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Biomedical subjects

K Hartung

Publications and source records attributed to K Hartung.

At least 19 recordsLinked to original sources

The genetic basis of Ro and La antibody formation in systemic lupus erythematosus. Results of a multicenter study. The SLE Study Group.

Antibodies against Ro and La, including recombinant La and recombinant 60 kD-Ro, were determined by counter immunoelectrophoresis and ELISA in over 300 central European systemic lupus erythematosus (SLE) patients. The presence of both Ro and La antibodies was strongly associated with the MHC haplotype B8-C4AQ0-DR3-DQ2, the association being strongest for DR3. After exclusion of all B8-DR3 positive patients only DR3 positive patients still showed an increased incidence of Ro and La antibodies, suggesting DR3 as the primary association factor. High titers of La antibody, but not of 60 kD-Ro antibody, were also significantly associated with the presence of DR3. Other DR and DQ antigens or heterozygous DQ combinations were not significantly associated with Ro and La antibodies.

Antibodies, Antinuclear

MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus. Results of a multicenter study. SLE Study Group.

Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies.

Antibody Specificity

Expanded macrophage precursor populations in BXSB mice: possible reason for the increasing monocytosis in male mice.

The BXSB mouse spontaneously develops an autoimmune disease that resembles human systemic lupus erythematosus (SLE). During their lifetime, male BXSB mice show an increasing monocytosis in the peripheral blood as opposed to their female littermates. This monocytosis is unique among autoimmune-prone mice. To test the hypothesis that alterations at the stem cell level may be responsible for this monocytosis, myeloid bone marrow precursor cells were examined in both male and female BXSB mice from 4 to 40 weeks of age. The number of M-CSF responding stem cells (CFU-M) and the number of GM-CSF responding stem cells (CFU-GM) were higher than in all other inbred mouse strains tested. In addition, male BXSB mice developed a progressive increase of CFU-M and CFU-GM in the bone marrow during their lifetime, which paralleled the peripheral blood monocytosis. The monocytosis in male BXSB mice is the result of a further expansion of the strain-specific high number of macrophage precursors by intrinsic factors, which may be attributed to the influence of the Yaa factor. The sex-specific expanded mononuclear phagocyte system may promote the autoimmune process and may be one reason for the dramatic course of murine SLE in male BXSB mice.

Animals

Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study.

In a multicenter study more than 300 central European systemic lupus erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4 phenotypes. For 174 SLE patients MHC haplotypes were determined by family segregation analysis, and for 155 patients C4 gene deletions were determined by TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQ0-C4B1-DR3 and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings were confirmed by applying the haplotype frequency difference (HFD) method, which uses nontransmitted haplotypes from the family study as internal controls. Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in SLE patients independently of the two risk haplotypes. C4A gene deletions, but not silent C4AQ0 alleles, were increased in SLE patients and neither C4BQ0 alleles nor C4B gene deletions were increased. The observed frequencies of homozygosity and heterozygosity for the two haplotypes and the frequencies of homozygotes for C4AQ0 and C4A deletions did not differ from the expected values, indicating that the risk for SLE is conveyed by single allele effects. In conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against C4Q0 alleles being the decisive factors increasing susceptibility to SLE.

Alleles

MHC gene products and anticardiolipin antibodies in systemic lupus erythematosus results of a multicenter study. SLE Study Group.

Anticardiolipin antibodies (aCL) and HLA-DR antigens were determined in 314 central European patients with systemic lupus erythematosus (SLE). Both HLA-DR4 and DR7 were increased in aCL-positive patients, and aCL were significantly associated with DRw53. The association between DRw53 and aCL was also apparent in those 17 patients with SLE and the anticardiolipin syndrome. There was no association between aCL and HLA-DQ or C4 alleles in SLE.

Antibodies, Anticardiolipin

[Radiation exposure of the hands and feet during x-ray studies in small animals].

In early years of radiology, many severe radiation injuries in radiologists were registered. Unfortunately, there are still cases of skin lesions of the hands of veterinarians. The main reason for this is careless handling during the examination. First of all the veterinarian should try to stay out of the primary beam. In addition, he must be aware that lead gloves are no protection against primary rays. In contrast, the risk of placing the feet in the primary beam is relatively low. Monitoring of radiation shows, that, if veterinarians are aware of the hazards, there is no danger of radiation damage. Advice for reducing the exposure dose to the hands is given.

Animals

[Estimation of the occupational radiation exposure during radiographic studies of horses].

Radiography of horses in veterinary practice is done normally with quite simple equipment. Thereby radiation protection is easily neglected. In this investigation sources of mistakes are demonstrated. The possible exposure of staff is evaluated by dose measuring over a long period of time. It can be stated that following the most simple radiation protection there will never be a significant exposure of staff.

Animals

Ion channel formation by synthetic transmembrane segments of the inhibitory glycine receptor--a model study.

The inhibitory glycine receptor (GlyR) of rat spinal cord contains an intrinsic transmembrane channel mediating agonist-gated anion flux. Here, synthetic peptides modelled after the predicted transmembrane domains M2 and M4 of its ligand-binding subunit were incorporated into lipid vesicle membranes and black lipid bilayers to analyze their channel forming capabilities. Both types of peptides prohibited the establishment of, or dissipated, preexisting transmembrane potentials in the vesicle system. Incorporation of peptide M2 into the black lipid bilayer elicited randomly gated single channel events with various conductance states and life-times. Peptide M4 increased the conductance of the bilayer without producing single channels. Exchange of the terminal arginine residues of peptide M2 by glutamate resulted in a significant shift towards cation selectivity of the respective channels as compared to peptide M2. In conclusion, the peptide channels observed differed significantly from native GlyR in both conductivity and ion-selectivity indicating that individual synthetic transmembrane segments are not sufficient to mimic a channel protein composed of subunits with multiple transmembrane segments.

Amino Acid Sequence

Testing for association in SLE families.

Systemic lupus erythematosus (SLE) is a complex disease which is partly determined by genetic factors which influence susceptibility to the disease phenotype. In this association study we try to define the high risk haplotypes which are responsible for this disease, together with other environmental factors. In many other association studies a set of SLE patients is compared to a set of controls. The basic assumption about the underlying population is that the disease and control sample should originate from the same genetic population, which is not always completely satisfied in many studies. Therefore, we analyse our family data by applying the Haplotype Frequency Difference (HFD) Method, which constructs its internal control group from those haplotypes not transmitted to the affected individual. Results partially conform with other studies, showing that the haplotypes B8 DR3 as well as B7 DR2 have a high positive association with SLE. When the DR locus was analyzed alone, we found besides the alleles DR2 and DR3 a negative association for DR1, DR5, and DR6.

Adult

Immunoglobulin allotypes are not associated with HLA-antigens, autoantibodies and clinical symptoms in systemic lupus erythematosus. Members of the SLE Study Group.

Immunoglobulin heavy chain (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies of 323 central European Caucasian patients with systemic lupus erythematosus (SLE) were examined and correlated with various genetic, serologic and clinical markers of SLE. No significant associations were found between immunoglobulin allotypes or phenotypes and all 20 parameters tested (nephritis, vasculitis, arthralgias, photosensitivity, discoid lesions, central nervous system disease, Raynaud's phenomenon, sex, anti-Ro, anti-La, anti-nRNP, HLA-DR1-DR7, HLA phenotypes B8-DR3, B7-DR2). It could therefore be assumed that Gm, A2m and Km allotypes were not associated with HLA-antigens and had no influence on the serologic and clinical expression of SLE.

Autoantibodies

Hetero- and homozygosity of MHC class II gene products in systemic lupus erythematosus. The Members of the Deutsche Multizentrische SLE-Studie.

An analysis of HLA class II antigens in 356 white patients with systemic lupus erythematosus (SLE) showed that all HLA-DR and -DQ homozygous and heterozygous combinations appear with frequencies expected from the observed gene frequencies. HLA-DR2 and HLA-DR3 gene frequencies were both increased in SLE, as were the odds ratios of all DR2 and DR3 hetero- and homozygous combinations. HLA-DR2/C4AQ0 heterozygotes were also not increased over expected values. Therefore, gene complementation at MHC loci does not contribute to susceptibility to SLE, but rather one or two MHC allele(s) in linkage with HLA-DR2 and HLA-DR3.

Alleles

Properties of three different ion channels in the plasma membrane of the slime mold Dictyostelium discoideum.

'Patch-clamp' experiments in the cell-attached configuration have shown the existence of three distinct types of ion channels in the plasma membrane of Dictyostelium discoideum. Channels DI (slope conductance 11 pS) and DII (slope conductance 6 pS) promote an outward current at depolarizing voltages. A third ion channel (HI, slope conductance 3 pS) opens preferentially at hyperpolarization and promotes inward current flow. It is suggested that under physiological conditions current through the DI and DII channels is carried by K+, whereas Ca2+ may be the current carrier in the HI channel. The density of these ion channels in the membrane of D. discoideum is low: approx. 0.1/micron 2 for the DI and HI channel and 0.02/micron 2 for the DII channel. The gating properties of the ion channels appear to be complicated because openings are grouped into bursts of activity. The probability of the DI channel being in the open state increases with depolarization. The mean channel life-time is about 20 ms and voltage-independent. The burst duration increases with depolarization whereas the interburst time decreases. The minimal kinetic model accounting for the behaviour of the DI channel is a three-state model with two closed and one open state. A detailed analysis of the gating of the DII and the HI channel was prevented by their low rate of occurrence (DII) or fast inactivation (HI). The formation of a seal resistance greater than or equal to 1 G omega depends critically on the composition of the pipette solution. Examination of a series of monovalent and divalent cations as well as different organic and inorganic anions has shown that 'gigaseals' are formed only in the presence of at least 1 mM Ca2+ or Sr2+, whereas Ba2+, Mg2+ and monovalent cations (Li+, Na+, K+, Rb+, Cs+) do not support the formation of high seal resistances. Anions seem not to affect the seal formation.

Calcium

[School medical findings in children of foreign workers].

A report on three investigations of the medical school-service on children from foreign countries is given. The foreign children are normally smaller than German children, but in relation to their stature more heavily built. Vaccination status and documentation are insufficient. Nevertheless, disturbances in organic functioning considered to be attributed to damages caused by our "society of civilization" are less prominent in foreign children. The necessary actions of improving the above mentioned situation are pointed out.

Body Height