Sex-related psychological effects on metabolic control in type 2 diabetes mellitus.

Aims/hypothesis: Women are at higher risk of diabetes-related cardiovascular complications than men. We tested the hypothesis that there are sex-specific differences in glucometabolic control, and in social and psychological factors. We also examined the influence of these factors on glucometabolic control.

UV-B irradiated cell lines execute programmed cell death in various forms.

We investigated changes typical for apoptosis in various cell lines after UV-B irradiation. Using established methods for detection of apoptosis we demonstrate changes of cellular morphology, phosphatidylserine (PS) exposure, ollgonucleosomal DNA fragmentation and generation of hypochrome nuclei. To isolated high-molecular-weight (hmwt) DNA fragments we engaged a new method avoiding pulse field gel electrophoresis.

Alternatively spliced mRNA molecules of the thrombospondin receptor (CD36) in human PBMC.

We employed reverse transcription polymerase chain reaction (RT-PCR) to detect alternatively spliced CD36 mRNA in human peripheral blood mononuclear cells (PBMC). Sequencing of cloned cDNA revealed alternatively spliced mRNA molecules in 13 out of 39 clones. We observed exon skipping of up to 10 out of 12 coding exons in eight alternative transcripts.

Transcriptional activation of endogenous retroviral sequences in human epidermal keratinocytes by UVB irradiation.

Ultraviolet radiation is a pathogenic factor in various diseases, e. g., autoimmune disorders such as lupus erythematosus.

Retrovirus-associated rheumatic syndromes.

The influence of environmental factors in the initiation of autoimmune rheumatic diseases is still under debate. Infections with viruses (e.g.

Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus.

Objective: To investigate whether the established impaired phagocyte function in systemic lupus erythematosus (SLE) patients also affects apoptotic cell clearance. Accumulation of apoptotic waste as a source for autoantigens that induce and maintain autoimmune responses is discussed.

Methods: Apoptosis was detected by morphology and propidium iodide staining.

Induction of apoptosis reduces immunogenicity of human T-cell lines in mice.

Apoptotic cells, e.g. postinflammatory neutrophils, were reported to be engulfed by phagocytes without induction of an inflammatory response.

Small DNA fragments isolated from human T-cell clones are enriched in sequences involved in DNA bending.

IL-2 deprivation induces apoptosis in human IL-2-dependent T-cell clones. This process is characterized by typical cell morphology, changes in the cellular membranes and fragmentation of chromatin into units of single and multiple nucleosomes. We isolated apoptotic DNA of an IL-2-deprived T-cell clone and sequenced randomly selected fragments representing single and multiple nucleosomes.

Retroviruses and systemic lupus erythematosus.

In some animal models of autoimmune diseases the roles of exogenous and endogenous retroviruses are clearly defined. In ungulates caprine arthritis encephalitis virus, equine infectious anemia virus or Maedi-Visna virus infections cause a well-defined autoimmune disease and the appearance of seropositivity of the animals is of diagnostic value. Likewise, in MRL lpr/lpr mice insertion of a retrotransposon into the fas gene could clearly be shown to cause survival of autoreactive lymphocytes.

What triggers anti-dsDNA antibodies?

Analysis of somatic mutations revealed that induction of anti-dsDNA autoantibodies from SLE patients are antigen driven and thus T cell dependent. Since DNA per se has repeatedly been shown not to be immunogenic, various mechanisms leading to the production of anti-dsDNA-antibodies have been discussed including the role of oligonucleosomes. In the present study we demonstrate that the percentage of macrophage engulfing apoptotic cell material was significantly reduced in SLE as compared to control patients.