Medizin - Open Access LMU - Teil 03/22
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Four porous synthetics were tested for their applicability as cartilage replacement in the reconstruction of the auricle: teflon velour, filamentous dacron, porous polyethylene and proplast II. After formation of a fold, the implants were sutured into subcutaneous cavities of the abdominal skin of rats or fixed with fibrin adhesive. Histological and scanning-electron-microscopic examinations have so far been performed after 1 and 3 months. Form stability with persistence of the desired skin fold was good when the material was not too thin or too thick. The infection rate was surprisingly low; skin necroses occurred largely in the area of transfixion sutures. The porosity appears to promote adaptation of the skin to the material and to thus counteract an effacement of the skin fold. The best form stability was evidenced by thermoplastic polyethylene, which was thus also chosen for first clinical applications.
A post-tetanic membrane hyperpolarization following repetitive neuronal activity is a commonly observed phenomenon in the isolated frog spinal cord as well as in neurons of other nervous tissues. We have now used double-barrelled Na+- and K+-ion-sensitive microelectrodes to measure the intracellular Na+- and K+-concentrations and also the extracellular K+-concentration of lumbar spinal motoneurons during and after repetitive stimulation of a dorsal root. The results show that the posttetanic membrane hyperpolarization occurred at a time when the intracellular [Na+] reached its maximal value, intracellular [K+] had its lowest level and extracellular [K+] was still elevated. The hyperpolarization was blocked by ouabain and reduced by Li+. These data support the previous suggestion that an electrogenic Na+/K+ pump mode may be the mechanism underlying the post-tetanic membrane hyperpolarization.
Twenty-nine randomly chosen, soluble antigens, many of them highly complex, were used to immunize mice of two strains, C3H and B10.RIII. Lymphnode cells from the immunized mice were restimulated in vitro with the priming antigens and the proliferative response of the cells was determined. Both strains were responders to 28 of 29 antigens. Eight antigens were then used to immunize 11 congenic strains carrying different H-2 haplotypes, and the T-cell proliferative responses of these strains were determined. Again, all the strains responded to seven of the eight antigens. These experiments were then repeated, but this time -antibodies specific for the A (AA) or E (EE) molecules were added to the culture to block the in vitro responsiveness. In all but one of the responses, inhibition with both A-specific and E-specific antibodies was observed. The response to one antigen (Blastoinyces) was exceptional in that some strains were nonresponders to this antigen. Furthermore, the response in the responder strains was blocked with A-specific, but not with E-specific, antibodies. The study demonstrates that responses to antigens not controlled by Irr genes nevertheless require participation of class II Mhc molecules. In contrast to Ir gene-controlled responses involving either the A- or the E-molecule controlling loci (but never both), the responses not Ir-controlled involve participation of both A- and E-controlling loci. The lack of Ir-gene control is probably the result of complexity of the responses to multiple determinants. There is thus no principal difference between responses controlled and those not controlled by Ir genes: both types involve the recognition of the antigen, in the context of Mhc molecules.
Lithium sensitive microelectrodes were used to investigate the transmembrane distribution of lithium ions (Li+) in motoneurons of the isolated frog spinal cord. After addition of 5 mmol·l–1 LiCl to the bathing solution the extracellular diffusion of Li+ was measured. At a depth of 500 m, about 60 min elapsed before the extracellular Li+ concentration approached that of the bathing solution. Intracellular measurements revealed that Li+ started to enter the cells soon after reaching the motoneuron pool and after up to 120 min superfusion, an intra — to extracellular concentration ratio of about 0.7 was obtained. The resting membrane potential and height of antidromically evoked action potentials were not altered by 5 mmol·l–1 Li+.
Es werden zwei Fälle von Neuromyelitis optica beschrieben, die jeweils eine hochgradige Erhöhung der Proteine im Liquor aufwiesen. Während ein Patient nach 6monatigem Krankheitsverlauf starb und pathologisch-anatomisch untersucht werden konnte, überlebte der andere Patient mit erheblichen Residuen. Dieser Fall zeichnete sich dadurch aus, daß deutlich erhöhte IgA- und IgM-Werte sowohl im Liquor als auch im Serum vorlagen. Es wird diskutiert, ob die gefundenen Liquorveränderungen möglicherweise eine Abgrenzung entsprechender Fälle gegenüber der multiplen Sklerose zulassen.
The effects of bath-applied 4-aminopyridine on neurones and extracellular potassium and calcium concentrations were recorded in slices of guinea-pig olfactory cortex. Neurones were orthodromically activated by stimulating the lateral olfactory tract. 4-Aminopyridine (3–10 μM) had the following effects: (1) an increase in the frequency and amplitude of spontaneous postsynaptic potentials: (2) a prolongation and oscillatory behaviour or orthodromically evoked postsynaptic potentials; (3) induction of spontaneous or stimulus-evoked seizure-type discharges which were accompanied by large rises in extracellular potassium and falls in calcium concentration; (4) a prolongation of the lateral olfactory tract population fibre spike. Prior to paroxysmal depolarization, membrane potential, input resistance and soma spike duration were unaffected. In the seconds before seizure discharges, a late hyperpolarizing potential (evoked by orthodromic stimulation) was reduced in amplitude or abolished. Diphenylhydantoin (50 μM) or magnesium ions (5 mM) prevented paroxysmal activity. Our results whow that 4-aminopyridine can produce seizure-type discharges in a brain slice preparation. The role of increased spontaneous potentials and possible loss of synaptic inhibition as causal factors for such discharges is discussed.
Intact secretory vesicles isolated from bovine adrenal medulla contain 94 nmol Na+ per mg of protein, and Ca2+ influx into the vesicles is inhibited by increasing concentrations of extravesicular Na+ (but not of K+, Li+ or choline+) or by addition of the Na+ ionophore monensin. Thus Ca2+ influx is determined by the Na+ gradient across the vesicular membrane. Half maximal inhibition of Ca2+ influx occurs with 34 mM Na+ extravesicularly. The fact that Ca2+ can also be released from the vesicles by inversion of the Na+ gradient provides direct evidence that an Na+-Ca2+ exchange may operate. According to an analysis of the inhibition of Ca2+ uptake by Na+ in a Hill plot 2 Na+ would be exchanged for 1 Ca2+. Ca2+ influx into the vesicles increases with temperature (energy of activation: 16 kcal/mol), can be observed already with 10−7 M free Ca2+ and increases up to 10−4 M Ca2+. Ca2+ influx is not affected by Mg2+ but Sr2+ is inhibitory. Since the process is only slightly influenced by the pH of the incubation medium and is insensitive to Mg2+-ATP or inhibitors of the proton translocating Mg2+-ATPase the electrochemical proton gradient across the vesicular membrane does not affect directly the Ca2+ influx into the secretory vesicles. Ca2+ uptake is insensitive to ruthenium red and oligomycin.
The aim of this study was to determine the number and state of activity of cytolytic T lymphocytes (CTL) and their precursors (CTL-P) present in vivo during the early stages of viral infection. The local response to lethal infection with rabies virus was used as a model system that is not accessible to analysis by secondary activation in vitro. The local response to alloantigen served as a control. Experimental protocols were established that allow frequency estimates of in vivo antigen-triggered CTL-P. Data allow a distinction between CTL-P activated in vivo by alloantigen and viral antigen with respect to their different capacity to utilize T cell growth factors (inter-leukins). In vivo alloantigen-primed CTL-P generate, in vitro, an active effector progeny in the presence of interleukins of xenogeneic origin, whereas the majority of virus-specific CTL-P, in spite of considerable expansion in vivo, fail to generate CTL in vitro unless antigen is added.
It is becoming increasingly clear that nerve cells in the mammalian central nervous system (CNS) have a very complex electroresponsiveness. They exhibit not only time- and voltage-dependent Na+ and K+ conductances, analogous to those in the squid giant axon1, but also a variety of other conductances that have a significant role in the control of cell excitability. Of the outward currents, there are, in addition to the delayed rectifier, the Ca2+-activated K+ current2,3 which underlies the long-lasting spike afterhyperpolarization, and the M current4, a non-inactivating K+ current evoked by membrane depolarization and blocked by muscarinic, cholinergic agonists. We demonstrate here the existence in a mammalian central neurone (hip-pocampal CA3 pyramidal cells) of yet another outward current, which is transient and may be carried by K+ ions. Further, the experiments show that this current is substantially reduced by the convulsant 4-aminopyridine (4-AP)5, resulting in a marked increase in cell excitability.
Cholesterol determinations in morning urine samples were taken in 235 selected patients with a positive test for microscopic hematuria. Values ranged from 0.2 to 76.0 mg (median 5.5) in 23 patients with urologic malignancies and from 0.1 to 33.4 mg (median 1.1) in 38 patients with various benign diseases of the kidney or urogenital tract. In the 28 patients with urinary tract infections and 146 subjects without evidence of disorders of the kidney and the urogenital system, urinary cholesterol excretion was usually normal (0.1 to 1.9 mg; median 0.35). Using 1.0 mg urinary cholesterol per morning urine as a cutoff point, sensitivity for urologic carcinomas is about 80 per cent with a comparable high specificity of 90 per cent. Therefore, subsequent measurements of urinary cholesterol in populations with microscopic hematuria could define two groups, one with high prevalence and one with low prevalence of urologic malignancies. The less complicated colorimetric instead of gas-liquid chromatographic determination of urinary cholesterol can be recommended as a screening test for urologic carcinomas in populations with microscopic hematuria.
Purified secretory vesicles isolated from bovine neurohypophyses were found to take up Ca2+ when incubated at 30°C in media containing 10−7 to 10−4 M free Ca2+. At 10−4 free Ca2+ 19 nmol/mg protein were taken up within 30 min. The initial uptake at this Ca2+ concentration was about 2 nmol/mg protein per min. The uptake of Ca2+ to secretory vesicles was not affected by ATP, oligomycin, ruthenium red, trifluoperazine, Mg2+ or K+, but was inhibited by Na+ and Sr2+. From these characteristics it can be concluded that the uptake system does not utilize directly ATP (as the Ca2+-ATPases known to be present in the cell membrane and the endoplasmic reticulum) and is different from the mitochondrial Ca2+ uptake system driven by respiration and/or ATP hydrolysis. However, Ca2+-Na+ exchange may well operate: In experiments using different concentrations of Na+ we found half-maximal inhibition of Ca2+ uptake with 33.3 mM Na+. An analysis of the data in a Hill plot indicated that at least 2 Na+ would be exchanged for 1 Ca2+. Also, it was found that Ca2+ previously taken up could be released again by external Na+ but not by K+.
In this study we report that alloantigen-activated spleen cells produce both amplifying and suppressive factors under the same conditions. Both types of soluble mediators--as detected in different assay systems-- were present in the supernatants of in vivo sensitized and in vitro restimulated spleen cell populations and were separable by gel filtration. As shown by others, the amplifying factor (IL 2) was eluted in the size range of 30,000 m.w. The suppressive factor(s) (SF) was eluted in the size range of 10,000 m.w. SF was shown to inhibit the proliferative response of T cells to alloantigen, as well as the generation of regulatory T cells and cytotoxic T cells from their precursors when added at the beginning of the in vitro culture. Furthermore, SF inhibited the release of IL 2 from producer T cells but had no detectable effect on the interaction of IL 2 with receptive T cells. In addition it was shown that SF does not affect the generation of PFC from their precursors after activation by T cell-independent antigens. The results indicate that SF selectively acts on T cells and that it is involved in the regulation of the immune response by modulating early events in T cell activation.
