Treatment of inflammatory dermatoses by tumour necrosis factor antagonists.

Background: The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches, based on an incomplete knowledge of the immune pathogenesis, are mostly unavailable. The currently applied treatments can in fact lead to remission of the disease; however, under certain circumstances undesirable side-effects must be expected. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the application of TNF-alpha inhibitors represents a novel, more specific, and effective therapeutic option for distinct chronic inflammatory diseases.

Retention forces and contact angles for critical liquid drops on non-horizontal surfaces.

Retention forces and drop parameters are investigated for drops on the verge of sliding on vertical and inclined surfaces. Using earlier observations of drop geometry, the retentive-force factor relating surface-tension forces to contact-angle hysteresis is reliably determined. The retention force for a drop is found to be insignificantly affected by the aspect ratio of its contour.

Dissemination of a Sjögren's syndrome-associated extranodal marginal-zone B cell lymphoma: circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements.

Objective: Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions.

Methods: Histopathologic and Ig heavy- and light-chain variable-region gene (V(H/L)) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL.

[Therapeutic application of TNF-alpha inhibitors infliximab and etanercept in inflammatory skin disorders].

Background: The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches are not available because of incomplete knowledge of the immune pathogenesis. The current therapeutic approaches can induce remission, but often produce undesirable side effects. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the use of TNF-alpha inhibitors could represent a further, more specific and effective therapeutic option for other selected inflammatory skin diseases.

Balancing diversity and tolerance: lessons from patients with systemic lupus erythematosus.

The autoimmune disease systemic lupus erythematosus (SLE) is caused by a failure of B cell tolerance. Recent studies in mouse models of SLE have identified several distinct tolerance checkpoints that must each function appropriately to protect against disease. However, studies of B cell repertoire selection in humans are essential to understand which checkpoints are defective in human autoimmune diseases.

Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome.

Objective: To assess whether abnormal chemokine receptor expression and/or abnormal responsiveness to the cognate ligands might underlie some of the disturbances in B cell homeostasis characteristic of primary Sjögren's syndrome (SS).

Methods: Chemokine receptor expression by CD27- naive and CD27+ memory B cells from patients with primary SS and healthy control subjects was analyzed using flow cytometry, single-cell reverse transcriptase-polymerase chain reaction (RT-PCR), and migration assays.

Results: In contrast to healthy subjects, significantly higher expression of both surface CXCR4 and CXCR4 messenger RNA (mRNA) was seen in peripheral blood B cells from patients with primary SS.

Infliximab in the treatment of moderate to severe atopic dermatitis.

Background: Chronic use of standard therapies for atopic dermatitis (AD) is associated with variable efficacy and potential side effects. Targeted therapeutic approaches, such as the inhibition of tumor necrosis factor-alpha, may be a novel option.

Objective: This investigator-initiated, open, prospective, single-center, pilot study was conducted to evaluate the long-term efficacy and safety of infliximab in patients with AD.

Hydrophilicity of elastomeric non-aqueous impression materials during setting.

Objectives: Clinically relevant accuracy of dental impressions depends on flowing and wetting properties of the applied impression materials. The major objective of this study was to develop an experimental set-up and an analysis strategy for wettability measurements of impression materials during their working time.

Methods: High-resolution drop shape analysis was used to study contact angles on thin unset films of two polyether and two vinyl polysiloxane (VPS) impression materials.

The complex between hydrogenase-maturation proteins HypC and HypD is an intermediate in the supply of cyanide to the active site iron of [NiFe]-hydrogenases.

Carbamoylphosphate has been shown to be the educt for the synthesis of the CN ligands of the NiFe metal centre of hydrogenases from Escherichia coli. In the absence of carbamoylphosphate, cells accumulate a complex of two hydrogenase maturation proteins, namely HypC and HypD for the synthesis of hydrogenase 3. A procedure for the purification of wild-type HypD protein or of a biologically active derivative carrying the Strep-tagII((R)) at the N terminus has been developed.

Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus.

Objective: In systemic lupus erythematosus (SLE), the increased generation of memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and destructive immunoglobulin deposits in the kidneys. We undertook this study to determine the biologic mechanism driving this overactivation of the B cell compartment, which is the central issue in SLE.

Methods: We used flow cytometry to analyze expression of the T cell-specific inducible costimulator (ICOS) and its ligand (ICOS-L) on B cells obtained from the peripheral blood of SLE patients.

Panel of Bacillus subtilis reporter strains indicative of various modes of action.

In a recent project, we collected the transcriptional profiles of Bacillus subtilis 168 after treatment with a large set of diverse antibacterial agents. One result of the data analysis was the identification of marker genes that are indicative of certain compounds or compound classes. We cloned these promoter regions in front of a luciferase reporter gene and reintroduced the constructs individually into the B.

Liquid drops on vertical and inclined surfaces; II. A method for approximating drop shapes.

In this article, a new method is proposed to approximate the shapes of liquid drops on vertical and inclined surfaces. Based on observations from Part I, the profile of a drop at a given azimuthal angle is approximated by two circles sharing a common tangent at the maximum height. The drop volume is obtained by integrating all profiles over the circumference of the base.

Liquid drops on vertical and inclined surfaces; I. An experimental study of drop geometry.

Experiments have been conducted to investigate the geometric parameters necessary to describe the shapes of liquid drops on vertical and inclined plane surfaces. Two liquids and eight surfaces have been used to study contact angles, contact lines, profiles, and volumes of drops of different sizes for a range of surface conditions. The results show the contact-angle variation along the circumference of a drop to be best fit by a third-degree polynomial in the azimuthal angle.

Immunglobulin repertoire analysis provides new insights into the immunopathogenesis of Sjögren's syndrome.

This review focuses on the use of immunglobulin (Ig) variable region genes by B cells from patients with primary Sjögren's syndrome (pSS) and the biologic insights that this provides. Comparison of the Ig repertoire from the blood and parotid gland of pSS patients with that of normal donors suggests that there are typical disturbances of B cell homeostasis with depletion of memory B cells from the peripheral blood and accumulation/retention of these antigen-experienced B cells in the inflamed tissue. Although there are clonally expanded B cells in the parotid gland, generalized abnormalities in the B cell repertoire are also found in pSS patients.

Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B cells in a patient with primary Sjögren's syndrome.

Myoepithelial sialadenitis (MESA) of the major salivary glands is a characteristic feature of primary Sjögren's syndrome (pSS). To delineate systemic and organ-specific influences on B cells in a patient with pSS and benign MESA, individual B cells were simultaneously obtained from the peripheral blood and inflamed parotid gland. Immunoglobulin variable heavy chain (VH) rearrangements in single sorted CD19+ B cells were subsequently amplified, sequenced and analysed.

Correlation between circulating CD27high plasma cells and disease activity in patients with systemic lupus erythematosus.

Objective: Disease activity in systemic lupus erythematosus (SLE) is usually assessed with complex disease activity scores comprising a variety of different parameters. In order to determine whether SLE disease activity correlates with abnormal B lymphocyte activity, B cell subsets were analyzed, and their relationship to clinical and humoral measures of disease activity was assessed.

Methods: The distribution of B cell subsets was determined by fluorescence-activated cell sorting analysis and assessed in relation to the autoantibody profile, disease activity measured by the SLE Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure scores, disease duration, and therapy.

Semiquantitative and qualitative assessment of B-lymphocyte V H repertoire by a fluorescent multiplex PCR.

We established a new tool to perform semiquantitative and qualitative screening for V(H) gene usage frequency during IgH rearrangements in human B-lymphocytes. In two separate multiplex PCRs, the rearranged VDJ regions were amplified with V(H) family-specific primers labeled with different fluorescent dyes (FAM, HEX, NED, or ROX). The relative amount of each of the particular V(H) family products and their ratios were determined by fragment analysis on a ABI PRISM 377 sequencer.

Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndrome.

Objective: To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sjögren's syndrome (SS).

Methods: The distribution of peripheral B cell subpopulations in 21 patients with primary SS was analyzed by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements were analyzed in single B cells isolated from the peripheral blood and parotid glands by fluorescence-activated cell sorting.

Analysis of immunoglobulin light chain rearrangements in the salivary gland and blood of a patient with Sjögren's syndrome.

Patients with Sjögren's syndrome (SS) have characteristic lymphocytic infiltrates of the salivary glands. To determine whether the B cells accumulating in the salivary glands of SS patients represent a distinct population and to delineate their potential immunopathologic impact, individual B cells obtained from the parotid gland and from the peripheral blood were analyzed for immunoglobulin light chain gene rearrangements by PCR amplification of genomic DNA. The productive immunoglobulin light chain repertoire in the parotid gland of the SS patient was found to be restricted, showing a preferential usage of particular variable lambda chain genes (V lambda 2E) and variable kappa chain genes (V kappa A27).

Immunoglobulin Vlambda light chain gene usage in patients with Sjögren's syndrome.

Objective: To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig Vlambda and Jlambda gene usage, differences in somatic hypermutation, defects in selection, or indications for perturbations of B cell maturation.

Methods: Individual peripheral B cells from SS patients were analyzed for their Vlambda gene usage by single-cell polymerase chain reaction amplification of genomic DNA and compared with those from normal controls.

Results: Molecular differences from controls in Vlambda-Jlambda recombination were identified that were reflected by findings in the nonproductive Vlambda repertoire of the patients, including enhanced rearrangement of Vlambda10A and Jlambda2/3 gene segments.

Coordination and Conversion of Urea at Dinuclear &mgr;-Acetato Nickel(II) Complexes with Symmetric and Asymmetric Cores.

A series of symmetric and asymmetric pyrazolate-based dinuclear Ni(II) complexes relevant to the active site of urease is reported, which have acetate ions as secondary bridges and which feature variations in the type (N or S) and number of donor sites provided within the individual coordination compartments of the primary pyrazolate ligand matrixes. X-ray crystallographic structures of the acetone adduct [L(1)Ni(2)(&mgr;-OAc)(acetone)(2)](ClO(4))(2) (1) as well as of the urea adducts [L(1)Ni(2)(&mgr;-OAc)(benzylurea)(2)](ClO(4))(2) (2c), [L(2)Ni(2)(&mgr;-OAc)(urea)](ClO(4))(2) (3a), and [L(3)Ni(2)(&mgr;-OAc)(N,N'-dimethylurea)(2)(MeOH)(2)](ClO(4))(2) (4) have been determined. They reveal that the urea substrates are tied up with the bimetallic cores by both O-coordination to the metal centers and hydrogen bonding between the urea NH and the O atoms of the bridging acetate.