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T Berger

Publications and source records attributed to T Berger.

At least 37 records · Page 2Linked to original sources
PubMed2003

Mutations in the gene for toll-like receptor 4 and multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system with heterogeneous pathological features, disease courses and genetical backgrounds. In this study we determined whether genetic variants of toll-like receptor (TLR) 4, which confer substantial differences in the inflammation elicited by bacterial lipopolysaccharide, are related to the development of MS. We found no differences in the frequencies of the cosegregating TLR4 Asp299Gly and Thr399Ile polymorphisms between Austrian MS patients (11.6%) and age-matched controls (13.7%). Furthermore, we could not detect any influence of these mutations on clinical parameters and serum levels of soluble adhesion molecules of MS patients. Our data indicate that these TLR4 polymorphisms have no influence on the incidence, progression and inflammatory parameters of MS.

Alleles↗
PubMed2003

A novel and rapid assay for the detection of neutralizing antibodies against interferon-beta.

There is evidence that neutralizing antibodies (NAB) have a negative influence on the clinical and magnetic resonance imaging effects of interferon-beta (IFNbeta) in multiple sclerosis (MS) patients. The current methods for NAB detection are restricted to specialized laboratories because they require a cell culture and sometimes a viral culture. Results are typically obtained after several weeks. Therefore, the development of a simple and rapid assay for the detection of NAB was sought. Whole blood samples from 28 NAB-positive patients and 110 NAB-negative patients (52 with IFNbeta and 58 without IFNbeta therapy) were incubated with IFNbeta 976 IU/mL for 24 hours. MxA protein levels--a specific marker of class I IFN bioactivity--were measured in paired samples with and without IFNbeta incubation and the difference in MxA levels was calculated. The mean increase of MxA levels after stimulation with IFNbeta in the NAB-positive group was 8 ng/mL (range 0-44 ng/mL) and in the NAB-negative group was 84 ng/mL (range 0-302 ng/mL). Using an increase of 22.5 ng/mL as cut-off) the specificity of the MxA stimulation assay was 81.2% and the sensitivity was 96.4%. The whole blood MxA stimulation assay is virtually as sensitive as the conventional NAB assay but somewhat less specific. However, this is outweighed by the procedural advantage of the assay, which is simpler, quicker and much less expensive.

Adjuvants, Immunologic↗
PubMed2003

Changes in oocyte plasma membrane binding sites on boar spermatozoa with capacitation and acrosome reactions.

The objective of this study was to determine the localization and distribution of oocyte plasma membrane binding sites on capacitated and acrosome-reacting live boar spermatozoa. Localization of oocyte plasma membrane binding sites on boar spermatozoa was determined with fluorescence microscopy and population distribution was examined with flow cytometry. The number of spermatozoa with oocyte plasma membrane bound to the equatorial segment and postacrosomal region of the sperm head significantly increased with capacitation. Equatorial segment labelling further increased with induced acrosome reactions. When the population distribution of oocyte plasma membrane binding sites on live boar spermatozoa was analysed, the percentage of spermatozoa with bound oocyte plasma membrane significantly increased after capacitation compared with that of washed spermatozoa. Binding of oocyte plasma membrane did not increase in control spermatozoa incubated under non-capacitating conditions and was not correlated with the percentage of dead spermatozoa. A change in localization of oocyte plasma membrane binding sites on the sperm head was demonstrated using fluorescence microscopy and an increase in oocyte plasma membrane binding sites after capacitation was shown using flow cytometry.

Acrosome Reaction↗
PubMed2002

Analysis of the neutron component at high altitude mountains using active and passive measurement devices.

The European Council directive 96/29/Euratom requires dosimetric precautions if the effective dose exceeds 1 mSv/a. On an average, this value is exceeded by aircrew members. Roughly half of the radiation exposure at flight altitudes is caused by cosmic ray-induced neutrons. Active (6LiI(Eu)-scintillator) and passive (TLDs) Bonner sphere spectrometers were used to determine the neutron energy spectra atop Mt. Sonnblick (3105 m) and Mt. Kitzsteinhorn (3029 m). Further measurements in a mixed radiation field at CERN as well as in a proton beam of 62 MeV at Paul Scherrer Institute, Switzerland, confirmed that not only neutrons but also charged particles contribute to the readings of active detectors, whereas TLD-600 and TLD-700 in pair allow the determination of the thermal neutron flux. Unfolding of the detector data obtained atop both mountains shows two relative maxima around 1 MeV and 85 MeV, which have to be considered for the assessment of the biologically relevant dose equivalent. By convoluting the spectra with appropriate conversion functions the neutron dose equivalent rate was determined to be 150 +/- 15 nSv/h. The total dose equivalent rate determined by the HTR-method was 210 +/- 15 nSv/h. The results are in good agreement with LET-spectrometer and Sievert counter measurements carried out simultaneously.

Aerospace Medicine↗
PubMed2002

Application of the high-temperature ratio method for evaluation of the depth distribution of dose equivalent in a water-filled phantom on board space station Mir.

A water-filled tissue equivalent phantom with a diameter of 35 cm was developed at the Institute for Biomedical Problems. Moscow. Russia. It contains four channels perpendicular to each other, where dosemeters can be exposed at different depths. Between May 1997 and February 1999 the phantom was installed at three different locations on board the Mir space station. Thermoluminescence dosemeters (TLDs) were exposed at various depths inside the phantom either parallel or perpendicular to the hull of the spacecraft. The high-temperature ratio (HTR) method was used for the evaluation of the TLDs. The method was developed at the Atominstitute of the Austrian Universities. Vienna, Austria, and has already been used for measurements in mixed radiation fields on earth and in space with great success. It uses the changes of peak height ratios in LiF:Mg,Ti glow curves in dependence on the linear energy transfer (LET), and therefore allows determination of an 'averaged' LET as well as measurement of the absorbed dose. A mean quality factor and, subsequently, the dose equivalent can be calculated according to the Q(LETinfinity) relationship proposed by the ICRP. The small size of the LiF dosemeters means that the HTR method can be used to determine the gradient of absorbed dose and dose equivalent inside the tissue equivalent body.

Aerospace Medicine↗
PubMed2002

Dose assessment of aircrew using passive detectors.

Radiation exposure of aircrew is a serious concern which has been given special emphasis in the European Council directive 96/29/Euratom. The cosmic ray induced neutron component can contribute more than 50% to the biologically relevant dose at aviation altitudes. Various computational approaches to route dose assessment, e.g. CARI, are in use nowadays and are compared with experimental data. Measurements of aircrew exposure usually involve extensive instrumentation in order to cover the whole particle spectrum and energy range present inside aircraft. Due to their small size and easy handling, thermoluminescence dosemeters represent an appropriate alternative. Previous measurements onboard aircraft applying the high-temperature ratio method with LiF:Mg,Ti dosemeters for the determination of an 'averaged' linear energy transfer of mixed radiation fields demonstrate the ability of this method to evaluate the dose equivalent, according to the Q(LETinfinity) relationship proposed by the ICRP. Measurements with CaF2:Tm dosemeters are currently in progress and are discussed here.

Aerospace Medicine↗
PubMed2002

Advantages of passive detectors for the determination of the cosmic ray induced neutron environment.

Due to the pronounced energy dependence of the neutron quality factor, accurate assessment of the biologically relevant dose requires knowledge of the spectral neutron fluence rate. Bonner sphere spectrometers (BSSs) are the only instruments which provide a sufficient response over practically the whole energy range of the cosmic ray induced neutron component. Measurements in a 62 MeV proton beam at Paul Scherrer Institute, Switzerland, and in the CERN-EU high-energy reference field led to the assumption that conventional active devices for the detection of thermal neutrons inside the BSS, e.g. 6Lil(Eu) scintillators, also respond to charged particles when used in high-energy mixed radiation fields. The effects of these particles cannot be suppressed by amplitude discrimination and are subsequently misinterpreted as neutron radiation. In contrast, paired TLD-600 and TLD-700 thermoluminescence dosemeters allow the determination of a net thermal neutron signal.

Aerospace Medicine↗
PubMed2002

Thermoluminescence dating of archaeological artefacts from the Middle Neolithic, Bronze Age and the Roman Empire period.

Thermoluminescence (TL) dating was applied for artefacts found near the small village of Michelstetten, Lower Austria. Settlements in this region can be traced hack a long time and, according to archaeologists, the discovered artefacts may be as old as 6000 years. A modified sample preparation technique based on the fine-grain method was developed. This technique results in a higher reproducibility and reduces the overall preparation time. For some artefacts the new information of the TL dating leads to an unforeseen re-interpretation of the archaeological age. Furthermore, an iron furnace from the period of the Roman Empire could be dated. For the first time, it was possible to estimate correctly the point of time of the burn-down of an ancient wooden house via an analysis of the house's clay plaster. The fire took place in the sixth century; this was confirmed by dating ceramic artefacts.

Archaeology↗
PubMed2002

Autonomic instability, as measured by pupillary unrest, is not associated with multiple sclerosis fatigue severity.

Multiple sclerosis (MS) fatigue is one of the most common symptoms in MS, but its pathophysiology is still not understood Sympathovagal imbalance was suggested as a reason for fatigue in chronic fatigue syndrome. We examined the role of an imbalance in the central autonomic nervous system (ANS) as a cause of MS fatigue in 51 MS patients and a control group of 22 healthy volunteers. Fatigue was assessed with the revised MS Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Depression was evaluated with the Beck Depression Inventory (BDI). Disintegration of the central ANS expressed by pupillary fatigue waves was measured with pupillography and documented in the pupillary unrest index (PUI). All subjects had less than five points on the seven-point Stanford Sleepiness Scale and were therefore not sleepy. MS patients had significant higher mean FSS scores (p=0.001) and mean MFIS scores (p=0.003) than our control group. Mean BDI scores were significant higher (p=0.001) in the MS group, but were in the lowest score range (0-10 points) in both groups. Surprisingly, we found a statistically significant inverse correlation between PUI values and either FSS scores (p=0.001; r=-0.521) or MFIS scores (p=0.002; r=-0.423) in the MS group, but not in healthy participants. We therefore conclude that autonomic instability, as measured by pupillary unrest is not associated with MS fatigue severity.

Adolescent↗
PubMed2001

Low-entanglement remote state preparation.

An outer bound on the low-entanglement remote state preparation ebits vs bits tradeoff curve [Bennett et al., quant-ph/0006044, 2000] is found using techniques of classical information theory. We show this bound to be optimal among an important class of protocols and conjecture optimality even without this restriction.

Journal Article↗
PubMed2001

Increased intrathecal production of apolipoprotein D in multiple sclerosis.

Apolipoprotein D (apoD) is a small glycoprotein responsible for the local transport of small hydrophobic ligands. Within the nervous system, apoD may be an acute phase protein that is upregulated in a variety of neuropathological conditions and is involved in the removal of lipids during nerve cell degeneration and provision of lipids during the regenerative phase. In this study, we measured cerebrospinal fluid (CSF) and serum apoD levels in patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré Syndrome (GBS), infectious inflammatory neurological diseases (IND) and non-inflammatory neurological diseases (NND). We found that mean CSF apoD levels are significantly increased in patients with CIDP/GBS reflecting an acute blood-nerve barrier leakage. In contrast, MS is characterized by an increased intrathecal apoD release as measured by the apoD index. Thus, the results of our study provide the first evidence of an increased intrathecal production of apoD in MS. Moreover, we demonstrate that mean apoD indices are highest in MS patients at the time of their first clinical exacerbation. CSF apoD levels and apoD indices correlate with MS disease duration but not with disability or age. Finally, we found that corticosteroid treatment resulted in significantly elevated CSF apoD levels.

Adrenal Cortex Hormones↗
PubMed2001

Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis.

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however. METHODS: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers. RESULTS: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03). CONCLUSIONS: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.

Adult↗
PubMed2001

Do sire-dam interactions contribute significantly to fertility comparisons in heterospermic insemination trials.

The percentage of offspring sired after heterospermic insemination of equal numbers of spermatozoa is believed to be a very sensitive measure of relative in vivo fertility of the inseminated samples. The objective of these trials was to evaluate whether there was a detectable male-female interaction in the fertilizing ability of spermatozoa. If there was such an interaction, we reasoned that the paternity of offspring from individual females in a heterospermic trial the second year would be similar to the paternity of offspring in the same individual females the first year if the same ejaculates were used. Five groups of ewes were inseminated with different combinations of semen (a single Merino ejaculate from one of five rams randomly paired with five different pools of Suffolk semen) in a heterospermic trial. Those ewes conceiving the first year were inseminated in a second breeding season with the same combination of semen used previously. The percentage of lambs sired by each ejaculate/pool of ejaculates was calculated for all lambs born from all ewes inseminated with each semen combination. These percentages would be the expected ratios of Merino-sired:Suffolk-sired lambs if there is no male-female interaction. Ewes in each group were divided into two subgroups: those conceiving only Merino-sired lambs the first year and those conceiving at least one Suffolk-sired lamb the first year. The ratio of Merino-sired lambs:Suffolk-sired lambs did not differ in either subgroup from those expected if there was no male-female interaction. These results are consistent with the absence of a male-female interaction in relative fertilizing ability of spermatozoa.

Animals↗
PubMed2001

Signaling lymphocytic activation molecule is expressed on mature CD83+ dendritic cells and is up-regulated by IL-1 beta.

Signaling lymphocyte activation molecule (SLAM), a 70-kDa costimulatory molecule that mediates CD28-independent proliferation of T cells and IFN-gamma production, has been identified on human T cells, immature thymocytes, and a subset of B cells. We have found that SLAM is expressed on mature but not immature dendritic cells (DC). However, the SLAM-associated protein, is missing in DC. SLAM surface expression is strongly up-regulated by IL-1beta. Addition of IL-1beta to the DC maturation mixture also increases the stimulatory properties of DC. These findings provide a new marker for DC maturation and help to explain two areas of DC biology. First, SLAM is a receptor for the measles virus, previously shown to infect DC. Second, SLAM could possibly contribute to the enhanced immunostimulatory functions of DC that are observed following the addition of IL-1.

Adjuvants, Immunologic↗
PubMed2001

Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood.

It has been known for years that rodents harbor a unique population of CD4(+)CD25(+) "professional" regulatory/suppressor T cells that is crucial for the prevention of spontaneous autoimmune diseases. Here we demonstrate that CD4(+)CD25(+)CD45RO(+) T cells (mean 6% of CD4(+) T cells) are present in the blood of adult healthy volunteers. In contrast to previous reports, these CD4(+)CD25(+) T cells do not constitute conventional memory cells but rather regulatory cells exhibiting properties identical to their rodent counterparts. Cytotoxic T lymphocyte-associated antigen (CTLA)-4 (CD152), for example, which is essential for the in vivo suppressive activity of CD4(+)CD25(+) T cells, was constitutively expressed, and remained strongly upregulated after stimulation. The cells were nonproliferative to stimulation via their T cell receptor for antigen, but the anergic state was partially reversed by interleukin (IL)-2 and IL-15. Upon stimulation with allogeneic (but not syngeneic) mature dendritic cells or platebound anti-CD3 plus anti-CD28 the CD4(+)CD25(+) T cells released IL-10, and in coculture experiments suppressed the activation and proliferation of CD4(+) and CD8(+) T cells. Suppression proved IL-10 independent, yet contact dependent as in the mouse. The identification of regulatory CD4(+)CD25(+) T cells has important implications for the study of tolerance in man, notably in the context of autoimmunity, transplantation, and cancer.

Abatacept↗
PubMed2001

The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls.

Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of the myelin oligodendrocyte glycoprotein (MOG(Igd)) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) and are implicated in the immunopathogenesis of multiple sclerosis (MS). In this study we investigated the epitope specificity of MOG(Igd)-specific autoantibodies immunopurified from MS patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of synthetic MOG(Igd) peptides, revealed that the epitope specificity of this response was heterogeneous in both groups. The most frequently recognised epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87 (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no association between MS and any particular peptide specificity. We therefore investigated the ability of the immunopurified antibodies to recognise native MOG(Igd) expressed on at the membrane surface by FACS. Unexpectedly, antibodies fulfilling this essential criterion for a demyelinating antibody response were detected only in one of the MS samples. These results indicate that the epitope specificity of the human B cell response to MOG is not only heterogeneous, but may only mediate demyelination in a limited subset of MS patients.

Adolescent↗
PubMed2001

Cysteine substitutions in apolipoprotein A-I primary structure modulate paraoxonase activity.

Paraoxonase (PON) is transported primarily on apolipoprotein A-I (apoA-I) -containing high-density lipoprotein (HDL) and is thought to protect against early atherogenic events including low-density lipoprotein (LDL) oxidation and monocyte migration. It has been proposed that apoA-I may be necessary for PON's association with plasma HDL. On the basis of this, we examined the effect of apoA-I on PON's enzymatic activity and its ability to associate with HDL. Additionally, we examined whether changes in apoA-I primary structure (cysteine substitution mutations) could modulate these effects. Chinese hamster ovary cells stably transfected with human PON1A cDNA were incubated in the presence and absence of recombinant wild-type apoA-I (apoA-I(WT)) and specific Cys substitution mutations. Extracellular accumulation of PON activity in the presence of apoA-I(WT) was 0.095 +/- 0.013 unit/mg of cell protein (n = 7) compared to 0.034 +/- 0.010 unit/mg of cell protein in the absence of apoA-I (n = 7), a 2.79-fold increase in activity when apoA-I was incubated with the cells. Lipid-free apoA-I did not increase PON activity, while preformed nascent HDL increased PON activity only 30%, suggesting that maximal PON activity is lipid-dependent and requires coassembly of PON and apoA-I on nascent HDL. The cysteine mutations R10C, R27C, and R61C significantly increased (p < 0.01) PON activity 32.6% +/- 14.7%, 31.6% +/- 18.9%, and 27.4% +/- 20%, respectively, over that of wild type (WT). No changes in PON activity were observed with apoA-I cysteine substitution mutations in the C-terminal portion of the protein. The data suggest that, for optimal PON activity, coassembly of the enzyme onto nascent HDL is required and that the N-terminal region of apoA-I may be important in the assembly process.

Amino Acid Substitution↗