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Biomedical subjects

G Müller

Publications and source records attributed to G Müller.

At least 343 records · Page 19Linked to original sources

Influence of HDL on the formation of 6-keto-PGF1 alpha and TXB2 in vitro: the importance of the source of HDL.

The influence of HDL, isolated from normolipidemic human blood and blood of normo- and hyperlipidemic rabbits, on in vitro 6-keto-PGF1 alpha synthesis by rabbit aorta and on TXB2 synthesis by platelets of clotting human and rabbit blood was tested. The HDL fraction from normolipidemic subjects, when incubated with blood from normolipidemic humans or rabbits, inhibited TXB2 formation. The same fraction stimulated the formation of 6-keto-PGF1 alpha after incubation with rabbit aorta taken from normolipidemic animals. HDL taken from hyperlipidemic rabbits inhibited 6-keto-PGF1 alpha formation in rabbits and had no influence on TXB2 formation. These results support the hypothesis that not only is the absolute amount of HDL important for its influence on prostanoid formation, but also the origin and the composition of the HDL fraction.

6-Ketoprostaglandin F1 alpha↗

[Mucoviscidosis screening with immunoreactive trypsin].

Up to now 49,116 immunoreactive trypsin (IRT) measurements have been carried out in Austrian newborns in the first week of life. Related to provisionally chosen cut-off points, 301 newborns (0.61%) showed an elevated IRT value; 253 of them were successfully recalled. According to a direct strategy, sweat tests were done without a second IRT measurement in 101 infants; eleven of them were identified as cystic fibrosis (CF) patients. In accordance with a 2-step strategy, 152 infants were reinvestigated by a second IRT determination. Twenty-eight of them again showed an elevated IRT value, as based on provisional, age-dependent reference values; seven were subsequently identified as CF patients by sweat testing. So far two false-negative findings were obtained on IRT screening: one child was later identified as having CF on the basis of typical clinical symptoms and a positive sweat test, the other patient presenting with meconium ileus showed a normal IRT value after surgery, but was subjected to a sweat test in view of the underlying condition. These preliminary results suggest a CF incidence of 1 to 2460 newborns in Austria. Hence, IRT screening appears to be a reliable method for identifying CF patients in the newborn period, thereby facilitating early treatment and genetic counselling.

Austria↗

[Laser in surgery of vascular anastomoses].

The disadvantages of present-day microvascular suturing techniques include suture-induced foreign-body granulomas, stenoses and aneurysms. In comparison, argon laser-assisted anastomoses show a more favorable histomorphology and a low rate of stenoses and aneurysms. Laser-assisted anastomoses pass through the same familiar healing phases seen in common wound-healing.

Anastomosis, Surgical↗

[Lowering peripheral vascular resistance by distal arteriovenous fistula surgery. Clinical and experimental studies].

Vascular run off has an important influence on patency rates of infrapopliteal bypasses especially when prosthetic grafts are used. Construction of a distal arteriovenous fistula can improve volume and velocity of graft flow. 39 patients, 14 of them diabetic, had femoro-crural PTFE-bypasses. A distal arteriovenous fistula in common ostium technique was established in 20 cases. The patency rate (early occlusions) was improved, especially diabetic patients seemed to profit by lowering the peripheral outflow resistance, which was measured intraoperatively. The influence of arteriovenous fistulas of different calibre on bypass flow and perfusion was analysed in a circulation model.

Arteriovenous Shunt, Surgical↗

[Acquired antithrombin III deficiency].

Acquired antithrombin III (AT III) deficiency is based on either decreased activity or synthesis, increased loss or increased consumption. The activity of AT III is decreased in metabolic acidosis, hyperlipoproteinemias and by lipid peroxides. Chronic liver diseases especially liver cirrhosis are associated with very low levels of AT III due to insufficient hepatic synthesis, reduced transcapillary flux ratios, diffuse intravascular coagulation and loss in the ascites. Gastrointestinal loss of AT III may occur in patients with active inflammatory bowel diseases. AT III deficiency is observed in nephrotic syndrome when urinary loss of protein exceeds 5 g/d. During hemodialysis we have not found low AT III levels. Disseminated intravascular coagulation is characterized by activation of the coagulation system and increased consumption of AT III. AT III complexes with activated coagulation factors are subsequently cleared by the reticuloendothelial system.

Antithrombin III↗

Present management of hepatic artery aneurysms. Symptomatic left hepatic artery aneurysm; right hepatic artery aneurysm with erosion into the gallbladder and simultaneous colocholecystic fistula--a report of two unusual cases and the current state of etiology, diagnosis, histology and treatment.

A left hepatic artery aneurysm has an incidence of 0.8% among the splanchnic artery aneurysms. 20% of splanchnic artery aneurysms are hepatic artery aneurysms. Atherosclerosis (32%) is the most prevalent etiology, followed by trauma (22%) and inflammatory lesions (10%). The average age is 40 (10-83) years, the male to female ratio 2:1. In 64-80% of cases rupture of the aneurysm is the first clinical manifestation. The mortality is then about 35%. The case of a 64 years old female with a symptomatic aneurysm of the left hepatic artery and the case of a 70 years old female, who underwent emergency laparotomy for acute colorectal hemorrhage, with a right hepatic artery aneurysm, which perforated into the gallbladder, with simultaneous colocholecystic fistula is reported and the etiology, histology, and present diagnostic and therapeutic management of hepatic artery aneurysms is discussed.

Aged↗

[Malondialdehyde concentration in blood plasma of patients with liver diseases].

Malondialdehyde (MDA) level was determined spectrophotometrically with thiobarbituric acid method on 50 healthy persons and 160 patients with alcoholic and nonalcoholic liver diseases. Alcoholics without liver damage show normal plasma MDA values. Alcoholic fatty liver, alcoholic hepatitis and alcoholic liver cirrhosis cause an increase of MDA values. The highest concentrations of MDA were found on patients with acute virus hepatitis. Also noninfectional hepatitis and nonalcoholic liver cirrhosis showed an elevated MDA-Level. Liver damage and lipid peroxidation are considered as closely connected processes.

Adult↗

Two lipid-anchored cAMP-binding proteins in the yeast Saccharomyces cerevisiae are unrelated to the R subunit of cytoplasmic protein kinase A.

We show that the yeast, Saccharomyces cerevisiae, contains two cAMP-binding proteins in addition to the well-characterized regulatory (R) subunit of cytoplasmic cAMP-dependent protein kinase (PKA). We provide evidence that they comprise a new type of cAMP receptor, membrane-anchored by covalently attached lipid structures. They are genetically not related to the cytoplasmic R subunit. The respective proteins can be detected in sral mutants, in which the gene for the R subunit of PKA has been disrupted and a monoclonal antibody raised against the cytoplasmic R subunit does not cross-react with the two membrane-bound cAMP-binding proteins. In addition, they differ from the cytoplasmic species also with respect to their location and the peptide maps of the photoaffinity-labeled proteins. Although they differ from one another in molecular mass and subcellular location, peptide maps of the cAMP-binding domains resemble each other and both proteins are membrane-anchored by lipid structures, one to the outer surface of the plasma membrane, the other to the outer surface of the inner mitochondrial membrane. Both anchors can be metabolically labeled by Etn, myo-Ins and fatty acids. In addition, the anchor structure of the cAMP receptor from plasma membranes can be radiolabeled by GlcN and Man. After cleavage of the anchor with glycosylphosphatidylinositol-specific phospholipase C from trypanosomes, the solubilized cAMP-binding protein from plasma membranes reacts with antibodies which specifically recognize the cross-reacting determinant from soluble trypanosomal coat protein, suggesting similarity of the anchors. Degradation studies also point to the glycosylphosphatidylinositol nature of the anchor from the plasma membrane, whereas the mitochondrial counterpart is less complex in that it lacks carbohydrates. The plasma membrane cAMP receptor is, in addition, modified by an N-glycosidically linked carbohydrate side chain, responsible mainly for its higher molecular mass.

Affinity Labels↗

A cAMP-binding ectoprotein in the yeast Saccharomyces cerevisiae.

Purified plasma membranes from the yeast Saccharomyces cerevisiae bind about 1.2 pmol of cAMP/mg of protein with high affinity (Kd = 6 nM). By using photoaffinity labeling with 8-N3-[32P]cAMP, we have identified in plasma membrane vesicles a cAMP-binding protein (Mr = 54,000) that is present also in bcy1 disruption mutants, lacking the cytoplasmic R subunit of protein kinase A (PKA). This argues that it is genetically unrelated to PKA. Neither high salt, nor alkaline carbonate, nor cAMP extract the protein from the membrane, suggesting that it is not peripherally bound. The observation that (glycosyl)phosphatidylinositol-specific phospholipases (or nitrous acid) release the amphiphilic protein from the membrane, thereby converting it to a hydrophilic form, indicates anchorage by a glycolipidic membrane anchor. Treatment with N-glycanase reduces the Mr to 44,000-46,000 indicative of a modification by N-linked carbohydrate side chain(s). In addition to the action of a phospholipase, the efficient release from the membrane requires the removal of the carbohydrate side chain(s) or the presence of high salt or methyl alpha-mannopyranoside, suggesting complex interactions with the membrane involving not only the glycolipidic anchor but also the glycan side chain(s). Topological studies show that the protein is exposed to the periplasmic space, raising intriguing questions for the function of this protein.

Carbohydrates↗

Arg-Gly-Asp constrained within cyclic pentapeptides. Strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment P1.

Cyclic Arg-Gly-Asp-Phe-Val peptides with either D-Phe or D-Val residues were 20- to more than 100-fold better inhibitors of cell adhesion to vitronectin and/or laminin fragment P1 when compared to a linear variant or Gly-Arg-Gly-Asp-Ser. No or only little increase in inhibitory capacity was observed for fibronectin adhesion and for the binding of platelet receptor alpha IIb beta 3 to fibrinogen. NMR studies of the two most active cyclic peptides showed for both an all-trans conformation with a beta II' and gamma turn. Subtle conformational differences, however, exist between both peptides and may contribute to selectivity of inhibition.

Amino Acid Sequence↗

Conformational analysis of a IgG1 hinge peptide derivative in solution determined by NMR spectroscopy and refined by restrained molecular dynamics simulations.

The hinge region links the antigen binding Fab part to the constant Fc domain in immunoglobulins. For the hinge peptide derivative [AcThr(OtBu)-Cys-Pro-Pro-Cys-Pro-Ala-ProNH2]2 the assignment of the 1H and 13C resonances was achieved by two-dimensional nmr techniques: total correlation spectroscopy (TOCSY), nuclear Overhauser enhancement spectroscopy (NOESY), rotating frame nuclear Overhauser enhancement spectroscopy (ROESY), heteronuclear multiple quantum coherence (HMQC) transfer, and a HSQC (modified Overbodenhausen experiment) with high resolution in F1, which was several times folded in F1 but still phase correctable. Conformational relevant parameters (78 nuclear Overhauser effect distance restraints, 3JHH for prochiral assignments, temperature gradients) were determined by nmr and served as input data for molecular dynamics (MD) structure refinement. A simulated model compound corresponding to the [Cys-Pro-Pro-Cys]2 core elongated by the peptide chains in the Fab and Fc direction served as a starting structure for the final MD run. The conformation calculated in in vacuo does not agree with the C2 symmetry required from nmr data, but the structure obtained by a water simulation fulfills the requirement. Here the core of the hinge peptide derivative adopts a polyproline II double helix as in the x-ray structure of IgG1. Hence, segments responsible for the internal flexibility are located outside the core as confirmed by the flexibility of the solvent exposed C termini.

Amino Acid Sequence↗

Amino acids determining operator binding specificity in the helix-turn-helix motif of Tn10 Tet repressor.

Each of 22 amino acids in the proposed alpha-helix-turn-alpha-helix operator binding motif of the Tn10 encoded Tet repressor was replaced by alanine and one residue was replaced by valine to determine their role in tet operator recognition by a 'loss of contact' analysis with 16 operator variants. One class of amino acids consisting of T27 and R28 in the first alpha-helix and L41, Y42, W43 and H44 in the recognition alpha-helix are quantitatively most important for wild-type operator binding. These residues are probably involved in the structural architecture of the motif. A second class of residues is quantitatively less important for binding, but determines specificity by forming base pair specific contacts to three positions in tet operator. This property is most clearly demonstrated for Q38 and P39 and to a lesser extent for T40 at the N-terminus of the recognition alpha-helix. The contacted operator base pairs indicate that the N-terminus of the recognition alpha-helix is located towards the palindromic center in the repressor-operator complex. Although the orientation of the recognition alpha-helix in the Tet repressor-tet operator complex is inversed as compared with the lambda- and 434 repressor-operator complexes, the reduced operator binding of the TA27 mutation in the first alpha-helix suggests that the hydrogen bonding networks connecting the two alpha-helices may be similar in these proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Comparative mapping of ZFY in the hominoid apes.

Within our project of comparative mapping of candidate genes for sex-determination/testis differentiation, we used a cloned probe from the human ZFY locus for comparative hybridization studies in hominoids. As in the human, the ZFY probe detects X- and Y-specific restriction fragments in the chimpanzee, the gorilla, the orangutan, and the gibbon. Furthermore, the X-specific hybridization site in the great apes resides in Xp21.3, the same locus defining ZFX in the human. The Y-specific locus of ZFY maps closely to the early replicating pseudoautosomal segment in the telomeric or subtelomeric position of the Y chromosomes of the great apes, again as found in the human. Thus, despite cytogenetically visible structural alterations within the euchromatic parts of the Y chromosomes of the human species and the great apes, a segment of the Y chromosome defined by the pseudoautosomal region and ZFY seems to be more strongly conserved than the rest of the Y chromosome.

Animals↗