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Biomedical subjects

K Dreher

Publications and source records attributed to K Dreher.

10 recordsLinked to original sources

MIA (melanoma inhibitory activity): a potential serum marker for rheumatoid arthritis.

OBJECTIVE: MIA (melanoma inhibitory activity) is correlated with metastasis in patients with malignant melanoma. As MIA is not only produced by melanoma cells, but also by differentiated chondrocytes, we examined whether serum levels of MIA are correlated with inflammation and/or joint destruction in rheumatic diseases. METHODS: MIA serum concentrations of patients with different rheumatic diseases were examined and compared with healthy individuals and malignant melanoma patients. In addition, MIA concentrations were correlated to inflammatory parameters and joint destruction. RESULTS: Increased MIA serum concentrations were found only in patients with rheumatic diseases associated with joint destruction, such as rheumatoid arthritis (RA), osteoarthritis, HLA B27-associated oligoarthritis, and psoriatic arthritis. Of these rheumatic diseases, a significant increase in MIA serum concentrations was seen only in patients with RA, associated with rheumatoid factor (RF) positivity and joint destruction. CONCLUSIONS: In addition to RF, MIA might therefore be useful in the differential diagnosis of RA vs non-destructive rheumatic diseases, and the presence of elevated levels of MIA in serum very likely reflects joint destruction in RA.

Arthritis, Rheumatoid↗

Prevention of unexplained recurrent spontaneous abortion using intravenous immunoglobulin: a prospective, randomized, double-blinded, placebo-controlled trial.

PROBLEM: The efficacy of intravenous immunoglobulin (IVIG) for treatment of unexplained recurrent spontaneous abortion was assessed in a prospective, randomized, double-blinded, and placebo-controlled study. METHOD OF STUDY: The study took place in a provincial recurrent pregnancy loss clinic, located in a tertiary/quaternary care academic center. The study subjects were women with a history of two or more documented consecutive spontaneous pregnancy losses under 20 weeks of gestation, excluding any associated with aneuploidy by karyotype analysis, and with no evidence of genetic, endocrine, infectious, anatomic, or autoimmune factors associated with a history of recurrent spontaneous abortion. The subjects were randomized to receive either intravenous immunoglobulin (Gamimune N) as treatment or normal saline as placebo. Randomization was stratified for primary, secondary, and unclassified unexplained recurrent spontaneous abortion. Success was defined as an ongoing pregnancy beyond 20 weeks of gestation. RESULTS: Sixty-two subjects enrolled in the trial. There were 37 index pregnancies and 6 cross-over pregnancies. There was no clinically significant difference between the treatment arm and the placebo arm in terms of subsequent pregnancy success. There seemed to be a higher success rate with the stratified analysis of couples with secondary unexplained recurrent spontaneous abortion, but the trial did not have sufficient power to confirm this. CONCLUSIONS: Based on this trial and three similar trials in the literature, a multicentered trial is needed to determine conclusively whether IVIG is effective in the treatment of unexplained recurrent spontaneous abortion.

Abortion, Habitual↗

Sensitivity of lungs of aging Fischer 344 rats to ozone: assessment by bronchoalveolar lavage.

Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability of protein changes was higher in senescent (24-mo-old) rats. By comparison to juvenile (2-mo-old) and adult (9-mo-old) rats, senescent animals had higher increases of interleukin-6 (up to 10-fold higher) and N-acetyl-beta-D-glucosaminidase (NAGA; 2-fold higher) in lung lavage after ozone. Ascorbic acid was lower in lungs of senescent rats (one-half of juvenile values), and acute ozone exposure brought a further decrease in lung ascorbate. Whereas alveolar protein transudation was attenuated after ozone exposure on 4 days, persistent elevation of NAGA in senescent rats suggested only partial adaptation. Injection of endotoxin did not modify the patterns of effects. Incorporation of 18O-ozone into macrophages and surfactant was not different between age groups, indicating that the magnified biological responses in senescent rats were not dominated by differences in internal dose of ozone. The results indicate that senescent rats respond differently than juvenile and adult rats to lung injury.

Acetylglucosaminidase↗

Effect of anti-Ig on rabbit B cell function and Ig expression.

We have examined the effect which xenogeneic anti-Ig has on rabbit B cell function and Ig expression in an effort to understand the phenomenon of antibody mediated suppression. Treatment of rabbit lymphocyte cultures with xenogeneic anti-rabbit Ig causes 2.5-3.8 fold decrease in the level of Ig secreting cells with little or no long-term effect on surface Ig. This suppression in B cell secretory function is not the result of suppression of Ig gene expression since xenogeneic anti-rabbit Ig treatment causes a 1.7-2.7 fold increase in Ig L and H chain mRNA levels. Collectively, these data are consistent with the hypothesis that antibody mediated suppression of B cell function occurs at a post-transcriptional level involving either the secretory pathway of Ig expression and/or blockage in B cell differentiation.

Animals↗

cDNA sequences encoding rabbit latent kappa 1 b5 and b6 Ig L chains.

Regulation of rabbit Ig C kappa 1 L chain gene expression is thought to be under allelic control. Four nominal allotypic variants designated b4, b5, b6, and b9 have been found to be co-dominantly expressed at the C kappa 1 gene locus. Latent allotypes are nonallelic and appear as unexpected and transitory molecules in the serum as well as on B cell surfaces. To determine the mechanism of latent kappa 1 allotype expression, rabbits were initially induced to produce latent b5 and b6 allotypes by infection with Trypanosoma brucei and RNA was extracted from the lymph nodes of these rabbits. The polymerase chain reaction using allele specific oligonucleotide primers was used to detect and amplify the mRNA encoding the latent b5 and b6 sequences. Nucleotide sequence analysis of the cloned products revealed that the latent b5 and b6 cDNA sequences were identical to their nominal allelic counterparts, b5 and b6, respectively. Thus, the identification of transcripts encoding latent b5 and b6 sequences rules out serologic artifacts and idiotypic mimicry as explanations of latent allotype expression.

Animals↗

Detection of large cDNA inserts within crude lambda gt11 lysates: a rapid and sensitive method.

A method is presented for the isolation of bacteriophage lambda DNA and the rapid identification of large cDNA inserts within crude phage lysates. The primary screening of a lambda gt11 cDNA library with a 32P-radiolabeled cDNA probe yielded 21 putative positive clones. A phage "spot-blot" analysis was employed to quickly screen these potential recombinants. This eliminated 9 of the 21 clones as the result of false positive signals. The remaining 12 recombinant phage were amplified on agarose-based media, and phage DNA was isolated using a modified plate lysate procedure. The DNA thus obtained from these crude lysates could be easily digested with EcoRI and examined by Southern blot analysis. The resulting blot was hybridized with the same cDNA probe used in the initial screening of the library. Thus, two clones harboring the longest cDNA insert were identified from a mixed phage population and were subsequently plaque purified. The procedure is rapid, sensitive, reproducible, inexpensive and allows the processing of several clones at once without sacrificing the quality or yields of the DNA preparation. Furthermore, the method obviates the need for plaque purifying all the positives obtained from the initial screening of a cDNA library.

Bacteriophage lambda↗

Rabbit immunoglobulin kappa genes: structure of a germline b4 allotype J-C locus and evidence for several b4-related sequences in the rabbit genome.

To investigate the genetic mechanism by which certain rabbits can express immunoglobulins unexpected on the basis of their pedigree (i.e., "latent" allotypes), we have begun a study of the rabbit immunoglobulin kappa gene locus. Here we report the structure of a germline genomic clone that encodes the b4 allotype of rabbit kappa immunoglobulin and corresponds to the kappa gene expressed by the rabbit-mouse hybridoma 12F2. The nucleotide sequences of the joining (J) and constant (C) regions reveal structures generally similar to the homologous mouse and human loci, although only one of the five J-like sequences of this rabbit gene is apparently expressed. Southern blotting analysis of DNA from several rabbit allotypic strains by using probes derived from the cloned b4 gene demonstrates that, in contrast to mouse and human, rabbits possess multiple kappa-related sequences. Rabbits of the nominal b4, b5, b6, and b9 allotypes each contain at least two b4-related sequences that are associated with their own J regions and that are highly homologous to the cloned b4 gene in both coding and flanking regions.

Animals↗

Anion channel blockade: effects upon erythrocyte membrane calcium response.

The influx of small amounts of calcium into normal human red cells adversely affects cellular metabolism, shape, ion and water content, and deformability. Because restriction of cation (potassium) efflux moderates these deleterious effects of Ca++ influx, we investigated the possibility that inhibition of anion permeability might be similarly beneficial. Human red cells were treated with 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS), which reacts preferentially with external sites on the transmembrane protein, band 3, and specifically inhibits inorganic anion transport. DIDS-treated and control cells were then exposed to the ionophore A23187 and Ca++. We find that DIDS treatment blocks Ca++-induced K+ and water loss and diminishes changes in osmotic fragility and cellular elasticity. Furthermore, DIDS reduces the "trapping" of hemoglobin by red cell membranes and increases the apparent affinity of the cell membrane for glyceraldehyde-3-phosphate dehydrogenase.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗