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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 35 (2005), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Although it is thought that both Th1- and Th2-type inflammations are involved in the pathogenesis of atopic dermatitis (AD), it is controversial which immune response is more involved in regulating the clinical severity of AD. We recently found that the squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 are novel biomarkers of bronchial asthma, downstream of IL-4 and IL-13.Objective We examined whether SCCA1 and SCCA2 could also serve as biomarkers of AD, reflecting its Th2-type immune responses, and whether the expression level of SCCA was correlated with clinical severity of AD.Method We compared the expression of SCCA1 and SCCA2 at the mRNA and protein levels in both involved and uninvolved skin of AD patients and in normal control skin. We next analysed induction of SCCA by IL-4 or IL-13 in keratinocytes. Finally, we compared the serum level of SCCA with laboratory parameters reflecting Th2-type inflammation and clinical severity in AD patients.Results SCCA1 and SCCA2 were highly expressed in involved skin of AD patients, compared with their uninvolved skin, at both mRNA and protein levels. SCCA protein was dominantly expressed in suprabasal keratinocytes in the epidermis of AD patients. Either IL-4 or IL-13, but not IFN-γ or TNF, induced production of SCCA in keratinocytes. These result suggest that SCCA is induced in AD skin, probably due to direct actions of IL-4 and/or IL-13 on keratinocytes. Serum levels of SCCA were well correlated with eosinophil numbers and serum lactate dehydrogenase levels, and weakly with serum IgE levels, in AD patients. Furthermore, serum levels of SCCA were strongly correlated with clinical severity.Conclusions Th2-type inflammation dominantly regulates the clinical severity of AD, and SCCA is a relevant biomarker of AD, reflecting both Th2-type inflammation and clinical severity.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Darier's disease (DD) and Hailey–Hailey disease (HHD) are skin disorders arising, respectively, from autosomal dominant mutations in ATP2A2, encoding the sacro/endoplasmic reticulum calcium ATPase, and ATP2C1, encoding the Golgi apparatus calcium ATPase. Exposure to ultraviolet (UV) B irradiation exacerbates the skin lesions, which can be treated with corticosteroids and retinoids.Objectives  To investigate the molecular basis for DD and HHD.Methods  We used quantitative reverse transcriptase-polymerase chain reactions to examine the effects of UVB irradiation on ATP2A2 and ATP2C1 mRNA levels in cultured normal keratinocytes.Results  We observed that UVB irradiation reduced ATP2A2 and ATP2C mRNA levels. The addition of retinoids or corticosteroids to the cell culture inhibited the UVB-induced suppression of both ATP2A2 and ATP2C1 mRNA levels, and UVB-induced suppression of ATP2C1 mRNA was also inhibited by the addition of ciclosporin, tacrolimus and vitamin D3. The addition of anti-interleukin (IL)-6 antibody to the cell culture prevented the UVB-induced suppression of ATP2A2 and ATP2C1 mRNA; in contrast, the addition of anti-IL-8 antibody slightly accelerated the suppression.Conclusions  These results suggest that drugs effective for DD and HHD act by modulating ATP2A2 and ATP2C1 mRNA expression, respectively, and that the proinflammatory cytokines IL-6 and IL-8 play important roles in the regulation of ATPA2 and ATP2C1 expression in homeostasis and/or inflammation of the skin.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  CDK5 is a member of proline-directed serine/threonin kinases. Although its cDNA was originally cloned as a homologue to those for the other members of the cyclin-dependent kinase (CDK) family, CDK5 has been shown to function differently from other CDKs. CDK5 is activated by non-cyclin partners, p35 and p39, and important during brain development by influencing adhesion, migration and differentiation of neurones.Objectives  We sought to investigate the expression and functions of CDK5 in human keratinocytes.Methods  Expression of CDK5/p35, interaction of CDK5/p35 with adhesion molecules, and its roles in cell–cell and cell–matrix adhesion were studied by reverse transcriptase–polymerase chain reaction, immunoblotting and aggregation/adhesion assays in primary cultured normal human keratinocytes from infant foreskins and a human keratinocyte HaCaT cell line. Localization of CDK5 and p35 in normal human epidermis and psoriatic epidermis was studied by immunohistochemistry.Results  Both CDK5 and p35 were expressed in primary cultured keratinocytes, HaCaT cells and normal human epidermis. Roscovitine, an inhibitor of CDK5, enhanced Ca2+-dependent (cadherin-dependent) aggregation of HaCaT cells whereas it inhibited adhesion of HaCaT cells to fibronectin associated with reduced active states of β1 integrin. Interestingly, psoriatic skin showed reduced CDK5 and p35 expression in the lower half of the epidermis, which might be associated with decreased amount of activated β1 integrin in the epidermis of psoriatic skin.Conclusions  CDK5/p35 may be involved in cell–cell and cell–matrix adhesion in human keratinocytes by differently regulating cadherins and integrins. Furthermore, reduced expression of CDK5/p35 in the epidermis might be involved in the pathogenesis of psoriasis.
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report a 6-month-old Japanese boy showing ichthyosis linearis circumflexa localized on the palms and soles. He showed bamboo hairs and aminoaciduria, and was positive for cow's milk and egg IgE antibodies by radioallergosorbent tests. Trypsin-like hydrolytic activity in the patient's lesional stratum corneum showed an activity seven times higher than that in age-matched controls. DNA analysis showed that the patient harboured the compound heterozygous mutations R790X and 1220+1 G→C in the SPINK5 gene, compatible with the diagnosis of Netherton syndrome (NS). As the genotype/phenotype correlations in NS have not yet been fully clarified, the position of the premature termination codon in the SPINK5 gene may contribute to explain such a mild form of NS in our patient.
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  • 7
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary  Background  Darier disease (DD) and Hailey–Hailey disease (HHD) are autosomal dominantly inherited skin disorders that histologically share the characteristics of suprabasal separation and acantholysis of epidermal keratinocytes. Various mutations in the DD gene (ATP2A2) and the HHD gene (ATP2C1) (respectively encoding the calcium pumps of the sarco/endoplasmic reticulum and the Golgi apparatus) have recently been described in multiple families with DD and HHD. Mutations in ATP2A2 or ATP2C1 have been suggested as causing the conditions via the mechanism of haploinsufficiency. Ultraviolet (UV) B irradiation is thought to be an aggravating factor in both diseases.Objectives  To examine the effects of various stimuli on ATP2A2 and ATP2C1 mRNA expression, and to examine the role of calcium pumps during keratinocyte differentiation.Methods  The effects of UVB irradiation, of UVB-inducible inflammatory cytokines produced by keratinocytes and of high-calcium medium (1·8 mmol L−1 as opposed to 0·08 mmol L−1 Ca2+) on ATP2A2 and ATP2C1 mRNA expression were quantified in cultured normal human keratinocytes using reverse transcription-polymerase chain reaction.Results  Expression of ATP2A2 and ATP2C1 mRNA was suppressed immediately after exposure to UVB irradiation, and modulation of mRNA expression was achieved in keratinocytes cultured with proinflammatory cytokines. The mRNA expression of both genes was increased significantly after the shift to high extracellular Ca2+ concentration.Conclusions  The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.
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  • 8
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and ...
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Journal of clinical periodontology 32 (2005), S. 0 
    ISSN: 1600-051X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objective: To determine the relationship between serum vitamin C and periodontitis as estimated by clinical attachment loss (CAL) in community-dwelling elderly Japanese.Material and Methods: This analysis was confined to 413 Niigata citizens aged 70 years in whom the data for serum vitamin C and CAL were available. High-pressure liquid chromatography method was used to ascertain the serum vitamin C levels while CAL was assessed on six sites of all teeth present including third molars by means of pressure-sensitive probes. Other variables included gender, smoking, toothbrushing frequency, number of teeth present and random blood sugar levels.Results: Serum vitamin C concentration was inversely related to CAL (r=−0.23, p〈0.00005) at bivariate level. Multiple linear regression analysis showed that CAL was 4% greater in subjects with lower serum vitamin C levels than in subjects with higher serum vitamin C levels notwithstanding smoking, diabetes, oral hygiene, gender or number of teeth present.Conclusion: The findings suggested that serum vitamin C might have relatively weak but a statistically significant relationship with periodontitis in this elderly population.
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Journal of clinical periodontology 32 (2005), S. 0 
    ISSN: 1600-051X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Objective: The main objective of this study was to determine the relationship between bleeding on probing (BOP) and periodontal disease progression in community-dwelling older adults.Methods: A 3-year longitudinal study was carried out in 229 non-smoking healthy older adults aged 70 years. Using pressure-controlled periodontal probes, BOP, pocket depth and attachment level at 13,289 sites were measured annually. Periodontal disease progression was defined as an increase in attachment loss of 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:03036979:JCPE834:ges" location="ges.gif"/〉3 mm from the baseline to the final examination. The backward stepwise logistic regression analysis was performed to assess the relationship between the total number of sites with BOP in the four examinations and periodontal progression.Results: Logistic regression analysis showed that the odds ratios of BOP frequency for periodontal disease progression ranged from 1.4 to 6.2 after controlling for pocket depth 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:03036979:JCPE834:ges" location="ges.gif"/〉4 mm at baseline, number of missing teeth, jaw type and tooth site.Conclusion: Increasing frequencies of bleeding might increase the probability of periodontal disease progression in community-dwelling older adults.
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