Search PubMed⌕ Search

Biomedical subjects

J Georgsen

Publications and source records attributed to J Georgsen.

At least 55 records · Page 3Linked to original sources

DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis.

We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments associated with the following HLA class II genes were increased in PJRA when compared to normal controls: DRB1*08 (DRw8) (35.2% vs 10.3%, RR = 4.6, p less than 10(-3), DRB3*01/02/03 (DRw52) (76.3% vs 48.1%, RR 3.5, p less than 10(-3)), DQA1*0401 (41.0% vs 7.4%, RR = 7.9, p less than 10(-3)), DQA1*0501 (55.6% vs 29.7%, RR = 3.0, p less than 10(-2), DQB1*0301 (DQw7) (46.2% vs 17.5%, RR = 4.0; p less than 10(-2)), DPA1*0201 (44.2% vs 7.9%, RR = 8.7, p less than 10(-5)), and DPB1*02 (DPw2) (40.7% vs 7.1%, RR = 8.5, p less than 10(-6)). The frequency of DRB1*11 was not significantly increased. The frequencies of DNA fragments associated with the following HLA class II genes were decreased in PJRA although not statistically significantly so after 'correction' of p values: DRB1*04 (14.8% vs 40.2%, RR = 0.27; p less than 10(-3)), DRB1*07 (0% vs 25.9%, RR = 0.04, p less than 10(-3)), DRB4*0101 (DRw53) (25.9% vs 53.6%, RR = 0.31, p less than 10(-3)), DQA1*0102 (11.6% vs 36.0%, RR = 0.25, p less than 10(-4)), and DQA1*0201 (2.6% vs 34.2%, RR = 0.05, p less than 10(-2)).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Juvenile↗

HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6.

The distribution of HLA class II (DR, DQ, and DP) antigens was studied in 41 patients with symptomatic sarcoidosis (SA) and ethnically matched healthy controls. HLA-DR, -DQw1 and -DQw3 typings were performed with alloantisera in the conventional microcytotoxic test, whereas -DP typings were done using primed lymphocyte typing. The frequencies of DRw6 were 41.5% in SA patients and 17.9% in controls (relative risk, RR = 3.2, p = 0.00087, p less than 0.05 when corrected). DR3 was decreased to 14.6% in SA patients compared to 25.9% in controls (RR = 0.49, p = 0.07, i.e., not statistically significant). The decreased frequency of DR3 was only seen in patients with severe, long-standing disease. In contrast, the DRw6 increase was most pronounced in patients with severe disease (RR = 6.4; p = 0.003). There were no statistically significant deviations in the frequencies of DQ and DP alleles between patients and controls. In conclusion, our data suggest that DRW6 confers susceptibility and DR3 resistance to severe, long-standing disease.

Female↗

Ranitidine improves certain cellular immune responses in asymptomatic HIV-infected individuals.

Human immunodeficiency virus (HIV) infection is characterized by a progressive impairment in immunocompetence leading to severe opportunistic infections and malignancies. In a double-blind, placebo-controlled study, the potential impact of immunomodulation by oral ranitidine, 600 mg daily, for 28 days was studied in 18 HIV-positive patients (CDC group II). All were without clinical signs of infections and were not treated with other known immunomodulating agents. Several immunological parameters related to HIV infection were studied and confirmed to be impaired early in HIV infection. Spontaneous and in vitro interleukin-2- and interferon-alpha-stimulated natural killer cell activity improved in the ranitidine-treated patients in contrast to a decrease in nontreated patients (#p less than 0.03, #p less than 0.01, #p less than 0.02 between groups, respectively). Furthermore, T-cell blastogenesis to phytohemagglutinin stimulation and soluble interleukin-2 receptors in serum increased in ranitidine-treated patients compared with nontreated patients (#p less than 0.01). However, ranitidine treatment did not change CD4+ cell counts. Although the significant improvement in immunocompetence shown in this study is small, the present result indicates the need for further trials with immunomodulation by ranitidine in HIV-infected individuals.

Adult↗

Accessory signals in T-T cell interactions between antigen- and alloantigen-specific, human memory T cells generated in vitro.

The potential of activated HLA class II-positive T cells as antigen-/alloantigen-presenting cells remains controversial. In our model system we use in vitro-primed, HLA class II-specific T cells of the memory T-cell phenotype, CD4+, CD29+ (4B4+), and CD45RO+ (UCHL-1). We have previously shown that alloactivated, HLA class II-positive T cells (Ta) are unable to stimulate proliferative responses in naive and primed allospecific T cells when 'back-stimulation' is avoided. The explanation of this feature of Ta is unknown, but it is due neither to suppression nor to insufficient HLA class II expression. Accordingly, we investigated the possibility that Ta have a deficient expression of accessory signals critical for the induction of proliferative T-cell responses. We found that (1) non-mitogenic concentrations of phorbol myristate acetate (PMA) in combination with either rIL-4, a CD28-reactive MoAb (Kolt-2), or a calcium ionophore (A23187) enabled Ta to elicit alloantigen-specific memory T-cell responses and to present purified protein derivative (PPD) to PPD-specific T-cell lines. The addition of irradiated, Epstein-Barr virus-transformed B-cell lines (EBV-LCL) (but not their supernatants) had a similar but less pronounced effect; (2) MoAb directed against HLA class II, CD25 (IL-2R), CD2, CD4, CD11a (LFA-1), or CD45RO molecules inhibited these responses; (3) PMA was required within the first hour of culture in order to induce optimal alloantigen-specific T-cell activation, while rIL-4 was fully effective when added after 20-44 h of culture; (4) incubation for 20 h of Ta with rIL-4 plus PMA markedly up-regulated CD54 expression on the Ta, and IL-4 seemed to potentiate the effect of PMA on the CD54 expression. In conclusion, the present data indicate that the inability of Ta to elicit (allo)antigen-specific, proliferative T-cell response is due to a lack of critical accessory signals. Up-regulation of CD54 was not sufficient for Ta to stimulate proliferative responses. Neither cytokines (IL-1, IL-6, and others) nor triggering of CD2 epitopes (T11.2 and T11.3) by soluble MoAb or solid phase support by MoAb against a number of accessory molecules provided the necessary signals. Thus, our data indicate that other, as yet unknown, signalling pathways play a key role in antigen- and alloantigen-specific T-T interactions. These pathways still need to be identified.

Antibodies, Monoclonal↗

HLA-DP antigens in patients with alopecia areata.

The distribution of HLA-DP antigens were studied in 41 patients with alopecia areata (AA) and 188 ethnically matched controls. An increase of DR4 and possibly DR5 in 24 of these patients has previously been reported. HLA-DP typing for DPw1 through w6 and the local specificity, CDP HEI, was performed using the primed lymphocyte typing (PLT) technique. The frequencies of DPw4 were 92.9% in AA patients and 71.3% in controls (relative risk, RR = 5.1, p = 0.0019 and p less than 0.03 when corrected). DPw1 was decreased to 4.9% in patients compared to 14.9% in controls, but the difference was not statistically significant. The frequency of DR4 was 48.8% compared to 31.9% in controls (RR = 2.0) whereas the frequency of DR5 did not differ from that in controls. DPw4 was not associated (in linkage disequilibrium) with DR4 or DR5 in patients or controls. Thus, in AA the association with DP and DR are independent of each other. However, individuals with both the DPw4 and DR4 alleles are at increased risk for AA, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to AA.

Alopecia Areata↗

Granulocyte chemotaxis. Influence of radiographic contrast media on the chemoattractive properties of serum.

One of the important functions of granulocytes is the ability to respond to a chemoattractive signal by migration. The influence of radiographic contrast media (CM) on the chemoattractive properties of serum was investigated by under agarose technique for chemotaxis. No chemotactic response was seen when serum was incubated with different concentrations of CM after heat inactivation. The CM did not generate the heat stable complement split product C5a-desarg which would have resulted in a chemotactic response. Without heat inactivation all complement available in the serum was activated by the agarose in the chemotaxis assay. Low concentrations of iohexol and iodixanol brought about an increased chemotactic response relative to a reference with saline instead of CM. This may be due to activation of heat labile chemoattractants from other sources than the complement cascade. At high concentrations of all five investigated CM, a decreased number of granulocytes migrated over a shorter distance when compared with the reference, and this may be due to interactions between the CM and chemoattractants or their precursors.

Chemotaxis↗

Typing for HLA-DPB1*03 and HLA-DPB1*06 using allele-specific DNA in vitro amplification and allele-specific oligonucleotide probes. Detection of "new" DPB1*06 variants.

DP gene typing using in vitro DNA amplification combined with sequence-specific oligonucleotide probes has recently been reported. The resulting DNA amplification was specific for the HLA-DPB locus. Typing for the individual DPB alleles was exclusively dependent on the hybridizations of the probes but hampered by close sequence homology between different DP alleles yielding complex patterns of reactivity with a panel of probes. We report the combined use of allele-specific DNA in vitro amplification and allele-specific oligonucleotides in typing for DPB1*03 and DPB1*06. Complete concordance with PLT typing was observed for the DPB1*03 alleles, while in the DPB1*06 group, at least three variant DPB1*06 alleles were identified which have not been described previously.

Alleles↗

NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes.

The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5 kb, which behaved as alleles. In a panel of 108 random, healthy, unrelated Danes, the phenotype frequencies of the 10.5 and 5.5 kb bands were 0.94 and 0.53 and the gene frequencies were 0.71 and 0.29, respectively. The test for Hardy-Weinberg equilibrium showed no significant deviation from the expected values. The 5.5 kb band was strongly positively associated with HLA-DR3, HLA-B8, and HLA-A1. In 22 patients with primary biliary cirrhosis a significantly (corrected P = 0.024) decreased frequency of the 10.5 kb fragment was found. Additional studies are in progress to substantiate this association.

Chromosome Mapping↗

NcoI restriction fragment length polymorphism (RFLP) of the tumor necrosis factor (TNF alpha) region in four autoimmune diseases.

The two-allele NcoI Restriction Fragment Length Polymorphism (RFLP) of the TNF alpha region yielding bands of 5.5 and 10.5 kb was investigated in patients with systemic lupus erythematosus (SLE), pauciarticular juvenile rheumatoid arthritis (P-JRA), rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). In all four disease, we found a decreased frequency of the 10.5 kb allele which, however, was significant only in the SLE group. In all conditions except RA, the frequency of the 5.5 kb fragment was increased. In pSS and SLE, the frequency of HLA-B8 was increased in 5.5 kb fragment positive patients compared with corresponding controls and thus, the increase of this band and the decrease of the 10.5 kb band may be secondary to HLA-B8 associations owing to strong positive linkage disequilibrium between HLA-B8 and the 5.5 kb band.

Arthritis, Juvenile↗

The effect of radiographic contrast media on the chemotaxis of granulocytes.

The direct in vitro effect of radiographic contrast media (RCM) on granulocyte locomotion was assayed using an under agarose technique. All RCM tested inhibited the chemotactic response to N-fmlp, a synthetic chemotactic N-formylated tripeptide, which is an analogue of natural bacterial products. The inhibition was most pronounced for diatrizoate, the most hyperosmolar of the RCM, but hyperosmolality per se was not the only inhibitive factor, since 0.5 M NaCl, which has an osmolality comparable to the RCM used, did not inhibit chemotaxis significantly. Furthermore, the inhibition was not caused by a nonspecific sticky effect of RCM on granulocytes, since spontaneous migration was normal. We propose that the inhibition might be caused by competitive binding of RCM to the N-fmlp receptor sited on leukocytes because the third amino acid in N-fmlp is phenylalanine, which, like the RCM, contains a benzene ring.

Chemotaxis↗

Hypotensive shock associated with bradycardia after intravenous injection of contrast medium.

A case of hypotensive shock associated with bradycardia that occurred after injection of nonionic monomeric contrast medium is described. Whether the pathogenesis of this type of reaction is solely vasovagal or is directly caused by the contrast medium is not known. The number of occurrences after administration of nonionic monomeric versus conventional contrast agents should be compared to solve this problem.

Adult↗