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K Hartung

Publications and source records attributed to K Hartung.

At least 19 recordsLinked to original sources
PubMed2006

Endothelial dysfunction in cold type complex regional pain syndrome.

The authors examined endothelial function in cold type chronic complex regional pain syndrome (CRPS) I using acetylcholine- and sodium nitroprusside-induced vasodilation combined with laser Doppler flowmetry in 14 patients and 10 controls. On the affected side, acetylcholine-induced vasodilation was significantly reduced in comparison to controls and the unaffected extremity. No significant differences were found after application of sodium nitroprusside. The results demonstrate impaired endothelial function in chronic CRPS I.

Acetylcholine↗
PubMed2006

[Laboratory diagnostics of systemic autoimmune diseases. Part 1. Collagenoses].

This is the first part of a series of articles on the laboratory diagnostics of rheumatic diseases and will consider the systemic autoimmune diseases lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermato/polymyositis and mixed connective tissue disease (MCTD, SHARP syndrome). The basis for diagnostics is the presence of antinuclear antibodies (ANA). Initially, these antibodies are detected using a screening test. This must be followed by the identification of the patient's individual autoantibody specificities, which then yields important diagnostic clues. Disease activity may be monitored serologically by following the titers of selected autoantibodies and, in certain patients, by examining complement consumption.

Antibodies, Antinuclear↗
PubMed2005

CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes.

The cystic fibrosis transmembrane conductance regulator (CFTR) plays a crucial role in regulating fluid secretion by the airways, intestines, sweat glands and other epithelial tissues. It is well established that the CFTR is a cAMP-activated, nucleotide-dependent anion channel, but additional functions are often attributed to it, including regulation of the epithelial sodium channel (ENaC). The absence of CFTR-dependent ENaC inhibition and the resulting sodium hyperabsorption were postulated to be a major electrolyte transport abnormality in cystic fibrosis (CF)-affected epithelia. Several ex vivo studies, including those that used the Xenopus oocyte expression system, have reported ENaC inhibition by activated CFTR, but contradictory results have also been obtained. Because CFTR-ENaC interactions have important implications in the pathogenesis of CF, the present investigation was undertaken by our three independent laboratories to resolve whether CFTR regulates ENaC in oocytes and to clarify potential sources of previously reported dissimilar observations. Using different experimental protocols and a wide range of channel expression levels, we found no evidence that activated CFTR regulates ENaC when oocyte membrane potential was carefully clamped. We determined that an apparent CFTR-dependent ENaC inhibition could be observed when resistance in series with the oocyte membrane was not low enough or the feedback voltage gain was not high enough. We suggest that the inhibitory effect of CFTR on ENaC reported in some earlier oocyte studies could be attributed to problems arising from high levels of channel expression and suboptimal recording conditions, that is, large series resistance and/or insufficient feedback voltage gain.

Animals↗
PubMed2001

Voltage and Ca(2+) dependence of pre-steady-state currents of the Na-Ca exchanger generated by Ca(2+) concentration jumps.

The Ca(2+) concentration and voltage dependence of the relaxation kinetics of the Na-Ca exchanger after a Ca(2+) concentration jump was measured in excised giant membrane patches from guinea pig heart. Ca(2+) concentration jumps on the cytoplasmic side were achieved by laser flash-induced photolysis of DM-nitrophen. In the Ca-Ca exchange mode a transient inward current is generated. The amplitude and the decay rate of the current saturate at concentrations >10 microM. The integrated current signal, i.e., the charge moved is fairly independent of the amount of Ca(2+) released. The amount of charge translocated increases at negative membrane potentials, whereas the decay rate constant shows no voltage dependence. It is suggested that Ca(2+) translocation occurs in at least four steps: intra- and extracellular Ca(2+) binding and two intramolecular transport steps. Saturation of the amplitude and of the relaxation of the current can be explained if the charge translocating reaction step is preceded by two nonelectrogenic steps: Ca(2+) binding and one conformational transition. Charge translocation in this mode is assigned to one additional conformational change which determines the equilibrium distribution of states. In the Na-Ca exchange mode, the stationary inward current depends on the cytoplasmic Ca(2+) concentration and voltage. The K(m) for Ca(2+) is 4 microM for guinea pig and 10 microM for rat myocytes. The amplitude of the pre-steady-state current and its relaxation saturate with increasing Ca(2+) concentrations. In this mode the relaxation is voltage dependent.

Acetates↗
PubMed2001

Non-specific activation of the epithelial sodium channel by the CFTR chloride channel.

The genetic disease cystic fibrosis is caused by mutation of the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Controversial studies reported regulation of the epithelial sodium channel (ENaC) by CFTR. We found that uptake of (22)Na(+) through ENaC is modulated by activation of CFTR in oocytes, coexpressing CFTR and ENaC, depending on extracellular chloride concentration. Furthermore we found that the effect of CFTR activation could be mimicked by other chloride channels. Voltage- and patch-clamp measurements, however, showed neither stimulation nor inhibition of ENaC-mediated conductance by activated CFTR. We conclude that the observed modulation of (22)Na(+) uptake by activated CFTR is due to the effect of CFTR-mediated chloride conductance on the membrane potential. These findings argue against the notion of a specific influence of CFTR on ENaC and emphasize the chloride channel function of CFTR.

Animals↗
PubMed2001

Sensitivity to brief changes of interaural time and interaural intensity.

The purpose of this study was to measure listeners' abilities to detect brief changes in interaural temporal disparities (ITDs) or interaural intensitive disparities (IIDs) conveyed by bursts of noise (probes) temporally and symmetrically flanked by segments of diotic or uncorrelated noise. Thresholds were measured using a four-interval, two-alternative, forced-choice adaptive task and the total duration of the bursts of noise was either 20, 40, or 100 ms. Probes were temporally centered within each burst and the durations of the probes ranged from 2 to 100 ms, depending upon the duration of the (longer) total burst of noise within which they were embedded. The results indicate that, for a given total duration of noise, there is a rapid decrease in threshold ITD or threshold IID as the duration of the probe is increased so that it occupies a larger portion of the total burst of noise. Mathematical analyses revealed that both threshold ITDs and threshold IIDs could be well accounted for by assuming that the listener processes both types of binaural cues via a single, symmetric, double-exponential temporal window. Interestingly, the shapes of the temporal windows that fit the data obtained from the human listeners resemble the shapes of the temporal windows derived by Wagner [H. Wagner, J. Comp. Physiol. A 169, 281-289 (1991)], who studied the barn owl. The time constants and relative weightings yielded temporal window functions that heavily emphasize information occurring within the very temporal center of the window. This temporal window function was found to be generalizable in the sense that it also accounts for classic data reported by Grantham and Wightman [D.W. Gratham and F.L. Wightman, J. Acoust. Soc. Am. 63, 511-523 (1978)] concerning sensitivity to dynamically changing interaural disparities.

Acoustic Stimulation↗
PubMed2001

Peripheral auditory processing and investigations of the "precedence effect" which utilize successive transient stimuli.

This article addresses how a consideration of peripheral auditory processing can help to understand experiments concerning binaural precedence that employ successive binaural transients. It appears that much of the patterning of the behavioral data is amenable to an explanation based on peripheral interactions that result from auditory filtering and the functioning of auditory hair cells in combination with a binaural model based on cross correlation. A noteworthy aspect of this approach is that it does not include inhibitory mechanisms like those commonly invoked to explain binaural precedence.

Acoustic Stimulation↗
PubMed2000

Voltage and substrate dependence of the inverse transport mode of the rabbit Na(+)/glucose cotransporter (SGLT1).

Properties of the cytoplasmic binding sites of the rabbit Na(+)/glucose cotransporter, SGLT1, expressed in Xenopus oocytes were investigated using the giant excised patch clamp technique. Voltage and substrate dependence of the outward cotransport were studied using alpha-methyl D-glucopyranoside (alphaMDG) as a substrate. The apparent affinity for alphaMDG depends on the cytoplasmic Na(+) concentration and voltage. At 0 mV the K(M) for alphaMDG is 7 mM at 110 mM Na(+) and 31 mM at 10 mM Na(+). The apparent affinity for alphaMDG and Na(+) is voltage dependent and increases at positive potentials. At 0 mV holding potential the outward current is half-maximal at about 70 mM. The results show that SGLT1 can mediate sugar transport out of the cell under appropriate concentration and voltage conditions, but under physiological conditions this transport is highly improbable due to the low affinity for sugar.

Animals↗
PubMed2000

Rheumatoid factors in systemic lupus erythematosus: association with clinical and laboratory parameters. SLE study group.

The prevalence and clinical and laboratory associations of IgM, IgG and IgA rheumatoid factors (RF) were determined in 352 patients with systemic lupus erythematosus (SLE). IgM, IgG, and IgA class RF were detected in 17.9%, 20.5%, and 20.5% of the sera, respectively. RF were associated with sicca syndrome, hypergammaglobulinemia, high titer of antinuclear antibodies, anemia, SSA- and SSB-antibodies, and with the presence of HLA-DR3. RF correlated negatively with nephritis and livedo racemosa. Moreover, we observed an association of RF and parameters of inflammatory activity such as elevated erythrocyte sedimentation rate (ESR) and leukopenia. Analysis of immunoglobulin classes revealed that laboratory parameters of inflammatory activity, SSA- and SSB-antibodies and HLA-DR3 correlated with IgA RF only. IgA RF define a subgroup of SLE patients characterized by distinct autoimmune phenomena and high disease activity in the absence of nephritis.

Antibodies, Antinuclear↗
PubMed2000

IgA and IgG autoantibodies against alpha-fodrin as markers for Sjögren's syndrome. Systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of IgA and IgG autoantibodies against alpha-fodrin in patients with primary and secondary Sjögren's syndrome (SS) and controls. METHODS: An ELISA detecting IgA and IgG antibodies against alpha-fodrin was developed. We examined the prevalence of IgA and IgG antibodies against alpha-fodrin in patients with primary and secondary SS, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and blood donors. RESULTS: IgA antibodies against alpha-fodrin were detected in 64% of patients with primary SS (n = 85), 47% of patients with secondary SS and SLE (n = 15), and 86% of patients with secondary SS and RA (n = 7). IgA autoantibodies against alpha-fodrin were detected in only one of 160 sera obtained from blood donors and in one of 50 and 2 of 12 sera obtained from SLE and RA patients without sicca syndrome, respectively. The prevalence of IgG antibodies against alpha-fodrin in SS was lower: they were detected in 55% of sera obtained from patients with primary SS, 40% of patients with secondary SS and SLE, and in 43% of patients with secondary SS and RA. Three of 160 sera from blood donors and one of 50 and 5 of 12 sera from SLE and RA patients without sicca syndrome, respectively, contained IgG antibodies against alpha-fodrin. CONCLUSION: IgA rather than IgG antibodies against alpha-fodrin are specific for and frequently observed in primary and secondary SS and are useful markers for this autoimmune disorder.

Adult↗
PubMed1999

Thrombomodulin in systemic lupus erythematosus: association with clinical and laboratory parameters.

Thrombomodulin is an endothelial cell membrane glycoprotein and is detected in plasma and serum after endothelial injury. In our study comprising 311 patients with systemic lupus erythematosus (SLE) clinical and laboratory associations of elevated thrombomodulin serum concentrations were examined. Elevated thrombomodulin concentrations were detected in 7.1% of the SLE patients and were associated with nephritis including the laboratory parameters proteinuria and erythrocyte casts, vasculitis and neurological involvement of the central nervous system. These correlations remained significant after consideration of the influence of renal function. In SLE, the serum thrombomodulin concentration may become a marker to monitor damage of endothelial cells and involvement of the central nervous system.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Polynucleotide probes that target a hypervariable region of 16S rRNA genes to identify bacterial isolates corresponding to bands of community fingerprints.

Temperature gradient gel electrophoresis (TGGE) is well suited for fingerprinting bacterial communities by separating PCR-amplified fragments of 16S rRNA genes (16S ribosomal DNA [rDNA]). A strategy was developed and was generally applicable for linking 16S rDNA from community fingerprints to pure culture isolates from the same habitat. For this, digoxigenin-labeled polynucleotide probes were generated by PCR, using bands excised from TGGE community fingerprints as a template, and applied in hybridizations with dot blotted 16S rDNA amplified from bacterial isolates. Within 16S rDNA, the hypervariable V6 region, corresponding to positions 984 to 1047 (Escherichia coli 16S rDNA sequence), which is a subset of the region used for TGGE (positions 968 to 1401), best met the criteria of high phylogenetic variability, required for sufficient probe specificity, and closely flanking conserved priming sites for amplification. Removal of flanking conserved bases was necessary to enable the differentiation of closely related species. This was achieved by 5' exonuclease digestion, terminated by phosphorothioate bonds which were synthesized into the primers. The remaining complementary strand was removed by single-strand-specific digestion. Standard hybridization with truncated probes allowed differentiation of bacteria which differed by only two bases within the probe target site and 1.2% within the complete 16S rDNA. However, a truncated probe, derived from an excised TGGE band of a rhizosphere community, hybridized with three phylogenetically related isolates with identical V6 sequences. Only one of the isolates comigrated with the excised band in TGGE, which was shown to be due to identical sequences, demonstrating the utility of a combined TGGE and V6 probe approach.

Actinobacillus↗
PubMed1999

PARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various autoantibodies that recognize autoantigens displayed on the surface of cells undergoing apoptosis. The genetic contribution to SLE susceptibility has been widely recognized. We previously reported evidence for linkage to SLE of the human chromosome 1q41-q42 region and have now narrowed it from 15 to 5 cM in an extended sample using multipoint linkage analysis. Candidate genes within this region include (a) PARP, poly(ADP-ribose) polymerase, encoding a zinc-finger DNA-binding protein that is involved in DNA repair and apoptosis; (b) TGFB2, encoding a transforming growth factor that regulates cellular interactions and responses; and (c) HLX1, encoding a homeobox protein that may regulate T-cell development. Using a multiallelic, transmission-disequilibrium test (TDT), we found overall skewing of transmission of PARP alleles to affected offspring in 124 families (P = 0.00008), preferential transmission of a PARP allele to affected offspring (P = 0.0003), and lack of transmission to unaffected offspring (P = 0.004). Similar TDT analyses of TGFB2 and HLX1 polymorphisms yielded no evidence for association with SLE. These results suggest that PARP may be (or is close to) the susceptibility gene within the chromosome 1q41-q42 region linked to SLE.

Alleles↗
PubMed1998

[Primary Sjögren's syndrome and glomerulonephritis].

HISTORY AND CLINICAL FINDINGS: An 82-year-old woman with hypertension for 20 years developed a nephrotic syndrome with severe oedema followed by acute oliguric renal failure after a bout of bronchitis and a gastrointestinal infection. She also complained of xerostomia and dry eyes of recent onset. INVESTIGATIONS: Biochemical tests showed a serum creatinine level of 6.1 mg/dl, a 1:5120 antinuclear antibody (ANA) titre, and positive values for Ro(SS-A) and La(SS-B) antibodies. HLA-DR typing demonstrated HLA-DR3 (HLA-DRB1*0301) and DR13 (HLA-DRB1*13) antigens. Renal biopsy revealed minimal glomerular lesions with focal and segmental glomerulo-sclerosis as well as (hypertension-induced) benign nephrosclerosis and focal tubular atrophy with interstitial fibrosis. TREATMENT AND COURSE: After two hemofiltrations and concomitant administration of 100 mg prednisone renal function quickly improved and the proteinuria fell to 1 g/dl. At the same time the xerostomia improved. The nephrotic syndrome recurred 7 months later after the prednisone dose had been reduced to 10 mg/d, but after the dose had been raised to 50 mg/d and cyclosporin A (150 mg/d) had been added a lasting remission occurred and renal function became stable though impaired. CONCLUSION: The relatively rare association of glomerular disease (here focal segmental glomerulosclerosis) with Sjögren's syndrome can, as in this case, be triggered by a viral infection. A genetic predisposition for Sjögren's syndrome is suggested by the demonstration of HLA-DR3 alleles. Administration of steroids is indicated for the treatment of the nephrotic syndrome and, in case of recurrence, can be combined with cyclosporin A. Both drugs also influence the symptoms of Sjögren's syndrome.

Aged↗
PubMed1998

Single-read sequence tags of a limited number of genomic DNA fragments provide an inexpensive tool for comparative genome analysis.

Single-read sequences from both ends of 415 3-kb average size genomic DNA fragments of Candida albicans were compared with the complete sequence data of Saccharomyces cerevisiae. Comparison at the protein level, translated DNA against protein sequences, revealed 138 sequence tags with clear similarity to S. cerevisiae proteins or open reading frames. One case of synteny was found for the open reading frames of RAD16 and LYS2, which are adjacent to each other in S. cerevisiae and C. albicans.

Adenosine Triphosphatases↗
PubMed1998

Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus. SLE Study Group.

Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, with necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE.

Antibodies, Antinuclear↗
PubMed1998

IgM anti-dsDNA antibodies in systemic lupus erythematosus: negative association with nephritis. SLE Study Group.

Antibodies against dsDNA of the IgM class were measured in sera of 352 patients with systemic lupus erythematosus, 81 blood donors and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgM anti-dsDNA antibodies were found in 52.3% of the sera from patients with systemic lupus erythematosus, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 37 laboratory parameters was calculated. There was a highly significant negative correlation between IgM anti-dsDNA antibodies and nephritis as well as all the laboratory parameters indicating renal disease (elevated serum creatinine concentration, proteinuria, erythrocyte casts in the urine). IgM anti-dsDNA antibodies indicate protection of lupus patients against the development of lupus nephritis. Further experiments will show whether application of IgM anti-dsDNA antibodies is effective in treating lupus nephritis.

Antibodies, Antinuclear↗