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T Haug

Publications and source records attributed to T Haug.

At least 19 recordsLinked to original sources
PubMed2005

Micromagnetic dissipation, dispersion, and mode conversion in thin permalloy platelets.

Micron-sized ferromagnetic Permalloy disks exhibiting an in-plane ferromagnetic vortex structure are excited by a fast rise time perpendicular magnetic field pulse and their modal structure is analyzed. We find azimuthal and axial modes. By a Fourier filtering technique we can separate and analyze the time dependence of individual modes. Analysis of the experimental data demonstrates that the azimuthal modes damp more quickly than the axial modes. We interpret these results as mode conversion from low-frequency azimuthal modes to the fundamental mode which is higher in frequency, i.e., mode-mode coupling in a system with a single Landau-Lifshitz-Gilbert phenomenological damping constant alpha.

Journal Article↗
PubMed2004

Fourier transform imaging of spin vortex eigenmodes.

Thin-circular lithographically defined magnetic elements with a spin vortex configuration are excited with a short perpendicular magnetic field pulse. We report the first images of excited magnetic eigenmodes up to third order, obtained by means of a phase sensitive Fourier transform imaging technique. Both axially symmetric and symmetry breaking azimuthal eigenmodes are observed. We observe strong oscillations of the magnetization in the central part of the magnetic elements. The experimental data are in good agreement with micromagnetic simulations.

Journal Article↗
PubMed2004

Gene expression analysis of peripheral T cells in a subgroup of common variable immunodeficiency shows predominance of CCR7(-) effector-memory T cells.

Common variable immunodeficiency (CVID) represents a heterogeneous group of antibody deficiency syndromes, characterized by defective antibody production in which T cell deficiency may play a pathogenic role. A subgroup of CVID patients has impaired in vitro T cell proliferation. Using microarray analyses of T cells from these patients, we found a gene expression pattern different from healthy controls and patients with X-linked agammaglobulinaemia. The profile of the differentially expressed genes suggests enhanced cytotoxic effector functions, antigen experienced or chronically activated T cells and a predominance of CCR7(-) T cells. Further experiments using flow cytometry revealed a striking predominance of CCR7(-) T cells in a subgroup of CVID patients, and an association with impaired T cell proliferation. Our observations indicate that a predominance of CCR7(-) T cells with effector-memory cell features and with reduced proliferative capacity may characterize a subgroup of CVID.

Adult↗
PubMed2003

Levels and patterns of persistent organochlorines in minke whale (Balaenoptera acutorostrata) stocks from the North Atlantic and European Arctic.

Regional variation in PCBs and organochlorine (OC) pesticide concentrations was examined using the blubber of 155 minke whales (Balaenoptera acutorostrata) sampled in seven regions in the North Atlantic and European Arctic, including western and southeastern Greenland, the Norwegian Sea, the North Sea and the Barents Sea. The levels and relative proportions of OCs were also used to examine the boundaries for North Atlantic minke whale stocks previously defined by the International Whaling Commission (IWC). Concentrations of major OC groups (sigmaPCB, 89.1-22 800 ng/g lipid; sigmaDDT, 65.3-6280 ng/g lipid; sigmaCHL, 33.3-2110 ng/g lipid) generally increased from west to east, while HCH concentrations (sigmaHCH, < 1-497 ng/g lipid) showed the opposite trend. Statistical comparison between six regions using sex-adjusted least squared mean concentrations showed that minke whales from the Barents Sea had significantly higher concentrations of EPCBs than those from the Vestfjorden/Lofoten, the North Sea, and west Svalbard, as well as significantly higher sigmaDDT concentrations compared to west Greenland animals. The differences in concentrations suggest that west and southeast Greenland minkes may represent one group of whales, which are distinct from both the Jan Mayen minkes and those from other IWC defined stocks in northern European waters. Principal components analysis using proportions of 71 PCB congeners and 20 OC pesticides (of total OCs) did not reveal any major differences among groups although minkes from the North Sea were distinguished from those from Greenland waters by higher loadings of more highly chlorinated PCBs and recalcitrant OC pesticides. The general similarity in mean levels of sigmaPCBs, sigmaDDT and sigmaCHL, as well as mean principal components analysis scores, among minkes sampled at Jan Mayen, Svalbard, Vestfjorden/Lofoten, the North Sea and the Barents Sea suggests that the whales are quite mobile and may feed in multiple areas within the northeastern Atlantic.

Analysis of Variance↗
PubMed2003

The use of modified primer competitors to enhance yields and specificity of HLA class I amplification by polymerase chain reaction (PCR).

Various PCR based techniques have been developed for genomic HLA typing. The fidelity of these techniques is highly dependent upon the specificity of the primers for the given HLA locus. Due to the high degree of homology between HLA class I loci, few primer sites that selectively amplify genes at a given HLA class I locus may be identified. To avoid coamplification of homologous loci, we designed and applied primer competitors for PCR amplification of HLA-A, -B and -C loci. Primer competitors identical to the 3' end of the specific primers and completely degenerate in the 5' end were designed and titrated into the respective HLA-locus PCR mixtures. We found that inclusion of primer competitors in the PCR reaction increased the specificity and yields of HLA class I amplifications, in particular when crude DNA preparation was used as template. This was particularly true for DNA preparations of low quality. The method described here may be useful for various protocols for downstream genomic typing of HLA-A, -B and -C alleles. In particular the method is useful when DNA is in scarce supply (i.e., for extensive PCR based allelic typing) or when high yields and locus specificity of amplicons are needed (i.e., sequencing-based typing).

Alleles↗
PubMed2002

Effects of interferon-alpha on gene expression of chemokines and members of the tumour necrosis factor superfamily in HIV-infected patients.

We examined the effect of interferon (IFN)-alpha on the expression of 375 genes relevant to inflammatory and immunological reactions in peripheral blood mononuclear cells (PBMC) from HIV-infected patients by cDNA expression array and real-time quantitative RT-PCR. Our main findings were: (i) IFN-alpha induced up-regulation of several genes in the tumour necrosis factor (TNF) superfamily including the ligands APRIL, FasL, TNF-alpha and TRAIL, with particularly enhancing effects on the latter in HIV-infected patients. (ii) While IFN-alpha markedly up-regulated the expression of anti-angionetic ELR- CXC-chemokines (e.g. MIG and IP-10), it suppressed the expression of angiogenic ELR+ CXC-chemokines (e.g. GRO-alpha, IL-8 and ENA-78), with similar patterns in both patients and controls. (iii) IFN-alpha induced a marked increase in gene expression of the HIV co-receptor CCR5 in both patients and controls. We suggest that these effects may contribute to both the therapeutic and toxic effects of IFN-alpha. Moreover, our findings underscore that the biological effects of IFN-alpha in HIV infection are complex and that the clinical net effects of IFN-alpha treatment may be difficult to predict. However, the potent enhancing effect of IFN-alpha on several pro-apoptotic genes in the TNF superfamily and the enhancing effect on CCR5 expression suggest a possible pathogenic role of IFN-alpha in the progression of HIV-related immunodeficiency and suggests caution in the therapeutic use of IFN-alpha in HIV-infected -individuals.

Adult↗
PubMed2001

[Therapy relevant weak sites in industrial quality assurance of 106Ru eye plaques].

BACKGROUND: Beta emitting 106Ru applicators manufactured by Bebig GmbH (Berlin, Germany) are widely used to treat intraocular tumors. The applicators are fixed to the bulbus and removed after several days. The following therapy relevant defects have been detected by an internal clinical acceptance test: risk of leakage and inconsistent dose-rate specifications by the manufacturer. In the meantime, components of the internal clinical acceptance test have been adopted successfully by the manufacturer of the 106Ru ophthalmic plaques. MATERIAL AND METHOD: 106Ru ophthalmic plaques were tested with the following internal clinical acceptance tests: visual inspection, surface contamination, leakage, and dose-rate verification. The surface contamination test consists of a wet wipe test at moderate pressure. For the leakage test of the 106Ru ophthalmic plaques a clinically relevant scenario was developed in which the contact of the applicator with human tissue is simulated. In the course of it the applicator is inserted into Ringer's solution for several days. The certified energy dose-rate statements of the manufacturer are examined with a 1 mm3 plastic scintillator for consistency. RESULTS: During the internal clinically acceptance tests of 106Ru ophthalmic plaques of different size the following results were obtained: The leakage test was performed with seven applicators and yielded measurements for two 106Ru ophthalmic plaques that were significantly higher than those of a dummy sample. The highest value of a wipe test was 57 Bq (Figure 1). The highest value in Ringer's solution was 520 Bq (Figure 2). During the dosimetry consistency checks of the certified dose-rate specifications for 14 applicators, six applicators were in good agreement with a variation coefficient of 2.6%. For the other eight applicators the deviations were between -37% and +74% (Figure 3), i.e. the range of the unaccepted applicators amounts to 111%. The results were representatively verified through external assessment. CONCLUSION: Grave therapy relevant shortcomings of the industrial quality assurance of ophthalmic plaques were uncovered by experimental cross-checks. It is necessary that every radioactive device is internally examined before its use. The internal clinical acceptance test of the 106Ru ophthalmic plaques can easily be adopted by other hospitals.

Brachytherapy↗
PubMed2000

[Aberrations of chromosome 18 and their significance in genetic counseling].

In order to get information on the origin of chromosome 18 aberrations trisomy 18 cases were analysed as well as different chromosome 18 rearrangements. In total, their study population consisted of 100 trisomy 18 patients and their parents, 67 out of which have already been published. Additionally, seven families were analysed with structural aberrations of chromosome 18 including four patients with tetrasomy 18p. Determination of parent and cell stage of origin was performed by short tandem repeat typing (STR, microsatellites). These investigations revealed that the additional chromosomal material in the majority of the chromosomal 18 aberrations was maternal in origin (97/107). In most of the cases the nondisjunction occurred during maternal meiosis II. This was in agreement with findings of other groups. Thus, independently from the type of aberration, there was a predisposition of chromosome 18 for nondisjunction in maternal meiosis II. In this respect, chromosome 18 seemed to be unique among human autosomes. Furthermore, these results showed that molecular genetic analyses of chromosomal aberrations and their formation mechanisms were meaningful tools in genetic counselling situations: in 5 cases where cytogenetic investigations could not performed, the clinical diagnosis of Edwards syndrome could be confirmed by molecular findings. Thus, in these cases other genetic diseases with differing types of inheritance could be excluded from being the cause of the observed malformations. In a further structural rearrangement of chromosome 18, the origin could be determined as being mitotic, therefore a recurrence risk could be excluded for this couple.

Chromosome Aberrations↗
PubMed2000

[Mutational analysis of the connexin26 gene in sporadic cases of moderate to profound deafness].

Non-syndromic neurosensory recessive deafness (NSRD) is one of the most common human sensory disorders. Mutations in the connexin 26 gene have been established as a major cause of inherited and sporadic non-syndromic deafness in different populations. The CX26 gene encodes the gap junction protein connexin 26 (beta-2, GJB2), whose expression was shown in several tissues and in the cochlea. The 30delG mutation is the most frequent mutation in the CX26 gene. It represents a deletion of guanosine (G) in a sequence of six Gs extending from position 30 to 35 of the CX26 cDNA. The deletion creates a frameshift resulting in a premature stop codon and a non-functional intracellular domain in the protein. The 30delG mutation can be detected at the molecular level using PCR followed by BsiYI digestion. We screened 164 mainly German patients with non-syndromic sporadic deafness for this mutation to determine its distribution in the German population. The frequency of the mutation in our analyzed patients was lower than in other studies and therefore indicates its dependency on geographically distinct populations.

Audiometry, Pure-Tone↗
PubMed2000

Protein kinase A mediates the modulation of the slow Ca(2+)-dependent K(+) current, I(sAHP), by the neuropeptides CRF, VIP, and CGRP in hippocampal pyramidal neurons.

We have studied modulation of the slow Ca(2+)-activated K(+) current (I(sAHP)) in CA1 hippocampal pyramidal neurons by three peptide transmitters: corticotropin releasing factor (CRF, also called corticotropin releasing hormone, CRH), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP). These peptides are known to be expressed in interneurons. Using whole cell voltage clamp in hippocampal slices from young rats, in the presence of tetrodotoxin (TTX, 0.5 microM) and tetraethylammonium (TEA, 5 mM), I(sAHP) was measured after a brief depolarizing voltage step eliciting inward Ca(2+) current. Each of the peptides CRF (100-250 nM), VIP (400 nM), and CGRP (1 microM) significantly reduced the amplitude of I(sAHP). Thus the I(sAHP) amplitude was reduced to 22% by 100 nM CRF, to 17% by 250 nM CRF, to 22% by 400 nM VIP, and to 40% by 1 microM CGRP. We found no consistent concomitant changes in the Ca(2+) current or in the time course of I(sAHP) for any of the three peptides, suggesting that the suppression of I(sAHP) was not secondary to a general suppression of Ca(2+) channel activity. Because each of these peptides is known to activate the cyclic AMP (cAMP) cascade in various cell types, and I(sAHP) is known to be suppressed by cAMP via the cAMP-dependent protein kinase (PKA), we tested whether the effects on I(sAHP) by CRF, VIP, and CGRP are mediated by PKA. Intracellular application of the PKA-inhibitor Rp-cAMPS significantly reduced the suppression of I(sAHP) by CRF, VIP, and CGRP. Thus with 1 mM Rp-cAMPS in the recording pipette, the average suppression of I(sAHP) was reduced from 78 to 26% for 100 nM CRF, from 83 to 32% for 250 nM CRF, from 78 to 30% for 400 nM VIP, and from 60 to 7% for 1 microM CGRP. We conclude that CRF, VIP, and CGRP suppress the slow Ca(2+)-activated K(+) current, I(sAHP), in CA1 hippocampal pyramidal neurons by activating the cAMP-dependent protein kinase, PKA. Together with the monoamine transmitters norepinephrine, serotonin, histamine, and dopamine, these peptide transmitters all converge on the cAMP cascade modulating I(sAHP).

Animals↗
PubMed1999

Post-replicative base excision repair in replication foci.

Base excision repair (BER) is initiated by a DNA glycosylase and is completed by alternative routes, one of which requires proliferating cell nuclear antigen (PCNA) and other proteins also involved in DNA replication. We report that the major nuclear uracil-DNA glycosylase (UNG2) increases in S phase, during which it co-localizes with incorporated BrdUrd in replication foci. Uracil is rapidly removed from replicatively incorporated dUMP residues in isolated nuclei. Neutralizing antibodies to UNG2 inhibit this removal, indicating that UNG2 is the major uracil-DNA glycosylase responsible. PCNA and replication protein A (RPA) co-localize with UNG2 in replication foci, and a direct molecular interaction of UNG2 with PCNA (one binding site) and RPA (two binding sites) was demonstrated using two-hybrid assays, a peptide SPOT assay and enzyme-linked immunosorbent assays. These results demonstrate rapid post-replicative removal of incorporated uracil by UNG2 and indicate the formation of a BER complex that contains UNG2, RPA and PCNA close to the replication fork.

Amino Acid Sequence↗
PubMed1998

Nuclear and mitochondrial splice forms of human uracil-DNA glycosylase contain a complex nuclear localisation signal and a strong classical mitochondrial localisation signal, respectively.

Nuclear (UNG2) and mitochondrial (UNG1) forms of human uracil-DNA glycosylase are both encoded by the UNG gene but have different N-terminal sequences. We have expressed fusion constructs of truncated or site-mutated UNG cDNAs and green fluorescent protein cDNA and studied subcellular sorting. The unique 44 N-terminal amino acids in UNG2 are required, but not sufficient, for complete sorting to nuclei. In this part the motif R17K18R19is essential for sorting. The complete nuclear localization signal (NLS) in addition requires residues common to UNG2 and UNG1 within the 151 N-terminal residues. Replacement of certain basic residues within this region changed the pattern of subnuclear distribution of UNG2. The 35 unique N-terminal residues in UNG1 constitute a strong and complete mitochondrial localization signal (MLS) which when placed at the N-terminus of UNG2 overrides the NLS. Residues 11-28 in UNG1 have the potential of forming an amphiphilic helix typical of MLSs and residues 1-28 are essential and sufficient for mitochondrial import. These results demonstrate that UNG1 contains a classical and very strong MLS, whereas UNG2 contains an unusually long and complex NLS, as well as subnuclear targeting signals in the region common to UNG2 and UNG1.

Alternative Splicing↗
PubMed1998

Molecular determinants of KATP channel inhibition by ATP.

ATP-sensitive K+ (KATP) channels are both inhibited and activated by intracellular nucleotides, such as ATP and ADP. The inhibitory effects of nucleotides are mediated via the pore-forming subunit, Kir6.2, whereas the potentiatory effects are conferred by the sulfonylurea receptor subunit, SUR. The stimulatory action of Mg-nucleotides complicates analysis of nucleotide inhibition of Kir6. 2/SUR1 channels. We therefore used a truncated isoform of Kir6.2, that expresses ATP-sensitive channels in the absence of SUR1, to explore the mechanism of nucleotide inhibition. We found that Kir6.2 is highly selective for ATP, and that both the adenine moiety and the beta-phosphate contribute to specificity. We also identified several mutations that significantly reduce ATP inhibition. These are located in two distinct regions of Kir6.2: the N-terminus preceding, and the C-terminus immediately following, the transmembrane domains. Some mutations in the C-terminus also markedly increased the channel open probability, which may account for the decrease in apparent ATP sensitivity. Other mutations did not affect the single-channel kinetics, and may reduce ATP inhibition by interfering with ATP binding and/or the link between ATP binding and pore closure. Our results also implicate the proximal C-terminus in KATP channel gating.

ATP-Binding Cassette Transporters↗
PubMed1998

MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.

ATP-sensitive potassium (KATP) channels in the pancreatic beta cell membrane mediate insulin release in response to elevation of plasma glucose levels. They are open at rest but close in response to glucose metabolism, producing a depolarization that stimulates Ca2+ influx and exocytosis. Metabolic regulation of KATP channel activity currently is believed to be mediated by changes in the intracellular concentrations of ATP and MgADP, which inhibit and activate the channel, respectively. The beta cell KATP channel is a complex of four Kir6.2 pore-forming subunits and four SUR1 regulatory subunits: Kir6.2 mediates channel inhibition by ATP, whereas the potentiatory action of MgADP involves the nucleotide-binding domains (NBDs) of SUR1. We show here that MgATP (like MgADP) is able to stimulate KATP channel activity, but that this effect normally is masked by the potent inhibitory effect of the nucleotide. Mg2+ caused an apparent reduction in the inhibitory action of ATP on wild-type KATP channels, and MgATP actually activated KATP channels containing a mutation in the Kir6.2 subunit that impairs nucleotide inhibition (R50G). Both of these effects were abolished when mutations were made in the NBDs of SUR1 that are predicted to abolish MgATP binding and/or hydrolysis (D853N, D1505N, K719A, or K1384M). These results suggest that, like MgADP, MgATP stimulates KATP channel activity by interaction with the NBDs of SUR1. Further support for this idea is that the ATP sensitivity of a truncated form of Kir6.2, which shows functional expression in the absence of SUR1, is unaffected by Mg2+.

ATP-Binding Cassette Transporters↗
PubMed1998

Regulation of expression of nuclear and mitochondrial forms of human uracil-DNA glycosylase.

Promoters PA and PBin the UNG gene and alternative splicing are utilized to generate nuclear (UNG2) and mitochondrial (UNG1) forms of human uracil-DNA glycosylase. We have found the highest levels of UNG1 mRNA in skeletal muscle, heart and testis and the highest UNG2 mRNA levels in testis, placenta, colon, small intestine and thymus, all of which contain proliferating cells. In synchronized HaCaT cells mRNAs for both forms increased in late G1/early S phase, accompanied by a 4- to 5-fold increase in enzyme activity. A combination of mutational analysis and transient transfection demonstrated that an E2F-1/DP-1-Rb complex is a strong negative regulator of both promoters, whereas 'free' E2F-1/DP-1 is a weak positive regulator, although a consensus element for E2F binding is only present in PB. These results indicate a central role for an E2F-DP-1-Rb complex in cell cycle regulation of UNG proteins. Sp1 and c-Myc binding elements close to transcription start areas were positive regulators of both promoters, however, whereas overexpression in HeLa cells of Sp1 stimulated both promoters, c-Myc and c-Myc/Max overexpression had a suppressive effect. CCAAT elements were negative regulators of PB, but positive regulators of PA. These results demonstrate differential expression of mRNAs for UNG1 and UNG2 in human tissues.

Alternative Splicing↗
PubMed1998

Modulation of the Ca2+-activated K+ current sIAHP by a phosphatase-kinase balance under basal conditions in rat CA1 pyramidal neurons.

The slow Ca2+-activated K+ current, sIAHP, underlying spike frequency adaptation, was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases (microcystin, calyculin A, cantharidic acid) caused a gradual decrease of sIAHP amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation turnover regulating sIAHP. Because selective calcineurin (PP-2B) inhibitors did not affect the amplitude of sIAHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are most likely involved in the basal regulation of this current. The ATP analogue, ATP-gamma-S, caused a gradual decrease in the sIAHP amplitude, supporting a role of protein phosphorylation in the basal modulation of sIAHP. When the protein kinase A (PKA) inhibitor adenosine-3', 5'-monophosphorothioate, Rp-isomer (Rp-cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the decrease in the sIAHP amplitude that was observed when microcystin alone was applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the sIAHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22, 536) and adenosine 3',5'-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20-1724 and rolipram) led to an increase or a decrease in the sIAHP amplitude, respectively. These findings suggest that a balance between basally active PKA and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of sIAHP, resulting in a continuous modulation of excitability and firing properties of hippocampal pyramidal neurons.

Adenylyl Cyclases↗
PubMed1997

Opposite base-dependent reactions of a human base excision repair enzyme on DNA containing 7,8-dihydro-8-oxoguanine and abasic sites.

The guanine modification 7,8-dihydro-8-oxoguanine (8-oxoG) is a potent premutagenic lesion formed spontaneously at high frequencies in the genomes of aerobic organisms. We have characterized a human DNA repair glycosylase for 8-oxoG removal, hOGH1 (human yeast OGG1 homologue), by molecular cloning and functional analysis. Expression of the human cDNA in a repair deficient mutator strain of Escherichia coli (fpg mutY) suppressed the spontaneous mutation frequency to almost normal levels. The hOGH1 enzyme was localized to the nucleus in cells transfected by constructs of hOGH1 fused to green fluorescent protein. Enzyme purification yielded a protein of 38 kDa removing both formamidopyrimidines and 8-oxoG from DNA. The enzymatic activities of hOGH1 was analysed on DNA containing single residues of 8-oxoG or abasic sites opposite each of the four normal bases in DNA. Excision of 8-oxoG opposite C was the most efficient and was followed by strand cleavage via beta-elimination. However, significant removal of 8-oxoG from mispairs (8-oxoG: T >G >A) was also demonstrated, but essentially without an associated strand cleavage reaction. Assays with abasic site DNA showed that strand cleavage was indeed dependent on the presence of C in the opposite strand, irrespective of the prior removal of an 8-oxoG residue. It thus appears that strand incisions are made only if repair completion results in correct base insertion, whereas excision from mispairs preserves strand continuity and hence allows for error-free correction by a postreplicational repair mechanism.

Amino Acid Sequence↗