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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The radial protein concentration profile in the interstitial space of the rat ileal mesentery.

The radial distribution of the protein concentration in the interstitium between arteriolar and venular vessels of the ileal mesentery of the rat was examined. Protein mass was determined by means of uv ultramicrospectrophotometry (UMS) and the relative volume distribution by means of fluorescence microscopy (FM) using the Na fluorescein and FITC-dextran (10,000 mol wt). UMS revealed gradients for protein mass from the vessels out into the interstitial space. FM showed a uniform distribution of fluorescence in the interstitium between the vessels. A gradient for protein mass without a gradient for volume distribution signifies the presence of a concentration gradient for protein in the interstitial space. The protein concentration across the arteriolar wall drops from 5.4 +/- 0.24 (SD) to 2.6 +/- 0.65% and across the venular wall from 5.4 +/- 0.24 to 3.3 +/- 0.43%. From the perivascular site the protein concentration declines exponentially reaching a minimum average interstitial concentration of 1.6 +/- 0.56%. Minimal protein concentration occurred at a point 37 +/- 6.4% of the 295 +/- 37 micron distance from the arteriolar to the venular vessels. In view of this distribution, it is unlikely that lymph or direct samples of interstitial fluid are representative of the perivascular protein concentration.

Animals↗

Measurement of the optical thickness of transparent tissue layers.

The method of Duc de Chaulnes was employed to determine the mechanical and optical thickness, as well as the refractive index, of transparent tissue layers in living specimens. To this end the reproducible accuracy of the method and its dependence on the adjustment in focusing and on the numerical aperture of the objective was evaluated on test specimens using the procedures of transmitted light, phase-contrast (PC), and differential interference contrast (DIC) microscopy. The best working conditions were then applied to the actual measurements.

Animals↗

[Incidence and significance of the gastric mucosal constellation in pernicious anemia].

1977 cases with gastric complains but without localized findings like ulcer or cancer were investigated by gastroscopy with biopsies of corpus and antrum ventriculi. We found in 5.5% an isolated mucosal atrophy of the gastric corpus (mean age 67.2 years compared to 59.4 years in cases with normal mucosa). 0.7% showed an atrophic gastritis of the antral mucosa, 0.9% an atrophic gastritis of the body and the antrum. Most of the cases with an isolated atrophy of the gastric body gave findings of hematologic disturbances. In all cases with isolated atrophy of the gastric body, including localized findings in the stomach, we found in 10.8% neoplastic processes, in another 3.9% hyperplasiogenic polyps. It seems to us of clinical importance to evaluate the gastric histology of the antral and body mucosa routinely because of the high incidence of pernicious anemia-like gastric atrophy and its relation to gastric neoplasias.

Adult↗

Analysis of the wall permeability of blood vessels in the rat mesentery.

The transport of fluorescent tracer molecules of various molecular weights (MW 340-300,000) within the blood vessels and through the vessel walls into the perivascular tissue of the rat mesentery was studied microscopically. Using a highly sensitive TV-tube the fluorescence intensities were transformed into video signals and recorded for subsequent analysis. The results show that small molecules, such as the water-soluble dye fluorescein-sodium ( F1Na ) (MW 340) can pass through the wall of all blood vessels with minimal delay, whereas the passage of large molecules, such as the serum proteins (MW greater than 60,000), depends very strongly on the diameter of the vessels and on the medium in which the mesentery is embedded during the observation. In this respect, no difference was registered between vessels of the arterial and of the venous part of the microcirculation. The large serum protein molecules moved through the blood vessel walls at specific leakage points. The small dye molecules, however, traversed the wall uniformly along the entire length of the blood vessel. The small-molecule behavior could be described by a passive diffusion model with a cylindrical diffusion source.

Animals↗

The role of blood coagulation in capillary permeability Vitalmicroscopic contributions.

It is our concept that the blood coagulation and fibrinolytic systems contribute to capillary permeability. By means of fluorescent intravital microscopy we measured in situ the permeability of proteins and fluorescent tracers through the walls of various kinds of microvessels (exposed rat mesentery). Fluorescent dyes applied intravenously pass across the walls of all kinds of microcirculatory vessels into the perivascular tissue in animals having a state of hypocoagulemia in a shorter time than in normals. Fluorescent-tagged fibrinogen accumulates at the vascular wall, especially at the inner lining of venules, thus marking free receptor sites for fibrinogen at these places. Blocking the fibrinolytic activity of the blood augments the fibrinogen deposition. Pretreatment by heparin does not prevent it, which speaks against the fibrinogen-fibrin coagulation during the accumulation phenomenon. In contrast to this behavior of fibrinogen, albumin, gammaglobulin, antithrombin III, plasminogen never accumulate at the vessel wall but pass through the vascular wall, mostly at venules. The speed and amount of the transvascular passage of these proteins depends on their molecular weight. Fibronectin shares the same receptor sites at the inner lining of microcirculatory vessels as fibrinogen. It seems possible, therefore, that both proteins, fibrinogen and fibronectin, interact with each other at the endo-endothelial cell border. A low molecular weight polypeptide fraction of factor VIII accumulates at the vascular wall similar to fibrinogen. At the same time it decreases the capillary permeability for serum proteins.

Animals↗

[Cytologic diagnosis of the upper gastrointestinal tract].

Three examples are given of new developments in applying cytological procedures in the diagnosis of gastro-intestinal tract disease. At first chinese results in early diagnosis of esophageal carcinoma are described. Then cytological diagnosis of pathological changes in the region of the Vater's ampulla are discussed. Finally trends of quantitative cytology are elaborated upon. We had the opportunity to examine cytological preparations from China, which had been collected in different regions with particularly high or low incidence of esophageal carcinoma. Preparations from regions with high incidence of carcinoma showed a sequence of lesions of esophageal cells starting from chronic esophagitis going over squamous cell hyperplasia and dysplasia of moderate and severe degree leading up to typical cancer cells. Cytological examination of cells collected in the region of Vater's ampulla by brushing technique may yield results demonstrating the presence of benign or malignant tumors. Cytological examinations of pancreatic juice collected after secretin stimulation may give hints in regard to the presence of pancreatitis or pancreatic carcinoma, and examination of bile collected endoscopically from the choledochus may allow diagnosis of cholangitis or primary bile duct tumors. Our own experiments in using quantitative gastroenterological cytodiagnostic procedures are described. They are based on single cell and continuous flow cytofluorometry of DNA in material collected during endoscopy by brushing technics from the stomach. The same material was examined with monochromatic UV microscopy, which allows electronic analysis with high resolving in power of absorption patterns of undyed cell nuclei.

Ampulla of Vater↗

Surface phenomena of coagulation factors in vivo, observed by fluorescence intravital microscopy.

The microcirculatory blood vessels of the exposed rat mesentery have been observed by incident fluorescence microscopy using various optical systems as well as image-intensifier devices and fast-scanning fluorometry techniques. As fluorescence-labeled proteins, albumin, gamma-globulin, fibrinogen, fibronectin, factor VIII-derived polypeptides, and antithrombin III have been injected intravenously. In some experiments two different-labeled proteins were administered consecutively. Whereas albumin and gamma-globulin did not accumulate at the inner surface of the microcirculatory blood vessels , fibrinogen and fibronectin showed a significant affinity to the vessels inner lining, mostly in venular vessels. Both substances accumulated at the same places of the microcirculatory endothelium. Blocking the fibrinolytic system of the animal increased the deposition of both substances. Factor VIII-derived polypeptides accumulated at the vessel inner surface in a different way. Antithrombin III did not show any affinities to the vascular wall. A receptor at the endothelial cell surface for both fibrinogen and fibronectin is postulated.

Animals↗

The measurement of density and its significance in blood rheology.

When viscoelasticity is measured with an oscillating capillary rheometer, the density of the fluid under study is an influencing factor (inertia). In the particular case of blood rheology hematocrit is also of interest. It can be measured more exactly on the basis of the density of blood and blood plasma than by conventional methods using a hematocrit centrifuge or Coulter counter, as these give too high readings when there is an increased tendency towards erythrocyte aggregation and reduced erythrocyte flexibility. Due to the double significance of blood density for blood viscoelasticity, an oscillating capillary rheometer and a new type of density-measuring device were attached to a computer in such a way that simultaneous evaluation is possible. The density-measuring device is a U-tube that is set into oscillation electronically. The duration of the oscillation is an indication of the density of the fluid in the U-tube.

Blood Physiological Phenomena↗

The endoendothelial lining as studied by a fluorescent labeling technique in situ.

The microcirculatory blood vessels of the exposed rat mesentery were observed by intravital microscopy using incident fluorescence excitation and transmitting bright field illumination. Fibrinogen conjugated with the fluorescent dye Fluorescein-Isothiocyanate and injected intravenously was found to accumulate at the vessel wall mostly at the inner lining of venules. The accumulation did not occur in an uniform manner, but appeared as circumscribed streaks, nets and bands in some areas whereas other parts of the microcirculation remained free of any fibrinogen wall adherence. Heparin pretreatment did not influence the phenomena. Blocking the fibrinolytic activity of the blood increased the fibrinogen deposition. Fibronectin labeled with a second fluorescent dye, Rhodamin B-Isothiocyanate, could be differentiated from fibrinogen in the same animal. Both proteins accumulated at the same places of the vessels inner lining. Since albumin and gamma globulin did not show any affinities to the vessel wall, we postulate receptors for fibrinogen and fibronectin at the endoendothelial surface of the microcirculatory endothelial cells.

Animals↗