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Biomedical subjects

P Friedrich

Publications and source records attributed to P Friedrich.

At least 73 records · Page 4Linked to original sources
PubMed1987

Molecular kinetic modelling of associative learning.

Three molecular (enzyme) kinetic models have been designed that exhibit the basic properties of associative learning (classical conditioning). The enzyme systems are acted upon by an 'unconditioned' and a 'conditioned' ligand: temporally paired application of the two ligands leads to covalent enzyme modification, which serves as 'memory trace'. The behaviour of the systems has been investigated by computer simulation. Although the models are hypothetic, they do not contain biochemically inconceivable steps. The models demonstrate that already fairly simple molecular events may produce the phenomenology of associative learning.

Adenylyl Cyclases↗
PubMed1987

Hypoxia-induced alterations of norepinephrine vascular reactivity in isolated perfused cat lung.

Past work in the isolated perfused cat lung has shown that acute hypoxia (H) changes the response to norepinephrine (NE) from vasoconstriction to vasodilation but has no effect on the response to serotonin (S). These results could be related to the increase in pulmonary arterial pressure or vascular resistance during the hypoxic pressor response or a direct effect of H. We addressed this question, in the same preparation, by comparing responses to NE under four conditions in each experimental animal (n = 12): 1) NE infused during normoxia; 2) NE infused after vascular resistance (Rpv) was increased with serotonin; 3) NE infused after Rpv was increased by H; 4) NE infused after lobar pressure was raised by an increase in flow (P/F). PO2 values during H were varied (27-56 Torr). S and H produced a 137 +/- 35 and 43 +/- 8% delta Rpv increase in lobar vascular resistance, respectively. P/F increased lobar pressure 91 +/- 10%. Only NE infusion during H demonstrated significant differences in lobar pressure and Rpv compared with control normoxic periods. There was no correlation between responses to NE during S, H, and P/F and degree to which each stimulus increased Rpv or lobar pressure (r = 0.003, 0.28, 0.24). A significant relationship between response to NE during H vs. PO2 during H was observed (r = 0.78; P less than 0.001). In a subset of animals, we repeated the infusion of NE during H and P/F post-beta-blockade. The decrease in vascular response to NE during H and the correlation of PO2 with NE response were abolished (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Pregnancy- and gender-related changes in pulmonary vascular reactivity.

Pregnancy is a state of altered pulmonary vascular reactivity, but the conclusions about changes in reactivity have varied with the agents or species chosen for study. The present study was designed as a comprehensive analysis of pregnancy-induced and gender-related differences in pulmonary vascular reactivity in one species. Using an isolated perfused feline lung preparation, the pulmonary vascular responses to angiotensin II, serotonin, histamine, epinephrine, norepinephrine, and acute hypoxia (FIO2, 8%) were compared between males, females, and pregnant females. Vascular reactivity (maximum response) and drug sensitivity (ED50) were compared using cumulative dose-response data for each pharmacological agent. The results demonstrate that (1) reactivity to angiotensin II, serotonin, epinephrine, and acute hypoxia is decreased during pregnancy, while the response to norepinephrine remain unchanged, (2) drug sensitivity is unchanged with serotonin and the catecholamines, increased with histamine, and decreased with angiotensin II, and (3) the responses to acute hypoxia and histamine have significant gender-related differences in reactivity independent of the changes observed during pregnancy.

Angiotensin II↗
PubMed1987

Cyclic AMP-induced phosphorylation of 27.5-kDa protein(s) in larval brains of normal and memory-mutant Drosophila melanogaster.

Whole brains dissected from third-instar larvae of Drosophila melanogaster increase their cAMP content when incubated with octopamine, dopamine and serotonin, especially in the presence of theophylline, a phosphodiesterase inhibitor. The most pronounced rise in cAMP was produced by forskolin. When brains prelabelled with [32P]orthophosphate were subjected to these treatments, the increased labelling of 27.5-kDa protein(s) of pI 6.3-6.6 (substrate A) was observed in all cases, as revealed by two-dimensional gel electrophoresis and autoradiography. Labelling of substrate A was enhanced without any drug addition in brains of the dunceM11 mutant strain, which has abnormally high basal cAMP levels. The labelling of substrate A was also promoted by the potassium channel blocker 4-aminopyridine. The data suggest that in Drosophila larval brain the 27.5-kDa protein is a target of cAMP-triggered phosphorylation and may be related to potassium channel(s).

Animals↗
PubMed1986

Ca2+-induced structural change in the Ca2+/Mg2+ domain of troponin C detected by crosslinking.

Rabbit muscle troponin C was selectively modified at Cys-98 by 1,3-difluoro-4,6-dinitrobenzene. The second function of the bifunctional reagent was triggered at alkaline pH in the presence and absence of Ca2+. The crosslinked troponin C was hydrolyzed by trypsin and the peptides containing a dinitrobenzene moiety were isolated. When troponin C was crosslinked in the presence of Ca2+, the single dinitrobenzene-containing peptide was Gly-89-Arg-100, in which Cys-98 was crosslinked with Lys-90. When crosslinking was performed in the absence of Ca2+, beside the above peptide two additional peptides containing dinitrobenzene were found. One of these peptides is made up of two fragments, Ser-91-Arg-100 and Asn-105-Arg-120, crosslinked between Cys-98 and Tyr-109. The second peptide, Ala-121-Lys-140, contains modified Lys-136, presumably crosslinked with His-135. The data indicate that the distances between the alpha-carbon of Cys-98 and those of Lys-90, Tyr-109, Lys-136 and probably the alpha-carbon distance His-125-Lys-136, do not exceed 14 A. Comparison with the X-ray structure of troponin C (Herzberg, O. and James, M.N.G. (1985) Nature 313, 653-659) indicates that some of the above distances increase on Ca2+-binding.

Amino Acids↗
PubMed1986

Structural and functional properties of Drosophila melanogaster phosphorylase: comparison with the rabbit skeletal muscle enzyme.

Glycogen phosphorylase isolated from Drosophila melanogaster contains one pyridoxal 5'-phosphate per subunit; the coenzyme is in a hydrophobic environment. Fruit-fly phosphorylase a has lower KM for glucose-1-phosphate and is less sensitive to allosteric inhibitors than the b form of the enzyme. The amino acid composition of Drosophila phosphorylase differs from that of rabbit skeletal muscle phosphorylase. These two enzymes give distinct one dimensional peptide maps. The distribution of reactive SH-groups is markedly different in the insect and vertebrate phosphorylase. Fruit-fly phosphorylase a is dephosphorylated by either rabbit or Drosophila protein phosphatase-1 at a slower rate than rabbit muscle phosphorylase a.

Amino Acids↗
PubMed1986

Altered autophosphorylation of adenosine 3',5'-phosphate-dependent protein kinase in the dunce memory mutant of Drosophila melanogaster.

The phosphorylation-dephosphorylation, in the presence of adenosine 5'-[gamma-32P]triphosphate, of a polypeptide of apparent molecular mass 53,000 has been compared in head homogenates of wild type and memory mutant dunceM11 strains of Drosophila melanogaster. In both strains, labelling of the 53 kilodalton protein required exogenous adenosine 3',5'-phosphate (cAMP), but in dunceM11 cAMP at higher concentration (above approximately 3 microM) caused the rapid disappearance of the label. This differential dephosphorylation can be attributed to the lack of a cAMP-specific phosphodiesterase isoenzyme in the mutant. Several lines of evidence indicate that the 53 kilodalton protein is identical with the regulatory subunit of cAMP-dependent protein kinase. The findings suggest that in the mutant's nerve cells the state of phosphorylation of the regulatory subunit of cAMP-dependent protein kinase is altered, which may contribute to the biochemical disorder leading to the memory deficit.

Adenosine Triphosphate↗
PubMed1986

Purification of a benzodiazepine from bovine brain and detection of benzodiazepine-like immunoreactivity in human brain.

An endogenous brain substance that binds to the central-type benzodiazepine receptors with agonist properties is present in both rat and bovine brains. This substance has been purified to homogeneity from bovine brain by immunoaffinity chromatography on immobilized monoclonal anti-benzodiazepine antibody followed by gel filtration on Sephadex G-25 and two reversed-phase HPLC steps. The purified substance was characterized as the benzodiazepine N-desmethyldiazepam (nordiazepam). The techniques used for the identification were mass spectrometry, HPLC, spectrophotometry, benzodiazepine receptor binding, and immunological techniques. Benzodiazepine-like immunoreactivity was also found in all the human brains tested, including six brains that had been stored in paraffin since 1940, fifteen years before the first synthesis of benzodiazepines. These results show that benzodiazepine-like molecules of natural origin--and possibly benzodiazepines themselves--are present in human and other mammalian brains.

Animals↗
PubMed1986

[Postoperative complications in space occupying processes of the base of the skull].

Tumours of the skull base become manifest by the nervous structures surrounding them. After the removal of the tumour, the complications are produced by the same disturbed structures. Proceeding under microsurgical conditions will reduce both the risk of subsequent haemorrhages in patients with olfactory--groove meningiomas and central disturbances of the respiratory and circulatory--functions.

Adolescent↗
PubMed1984

Crosslinking of troponin complex with 1,3-difluoro-4,6-dinitrobenzene. Identification of the crosslink formed between troponin C and troponin I in the absence of Ca2+.

The single SH-group of rabbit skeletal muscle troponin C (Cys-98) was reacted with the bifunctional reagent, 1,3-difluoro-4,6-dinitrobenzene. This labelled troponin C was used to reconstitute the troponin complex by the addition of equimolar amounts of troponin T and troponin I. The second function of the bifunctional reagent was triggered in the complex by an increase of pH. A crosslink was formed between troponin C and troponin I both in the presence and absence of Ca2+, but the probability of crosslinking was decreased by Ca2+. Covalently linked troponin C-troponin I was isolated from the complex crosslinked without Ca2+, and cleaved by CNBr. The analysis of crosslinked peptides has revealed that in the presence of Mg2+ and absence of Ca2+ the crosslink in the troponin complex is formed between Cys-98 of troponin C and Cys-133 of troponin I.

Amino Acids↗
PubMed1984

Microcompartmentation of cAMP in wild-type and memory-mutant dunce strains of Drosophila melanogaster.

The "enzyme-probe" method [Solti M, Friedrich P: Eur J Biochem 95:551, 1979] has been applied to characterize the cyclic AMP pool in wild-type Canton-S and memory-mutant dunceM11 strains of Drosophila melanogaster. The kinetics of cyclic AMP breakdown in whole fly homogenates by endogenous cyclic nucleotide phosphodiesterase(s) indicate that the cyclic AMP pool is divided into free and bound fractions. The bound fraction in Canton-S and dunceM11 is 0.5 and 1.5 pmole/mg fly, respectively. Considering the total cyclic AMP content of the two strains, 1.6 and 10 pmole/mg fly, respectively, we conclude that the bulk of excess cyclic AMP in the mutant is free nucleotide.

Animals↗
PubMed1984

Differences in protein phosphorylation in vivo and in vitro between wild type and dunce mutant strains of Drosophila melanogaster.

The protein phosphorylation patterns of wild type and dunce mutant strains of Drosophila melanogaster, as detected by sodium dodecylsulfate-gel electrophoresis and autoradiography, have been compared. After labelling in vivo with 32Pi or in vitro in homogenates with [gamma-32P]ATP, radioactive bands at and above apparent polypeptide mol. wt approximately 110,000 were more pronounced in dunce fly heads than in wild type heads. When labelling in vitro, in dunceM11 there appeared a radioactive band at apparent mol. wt approximately equal to 53,000 that was faintly visible in the wild strain. The same band could be intensified in both strains by adding cyclic AMP to the homogenate or by performing homogenization in the presence of theophylline. The data suggest that the mol. wt approximately equal to 53,000 protein is a substrate for cyclic AMP-dependent protein kinase.

Adenosine Triphosphate↗
PubMed1984

[Postoperative courses in space occupying processes of the cranial base].

The postoperative complications of two collectives are compared: 100 patients with space-occupying processes in the base of the skull and 100 patients with mainly space occupying intracerebral processes. The first collective was exclusively, the second mainly operated on microsurgically. The group showing processes of the base of the skull shows a greater number and more frequently occurring complications than the comparative group. The relation to the brain stem as a cause of this fact is discussed. In all studied patients, no cerebellar stupor occurred. This seems to be in relation with the less stressing procedure in the employment of microtechniques.

Brain Neoplasms↗
PubMed1983

Cyclic nucleotide phosphodiesterases in larval brain of wild type and dunce mutant strains of Drosophila melanogaster: isoenzyme pattern and activation by Ca2+/calmodulin.

Like adult heads and whole flies, larval brains of wild type Drosophila melanogaster contain two major soluble cyclic nucleotide phosphodiesterases, forms I and II. Larval brains of the learning-defective mutant strain, dunceM11, contain only the form I enzyme. In both wild type and dunce strains the form I enzyme is activated by Ca2+/calmodulin. A time-dependent loss of this Ca2+ activation was observed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

[Therapy of intracerebral hematomas].

On the basis of own experiences, fundamentals with respect to the treatment of intracerebral and intracerebellar haematomas are established. Computer tomography permits a narrowing of the indication for a surgical intervention, but only under the condition that this examination can be carried out at any time in the direct vicinity of the neurosurgical establishment.

Adult↗