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M Bruns

Publications and source records attributed to M Bruns.

At least 19 recordsLinked to original sources
PubMed2006

Nitrogen diffusion in amorphous silicon nitride isotope multilayers probed by neutron reflectometry.

Amorphous silicon nitride is a model system for a covalently bound amorphous solid with a low atomic mobility where reasonable values of self-diffusivities are still lacking. We used neutron reflectometry on isotope enriched Si3 14N4/Si3 15N4 multilayers to determine nitrogen self-diffusivities ranging from 10(-24) to 10(-21) m2/s between 950 and 1250 degrees C. Time dependent diffusivities observed at 1150 degrees C indicate the presence of structural relaxation. For long annealing times (relaxed state) the diffusivities follow an Arrhenius law with an activation enthalpy of (3.6 +/- 0.4) eV. The results are indicative of a direct diffusion mechanism without the involvement of thermal point defects.

Journal Article↗
PubMed2006

[Problems in the vocational rehabilitation of mentally ill subjects--a simple procedure to identify persons with an increased risk for premature termination of a training programme].

UNLABELLED: A small number of young mentally ill persons consumes a disproportionate amount of psychiatric service resources. These persons are characterised by emotional instability, aggressive or delinquent behaviour, substance misuse and personality disorders. They are sometimes referred to as young adult chronic patients (YACP). To date there has been no investigation as to what impact this pattern of problem behaviour has on vocational rehabilitation. AIM: The aim of this study was to find out whether belonging to the YACP group, as determined by an operational definition, reduces the outcome of vocational rehabilitation. METHOD: A chart review was done of the files of all 174 participants of a 15-month vocational training course held between 1.1.1993 and 2.5.1998 in the vocational training centre at Cologne. A 15-item score was used to assess YACP status. RESULTS: 30 % were classified as high scorers, i. e. YACP. 59 % of the high scorers vs. 22 % of the low scorers terminated training prematurely. Of the high scorers who completed training, only 47 (vs. 74 % of low scorers) were judged to be able to work at the end of training. CONCLUSION: At the very beginning of the vocational training persons in need of a highly individualised format can be discerned by a few, easy to assess items. Concepts of vocational training should be developed to better suit the needs of young mentally ill persons with personality disorders and substance abuse.

Adult↗
PubMed2001

Cutting edge: neosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein.

CTLs recognize peptide epitopes which are proteolytically generated by the proteasome and presented on MHC class I molecules. According to the defective ribosomal product (DRiP) hypothesis, epitopes originate from newly synthesized polypeptides which are degraded shortly after their translation. The DRiP hypothesis would explain how epitopes can be generated from long-lived proteins. We examined whether neosynthesis is required for presentation of the immunodominant epitope NP118 of the lymphocytic choriomeningitis virus nucleoprotein, which has a half-life of >3 days. Two days after nucleoprotein biosynthesis was terminated in a tetracycline-regulated transfectant, the presentation of the NP118 epitope ceased. This indicates that NP118 epitopes are generated from newly synthesized nucleoproteins rather than from the long-lived pool of nucleoproteins in the cell. Therefore, the lymphocytic choriomeningitis virus nucleoprotein is the first substrate for which a major prediction of the DRiP hypothesis, namely the requirement for neosynthesis, is shown to hold true.

Animals↗
PubMed2001

Identification and analysis of a new hepadnavirus in white storks.

We identified, cloned, and functionally characterized a new avian hepadnavirus infecting storks (STHBV). STHBV has the largest DNA genome of all avian hepadnaviruses and, based on sequence and phylogenetic analysis, is most closely related to, but distinct from, heron hepatitis B virus (HHBV). Unique for STHBV among the other avian hepadnaviruses is a potential HNF1 binding site in the preS promoter. In common only with HHBV, STHBV has a myristylation signal on the S and not the preS protein, two C terminally located glycosylation sites on the precore/core proteins and lacks the phosphorylation site essential for the transcriptional transactivation activity of duck-HBV preS protein. The cloned STHBV genomes were competent in gene expression, replication, and viral particle secretion. STHBV infected primary duck hepatocytes very inefficiently suggesting a restricted host range, similar to other hepadnaviruses. This discovery of stork infections unravels novel evolutionary aspects of hepadnaviruses and provides new opportunities for hepadnavirus research.

Amino Acid Sequence↗
PubMed2001

Al(22)Cl(20).12L (L = THF, THP): the first polyhedral aluminum chlorides.

Aluminum subhalides of the type Al(22)X(20).12L (X = Cl, Br; L = THF, THP) are the only known representatives of polyhedral aluminum subhalides and exhibit interesting multicenter bonding properties. Herein, we report on the synthesis and structural investigation of the first chlorides of this type. Additional investigations applying solid-state (27)Al NMR (MAS), XPS (of Al(4)Cp(4) and Al(22)X(20).12L), and quantum chemical calculations shed more light upon the structure of the molecules and possible Al modifications.

Journal Article↗
PubMed2001

First outbreak of callitrichid hepatitis in Germany: genetic characterization of the causative lymphocytic choriomeningitis virus strains.

Callitrichid hepatitis (CH) is a highly fatal, rodent-borne zoonosis of New World primates (family Callitrichidae) caused by lymphocytic choriomeningitis virus (LCMV). It is unclear whether virulence in Callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial S RNA sequence of a single CH-associated isolate is known. In a period of 10 months, three pygmy marmosets (Cebuella pygmaea) and one Goeldi's monkey (Callimico goeldii) died from CH in a German zoo. LCMV was most likely transmitted by wild mice. Infection was associated with characteristic histopathological lesions in liver, brain, and lymphoid tissue. Virus sequences from all callitrichids and a captured mouse were > or =99.2% identical. LCMV strains from a pygmy marmoset and the Goeldi's monkey were isolated in cell culture and the 3.4-kb S RNA was completely sequenced. Both strains differed considerably in their genetic and phylogenetic characteristics from known LCMV strains, including the previously described CH-associated strain. These data show that CH is widespread and can be caused by distantly related LCMV strains.

Amino Acid Sequence↗
PubMed2001

Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH)-Re-evaluation of chromosome aberration rates in early spontaneous abortions.

Comparative genomic hybridisation (CGH) represents an alternative molecular-cytogenetic technique capable of detecting chromosomal imbalances by reverse fluorescence in situ hybridisation. As the technique uses genomic DNA for assessment it does not rely on metaphase chromosomes in the test material and thus circumvents technical problems associated with tissue culturing. In the present study, we applied CGH to identify chromosome anomalies in 60 spontaneous abortions of the first trimester, that had failed to grow in culture. In 57 out of 60 cases CGH analyses were successful. The overall aneuploidy rate detected was 72%. Trisomy was the predominant chromosome anomaly accounting for 68.0% of abnormal abortions, followed by triploidy (17.1%) and monosomy X (9.8%). An unbalanced structural rearrangement was found in one (2.4%) abortion. Most frequently involved in trisomies were chromosomes 16 (32.1%), 7 and 22 (10.7% each), 4, 13, 15, and 21 (7.2 % each). Three triploid cases and one complete mole were detected by microsatellite analysis as supplementary method. CGH data on culture failures were compared with data derived from 4693 successfully karyotyped first trimester spontaneous abortions, resulting in a chromosome aberration rate of 64.8%. The distribution of the different chromosome anomalies was similar with the exception of a higher rate of trisomies 7 and of XYY-triploidies in the culture failures. Based on our data we suggest that the genetic contribution to pregnancy loss is still underestimated. Investigating abortion tissues hitherto unassessed by conventional methods, we suggest that the contribution of chromosome aberrations to first trimester pregnancy loss is nearly 70%.

Abortion, Spontaneous↗
PubMed1999

A new avian hepadnavirus infecting snow geese (Anser caerulescens) produces a significant fraction of virions containing single-stranded DNA.

We describe the identification and functional analysis of an evolutionary distinct new avian hepadnavirus. Infection of snow geese (Anser caerulescens) with a duck hepatitis B virus (DHBV)-related virus, designated SGHBV, was demonstrated by detection of envelope proteins in sera with anti-DHBV preS and S antibodies. Comparative sequence analysis of the PCR-amplified SGHBV genomes revealed unique SGHBV sequence features compared with other avian hepadnaviruses. Unlike DHBV, SGHBV shows an open reading frame in an analogous position to orthohepadnavirus X genes. Four of five cloned genomes were competent in replication, gene expression, and virus particle secretion in chicken hepatoma cells. Primary duck hepatocytes were permissive for infection with SGHBV, suggesting a similar or identical host range. SGHBV was found to secrete a significant fraction of virion-like particles containing single-stranded viral DNA. This was observed both in cell culture medium of SGHBV DNA-transfected LMH cells and in viremic sera of several birds, suggesting that it is a stable trait of SGHBV. Taken together, SGHBV has several unique features that expand the knowledge of the functional and evolutionary diversity of hepadnaviruses and offers new experimental opportunities for studies on the life cycle of hepadnaviruses.

Amino Acid Sequence↗
PubMed1999

Retroviral vectors pseudotyped with lymphocytic choriomeningitis virus.

Pseudotyping can improve retroviral vector stability and transduction efficiency. Here, we describe a novel pseudotype of murine leukemia virus packaged with lymphocytic choriomeningitis virus (LCMV). This pseudotype was stable during ultracentrifugation and infected several cell lines from different species. Moreover, LCMV glycoproteins were not cell toxic.

Animals↗
PubMed1998

Induction of protective cytotoxic T cell responses in the presence of high titers of virus-neutralizing antibodies: implications for passive and active immunization.

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infections in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred immediate protection against systemic virus spread and controlled the virus below detectable levels. However, presence of protective antibody serum titers did not impair induction of antiviral cytotoxic T lymphocyte (CTL) responses after infection with 10(2) PFU of LCMV. These CTLs efficiently protected mice independent of antibodies against challenge with LCMV-glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intracerebral challenge with LCMV-WE, whereas transfused antibodies alone did not protect, and in some cases even enhanced, lethal lymphocytic choriomeningitis. Against the cytopathic vesicular stomatitis virus (VSV), specific CTLs and Th cells were induced in the presence of high titers of VSV-neutralizing antibodies after infection with 10(6) PFU of VSV, but not at lower virus doses. Taken together, preexistent protective antibody titers controlled infection but did not impair induction of protective T cell immunity. This is particularly relevant for noncytopathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccinate against such viruses parallel or sequential passive and active immunization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.

Animals↗
PubMed1998

Enhancement of hepatitis B virus infection by noninfectious subviral particles.

The biological function of the huge excess of subviral particles over virions in hepatitis B virus infections is unknown. Using the duck hepatitis B virus as a model, we unexpectedly found that subviral particles strongly enhance intracellular viral replication and gene expression. This effect is dependent on the multiplicity of infection, the ratio of virions over subviral particles, and the time point of addition of subviral particles. Most importantly, we show that the pre-S protein of the subviral particles triggers enhancement and requires the presence of the binding regions for putative cell-encoded virus receptor proteins. These data suggest that enhancement is due either to the recently described transactivation function of the pre-S protein or to signalling pathways which become activated upon binding of subviral particles to cellular receptors. The findings are of clinical importance, since they imply that infectivity of sera containing hepadnaviruses depends not only on the amount of infectious virions but also decisively on the number of particles devoid of nucleic acids. A similarly dramatic enhancing effect of noninfectious particles in other virus infections is well conceivable.

Animals↗
PubMed1997

Protection of mice by an attenuated variant against the wild-type lymphocytic choriomeningitis virus.

L cells persistently infected with strain Armstrong lymphocytic choriomeningitis virus generated a variant which failed to develop the lethal neurologic disease after application to the brain. This virus was able to protect mice from the fatal consequences when inoculated intracerebrally prior to challenge with wild-type (wt) virus. After infection of mice with the attenuated variant and thereafter with the wt virus, production of the latter was extraordinarily reduced. As expected, virus elimination was finally achieved by cytotoxic T lymphocytes, whose activation was accelerated. Furthermore, two events seem to play an important part in this enhanced virus reduction. First, from the beginning of the infection with wt virus, neutralizing antibodies could be noticed. The second observation was an excessive production of interferon-alpha 1 day after the challenge infection.

Animals↗
PubMed1996

ISFETs with sputtered sodium alumino-silicate glass membranes.

Sodium ion sensitive field-effect transistors (ISFETs) based on reactively sputtered sodium aluminosilicate (NAS) glass membranes are investigated. Using an inverted cylindrical magnetron, NAS films with defined and reproducible composition are obtained. Radiation damage in the gate dielectric is largely eliminated by annealing at 450 degrees C. The Na(+) sensitivity, the selectivity with respect to H(+) and K(+) ions, the response time, the conditioning period, the long-term drift, and the lifetime are evaluated. The ISFETs exhibit a near-Nernstian Na(+) response down to 10(-4) mol/l in solutions of pH>/=7. The NAS films are physically very robust and have excellent chemical durability, e.g., a sensor with a 110 nm thick membrane lasts for about 8 months. The overall sensor properties compare well with those of a commercial Na(+) selective glass electrode.

Journal Article↗
PubMed1996

Novel fibroblast-specific monoclonal antibodies: properties and specificities.

Specific detection of fibroblasts has been one of the unsolved problems in cell biology. Because monoclonal antibodies (MoAbs) might provide an easy and reproducible method of fibroblast detection, we have produced a panel of MoAbs raised against cell surface proteins of human dermal fibroblasts. Using flow cytometry and immunohistochemistry, we have shown that two of these MoAbs, FibAS01 and FibAS02, react exclusively with human fibroblasts. They do not react in vitro with human keratinocytes, endothelial cells, or blood cells. Immunohistologic experiments investigating the binding pattern of the MoAbs FibAS01 and FibAS02 in cryostat sections of different tissues confirmed the flow cytometric results. In human skin, the antibodies exclusively labeled fibroblasts. In other human tissues such as lymph nodes, placenta, kidney, muscle, thyroid gland, gall bladder, cartilage, and tendon, the specificity for fibroblasts was borne out. Neither antibody reacts with fibroblasts from mouse, rat, or pig. The isotype was defined as an IgG1 for both. By western blot analysis, both antibodies detected a molecule of 60-65 kDa under reducing and nonreducing conditions. By immunoelectron microscopy, we observed the antigens on the cell surface without any clustering at specific sites. These data demonstrate that the two MoAbs, FibAS01 and FibAS02, exclusively recognize human fibroblasts.

Animals↗
PubMed1995

Skin fibroblasts are the only source of nidogen during early basal lamina formation in vitro.

The purpose of this study was to determine whether nidogen, the linkage protein of the basal lamina, is of epidermal or dermal origin. The development of the basal lamina was studied in an in vitro skin model. Preputial fibroblasts seeded onto a nylon mesh attached, proliferated, and developed a rich extracellular matrix (dermal model). Preputial keratinocytes were added to the dermal model to form a keratinocyte dermal model that ultrastructurally resembled in many respects human skin. Ultrastructural analysis revealed early stages of dermal development, including an incomplete basal lamina, aggregates of dermal filamentous material connecting to the lamina densa, bundles of 10-nm microfibrils, formation of premature hemidesmosomes, anchoring filaments, and anchoring fibrils. The cell origin of nidogen was determined in the dermal model and in the epidermal and dermal components of the keratinocyte dermal model. Specific antibodies and a cDNA probe for nidogen were used for immunofluorescence microscopy, Western and Northern blots, and for in situ hybridization studies. Our data show that fibroblasts are the only source of nidogen during early basal lamina formation. Although fibroblasts can synthesize nidogen and deposit it in the dermal matrix, no basal lamina will form unless they are recombined with keratinocytes. This suggests that the epidermis plays a major regulatory role in the production and assembly of nidogen into the basal lamina.

Basement Membrane↗
PubMed1994

Characterization of a virus variant produced by L cells persistently infected with lymphocytic choriomeningitis virus.

Continuous cultivation of murine L cells infected with lymphocytic choriomeningitis virus strain Armstrong leads to production of L(Arm) cells, which produce a predominantly cell-associated attenuated variant, the L(Arm) virus. The relatively few infectious particles that are released have lost the ability to form plaques on L cells and to cause illness in mice even if inoculated intracerebrally. Based on equal protein M(r)s, antigenicity and protein kinase activity, essentially identical results were obtained for the purified Armstrong and L(Arm) viruses. There was also no difference in production and release of particles with the potential to cause homologous interference. Such particles consisted of two types, one of which was highly susceptible to u.v.-irradiation, the other was highly resistant. In the case of the L(Arm) virus interfering particles, it appears that the u.v.-irradiation-susceptible forms represented infectious virus. Purified L(Arm) virus particles contained considerable quantities of subgenomic forms of (small) S- and (large) L-RNA and their complementary counterparts, which all appeared to be replicated autonomously in an unenriched manner.

Animals↗
PubMed1994

Immunologic parameters in systemic sclerosis.

BACKGROUND: Immunologic abnormalities seem to play an important role in important role in systemic sclerosis (SSc). METHODS: We studied the following immune parameters to get more insight into SSc: autoantibodies (antinuclear antibodies (ANA), anti-Scl-70, anticentromere antibodies (ACA) subsets of lymphocyte subpopulations and markers of their activation, as well as serum levels of IL-2, the soluble IL-2 receptor (SIL-2R), IL-6 and its correlation to N-terminal procollagen-III propeptide (P III P), and finally, the IL-6 production by SSc and normal dermal fibroblasts. RESULTS: In patients with active SSc, we found a reduced number of CD2+ T-lymphocytes and an increase in the expression of T-lymphocyte activation markers such as CD25+ and CD71+, HLA-DR Ia, as well as elevated serum levels of SIL-2LR and IL-6. SSc fibroblasts did not produce more IL-6 than normal fibroblasts in monolayer cultures. CONCLUSIONS: Our data show that a wide range of immunologic parameters are altered in SSc. In general, T-helper (TH) lymphocytes are activated possibly because of reduced T-suppressor (TS) and natural killer (NK)-cell levels. TH may polyclonally stimulate B cells, which in turn produce higher amounts of autoantibodies. Our findings support the concept that TH cell-derived cytokines/growth factors stimulate matrix protein synthesis by fibroblasts, resulting in generalized fibrosis.

Adolescent↗