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D Wedekind

Publications and source records attributed to D Wedekind.

31 records · Page 2Linked to original sources
PubMed1999

Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson's syndrome from multiple system atrophy and progressive supranuclear palsy.

By using three-dimensional magnetic resonance imaging-based volumetry, we studied atrophy of the caudate nucleus, putamen, brainstem, and cerebellum in patients with idiopathic Parkinson's syndrome (IPS, n = 11), progressive supranuclear palsy (PSP, n = 6), and multiple system atrophy with predominant parkinsonism (MSA-P, n = 12) or ataxia (MSA-C, n = 17). Patients were compared with a total of 46 controls, of whom 16 were age matched. Mean striatal, cerebellar, and brainstem volumes were normal in patients with IPS. We found significant reductions in mean striatal and brainstem volumes in patients with MSA-P, MSA-C, and PSP, whereas patients with MSA-C and MSA-P also showed a reduction in cerebellar volume. On an individual basis, volumes of structures in patients with MSA and PSP showed an extensive overlap with the normal range with the exception of brainstem volumes in patients with MSA-C. Therefore, groups could not be discriminated on the basis of individual structure volumetry. Application of stepwise discriminant analysis, however, allowed discrimination of all 12 patients with MSA-P, 15 of 17 patients with MSA-C, and 5 of 6 patients with PSP from the normal and IPS cohorts. However, patients with IPS could not be separated from controls and patients with MSA-P could not be separated from patients with PSP. In conclusion, total intracranial volume-normalized magnetic resonance imaging-based volumetric measurements provide a sensitive marker to discriminate typical and atypical parkinsonism.

Adult↗
PubMed1998

Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3.

Twenty-six patients suffering from autosomal dominant cerebellar ataxia type I were subjected to a genotype-phenotype correlation analysis using molecular genetic assignment to the genetic loci for spinocerebellar ataxia type 1, 2 or 3 (SCA1, SCA2, SCA3) and MRI-based volumetry of posterior fossa structures and basal ganglia nuclei. There was significant atrophy of the cerebellum and brainstem in all three SCA mutations compared with a group of 31 age- and sex-matched controls. Comparison between the SCA groups showed that cerebellar and brainstem atrophy was more severe in SCA2 than in SCA1 and SCA3. Putaminal and caudate volume was reduced only in SCA3, but not in SCA1 and SCA2. A set of three morphological criteria was defined that enabled us to assign all SCA2 and SCA3 patients correctly to the underlying genotype. In contrast, these criteria did not distinguish SCA1 from SCA2 and SCA3. Regression analysis failed to reveal a significant association between CAG repeat length and the volumes of the respective brain structures in any of the SCA mutant types. The present data provide in vivo evidence that SCA2 and SCA3 lead to distinct patterns of brain atrophy, while the atrophy changes in SCA1 overlap with both SCA2 and SCA3.

Adult↗
PubMed1997

No evidence for a physiological coupling between melatonin and glucocorticoids.

Much has been speculated about the existence of a physiological coupling between melatonin and glucocorticoid secretion and about a possible anti-stress action of melatonin. We examined the relationship between melatonin and glucocorticoid secretion under close-to-physiological conditions, when the plasma concentration of either melatonin or glucocorticoids was elevated acutely or chronically in both rats and humans. Tryptophan administration caused a massive rise of plasma melatonin, but had no effect on corticosterone levels in rats or on cortisol levels in humans. The acute and long-lasting exposure of rats to uncontrollable stress resulted in a significant rise of adrenal corticosterone secretion, but had no effect on circulating melatonin levels. Orchectomy caused an initial increase in circulating corticosterone (when melatonin was unaffected) and a delayed rise in circulating melatonin (when corticosterone levels were normalized). In humans, no correlation was found between the nocturnal urinary excretion of melatonin and cortisol, either among healthy subjects, or among patients suffering from panic disorder (with an increased urinary excretion of cortisol) or among insomnia patients (with a high incidence of low melatonin secretion). Furthermore, no evidence was found for a suppressive action of melatonin on dexamethasone-mediated thymus regression in rats and on dexamethasone-mediated suppression of lymphocyte proliferation in vitro. Taken together, the results of this study provide no evidence for the existence of mutual influences between melatonin and glucocorticoid secretion, nor do they support the proposed attenuation of glucocorticoid-mediated effects on target cells or tissues by melatonin under physiological conditions.

Adult↗
PubMed1997

Urinary excretion of cortisol, norepinephrine, testosterone, and melatonin in panic disorder.

Nocturnal urinary cortisol, norepinephrine, epinephrine, testosterone, and melatonin secretion patterns were studied in male patients with DSM IV/ICD-10 panic disorder (n = 16) over two series of 5 consecutive nights each. Night-time urinary excretion of cortisol, norepinephrine, and epinephrine was significantly elevated in drug-free patients compared to normal individuals (n = 13). Measurements were repeated after 4 weeks, and the same differences were found again. There were high correlations between the first and the second series of measurements. Testosterone and melatonin levels did not differ between panic patients and controls.

Adult↗
PubMed1997

Endocrine correlates of personality traits: a comparison between emotionally stable and emotionally labile healthy young men.

An initial sample of 120 healthy young men was screened by a personality questionnaire and 15 subjects each with highest and lowest scores respectively on emotionality (emotionally labile, EL subjects and emotionally stable, ES subjects) were recruited for a study on the relationship between the degree of emotionality and the basal secretion of stress-sensitive hormones during night-time. The nocturnal urinary excretion of cortisol, testosterone, adrenaline, noradrenaline and melatonin was measured over a period of 5 consecutive nights. The average amounts of each hormone excreted per night were not different between the two extreme groups. The variability of the excretion during the 5 nights of cortisol and testosterone, but not of adrenaline, noradrenaline and melatonin, was significantly higher in EL compared to ES subjects. The larger fluctuations in the nocturnal secretion of these two (and no other) hormones in EL subjects indicate that emotional lability is associated with a more labile regulation of cortisol and testosterone secretion. The observed intraindividual variability of basal stress hormone secretion may contribute to the vast interindividual variability noticed in psychoneuroendocrine stress research, especially in emotionally labile subjects.

Adolescent↗
PubMed1993

Expansion of the liver-associated macrophage system in systemic lupus erythematosus-prone NZB/W mice.

Systemic lupus erythematosus is characterized by profound changes of the immune system. We report on alterations of the macrophage system in the murine NZB/W model of this disease. A greatly increased number of mature macrophages was isolated from the liver of NZB/W mice as compared to BALB/c mice and several other inbred strains used as healthy controls. In addition, the macrophage precursor compartment in the liver of NZB/W mice was expanded severalfold as measured by proliferation of light-fraction nonadherent nonparenchymal cells (NPCs) in response to colony-stimulating factors. Functional properties of the macrophages isolated from various anatomic sites of the lupus-prone mice were tested. Production of monokines by macrophages from liver, spleen, and peritoneal cavity, calculated on a per cell basis, was in the same range as in several healthy control strains tested. Yet the overall production of these immunoregulatory molecules by the increased liver macrophage system, the body's largest compartment of macrophages, is likely to result in increased levels of circulating monokines in the plasma of lupus-prone NZB/W mice. Indeed, significantly elevated levels of interleukin-6, interleukin-1, and colony-stimulating activity could be demonstrated in the plasma of these mice both spontaneously and after stimulation with lipopolysaccharide. A possible contribution of the expansion of the macrophage system to the development of the disease is discussed.

Animals↗
PubMed1989

The influence of structural variations in the F- and FG-helix of the beta-subunit modified oxyHb-NES on the heme structure detected by resonance Raman spectroscopy.

The dispersion of the depolarization ratio of two prominent Raman lines (1,375 cm-1 and 1,638 cm-1) of oxyhemoglobin-N-ethyl succinimide have been examined for pH values between pH = 6.0 and 8.5. Both exhibit a significant pH dependence. Calculation of the Raman tensor in terms of a fifth-order time dependent theory provides information about the pH-dependence of parameters reflecting symmetry classified distortions of the prosthetic heme group. To correlate these distortions with the functional properties of the molecule the following protocol was used: 1) An allosteric model suggested by Herzfeld and Stanley (1974) has been applied to O2-binding curves measured at different pH values between 6.5 and 9.0. From this calculation one obtains both, the energy differences between different molecular conformations and the equilibrium constants of oxygen and proton binding. 2) A titration model was formulated relating each conformation of a molecule to a distinct set of distortion parameters of the heme group. 3) The distortion parameters resulting from the analysis of our Raman data were assigned as an effective value due to incoherent superposition of the distortion parameters related to the different titration states. The application of this procedure yields an excellent reproduction of the pH-dependent effective distortion parameters of both Raman lines investigated. It is shown that the protonation of two tertiary effector groups located in the beta-subunits affect the symmetry of the heme in a contrary manner: the protonation of a His-residue (pK = 8.2, probably His(FG4) beta) causes a symmetric position of the proximal imidazole thus lowering the perturbations of the heme core. Further it influences the interaction between amino acid residues of the heme cavity and pyrrole side chains (probably Val(FG5) beta-vinyl (pyrrole 3) thus causing a decrease of the distortions related to the peripheral part of the heme. In contrast, the protonation of Lys (EF6) beta causes a tilt position of the proximal imidazole and an increase of asymmetric perturbations of the heme core, whereas the interaction between the pyrrole side chains and the heme cavity is weakened. Our results are consistent with stereochemical predictions of Moffat (1971) concerning the existence of a H-bond between His(FG4) beta and Cys(F9) beta.

Adult↗
PubMed1989

Detection of the heme perturbations caused by the quaternary R----T transition in oxyhemoglobin trout IV by resonance Raman scattering.

The depolarization ratio dispersion and the respective excitation profiles of two structural sensitive Raman lines of oxyhemoglobin-trout IV (1,375 and 1,638 cm-1) have been measured at pH-values between 6.5 and 8.5. They were analyzed by employing a fifth order time dependent perturbation theory to calculate the polarizability tensor. This provides information about the pH-dependence of parameters reflecting symmetry classified distortions of the prosthetic heme groups. In order to correlate these distortions with functional properties of the molecule the following protocol has been employed: (a) a titration model was formulated relating each conformation of the molecule to a distinct set of distortion parameters the incoherent superposition of which provides the respective distortion parameter obtained from our Raman data. (b) The thermodynamic constants determining the equilibrium between these molecular conformations (i.e., the quaternary T and R-states, the low affinity t and the high affinity r-states of the distinct subunits, the pK-values of the Root- and Bohr groups) were obtained from a set of O2-binding curves that were analyzed in terms of an allosteric model suggested by Herzfeld and Stanley 1974. J. Mol. Biol. 82:231. The application of this procedure yields excellent reproduction of the pH-dependent effective distortion parameters of both Raman lines investigated. Thus established correlation between hemoglobin function (O2-binding) and structure (asymmetric perturbation of the hemegroup) provides some interesting insights into the molecular basis of the allosteric Root effect.

Animals↗
PubMed1986

Correspondence of the pK values of oxyHb-titration states detected by resonance Raman scattering to kinetic data of ligand dissociation and association.

The dispersion of the depolarization ratio of oxidation and spinmarker lines of oxyhemoglobin at low C1- concentration (less than 0.08 M) have been examined for different pH values in the acid and alkaline region. Interpreting the depolarization ratio dispersion curves by fifth order Loudon theory of the polarizibility tensor, we obtain tensor parameters depending linearly on symmetry classified distortions of the functional hemegroup. The pH dependence of these parameters are explained by assuming the influence of three titrable groups with pK = 7.8, 6.6, and 5.8 on the heme. Using these pK values, we are able to interpret the pH dependence of CO(O2)-dissociation and CO-association of the fourth hemoglobin subunit. We conclude from our measurements that the change of the Tyr HC2 beta-configuration induces heme-apoprotein interaction via the Tyr HC2 beta-Val FG5 beta H-bond, which are transduced to the heme via central and peripheral coupling.

Chlorides↗
PubMed1985

Heme-apoprotein interaction in the modified oxyhemoglobin-bis(N-maleimidomethyl)ether and in oxyhemoglobin at high Cl-concentration detected by resonance Raman scattering.

The dispersion of the depolarization ratio of oxidation and spin-marker lines of oxyhemoglobin-bis(N-maleimidomethyl)ether and oxyhemoglobin at high Cl- concentration (1 M) have been examined for different pH values in the neutral and alkaline regions. The oxidation marker line at 1375 cm-1 shows no pH-dependence in the physiological region for oxyHb-bis(N-maleimidomethyl)ether and a comparatively small variation for oxyHb at a Cl- concentration higher than 0.4 M. The spin-marker line at 1638 cm-1 exhibits a strong pH-dependence of depolarization ratio for high Cl- concentration, but a minor pH-induced variation for oxyHb-bis(N-maleimidomethyl)ether. Interpretation of these data yield the following conclusions: (1) The oxidation marker line monitors symmetry-lowering distortions of the heme group introduced by central coupling to the protein via the Fe-N bond, whereas the spin-marker line monitors peripheral coupling due to heme-protein interaction in the heme pocket. (2) At low Cl- concentrations (below 0.3 M) both types of coupling are present. These are induced by the salt bridge between His 146 beta and Asp94 beta and flexibility of the FG corner. (3) At high Cl- concentrations the salt bridge is missing, eliminating central coupling. (4) In oxyhemoglobin-bis(N-maleimidomethyl)ether, due to constraint of the bis(N-maleimidomethyl)ether bridging the FG corner and eliminating its flexibility and the missing salt bridge, both central and peripheral coupling are drastically reduced.

Adult↗
PubMed1984

Investigation of pH-induced symmetry distortions of the prosthetic group in oxyhaemoglobin by resonance Raman scattering.

The depolarisation ratio and the excitation profiles of some prominent Raman lines of the oxyhaemoglobin spectrum (1,375 cm-1, 1,583 cm-1, 1,638 cm-1) have been measured as functions of the exciting laser frequency. The depolarisation ratio shows a complicated minimum-maximum structure in the preresonant region between Soret- and beta-band of the optical spectrum, which depends on the pH-value of the solution. These dispersion curves are interpreted by fifth-order Loudon theory of the polarizability tensor including static distortions of the haem group, which lower its symmetry from the ideal D4h-symmetry, and enhancement by a second, non-Raman-active phonon. The fitting constants needed to fit the experimental data are related to static distortions of A1g, B1g, B2g, and A2g symmetry types and thus give information on the symmetry lowering from D4h. The variation of the fitting constants with the pH-value of the solution is interpreted to be caused by protonation/deprotonation processes of titrable amino acid groups contributing to the alkaline and acid Bohr effect. The protonation changes the electrostatic interaction energies in the globular protein and destabilizes the salt bridge between His(HC3)beta and Asp(FG1)beta in the R-state. These processes induce distortions of the haem group via haem-apoprotein interactions. Our results give no indication for a dominant role of the covalent Fe2+-N [His(F8)] bond in this process. They are in agreement, however, with the allosteric model of Hopfield, which assumes all interactions to be evenly distributed all over the protein molecule.

Adult↗