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  • 1
    Electronic Resource
    Electronic Resource
    Intraglomerular fibronectin accumulation and degradation in obese Zucker rats (1991)
    Springer
    Diabetologia 34 (1991), S. 786-789 
    Details
    ISSN: 1432-0428
    Keywords: Fibronectin ; diabetes mellitus ; isolated glomeruli
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The obese Zucker rat is a classic model of non-immune mediated spontaneous focal glomerulosclerosis. An important initiating hallmark of glomerulosclerosis in this model is mesangial matrix expansion. Fibronectin, a highly biologically active glycoprotein, is a normal constituent of mesangial extracellular matrix. Using a quantitative method based on enzyme immunoassay we assessed the intraglomerular fibronectin content and its degradation in obese Zucker rats and their lean littermates. In the obese Zucker rats the glomerular fibronectin content was significantly higher in comparison to the controls (88±6 vs 48±4 ng/103 glomeruli). Furthermore, proteinase activity against fibronectin was significantly reduced in the glomeruli of obese Zucker rats when compared to control animals (at pH 5.4: 186±6 U/mg protein vs 286±14 U/mg protein, at pH 7.4: 152±12 U/mg protein vs 193±12 U/mg protein). These data demonstrate that in obese Zucker rats there is a glomerular accumulation of fibronectin which we propose is at least partly due to diminished proteolytic digestion. Whether accumulation of intraglomerular fibronectin contributes to progressive glomerulosclerosis remains a matter of debate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408351
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  • 2
    Electronic Resource
    Electronic Resource
    Renal proteinases and kidney hypertrophy in experimental diabetes (1994)
    Springer
    Diabetologia 37 (1994), S. 567-571 
    Details
    ISSN: 1432-0428
    Keywords: IDDM ; streptozotocin ; tubules ; glomeruli ; collagenase ; gelatinase ; cathepsins ; hypertrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary IDDM is associated with an increase in kidney size, which is due to cellular hypertrophy and progressive matrix accumulation within the glomerulus and throughout the tubulointerstitium. The present study addressed the potential role of cysteine and metalloproteinases in renal hypertrophy of short-term diabetes. Three weeks after induction of streptozotocin diabetes in rats, intraglomerular gelatinase activity (streptozotocin: 23±4 vs control: 44±3 mU/μg DNA) and cathepsin L + B activity (streptozotocin: 6.7±0.8 vs control: 9.3±0.7 U/μg DNA) were significantly decreased. Insulin treatment completely prevented the decline in glomerular proteinase activity (gelatinase: 37±6 mU/μg DNA; cathepsin L + B: 9.6±0.9 U/μg DNA). In isolated proximal tubules a similar pattern of enzyme activity could be observed. Three weeks of diabetes caused a significant decline in cathepsin L + B activity (streptozotocin: 28±2 vs control: 37±3 U/μg DNA). Insulin treatment again prevented the decline in these tubular proteinase activities. In parallel, kidney weight increased by 22% and glomerular protein/DNA ratio rose by 17% in untreated diabetic rats. Diabetic rats receiving insulin displayed a normal glomerular protein/DNA ratio and the kidney weight was increased by only 5%. These results show that renal hypertrophy of early diabetes is closely associated with a decline in both glomerular and tubular proteinase activity. Adequate insulin substitution prevented renal hypertrophy and the reduction in proteinase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403374
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  • 3
    Electronic Resource
    Electronic Resource
    Renal proteinases and kidney hypertrophy in experimental diabetes (1994)
    Springer
    Diabetologia 37 (1994), S. 567-571 
    Details
    ISSN: 1432-0428
    Keywords: Key words IDDM, streptozotocin, tubules, glomeruli, collagenase, gelatinase, cathepsins, hypertrophy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary IDDM is associated with an increase in kidney size, which is due to cellular hypertrophy and progressive matrix accumulation within the glomerulus and throughout the tubulointerstitium. The present study addressed the potential role of cysteine and metalloproteinases in renal hypertrophy of short-term diabetes. Three weeks after induction of streptozotocin diabetes in rats, intraglomerular gelatinase activity (streptozotocin: 23±4 vs control: 44±3 mU/µg DNA) and cathepsin L+B activity (streptozotocin: 6.7±0.8 vs control: 9.3±0.7 U/µg DNA) were significantly decreased. Insulin treatment completely prevented the decline in glomerular proteinase activity (gelatinase: 37±6 mU/µg DNA; cathepsin L+B: 9.6±0.9 U/µg DNA). In isolated proximal tubules a similar pattern of enzyme activity could be observed. Three weeks of diabetes caused a significant decline in cathepsin L+B activity (streptozotocin: 28±2 vs control: 37±3 U/µg DNA). Insulin treatment again prevented the decline in these tubular proteinase activities. In parallel, kidney weight increased by 22 % and glomerular protein/DNA ratio rose by 17 % in untreated diabetic rats. Diabetic rats receiving insulin displayed a normal glomerular protein/DNA ratio and the kidney weight was increased by only 5 %. These results show that renal hypertrophy of early diabetes is closely associated with a decline in both glomerular and tubular proteinase activity. Adequate insulin substitution prevented renal hypertrophy and the reduction in proteinase activity. [Diabetologia (1994) 37: 567–571]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403374
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  • 4
    Electronic Resource
    Electronic Resource
    Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats (1997)
    Springer
    Diabetologia 40 (1997), S. 1035-1043 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Glomerulosclerosis ; matrix metalloproteinase ; tissue inhibitor of metalloproteinases ; obese Zucker rat.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The obese Zucker rat represents a model of obesity combined with insulin resistance and hyperlipidaemia, which over a period of several months develops spontaneous glomerulosclerosis. The present study addressed the question as to whether glomerular sclerosis was associated with alterations in the degradation of matrix components. In the early phase (up to 6 months) glomeruli from obese rats displayed increased total collagen content (+ 64 %) and decreased gelatinolytic activity (− 34 %) as compared to lean control animals. This decline in glomerular gelatinolytic activity was due to a reduction in gelatinase B [matrix metalloproteinase (MMP)-9]. Glomerular MMP-9 mRNA was reduced 4.6 ± 0.6-fold (n = 3; p 〈 0.05), MMP-9 protein was not detectable by Western blotting and MMP-9 activity was considerably suppressed in gelatin zymograms. MMP-2, in terms of mRNA expression and activity, was unchanged. Tissue inhibitor of metalloproteinases (TIMP)-1 mRNA expression, TIMP-1 protein (immunohistochemistry) and TIMP-1 activity (reverse zymography) were enhanced in glomeruli from obese rats, while TIMP-2 mRNA remained unchanged. Moreover, mRNA for the α1 IV collagen chain was 2.1 ± 0.8-fold higher in glomeruli isolated from obese animals (n = 3; p 〈 0.05). These findings indicate that matrix expansion in glomeruli from obese Zucker rats is due to both enhanced synthesis of matrix components as well as reduced degradation by matrix metalloproteinases. Apparently the latter effect is based on a reduction in MMP-9 and up-regulation of its inhibitor TIMP-1. [Diabetologia (1997) 40: 1035–1043]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050785
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  • 5
    Electronic Resource
    Electronic Resource
    Calciumantagonisten in der Therapie der Hypertonie (1983)
    Springer
    Journal of molecular medicine 61 (1983), S. 633-640 
    Details
    ISSN: 1432-1440
    Keywords: Calcium antagonists ; Nifedipine ; Verapamil ; Diltiazem ; Effects in experimental and essential hypertension ; Side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Calcium antagonists (nifedipine, verapamil, diltiazem) are potent vascular smooth muscle relaxants. Experimental and clinical investigations provide growing evidence that they are effective in acute and (sub)chronic therapy of arterial hypertension by lowering peripheral vascular resistance and improvement of altered hemodynamics — independent from pathogenesis of hypertension. Due to its prompt and profound hypotensive action, sublingual or oral nifedipine has been used successfully in hypertensive crises. The hypotensive effect usually correlates closely with the severity of hypertension and is nearly absent in normotensive controls. Since the blood pressure drop may occasionally result in absolute or relative hypotension, the initial dose should be as low as possible. The activation of the adrenergic and renin angiotensin systems seen after nifedipine administration is less pronounced after chronic administration of the drug and is nearly absent after verapamil and diltiazem. Plasma aldosterone concentrations remain constant or are slightly decreased. In contrast to classic vasodilators, the long-term administration of calcium antagonists usually does not result in tachycardia (nifedipine), but slight sinus bradycardia (verapamil, diltiazem). Peripheral edema may occasionally occur after nifedipine. A tolerance has been observed during long-term treatment of hypertension. Combining these drugs (verapamil, diltiazem) with betablockers is not recommended due to the negative inotropic and bathmotropic effects. Simultaneous administration of nifedipine and beta-blockers enhances the hypotensive action, but favours the development of peripheral edema and in rare cases (especially in severe coronary heart disease) results in a dramatic drop in blood pressure and/or congestive heart failure. Further clinical evaluation and long-term trials of calcium antagonists as antihypertensive agents will be needed before definite conclusions can be drawn.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01487579
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  • 6
    Electronic Resource
    Electronic Resource
    Role of alcohol in clinical nephrology (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 948-958 
    Details
    ISSN: 1432-1440
    Keywords: Alcoholism ; Fetal alcohol syndrome ; Genitourinary tract malformations ; Phosphate and magnesium depletion ; Rhabdomyolysis ; Acute renal failure ; Hypertension ; Alkohol ; Alkoholische Embryopathie ; Urogenitaltraktschädigung ; Phosphatund Magnesiumdepletion ; Rhabdomyolyse ; Akutes Nierenversagen ; Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nephrologisch wichtige Störungen des schwereren Alkoholismus manifestieren sich auf verschiedenen Ebenen. Eine direkte Schädigung der Nieren und abführenden Harnwege ist bislang ausschließlich bei alkoholischer Embryopathie nachgewiesen. Beim Erwachsenen dominieren unspezifische und komplexe Elektrolytstörungen mit Akzentuierung im Alkohol-Entzugssyndrom. Die Niere ist nicht selten primäre Ursache verschiedener Störungen, sie trägt ferner zur — oft inadäquaten — Kompensation extrarenal entstandener Stoffwechselstörungen (z.B. Phosphatmangel, Hypoglykämie) bei. Der alkoholassoziierten Uratretention, hervorgerufen durch Hyperlaktatämie oder Erhöhung derβ-Hydroxybuttersäure, kommt — wegen meist mäßiger Ausprägung — für die Entwicklung einer hyperurikämischen Nephropathie nur geringe Bedeutung zu. Alkoholexzeß (akut oder chronisch) prädisponiert zur Rhabdomyolyse mit konsekutivem Nierenversagen. Möglicherweise ist bei schwerem Alkoholismus und Myopathie die Vulnerabilität der Nieren für andere Noxen gesteigert. Bei der Ratte wird das Glyzerin-induzierte akute Nierenversagen durch Alkoholvorbehandlung verstärkt. Alkohol begünstigt ferner bei Normotonikern und Hypertonikern einen Blutdruckanstieg, der seinerseits das Risiko einer Nierenschädigung erhöht.
    Notes: Summary Different nephrological derangements are observed in severe alcoholics. Until now the direct toxicity of ethanol is only shown in the fetal alcohol syndrome with various malformations of the genitourinary tract. In the adult the kidney is often involved in the development, maintenance and counterregulation of complex electrolyte disturbances like phosphate and potassium hypoglycemia etc. The alcohol associated retention of urate, induced by hyperlactatemia and/or increasedβ-hydroxybutyrate concentration is only rarely complicated by urate nephropathy. Alcohol intoxication (acute and chronic) predisposes to rhabdomyolysis with the risk of acute renal failure. There are some hints that chronic alcoholism with myopathy increases the vulnerability of the kidney for further toxic agents. In rats glycerol induced renal failure is enhanced by alcohol pretreatment. Finally, regular alcohol consumption raises the blood pressure, which per se is a risk factor for renal damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01738150
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  • 7
    Electronic Resource
    Electronic Resource
    Häufigkeit und Wertung der epitheloidzelligen Granulome in der Milz bei Morbus Hodgkin (1977)
    Springer
    Journal of molecular medicine 55 (1977), S. 231-237 
    Details
    ISSN: 1432-1440
    Keywords: Lymphogranulomatosis ; Epitheloid cell ; Spleen ; Mononuclear phagocyte system ; Lymphogranulomatose, Épithěloidzelle ; Milz ; mononucleäres phagozytierendes System
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 154 Patienten mit Lymphogranulomatose wurden die exstirpierten Milzen gewogen, makroskopisch beurteilt und histologisch untersucht. Dabei fanden sich histologisch 71mal (46%) granulomatöse Veränderungen, von denen 55 (36%) typische Hodgkingranulome, 16 (10%) reine Epitheloidzellgranulome aufwiesen. Beide Veränderungen können makroskopisch als Herdbildungen erkennbar sein und sowohl bei vergrößerten (〉250 g) als auch bei normalgewichtigen Milzen beobachtet werden. Weiterhin können Splenomegalien bei M. Hodgkin auch Folge unspezifischer Veränderungen sein. Zum Problem der Epitheloidzellgranulome in der Milz bei M. Hodgkin ergibt sich, daß diese zwar kausalpathogenetisch mit der Lymphogranulomatose verknüpft, jedoch wesensmäßig von ihr zu trennen sind. Epitheloidzellgranulome sind als Reaktion des mononucleären phagozytierenden Systems bei Lymphogranulomatose und nicht als Lymphogranulomatosemanifestation selbst aufzufassen. Dies muß bei der klinischen Stadieneinteilung berücksichtigt werden.
    Notes: Summary Macroscopic and microscopic examination of 154 spleens from patients with lymphogranulomatosis revealed focal alterations in 71 (46%) specimens, 55 (=36%) of which showed typical Hodgkin granuloma while in 16 cases (=10%) the granulomas present were composed of epitheloid cells only. In casu, both Hodkin and epitheloid cell granulomas were macroscopically visible and occurred in normal-sized as well as in enlarged (〉250 g) spleens. However, unspecific alterations had led to splenomegaly, too. The presence of epitheloid cell granulomas in spleens in M. Hodgkin proves that the granulomas indeed are causal pathogenetically linked with lymphogranulomatosis, but are to separate from it substantially. Epitheloid cell granulomas are interpreted as a reaction of the mononuclear phagocyte system in lymphogranulomatosis and not as a manifestation of lymphogranulomatosis itself. This should be considered in clinical staging.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01487716
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  • 8
    Electronic Resource
    Electronic Resource
    Granulocyte lysosomal factors and plasma elastase in uremia: A potential factor of catabolism (1984)
    Springer
    Journal of molecular medicine 62 (1984), S. 218-224 
    Details
    ISSN: 1432-1440
    Keywords: Granulocyte lysosomal factors ; Elastase ; Acute and chronic uremia ; Catabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In uremic intoxication proteolytic activity in plasma and striated muscle is enhanced. To get further insights into the underlying mechanisms the lysosomal factors of polymorphonuclear (PMN) leukocytes and the plasma elastase-α 1-proteinase inhibitor complex were investigated in patients with acute and chronic renal failure. Lysosomal activity was evaluated in peripheral blood smears by the lysis of erythrocytes and plasma (halo formation) around each neutrophil induced by 0.25 M NaCl borate buffer. In about half of the patients with chronic renal insufficiency on dietary treatment lysosomal activity of PMN leukocytes was reduced. The plasma concentration of elastase-α 1-proteinase inhibitor complex was normal in most subjects, but increased in three patients with the highest serum creatinine levels (〉13 mg/dl). In the patients with acute renal failure (ARF) of various origin (postoperatively, septicemia, pancreatitis, or dye-induced) halo formation was either reduced or absent. The plasma elastase-α 1-proteinase inhibitor complex was increased in 5/6 of the patients by a factor of two to four. Also in the patients on regular hemodialysis treatment halo formation of PMN leukocytes was substantially reduced, whereas the plasma levels of elastase-α 1-proteinase inhibitor complex was slightly increased. The finding of reduced lysosomal activity of PMN neutrophils in uremia may be partly due to an enhanced release of neutral proteinases into the circulation as indicated by the elevated plasma levels of elastase-α 1-proteinase inhibitor complex in some patients. This release might be in part due to the effect of “uremic toxins”. In the patients on hemodialysis treatment the contact of the blood with the dialyzer (cuprophane) membrane might be an additional factor. Moreover, in the patients with acute renal failure the underlying disease (infection, shock, trauma) contributes to the release of proteinases. These disturbances may be harmful to the patient if the blood concentration or function of the most important proteinase inhibitors (α 1-proteinase inhibitor,α 2-macroglobulin) is reduced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01721047
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of diuresis on urinary erythrocyte morphology in glomerulonephritis (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 575-577 
    Details
    ISSN: 1432-1440
    Keywords: Glomerular haematuria ; Glomerulonephritis ; Diuresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The differentiation between glomerular and non-glomerular haematuria by phase-contrast microscopy has proved to be a useful tool in the diagnosis of glomerulonephritis. In an attempt to evaluate the effect of marked diuresis on the altered red cell morphology in patients with biopsy proven glomerulonephritis, urinary sediments were examined following water or furosemide-induced diuresis. In both diuretic states urine flow increased, urine osmolality decreased and the percentage of glomerular erythrocytes was significantly reduced in the urinary sediment. These data demonstrate that the alteration in urinary red cells in glomerulonephritis is mainly caused by tubular forces. The diagnostic significance is reduced during increased diuresis and the evaluation of urinary red cell morphology should not be performed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01733007
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  • 10
    Electronic Resource
    Electronic Resource
    Viral tropisms in mouse brain cell cultures (1982)
    Springer
    Medical microbiology and immunology 170 (1982), S. 201-208 
    Details
    ISSN: 1432-1831
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fourteen-day-old cultures of dissociated newborn mouse brain cells were infected separately with different strains of vaccinia virus and a strain of measles virus. Using the indirect immunofluorescence technique we found that under the experimental conditions in these cultures both measles and the neurotropic strain of vaccinia infected oligodendrocytes whereas the dermatropic strain of vaccinia did not. Astrocytes were neither infected by vaccinia strains nor by measles virus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02298200
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