Li self-diffusion in lithium niobate single crystals at low temperatures.

Li self-diffusion in Li(2)O-deficient LiNbO(3) single crystals is investigated in the temperature range between 423 and 773 K (150-500 °C) by secondary ion mass spectrometry. A thin layer of ion-beam sputtered isotope enriched (6)LiNbO(3) was used as a tracer source, which allows one to study pure isotope interdiffusion. The diffusivities can be described by the Arrhenius law with an activation enthalpy of (1.33 ± 0.03) eV, which is in acceptable agreement with the migration energy of a single Li vacancy as determined by ab initio calculations given in the literature. Charge diffusivities as derived from impedance spectroscopy measurements on the same type of samples are identical to the tracer diffusivities within error limits. No indication of the formation of defect-complexes at low temperatures could be found in the diffusion behaviour.

Ultra-slow Li ion dynamics in Li(2)C(2)--on the similarities of results from (7)Li spin-alignment echo NMR and impedance spectroscopy.

Li diffusion and transport parameters of binary lithium carbide Li(2)C(2) were complementarily investigated by (7)Li (nuclear magnetic resonance) NMR and impedance spectroscopy. Long-range Li diffusion parameters were measured by using mixing-time-dependent and temperature-variable stimulated echo NMR spectroscopy. The method is sensitive to ultra-slow Li hopping processes which were probed from an atomic-scale point of view. Two-time phase correlation functions S(2) obtained can be parameterized by stretched exponentials only. The corresponding echo decay rates τ(-1), which were recorded at a resonance frequency of e.g. 155.5 MHz, show Arrhenius behaviour revealing an activation energy of 0.80(2) eV. This value is in very good agreement with that deduced from dc conductivity measurements (0.79(2) eV) probing Li transport processes on a macroscopic length scale. The comparison of impedance data with the measured NMR echo decay functions showed that both methods reflect diffusion processes being characterized by very similar motional correlation functions.

High anion conductivity in a ternary non-equilibrium phase of BaF(2) and CaF(2) with mixed cations.

A highly conductive ternary fluoride with mixed cations is prepared by joint high-energy ball milling of cubic BaF(2) and CaF(2) in the ratio 0.4 : 0.6. The sample produced at room temperature consists of a nanocrystalline, defect-rich mixed (Ba,Ca)F(2) phase with retained cubic symmetry as well as of single-phase CaF(2) particles. The anion conductivity of the mixed phase, which decomposes at higher temperature (770 K) into BaF(2) and CaF(2), exceeds that of single-phase nanocrystalline BaF(2) by two and that of CaF(2) by four orders of magnitude. In turn, these conductivities are each greater by about two orders than those of the respective microcrystalline counterparts. Structural features of the samples are characterized by X-ray diffraction, TEM and (19)F MAS NMR spectroscopy. Static (19)F NMR spectra confirm the unexpectedly high anion conductivity probed by impedance spectroscopy.

Gene polymorphisms of ACE and the angiotensin receptor AT2R1 influence serum ACE levels in sarcoidosis.

Angiotensin converting enzyme (ACE) is thought to influence susceptibility, disease progression, and/or outcome of sarcoidosis by functional mutations/polymorphisms of the ACE gene, such as the ACE gene deletion/insertion (D/I) polymorphism or the angiotensin receptors like the angiotensin II receptor type 1 (AT2R1) A1166 --> C polymorphism. The aim of our study was to examine the distribution of the ACE D/I genotypes and the AT2R1 A1166 --> C genotypes in sarcoidosis and healthy controls, and to test their influence on disease progression. In this study, we assessed ACE and AT2R1 genotypes by PCR in 264 healthy Caucasians and 95 sarcoidosis patients. Serum ACE levels were determined using a kinetic test. Genotyping sarcoidosis patients for the AT2R1 A166 --> C polymorphism revealed an increase in homozygous genotypes CC (sarcoidosis: 11.6%, controls: 9.2%) and AA (sarcoidosis: 61.1%, controls: 47.3%) but a lower frequency in heterozygous genotypes (sarcoidosis: 27,4%, controls: 43,5%; p = 0.024) which was more pronounced in male patients. The co-incidence of DI and AC was less frequent in patients with sarcoidosis, suggesting protection by the combination of DI and AC. The AT2R1 A1166 --> C gene polymorphism modulated the effect of the ACE D/I polymorphism on serum ACE levels with the A allele promoting its influence and the C allele reducing it. We conclude that neither the ACE D/I nor the AT2R1 A1166 --> C polymorphism has a role in sarcoidosis disease progression. In males, the homozygous AT2R1 genotypes CC and AA possibly increase the risk for sarcoidosis. Co-incidence of the heterozygous genotypes DI and AC might be protective against sarcoidosis.

Genotype-corrected reference values for serum angiotensin-converting enzyme.

The deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene has the greatest impact on serum ACE level in Caucasians of any factor yet discovered. The aim of the present study was to establish new ACE genotype-corrected normal ranges for serum ACE level in a population of central European origin. After a medical examination, 159 healthy Caucasians volunteered to donate blood for the study. ACE genotypes were assessed by PCR and serum ACE levels were determined using two different kinetic tests. The distribution of the D/I polymorphism of the ACE gene was in accordance with the Hardy-Weinberg equilibrium. Serum ACE levels and ACE genotypes correlated significantly, with the highest serum ACE levels in subjects with ACE genotype D/D, and the lowest serum ACE levels in subjects with genotype I/I (mean+/-sd, assay 1: D/D 59.3+/-15.1 U x L(-1), D/I 45.5+/-15.2 U x L(-1), I/I 34.8+/-13.7 U x L(-1); assay 2: D/D 43.7+/-14.1 U x L(-1), D/I 33.7+/-12.1 U x L(-1), I/I 25.4+/-9.5 U x L(-1)). Although they gave different absolute values of serum ACE levels, the results of the two test kits correlated significantly. In conclusion, the present authors recommend the use of new, genotype-specific reference values for serum angiotensin-converting enzyme levels, especially to improve the sensitivity and specificity of tests for angiotensin-converting enzyme in the follow-up of sarcoidosis.

[Subacute sclerosing panencephalitis: fulminant form]. / Panencefalitis esclerosante subaguda: forma fulminante.

INTRODUCTION: Subacute sclerosing panencephalitis (SSPE) has become less frequent as a consequence of massive anti measles vaccination. Early infection or immunological factors could increase the risk of its appearing and of evolved forms of the disease. CASE REPORTS: We describe the cases of four patients with fulminating forms of SSPE: a girl who had measles at the age of eight months; a male who, without actually suffering the clinical disease, came into contact with measles in the family and, despite having been vaccinated, presented SSPE 18 months after the contact; a boy aged 4 years and 4 months who had measles at the age of 6 months, and a boy of a similar age who had the illness when he was one year old. They all developed ataxia, with focal and generalised neurological signs, myoclonic and atonic seizures with rapid deterioration of language and the cognitive functions. In the four cases, the computerised tomography scans were normal, the electroencephalograms showed bilateral paroxysms and periods of recurrent bioelectrical attenuation. The magnetic resonance images of the four patients revealed disseminated hyperintense lesions, and one of the patients presented hyperintense lesions in the cervical spinal cord. The anti measles IgG titres were high in the cerebrospinal fluid. Anti convulsive drugs were ineffective. In the third and fourth patients, intrathecal intraventricular treatment with interferon did not modify the course of the disease and neurological deterioration was seen in the subsequent follow up of all the cases. CONCLUSION: As a consequence of vaccination against measles, SSPE has become less frequent. Infection of infants, prior to the immunisation stage, can induce SSPE with periods of latency that are shorter than usual and with a fast progression of the disease.

Panencefalitis esclerosante subaguda: forma fulminante / Subacute sclerosing panencephalitis: fulminant form

Introducción. La panencefalitis esclerosante subaguda (PEES) ha disminuido su frecuencia como consecuencia de la vacunación masiva antisarampionosa. La precocidad de la infección o factores inmunológicos podrían aumentar el riesgo de aparición y formas evolutivas de la enfermedad. Casos clínicos. Presentación de cuatro pacientes con formas fulminantes de PEES: una niña que padeció sarampión a los ocho meses de vida; un varón que, sin padecer la enfermedad clínica, tuvo contacto con sarampión familiar y, a pesar de haberse vacunado, presentó PEES a los 18 meses del contacto; un niño de 4 años y 4 meses, que tuvo sarampión a los 6 meses de edad, y un niño de similar edad, que padeció la enfermedad al año de vida.Todos desarrollaron ataxia, con signos neurológicos focales y generalizados, crisis mioclónicas y atónicas con un rápido deterioro de las funciones cognitivas y del lenguaje. En los cuatro casos, las tomografías computarizadas fueron normales, los electroencefalogramas mostraron paroxismos bilaterales y períodos de atenuación bioeléctrica periódica. En las resonancias magnéticas de los cuatro pacientes se encontraron lesiones hiperintensas diseminadas, y uno de los pacientes presentó lesiones hiperintensas en la médula cervical. En el líquido cefalorraquídeo, los títulos de IgG antisarampionosas estaban elevados. Los fármacos anticonvulsionantes fueron ineficaces. El tratamiento intratecal-intraventricular con interferón, en el tercer y cuarto pacientes, no modificó el curso de la enfermedad, y el deterioro neurológico fue progresivo en el seguimiento ulterior de todos los casos. Conclusión. Como consecuencia de la vacunación contra el sarampión, la PEES ha disminuido su frecuencia. La infección en lactantes, previa a la etapa de inmunización, puede inducir PEES con períodos de latencia menores a los habituales, con un curso rápido de la enfermedad (AU)

Introduction. Subacute sclerosing panencephalitis (SSPE) has become less frequent as a consequence of massive antimeasles vaccination. Early infection or immunological factors could increase the risk of its appearing and of evolved forms of the disease. Case reports. We describe the cases of four patients with fulminating forms of SSPE: a girl who had measles at the age of eight months; a male who, without actually suffering the clinical disease, came into contact with measles in the family and, despite having been vaccinated, presented SSPE 18 months after the contact; a boy aged 4 years and 4 months who had measles at the age of 6 months, and a boy of a similar age who had the illness when he was one year old. They all developed ataxia, with focal and generalised neurological signs, myoclonic and atonic seizures with rapid deterioration of language and the cognitive functions. In the four cases, the computerised tomography scans were normal, the electroencephalograms showed bilateral paroxysms and periods of recurrent bioelectrical attenuation. The magnetic resonance images of the four patients revealed disseminated hyperintense lesions, and one of the patients presented hyperintense lesions in the cervical spinal cord. The antimeasles IgG titres were high in the cerebrospinal fluid. Anti-convulsive drugs were ineffective. In the third and fourth patients, intrathecal-intraventricular treatment with interferon did not modify the course of the disease and neurological deterioration was seen in the subsequent follow-up of all the cases. Conclusion. As a consequence of vaccination against measles, SSPE has become less frequent. Infection of infants, prior to the immunisation stage, can induce SSPE with periods of latency that are shorter than usual and with a fast progression of the disease (AU)

Gene polymorphisms of immunoregulatory cytokines and angiotensin-converting enzyme in Wegener's granulomatosis.

Wegener's granulomatosis is a granulomatous and vasculitic disease of unknown origin. Gene polymorphisms are known to affect phenotypes of numerous diseases. Polymorphisms within the angiotensin-converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), and interleukin-10 (IL-10) genes are suspected to modify the course of granulomatous disorders. We examined whether the genotype frequencies of the named polymorphisms differ in Wegener's granulomatosis from those in healthy controls. Thirty-nine patients with Wegener's granulomatosis were genotyped for the deletion/insertion polymorphism in intron 16 of the ACE gene, a biallelic polymorphism in codon 25 of the TGF-beta1 gene and a biallelic polymorphism at position -1082 of the IL-10 gene and compared with healthy blood donors. For the ACE polymorphism no significant differences were detected neither in the allele frequencies nor in the genotype frequencies. For TGF-beta1 a trend to genotype CG was found. The most interesting result was the observed, significant shift to genotype AA of the IL-10 polymorphism in Wegener's granulomatosis. IL-10 and TGF-beta1, immunoregulatory cytokines capable of down-regulating T helper cell type 1 response, showed a significant shift or a trend, respectively towards genotypes associated with reduced cytokine release, leading to the hypothesis that different immunoregulatory cytokine patterns dependent on gene polymorphisms might be involved in the pathogenesis of Wegener's granulomatosis.

[Corrected normal values for serum ACE by genotyping the deletion-/insertion-polymorphism of the ACE gene]. / Korrigierte Normwerte für das Serum-ACE durch Genotypisierung eines Deletions-/Insertions-Polymorphismus des ACE-Gens.

BACKGROUND: In sarcoidosis, serum ACE is widely recognised as a marker of disease activity. Since 1990 a deletion-/insertion polymorphism of the ACE gene is known and a correlation between the genotypes of this polymorphism and serum ACE levels has been observed. Homzygotes for the deletion allele (DD) have the highest levels and homozygotes for the insertion allele (II) the lowest. Heterozygote (DI) persons show intermediate levels. The extent of this influence varies in populations of different ethnic origin. In a large cohort of healthy individuals from North of Germany, genotype-based normal ranges for serum ACE were determined for the population of Germany for the first time. METHODS: In 262 healthy individuals the genotype of the ACE D/I gene polymorphism was determined from genomic DNA by a PCR method. In addition, in serum samples of all these individuals ACE level was measured with a kinetic test. RESULTS: The genotype DD was found in 29.4 % of the individuals examined, the genotype DI in 49.6 % and the genotype II in 21.0 %, respectively. These results are similar to those found in previous investigations in other populations of Central European origin. The mean serum ACE levels (95 % confidence interval) in individuals with the genotypes DD, DI and II are 59.8 U/l (31.8 - 87.8), 47.7 U/l (18.6 - 76.8) and 32.2 U/l (13.7 - 50.7), respectively. Without taking the genotype into account, the average value is 48.0 U/l (15.0 - 80.9). Differences between all genotype groups are highly significant (p < 0.0001). CONCLUSIONS: In sarcoidosis patients, the determination of this ACE gene polymorphism once in the course of the disease allows a better interpretation of the serum ACE levels measured.

[The quality of integration and care in workshops for the handicapped--The path to TQM in the workshops of the Gemeinschaftswerks fu"r Be- hinderte GmbH, Landstuhl]. / Eingliederungs- und Betreuungsqualität in Werkstätten für Behinderte--Der Weg zu TQM in den Werkstätten des Gemeinschaftswerks für Behinderte GmbH (Landstuhl).

Workshops for the Handicapped are exposed, as are other providers of social services, to powerful changes in social and economic conditions. Legal obligations (e.g. under the Federal Social Assistance Act BSHG), increasing customer demands and stronger competition make the ability to change a prerequisite, so that the quality and cost of providing services to the handicapped become a central theme. These changes in conditions have led the Gemeinschftswerk für Behinderte GmbH, Landstuhl, to intensively consider the themes Quality and Total Quality Management (TQM). The efforts to introduce TQM were concentrated initially on the DIN EN ISO 9000 certification of the production processes in the workshops. Currently, the themes of Integration and Care were examined. After the central processes had been identified the performance descriptions of system, structure, process, result, and steering committee were extended by process diagrams and responsibility matrixes. This paper describes the path that workshops of the Gemeinschaftswerk für Behinderte GmbH have taken towards TQM, with emphasis on presentation of the themes regarding quality of Integration and Care.

Interaction of lipoproteins with type II pneumocytes in vitro: morphological studies, uptake kinetics and secretion rate of cholesterol.

Apart from dipalmitoyl phosphatidylcholine, cholesterol is the most abundant surfactant lipid. About 90 to 99% of cholesterol of the alveolar surfactant is derived from serum lipoproteins. The aim of this study was to identify the lipoprotein which preferentially supplements type II pneumocytes with cholesterol destined for surfactant production. Ultrastructural investigations revealed that type II pneumocytes bind and take up HDL, LDL and VLDL. Binding and uptake of VLDL occurred even in the presence of excess LDL indicating that, besides LDL receptors, type II pneumocytes express additional binding sites for VLDL. Type II pneumocytes in primary culture are able to take up cholesterol added in the form of HDL, LDL and VLDL. Cholesterol uptake was lowest from HDL and highest from VLDL. The maximal velocity of cholesterol uptake from VLDL was more than three times that of cholesterol uptake from LDL. The half-maximal saturation of cholesterol uptake from VLDL was nearly half that of LDL. From these kinetic data and the distribution of free cholesterol among the serum lipoproteins, we calculated that the cholesterol uptake from VLDL is more than three times that of cholesterol uptake from LDL. In double-labeling experiments type II pneumocytes secreted palmitic acid-labeled phospholipids together with labeled free cholesterol taken up from lipoproteins. The secretion rates of both phospholipids and free cholesterol were stimulated to nearly the same extent by isoproterenol. From our results we conclude that type II pneumocytes interact specifically with HDL, LDL and VLDL. Cholesterol taken up in the form of the individual lipoproteins shows no difference in its availability for the formation of cholesterol ester and surfactant by type II pneumocytes in vitro. Based on the kinetic studies, it appears that VLDL is the major gateway through which cholesterol is provided to satisfy the cholesterol requirements of type II pneumocytes for the synthesis of surfactant.

Interaction of apo E-containing lipoproteins with the LDL receptor-related protein LRP.

The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional cell surface receptor that interacts with apolipoprotein E (apo E)-rich lipoproteins, and alpha2-macroglobulin (alpha2-M) in the activated state (alpha2-M*). Whether LRP is a physiologically relevant lipoprotein receptor for naturally occurring apo E-rich lipoproteins, however, is still under discussion. To address this question, we isolated beta-migrating very low density lipoprotein (beta-VLDL) from rabbits by using gel filtration chromatography. Biochemical analysis of beta-VLDL subfractions demonstrated that we isolated apo E- and cholesterol-rich triglycerides with differences in composition and size. Binding and uptake characteristics of beta-VLDL subfractions and alpha2-M* on mouse peritoneal macrophages (MPM) and Hep G2 cells were examined by electron microscopy. One of the beta-VLDL subfractions, beta-VLDL(II), bound specifically to LRP on MPM and Hep G2. beta-VLDL(II) competed with the binding of alpha2-M* without addition of exogenous apo E. Furthermore, binding and uptake of beta-VLDL(II) and alpha2-M* were not affected by either lactoferrin or Ca2+-free medium. The results indicate that naturally occurring apo E-rich lipoproteins do exist and that they very likely interact with LRP via the same binding site as alpha2-M*.

Interaction of apo E-containing lipoproteins with the LDL-receptor-related protein, LRP.

The low density lipoprotein receptor-related protein (LRP) discovered in 1988 (1) was proposed as a candidate for the postulated apo E-binding chylomicron remnant receptor. Recent results suggest LRP to be a multifunctional cell surface receptor which might have a pivotal function in linkage of diverse metabolic pathways not previously considered to be related. Although biochemical evidence for lipoprotein binding to LRP has been presented (rev in 2), the need to add apo E to lipoproteins to demonstrate lipoprotein binding to LRP has raised doubts as to its lipoprotein receptor function. Therefore, it has yet to be established whether there is a physiologically relevant binding of naturally occurring apo E-containing lipoproteins to LRP. Here we describe cytochemical studies in which naturally occurring apo E-containing lipoproteins carefully isolated by gelfiltration chromatography were found to bind specifically to the cell surface of mouse peritoneal macrophages (MPM). These lipoproteins compete specifically with the binding of activated alpha 2-macroglobulin, which is a generally accepted ligand of LRP, to these cells without previous enrichment with exogenous apo E. We therefore conclude that LRP is indeed a physiologically relevant lipoprotein receptor.

Oxidized LDL induces serotonin release from blood platelets.

Oxidized low-density lipoprotein (LDL) induces a release of serotonin from morphologically resting platelets and shape changed platelets. This suggests that oxidized LDL, a newly reported weak agonist, contributes to atherogenesis and thrombogenesis by stimulating platelets.

Cell adhesion to the apical pole of epithelium: a function of cell polarity.

Human uterine epithelium displays a distinct polarized organization with apical, lateral, and basal plasma membrane domains. Although non-adhesive throughout most of the menstrual cycle, epithelial cells allow attachment of trophoblast cells to their apical pole during embryo implantation. A recent hypothesis postulates that epithelial cells turn off genes for apical-basal polarity and turn on genes for a more mesenchyme-like phenotype allowing cell-cell interaction with trophoblast. Using an in vitro assay human uterine cell lines (RL95-2, HEC-1-A, AN3-CA) were selected on the basis of adhesiveness for trophoblast-type cells (JAR). Subsequently, uterine cells were examined for epithelium-specific ultrastructure using transmission electron microscopy, and for the expression of E-cadherin, alpha 6-, beta 1-, beta 4-integrin subunits and cytokeratin using immunocytochemistry, confocal laser scanning microscopy, and surface replication technique. HEC-1-A monolayers are non-adhesive for JAR cells and appear highly polarized expressing E-cadherin, alpha 6-, beta 1-, beta 4-integrin subunits, and cytokeratin. Both, integrins and E-cadherin, are present at the lateral membrane. RL95-2 monolayers which are adhesive for JAR cells appear non-polarized. Like HEC-1-A cells, RL95-2 cells express E-cadherin, alpha 6-, beta 1-, and beta 4-integrin subunits, and cytokeratin. In contrast to HEC-1-A cells, integrins and E-cadherin are distributed at the entire cell surface. AN3-CA monolayers are non-adhesive for JAR cells and appear non-polarized. Cells lack epithelial-specific markers such as keratin and E-cadherin. They show only low expression of alpha 6-, beta 1-integrin subunits and lack beta 4-integrin subunit. Conversely, they express vimentin. Thus, modulation of the epithelial phenotype of uterine cells, i.e. loss of apical-basal polarity, might prepare the apical cell pole for cell-cell interaction with trophoblast. However, loss of cell polarity would not lead to enhancement of adhesiveness for trophoblast if accompanied by a loss of epithelium-specific adhesion molecules.