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Biomedical subjects

K Siepmann

Publications and source records attributed to K Siepmann.

7 recordsLinked to original sources
PubMed1999

[Hyperplasia of sebaceous glands (Fordyce's disease) in an oral mucocutaneous graft: 45-year follow-up].

BACKGROUND: Diffuse sebaceous gland hyperplasia in transplanted buccal mucosa is a very rare condition. We report on a further patient with this entity. PATIENT: In 1953, a now 68-year-old man suffered a severe alkali burn. Transplantation of oral mucosa was performed that same day in order to prevent perforation of the eye. Over the following 45 years, the patient developed multiple yellowish nodules within the grafts. Histologically, these nodules proved to be normally differentiated sebaceous glands. CONCLUSIONS: Diffuse sebaceous gland hyperplasia originating from within oral mucosa and developing over an extended period of time is a clinical entity known as Fordyce's disease. It is this a late complication of mucocutaneous transplantation, and although it constitutes mainly a problem of cosmesis, functionally it can lead to aberrant secretion of sebum.

Aged↗
PubMed1999

Fas-Fas ligand-mediated apoptosis within aqueous during idiopathic acute anterior uveitis.

PURPOSE: Despite ocular immune privilege, (auto)immune-mediated acute anterior uveitis (AAU) is relatively common. However, although relapses of AAU are usually self-limiting, possible regulatory mechanisms remain undefined in humans. Experimentally, Fas-Ligand (FasL)-mediated apoptosis of Fas+ inflammatory cells contributes to the immune privilege within the anterior chamber and provides an explanation for the success of corneal allograft transplantation. Therefore, whether such mechanisms regulate the immune response in AAU was investigated. METHODS: Aqueous and peripheral blood samples from consecutive patients presenting with idiopathic AAU were obtained with consent. Leukocytic phenotype was analyzed by flow cytometry, and apoptosis was determined by both flow cytometry and TdT-dUTP terminal nick-end labeling analysis. Presence of soluble Fas and FasL was determined by western blot analysis and enzyme-linked immunosorbent assay and compared with control aqueous from patients undergoing cataract surgery. The ability of the aqueous to induce apoptosis in a Fas+ Jurkat cell line was also determined. RESULTS: During AAU aqueous-infiltrating Fas+ cells included CD3+ T cells and granulocytes, whereas FasL+ cells comprised predominantly of non-CD3+ T cells. Higher levels of functional soluble FasL were found in aqueous of AAU patients than in normal aqueous, capable of inducing apoptosis in 68.9% +/- 7.6% of Fas+ lymphoid cells. Compared with peripheral blood, the CD4+ T cells infiltrate within aqueous showed significantly increased CD69 and CD25(IL-2r) expression. Flow cytometric analysis of aqueous showed that 9.32% +/- 1.2% of infiltrating non-granulocyte CD45+ cells were apoptotic, confirmed as T cells on subsequent three-color flow cytometric analysis. CONCLUSIONS: Taken together with published experimental data, the present study provides evidence for FasL-mediated apoptotic cell death contributing to the local immune regulation of ocular inflammatory disease and provides a mechanism to account for the self-limiting clinical course of AAU.

Acute Disease↗
PubMed1997

Observations on memory B-cell development.

We dissect in this article the roles of CD40 and its ligand in memory B-cell formation. Our data indicate that CD40 ligation does not directly lead to GC formation but it plays an indirect role related to maturation of helper T cells; signalling is bidirectional, to B cells, via CD40, upregulating cytokine receptor expression and to T cells, via CD40L, causing secretion of cytokines necessary for GC initiation. Later in the GC, CD40 selects mutated B cells for entry into the memory pool. This second T-cell-mediated CD40 ligation has consequences distinct from the first (rescue versus proliferation) that arise from rewiring of CD40 signal transduction pathways.

Animals↗
PubMed1996

CD40-mediated regulation of interleukin-4 signaling pathways in B lymphocytes.

The importance of cytokines in controlling immunoglobulin isotype switching is well known. Given the defect in switching to IgG, IgA and IgE isotypes in mice and humans that carry mutations in the CD40 and CD40 ligand genes, we have investigated the role of CD40 ligation in controlling B cell responses to interleukin (IL)-4. We have found that CD40-mediated signals cause a fivefold upregulation of IL-4 receptor (IL-4R) on the B cell surface and that this is associated with a 100-1000-fold increase in the cells' responsiveness to the cytokine. While we found no evidence of increased affinity or structural change of the receptor, we do find that prestimulation of B cells with anti-CD40 antibodies brings about several changes in the IL-4 signaling pathways. Subsequent delivery of IL-4 to CD40-prestimulated cells provokes intracellular signals distinct from those induced in resting B cells in response to IL-4. While resting B cells phosphorylate Jak3 kinase shortly after IL-4 activation, cells pre-incubated with anti-CD40 exhibit active dephosphorylation of this molecule and phosphorylation of proteins of around 45 kDa upon addition of IL-4. The common gamma chain, Jak3 and Jak1 can all be immunoprecipitated in normal amounts with the IL-4R chain after CD40 prestimulation. We show that the observed dephosphorylation of Jak3 may be due to a stable association with the src-homology protein tyrosine phosphatase SH-PTP2. In contrast, the enzyme appears to be inactive and to dissociate very quickly from the signaling complex in cells that are stimulated with IL-4 alone.

Animals↗
PubMed1994

CD40 ligation in B cell activation, isotype switching and memory development.

Interaction of CD40 on B cells with its ligand on activated T helper cells is crucial for the generation of mature T-dependent antibody responses. Experimental observations suggest that CD40 ligation acts at several points in B cell differentiation; however, it is not clear whether the consequences of ligation are direct or indirect. While its role in B cell activation is clearly direct we discuss the several ways in which it might drive isotype switching, the influence that it has on the development of memory B cells and the possibility that certain types of T-dependent antibody response are CD40L-independent. Experiments in which the ligation of CD40 is blocked in vivo reveal that early CD40 signals are important for the development of memory B cells but this may only reflect the ability of 'memory precursors' generated by CD40 ligation to accept subsequent programming or survival signals.

Animals↗
PubMed1980

[Therapeutic stereotypes among the mentally ill].

Using mathematical models described by Overall, the authors investigated in a sample of 301 psychiatric inpatients the therapeutic stereotypes in medicating psychotropic drugs and its dependence on symptom, syndrome and diagnostic level. The psychotropic drugs were described in a dimensional representation of psychopathology ('symptomatic space'). Besides dependencey from patient's characteristics as age and clinician's characteristics as special orientation, the therapeutic stereotype is mostly influenced by the symptom level. Only lithium therapy and electroconvulsive therapy are keyed to diagnosis. Getting more familiar with a psychotropic drug increases indications and contraindications on symptom level, the therapeutic stereotype gets more differentiated. The comparison between the therapeutic stereotypes of German and French psychiatrists shows a satisfactory congruence relating to dimensionality and relationships among the drugs.

Adult↗