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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 136 (1986), S. 665-671 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0009-8981
    Keywords: Alcoholic cirrhosis of the liver ; Biliary excretion ; Iron
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 70 (1992), S. 865-874 
    ISSN: 1432-1440
    Keywords: Glomerular mesangium ; Glomerulonephritis ; Glomerulosclerosis ; Integrins ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mesangial cells play an important role in the development and progression of human glomerular disease. This article summarizes some important aspects of mesangial properties and behaviour in situ. Intrinsic mesangial cells express α-smooth muscle actin and are best characterized as myofibroblasts or glomerular pericytes. The main intergin receptor in the mesangium is the α1\1 integrin. The \2 and \3 integrins have not been detected. Mesangial cells in situ fail to react with many monoclonal antibodies which stain human mesangial cells in culture, including leukocyte activation antigens. Prominent reactions in glomerular disease are mesangial expansion and progressive glomerular sclerosis, which are preceded by or associated with mesangial cell hypertrophy and/or proliferation. Mesangial enlargement is accompanied by an altered integrin expression and an abnormal composition of extracellular mesangial matrix. From the numerous autocrine and paracrine mediators identified in vitro which stimulate or inhibit mesangial cell growth and extracellular matrix synthesis, up to now only a few factors have been shown to be present in selected human glomerulopathies. These include platelet derived growth factors and platelet derived growth factor receptor β, transforming growth factors \, interleukin 1β, tumor necrosis factor α, and interleukin 6. Further identification of such mediators in situ will improve our understanding of pathological glomerular processes, particularly with respect to the multifunctional properties of the mesangial cell.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 70 (1992), S. 802-808 
    ISSN: 1432-1440
    Keywords: Familial juvenile nephronophthisis ; Medullary cystic disease ; Linkage analysis ; Renal cystic disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Familial juvenile nephronophthisis (NPH) and medullary cystic disease (MCD) are hereditary forms of early-onset chronic renal failure caused by the bilateral formation of cysts at the corticomedullary junction of the kidney. Polyuria, polydipsia, anemia, and growth retardation precede end-stage renal failure. The absence of edema and hypertension frequently leads to a delay in the diagnosis and commencement of therapy. The condition is a major cause of end-stage renal disease (ESRD) in children, accounting for 10%–25% of these patients. About 300 cases of NPH or MCD have been described. Although they are almost indistinguishable clinically and pathologically, the two conditions are separated by a characteristic age of onset (11.5 years in NPH vs. 28.5 years in MCD) and by the mode of inheritance (autosomal recessive in NPH vs. autosomal dominant in MCD). An association of NPH with retinitis pigmentosa is known as the Senior-Løken syndrome (SLS). Hepatic fibrosis, skeletal defects, and central nervous system abnormalities have been described in association with NPH but are typically absent in MCD. Since the pathology of NPH and MCD is similar, the term “nephronophthisis complex” has been introduced to summarize the related diseases. At present, there are no means of identifying heterozygotes, conducting prenatal diagnosis, or screening children in affected families. The histologic changes of NPH are characteristic but not specific for the disease. Cysts of 1–15 mm in diameter, located primarily at the corticomedullary junction, are seen in 70% of the patients. Light microscopy reveals a chronic sclerosing tubulo-interstitial nephropathy. Characteristic changes on electron microscopy are thickening, splitting, attenuation, and granular disintegration of the tubular basement membrane with abrupt transitions between the alterations. Since the pathophysiology of the disease complex is obscure, a reverse genetics approach is currently being used to localize a gene or several genes for the NPH/MCD complex.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric radiology 9 (1980), S. 19-26 
    ISSN: 1432-1998
    Keywords: Nephrocalcinosis ; Radiographs ; Computed tomography ; Sonography ; Histology ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 12 patients with nephrocalcinosis, radiographs were compared with computed tomography, sonography and histology. Computed tomography detects nephrocalcinosis at a very early stage of the disease, gives a better picture of the density and exten of nephrocalcinosis and may detect other findings (e. g. cysts). Radiographs may show many more details than computed tomography; they seem to be more suitable for observing the course of the disease and have a lower radiation dose. Sonography has not been helpful in the diagnosis of nephrocalcinosis. Histology correlates only moderately with the degree of nephrocalcinosis demonstrated in radiographs and computed tomography.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 1149-1157 
    ISSN: 1432-1440
    Keywords: Hemodialysis ; Foreign body reaction ; Silicone ; Hepatosplenomegaly ; NonA, non-B Hepatitis ; Hämodialyse ; Fremdkörperreaktion ; Silikon ; Hepatosplenomegalie ; Non-A, non-B Hepatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Untersuchung wurde das Sektionsgut von 47 Patienten überprüft, die zwischen 1965 und 1980 unter Verwendung von Silikonschläuchen dialysiert wurden. Ferner wurde das Sektionsgut von zehn Patienten aus zwei Dialysezentren untersucht, in denen routinemäßig PVC Schläuche verwandt wurden. Bei 40 Patienten aus dem Zentrum mit Silikonschläuchen, bei denen die Dialysezeit unter 53 Monaten lag, konnte kein Fremdmaterial nachgewiesen werden. Bei sieben Patienten, die zwischen 52 und 165 Monaten dialysiert worden waren, zeigten sich bei der licht- und elektronenmikroskopischen Untersuchung Fremdkörpereinschlüsse in Makrophagen und Riesenzellen in folgenden Organen: Lunge, Leber, Milz, Knochenmark, Haut, thorakale und abdominale Lymphknoten. Das Material konnte in Hirn, Herz, Niere und endokrinen Organen nicht nachgewiesen werden. Fibrose, Nekrose oder Epitheloidzellreaktionen wurden nicht beobachtet. Das Fremdmaterial war nicht-isotrop, nicht kristallin und färbte sich mit Routine-Färbeverfahren nicht an. Die Elektronenmikroskopie zeigte, daß es von lysosomalen Membranen umschlossen war. Bei Patienten mit wesentlich kürzerer Dialysezeit konnte das Material in vivo durch Leberbiopsie eindeutig nachgewiesen werden. Hingegen wurde das Fremdkörpermaterial nicht gefunden bei den zehn Langzeithämodialyse-Patienten aus den zwei Zentren, die nicht routinemäßig Silikonschläuche verwandten. Alle Patienten mit positivem Nachweis wiesen eine Hepatosplenemegalie auf, viele Patienten hatten Transaminasen-Erhöhungen, ein Patient hatte Hypersplenismus mit Panzytopenie und ein Patient hatte ein Gallengangskarzinom. Durch Gaschromatographie und Massenspektrometrie konnten in der Leber von Dialysepatienten in hoher Menge Phthalatweichmacher nachgewiesen werden (5–11 ppm); daneben fanden sich bei einem Patienten in beträchtlicher Menge normalerweise nicht vorkommende, cholesterinähnliche Steroide. Durch Rasterelektronenmikroskopie und Röntgenfluoreszenz-Mikroanalyse ließen sich in Leber und Milz zahlreiche Partikel von mehreren μ-Größe in Makrophagen nachweisen. Entsprechende Einschlüsse konnten bei nichtdialysierten Kontrollindividuen nie gefunden werden. Das Energiespektrum der Partikel zeigte einen scharfen Si-Peak mit geringer Beimengung von Al und Cl. Die Partikel entsprachen in Form und Energiespektrum dem Abrieb von Silikonschläuchen nach Einwirkung von Rollerpumpen. Partikel mit reinem Cl-Peak als Hinweis auf PVC-haltige Partikel konnten bei Patienten mit Silikoneinschlußkörpern nicht nachgewiesen werden. Wegen der beobachteten klinischen Komplikationen müssen aus den vorgelegten Ergebnissen Konsequenzen für die Herstellung von Dialysematerial gezogen werden.
    Notes: Summary We studied autopsy material of 47 patients who were dialysed between 1969 and 1980 in one center in which silicone tubing was used. In addition, we examined ten patients from two other centers where silicone tubing was not routinely used. In 40 patients with exposure to silicone tubing who were dialysed for up to 53 months, no foreign material was demonstrable. In seven patients who were dialysed for periods between 52 and 165 months, light microscopy and electron microscopy showed varying amounts of foreign material in macrophages and giant cells of lung, liver, spleen, bone marrow, skin, thoracic and abdominal lymph nodes. No such material was found in brain, heart, kidney or endocrine organs. No epitheloid cell reaction, necrosis or fibrosis was observed. The material was non-isotropic, non-crystalline, and did not take up routine stains. Electron microscopy showed its presence within lysosomal membranes. In addition, in some patients who had been dialysed for much shorter periods of time, similar material could be demonstrated in liver biopsies obtained in vivo. No such material was observed in ten long-term dialysis patients of two centers where silicone tubing was not routinely used. All positive patients had hepatosplenomegaly, some had elevated transaminases, one patient had hypersplenism with pancytopenia and one patient had bile duct carcinoma. Gaschromatography with mass spectrometry of livers of dialysed patients showed high concentrations of phthalate plasticizer (5–10 ppm) and in one patient cholesterol-like steroids which were not found in normal livers. Surface scanning electron microscopy with non-dispersive X-ray fluorescence analysis revealed the presence of numerous particles up to 10 µ, in liver and spleen of dialysed patients but of not control patients. The particles showed a characteristic Si peak with a concomitant small contribution of Al and Cl. The particles were identical with filing of silicone tubing exposed to roller pumps. No material exhibiting a pure Cl peak (as evidence for PVC) was demonstrable in patients with positive silicone inclusions. Because of its clinical consequences, the observation will have implications for manufacturing of dialysis devices.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 61 (1983), S. 911-915 
    ISSN: 1432-1440
    Keywords: Mesangial IgA-glomerulonephritis ; IgA1 ; Polymeric IgA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary IgA deposits in kidney and skin biopsies from patients with idiopathic mesangial IgA-glomerulonephritis were characterized with immunofluorescence microscopy using monoclonal antibodies against the IgA subclasses IgA1 and IgA2. IgA1 was the major constituent in all biopsy specimens. Double immunofluorescence microscopy showed that IgA deposits were constantly associated with J-chain. Secretory component was never found in the deposited material. In vitro fixation of free secretory component, however, was observed in some biopsies. These findings indicate that most if not all of the deposited IgA in patients with idiopathic IgA-glomerulonephritis is polymeric in nature.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 978-987 
    ISSN: 1432-1440
    Keywords: Glomerulonephritis ; Extramembraneous glomerulonephritis ; Membranoproliferative glomerulonephritis ; Lupus erythematosus ; Steroids ; Antiplatelet agents ; Glomerulonephritis ; Extramembranöse Glomerulonephritis ; Membranoproliferative Glomerulonephritis ; Lupus erythematodes ; Steroide ; Plättchenhemmer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Thema der therapeutischen Beeinflussung der entzündlichen Pathomechanismen bei chronisch-idiopathischer Glomerulonephritis bedarf einiger kritischer Anmerkungen. Eine ätiologische Behandlung ist nur in Ausnahmefällen möglich (infektiöse Tropenkrankheiten, infizierter ventrikuloatrialer Shunt etc.). Einer erfolgreichen Beeinflussung der Pathomechanismen, welche die glomeruläre Entzündung auslösen und unterhalten, steht unsere Unkenntnis über die im einzelnen verantwortlichen Schritte entgegen. Neuere Untersuchungen legen Schlüsselrollen für die terminale Komponente des Komplementsystems, Produkte des Lipoxygenaseabbauweges der Arachidonsäure sowie Sauerstoffradikale nahe, welche therapeutisch nicht oder nur beschränkt beeinflußbar sind. Ferner beruht die Progredienz glomerulärer Entzündungen in die Niereninsuffizienz in der Regel auf fortschreitender Sklerosierung von Glomerulus, Gefäßen und Interstitium und nicht auf zunehmenden aktiv entzündlichen glomerulären Läsionen. Beispielhaft wurden bei der Sichtung der veröffentlichten kontrollierten Therapiestudien die Untersuchungen bei extramembranöser und membranoproliferativer Glomerulonephritis herausgegriffen. Hierbei wurde eine im Ausmaß nur beschränkte, und nicht in allen Studien gesicherte, Beeinflussung der Nierenfunktion gefunden, der andererseits erhebliche Nebenwirkungen gegenüberstehen. Eine abschließende Wertung kommt zu dem Urteil, daß eine medikamentöse Beeinflussung der entzündlichen Pathomechanismen fragwürdig ist, daß jedoch ein therapeutischer Nihilismus nicht angezeigt ist angesichts der Beeinflußbarkeit unspezifischer Schädigungsmechanismen (antihypertensive Behandlung, diätetische Intervention).
    Notes: Summary It is controversial whether the pathomechanisms involved in chronic idiopathic glomerulonephritis are susceptible to therapeutic intervention. Etiological therapy, i.e. elimintion of the responsible antigen, is possible only in exceptional cases, e.g. tropical diseases, infected ventriculoatrial shunt etc. Antiinflammatory therapy directed against pathomechanisms initiating or maintaining glomerular inflammation has an uncertain theoretical foundation because of lack of knowledge relating to the exact steps mediating tissue injury. Recent studies suggest keyroles for terminal components of complement system, products of lipoxygenase pathway of arachidonic acid and oxygen radicals — all of which are not readily influenced by available therapeutic modulaties. Finally, progression of glomerular inflammation to renal failure is usually not the cause of cumulative acute inflammatory glomerular lesions but rather the consequence of progressive sclerosis of glomeruli, arterioles and interstitium. As examples of controlled intervention trials, studies on extramembranous and membranoproliferative glomerulonephritis are discussed. The studies show limited and not always statistically significant influence on renal function, however, at the expense of considerable side effects. It is concluded that it is highly questionable whether inflammatory pathomechanisms are influenced by currently available drugs. However, therapeutic nihilism is not appropriate given modalities to influence mechanisms of nonspecific damage, e.g. by antihypertensive medication or dietary intervention.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Xenotransplantation ; Komplement ; Löslicher Komplementrezeptor Typ 1 (sCR1) ; Key words Xenotransplantation ; Complement ; Soluble complement receptor type 1 (sCR1)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In this study a modified experimental kidney xenograft model was developed, which reproduced, in a reliable way, the course of hyperacute rejection. In this model guinea-pig kidneys were transplanted to rats using end-to-side anastomoses with recipient aorta and vena cava, respectively, and ureter drainage for diuresis monitoring. The aim of this study was to investigate the protective effects of complement modulation by soluble complement receptor 1 (sCR1) on the xenografts. Twenty-four xenotransplantations were performed and recipients randomized for treatment either by 3 ml saline or 50 mg/kg sCR1 as a 3-ml bolus. It was found that sCR1 was highly efficient in delaying hyperacute rejection from 10.5 ± 2.1 min in the control group to at least 2 h in the therapy group and in prolongation of graft function. The complement activity was significantly reduced in the sCR1-treated rats, even at the time of rejection, as a result of complement modulation in this group of xenograft recipients. Xenografts from saline-treated animals showed necroses, interstitial haemorrhages and platelet aggregates occluding the vessels as soon as 10 min after the reperfusion started. No such changes could be seen even after 120 min in the xenografted kidneys of sCR1-treated rats. Also C3 deposits in the glomeruli and interstitium were markedly reduced.
    Notes: Zusammenfassung In der vorliegenden Arbeit wurde ein modifiziertes tierexperimentelles Modell der Nierenxenotransplantation entwickelt, im Rahmen dessen der Verlauf einer hyperakuten Abstoßungsreaktion hochgradig reproduzierbar ist. In diesem Modell wurden Meerschweinchennieren als Spenderorgane auf Wistarratten als Empfängertiere verpflanzt, wobei End-zu-Seit-Gefäßanastomosen mit Spenderaorta, bzw. V. cava und Harnleiterdrainage mittels Schienung zur Diureseüberwachung zum Einsatz kamen. Ziel der vorliegenden Untersuchung war es die protektive Wirkung der Komplementmodulation mit Hilfe des löslichen Komplementrezeptors Typ 1 (sCR1) auf die Nierenxenotransplantate zu analysieren. Insgesamt wurden 24 Xenotransplantationen vorgenommen und randomisiert mit 3 ml 0,9 % NaCl (Kontrollgruppe), bzw. 50 mg/kg sCR1 als 3-ml-Bolus (Behandlungsgruppe) therapiert. Der lösliche Komplementrezeptor Typ 1 (sCR1) war wirksam in bezug auf die Verlängerung der Transplantatüberlebenszeit (von 10,5 ± 2,1 min in der Kontrollgruppe auf mindestens 2 h in der Behandlungsgruppe) und seine Funktion. Serologisch konnte eine deutliche Reduktion der Komplementaktivität in der sCR1-Gruppe festgestellt werden, die auf eine modulatorische Wirkung des sCR1 zurückzuführen ist. Bereits 10 min nach Reperfusionsbeginn zeigten sich histologisch in der Kontrollgruppe massenhaft Thrombozytenaggregate, Fibrinablagerungen in den Kapillaren und interstitielle Infiltrate. Die mit sCR1 behandelten Nierentransplantate wiesen dagegen nach 120 min eine deutlich reduzierte intravasale Thrombenbildung und geringere interstitielle Infiltration auf. Die immunhistologische Studie ließ eine gleichermaßen verminderte Ablagerung von C3 in den Glomeruli und im Interstitium in der Therapiegruppe erkennen.
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  • 10
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Thrombotisch-thrombozytopenische Purpura ; Hämolytisch-urämisches Syndrom ; Systemischer Lupus erythematodes ; Plasmapherese ; Key words Thrombotic thrombocytopenic purpura ; Hemolytic uremic syndrome ; Systemic lupus erythematosus ; Lupus-like-syndrome ; Plasma exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A 139/12 year old boy presented with the clinical and laboratory signs of a systemic lupus erythematosus (SLE)-like illness. Three months later he developed acute renal failure associated with hemolytic anemia and thrombocytopenia while being treated with prednisone and a non-steroidal antiphlogistic agent. Kidney biopsy revealed endotheliotropic microangiopathy. A thrombocytopenic purpura/hemolytic uremic syndrome was diagnosed according to clinical and histological findings. Plasma exchange, hemodialysis and immunosuppressive therapy with prednisone and cyclophosphamide resulted in a normalization of the hematologic findings, and the kidney function improved. The cyclophosphamide therapy was continued over 21/2 years. Three years after the acute episode the boy is free of symptoms with glomerular filtration rate of 71 ml/min/1.73 qm. Discussion. The association of SLE with thrombotic thrombocytopenic purpura is rare, has predominantly been described in adults and has a high mortality rate. Our case demonstrates the success of an early aggressive therapy including plasma exchange, hemodialysis, prednisolone and cyclophosphamide.
    Notes: Zusammenfassung Ein 139/12 Jahre alter Knabe entwickelte 3 Monate nach Beginn einer Lupus-ähnlichen Systemerkrankung unter Prednisontherapie ein akutes Nierenversagen mit hämolytischer Anämie und Thrombozytopenie. Die Nierenbiopsie zeigte eine thrombotische Mikroangiopathie. Unter Behandlung mit Plasmaaustausch, immunsuppressiver Therapie und Hämodialyse normalisierten sich die hämatologischen Befunde, und die Nierenfunktion besserte sich. Die Cyclophosphamidtherapie wurde über 21/2 Jahre fortgesetzt. Drei Jahre nach dem akuten Nierenversagen ist der Junge unter antihypertensiver Behandlung symptomfrei und hat eine normale glomeruläre Filtrationsrate. Diskussion. Die Assoziation eines systemischen Lupus erythematodes mit einer thrombotisch-thrombozytopenischen Purpura ist in der Literatur bisher nur selten und fast nur bei Erwachsenen beschrieben worden; sie hat eine hohe Mortalität. Der dargestellte Fall demonstriert den Erfolg einer frühzeitigen aggressiven Therapie.
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