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Biomedical subjects

G Tilz

Publications and source records attributed to G Tilz.

11 recordsLinked to original sources

Blockade of tumour necrosis factor {alpha} significantly alters the serum level of IgG- and IgA-rheumatoid factor in patients with rheumatoid arthritis.

OBJECTIVE: To determine the effect on the humoral immune system of long term treatment of patients with RA with etanercept. METHODS: 12 consecutive patients with seropositive RA treated with etanercept were studied and followed up for 9 months. Clinical efficacy of treatment was evaluated using the 28 joint count Disease Activity Score (DAS28). Serum samples were collected at baseline and after 9 months and serum immunoglobulin, RF isotypes, and anti-cyclic citrullinated peptide (aCCP), antinuclear, nucleosome, and dsDNA antibodies determined. For comparison 7 patients with seropositive RA treated with adalimumab were studied. RESULTS: DAS28 decreased significantly after the first month and then was constant for the whole study (5.7 (0.3) v 3.8 (0.2), p< or=0.000). Serum IgA-RF and IgG-RF increased significantly after 9 months' etanercept treatment (mean (SEM) IgA-RF rose from 19.5 (4.8) to 30.5 (5.9) IU/ml, p< or=0.01; IgG-RF from 20.6 (8.1) to 33.8 (11.5) IU/ml, p< or=0.04). Serum levels of total immunoglobulin and specific autoantibodies remained unchanged during the study. In patients treated with adalimumab, no significant changes in serum levels of RF isotypes and aCCP antibodies were seen. CONCLUSION: Etanercept, although effective in treating the clinical symptoms of RA, seems to have a pivotal effect on RF-producing B cells either directly or indirectly.

Aged↗

Clinical interpretation of antineutrophil cytoplasmic antibodies: parvovirus B19 infection as a pitfall.

BACKGROUND: While antibodies directed against proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA) have a high specificity for the diagnosis of systemic vasculitis, they may also be found as an epiphenomenon of acute viral infection. OBJECTIVE: To investigate whether positive ANCA test results may be a common feature of acute parvovirus B19 infection. METHODS: Sera were analysed from 1242 patients from a rheumatology outpatient clinic for reactivity with parvovirus B19 and EBV antibodies. They were tested for the presence of PR3-ANCA and MPO-ANCA, along with sera known to contain IgM antibodies to these viruses obtained from among 41,366 samples submitted for virological screening. RESULTS: ANCA were found in 10% (5/50) of the sera positive for IgM antibodies to parvovirus and in 3/51 sera containing IgM antibodies to EBV. Three of six patients with arthritis and concomitant parvovirus infection were found positive for PR3-ANCA and two were found positive for MPO-ANCA. All six patients tested negative for ANCA after six months of follow up. CONCLUSIONS: PR3-ANCA and MPO-ANCA may occur transiently in patients with acute B19 infection or infectious mononucleosis, highlighting the importance of repeated antibody tests in oligosymptomatic clinical conditions in which systemic autoimmune disease is suspected.

Acute Disease↗

Detection and quantification of small numbers of circulating tumour cells in peripheral blood using laser scanning cytometer (LSC).

The detection of circulating tumour cells disseminated from solid tumours requires extremely sensitive methods. Molecular genetic methods, which are most sensitive, are not applicable to solid tumours because no tumour-specific genetic markers are available. Detection of disseminated tumour cells by immunocytochemistry is time-consuming, whereas fluorimetry is fast and quantitative. The laser scanning cytometer (LSC) provides an automated microscopic procedure for screening up to 5x10(4) cells in suitable time. Using this system together with an enrichment procedure which allows up to ten thousand-fold enrichment, we have quantified minimal numbers of tumour cells. In a model system, breast cancer cell line cells diluted into peripheral blood mimicked seeding of tumour cells into the periphery. After staining with fluorochrome-conjugated anti-epithelial antibody, slides were screened for positive events directly or after enrichment with antibody-coated magnetic beads. One positive cell was unequivocally detectable in 10(4) cells and 50 out of 60 tumour cells were reliably recovered from a 20 ml blood volume, equal to 1-2 cells per 10(7), after magnetic bead enrichment. This method allows quantitation of tumour cells in peripheral blood and bone marrow in reasonable time and will, for the first time, enable extensive investigation of the seeding behaviour of tumours.

Breast Neoplasms↗

Immunologic changes after transfusion of autologous or allogeneic buffy coat-poor versus WBC-reduced blood transfusions in patients undergoing arthroplasty. II. Activation of T cells, macrophages, and cell-mediated lympholysis.

BACKGROUND: To estimate the impact of RBC preparations on the status of postoperative immune activation, the soluble cytokine receptors of TNFalpha (sTNF-R) and IL-2 (sIL-2R), as well as neopterin and cell-mediated lympholysis (CML), were measured. STUDY DESIGN AND METHODS: Patients undergoing strictly standardized anesthesiologic management for elective orthopedic surgery were enrolled in a prospective study. The perioperative course (Days 0, 3, 7, and 10) of sTNF-R, sIL-2R, neopterin, and CML was compared after random assignment to allogeneic buffy coat-reduced (Group 2, n = 8) or WBC-reduced (Group 3, n = 11) RBC transfusion regimen. Recipients of autologous buffy coat-reduced RBC transfusions (Group 1, n = 15) served as controls. Patients receiving intraoperatively and postoperatively salvaged blood only (n = 10) were separately analyzed as Group 4. RESULTS: In Group 1, a short-lasting increase in soluble cytokine receptors, a diminished cytolytic response (Day 0 vs. Day 7: sTNF-R, p = 0.0001; sIL-2R, p = 0.0004; CML, p = 0. 0238), and an elevation of neopterin (Day 0 vs. Day 3: p = 0.0064) were observed. In contrast, in allogeneically transfused patients, sTNF-R (Group 2, p = 0.0469: Group 3, p = 0.0039), sIL-2R (Group 3, p = 0.002) and neopterin (Group 3, p = 0.0164) increased further from baseline to Day 10 (Day 0 vs. Day 10), and this increase was accompanied by a diminished cytolytic response (Day 0 vs. Day 10: Group 2, p = 0.05; Group 3, p = 0.0076). Patients in Group 4 showed a short-lasting increase in sIL-2R (Day 0 vs. Day 3: p = 0.0078), neopterin (Day 0 vs. Day 3: p = 0.0156) and sTNF-R (Day 0 vs. Day 7: p = 0.0781). CONCLUSION: Allogeneic transfusions seem to prolong the postoperative status of immune activation, even when WBC-filtered RBCs are used for the transfusion regimen.

Arthroplasty↗

[Neopterin: new immunological marker of autoimmune rheumatic disease].

Serum neopterin (SN), concentration of soluble (s) TNF-receptors (R) with molecular mass 55 kD and sIL-2R, C-reactive protein (CRP), Willebrand factor antigen (WF Ag) were measured in enzyme immunoassay (EIA) or radioimmunoassay (BRAHMS, Berlin, Germany) in 189 patients with autoimmune rheumatic diseases: 52 patients with systemic lupus erythematosus (SLE), 67 patients with rheumatoid arthritis (RA), 44 patients with polymyositis/dermatomyositis and 26 patients with Wegener granulomatosis. SN appeared elevated in autoimmune rheumatic diseases correlating with the disease activity and concentrations of sTNF R and sIL 2R. Assay for neopterin is clinically essential for examination of the immunopathological process activity, prediction of the outcomes, better knowledge about cytokine synthesis profile in autoimmune rheumatic diseases.

Adult↗

A 47-kDa human nuclear protein recognized by antikinetochore autoimmune sera is homologous with the protein encoded by RCC1, a gene implicated in onset of chromosome condensation.

Several autoimmune sera from patients with Raynaud phenomenon decorated mammalian kinetochores and bound to a 47-kDa protein on immunoblots of nuclear lysates. Antibody affinity-purified from immunoblots of the 47-kDa band recognized kinetochores, but due to crossreaction with an 18-kDa protein, localization remains elusive. We used one of these sera to purify the antigen from HeLa cells synchronized in mitosis as a noncovalent complex with a 25-kDa protein. The antigen was released from DNA by intercalation with 25 mM chloroquine. Ion-exchange chromatography yielded the pure complex with an apparent molecular size of 68 kDa, which was separated into its components by gel filtration in 6 M guanidinium chloride. Upon two-dimensional gel electrophoresis the 47-kDa protein gave two main spots of pI 6.6 and 6.7, respectively. Posttranslational modification is indicated by additional antigenic spots, by lack of a free alpha-amino group, and by chromatographic behavior of peptides on reversed-phase chromatography. The amino acid sequence for 205 residues of the 47-kDa protein has been established. This sequence is highly homologous with the translated reading frame of RCC1, a gene reportedly involved in regulating onset of mammalian chromosome condensation.

Amino Acid Sequence↗

[False-positive results in the detection of anti-LAV/HTLV-III antibodies by enzyme immunoassay].

Two groups of sera were investigated with two different enzyme immunoassays for the detection of anti-LAV/HTLV-III-antibodies: 50 sera collected from patients with lupus erythematosus and 5 sera containing anti-HLA-DR4 antibodies. Of the 50 sera of the lupus erythematosus patients, 2 were positive in each of the tests. Of the 5 sera that contained anti-HLA-DR4 antibodies, one was positive. In addition, 11 sera showed positive results after heat treatment (56 degrees C, 1 h) in one of the tests. However, all sera in this group gave negative results in the other test. The positive results could not be confirmed with the immunoblot. These findings show that one must be aware of false-positive results when the sera of certain types of patients are investigated in anti-LAV/HTLV-III enzyme immunoassays. The sera of patients with lupus erythematosus, as well as that of polytransfused persons or multiparous women, that have been sensitized with HLA-DR4 antigens; heat treatment in one test has an effect on sera.

Acquired Immunodeficiency Syndrome↗

[Intracranial arteritis with circulating immune complexes].

Thirty-eight patients below the age of 50 years were investigated and in twelve, circulating immune complexes were found. Eight of these had angiographic evidence of an arteritis of the intracranial vessels. The causative factors, the role of the circulating immune complexes and the angiographic appearances in intracranial arteritis are discussed.

Adolescent↗

[Clinical experience in a case of orthotopic liver transplantation by use of an atypical caval vein anastomosis (author's transl)].

The two main indications for liver grafting are primary malignancy and parenchymatous liver disease. In both cases orthotopic transplantation remains the preferred technique. Since graft rejection was considered not to be the main problem in clinical liver transplantation, recent improved survival rates were reported to be due to a more aggressive diagnostic management and consequent treatment of postoperative complications nonrelated to graft rejection. Because of the limited number of organs available for organ grafting sometimes technical modifications may become necessary. This was the case in a 40-year old male patient suffering from primary malignant hepatoma. The donor was a child, and during operation a great difference between organ size and length and diameter of the hepatic vessels became evident. Orthotopic transplantation was performed using an unusual method of caval vein anastomosis. Initially the patient did very well, but later on liver function deteriorated and the patient died in the eighth postoperative week because of hepatic artery thrombosis. The autopsy showed that all other vascular anastomosis were patent and no signs of portal hypertension were evident. The surgical technique used in this case is described in detail and some interesting aspects are discussed.

Adult↗