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T Friedrich

Publications and source records attributed to T Friedrich.

142 records · Page 8Linked to original sources
PubMed1987

Bronchial and vascular effects of Paf in the rat isolated lung are completely blocked by WEB 2086, a novel specific Paf antagonist.

1 The effect of the platelet-activating factor (Paf) antagonist, WEB 2086, on Paf-induced increase of pulmonary artery perfusion pressure (Pp), bronchial inflation pressure (Pi) and wet-to-dry lung weight ratios (W/D) was investigated in the rat isolated lung. 2 Lungs were perfused with Krebs-Ringer solution (KRS) as controls or with KRS containing WEB 2086 (0.1, 1.0, 10.0 or 100 micrograms ml-1) and then injected with a bolus of 20 micrograms Paf. 3 A dose-related inhibition of the Paf-induced increase of Pp, Pi and W/D was observed, being almost maximal for the 10.0 micrograms ml-1 and complete for the 100 micrograms ml-1 doses of WEB 2086 when compared to controls. 4 It is concluded that WEB 2086 is a highly effective and specific Paf antagonist in the pulmonary vasculature and bronchial tract.

Animals↗
PubMed1986

Safety and efficacy of alinidine in symptom-free asthmatics.

Alinidine is a new bradycardic agent which has been shown to be beneficial in the treatment of coronary heart disease. Patients with both coronary heart disease and obstructive lung disease are difficult to treat, because the use of beta-blockers in them is greatly limited by their potential to provoke bronchospasm. Alinidine has no beta-blocking, muscarinic or quinidine-like properties. In a randomized double-blind cross-over study the heart rate reducing effect and safety of alinidine 40 mg p.o. has been examined in 12 symptom-free asthmatics. Alinidine significantly reduced mean heart rate from 81 +/- 10.5 beats/min to 65 +/- 9.7 beats/min two hours after administration. Forced expiratory volume in one second (FEV1), vital capacity (CV), airway resistance (Raw), functional residual capacity (FRC), and specific airway conductance (SGaw) were not affected. It is concluded that alinidine did not influence respiratory function in patients with bronchial hypersensitivity.

Adult↗
PubMed1986

Identification of the renal Na+/H+ exchanger with N,N'-dicyclohexylcarbodiimide (DCCD) and amiloride analogues.

Dicyclohexylcarbodiimide (DCCD) and the 5-ethyl-isopropyl-6-bromo-derivative of amiloride (Br-EIPA) have been used as affinity and photoaffinity labels of the Na+/H+ exchanger in rat renal brush-border membranes. Intravesicular acidification by the Na+/H+ exchanger was irreversibly inhibited after incubation of vesicles for 30 min with DCCD. The substrate of the antiporter, Na+, and the competitive inhibitor, amiloride, protected from irreversible inhibition. The Na+-dependent transport systems for sulfate, dicarboxylates, and neutral, acidic, and basic amino acids were inhibited by DCCD, but not protected by amiloride. An irreversible inhibition of Na+/H+ exchange was also observed when brush-border membrane vesicles were irradiated in the presence of Br-EIPA. Na+ and Li+ protected. [14C]-DCCD was mostly incorporated into three brush-border membrane polypeptides with apparent molecular weights of 88,000, 65,000 and 51,000. Na+ did not protect but rather enhanced labeling. In contrast, amiloride effectively decreased the labeling of the 65,000 molecular weight polypeptide. In basolateral membrane vesicles one band was highly labeled by [14C]DCCD that was identified as the alpha-subunit of the Na+,K+-ATPase. [14C]-Br-EIPA was mainly incorporated into a brush-border membrane polypeptide with apparent molecular weight of 65,000. Na+ decreased the labeling of this protein. Similar to the Na+/H+ exchanger this Na+-protectable band was absent in basolateral membrane vesicles. We conclude that a membrane protein with an apparent molecular weight of 65,000 is involved in rat renal Na+/H+ exchange.

Amiloride↗
PubMed1986

Effect of diltiazem on methacholine-induced bronchoconstriction in extrinsic asthmatics.

The protective effect of the calcium antagonist diltiazem on methacholine-induced bronchoconstriction was investigated in 19 extrinsic asthmatics. A double-blind cross-over design was used (diltiazem vs. placebo, administered orally for 1 week). We found no significant difference between the two treatment regimens when expressed as the provocation dose of methacholine causing a 20% drop in forced expired volume in 1 s (PD20 FEV1). Some individual patients might nevertheless gain some benefit from diltiazem as an additional treatment in difficult-to-manage asthma.

Adolescent↗
PubMed1985

Follow-up of prostaglandin plasma levels after acute myocardial infarction.

Prostaglandin plasma levels are elevated in patients with transient myocardial ischemia. We measured 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (B2(TXB2) in venous blood of 32 patients with myocardial infarction on the first, third, and seventh days. TXB2 and 6-keto-PGF1 alpha levels in these patients (up to 117 +/- 237 pg/ml and 96 +/- 105 pg/ml mean +/- SD, respectively) differed significantly from levels in normal control subjects (10 +/- 12 pg/ml and 4 +/- 7 pg/ml mean +/- SD, respectively) (p less than 0.01). Prostaglandin values remained elevated from day 1 through day 7. In most patients, 6-keto-PGF1 alpha levels prevailed over those of TXB2. In a subgroup suffering from cardiac arrhythmias, the ratio of 6-keto-PGF1 alpha/TXB2 was inverse. It is concluded that prostaglandin generation is increased for at least 7 days after myocardial infarction. A disturbed ratio of 6-keto-PGF1 alpha/TXB2 in favor of the latter might be associated with cardiac arrhythmias in myocardial infarction.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Properties of an anion exchanger in rat renal basolateral membrane vesicles.

Sulfate uptake in basolateral membrane vesicles from rat kidney cortexes was studied to test for the presence of an anion exchanger in these membranes. A pH difference (pHout = 6.4, pHin = 8.4) and a sodium gradient (out greater than in, pHout = pHin = 7.4) provided the driving force for intravesicular sulfate accumulation above the equilibrium content ("overshoot"). Sulfate uptake in vesicles preloaded with 25 mM of sulfate, thiosulfate, phosphate, chloride, or bicarbonate, or 10 mM of formate, acetate, L-lactate, pyruvate, p-aminohippurate, or oxalate was stimulated with respect to uptake in unpreloaded vesicles. Probenecid inhibited these trans stimulations. When the uptake of 0.1 mM labeled sulfate was determined in the presence of 5 mM of various anions in the incubation medium, cis inhibitions were observed when sulfate was driven by a proton gradient (out greater than in), a sodium gradient (out greater than in), or a p-aminohippurate gradient (in greater than out). All anions that trans stimulated sulfate uptake also showed a cis inhibition. Only small cis inhibitions were seen with maleate and succinate. No inhibition by any of the anions was found when sulfate uptake was studied in the absence of driving cation or anion gradients. Our data indicate a common exchanger for inorganic and organic anions that can additionally be driven by a sodium gradient and a pH difference. This exchanger may be involved in reabsorption and secretion of anions in the proximal tubule of the rat kidney.

Animals↗
PubMed1984

Pressure effects and uptake of platelet-activating factor in isolated rat lung.

The aim of this study was, first, to examine pressure effects of platelet-activating factor (PAF) on pulmonary vasculature and bronchi in isolated perfused and ventilated rat lungs and, second, to investigate pulmonary uptake of tritium-labeled PAF injected into the pulmonary artery. Four different perfusates were used: Krebs-Ringer solution (KRS) and KRS with 0.2, 2.0, and 4% albumin. In the KRS, perfusion and inflation pressure increased by 100 and 47%, respectively, after 100 micrograms PAF. By increasing the albumin concentration, the pressure effects were reduced significantly (P less than 0.01). These changes were paralleled by increasing tritium outflow rates (15.9 +/- 3.6, 49.7 +/- 12.5, 78.3 +/- 8.7, 87.8 +/- 2.6%, respectively). Comparable changes in tritium outflow rates (19.2 +/- 3.9, 38.2 +/- 7.2%) occurred when tracer amounts of labeled PAF were injected, but, in KRS with 2.0 and 4.0% albumin, tritium outflow was significantly lower (52.8 +/- 8.0 and 60.8 +/- 11.8%, respectively). Pressure effects are related to extraction rates. Both pressure effects and extraction rates depend on binding to the albumin in the perfusion medium used. PAF might act on smooth muscle tissue of the pulmonary vasculature. Inflation pressure increases are probably due to concomitant occurrence of edema.

Animals↗
PubMed1984

Prostaglandin production in patients with pulmonary embolism.

Release of prostaglandins (PG's) after experimental pulmonary embolism has been reported. Therefore, prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were determined in venous plasma of 21 patients with acute pulmonary embolism. Venous plasma levels were followed up for one week after admission. Arterial and mixed-venous PG levels were additionally determined in 6 patients with acute pulmonary embolism prior to pulmonary angiography. Venous levels were substantially elevated (PGE2 16-1300, PGF2 alpha 48-592, TXB2 1-247, 6-ketoPGF1 alpha 1-248 pg/ml), differing significantly from normal controls (p less than 0.001). PG's remained elevated throughout the 7-day postadmission study period. No significant arterial-venous PG differences were detected, though 6-keto-PGF1 alpha and TXB2 levels were somewhat higher in arterial blood. There was no correlation between clinical data (blood pressure, mean pulmonary artery pressure, etc.) and PG levels. These data suggest that elevated prostaglandin levels are probably not, or only in part, responsible for the cardiopulmonary changes that occur in patients with acute pulmonary embolism.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Functional mapping of the EcoRV DNA methyltransferase by random mutagenesis and screening for catalytically inactive mutants.

M.EcoRV is an alpha-adenine DNA methyltransferase. According to structure predictions, the enzyme consists of a catalytic domain, which has a structure similar to all other DNA-methyltransferases, and a smaller DNA-recognition domain. We have investigated this enzyme by random mutagenesis, using error-prone PCR, followed by selection for catalytically inactive mutants. 20 single mutants were identified that are completely inactive in vivo as His6- and GST-fusion proteins. 13 of them could be overexpressed and purified. All of these mutants are also inactive in vitro. 5 of the mutations are located near the putative binding site for a flipped adenine residue (C192R, D193G, E212G, W231R, N239H). All of these variants bind to DNA, demonstrating the importance of this region of the protein in catalysis. Only the W231R mutant could be purified with high yields. It binds to DNA and AdoMet and, thus, behaves like a bona fide active site mutant. According to the structure prediction Trp231 corresponds to Val121 in M.HhaI, which forms a hydrophobic contact to the flipped target cytosine. 4 of the remaining purified variants are located within a small region of the putative DNA-recognition domain (F115S, F117L, S121P, C122Y). F117L, S121P and C122Y are unable to bind to DNA, suggesting a critical role of this region in DNA binding. Taken together, these results are in good agreement with the structural model of M.EcoRV.

Catalysis↗
PubMedDate not supplied

Structural characterization of a 14-residue peptide ligand of the retinoblastoma protein: comparison with a nonbinding analog.

The retinoblastoma protein, a 110-kDa nuclear anti-oncoprotein, complexes specifically with transforming proteins of several oncogenic DNA viruses. A peptide [NLFCSEEMPSSDDE] derived from one of the viral proteins (simian virus 40 large T antigen) is known to competitively bind retinoblastoma protein, but a mutant analog [NLFCSKEMPSSDDE] does not. We studied the T peptide with HPLC to determine whether it can dimerize, and we employed circular dichroism spectroscopy to determine whether both peptides can exist in stable secondary structural conformations. HPLC analyses revealed that the T peptide is subject to oxidation and readily dimerizes. Circular dichroism analyses showed that both peptides can be induced to form stable secondary structural conformations under conditions that stabilize intramolecular hydrogen bonding in short peptides (90% 2,2,2-trifluoroethanol; 4 degrees C). The circular dichroism spectra of both peptide species were similar except for a statistically significant difference in the contour near 210 nm. Spectral analysis of the T-derived peptide species predicted elements of alpha-helix (18%), antiparallel beta-sheet (21%), beta-turn (22%) and unordered conformations (41%). An analysis of the mutant peptide species also predicted elements of alpha-helix (8%), antiparallel beta-sheet (28%), beta-turn (22%) and unordered conformations (40%). Thus, a small difference in the stabilized secondary structural conformations of the two sets of peptide species might partly explain their differential binding affinities for retinoblastoma protein, but it is likely that electrostatic charge differences resulting from the glutamic acid to lysine substitution play a dominant role.

Amino Acid Sequence↗
PubMedDate not supplied

Rare fatal simultaneous mould infection of the lung caused by Aspergillus flavus and the basidiomycete Coprinus sp. in a leukemic patient.

The basidiomycete Coprinus sp. was isolated repeatedly from bronchial secretions and bronchoalveolar lavage of a 40-year-old woman suffering from a relapse of acute lymphoblastic leukemia 5 years after she underwent autologous bone marrow transplantation. Post-mortem microbiological investigation of lung tissue revealed simultaneously growing Coprinus sp. and Aspergillus flavus. Histopathological examination of the lung demonstrated septate hyphae characteristic of both Aspergillus and Coprinus. The basidiomycete Coprinus sp. should be considered as a potential opportunistic pathogen because of its excellent growth at 37 degrees C.

Adult↗