Checkpoint kinase 2 is required for efficient immunoglobulin diversification.

Maintenance of genome integrity relies on multiple DNA repair pathways as well as on checkpoint regulation. Activation of the checkpoint kinases Chk1 and Chk2 by DNA damage triggers cell cycle arrest and improved DNA repair, or apoptosis in case of excessive damage. Chk1 and Chk2 have been reported to act in a complementary or redundant fashion, depending on the physiological context.

Analysis of SHPRH functions in DNA repair and immunoglobulin diversification.

During replication, bypass of DNA lesions is orchestrated by the Rad6 pathway. Monoubiquitination of proliferating cell nuclear antigen (PCNA) by Rad6/Rad18 leads to recruitment of translesion polymerases for direct and potentially mutagenic damage bypass. An error-free bypass pathway may be initiated via K63-linked PCNA polyubiquitination by Ubc13/Mms2 and the E3 ligase Rad5 in yeast, or HLTF/SHPRH in vertebrates.

Checkpoint kinase 1 negatively regulates somatic hypermutation.

Immunoglobulin (Ig) diversification by somatic hypermutation in germinal center B cells is instrumental for maturation of the humoral immune response, but also bears the risk of excessive or aberrant genetic changes. Thus, introduction of DNA damage by activation-induced cytidine deaminase as well as DNA repair by multiple pathways need to be tightly regulated during the germinal center response to prevent lymphomagenesis. In the present study, we show that DNA damage checkpoint signaling via checkpoint kinase 1 (Chk1) negatively regulates somatic hypermutation.

Extracorporeal photochemotherapy as systemic monotherapy of severe, refractory atopic dermatitis: results from a prospective trial.

Background: Previous work has indicated that extracorporeal photochemotherapy (ECP) may be a safe and effective treatment in patients with severe atopic dermatitis.

Methods: We performed a prospective study to investigate the effect of a defined 20-week ECP protocol in patients with severe, refractory atopic dermatitis. The patient inclusion criteria included (i) disease duration of at least 1 year, (ii) SCORAD > 45, and (iii) resistance to first-line therapy, including topical steroids, topical calcineurin inhibitors, and one form of phototherapy (UVA, UVB, or PUVA) or one second-line therapy, including systemic steroids or cyclosporine.

A liquid-film forming acrylate cream for the treatment of anal pruritus.

Pruritus ani is a hidden but frequently occurring clinical condition, with a large impact on patients' quality of life. Currently, therapeutic options are scarce, offering mainly limited success. The authors performed a prospective, open-label, two-centre pilot study to analyse the efficacy and safety of a liquid-film forming acrylate cream for the treatment of pruritus ani and peri-anal skin irritation.

Motor imagery facilitates force field learning.

Humans have the ability to produce an internal reproduction of a specific motor action without any overt motor output. Recent findings show that the processes underlying motor imagery are similar to those active during motor execution and both share common neural substrates. This suggests that the imagery of motor movements might play an important role in acquiring new motor skills.

Ubc13 dosage is critical for immunoglobulin gene conversion and gene targeting in vertebrate cells.

In contrast to lower eukaryotes, most vertebrate cells are characterized by a moderate efficiency of homologous recombination (HR) and limited feasibility of targeted genetic modifications. As a notable exception, the chicken DT40 B cell line is distinguished by efficient homology-mediated repair of DNA lesions during Ig gene conversion, and also shows exceptionally high gene-targeting efficiencies. The molecular basis of these phenomena is elusive.

Impedance control complements incomplete internal models under complex external dynamics.

In this paper, we investigate motor adaptation of human arm movements to external dynamics. In an experiment, we tried to determine whether humans can learn an internal model of a mixed force field (V+P) that was the sum of a velocity-dependent force field (V) and a position-dependent force field (P). The experimental results show that the subjects did not learn the internal model of V+P accurately and they compensated for the loads by using impedance control.

Medium-dose ultraviolet (UV) A1 vs. narrowband UVB phototherapy in atopic eczema: a randomized crossover study.

Background: Ultraviolet (UV) A1 and narrowband (NB)-UVB have been reported to be effective treatments for atopic eczema (AE).

Objectives: We aimed to compare the efficacy of medium-dose UVA1 and NB-UVB mono-phototherapy in patients with AE.

Methods: A randomized double-blind controlled crossover trial (ClinicalTrials.

Differential mRNA expression of antimicrobial peptides and proteins in atopic dermatitis as compared to psoriasis vulgaris and healthy skin.

Background: Patients with atopic dermatitis (AD) are prone to have skin infections. We aimed to investigate mRNA expression levels of various antimicrobial peptides and proteins (AMPs) in AD patients, and compare it with psoriasis vulgaris (PV) patients and healthy subjects.

Methods: Skin biopsies were obtained from healthy subjects and patients with AD and PV.

Gene expression of cytokines in atopic eczema before and after ultraviolet A1 phototherapy.

Background: Atopic eczema (AE) is a common pruritic and chronically relapsing inflammatory skin disease in which cytokines seem to represent important factors in the pathogenesis.

Objectives: We aimed to investigate cytokine mRNA expression in the skin of patients with AE who underwent a course of ultraviolet A1 (UVA1) phototherapy.

Methods: We studied 21 patients diagnosed with extrinsic AE who were treated with a 6-week course of UVA1 phototherapy.

Pro-inflammatory cytokine production from normal human fibroblasts is induced by Tannerella forsythia detaching factor.

Background And Objective: Tannerella forsythia is a periodontal pathogen. Recently, we have reported that the cytopathic component of T. forsythia contains two distinct factors.

Tacrolimus ointment neither blocks ultraviolet B nor affects expression of thymine dimers and p53 in human skin.

Background: There is a lack of data with regard to the interaction between ultraviolet (UV) radiation and topical calcineurin inhibitors.

Objective: We aimed to investigate (1) the UV transmission through tacrolimus ointment and (2) the impact of topical exposure to tacrolimus on the protein expression of thymine dimers (TD) and p53 in human skin.

Methods: Spectrophotometric measurements (290-400 nm) of tacrolimus ointment and the vehicle were performed.

Increased expression of TGF-beta/Smad proteins in basal cell carcinoma.

Background: Basal cell carcinoma (BCC) is the most common cancer in humans placing a significant burden on healthcare services worldwide. There is an increasing evidence that the development of cutaneous epithelial tumours is pathogenetically linked to dysregulations of the transforming growth factor beta (TGF-beta) and its signalling molecules, the Smads.

Objective: In the present study we aimed to investigate the mRNA as well as protein expression of TGF-beta/ Smad signalling proteins in patients with BCC and healthy controls.

Quantification of ultraviolet protective effects of pityriacitrin in humans.

Pityriacitrin (PIT), produced by Malassezia yeasts, is an UV absorbing substance that might cause hypopigmentation in pityriasis versicolor alba. We aimed to investigate the UV protective effect of PIT in humans using in vitro and in vivo test methods. Spectrophotometry of PIT cream and the vehicle was performed in the wavelength range from 290 to 400 nm.

Extracorporeal photopheresis as a treatment for patients with severe, refractory atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a complex disease with a variety of possible treatment regimens. The study objective was to demonstrate that methoxsalen used in conjunction with the Uvar XTS photopheresis system (Therakos, Exton, Pa., USA) is safe and can have a clinical effect on the skin manifestations and the quality of life in patients with severe, refractory AD.

Repeat liposuction-curettage treatment of axillary hyperhidrosis is safe and effective.

Background: Liposuction-curettage (LC) is an effective surgical therapy option for axillary hyperhidrosis, with less scarring compared with radical excision of axillary skin. Although this method has proven to be effective, the treatment of nonresponders to minimally invasive surgery has not been previously defined. Whether these patients benefit from a second surgical procedure has not been evaluated so far.

Expression of human beta-defensins in patients with mycosis fungoides.

The human beta-defensins (hBDs) are peptides with a strong antimicrobial activity. Patients with atopic dermatitis (AD) and mycosis fungoides (MF) are prone to skin infections. We aimed to investigate the mRNA expression of hBDs in lesional and non-lesional skin of MF patients, and to compare the data with hBD levels found in AD patients and healthy controls.

Mycophenolate sodium for subacute cutaneous lupus erythematosus resistant to standard therapy.

Background: Approximately 75-95% of patients with cutaneous lupus erythematosus respond to antimalarial therapy and/or topical glucocorticosteroids. Immunosuppressive agents are usually considered a second-line approach in patients with resistant disease.

Objectives: This was a prospective, nonrandomized, open pilot study to evaluate the efficacy of mycophenolate sodium monotherapy in patients with recalcitrant subacute cutaneous lupus erythematosus (SCLE).

Significant downregulation of transforming growth factor-beta signal transducers in human skin following ultraviolet-A1 irradiation.

Background: Despite the significant role of the transforming growth factor (TGF)-beta/Smad pathway in cell growth and extracellular matrix regulation, relatively little is known regarding the effect of ultraviolet (UV) radiation on the TGF-beta/Smad signalling in human skin.

Objectives: We aimed to investigate the impact of UVA1 and UVB on the mRNA and protein expression of TGF-beta/Smad signal transducers in human skin in vivo.

Methods: Fifteen subjects were exposed to 1.