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Harald Löffler

Publications and source records attributed to Harald Löffler.

12 recordsLinked to original sources
PubMed2006

Chk1-dependent regulation of Cdc25B functions to coordinate mitotic events.

The coordination of mitotic spindle formation and chromatin condensation is an essential prerequisite for successful mitosis. Both events are thought to be initiated by cyclin B/Cdk1, whose initial activation occurs in late prophase at the centrosomes. Recently, we have shown that Chk1 localizes to interphase centrosomes and thereby negatively regulates entry into mitosis by preventing premature activation of cyclin B/Cdk1. Here, we demonstrate that inhibition of Chk1 kinase induces mitotic entry with regular spindle assembly but aberrant and mislocalized chromatin. This effect, which we have termed the 'paraspindle' phenotype, was reverted by downregulation of Cdc25B phosphatase using siRNA, which restored normal mitosis with regular chromatin. Analogous to Chk1 inhibition, the 'paraspindle' phenotype was induced by overexpression of Cdc25B but not Cdc25A. Our results suggest that Chk1 functions to coordinate mitotic events through regulation of Cdc25B.

Cell Cycle↗
PubMed2006

Structure meets function--centrosomes, genome maintenance and the DNA damage response.

Centrosomes are cytoplasmic organelles playing a fundamental role in organizing both the interphase cytoskeleton and the bipolar mitotic spindle. In addition, the centrosome has recently come into focus as part of the network that integrates cell cycle arrest and repair signals in response to genotoxic stress--the DNA damage response. One important mediator of this response, the checkpoint kinase Chk1, has been shown to negatively regulate the G(2)/M transition via its centrosomal localization. Moreover, there is growing evidence that a centrosome inactivation checkpoint exists, which utilizes DNA damage-induced centrosome fragmentation or amplification to provoke a "mitotic catastrophe" and eliminate damaged cells. Candidate regulators of this centrosomal checkpoint include the checkpoint kinase Chk2 and its upstream regulators ATM and ATR. In addition, a growing number of other proteins have been implicated in centrosomal regulation of the DNA damage response, e.g. the tumor suppressor p53, the breast cancer susceptibility gene product BRCA1 and mitotic regulators such as Aurora A, Nek2 and the Polo-like kinases Plk1 and Plk3. However, many missing links and discrepancies between different model systems remain.

Animals↗
PubMed2006

Effect of a 1 min hand wash on the bactericidal efficacy of consecutive surgical hand disinfection with standard alcohols and on skin hydration.

BACKGROUND: In most surgical theatres, a 1 min or even longer hand wash is routine as part of the pre-operative hand disinfection. But its benefit has recently been seen critically. METHODS: We have therefore investigated the effect of a 1 min hand wash on skin hydration and on the efficacy of consecutive surgical hand rubbing with three standard alcohols (60% propan-1-ol, 60% propan-2-ol, 80% ethanol; all v/v) on the resident hand flora. Three types of treatment were performed: (i) a 1 min pre-wash before surgical hand disinfection, (ii) no pre-wash before surgical hand disinfection and (iii) no pre-wash but use of a brush for 1 min during disinfection procedure. The efficacy of the alcohols was determined according to prEN 12791 with the same 20 volunteers in paired groups. To assess the effect of the hand wash on skin hydration, 10 volunteers washed their hands with sapo kalinus for 1 min and dried hands with a paper towel. Skin hydration was measured with a corneometer before the hand wash and subsequently up to 10 min thereafter both on the palm and dorsum of hands. We also tested the reduction of bacterial spores by a 15 s hand wash according to EN 1499 after artificial contamination of hands of 14 volunteers with spores of B. stearothermophilus. RESULTS: Propan-1-ol (60%) was most effective with a mean log10 reduction of 2.11, followed by ethanol (80%) with a mean log10 reduction of 1.76 and propan-2-ol (60%) with a mean log10 reduction of 0.57 (all immediate effect without hand wash). The efficacy of the alcohols was neither significantly improved nor impaired by a preceding 1 min hand wash, but there is a trend towards better efficacy on dry hands. Using a brush for 1 min during disinfection resulted in a better efficacy with all alcohols. An anaylsis of variance revealed that the immediate effect of ethanol (p = 0.013) and propan-2-ol (p = 0.001) is significantly influenced by the variation of treatments which is mainly explained by the effect of brushing during disinfection. But no significant difference between treatment variations was found in the sustained effect with any of the alcohols. Skin hydration increased significantly by a 1 min hand wash for up to 10 min despite drying hands with a paper towel. A 15 s hand wash reduced the number of bacterial spores significantly from log10 3.84 to log10 1.99 (p = 0.001). CONCLUSIONS: There is no benefit of a hand wash as part of surgical hand disinfection except that a short hand wash of 15 s can effectively reduce spores. The best time for this short hand wash is at the beginning of work in hospital, but at the latest in the sluice of the operating theatre about 10 min before applying an alcohol-based hand rub to give the skin enough time to dry.

Adult↗
PubMed2006

Primary prevention in health care employees: a prospective intervention study with a 3-year training period.

Irritant contact dermatitis is a mayor problem in health care employees. Because educational programs have shown convincing success in certain occupations (e.g. in hairdressers), this study investigates the effect of a special training program in health care trainees. 521 trainees from 14 nursing schools in Central Germany were randomly divided in 2 groups, (i) an intervention group with a regular teaching protocol regarding all aspects of primary prevention and (ii) a control group without any further teaching. Morphological changes of the hands, use of hand care creams and knowledge regarding skin care were evaluated regularly during their 3 years lasting training period (1999-2002). In the intervention group, we found at the end of the 3-year training period a significant better skin condition of the hands than in the control group: a 3-year prevalence of morphological skin changes of 66.7% versus 89.3%. The unteached trainees (control group) had an odds ratio (OR) of 4.8 [95% confidential interval (CI): 2.9-7.8] for developing any skin changes on the hands after 3 years. Besides the effect of the teaching, the history of hand dermatitis before the study start was an independent risk factor for development of further hand dermatitis [OR 1.9, 95% CI: 1.0-3.6). Age and sex showed no influence on the skin condition. Atopic constitution had an influence on the development of skin changes only at the evaluation after 18 month. The observed effect in the intervention group may best be explained by different behaviour of the trainees, e.g. the amount of hand washing was reduced, while procedure of hand disinfection remained unchanged compared with the control group. However, the amount of used skin care cream did not differ between the both groups. This study shows that primary prevention of skin disease by regularly teaching during the training period of medical employees can effectively reduce the risk of development of irritant skin changes of the hands. Therefore, teaching and continuous motivation regarding preventive individual and collective measures during the training of medical staff should be an obliged part of the curriculum.

Adult↗
PubMed2006

Positive patch test reactions to nickel sulphate are not modified by neighbouring negative fragrance patch tests. A multicenter-study by the German contact dermatitis research group.

It is tacitly assumed that a positive patch test reaction is not affected by adjacent negative tests. However, despite its fundamental importance for the interpretation of test reactions this assumption has not been proven. To test this assumption, special TRUE-test strips were prepared containing placebo, nickel sulphate and fragrance mix as the only allergens, separated by distances of 1 cm and 7 cm and blinded to the investigators. Patients were synchronously tested with two strips. Out of 493 patients tested in 6 centres, the 93 with positive reactions to nickel sulphate only were evaluated. No relevant difference was found between positive nickel reactions in the two different distances to a negative fragrance patch test. We conclude that a positive patch test reaction is not affected by adjacent negative patch tests, which therefore can be neglected for the interpretation of positive reactions.

Allergens↗
PubMed2004

The "strip" patch test: results of a multicentre study towards a standardization.

BACKGROUND: The "strip" patch test (SPT) is a variant of patch testing which is used for substances with a poor percutaneous penetration. Penetration of the substances is enhanced by repeated applications of adhesive tape prior to their application to the skin. However, no guidelines exist for standardized performance of the SPT. OBJECTIVES: The aim of this multicentre study was to obtain a first practical approach towards a standardized SPT procedure. METHODS: Intact noninflamed skin of the upper back of 83 healthy volunteers was tape-stripped. For sequential strips, a 25-mm diameter 3M Blenderm surgical tape was vertically applied and gently pressed downward using the fingertips for about 2 s. The tape was removed in one quick movement at an angle of 45 degrees in the direction of adherence. Each strip was performed with a new piece of tape on exactly the same skin area. RESULTS. In each subject, we first determined the number of strips (A) until the skin surface started to glisten and calculated the median number of strips (A) in the sample (A=26 strips). We then ascertained the median number of strips (a) in the sample that was necessary to achieve a statistically significant and twofold increase in TEWL (a=11 strips), revealing a "critical" stratum corneum strip depth. The unknown number of strips (a) for each subject was finally calculated from the formula a/A=a/A, i.e. the individual number of strips (A) until the skin surface started to glisten was multiplied by a derived tape-specific correction factor (cf=a/A=11/26=0.4). The increase in percutaneous penetration in strip patch testing by performing "a" strips versus conventional patch testing was shown by scoring of clinical and subjective SLS irritant reactions. CONCLUSIONS: The present multicentre study outlines an experimentally derived approach for a uniform SPT procedure, which does not require the use of complex technical equipment. This first approach now requires validation by a study involving the application of allergens to obtain evidence of enhancement in the sensitivity of patch testing.

Adhesives↗
PubMed2003

Distinct modes of deregulation of the proto-oncogenic Cdc25A phosphatase in human breast cancer cell lines.

The rapid cell cycle arrest in response to DNA damage is mediated by degradation of the Cdc25A phosphatase, a proto-oncogene whose mRNA is frequently overexpressed in human tumours. Here, we study the occurrence and mechanisms of Cdc25A deregulation in human breast cancer cell lines. We demonstrate aberrantly elevated Cdc25A protein abundance and phosphatase activity in eight out of 15 cell lines, in some cases resulting in abrogation of the Cdc25A-mediated checkpoint response to ionizing radiation (IR), and this defect correlated with hypersensitivity to IR. Furthermore, we present evidence that deregulation of Cdc25A occurs predominantly on the post-transcriptional level, as overabundant Cdc25A protein was usually not accompanied by adequate mRNA overexpression. Instead, we demonstrate that aberrantly enhanced protein stability is an important mechanism underlying Cdc25A overabundance in a subset of breast cancer cell lines. Given the frequency of this mechanism, we propose that the DNA integrity checkpoint controlling Cdc25A protein stability might be a common target for deregulation in breast cancer.

Breast Neoplasms↗
PubMed2003

Allergy and irritation: an adverse association in patients with atopic eczema.

The pathomechanism of atopic eczema is complex. Two of the most important exogenous factors for atopic eczema are allergenic and irritant substances. In this study we investigate the combined effect of topical aeroallergens and irritation on the skin of atopic individuals. We performed patch testing with several aeroallergens (atopy patch test) and with an irritant, sodium lauryl sulphate, on clinically unaffected skin of 30 sensitized patients with atopic eczema. Application was conducted alone and as a consecutive application. Healthy volunteers served as controls. Evaluation was made by measurement of transepidermal water loss 2 h after removal of the patches. In atopic patients, we found increased levels of transepidermal water loss induced by the aeroallergens as well as by sodium lauryl sulphate. The most impressive barrier disruption was seen after application of house dust mite, followed by cat dander and grass pollen. However, the consecutive application of aeroallergens and sodium lauryl sulphate led to a highly pronounced increase in transepidermal water loss. Hence, in sensitized atopic subjects the combined effect of aeroallergens and detergents may cause severe skin problems, and this may be relevant in daily practice.

Adolescent↗
PubMedDate not supplied

The MOAHLFA index of irritant sodium lauryl sulfate reactions: first results of a multicentre study on routine sodium lauryl sulfate patch testing.

In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25% and 0.5% aq. has been added to routine allergen patch tests to assess its properties as a convenient diagnostic indicator of individual susceptibility to irritation at the time of patch testing. Previous studies indicated that irritant SLS reactivity may be related to individual factors such as age and sex. As these factors are, in turn, among the important predictors of contact allergy to many allergens, e.g. summarized in the 'MOAHLFA index', the impact of the MOAHLFA factors on irritant SLS patch test reactivity, and thus a potential for confounding, was assessed in the 5971 participating patients. As a result of 2 logistic regression analyses with an irritant reaction to 0.25% and 0.5% SLS, respectively, as outcome, male sex was identified as a relatively weak but significant risk factor (OR 1.38), while age 40 years or older was an even weaker risk factor (OR 1.22 and 1.15, respectively). Upon detailed analysis, no clear age gradient could, however, be identified. 1-day exposure time almost halved the odds of an irritant SLS reaction. In conclusion, this type of SLS patch test can be regarded as robust, indicating individual irritability relatively independent from the individual factors analysed here.

Adult↗
PubMedDate not supplied

Prevention of irritant contact dermatitis.

The prevention of skin diseases is accepted as an important part of occupational dermatology. Irritant dermatitis in particular, is a skin disease which can be avoided by preventional measures. Hence, an early introduction of trainees to preventional measures seems to be necessary to avoid bad habits which then become a matter of routine. The role of the dermatologist is not only the identification of individuals with a higher risk for developing irritant dermatitis, he should also inform his patients about the relevant irritants in their occupation (or of irritants in the household or leisure activities). Prevention by collective measures must be combined with individual measures (like gloves and protective clothing, correct skin cleaning and external creams). Periodical training and motivation of individuals at most risk is of utmost importance, because the best preventive measures are of no effect when they are not used regularly.

Dermatitis, Irritant↗
PubMedDate not supplied

Skin changes in geriatric nurses prior to training heralding a particular risk of hand dermatitis.

Irritant skin changes are a well known problem in nursing services. Especially geriatric nurses often complain of hand dermatitis, most likely induced by frequent washing and hand disinfections. In this cohort study, demographic data and skin changes from 521 nurse trainees were recorded. The data of geriatric nurse trainees (n = 149) were compared to that of other nurse trainees (n = 372), mostly of surgery, internal medicine, pediatric and obstetrics. Geriatric nurse trainees were significantly older and had noticeably severer irritant skin changes at the start of the training. Geriatric nurse trainees were more often undergoing retraining, because they had other jobs before. Interestingly, some nurses performed the retraining because they had problems with hand dermatitis in their previous job. More education concerning the risk of irritant dermatitis in health care occupations is desirable, not only for the starting nurse but also for the employment offices.

Adult↗