Johannes Möst

Pathways for the regulation of interferon-γ-inducible genes by iron in human monocytic cells

To elucidate iron‐regulated interferon‐γ (IFN‐γ) effector functions, we investigated three IFN‐γ‐inducible genes [intercellular adhesion molecule‐1 (ICAM‐1), human leukocyte antigen (HLA)‐DR, guanosine 5′‐triphosphate‐cyclohydrolase I (GTP‐CH)] in primary human monocytes and the cell line THP‐1. IFN‐γ increased the surface expression of ICAM‐1 and HLA‐DR and stimulated GTP‐CH activity. Addition of iron before cytokine stimulation resulted in a dose‐dependent reduction of these pathways, and iron restriction by desferrioxamine (DFO) enhanced ICAM‐1, HLA‐DR, and GTP‐CH expression. Iron neither affected IFN‐γ binding to its receptor nor IFN‐γ receptor surface expression. IFN‐γ‐inducible mRNA expression of ICAM‐1, HLA‐DR, and GTP‐CH was reduced by iron and increased by DFO by a transcriptional mechanism. Moreover, ICAM‐1 and to a lesser extent, GTP‐CH and HLA‐DR mRNA expression were regulated post‐transcriptionally, as iron pretreatment resulted in shortening the mRNA half‐life compared with cells treated with IFN‐γ alone. Thus, iron perturbations regulate IFN‐γ effector pathways by transcriptional and post‐transcriptional mechanisms, indicating that iron rather interferes with IFN‐γ signal‐transduction processes.

Correlation of hepatitis C virus antibodies with HIV-1 seropositivity in intravenous drug addicts

Since Choo, Kuo, and co-workers [1, 2] used a yeast expression system to synthesize a recombinant polypeptide of the hepatitis C virus (HCV) (a major etiologic virus of blood-borne non-A, non-B hepatitis (NANBH) many investigators have studied the prevalence of antibodies to HCV. High percentages of antibodies were detected in patients with post-transfusion NANBH [2, 3], in patients with hepatocellular carcinoma, hepatic cirrhosis [4, 5] and in haemophiliacs [3, 6]. In healthy blood donors the percentage of antibodies detected against HCV varied from 0.42% [7], 0.5% [2], 0.68% [8], to 7.3% [4]. We studied HCV-antibody prevalence in anti-H/V-1 positive (referred to as HIV +) and negative (HIV-) intravenous drug addicts (IVDA) in Western Austria. Antibodies to HCV were determined by ELISA purchased from Ortho Diagnostic Systems Inc., Raritan, N.Y., USA; code 933440, lot# hcvl03. All tests for detection of Hepatitis B markers were obtained from ABBOTT LAB., North Chicago, I1, USA: HBs-antigen Auszyme monoclehal, # 32281 M201), anti-HBc (~orzyme # 32565 M301), and anti-HBs (Ausab-eia, #32591 M202). In the sere of 30 HIV-positive and 36 H/V-negative IVDA we found 20 (66.6%) and 13 (36.1%), respectively, positive for anti-HCV in an ELISA system obtained from ORTHO whereas only three (4.1%) out of 73 healthy, young volunteers reacted to this test (Table 1 ). In addition, the prevalence of hepatitis B in these persons Was tested by the determination of hepatitis virus B surface antigen, of antiHBc, and anti-HBs antibodies. HBs-antigen and/or anti-HBs could be detected in 17 (56.6%) of HIV +, in 19 (52.7%) of H/VIVDA and in two (2.7%) of the healthy volunteers. Anti-HBc could be detected in 22 (73.3%) of HIV + and in 14 (38.8%) of the HIVIVDA, but in only one (1.37%) of the healthy volunteers. Our findings indicate that: a high prevalence of anti-HCV exists in IVDA, which is in agreement with data previously reported [3]; a higher prevalence of anti-HCV in H/V + IVDA is detectable when compared to HIVIVDA. A similar observation was made by Mortimer et al. [9] studying HCV seropositivity in H/V + and HIVhomosexual men;

Class II antigens in Hashimoto thyroiditis. I. Synthesis and expression of HLA-DR and HLA-DQ by thyroid epithelial cells.

Aberrant expression of HLA-DR antigens on epithelial cells is seen in various organ-specific autoimmune disorders including Hashimoto thyroiditis (HT). Expression of HLA-DQ has so far not been demonstrated on these cells. We report here that thyroid epithelial cells (TEC) in HT, in addition to the known aberrant expression of HLA-DR, coexpress HLA-DQ antigens. Furthermore we provide evidence that class II antigens are synthesized by TEC themselves by demonstration of intracellular HLA-DR gamma-chain. These findings support the theory that TEC may be able to present (auto)antigens in vivo thus perhaps contributing to the perpetuation of thyroid destruction. As expression of class II antigens on TEC was never observed in non- or weakly infiltrated areas, we propose that infiltration by T cells is necessary to induce this aberrant expression of class II antigens.

Fully vaccinated children are rare: Immunization coverage and seroprevalence in Austrian school children

Vaccination coverage for vaccine-preventable diseases in Austria as well as in many Central European countries has been reported to be too low to eradicate such diseases and prevent further outbreaks. Austria lacks an adequate surveillance system to monitor prevalence of the diseases, the vaccination coverage and seroconversion. School children aged 10–14 years (n = 1077) were recruited in all four schools in the city of Schwaz, Austria, to present their vaccination documents and to give blood for serological testing (diphtheria, pertussis, measles, mumps, rubella, varicella). All participants received a report with a personal guideline for (re-) vaccination. Overall vaccination coverage was 86.4% for measles, 85.5% for mumps and 35.0% for rubella. Tetanus vaccination coverage was 98.4% for the first, 97.8% for the second and 96.7% for the third dose, while 55.4% of the study subjects received the recommended two booster injections. For diphtheria the corresponding vaccination coverage was found to be almost identical. Pertussis coverage was lower in general (first dose: 90.9%; second dose: 89.0%; third dose: 86.5%). Oral poliomyelitis vaccination showed a coverage of 98.6, 96.5, 95.3%, with 78.7% receiving the fourth dose. Overall 38.7% were classified as fully vaccinated. Seropositivity for measles was found in 90.4%, for mumps in 61.8%, for rubella in 82.3%, for diphtheria in 65.8%, for pertussis in 35.6% and for varicella in 95.0%. In summary, fully vaccinated children are rare and intensive public health efforts will be necessary to reach higher levels of immunity and prevent further outbreaks.

Recombinant versus plasma-derived hepatitis B vaccine: comparison of immunogenicity in medical students.

A group of 92 medical students were immunized with a commercial recombinant hepatitis B vaccine (Engerix B). Antibody responses were determined and compared with those to plasma-derived Pasteur vaccine, obtained in 1986. Antibody concentrations were significantly higher in the group given recombinant vaccine, therefore this vaccine has superior immunogenicity and probably confers extended duration of protection.

Class II antigens in Hashimoto thyroiditis: II. Expression of HLA-DR on infiltrating mononuclear cells in peripolesis

Surgical specimens from patients with Hashimoto thyroiditis (HT) or colloid goiter (CG) were analyzed using an immunofluorescence double staining technique to characterize the infiltrating mononuclear cells (MNC) and to determine the possible expression of HLA-DR antigens by these cells. In HT the majority of infiltrating MNC were T cells. In the interstitium T cells with helper/inducer phenotype (Leu 3a+) were more abundant than those with suppressor/cytotoxic phenotype (OKT8+) and approximately 10-25% of all T cells expressed HLA-DR. Among the cells in peripolesis [i.e., protruding between thyroid epithelial cells (TEC)] OKT8+ cells were observed more frequently than Leu 3a+ cells, expression of DR antigens being 7 and 12%, respectively. The occurrence of Leu 3a+ cells in peripolesis is in marked contrast to the findings in colloid goiter where the intraepithelial population of MNC is almost exclusively composed of OKT8+ cells. The various ways in which the peripoletic Leu 3a+ cells could contribute to the special pathogenesis of HT are discussed.

Immunomodulatory effect of sodium dodecyl sulfate on human neutrophils and the human promyelocytic HL-60 cell line

The effect of sodium dodecyl sulfate (SDS), an anionic amphiphilic detergent, on the function of human neutrophils and of the human promyelocytic leukemia cell line HL-60 was investigated. SDS modulated the respiratory burst in human neutrophils and HL-60 cells which were stimulated with phorbol 12-myristate 13-acetate (PMA). In concentrations above 1 X 10(-6) M it also caused release of lysosomal enzymes (beta-D-glucuronidase, myeloperoxidase and lysozyme) from neutrophils. Our results demonstrate that SDS at concentrations 1 X 10(-6) M-1 X 10(-4) M strongly affect properties of human phagocytic cells.