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Biomedical subjects

A Heine

Publications and source records attributed to A Heine.

At least 37 records · Page 2Linked to original sources
PubMed2000

A new functional domain of guanine nucleotide dissociation inhibitor (alpha-GDI) involved in Rab recycling.

Guanine nucleotide dissociation inhibitor (GDI) is a 55-kDa protein that functions in vesicular membrane transport to recycle Rab GTPases. We have now determined the crystal structure of bovine alpha-GDI at ultra-high resolution (1.04 A). Refinement at this resolution highlighted a region with high mobility of its main-chain residues. This corresponded to a surface loop in the primarily alpha-helical domain II at the base of alpha-GDI containing the previously uncharacterized sequence-conserved region (SCR) 3A. Site-directed mutagenesis showed that this mobile loop plays a crucial role in binding of GDI to membranes and extraction of membrane-bound Rab. This domain, referred to as the mobile effector loop, in combination with Rab-binding residues found in the multi-sheet domain I at the apex of alpha-GDI may provide flexibility for recycling of diverse Rab GTPases. We propose that conserved residues in domains I and II synergize to form the functional face of GDI, and that domain II mediates a critical step in Rab recycling during vesicle fusion.

Amino Acid Motifs↗
PubMed2000

Gaussian unitary ensemble statistics in a time-reversal invariant microwave triangular billiard

The spectrum of a chaotic two-dimensional quantum billiard with threefold symmetry has been studied in an experiment with a superconducting microwave cavity. In total 622 eigenvalues were identified experimentally and compared with numerical calculations. The statistical analysis of the data shows that Gaussian unitary ensemble statistics can be observed for a spectrum of a time-reversal invariant system.

Journal Article↗
PubMed1999

Psychobiological markers of stress in pregnancy: 6-sulfatoxymelatonin--a longitudinal study.

Maternal stress, physical and psychological, has been associated with adverse pregnancy outcome. The pineal gland is a physiological transducer that reflects adrenergic input. In a recent pilot study, we found urinary 6-sulfatoxymelatonin, the melatonin metabolite, to be elevated after a women spent a day at work compared to levels after a day off work, a leisure day. To evaluate the value of melatonin as a marker of stress, we evaluate melatonin metabolite levels in 121 women, along with perceived anxiety levels and urinary cortisol. Urinary cortisol and maternal anxiety levels each were significantly higher after a work day compared to a leisure day p = .03 and p = .001, respectively. 6-Sulfatoxymelatonin was not significantly different between work and leisure. Changes in cortisol levels were correlated with changes in melatonin metabolite levels (r = .62, p = .001). There was no correlation between changes in anxiety between work and leisure and changes in 6-sulfastoxymelatonin. We found no correlation with 28 week 6-sulfatoxymelatonin or 28-week cortisol and birth weight or gestational age at delivery. Results of this study suggest that melatonin secretion may not be a valuable marker for stress in pregnancy.

Adult↗
PubMed1999

In vitro and in vivo activation of hypericin with the incoherent light source PDT 1200 SOA (520-750 nm) and with solar simulated radiation (290-2500 nm).

The photodynamic active plant pigment hypericin is a possible new photosensitizer for photodynamic therapy. Hypericin shows absorption maxima in the ultraviolet (330 nm) and visible light range (550 and 588 nm). The present study compared the photoactivation of hypericin with the incoherent light source PDT 1200 SOA (520-750 nm) to that with a 1000 watt solar simulator (290-2500 nm). Hypericin displayed dose and time dependent phototoxic effects in the keratinocyte cell line HaCaT in vitro and after intracutaneous in vivo application with both light sources. In vivo, delayed (48 h) photosensitivity in hypericin-sensitized skin was observed. With intracutaneous application of 100 ng/ml hypericin, no phototoxic reaction could be produced. The PDT 1200 SOA was about four times more effective in vitro and about ten times more effective in vivo when compared to the solar simulator. Since the PDT 1200 SOA allows homogenous irradiation of large areas, we conclude that the PDT 1200 SOA is an effective and convenient light source for in vitro and in vivo studies using hypericin.

Anthracenes↗
PubMed1998

An antibody exo Diels-Alderase inhibitor complex at 1.95 angstrom resolution.

A highly specific Diels-Alder protein catalyst was made by manipulating the antibody repertoire of the immune system. The catalytic antibody 13G5 catalyzes a disfavored exo Diels-Alder transformation in a reaction for which there is no natural enzyme counterpart and that yields a single regioisomer in high enantiomeric excess. The crystal structure of the antibody Fab in complex with a ferrocenyl inhibitor containing the essential haptenic core that elicited 13G5 was determined at 1.95 angstrom resolution. Three key antibody residues appear to be responsible for the observed catalysis and product control. Tyrosine-L36 acts as a Lewis acid activating the dienophile for nucleophilic attack, and asparagine-L91 and aspartic acid-H50 form hydrogen bonds to the carboxylate side chain that substitutes for the carbamate diene substrate. This hydrogen-bonding scheme leads to rate acceleration and also pronounced stereoselectivity. Docking experiments with the four possible ortho transition states of the reaction explain the specific exo effect and suggest that the (3R,4R)-exo stereoisomer is the preferred product.

Antibodies, Catalytic↗
PubMed1997

Immune versus natural selection: antibody aldolases with enzymic rates but broader scope.

Structural and mechanistic studies show that when the selection criteria of the immune system are changed, catalytic antibodies that have the efficiency of natural enzymes evolve, but the catalytic antibodies are much more accepting of a wide range of substrates. The catalytic antibodies were prepared by reactive immunization, a process whereby the selection criteria of the immune system are changed from simple binding to chemical reactivity. This process yielded aldolase catalytic antibodies that approximated the rate acceleration of the natural enzyme used in glycolysis. Unlike the natural enzyme, however, the antibody aldolases catalyzed a variety of aldol reactions and decarboxylations. The crystal structure of one of these antibodies identified the reactive lysine residue that was selected in the immunization process. This lysine is deeply buried in a hydrophobic pocket at the base of the binding site, thereby accounting for its perturbed pKa.

Animals↗
PubMed1996

[Behavior medicine indications and evaluation of cognitive-behavioral therapy with attention-deficit/hyperkinetic children].

The president study evaluates the efficacy of a cognitive-behavioral intervention for children with attention-deficit hyperactivity disorders. Twenty-seven children (mean age: 9 years, 9 months) took part in the study. They had been diagnosed as having attention-deficit hyperactivity disorder according to the DSM-III-R criteria. Of these 27 children, 14 were treated individually (15 sessions each) and 13 were assigned to an untreated control group. The children were evaluated before and after the intervention. Dependent measures included parent and teacher ratings, measures of cognitive performance and event-related potentials during attentional tasks. The intervention resulted in improved ratings of the children's behavior at home and at school by parents and teachers, respectively, and improved attentional performance. Furthermore, the intervention enabled the children to use their central nervous system activation (event-related potentials) more adequately. These effects are interpreted with reference to a multifactorial model of attention-deficit hyperactivity disorder. The results also provide evidence for the influence of cognitive-functional behavior preconditions on central nervous system activation.

Attention Deficit Disorder with Hyperactivity↗
PubMed1995

Structures of quinoxaline antibiotics.

The crystal structures of three quinoxaline antibiotics-echinomycin 2QN, triostin C and the C222(1) form of triostin A--have been determined, and the structure of the P2(1)2(1)2(1) form of triostin A has been re-refined against our previously reported data. The molecular conformations are compared with those deduced from NMR data and those reported for two complexes of triostin A with oligonucleotides. Although the depsipeptide ring conformations are basically similar, the effective twofold molecular symmetry is violated by the folding of one of the quinoxaline chromophores in echinomycin 2QN and by a rotation of one of the ester planes with the formation of an intramolecular hydrogen bond in triostin C. In the oligonucleotide complexes of triostin A the chirality of the disulfide bridge is inverted. The alanine NH groups are involved in intermolecular hydrogen bonds in all four structures, and (except in echinomycin 2QN) the stacking of the chromophores in the crystal emulates the intercalation involved in DNA complex formation. In echinomycin 2QN, the antibiotic molecules are hydrogen bonded to form a helix along the crystallographic 6(5) screw axes, with a channel of disordered solvent running through the middle of the helix. Crystal data: (1), echinomycin 2QN, C53H66N10O12S2.2.5(C3H6O).2.5(H2O), M(r) = 1289.5, hexagonal, P6(5), a = b = 22.196(15), c = 24.64 (2) A, V = 10,513 (13) A3, Z = 6, Dx = 1.222 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu = 1.275 mm-1, T = 193 K, R = 9.0% for 4828 I > 2 sigma (I) and 11.8% for all 7102 unique reflections; (2), triostin C, C54H70N12O12S2.0.67(CHCl3).0.67(H2O), M(r) = 1234.2, orthorhombic, P2(1)2(1)2(1), a = 16.054 (8), b = 17.128 (9), c = 22.706 (12) A, V = 6244 (6) A3, Z = 4, Dx = 1.313 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.239 mm-1, T = 188 K, R = 7.7% for 4678 I > 2 sigma (I) and 14.0% for all 7260 unique reflections; (3), triostin A, C50H62N12O12S2.2(C7H14O2), M(r) = 1347.6, orthorhombic, P2(1)2(1)2(1), a = 20.94 (2), b = 18.53 (2), c = 18.80 (2) A, V = 7292 (13) A3, Z = 4, Dx = 1.228 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu = 1.245 mm-1, T = 293 K, R = 6.8% for 2116 I > 2 sigma (I) and 9.3% for all 2928 unique reflections; (4), triostin A, C50H62N12O12S2.HCl.2(C3H7NO), M(r) = 1269.9, monoclinic, C222(1), a = 10.622 (10), b = 17.035 (17), c = 35.21 (3) A, V = 6371 (10) A3, Z = 4, Dx = 1.324 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.199 mm-1, T = 153 K, R = 7.5% for 2164 I > 2 sigma (I) and 13.2% for all 3402 unique reflections. Extensive use was made of restraints on the geometrical and displacement parameters in the successful anisotropic refinement of these structures against weak data.

Anti-Bacterial Agents↗
PubMed1995

Structure of octreotide, a somatostatin analogue.

Octreotide, a synthetic somatostatin analogue, is an octapeptide with one disulfide bridge. Crystals of octreotide are orthorhombic, space group P2(1)2(1)2(1), a = 18.458 (5), b = 30.009 (7), c = 39.705 (27) A, with three molecules of octapeptide, one ordered oxalate dianion and 52 water molecules in the asymmetric unit. Complete protonation of the NH(2) groups (as assumed in the refinement) would require three oxalate dianions in the asymmetric unit for charge neutrality; a chemical analysis indicated that four are present. In either case they are so disordered that they cannot be distinguished from the water molecules. The 18 951 unique reflections (R(sym) = 0.026) used for structure solution and refinement were recorded with the EMBL imaging-plate scanner using synchrotron radiation. The structure was solved by Patterson interpretation, locating the three disulfide bridges, followed by tangent phase expansion and E-Fourier recycling. The anisotropic refinement against all F(2) data between 1.04 and 10.0 A resolution by blocked restrained full-matrix least-squares techniques converged to a conventional R index based on F of 0.084 [I > 2a(I) and 10.0 > d > 1.04 A] and wR2, the weighted R-index on F(2), of 0.246 (for all data). One peptide molecule adopts a flat beta-sheet structure; the other two possess different irregular backbone conformations, but are similar to each other. All three molecules have a distorted type II' beta-turn around the D-Trp-Lys region, but exhibit different side-chain conformations. The crystal structure is stabilized by a network of inter- and intramolecular hydrogen bonds.

Journal Article↗
PubMed1995

Comparison of different X-ray data-collection systems using the crystal structure of octreotide.

The octapeptide octreotide crystallizes with three peptide molecules and about 20% water in the asymmetric unit, and in many ways possesses diffraction properties similar to those of a 'mini-protein' consisting of 24 amino-acid residues. It diffracts to about 1.0 A but data in the range 1.4-1.0 A are weak. It provides a suitable test of different macromolecular X-ray data-collection techniques, especially of their ability to measure weak reflections accurately. In contrast to typical proteins it is possible to perform a full anisotropic refinement, that we believe provides a more objective test of the quality of the data than the internal consistency of equivalent reflections. We have collected a total of six data sets. The X-ray sources included synchrotron radiation, Cu Kalpha rotating anodes and Mo Kalpha sealed tubes; position-sensitive two-dimensional detectors from four manufacturers and a four-circle diffractometer with scintillation counter were employed. Two of the six data sets were collected at low temperature. Reasonable anisotropic refinement was possible with all area-detector data sets, although significant differences in the precision of the final model were observed. In addition we tested the ability of automated Patterson interpretation to solve the structure using the six independent data sets. The structure solution was only successful using the synchrotron or rotating-anode data sets, i.e. for the more intense sources. It appears that for structure solution the maximum resolution of the data is critical, whereas for refinement the accuracy of the data is more important.

Journal Article↗
PubMed1995

Unilateral localized basaliomatosis: treatment with topical photodynamic therapy after application of 5-aminolevulinic acid.

A 74-year-old woman presenting with multiple unilateral localized basal cell carcinomas present for 30 years on the left side of her body is reported. There was no history of arsenic ingestion or X-ray exposure. Typical signs of nevoid basal-cell carcinoma syndrome (Gorlin's syndrome) like jaw keratocysts, skeletal malformations, and small palmoplantar pits were missing. Although treatment with many therapeutic regimens was tried, there were still tumor recurrences. Photodynamic therapy was performed after topical application of 5-aminolevulinic acid. This treatment resulted in good tumor control with an optimal cosmetic result.

Administration, Cutaneous↗
PubMed1995

Inflammatory pseudotumor of the anterior orbit. A symptom in allergic granulomatous angiitis (Churg-Strauss syndrome).

Allergic granulomatosis accompanied by angiitis (Churg-Strauss syndrome) constitutes an unusual disorder which is characterized clinically by bronchial asthma and hypereosinophilia, accompanied by systemic symptoms of histopathologically and by necrotizing vasculitis, extravascular granulomas and tissue infiltration by eosinophils. We report a case of a 4 year-old child presenting with acute pneumonia and deteriorated general condition. The biopsy of an inflammatory pseudotumor of the right anterior orbit revealed necrotizing vasculitis, extravascular epitheloid granuloma and eosinophilic tissue infiltration. These are characteristic changes of allergic granulomatous vasculitis (Churg-Strauss syndrome. Laboratory findings were characterized by blood eosinophilia, increased IgE value and the presence of antineutrophil cytoplasmic ant antibodies (p-ANCA). Local and systemic manifestations quickly regressed after parenteral application of corticosteroids. Two exacerbations of inflammatory pseudotumor occurred after reduction of the corticosteroid dosage. Systemic vasculitic syndromes are rare in childhood. Orbital manifestations in Churg-Strauss syndrome in childhood have never been reported.

Biopsy↗
PubMed1994

Naftopidil inhibits 5-hydroxytryptamine-induced platelet aggregation and 5-hydroxytryptamine uptake in platelets of healthy volunteers.

Naftopidil exerts its antihypertensive action via alpha 1-adrenoceptor blockage and Ca2+ antagonism in vascular smooth muscle. Since the chemically similar 1-(1-naphthyl) piperazine is known to be a 5-hydroxytryptamine2 receptor antagonist, the 5-hydroxytryptamine (5-HT) antagonistic properties of naftopidil were tested by examining 5-HT-induced aggregation and 5-HT uptake in platelets from 12 healthy volunteers after oral administration of 60 mg naftopidil or placebo. Platelet aggregation in vitro was inhibited by naftopidil with a Ki value of 1.1 microM, the pIC50 was 5.09 with induction of aggregation by 1 microM 5-HT. After oral administration of naftopidil, 5-HT-induced aggregation was significantly inhibited by 36%. 4 h after naftopidil administration, 5-HT uptake velocity was reduced by 33%. Naftopidil not only cancelled the circadian increase in 5-HT-induced aggregation velocity observed during placebo application, but also caused a decrease in aggregation velocity directly after peak plasma naftopidil levels. 5-HT uptake in platelets was also reduced following peak naftopidil plasma concentrations. The 5-HT inhibitory action of naftopidil adds a third possible antihypertensive property to naftopidil's alpha 1-adrenoceptor blocking and Ca2+ antagonistic properties.

Adult↗
PubMed1994

A possible new incoherent lamp for photodynamic treatment of superficial skin lesions.

Since coherence of laser light is not necessary for photodynamic therapy of skin lesions, attempts have been made to construct incoherent lamps. A recent development is the PDT 1200 (Waldmann Medizintechnik/Germany), a light source consisting of a 1200 watt metal halogen lamp. Emission of 600 to 800 nm radiation is achieved by using cut-off filters. Power density can be varied from 30 mW/cm2 to 200 mW/cm2 in an area from 100 to 300 cm2. Biological effectiveness was proved by comparison with the radiation of an argon-pumped dye laser (Kiton red) emitting light at 630 nm. Three human cell lines were incubated with photofrin at different concentrations. After irradiation, cell viability was tested (MTT assay). Results proved biological effectiveness of the light source PDT 1200. No significant difference in cell viability was detected using either concentration of sensitizer. Therefore, we believe that PDT 1200 is a promising new light source for photodynamic therapy of skin lesions.

Cell Survival↗
PubMed1992

[Conventional roentgen functional diagnosis--videodensitometry. 2. Clinical imaging site for noninvasive diagnosis of organ motion].

By means of the described system it is possible to measure and as well analog as digital process the organ movement, needing a X-ray television system for flouroscopy and a videotape for continuously recording. Using the densitometric principle measurements of time and a quantitative form analysis of the curves are performed. After border recognition and using the topometric principle, the local organ motion can be evaluated. The levels of signal and noise in the measured curves are computed by a fourier transformation. In the field of functional cardiology the video signal is recorded and processed synchronously with the electrocardiogram.

Computer Systems↗