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Biomedical subjects

M Zulauf

Publications and source records attributed to M Zulauf.

At least 73 records · Page 4Linked to original sources
PubMed1985

The domain structure of tryptophan synthase. A neutron scattering study.

Tryptophan synthase from Escherichia coli is a complex of two alpha subunits and two beta subunits. Small-angle neutron scattering involving deuterium-labelled isomers revealed the quaternary structure of the enzyme at the level of the beta 2 subunit and the two structural domains P1 and P2 which constitute the alpha subunits. Within the alpha 2 beta 2 complex, the two alpha subunits are completely separated. They are situated on opposite sides of the beta 2 subunit. The most probable distance between the two alpha protomers is 10.5 +/- 1 nm; the nearest distance is 5.8 +/- 0.5 nm, and the largest distance is 13.5 +/- 0.5 nm. The two domains of the same alpha subunit are intimately juxtaposed. The distances between two like or unlike domains belonging to opposite alpha subunits are roughly equal. All domains exhibit about equal distances to the beta 2 subunit which is situated in the centre of the complex. Thus the cleft between P1 and P2, which probably contains the active site of the alpha subunit, makes intimate contact with the beta 2 subunit. Neutron scattering allows us to determine the shape of the beta 2 subunit within the complex. Comparison with the free dimer suggests a conformational change, upon assembly, from an elongated into a more compact form.

Deuterium↗
PubMed1984

Differential light threshold. Short- and long-term fluctuation in patients with glaucoma, normal controls, and patients with suspected glaucoma.

In the diagnosis and evaluation of progression of chronic open-angle glaucoma, a quantitative comparison of visual fields is important for which a knowledge of the spontaneous fluctuation of the visual field is essential. This study shows that in patients with glaucoma, the components of the short- and long-term fluctuation are substantially greater than in patients without the disease. Patients with suspected glaucoma show fluctuation in between, and all components of the fluctuation are greater in them than in normals and smaller than in patients with open-angle glaucoma.

Differential Threshold↗
PubMed1984

Quantitative studies in stereochronoscopy (Sc): application to the disc in glaucoma. II. Statistical evaluation.

The statistical method of control charts applied to quantitative stereochronoscopy of the disc in glaucoma enables differentiation of cases of to and fro displacements of disc elements ("papillary unrest") from continuous or discontinuous progression. In all cases of discontinuities we are obliged to search for their cause. The control chart method helps to determine the approximate time of incidence of these events. Stereochronoscopy should be well adapted to supervise treated glaucoma cases.

Circadian Rhythm↗
PubMed1984

Retinopathy of prematurity: a risk factor analysis with univariate and multivariate statistics.

Seventy-three out of 639 ophthalmoscopically examined newborns (11.4%) showed varying degrees of retinopathy of prematurity (ROP). Three infants were blind (0.5%). Sixty-six patients were matched with controls according to gestational age, birth weight, birth date and neonatal unit. Using univariate statistics, the variables representing the extent of O2-exposure, elevated paO2, elevated paCO2, paCO2-fluctuations, acidosis, blood transfusions, and artificial ventilation were found to be significantly associated with ROP. In contrast, the variables representing hypocapnia, Hb-levels, parenteral fluid administration and fluid retention showed no correlation with ROP. When a multivariate statistical method was used, the variables representing gestational age, elevated paO2, elevated paCO2 and paCO2-fluctuations as well as the ones defining blood transfusions lost their association with ROP. Episodes of acidosis, multiple birth, birth weight, total hours with Fio2 greater than 0.4, and total duration of artificial ventilation remained in the regression, and hypocapnia gained a significant negative correlation with ROP. This comparative survey based on univariate and multivariate statistics demonstrates that significance levels of identically defined biological and therapeutic variables obtained from the same population of patients are to be interpreted with caution. This fact may also explain contrasting opinions on risk factors in the literature. Multivariate statistical analyses are useful for a relative comparison of significance within a given set of variables. Conclusions on a possible causal relationship as well as on prophylactic measures are not possible.

Humans↗
PubMed1983

Self-assembly of brome mosaic virus protein into capsids. Initial and final states of aggregation.

The pH and ionic strength dependence of the states of aggregation of brome mosaic virus protein has been investigated by small angle neutron scattering, quasielastic light-scattering, analytical centrifugation and electron microscopy. At pH above neutrality, protein oligomers are found in dynamical equilibrium, comprising monomers, dimers and aggregates of higher molecular weight. By lowering the pH, capsids assemble spontaneously with dimensions in solution which depend on ionic strength. If formed by dialysis, they contain 180 monomers, but are 30 A larger in diameter than the native virus. If formed by pH-jump, they contain less monomers: the deficiency decreases with decreasing the final pH and the initial protein concentration. Upon dehydration for electron microscopy, capsids contract by 10%.

Capsid↗
PubMed1982

Dependence of melittin structure on its interaction with multivalent anions and with model membrane systems.

The conformation and the aggregation state of melittin were investigated in aqueous solutions having different pH values and ionic composition as well as upon interaction with phospholipids. While circular dichroism could only show the existence, in aqueous solution, of either a random-coil or of a right-handed helical conformation, high resolution 1H and 13C n.m.r. spectra, together with the results of photon correlation spectroscopy, produced evidence in favour of a number of different well-defined structural states, depending on anion concentration and charge and on pH. In pure water at neutral pH melittin appeared to exist as a flexible random-cell monomer; in dilute NaCl a monomeric form was found which was still essentially unordered, but presented a pronounced rigidity of structure, and could be approximated to a prolate ellipsoid. When divalent anions were present (or when high ionic strengths were reached even with monovalent anions) melittin molecules associated into a compact disc-like tetramer; by 31P n.m.r., correlations could be established between the binding of phosphate ions and the variations in the structure or in the aggregation state of the polypeptide chains. As alkaline pH a helical tetramer was also found, different, however, from that formed on the presence of divalent anions at neutral pH. Upon binding to phospholipids, melittin molecules can be visualized, similarly to what happens in aqueous phosphate solutions, as consisting essentially of a bent right-handed helix, with a grouping of polar residues along one face of the molecule. The glutamine and lysine residues were strongly immobilized, while there was no n.m.r. evidence for any self-aggregation of the peptide; the ability of melittin to induce dichromate efflux from phospholipid vesicles was in fact higher when the peptide was in the monomeric state than in the tetrameric one.

Anions↗
PubMed1979

Fibrinogen: agreement of experimental and calculated hydrodynamic data with electron-microscopic models.

There is no general agreement on the size and shape of the fibrinogen molecule. We have studied the diffusion of the fibrinogen in solution by means of dynamic light scattering, nanosecond fluorescence depolarization and analytical ultracentrifugation. The results obtained under physiological concentration, pH an ionic strength are DT = 2.0 X 10(7) cm2sec-1, DR perpendicular = 40'000 sec 1. Nanosecond fluorescence depolarization yielded DR parallel = 1.6 x 10(6) sec-1. Tentatively this value is interpreted as DR parallel, namely rotational diffusion about the major axis of the molecule. The sedimentation coefficient is 8.1 S. The hydrodynamic parameters derived from our measurements were compared with those calculated on the basis of the models proposed by Hall and Slayter, Hudry-Clergeon and Marguerie et al., Bachmann and Lederer, and Köppel. The agreement is poor even if the degree of hydration is varied within wide limits. However, satisfactory agreement can be achieved by assuming a flexible molecule of about 900 A length corresponding to two end-to-end bound trinodular structures of the Hall and Slayter type, with a nodule diameter of about 45 A. Experimental evidence indicates that the discrepancies between the different models might be due to different techniques of sample preparation leading to different conformations of the molecule.

Fibrinogen↗
PubMedDate not supplied

Assembly of 2-D membrane protein crystals: dynamics, crystal order, and fidelity of structure analysis by electron microscopy.

Membrane protein reconstitution into two-dimensional (2-D) ordered arrays is described. The assembly of 2-D crystals may be modeled as a two-step process: the membrane protein is first integrated in the lipid bilayer and then crystallized by removal of excess detergent or lipid and/or by precipitating agents. Lipid-detergent, protein-detergent, and lipid-protein interactions are critical during the first step, while lipid-protein and protein-protein interactions dominate events in the second step. The evidence supporting this model results from quasielastic light scattering analyses and electron microscopy of different lipid-detergent systems and reconstitution experiments with Escherichia coli porin OmpF, Phormidium laminosum photosystem I reaction centers, and integral membrane proteins of mammalian lens fiber cells.

Animals↗
PubMedDate not supplied

Pyrrolo[2,3-d]pyrimidine nucleosides: synthesis and antitumor activity of 7-substituted 7-deaza-2'-deoxyadenosines.

A one step synthesis, using the nucleoside 7-iodo-2'-deoxytubercidin (2b) in a Pd(0)/Cu(I)-catalyzed cross coupling reaction furnished a series of 7-alkynyl-2'-deoxytubercidin derivatives. The 7-iodo-, 7-chloro- or 7-bromo 2'-deoxytubercidins 2b-d as well as certain 7-alkynyl derivatives show significant activity against several tumor cell lines, with 7-iodo-2'-deoxytubercidin (2b) as the most effective compound.

Animals↗