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  • 1
    ISSN: 1432-2307
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Alterations of the glomerular basement membrane are the earliest ultrastructurally demonstrable lesions in the course of hereditary nephropathy. The basement membranes may be either focally or diffusely thickened. They may be (a) homogeneously broadened, (b) show a typically split lamina densa, or (c) show a focally or diffusely thinned lamina densa layer. The latter may be one third or one half of the normal thickness. These findings provide further evidence for the hypothesis of basement membrane alterations as the basic lesion in hereditary nephritis.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-1912
    Schlagwort(e): Nitric oxide ; NG-nitro-L-arginine methyl ester ; Kidney ; Heart ; Hypertension ; Renal haemodynamics ; Renin-angiotensin system ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by NG-nitro-l-arginine methyl ester (l-NAME). Chronic treatment with l-NAME in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 ± 16 mmHg) as compared to controls (155+4 mmHg). Animals receiving simultaneously l-NAME and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-NAME caused a significant reduction in glomerular filtration rate (GFR: 2.56+0.73 ml·kg−1·min−1) and renal plasma flow (RPF: 6.93±1.70ml·kg−1·min−1) as compared to control (GFR: 7.29±0.69, RPF: 21.36±2.33ml·kg−1·min−1). Addition of ramipril prevented l-NAME-induced reduction in GFR and renal plasma flow. l-NAME produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-NAME-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with l-NAME showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischaemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased. Coadministration of ramipril reversed these effects. l-NAME treatment reduced the cyclic GMP content in urine and renal arteries, and was not changed by additional ramipril-treatment. In the kidney hyalinosis of arterioles and of glomerular capillaries, as well as mesangial expansion and tubular atrophies seen after long-term inhibition of NO synthase were reduced by coadministration of ramipril. In conclusion, long-term ACE inhibition by ramipril prevented l-NAME-induced hypertension and cardiac hypertrophy, and attenuated functional and morphological changes in the kidneys. In addition, cardiac-dynamic and -metabolic deterioration induced by L-NAME was normalised by co-treatment with ramipril.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 46 (1968), S. 696-708 
    ISSN: 1432-1440
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary In an experimental study the functional and morphological behavior of convoluted kidney tubules under conditions of energy insufficiency was investigated: An isotonic (300 mosm) and buffered (pH 7.4) solution of 1/50 molar potassium cyanide was dripped onto a circumscribed area of the surface of rat kidney in vivo over a period of 20 minutes. Stereomicroscopic, light and electron microscopic observations of the subcapsular convoluted tubules in the cyanide poisened area (in vivo as well as after intravital fixation) led to following results: 1. Proximal and distal convoluted tubules show a significant dilatation (luminal diameter increased about 40% in proximal, about 70% in distal tubules). 2. The occlusion time of the proximal tubule (after clamping the renal artery) was prolonged 12–15 times. 3. The rate of fluid movement along the tubule lumen was greatly reduced (by a factor of approximately 0.3). 4. The marked functional disturbances in the convoluted tubular system are considered to be predominantly a consequence of a tubular reabsorption insufficiency. However, the tubular epithelium shows either no alteration or only distinct structural changes (Figs. 3–5). Hydropic changes of cytoplasmic matrix and mitochondria are not detectable, except in a few single cells, which were found in state of hydropic necrosis (cytolysis) (Fig. 6). It is suggested that the inhibition of cellular oxidative energy metabolism only led to a reduction of the epithelial transport activity. Thus, a diffuse tubule dilatation can be the main pathomorphological substrate of the energy determined tubulopathy. These observations are similar to those in many cases of acute renal failure in humans. 5. “Unselective” back diffusion through necrotic tubular epithelium can be demonstrated morphologically with the aid of intratubular ferritin injection. However, an important role in the pathogenesis of oliguria cannot be ascribed to this tubulo-capillary reflux.
    Notizen: Zusammenfassung In einem Modellversuch (unter Mikropunktionsbedingungen präparierte Rattennieren, Auftropfen einer 1/50 m gepufferten, plasmaisotonen Kaliumcyanidlösung auf die Nierenoberfläche in vivo, über 20 min) wird das funktionelle und morphologische Verhalten des Nierentubulus im Konvolutbereich bei energetischer Insuffizienz untersucht: 1. Proximales und distales Konvolut zeigen eine deutliche diffuse Dilatation (Zunahme des Lumendurchmessers proximal um 40%, distal um 70%). 2. Die proximale Kollapszeit (nach Arterienabklemmung) ist auf das 12–15fache verlängert. 3. Die tubuläre Strömungsgeschwindigkeit ist in beiden Tubuluskonvoluten stark herabgesetzt. 4. Trotz der ausgeprägten funktionellen Störungen, die mindestens zum überwiegenden Teil aus der tubulären Resorptionsinsuffizienz zu erklären sind, zeigt das intravitalfixierte Tubulusepithel licht- und elektronenmikroskopisch nur sehr diskrete Veränderungen, insbesondere keinen Hydrops des Grund-plasmas und der Mitochondrien, wenn man von seltenen, keineswegs obligaten Einzelzellnekrosen absieht. Es wird angenommen, daß sich das energetisch insuffiziente Tubulusepithel im Zustand der reinen Funktionsdrosselung befindet. Das morphologische Substrat einer energetisch bedingten Tubulopathie kann somit allein in einer diffusen Tubulusdilatation bestehen. Parallelen zum pathomorphologischen Befund beim akuten Nierenversagen des Menschen liegen auf der Hand. 5. Mit Hilfe der intratubulären Ferritin-Injektion wird gezeigt, daß eine „unselektive“ Rückdiffusion durch nekrotische Tubulusepithelien möglich ist. Für die Oligurie-Entstehung kann dem tubulocapillären Reflux jedoch eine wesentliche Bedeutung nicht beigemessen werden.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 48 (1970), S. 1195-1197 
    ISSN: 1432-1440
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Im Blutplasma von intravital fixierten Organen der Ratte (Leber, Milz, Niere) und des Menschen (Niere) konnten elektronenmikroskopisch oval geformte Körperchen (Durchmesser ca. 0,4 µm bzw. 0,2 µm) nachgewiesen werden. Wegen der vorwiegend tubulären Binnenstruktur wird für die beschriebenen Gebilde die Bezeichnung „multitubuläre Körperchen“ (mtK) vorgeschlagen. — Die tubulären Strukturen erfahren z.T. eine perlschnurartige bzw. kleinvesiculäre Umwandlung. Außerdem finden sich regelmäßig 1–2 größere Vesikel mit homogenem oder flockigem Inhalt. — Die Hüllmembran kann sich auflösen. — Die mtK finden sich offenbar gehäuft nach Heparinisierung bzw. nach Heparinisierung mit angeschlossenem hämorrhagischem Schock. — Über die Herkunft der mtK ist eine sichere Aussage vorerst nicht möglich. Beziehungen zu sog. endothelspezifischen Organellen werden diskutiert.
    Notizen: Summary Oval bodies (diameter approx. 0.4 µm and 0.2 µm) were demonstrated in the capillary lumen of rat organs (liver, spleen, kidney) and of human kidney. On account of the predominantly tubular structures the term “multitubular bodies” (mtb) is proposed for these corpuscles. — The internal tubular structures may be transformed into beaded or vesicular structures. One or two larger vesicles containing moderately dense material are also found regularly. The enveloping membrane may dissolve. — In experiments, the mtb occur apparently mere frequently after heparinization or after heparinization with subsequent hemorrhagic shock. — No definite statements about the origin of mtb are possible as yet. The relationship to endothelial-specific organelles is discussed.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 63 (1985), S. 835-849 
    ISSN: 1432-1440
    Schlagwort(e): Renal glomerulus ; Filtration apparatus ; Polyanion ; Tracer studies ; Electron microscopy ; Nierenglomerulus ; Filterapparat ; Polyanion ; Traceruntersuchungen ; Elektronenmikroskopie
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Die Feinstrukturen sowie die biophysikalischen und biochemischen Eigenschaften des glomerulären Filters für die Permeation von Makromolekülen werden dargestellt. Unter Berücksichtigung der unterschiedlich lokalisierten Immunkomplexablagerungen bei den verschiedenen Formen der Glomerulonephritis des Menschen orientieren sich Beschreibung und Diskussion an bestimmte Schichten des Filters: 1. endothelial — subendothelial (=porenhaltiges Endothel und lamina rara interna der Basalmembran), 2. membranös (=Lamina densa der Basalmembran) und 3. subepithelial — epithelial (=Lamina rara externa der Basalmembran und Podozyten mit Fußfortsätzen und Schlitzmembranen). Dabei wird hervorgehoben, daß die genannten Schichten Eigenschaften aufweisen, die eine zunehmend feinere Siebung von Makromolekülen aus dem Blut gewährleisten. Auf bekannte feinstrukturelle Besonderheiten des glomerulären Filters aufbauend, haben die experimentellen Untersuchungen der letzten 10 Jahre offenbart, daß ein Netzwerk von insbesondere Typ IV Collagen und die Existenz negativ geladener Heparansulfat-Proteoglykane („glomeruläres Polyanion“) wichtig für eine solche Siebung sind. Die Tatsache, daß die genannten Komponenten innerhalb der einzelnen Schichten in bestimmter Folge zellulär und extrazellulär lokalisiert sind, führt zu einem differenziert siebenden Filterapparat, der die Molekülgröße, die Konfiguration sowie die Ladung der Makromoleküle berücksichtigt. Dadurch wird der Durchtritt der zumeist negativ geladenen Blutproteine, insbesondere der von Albuminen, normalerweise verhindert.
    Notizen: Summary The ultrastructural and the biophysical and biochemical qualities of glomerular permeability to protein molecules are reviewed. With regard to differently located immune deposition in human glomerulonephritis, description and discussion are addressed in a fixed order of layers: 1. endothelial-subendothelial, i.e. the endothelial cells with fenestrae and the lamina rara interna of the basement membrane (bm), 2. membranous, i.e. the lamina densa of the bm, 3. subepithelial-epithelial, i.e. the lamina rara externa of the bm and the podocytes with food processes and slit diaphragms. It is emphasized that the 3 layers act as gradually (coarse to fine) filter barriers. On the basis of well known structural peculiarities, in the last 10 years experimental studies revealed that the meshwork of type IV collagen and the negatively charged heparan sulfate-proteoglycans — “the glomerular polyanion” — are integrated in sieving of protein molecules. These components are differently located in the stratified cellular and extracellular layers of the glomerular filter and their combined action is the basis of a size, charge and configuration dependend filtration of macromolecules. In this way the passage of the mostly negative charge blood proteins, expecially albumin, is prevented under normal conditions.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 44 (1966), S. 1379-1381 
    ISSN: 1432-1440
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary In a combined micropuncture and morphological study ferritin has been characterized as a suitable tracer substance for electron microscopic analysis of certain transport processes when injected directly into the proximal convolution of the rat kidney. It has been demonstrated that the ferritin molecules are absorbed by means of pinocytosis. Within 2–5 min following intratubular injection they gain access to large apical absorption vacuoles. Cytopempsis as a mode of transtubular transport has not yet been observed. — It could be conformed that the zonula occludens of junctional complexes constitutes a tight barrier for larger molecules, especially for proteins. From the described observations, using the split oil droplet method, the conclusion can be drawn that the proximal tubular epithelium maintained its normal functions even after contact with oil in split oil droplet experiments.
    Notizen: Zusammenfassung Die vorliegenden Befunde erbringen den Beweis, daß Ferritin als Tracer-Substanz für elektronenmikroskopische Untersuchungen bestimmter Transportphänomene am Tubulusepithel der Säugerniere geeignet ist. Da jedes einzelne Molekül durch den eisenhaltigen Kern markiert ist, sollte die Möglichkeit bestehen, den Vorgang der Eiweiß-resorption auch in zeitlicher und quantitativer Beziehung besser zu verfolgen. Die Aufnahme des Ferritin in die Tubuluszelle folgt den Gesetzen der Pinocytose und der vorübergehenden vacuolären Speicherung, deren erste Station (subapikale Resorptionsvacuolen) bereits nach 2 min erreicht ist. Für die Existenz eines cytopemptischen Transportes [7] im Tubulusepithel ergibt sich bislang kein Anhalt. Die Zonula occludens des Schlußleistenkomplexes bestätigt sich crneut als impermeable Barriere für höhermolekuläre Stoffe, insbesondere Eiweißkörper. — Die mitgeteilten Beobachtungen sind zugleich ein Beleg für die erhaltene Funktionsfähigkeit des Epithels nach Kontakt mit Ricinusöl im Bereich einer mit der Methode des „gespaltenen Öltropfens“ erzeugten Teststrecke des proximalen Konvolutes.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Human genetics 〈Berlin〉 27 (1975), S. 185-197 
    ISSN: 1432-1203
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The lipoproteins from two sibs with familial lecithin-cholesterol-acyltransferase(LCAT)-deficiency were further characterized. Comparatively lipoproteins from patients with secondary LCAT-deficiency were studied. Both groups of patients had particles of unusual size and shape in the α1-(HD-2)-lipoprotein subfraction. The abnormal HDL-2 particles were disk-like in appearance with a major axis of about 180 Å and a minor axis of about 40 Å and tended to aggregate into long coinlike stacks. The abnormal HDL-2 particles contained the normal protein constituents of HDL Apo A-I, Apo A-II and Apo C but in addition a major polypeptide with a M.W. of 39 000 not seen in significant amounts in normal high-density-lipoproteins. This polypeptide was found identical in size, isoelectric focusing and immunochemically with an arginine-rich normal polypeptide constituent of very-low-density-lipoproteins designated apoprotein E. Presence of this protein marker in the HDL allowed the specific immunological detection of the abnormal HDL-2 (LP-E) in plasma. Further minor biochemical abnormalities were observed in the lipoproteins of the patients with familial LCAT-deficiency. However, the main protein constituents of their HDL, the Apo A, Apo C and Apo E polypeptides, were found to be identical electrophoretically and by analytical isoelectric focusing with their normal counterparts. The data suggest that the basic genetic defect in the hereditary disease leads to a deficient activity of the LCAT-enzyme and that all abnormalities in the lipoprotein spectrum are secondary.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-0584
    Schlagwort(e): Acute graft-versus-host disease ; Drug treatment ; Leflunomide
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The grafting of immunocompetent allogeneic cells into MHC-discordant, genetically nonresponsive F1 hybrids of inbred rat strains consistently leads to an acute, lethal graft-versus-host disease (GVHD). The novel immunomodulating drug leflunomide, which has been shown to be efficacious in animal models of autoimmunity and adverse transplantation reactions, was studied in a rat model of GVHD. It was found that this drug not only was a powerful agent to prevent this otherwise terminal disorder, but was also proficient when used as a therapy of an established GVHD. Since leflunomide has been shown to be efficacious and safe in patients with chronic rheumatoid arthritis, it would also be reasonable to investigate this drug in clinical trials for bone marrow transplantation and GVHD in human beings.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-2013
    Schlagwort(e): Split-Oil Droplet Method ; Proximal and Distal Convolution ; Ultrastructure of Kidney ; Na- and Fluid Reabsorption ; Adrenalectomy ; Öltropfenmethode ; proximales und distales Tubuluskonvolut ; Ultrastruktur der Niere ; Natrium- und Flüssigkeitsresorption ; Adrenalektomie
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Micropuncture experiments have been carried out in proximal and distal convolutions of the rat kidney in order to test the reliability of the split-oil droplet method. 1. Light- and electronmicroscopic results: In castor oil filled segments a sufficient blockade is achieved, as judged from the compression of the brush border. In the test segments, interposed between two oil filled segments which are injected with ferritin containing saline, the tubular epithelium and especially the luminal brush border exhibit a normal histology. The tight junctions are intact and pinocytosis is indicated by ferritin resorption. Only in very few instances were oil droplets found to adhere to the brush border of the test segment, sometimes forming circumscript deposits protruding towards the cells. In such areas mechanical lesions of the cell membrane were only very rarely observed. In the proximal and distal convolutions of adrenalectomized rats the same experimental procedure did not lead to differences in the morphology of the epithelium. 2. Physiological data: a) Half time of volume reabsorption was unchanged when the split-oil droplet procedure was applied repeatedly to the same tubular segment. b) Intraluminal application of KCN (10−3–10−2 Mol/l) inhibited reabsorption of NaCl and fluid out of the test segment. c) Addition of the non-permeating polyethyleneglycol to the test solution prolongedt1/2 to infinity. d) In experimental diabetes insipidus half time of fluid reabsorption was greatly increased in the distal convolution, but could be normalized by intravenous injection of vasopressin. This was true even when the tubular epithelium was in contact with castor oil for more than 60 min prior to the administration of the hormone. From the results obtained in this and earlier studies it is concluded that contact with castor oil and tubular dilatation (to the extent that occurs during the procedure of the split-oil droplet method) does not damage tubular epithelium to a measureable degree as judged both by functional and morphological criteria. This holds also for adrenalectomized rats.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-2013
    Schlagwort(e): Tubules ; Kidney ; Intraluminal Oil Injection ; Ultrastructure of Kidney ; Proximales Tubuluskonvolut ; Rattenniere ; intraluminale Ölinjektion ; Ultrastruktur der Niere
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Light- and electronmicroscopic evaluation of proximal convolutions of the rat kidney were made following injection with either mineral oil or castor oil. The following observations were made: 1. Injection of mineral oil does not result in a complete blockade of the tubular lumen and leads to morphological lesions of epithelial cells. 2. Injection of the more viscous castor oil, in contrast, leads to a dilatation of the tubular lumen and a compression of the brush border of proximal tubular cells. Thus a better blockade of longitudinal flow is achieved. A toxic effect of castor oil on the tubular epithelium could not be detected. Mechanical lesions, similar to those observed after mineral oil injection, were less frequent. They consisted in a penetration of oil into the cells, perhaps as consequence of the tubular dilatation. 3. In oil-injected proximal tubular segments the following cytologic phenomena were observed: a) a cessation of the normal pinocytosis, which is induced in the presence of tubular fluid, b) simultaneously the “large resorption vacuoles” disappear, indicating that they originate from confluence of pinocytotic vesicles, c) in dilated tubules protein resorption vacuoles are found to have ruptured towards the tubular lumen suggesting a high hydrostatic pressure within the vacuoles.
    Materialart: Digitale Medien
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