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Biomedical subjects

M Teschner

Publications and source records attributed to M Teschner.

At least 55 records · Page 3Linked to original sources
PubMed1996

Low-density lipoprotein suppresses cathepsins B and L activity in rat mesangial cells.

Disturbances of lipid metabolism are considered to play a pathogenetic role in glomerulosclerosis. Since intraglomerular have been proposed to be involved in the pathogenesis of the glomerulosclerosis, we have investigated the influence of LDL on the activity of the cellular proteases. Cathepsins B and L were measured with the aid of fluorometry, and 7-amido-4-methylocoumarin derivates were used as substrates; Z-Arg-Arg-AMC for cathepsin B, Z-Phe-Arg-AMC for cathepsins B and L together. Rat mesangial cells cultured 24 h in medium supplemented with LDL revealed inhibition of cathepsin B activity at concentrations of 250 micrograms LDL/ml medium, lower LDL concentrations were without apparent effect. Since the glomerular accumulation of structural and nonstructural proteins plays an important role in glomerulosclerosis, we conclude that the augmented proteolytic activity of mesangial cells might be one of the pathways located by which hyperlipidemia causes an increased susceptibility to glomerular damage.

Animals↗
PubMed1995

Virtual reality modeling language in chemistry.

A new concept in the field of molecular modeling using the information transfer mechanism of the World Wide Web (WWW) is presented. The Virtual Reality Modeling Language (VRML) provides an object-oriented method for the description of molecular models. The structure and capabilities of this new language are introduced. It is shown that the transport of molecular models over the WWW using VRML is a very efficient and powerful method for the exchange of molecular information.

Computer Communication Networks↗
PubMed1995

Prevention of cardiac hypertrophy in experimental chronic renal failure by long-term ACE inhibitor administration: potential role of lysosomal proteinases.

The pathogenesis of cardiac hypertrophy in chronic uremia is poorly understood. In the present study, the long-term effects of chronic uremia on cardiac morphology and various cysteine proteinases of the heart were investigated in rats with and without antihypertensive therapy by the angiotensin converting enzyme inhibitor enalapril or by the calcium channel blocker verapamil. 16 weeks after subtotal nephrectomy considerable uremia had developed associated with arterial hypertension, rise in heart weight and heart weight/body weight ratio. Morphologically myocardial cells developed marked hypertrophy. Determination of various cysteine proteinases by fluorometry revealed a significant decline of cathepsin B activity while the activities of cathepsin H and L were unchanged. Antihypertensive treatment with enalapril and verapamil normalized the blood pressure and improved renal function significantly. Myocardial cell hypertrophy and the enhanced heart weight/body weight ratio were normalized under treatment with enalapril but not with verapamil. Simultaneously, the impaired cathepsin B activity returned to the normal range after enalapril treatment. It is concluded that the cardiac hypertrophy in uremia is at least partly caused by an activation of the circulating and/or cardiac renin-angiotensin system. Impaired proteinase activity in the uremic state may be involved in the development of cardiac hypertrophy.

Animals↗
PubMed1995

Insulin-like growth factor I induced reduction in cysteine proteinase activity in freshly isolated proximal tubule cells of the rat.

The potential effects of insulin-like growth factor I (IGF-I) on lysosomal cysteine proteinases (cathepsin B, H and L+B activities) were investigated in the freshly isolated proximal tubule cells of rats. IGF-I significantly inhibited these enzyme activities after an incubation time of 80 min. This effect was associated with a dose-dependent increase in cellular protein content. The study suggests that, besides the established enhanced protein synthesis, IGF-I-induced cellular hypertrophy is mediated by a suppression of the proteolytic enzyme activity in proximal tubular cells.

Animals↗
PubMed1994

Renal proteinases and kidney hypertrophy in experimental diabetes.

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 tubulo-interstitium. 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/microgram DNA) and cathepsin L+B activity (streptozotocin: 6.7 +/- 0.8 vs control: 9.3 +/- 0.7 U/microgram DNA) were significantly decreased. Insulin treatment completely prevented the decline in glomerular proteinase activity (gelatinase: 37 +/- 6 mU/microgram DNA; cathepsin L+B: 9.6 +/- 0.9 U/microgram 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/microgram 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.

Animals↗
PubMed1994

Lovastatin ameliorates depressed intraglomerular proteolytic activities in experimental nephrotic syndrome.

Lipid abnormalities have been implicated in the pathogenesis of glomerulosclerosis in experimental models of kidney disease. In previous studies it has been shown that Adriamycin-induced nephropathy is associated with reduced activities of glomerular proteinases. This observation led to the hypothesis that reduced proteolytic activities may be responsible for mesangial protein accumulation, which ultimately leads to global sclerosis of the glomerular tuft. The aim of the present study was to investigate whether lovastatin treatment, which prevents progressive glomerulosclerosis in experimental nephrotic syndrome, would also have an effect on glomerular proteinase activities. Adriamycin administration resulted in a persistent nephrotic syndrome with gross proteinuria (377 +/- 26 mg/24 h), hypoalbuminemia (2.1 +/- 0.12 vs. 2.8 +/- 0.02 g/dl), hypercholesterolemia (575 +/- 74 vs. 68 +/- 1.5 mg/dl) and elevated triglyceride levels (1,155 +/- 78 vs. 57 +/- 8 mg/dl). Glomerular azocaseinolytic activities both at pH 5.4 (-21%) and 7.4 (-37%) were significantly reduced. In contrast to human subjects, nephrotic rats that were treated with lovastatin displayed reduced triglyceride levels (767 +/- 134 mg/dl); their serum cholesterol, however, remained unchanged. In terms of glomerular proteolytic enzyme activities, the decline in azocaseinolysis at both pH values was, at least partly, prevented by lovastatin. On the basis of these data, it appears that the beneficial effect of lovastatin on the evolution of glomerulosclerosis in the nephrotic rat is associated with the conservation of glomerular proteolytic activities.

Albuminuria↗
PubMed1994

Texture mapping: a new tool for molecular graphics.

The real-time texture mapping capabilities of modern graphics workstations are explored with respect to their applications in a variety of relevant scenarios in interactive molecular modeling techniques. The common usage of texture mapping to reduce geometric complexity while enhancing realism is extended, opening new ways to visualize large amounts of molecular data in a comprehensive fashion. Thus, texture mapping may be employed to (1) display and filter multichannel information of structural properties on molecular surfaces, (2) improve the quality and accuracy of highly complex isodensity contours, (3) increase the rendering speed of space-filling atomic representations by two orders of magnitude and (4) apply volume-rendering techniques to large, three-dimensional density distributions in real time. Implementation of these novel techniques requires only moderate modifications or extensions to existing molecular modeling applications.

Computer Graphics↗
PubMed1994

The aging rat kidney displays low glomerular and tubular proteinase activities.

The present study was conducted to investigate the relationship of age-related changes in renal function and structure with changes in glomerular and tubular proteinase activities in young (3 weeks), mature (3 months), and older (18 months) male Wistar rats. Glomerular filtration rate, expressed per 100 g body weight, remained unchanged during adolescence, but declined significantly (-44%) in aging animals. In parallel, albuminuria, which was barely detectable in young and mature rats, increased almost 10-fold in the aging animals. In comparison to young animals, the kidney weight in aging rats was 10-fold higher, signifying considerable tubular hypertrophy. The glomerular protein to DNA ratio increased by almost 70%, suggesting deposition of mesangial matrix within the glomerulus. These structural changes were associated with significant reductions in glomerular cysteine and metalloproteinase activities in the adolescent and older animals. Similarly, lower activities of both types of proteinases were observed in isolated proximal tubules. This behavior of proteolytic enzyme activities in the aging rat kidney corresponds well to the 10-fold increase in kidney weight (proximal tubular hypertrophy) and to the enhanced deposition of glomerular matrix. This study suggests a causal involvement of renal cysteine proteinases and metalloproteinases in the protein accumulation of the aging rat kidney.

Aging↗
PubMed1994

Human chronic kidney allograft rejection is accompanied by increased intraglomerular cathepsin B and L activity.

The major reason for late graft losses is chronic rejection. Recently, a large number of studies have indicated that proteolytic enzymes play an important role as mediators of glomerular injury. The cysteine proteinases cathepsins B and L degrade structural matrix proteins such as type I collagen and laminin. We investigated intraglomerular protease activities in 12 patients after kidney graftectomy because of end-stage renal disease following chronic rejection. A group of 12 patients undergoing nephrectomy because of cancer served as controls using only non-involved parts of the kidney. The activities of cathepsins B and L in homogenates of isolated glomeruli were measured fluorometrically methylcoumarylamide substrates and related to DNA content. In rejected kidney allografts we observed significantly enhanced intraglomerular cathepsin B activity and cathepsin B + L activity.

Adult↗
PubMed1994

Effect of metabolic acidosis on tubular proteinase activity.

Metabolic acidosis is a well-known mediator of compensatory renal hypertrophy; however, the underlying mechanism is still poorly understood. The aim of the present study was to investigate whether metabolic acidosis can influence the proteolytic activity in the proximal tubule. Metabolic acidosis was induced in rats by 0.28 M NH4Cl which was mixed to drinking water. The development of metabolic acidosis was documented by a significant increase in urinary pH. After 11 days of 0.28 M NH4Cl treatment, the experimental animals developed mild proteinuria (9.52 +/- 0.99 versus 17.65 +/- 1.63 mg/day). The kidney weight increased significantly (1,653.56 +/- 27.84 versus 1,753.33 +/- 56.11 mg) and tubular proteinase activity, measured at pH 5.4, was markedly reduced (60.3 +/- 1.2 versus 52.2 +/- 2.4 U/mg protein, or 2,105.5 +/- 92.0 versus 1,631.0 +/- 97.2 mU/micrograms DNA). In summary, these results suggest that compensatory renal hypertrophy induced by metabolic acidosis might at least partly be due to the suppression of tubular proteinase activity.

Acidosis, Renal Tubular↗
PubMed1993

[Acute pancreatitis and stomach wall necrosis caused by cholesterol embolisms].

A 60-year-old man was hospitalized because of a sudden onset of severe pain in the epigastrium and haematemesis. Acute pancreatitis was diagnosed on the basis of an increased serum amylase concentration (642 U/l). Abdominal ultrasound and computed tomography demonstrated a necrotic zone with central liquefaction in the tail of the pancreas adjoining the stomach wall. Gastroscopy revealed as source of the bleeding an extensive mucosal necrosis at the greater curvature of the stomach. At laparotomy, partial resection of the pancreas, gastrectomy and splenectomy were performed. Histological examination of the resected specimens showed multiple cholesterol emboli in the small arteries of the pancreas and the gastric submucosa.

Acute Disease↗
PubMed1992

Intraglomerular proteinase activity in adriamycin-induced nephropathy.

Adriamycin (ADR)-induced nephropathy is characterized by focal and segmental glomerulosclerosis and is supposed to be an ideal model of chronic progressive renal disease. The aim of our study was to investigate whether there might be an altered activity of glomerular proteinases in ADR nephropathy, thereby aggravating glomerular protein accumulation as an important initiating hallmark of glomerulosclerosis. In fact, we could demonstrate significantly enhanced levels of intraglomerular protein and DNA content in the experimental animals at week 7, 12 and 22 after administration of ADR. When relating intraglomerular proteinase activity, which was measured in ultrasonically destroyed isolated glomeruli, obtained by differential sieving techniques, to the intraglomerular protein and DNA content, this enzyme activity was significantly reduced throughout the observation period. Based on these data, we suggest that this relatively decreased proteinase activity in glomeruli exposed to ADR might play a pathogenetic role in the development of glomerular hypertrophy, an important harbinger of glomerulosclerosis.

Animals↗
PubMed1992

Effect of disease on glomerular proteinases.

Up to now, little is known about the self-perpetuating mechanism leading to terminal renal failure in chronic renal disease. The common pathological feature of progressive renal insufficiency is focal and segmental glomerulosclerosis. The experimental counterpart of this process is represented for instance by the models of streptozotocin diabetes, Adriamycin nephropathy and Goldblatt hypertension. In fact, the main initiating hallmark of glomerulosclerosis is an accumulation of glomerular proteins, whose balance is apparently influenced by the activity of glomerular proteinases. In isolated glomeruli of kidneys from the experimental animals, the total proteinase activity was assayed with the unspecific but sensitive azocasein assay. In fact, the activity was significantly reduced in all experimental models at acid and neutral pH when relating enzyme activity to the glomerular protein and DNA content. We believe, that our data of reduced glomerular proteinase activity in the animal models of glomerulosclerosis represent perhaps a new additional common pathogenetic mechanism. The glomerular protein accumulation could be a result of a synergistical interaction between hemodynamic factors and biochemical ones; the latter, we suggest to be a decrease of glomerular proteinase activity.

Animals↗
PubMed1992

Effect of dietary protein on glomerular proteinase activities.

Recent studies suggest that proteolytic enzymes are involved in the degradation of extracellular matrix components of the renal glomerulus. In the present study, the effects of feeding 3 different protein diets on glomerular cysteine proteinase and metalloproteinase activities to healthy rats for 6 weeks were examined. The diets contained 5, 20, or 60% casein and were made isocaloric by starch. On sacrifice, the glomeruli were isolated by differential sieving. Proteolytic activities were measured using fluorogenic substrates and were expressed per glomerular DNA content. Body weight was virtually unchanged by the amount of protein ingested, whereas kidney weight was closely correlated with dietary protein content (5%: 1,625 +/- 324; 20%: 2,110 +/- 326; 60%: 2,705 +/- 910 mg). Activity of cathepsin B, the most abundant cysteine proteinase in the glomerulus, decreased with protein loading (5%: 1,498 +/- 110; 20%: 1,321 +/- 82; 60%: 914 +/- 84 pmol/min/micrograms DNA). The same pattern emerged with cathepsin L (5%: 869 +/- 71; 20%: 846 +/- 70; 60%: 517 +/- 83 pmol/min/micrograms DNA) and cathepsin H (5%: 498 +/- 45; 20%: 478 +/- 55; 60%: 330 +/- 39 pmol/min/micrograms DNA). The differences between the 20 and 60% groups were statistically significant for all 3 cathepsins measured. The intraglomerular activity of the metalloproteinase collagenase declined significantly with the amount of protein ingested (5%: 233 +/- 14; 20%: 189 +/- 13; 60%: 137 +/- 11 microU/micrograms DNA). Gelatinase activity also fell as protein intake increased (5%: 183 +/- 18; 20%: 115 +/- 10; 60%: 94 +/- 11 F/micrograms DNA).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Fibronectin metabolism in isolated glomeruli from obese Zucker rats.

The obese Zucker rat develops non-immune-mediated spontaneous focal glomerulosclerosis. Mesangial matrix expansion is an important initiating hallmark of such glomerular damage and fibronectin is a normal constituent of mesangial extracellular matrix. Using a quantitative method based on enzyme immunoassay, we have 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 than in the control animals. Furthermore, proteinase activity against fibronectin was significantly reduced in the glomeruli of obese Zucker rats compared to the control animals. 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. We speculate that this result might indicate a possible mediator of progressive glomerulosclerosis in this animal model.

Animals↗