Search PubMed⌕ Search

Biomedical subjects

G Friedlander

Publications and source records attributed to G Friedlander.

119 records · Page 7Linked to original sources
PubMed1983

PGE2 binding sites and PG-stimulated cyclic AMP accumulation in rat isolated glomeruli and glomerular cultured cells.

[3H]PGE2 specifically bound to isolated glomeruli. The KD value and the number of sites were 80 nM and 528 fmoles/mg respectively. PGE1 and PGE2 resulted in equipotent inhibition of binding whereas PGI2 was markedly less active. It was not possible to demonstrate specific receptors for PGE2 in glomerular mesangial and epithelial cultured cells. PGE1, PGE2 and PGI2 (0.1-100 microM) stimulated cyclic AMP concentration both in isolated glomeruli and glomerular cultured cells. Basal cyclic AMP in epithelial cells was greater than in mesangial cells or glomeruli. The cyclic AMP accumulation in the presence of PGs was greatest in mesangial cells. Maximum stimulation was in the range 300-1400%. For the three preparations, PGE2 and PGE1 produced a greater effect than PGI2. ED50 values were identical for PGE1 and PGE2 (5 microM for epithelial cells and glomeruli, 20 microM for mesangial cells). ED50 value for PGI2 were lower than those for PGE1 or PGE2 (0.2, 2 and 5 microM for glomeruli, epithelial cells and mesangial cells, respectively). The effects of the three PGs were not additive when tested at maximally effective concentrations. These results demonstrate that PGE1, PGE2 and PGI2 stimulate glomerular and cellular cyclic AMP. A relationship between [3H]PGE2 binding sites and this biological effect has not been established. The physiological events secondary to the increase in glomerular cyclic AMP are also yet to be determined.

Animals↗
PubMed1981

[Bacterial endocarditis in drug addicts. 20 cases (author's transl)].

The authors report on 20 cases of bacterial endocarditis in heroin addicts, i.e. 9.1% of all cases of that infection observed over an 8-year period. The disease involved the tricuspid valve in 80% of the cases and was due to Staphylococcus aureus in the same percentage of patients. Diagnosis was sometimes difficult in the right heart but was confirmed by repeated echocardiography. Combined antibiotic therapy was administered for 45 days. Only one patient died of relapsing endocarditis on valve prosthesis. Six patients were operated upon: 2 for cardiac failure, 2 for persistent infection and 2 for recurrent pulmonary embolism. Three patients underwent valve replacement and 3 tricuspidectomy. The persistence of pulmonary embolism after eradication of the infecting organism does not seem to warrant surgery.

Adult↗
PubMed1977

[Activities of pulmonary phospholipases of fetal rats. Variations during development].

Turnover of adult rat lung phospholipids implies intervention of phospholipases. This work clearly demonstrates: There is in fetal or adult rat lung an inactive form of phospholipase that is convertible to an active form by the action of lysed platelets. An increase of both active and inactive forms of the fetal enzyme with gestational age. The fact that an important part of these activities, at the time of birth, are in the inactive form implies a control mechanism affecting levels of each form of lung phospholipases. These data are discussed in relation to the possible role of the lung phospholipases in Respiratory Distress Syndrome.

Aging↗
PubMedDate not supplied

Pathophysiology of middle ear epithelium: a new role for prostaglandin E2.

INTRODUCTION: Otitis media with effusion is a disease of the middle ear epithelium resulting from a decreased sol layer as well as increased mucus secretion and plasma-derived protein transudation, which causes mucus plugging. Because the epithelium keeps the middle ear cavities fluid-free and air-filled, we investigated its fluid transport capacities, which may be involved in both efficacy of the mucociliary clearance and drying-out of the posterior ear cavities (Yen PT et al: Acta Otolaryngol (Stockh) 113, 1993). We have established the absorptive capacity of middle ear epithelial cells in primary culture (Herman P, et al: Am J Physiol 262, 1992). However, the paucity of cells obtained by enzymatic digestion led us to develop a new model for further investigation of middle ear epithelial cell. METHODS: We established a middle ear cell line (MESV) using simian virus 40 (SV40) infection of middle ear epithelial cells from the Mongolian gerbil. RESULTS: Investigation of the transport processes using the short-circuit current technique showed that MESV cells retain most characteristics of the original middle ear epithelial cells. Transepithelial sodium transport from the apical to the basal side was responsible for the transepithelial lumen-negative potential difference. CONCLUSION: The presence of high concentrations of prostaglandin E2 in the middle ear effusions has been documented. This work investigates the effect of prostaglandin E2 on the rate of transepithelial ion transport of MESV cells. Prostaglandin E2 increased the rate of electrogenic sodium transport by means of increase in the intracellular cyclic adenosine monophosphate (cAMP) content. Such a modulation of sodium transport in the course of otitis media could be responsible for the reduced periciliary sol layer that impairs the mucociliary clearance.

Animals↗
PubMedDate not supplied

Regulation of phosphate transport in the renal tubule through parathyroid hormone receptor: unexpected pathways.

The recent molecular identification of parathyroid hormone (PTH) receptors, on the one hand, and Napi cotransporters, on the other hand, has enabled the development of powerful tools to boost the study of the regulation of renal Pi transport by PTH, a regulation which stands at a crucial point in the physiology and pathophysiology of Pi homeostasis. The aim of this review is to summarize these recent findings.

Animals↗
PubMedDate not supplied

Renal tubular cells cultured from genetically modified animals.

The culture of renal tubular cells from genetically modified animals opens the opportunity of biochemical, cell biology and physiological studies under strictly controlled conditions. Either primary cultures or cell lines can be used. Through two examples of primary cultures of proximal tubular cells obtained from knock-out mice, important information about the function of proteins were obtained. Mice lacking vimentin, an intermediate filament normally reexpressed in tubular cells during regeneration and culture, have a normal tubular function under basal conditions. Proximal cells grown from these animals exhibit a defect in sodium-glucose cotransport activity, most likely related to alterations in the dimer/monomer ratio of the transporter in the apical membranes. These alterations may be important in terms of tubular function during the recovery phase following acute tubular necrosis. The situation is strikingly different with regard to mice lacking HNF-1, a transactivator involved in the transcription of multiple genes. These animals suffer from severe Fanconi syndrome related to decreased expression of proximal transporters including isoforms of sodium-glucose (SGLT2) and sodium-phosphate (NPT1) cotransporters. Whereas transport defects are observed in isolated tubules, they are no longer apparent in cultured proximal cells because the expression of these isoforms is suppressed under culture conditions. These observations illustrate the interest and limits of the in vitro models for studying renal function in transgenic animals.

Animals↗
PubMedDate not supplied

Sodium restriction decreases AP-1 activation after nephron reduction in the rat: role in the progression of renal lesions.

Renal hyperplasia and hypertrophy are early events after nephron reduction which precede progressive destruction of the remnant kidney. Restriction of dietary sodium content was shown to reduce renal lesions following nephron reduction. AP-1 is a transcription factor, resulting from heterodimerization of fos and jun proteins, which mediates the effects of mitogenic growth factors. To elucidate the role of AP-1 in growth processes involved in renal deterioration, we evaluated whether restriction of dietary sodium content (0.25 vs. 0.50% sodium w/w) affected AP-1-DNA binding and hyperplasia in the remnant kidney after nephron reduction (70% nephrectomy). Cell proliferation, evaluated by PCNA immunostaining, increased progressively from day 7 to day 60 in glomeruli, proximal and distal tubules and loops of Henle of nephrectomized (Nx) rats compared to control sham-operated (C) animals. AP-1-DNA binding activity increased 7 and 14 days after surgery, but it was reduced below C values at day 60. c-fos and c-jun expression were also reduced in Nx rats at day 60. Sodium restriction significantly reduced the number of PCNA-stained cells in glomeruli and tubules at days 14 and 60, but not at day 7, whereas it decreased AP-1 activation at all times of the study. This effect was associated to a marked reduction of renal lesions in Nx rats. In conclusion, we showed that, after nephron reduction, the beneficial effect of sodium restriction was associated with a reduction of hyperplasia and AP-1 activation, but that the latter did not parallel delayed cell proliferation rate in remaining nephrons. Thus, we propose that different transduction pathways are involved in cell proliferation after nephron reduction, according to the time of evolution of renal lesions.

Animals↗
PubMedDate not supplied

Extracellular ATP modulates ion transport via P2Y purinoceptors in a middle-ear epithelial cell line.

Mucus and cellular debris are eliminated from the middle-ear cavity through the E-tube by the mucociliary system. Depth of the periciliary fluid layer is thought to be regulated by epithelial ion transport activity. Since impairment of the mucociliary system is a key step in the development of otitis media with effusion, we investigated the ion transport mechanisms of the middle-ear epithelium using the middle-ear MESV cell line. ATP has been shown to modulate ion transport as well as various cellular functions in several cell types via purinoceptors. In order to investigate a possible modulation of the transport activity of MESV cells, we evaluated short-circuit current (Isc) changes in response to specific stimulation of putative purinoceptors by ATP and its various analogs. ATP dramatically increased Isc, while adenosine had no effect, thus demonstrating the presence of P2 receptors according to the original classification by Burnstock. The rank order of potency of purinoceptor agonists for stimulation of Isc on the apical side (ATP > UTP > gamma-SATP >> beta-SADP > 2-methylthio-ATP, 2MeSATP > beta, gamma-methylene-ATP, beta,gamma-MeATP) and on the basolateral side (ATP > gamma-SATP > UTP >> beta-SADP > 2 MeSATP > beta,gamma-MeATP), along with studies using selective antagonists and intracellular calcium measurements are consistent with a P2Y receptor subtype. The ATP-induced increase in Isc was related to sodium transport. This modulation might be of importance in stress conditions such as inflammation.

Adenosine Triphosphate↗
PubMedDate not supplied

[Inhibitors of HMG CoA reductase: new modes of action, new indications?].

3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors, or statins, are hypocholesterolaemic agents used in the treatment of hypercholesterolaemia and cardiovascular diseases. Their hypocholesterolaemic action results from the inhibition of the intracellular synthesis of cholesterol via the mevalonate pathway. Recent studies have demonstrated that cholesterol is not the only intracellular target of statins. Indeed, statins have been shown to inhibit protein isoprenylation, a post-translational modification involved in membrane localization and protein activity. By inhibiting isoprenylation of Ras protein, statins induce the inhibition of the Ras-AP1 pathway and the decrease in cell proliferation. Similarly, inhibition of Rho protein insoprenylation leads to the disorganization of the cytoskeleton and the induction of the fibrinolytic system. All these effects need to be confirmed in vivo and in the human, and open new areas for these therapeutics agents.

Anticholesteremic Agents↗