed by the selective stabilization of a small fraction of the new branches and the retraction of the majority of branches. Stabilized branches can then elongate and support the addition of more branches. These data show that structural changes in presynaptic axons can occur very rapidly even in complex arbors and can therefore play a role in forms of neuronal plasticity that operate on a timescale of minutes.

Animals↗
PubMed1995

Telemicroscopy stations for telepathology based on broadband and ISDN connections.

Telemicroscopy equipment is a key tool to perform Telepathology successfully. It allows the local separation of the microscope with the tissue samples from the investigating pathologist. The Telemicroscopy stations presented provide the user with a full access to the functions such as scanning stage, focus, illumination and magnification selection of a remote microscope. One system applies as communication link a broadband video conference net of the German Telekom with full realtime capabilities and color TV-image quality. As this network provides adequate interfaces for video and computer net signals, it is well suited to establish within a short time interval a very comfortable Telemicroscopy connection without the development of additional equipment. As the broadband network is expensive the application is economically restricted to special applications. The other system relies on the narrow band connections of the ISDN telephone network. This design is inexpensive with respect to data transmission and is available nearly worldwide everywhere. But on the other hand this strategy is limited concerning realtime capabilities. To reduce these limitations to an acceptable level intelligent coding and operation concepts of the stations have to be developed.

Computer Communication Networks↗
PubMed1993

Synaptic mechanisms of cortical representational plasticity: somatosensory and corticocortical EPSPs in reorganized raccoon SI cortex.

1. Reorganizations of representational maps have been described for a variety of sensory and motor regions of cerebral neocortex in several species. The purpose of this study was to investigate synaptic mechanisms of the reorganizations of primary somatosensory cortex that follow removal of a digit or the joining of two digits into a syndactyly. We examined neurons in the cortical representation of digit 4 (d4). Intracellular recording was used to compare somatosensory and corticocortical excitatory postsynaptic potentials (EPSPs) in normal raccoons, with EPSPs recorded in two experimental groups of animals surviving for a mean of 22 wk after removal of d4, or union of d4 with digit 3 (d3). 2. In normal animals with d4 intact, EPSPs were evoked from this on-focus digit in 100% of cortical neurons. EPSPs were evoked from d3 and digit 5 (off-focus digits) in only a minority of neurons in normal raccoons. The incidence of somatosensory EPSPs from off-focus digits increased dramatically after removal of d4 or its union with d3. Latencies of EPSPs evoked from off-focus digits decreased after d4 removal, so that they were as short as latencies from d4 in normal animals. In contrast, for the group of animals with d3-d4 syndactyly, latencies of EPSPs from off-focus digits were not shorter than responses from these digits in normal animals. 3. Corticocortical EPSPs were no more common in animals with d4 removed than in intact animals. Furthermore, corticocortical EPSPs after d4 removal did not differ in their latencies, amplitudes, half-widths, or integrated amplitudes. The only detected change was that corticocortical EPSPs had faster rising phases after removal of d4. In contrast, after d3-d4 syndactyly, corticocortical EPSPs were more common than in normal animals. 4. Digit removal and digital syndactyly had distinctive effects on somatosensory and corticocortical EPSPs. These results do not identify unique synaptic mechanisms for cortical representational plasticity, nor do they specify the involved CNS site(s). Several synaptic mechanisms consistent with the results are considered in the DISCUSSION, including synaptic proliferation to form new synaptic connections and enhanced effectiveness of existing corticocortical synapses.

Afferent Pathways↗
PubMed1992

[Improvement of hemorheology with ginkgo biloba extract. Decreasing a cardiovascular risk factor].

STUDY DESIGN: Open prospective study. PATIENTS: 20 outpatients with a long history of elevated fibrinogen levels and plasma viscosity, and a variety of underlying diseases. INTERVENTION: Treatment with the special ginkgo biloba extract (EGb 761), 240 mg tablets a day for a period of 12 weeks. RESULTS: The clinical diagnoses included coronary heart disease, hypertension, hypercholesterolemia and diabetes mellitus. A significant improvement in the fibrinogen levels and hemorrheological properties was seen. The medication can thus positively influence these cardiovascular risk factors over the long term.

Aged↗
PubMed1992

Fluorescence microscopic techniques in intravital microvascular studies: plasma proteins and cells.

Microcirculation research preferentially uses fluorescent microscopic techniques. This applies in particular to experimental investigations. In the example of the everted rat mesentery, our own results obtained with the following vital microscopic methods are presented: fluorescent labelling of proteins, in particular of the components of blood plasma, detection with the image amplifier TV technique, quantitative detection by microfluorometry with rapid scanning facilities, image analysis techniques with computer control. The results on the relationships between plasma proteins and the vessel wall, accumulation of individual proteins on the endothelium (fibrinogen, fibronectin, polypeptide from factor VIII, annexin PP4), their permeation through the vessel wall and its experimental modification by blood clotting and by the vessel wall collagen are described. Finally, results on fluorochroming of cells (endothelium, leukocytes) and microspheres with which phenomena of adherence on the endothelium can be demonstrated are reported.

Animals↗
PubMed1991

[Endoscopic cytodiagnosis of the pancreas and bile ducts].

During the last twelve years we made in 3868 cases cytological investigations of the pancreatic and bile duct systems. The techniques for endoscopic cell collection and microscopic observation are demonstrated. Cellular material consists of epithelia, inflammatory cells and tumor cells. Their cytological details are described. Of primary importance are the differentiations of the epithelial cells in cases of chronic cholangitis and pancreatitis from tumor cells. We found 211 cases with proven malignant tumors of the papilla, the pancreas or the bile ducts. In 81.5% of these cases a significant cellular material could be collected with 59.3% tumor cell diagnoses. No false-positive tumor cell diagnosis was found (n = 3657). A comparison with preoperative bioptic histology was possible only in the papilla region. Here, the sensitivity of histology was 60% compared to 86% sensitivity of cytology. We conclude that the cytodiagnosis of the papilla, the pancreas and the bile duct by means of endoscopic techniques can be done routinely in order to obtain a preoperative diagnosis of inflammatory as well as malignant cellular findings in these organs.

Aged↗
PubMed1991

Adrenoceptors of the human internal thoracic artery.

Adrenoceptor function in the human internal thoracic artery (ITA) was characterized in vitro using segments of the artery obtained during coronary bypass operations. Specimens were prepared as isolated arterial rings mounted in a tissue bath, and mechanical activity (isometric tension) was measured in response to drugs. The ITA responded to phenylephrine (PE), epinephrine, and norepinephrine with concentration-dependent contractions. The PE-induced contractions were antagonized by phenoxybenzamine, prazosin, and high concentrations of yohimbine. The ITA was not effectively contracted by clonidine in the concentration range normally associated with alpha 2-adrenoceptor stimulation. The beta-adrenoceptor agonist, isoproterenol, had a weak and variable effect on the ITA; samples from 9 out of 12 subjects did not respond to isoproterenol, whereas samples from 3 subjects responded with relaxations of between 33 and 42%. These in vitro studies indicate that the most important adrenoceptors of the human ITA are alpha-adrenoceptors; this may be relevant for the pharmacologic management of patients undergoing coronary bypass surgery using the ITA.

Adrenergic alpha-Antagonists↗
PubMed1991

Synaptic potentials evoked by convergent somatosensory and corticocortical inputs in raccoon somatosensory cortex: substrates for plasticity.

1. "Unmasking" of weak synaptic connections has been suggested as a mechanism for the early changes in cortical topographic maps that follow alterations of sensory activity. For such a mechanism to operate, convergent sensory inputs must already exist in the normal cortex. 2. We tested for topographic and cross-modality convergence in primary somatosensory cortex of raccoon. The representation of glabrous skin of forepaw digits was chosen because, even though it is dominated by inputs from the glabrous skin of a single digit, it nevertheless comes to respond to stimulation of other digits when, e.g., a digit is removed. 3. Intracellular recordings were made from 109 neurons in the representation of glabrous skin of digit 4. Neurons were tested for somatosensory inputs with electrical and natural stimulation of digits. 4. Excitatory postsynaptic potentials (EPSPs) were evoked in 100% of the neurons (109/109) by electrical stimulation of glabrous skin of digit 4, and in 79% (31 of 39) by vibrotactile stimulation. 5. Glabrous skin of digit 4 was not the sole source of somatosensory inputs. A minority of neurons generated EPSPs after electrical stimulation of hairy skin of digit 4 (10 of 98 neurons, 10%). Electrical stimulation of digits 3 or 5 evoked EPSPs in 22 of 103 neurons (21%). Natural stimulation (vibrotactile or hair bending) was also effective in most of these latter cases (digit 3, 6/7; digit 5, 9/10). 6. Intracortical microstimulation of the "heterogeneous zone" was used to test for corticocortical connections to neurons in the glabrous zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Blood rheology and oxygen uptake.

Continuously measured oxygen uptake during constant work exercise (15' 50W) reveals increasing oxygen consumption in individuals with elevated blood viscosity parameters, indicating persistent contribution of anaerobic glycolysis during steady state exercise far below expected "anaerobic threshold". Improvement of viscosity parameters by prostaglandin E1--infusion (Prostavasin) 40 micrograms i.v., naftidrofurylhydrogenoxalat (Dusodril pi) 400 mg i.v. or hemodilution with 500 ml 6% hydroxyethylamylum MW 40000 (Onkohaes) in 5 patients results in significant reduction of this oxygen gradient in subsequent exercise test. Integrated VO2 during exercise above the mean value at rest or the quotient of VO2 during 15 min by VO2 during 30 min (including recovery time) are not differing significantly due to high variations inter- and intraindividually. Oxygen gradient during submaximal constant exercise permits direct clinical determination of microcirculatory performance in involved muscle tissue as a function of blood viscosity.

Adult↗
PubMed1989

Scanning microfluorometry in intravital microvascular research.

Our own development of fluorometric scanning techniques in intravital microscopy of the microcirculation is described. Very tiny amount of fluorometric substances are detected with a high temporal and locational resolution. The everted small intestinal mesentery of the rat serves as a model. We have given a detailed description of the microscopes used, the optical systems, the conditions of measurement of the microfluorometry, the scanning techniques and the evaluation of the measurement data. The present state of technical development detects 10(-12) g of a fluorochromed plasma protein in 8 ms in a measurement field of 2 microns 2. The four-digit measurement data of a scanning line of 200 microns length in 0.25 micron locational resolution are registered in about 2 s.

Animals↗
PubMed1989

Influence of an ionic and a nonionic (sodium meglumine diatrizoate and iopromide) x-ray contrast medium of hemorrheology.

In two groups of ten patients each, an ionic and a nonionic contrast medium was injected intravenously, for digital subtraction angiography of the supra-aortic branches, to examine the influence of hemorrheologic properties. Afterward, blood samples were obtained through a central venous catheter and evaluated by a new instrument (oscillating capillary rheometer and densitometer). The viscous and elastic components of the complex blood viscosity and the hematocrit decreased after injection of ionic and nonionic contrast media. A statistically significant difference between the patient groups could not be found. The evaluated results describe an improvement of the hemorrheologic properties after contrast media injection.

Angiography↗
PubMed1988

The influence of the fibrinolytic system on the affinity of fibrinogen for the endothelial-plasma interface.

We use intravital fluorescence microscopy to study the endo-endothelial lining of microcirculatory vessels in vivo and in situ (exposed rat mesentery). In earlier experiments we found that fibrinogen had an affinity for the inner lining of microvessels, particularly venules. This affinity was specific to fibrinogen (and fibronectin); most other plasma proteins (albumin, antithrombin III, gamma-globulin) did not accumulate on the inner surface of microcirculatory blood vessels. We postulated the existence of receptors for fibrinogen and/or fibronectin on the endo-endothelial surface, whose turnover rate differed in arterioles and venules. Blockade of the intravascular coagulation process by heparin did not alter the interaction between fibrinogen and endothelium, but blockade of fibrinolytic activity by tranexamic acid increased the deposition of fibrinogen at the endothelial surface. In the present study we administrated a drug containing the bioflavonoids diosmin and hesperidin, which may activate tissue plasminogen activator. Such pretreatment significantly decreased the accumulation of fibrinogen at the endo-endothelial surface of the venules. We therefore conclude that the endothelial plasma interface is characterized by accumulation of fibrinogen which is not affected by thrombin-mediated activation of the coagulation system. In contrast, interactions between fibrinogen and endothelium are influenced by the fibrinolytic system, both of plasmatic and endothelial origin, thus representing an important aspect of the antithrombotic potential of the endothelium.

Animals↗
PubMed1988

Evaluation of viscoelasticity measurements of human blood.

The dependence on hematocrit of whole blood viscoelasticity must be considered in order to compare pathological blood samples to normal ones. If one wants to calculate the measured values to a standard hematocrit value, the hematocrit dependence for the pathological sample must be available. As the latter however is unknown, the same dependence is assumed for both normal and pathological blood samples. To prove the validity of this assumption, hematocrit dependence of random blood samples from different diseases (cerebral and coronary vascular and myocardial disorders) were investigated. A statistical analysis showed the assumption as invalid. Therefore, it will be recommended to evaluate pathological blood samples at the measured hematocrit.

Blood Viscosity↗