Biomedical subjects

G Zahner

Publications and source records attributed to G Zahner.

30 records · Page 2Linked to original sources

PubMed1996

Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury.

To study whether prostaglandins (PG) can regulate the mRNA expression of monocyte-chemoattractant protein 1 (MCP-1) in glomerular immune injury, MCP-1 mRNA levels were evaluated in anti-thymocyte antibody (ATS) -induced glomerular injury by Northern blotting and reverse transcription-polymerase chain reaction. Immune injury was induced in vivo by the intravenous application of ATS to male Wistar rats and in vitro by the perfusion of isolated rat kidneys with ATS and rat serum. In vivo 3 h and 5 days after antibody application, glomerular mRNA expression of MCP-1 was markedly enhanced compared with controls. In the isolated perfused kidney, antibody and complement also induced an increase in MCP-1 expression at 10 min and 60 min after antibody perfusion. When the rats were treated with PGE (250 micrograms, twice daily), the increase in MCP-1 expression was reduced. This was associated with a reduction of intraglomerular recruitment of monocytes/macrophages. In the isolated perfused kidneys, PGE1 (1 mg/L) prevented the antibody- and rat serum-stimulated increase in glomerular MCP-1 mRNA expression. These data demonstrate that PGE1 reduces glomerular MCP-1 mRNA expression in glomerulonephritis and in the isolated perfused rat kidney after induction of immune injury with antibody and complement. The data suggest that prostaglandins might mediate MCP-1 effects in glomerular immune injuries.

Alprostadil↗

PubMed1995

Angiotensin II-stimulated expression of transforming growth factor beta in renal proximal tubular cells: attenuation after stable transfection with the c-mas oncogene.

Angiotensin II (Ang II) stimulates cellular hypertrophy of cultured murine proximal tubular cells (MCT cells). This Ang II-mediated hypertrophy depends on the endogenous induction and autocrine action of transforming growth factor-beta (TGF-beta). We have previously demonstrated that permanent transfection of MCT cells with the c-mas oncogene, whose protein product encodes a serpentine receptor-like moiety coupled to G proteins without an hitherto identified ligand, changes the hypertrophic actions of Ang II into a proliferative response (Am J Physiol 263: F931-F938, 1992). The present study demonstrated that Ang II failed to stimulate induction of TGF-beta 1 protein in c-mas transfected MCT cells under the control of SV 40 promoter/enhancer (pSV2mas) as measured by mink cell bioassay and specific ELISA for TGF-beta 1. Moreover, in contrast to either wild-type MCT cells or to cells permanently transfected with the SV 40 based expression plasmid only (pSV2 cells), Ang II stimulated gene transcription and mRNA expression of TGF-beta 1 were decreased in c-mas transfected cells. Our findings demonstrate that the Ang II-induced proliferation of c-mas transfected MCT cells most likely depends on failure of TGF-beta 1 induction in these cells. c-mas transfected cells are a useful tool to further investigate the complex relationships between activation of second messengers subsequent to binding of Ang II to AT1-receptors and gene regulation like transcription of TGF-beta 1.

Angiotensin II↗

PubMed1995

ANG II is a mitogen for a murine cell line isolated from medullary thick ascending limb of Henle's loop.

A murine SV40-transformed renal epithelial cell line derived from medullary thick ascending limb of Henle's loop (MTAL) was established and characterized by morphology, antigen expression, and biochemical criteria. These MTAL cells express a single class of high-affinity receptors for angiotensin II (ANG II) and transcripts for the AT1 subtype of ANG II receptors. ANG II, in a dose-dependent manner, induced proliferation of MTAL cells. This observation is in striking contrast to syngeneic proximal tubular cells in which it was previously shown that the peptide induced cellular hypertrophy and slightly inhibited proliferation [G. Wolf and E. G. Neilson. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28: F768-F777, 1990]. The AT1-receptor antagonist losartan (10(-6) M), but not an AT2-receptor antagonist, blocked the mitogenic effects of ANG II in MTAL cells. Coincubation of quiescent MTAL cells with ANG II and 5% fetal calf serum further increased proliferation compared with cells grown only in serum. In contrast to proximal tubular cells, ANG II failed to induce transforming growth factor-beta 1 mRNA and protein synthesis in MTAL cells. Our data collectively suggest that ANG II is a mitogen for MTAL cells in vitro. Therefore, epithelial cells derived from different parts of the nephron, even when transformed with SV40 virus and while under cell culture conditions, exhibit a distinct pattern of growth behavior after stimulation with ANG II.

Angiotensin II↗

PubMed1994

The effect of prostaglandin E2 on mRNA expression and secretion of collagens I, III, and IV and fibronectin in cultured rat mesangial cells.

The possible role of prostaglandin E2 (PGE2) on the formation of collagens and fibronectin in cultured rat mesangial cells (MC) was studied. The effect of exogenous PGE2 was analyzed by the measurement of steady-state mRNA levels of the extracellular matrix components and by the secretion of these matrix components into cell culture supernatants. PGE2, in a dose-dependent manner, reduced mRNA levels of alpha 1(I) and alpha 1(III) procollagens but had little effect on alpha 1(IV) procollagen and fibronectin mRNA. In addition to its role on mRNA levels, PGE2 reduced the secretion of all studied collagen types into the cell culture supernatants. To evaluate a possible role of intracellular cAMP in the mediation of the PGE2 effects, MC were incubated with the cAMP analogue 8-bromo-cAMP (8brcAMP). In contrast to PGE2, 8brcAMP (1 mM) had no effect on mRNA expression of procollagen Types I and III over the studied time period (1 to 48 h). Furthermore, 8brcAMP stimulated collagen secretion into the cell supernatant after 48 h of incubation. These data demonstrate that PGE2 reduces mRNA levels of procollagen Types I and III in cultured MC, although the biosynthesis of all studied extracellular matrix components is inhibited. These alterations seem to be independent of intracellular cAMP, because the cAMP analogue 8brcAMP does not mimic the PGE2 effects on steady-state mRNA expression and collagen secretion of the studied extracellular matrix components.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

TGF-beta stimulates rat mesangial cell proliferation in culture: role of PDGF beta-receptor expression.

Transforming growth factor (TGF)-beta is known to increase mesangial cell (MC) matrix; however, its possible role on MC proliferation is controversial. We therefore studied the influence of TGF-beta on MC proliferation in culture and evaluated its effect on the platelet-derived growth factor (PDGF) B-chain as well as the expression of the PDGF beta-receptor. TGF-beta (1 ng/ml) increases MC DNA synthesis by approximately threefold after 48 h of incubation. TGF-beta-induced MC proliferation was also confirmed by cell counts. A neutralizing anti-TGF-beta antibody completely blocked this growth promoting activity. The levels of PDGF beta-receptor steady-state mRNA were increased by TGF-beta at 48 h. This was associated with an increase in receptor density per cell as measured by receptor kinetic studies. PDGF B-chain mRNA was also increased by TGF-beta at 48 h. A neutralizing anti-PDGF B-antibody causes no reduction of TGF-beta-induced DNA synthesis; however, suramin completely inhibited the mitogenic effect of TGF-beta. We conclude that TGF-beta stimulates MC growth in long-term culture, a process in which upregulation of the PDGF beta-receptor and enhanced synthesis of PDGF B-chain might be involved.

Animals↗

PubMed1993

Angiotensin II stimulates cellular hypertrophy of LLC-PK1 cells through the AT1 receptor.

We have investigated possible growth-promoting effects of angiotensin II (ANG II) in the pig tubular epithelial cell line LLC-PK1. 10(-6)-10(-10) M ANG II inhibited proliferation as measured by [3H]thymidine incorporation. However, the same concentration of peptide induced tubular hypertrophy as assessed by increases in de novo protein synthesis, total protein, and RNA content. These effects were mediated through AT1 receptors. Furthermore, LLC-PK1 cells exhibited specific binding sites for ANG II and expressed mature mRNA for the vascular smooth muscle AT1 receptor. ANG II incubation of cells significantly lowered intracellular cAMP, and the hypertrophogenic action of ANG II was abolished by co-incubation with the relative stable analogue dibutyryl-cAMP, suggesting the involvement of intracellular nucleotides in the signal-transduction processes leading to hypertrophy. Our results collectively suggest that ANG II is a hypertrophogenic growth factor for LLC-PK1 cells. Considering the importance of tubular hypertrophy in the progression of renal failure in many models, strategies to block the action of ANG II on tubular cells may offer an attractive alternative way to control deterioration of renal function besides modulation of haemodynamics.

Angiotensin II↗

PubMed1992

Rated performance, cardiovascular and quantitative EEG parameters during simulated instrument flight under the effect of terfenadine.

In a double-blind placebo-controlled randomized two-phase cross-over study comprising 10 (5/5) male subjects the effect of oral therapeutic doses of terfenadine (Teldane, CAS 50679-08-8) on rated performance, systolic and diastolic blood pressure, heart rate and the electroencephalogram of the subjects in an instrument flight (IF) procedure trainer was investigated. Terfenadine did not influence systolic and diastolic blood pressure, heart rate and the specific performance of subjects during instrument flight procedures. Under terfenadine the quantitative EEG (qEEG) showed more %alpha, especially %alpha 2 during rest and to a lesser extent during instrument flight procedures of the subjects. As a result the vigilance dynamics was increased. In the %beta band especially %beta 2 was increased only during instrument flight activities. The ratio theta/alpha was reduced during rest and during activities. Thus all these quantitative EEG indicators do not show a decrease in the level of vigilance nor are they indicative of signs of drowsiness during rest and during instrument flight activities under terfenadine. The results are discussed.

Adult↗

PubMed1988

Platelet monoamine oxidase activity and tardive dyskinesia.

A few studies of chronic psychiatric inpatients have reported an inverse association between platelet monoamine oxidase (MAO) activity level and tardive dyskinesia (TD). In contrast to these earlier findings, we found no significant or consistent association between platelet MAO activity level and TD occurrence when we controlled for other TD predictors in a case-control study of 80 outpatients maintained on neuroleptic medications. We did find, however, that black subjects had significantly lower levels of MAO activity than did whites in an analysis controlling for age, sex, and neuroleptic dose.

Adult↗

PubMed1987

Serum dopamine beta hydroxylase activity and tardive dyskinesia.

A case-control study was done to test the effect of serum dopamine-beta-hydroxylase (DBH) activity on tardive dyskinesia (TD) among 85 schizophrenic outpatients treated with neuroleptics. In contrast to the results of several previous studies, we found no significant association between serum DBH activity and the occurrence or severity of TD, controlling for other TD predictors.

Adult↗

PubMed1986

[Comparative in-flight study of a scopolamine-containing membrane plaster versus dimenhydrinate under defined acceleration conditions].

The efficacy and tolerability of Scopoderm TTS (SCOTTS), a transdermal system containing scopolamine, were compared with those of the oral antiemetic dimenhydrinate (double-dummy technique) in a controlled, double-blind, within-patient study including 20 test persons with proven motion sickness. During a 1-h test flight, SCOTTS proved to be as effective as dimenhydrinate. The efficacy and tolerability of both SCOTTS and dimenhydrinate were assessed as to be equally good. Due to its galenic properties, SCOTTS is effective over a 72-h period and therefore is useful in the prevention of motion sickness during long-distance flights, where it is superior to dimenhydrinate.

Acceleration↗

PubMedDate not supplied

Glomerular mRNA expression of angiotensinase A after renal ablation.

The local concentration of angiotensin II (ANG II) in the renal microenvironment is not only controlled by the generation of this peptide but also by its enzymatic degradation. Angiotensinase A (ATA; aminopeptidase A, A.C.3.4.11.7) is a major exopeptidase of the glomerulus involvement in the metabolism of ANG II. We studied the glomerular mRNA levels of ATA in a remnant kidney model 1-12 weeks after 1 1/3 nephrectomy. Functional parameters (systolic blood pressure and albuminuria) demonstrated the progression of renal disease in this model. Glomerular ATA enzyme activity significantly increased 1-5 weeks after nephrectomy and returned to control levels 12 weeks after ablation. In general, changes in steady-state mRNA expression for ATA were rather small. mRNA expression for ATA in isolated glomeruli as evaluated by northern blots was slightly increased 1 and 3 weeks after 1 1/3 nephrectomy but was suppressed 5 and 12 weeks after renal ablation compared to age-matched 2-kidney controls. Treatment of animals with the ACE inhibitor ramipril for 5 and 12 weeks partly inhibited the decrease in ATA transcripts after 1 1/3 nephrectomy and stimulated expression in 2-kidney controls whereas the ACE inhibitor decreased glomerular ATA enzyme activity in nephrectomized rats at 5 weeks. Isolated glomeruli from normal controls superfused with 10(-6) M ANG II for 60 min demonstrated no change in ATA transcripts. Our results show that ATA steady-state mRNA levels are slightly elevated early (1-3 weeks) after renal ablation, and are subsequently suppressed (5-12 weeks). ATA enzyme activity is also increased early and returned (12 weeks) to levels measured in age-matched 2-kidney controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

PubMedDate not supplied

Cyclosporin A induces transcription of transforming growth factor beta in a cultured murine proximal tubular cell line.

One pathological feature of chronic cyclosporin A (Cs-A) nephrotoxicity is striped interstitial fibrosis, the pathogenesis of which is not completely understood. We have previously reported that Cs-A directly stimulates the synthesis of various collagens in a cultured murine proximal tubular cell line (MCT cells). In addition, we have recently observed that Cs-A stimulates the synthesis of transforming growth factor beta (TGF-beta) in MCT cells. To this end, we investigated whether Cs-A directly stimulates transcription of TGF-beta in this cell line. A single dose of 2,000 ng/ml Cs-A stimulates the expression of TGF-beta1 transcripts in MCT cells. This stimulation is abrogated in the presence of 150 and 250 ng/ml actinomycin D without significantly influencing basal mRNA expression, suggesting that the increase in mRNA is due to stimulated transcriptional activity. Furthermore, nuclear runoff experiments demonstrate that Cs-A directly stimulates the transcriptional activity of the TGF-beta1 gene in MCT cells. The results of transient transfection of reporter gene constructs containing regulatory elements of the murine TGF-beta1 promoter into MCT cells and subsequent treatment with Cs-A further suggest direct effects of Cs-A on TGF-beta1 gene transcription. This is the first report demonstrating Cs-A-mediated TGF-beta1 gene transcription in renal cells. Considering the well-known profibrogenic effects of TGF-beta, our results suggest a novel mechanism of Cs-A nephrotoxicity.

Animals↗