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Biomedical subjects

U Schramm

Publications and source records attributed to U Schramm.

At least 19 recordsLinked to original sources

Analytical model for ion acceleration by high-intensity laser pulses.

We present a general expression for the maximum ion energy observed in experiments with thin foils irradiated by high-intensity laser pulses. The analytical model is based on a radially confined surface charge set up by laser accelerated electrons on the target rear side. The only input parameters are the properties of the laser pulse and the target thickness. The predicted maximum ion energy and the optimal laser pulse duration are supported by dedicated experiments for a broad range of different ions.

Journal Article↗

Apoptosis of CD4+ T and natural killer cells in Alzheimer's disease.

BACKGROUND: Immunotherapy appears to be a potent treatment against Alzheimer's disease (AD), but the mechanisms underlying neural-immune interaction are still not known. METHODS: Here, we determined cell death and distribution of lymphocyte subsets of peripheral blood mononuclear cells (PBMC) in AD and aging, e.g. T (CD4+ CD3+, CD8+ CD3+), B (CD19+) and NK (CD16++CD56+) cells. RESULTS: Increased apoptosis was found in CD4+ T and NK cells in AD, while in aging all subsets were affected. The expression of anti-apoptotic Bcl2 correlated with observed cell death in T-helper and B cells irrespective of dementia. The levels of Bcl2 in T-cells were significantly increased in mild AD. Apoptosis and Bcl2 levels were also elevated in the APP (751SL)xPS1 (M146L) transgenic mouse model. CONCLUSION: The mechanisms triggering apoptosis and activation of lymphocytes in AD appear therefore to be different than those in immunosenescence and possibly bear an important biomarker to monitor immunotherapy in AD.

Adult↗

Three-dimensional crystalline ion beams.

We report on the experimental realization of two- and three-dimensional crystalline ion beams in the rf quadrupole storage ring PALLAS (LMU, Munich). At a beam energy around 1 eV the phase transition to the Coulomb ordered state is identified by a sudden decrease of the spatial width and of the velocity spread of the beam. The focusing conditions required to attain crystalline beams up to structures of helices surrounding a string are systematically investigated and related to the situation in typical heavy ion storage rings.

Journal Article↗

Impact of innervation and exercise on muscle regeneration in neovascularized muscle grafts in rats.

The direction of known staged process of regeneration of free muscle grafts was inverted in our experimental rat model from a centripetal to a centrifugal by central implantation of blood vessels into isolated free muscle grafts. The effects of innervation, reinnervation and exercise on muscle fiber regeneration were analyzed at various intervals from 4 to 90 days by morphological and morphometric methods. Reinnervation occurred as well in grafts with the motor nerve left intact as it did in grafts with a severed and reimplanted nerve. Reinnervation proved to be prerequisite for a lasting muscle regeneration. Denervated muscle grafts even after neovascularization underwent irreversible fibrosis. A positive effect of exercise on the early states (30 days) of muscle regeneration was revealed by morphometrical analysis. In the long term (90 days) fiber diameter assimilated in all groups. The animal model mimics a clinical situation of flap prefabrication demonstrating the relationship of functional tissue regeneration and neovascularization. It can be transferred into the acute clinical situation as well as in tissue engineering.

Animals↗

Crystalline ion beams.

By freezing out the motion between particles in a high-energy storage ring, it should be possible to create threads of ions, offering research opportunities beyond the realm of standard accelerator physics. The usual heating due to intra-beam collisions should completely vanish, giving rise to a state of unprecedented brilliance. Despite a continuous improvement of beam cooling techniques, such as electron cooling and laser cooling, the ultimate goal of beam crystallization has not yet been reached in high-energy storage rings. Electron-cooled dilute beams of highly charged ions show liquid-like order with unique applications. An experiment using laser cooling suggested a reduction of intra-beam heating, although the results were ambiguous. Here we demonstrate the crystallization of laser-cooled Mg+ beams circulating in the radiofrequency quadrupole storage ring PALLAS at a velocity of 2,800 m s-1, which corresponds to a beam energy of 1 eV. A sudden collapse of the transverse beam size and the low longitudinal velocity spread clearly indicate the phase transition. The continuous ring-shaped crystalline beam shows exceptional stability, surviving for more than 3,000 revolutions without cooling.

Journal Article↗

Chronic inborn erythrocytosis leads to cardiac dysfunction and premature death in mice overexpressing erythropoietin.

The most common cause of an increase of the hematocrit is secondary to elevated erythropoietin levels. Erythrocytosis is assumed to cause higher blood viscosity that could put the cardiovascular system at hemodynamic and rheological risks. Secondary erythrocytosis results from tissue hypoxia, and one can hardly define what cardiovascular consequences are caused by chronic erythrocytosis or hypoxia. Herein, a novel transgenic (tg) mouse line is characterized that is erythrocytotic because of chronic overexpression of the human erythropoietin gene. These mice grow up well, reaching a hematocrit of about 0.80 in adulthood. Blood volume of adult tg mice was markedly increased by 75%. Unexpectedly, blood pressure was not elevated and cardiac output was not decreased. Still, the adult tg mice showed features of cardiac dysfunction with increased heart weight. In vivo, high-frequency echocardiography revealed marked ventricular dilatation that was confirmed by histologic examination. Furthermore, by transmission electron microscopy, a prominent intracellular edema of the cardiomyocytes was seen. Exercise performance of the tg mice was dramatically reduced, unmasking the severity of their compromised cardiovascular function. In addition, life expectancy of the tg mice was significantly reduced to 7.4 months. Our findings suggest that severe erythrocytosis per se results in cardiac dysfunction and markedly reduced life span.

Age Factors↗

Analysis of the vascular anatomy of the palm and its clinical relevance in Morbus Dupuytren.

The triangular center of the palm is supposedly hypovascularized. Intraoperative clinical studies have shown numerous vessels and nerves rising through the palmar aponeurosis into the skin in this area. To investigate these findings we have dissected 7 cadaver hands in order to analyze the vascular and neural structure of the palm. On an average we have found 30 bundles in the center of the palm. At least half of them were vascular-nerve bundles, the other bundles consisted either of a nerve, an artery or a vein. By means of histological testing we have also found lymphatic vessels accompanying the blood vessels and the nerves. Our study shows a greater number of vessels rising into the skin than has been previously described in the literature, so that we cannot confirm the triangular hypovascular zone in the center of the palm.

Arteries↗

Influence of magnetic fields on electron-Ion recombination at very low energies

Radiative recombination (inverse photoionization) is believed to be well understood since the beginning of quantum mechanics. Still, modern experiments consistently reveal excess recombination rates at very low electron-ion center-of-mass energies. In a detailed study on recombination of F6+ and C6+ ions with magnetically guided electrons we explored the yet unexplained rate enhancement, its dependence on the magnetic field B, the electron density n(e), and the beam temperatures T( perpendicular) and T( ||). The excess scales as T(-1/2)( perpendicular) and, surprisingly, as T(-1/2)( ||), increases strongly with B, and is insensitive to n(e). This puts strong constraints on explanations of the enhancement.

Journal Article↗

Effect of PSC 833, verapamil and amiodarone on adriamycin toxicity in cultured rat cardiomyocytes.

Primary cultures of heart myocytes from neonatal rats were used as an in vitro cardiac cell system to study the effects of the p-170kDa glycoprotein (Pgp) blockers PSC 833 [(3'-keto-Bmt1)-(Val2)-cyclosporine], verapamil and amiodarone on adriamycin cardiotoxicity. Immunostaining revealed the presence of Pgp in the cardiomyocytes. Adriamycin induced a concentration-dependent increase in creatine kinase (CK) leakage, a parameter indicating cell death. None of the Pgp blockers was toxic up to 10 microM, but amiodarone markedly increased CK leakage at 25 microM. 1 microM of the Pgp blockers did not increase adriamycin induced CK leakage, whereas 10 microM of the Pgp blockers significantly augmented adriamycin-induced CK leakage. In parallel, cytoplasmic vacuolization and plasma membrane disruptions were observed. Frequency of contraction of cardiomyocytes, as determined by digital image analysis, was concentration-dependently decreased by adriamycin. 1 microM PSC 833 had no additional effect on contractility, only 10 microM PSC 833 enhanced the impairment of contractility induced by adriamycin. Amiodarone and verapamil alone and in combination with adriamycin already at concentrations of 1 microM completely blocked contractility of cardiomyocytes. The results suggest that the increased toxicity of adriamycin in the presence of amiodarone, verapamil and PSC 833 is mediated by an effective blockage of the Pgp efflux pump. The results further indicate that the combination of adriamycin and PSC 833 might be better tolerated with regard to cardiac side-effects, than the combination of adriamycin and verapamil or amiodarone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Studies on an immunologically induced synovitis model in pigs and sheep.

Chronic synovitis was induced in seven sheep and nine pigs to investigate the potential applicability of laser treatment in arthroscopic synovectomy. Systemic sensitization was accomplished using chicken egg or turkey egg albumin antigens with Freund's incomplete adjuvant, enriched with killed and dried Mycobacterium tuberculosis. Ten days after the second immunizing dose, skin sensitization testing was undertaken. After a satisfactory systemic reaction had been observed, the respective antigen was injected once or twice into the left knee of each animal at 2-week intervals. After chicken egg albumin sensitization at varying systemic immunization and joint injection doses, sheep (five of five) showed neither strong morphologic nor continuous synovitis, despite a positive systemic reaction. In pigs (three of three) the inflammatory signs also were unsatisfactory for the manifestation and characterization of a synovitis model. In contrast, the application of turkey egg albumin to pigs (six of six) during the 4-month study provided a persistent, clearly manifested synovitis that developed visible villi formation and an amber to gray synovial fluid and microscopically showed follicular aggregations of lymphocytes and plasma cells. In similarly immunized sheep (two of two), only a light synovitis developed with occasional perivascular inflammatory foci.

Animals↗

Whole-body hyperthermia combined with ifosfamide and carboplatin causes hypotension and nephrotoxicity.

It was previously postulated on the basis of clinical data that the cardiovascular sequelae of extracorporeal whole-body hyperthermia (e-WBH), i.e., hypotension (which requires catecholamine support) results in unique nephrotoxicity in combination with select chemotherapeutic agents. In an attempt to explain this phenomenon, we mimicked e-WBH physiological conditions in a rat model. Animals were treated with and without ifosfamide (IFO) and/or carboplatin (CBDCA) at 37 degrees C or 41.5-41.8 degrees C, with blood pressure monitoring and catecholamine support comparable to the clinical setting. Ex vivo post-treatment data (24 h) from artificially perfused kidneys (i.e., histology, urine volume, perfusion rate, glomerular filtration rate, and the reabsorption of sodium, glucose, and water) demonstrated unique toxicity including proximal tubular necrosis for the combination of WBH and IFO, for WBH and CBDCA and for WBH and IFO plus CBDCA, but not for IFO and CBDCA without WBH. These data, considered together with results derived from a subsequent clinical trial and the laboratory work of others were consistent with the hypothesis.

Animals↗

Tropical rat mite dermatitis: case report and review.

Six medical students inhabiting a centuries-old, rat-infested house in Lübeck, in northern Germany, were suffering from itching papules and seropapules. Prior to these patients' visit to our institute, their conditions had been diagnosed as pediculosis, scabies, or pulicosis and treated unsuccessfully with the antiparasitic agent lindane (0.3%). The final diagnosis, tropical rat mite dermatitis, was based on the identification of the arthropod Ornithonyssus bacoti, which has an unsegmented body with eight legs. No treatment was recommended, and the dermatitis disappeared within 2 weeks. Measures taken to prevent reinfestation included extermination of the rats and treatment of the rooms of the house with the acaricide benzyl benzoate. Because the mite O. bacoti spends a relatively short time on a host and penetrates the skin for feeding only, the application of an antiparasitic agent is not necessary. If indicated, treatment should be symptomatic.

Adult↗

Hepatocellular effects of cyclosporine A and its derivative SDZ IMM 125 in vitro.

The novel immunosuppressive drug O-hydroxyethyl-D(Ser)8-cyclosporine (SDZ IMM 125) and cyclosporine A (CyA) were compared in different in vitro models with respect to hepatocellular side effects. SDZ IMM 125 was less lipophilic than CyA and also decreased liposomal membrane anisotropy less. Furthermore, SDZ IMM 125 increased Na+ and Ca++ permeability across the liposomal membranes significantly more than CyA. The uptake of CyA and SDZ IMM 125 into freshly isolated rat hepatocytes was neither saturable, Na+ dependent or temperature sensitive, nor could it be inhibited vice versa, indicating passive diffusion. The diffusion coefficient of CyA was about two times higher than that of SDZ IMM 125, reflecting its higher lipophilicity. In primary hepatocyte monolayers the cellular concentrations of CyA were about two times higher than that of SDZ IMM 125. As an indicator of cholestasis the saturable uptake of cholyltaurine into isolated cells was found to be apparently competitively inhibited to the same extent by both compounds. In isolated perfused rat livers SDZ IMM 125 caused a significantly greater decrease in bile flow than did CyA. Release of lactate dehydrogenase from hepatocyte primary cultures and from isolated perfused livers were determined as parameter of cell damage. In both systems the cytotoxicity of SDZ IMM 125 was significantly higher than that of CyA. The data suggest that SDZ IMM 125 causes greater cholestatic and cytotoxic effects than CyA at equimolar cellular exposure.

Animals↗

[Arterial and neural supply of the skin of the palm. Surgical-anatomical findings in Dupuytren's contracture].

It has been reported that the skin of the palm is supplied by arteries receiving their blood from a radial, thenar, ulnar, or hypothenar arterial system. Interestingly, the middle of the palm has been described as hypovascularized, but detailed informations on number and distribution of blood vessels are not available. By surgical treatment of the Dupuytrens contracture we could show that preservation of the blood vessels and nerves supplying the skin leads to excellent postoperative results. However, our intraoperative observations do not correspond to the picture of a poorly vascularized region of skin in the middle of the hand. During surgical treatment we found between six and nine bundles consisting of one artery, at least one vene, and one nerve in each case. The bundles perforate the palmar aponeurosis through channels, and subaponeurotically a lot of them originate from further proximal than expected. This information should be taken into consideration during the exstirpation of the palmar aponeurosis.

Adult↗

Electron microscopic observations of the lymphatic vessels of the mammalian testis.

This paper is a report on preliminary investigations into the morphology of elastic fibers surrounding the lymphatic vessels of the testis, and it includes a description of the three-dimensional architecture of the lymph vessels and elastic fibers of the mammalian testis obtained by indirect injection of glutaraldehyde and Mercox. Different types of filaments and blind ends were observed. The filaments repeatedly divide and fuse to form the reticular networks. These networks provide a specific microenvironment for the lymphatic vascular system under different physiological and pathological conditions.

Animals↗

Active microtubule-dependent secretion of a fluorescent bile salt derivative in skate hepatocyte clusters.

Fluorescence microscopy and video image analysis were used to study the transport of a fluorescent bile acid derivative [N-[7-(4-nitrobenzo-2-oxa-1,3-diazol)]-7 beta-amino-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oyl-2-aminoethanesulfonate (NBD-TC)] in isolated clusters of hepatocytes from the little skate Raja erinacea. Analysis of images of hepatocyte clusters that were incubated in medium with 0.5-1 microM NBD-TC showed that the fluorescent derivative accumulated in the cells and that the clusters retained a patent canalicular lumen as well as the ability to actively transport the bile acid derivative from the cells into the lumen; i.e., the lumen-to-cell fluorescence ratio greatly exceeded unity. NBD-TC uptake by hepatocytes was inhibited by several organic anions, of which taurocholate was the most effective. Uptake was also blocked by metabolic inhibitors and by incubation in the cold. Neither Na replacement nor increased medium K, which depolarizes the membrane electrical potential [potential difference (PD)], affected NBD-TC accumulation by hepatocytes. Transport of NBD-TC into the canalicular lumen was inhibited by incubation in the cold and was substantially reduced by high-K medium; these blocks were removed by warming and transfer to normal-K medium, respectively. Treatment of hepatocytes with 20-40 microM nocodazole, a drug that reversibly depolymerizes microtubules, reduced cellular NBD-TC accumulation and blocked its secretion into the canalicular lumen; nocodazole effects were reversed by washing the hepatocyte clusters in drug-free medium. Thus uptake of NBD-TC by skate hepatocytes is active and carrier mediated but not dependent on the PD or Na gradient. NBD-TC secretion from cell to canalicular lumen also appears to be active and carrier mediated. Canalicular secretion appears to be driven at least in part by the PD and is highly dependent on an intact microtubular system in this marine species.

Alkanesulfonates↗

First clinical application of the Medos-HIA ventricular support system: monitoring of the thrombotic risk by means of the biomarker prothrombin fragment F1 + 2 and scanning electron microscopy evaluation.

BACKGROUND: The medos-HIA ventricular support system was designed as an artificial heart assist device for intractable heart failure to act as a bridge for transplantation or recovery. The aim of this study is to report on the first clinical application of the system and to evaluate the thrombotic risk with the use of the biomarker prothrombin fragment F1 + 2 and scanning electron microscopy of the blood contacting surface. METHODS AND RESULTS: This device worked without any failure for 462 hours, and a sufficient output of 5.2 to 6 L was observed. No activation of the procoagulatory system occurred during pumping until the occurrence of the septicemia. Preseptic F1 + 2 levels were normal, at about 1 nmol/L. The blood contacting surfaces of the pump and the polyurethane valves were examined by means of scanning electron microscopy, and the surfaces were found to have smooth fibrin layers with no thrombogenic deposits. This fibrin layer is considered to prevent thrombotic adhesions, thereby minimizing the risk of thromboembolic complications. Post mortem examinations after pneumonia with septic shock showed no thrombus formation in this support system and around the inserted cannulas. CONCLUSIONS: The low risk for thromboembolic complications, no measurable activation of the coagulation system, and the excellent surface characteristics encourage further use of this inexpensive working device.

Cardiac Output↗