| 1001. |
- Simonsson, Carl, 1976, et al.
(författare)
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Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis.
- 2011
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Ingår i: The Journal of investigative dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 131:7, s. 1486-93
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis (ACD) is the most prevalent form of human immunotoxicity. It is caused by skin exposure to haptens, i.e., protein-reactive, low-molecular-weight chemical compounds, which form hapten-protein complexes (HPCs) in the skin, triggering the immune system. These immunogenic HPCs are elusive. In this study a series of thiol-reactive caged fluorescent haptens, i.e., bromobimanes, were deployed in combination with two-photon fluorescence microscopy, immunohistochemistry, and proteomics to identify possible hapten targets in proteins in human skin. Key targets found were the basal keratinocytes and the keratins K5 and K14. Particularly, cysteine 54 of K5 was found to be haptenated by the bromobimanes. In addition, elevated levels of anti-keratin antibodies were found in the sera of mice exposed to bromobimanes in vivo. The results indicate a general mechanism in which thiol-reactive haptens generate cryptic epitopes normally concealed from the immune system. In addition, keratinocytes and keratin seem to have an important role in the mechanism behind ACD, which is a subject for further investigations.
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| 1002. |
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| 1003. |
- Simonsson, Carl, 1976, et al.
(författare)
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The pilosebaceous unit-a phthalate-induced pathway to skin sensitization
- 2012
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 264:1, s. 114-120
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. (C) 2012 Elsevier Inc. All rights reserved.
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| 1004. |
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| 1005. |
- Sjöström, Lars, et al.
(författare)
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Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state
- 1992
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Ingår i: International Journal of Obesity. ; 19, s. 465-479
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Tidskriftsartikel (refereegranskat)abstract
- Department of Medicine, Sahlgren's Hospital, University of Göteborg, Sweden. SOS (Swedish obese subjects) is an on-going intervention trial designed to determine whether the mortality and morbidity rates among obese individuals who lose weight by surgical means (gastric banding, vertical banded gastroplasty and gastric by-pass) differ from the rates associated with conventional treatment. For this purpose, the study is recruiting a sample of obese men and women who constitute a registry of potential subjects from which the participants are drawn. Eligibility criteria for participation in the registry were: age at application 37-57 years and BMI greater than or equal to 34 kg/m2 for men and greater than or equal to 38 kg/m2 for women. Before receiving a health examination, all patients complete extensive questionnaires on current and past health status, utilization of medical care and medications, socio-economic status, psychological profiles, dietary habits, physical activity, weight history, and familial disposition to obesity. Each surgical case is matched to its optimal control in the registry, to ensure that the two groups do not differ systematically with respect to any of 18 matching variables that may affect prognosis. The first 1006 subjects included in the registry have been studied with respect to morbidity and compared with on-going population studies of men and women in Göteborg, Sweden. The relative risks of prevalent disease and symptoms associated with obesity in 50-year-old males and females respectively were 4.3 and 4.7 (dyspnoea), 14.7 and 11.8 (angina), 6.3 (myocardial infarction, males only), 2.1 and 4.5 (hypertension), 5.2 and 6.6 (diabetes), 4.6 and 26.1 (claudication) and 1.7 and 1.8 (gall bladder disease). Correspondingly, obese males and females display elevations of systolic and diastolic blood pressure, fasting glucose, insulin, triglyceride, and uric acid levels. However, total cholesterol was not increased in obese males and was in fact significantly lower in obese compared with reference women. HDL-cholesterol was lower in obese than reference men (data were not available in reference women). The rate of taking sick pensions was over twice as high in SOS obese patients than in population controls. Finally, comparison of measurements with self-reported prevalence estimates revealed a considerable amount of previously undiagnosed hypertension and diabetes in the obese subjects. These data suggest that the excess health risks associated with obesity may not be fully appreciated. PMID: 1322873 [PubMed - indexed for MEDLINE]
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| 1006. |
- Skovbjerg, Susann, 1973, et al.
(författare)
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Sequetyping Validation of Streptococcus pneumoniae Clinical Isolates
- 2016
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Ingår i: 10th International Symposium on Pneumococci and Pneumococcal Diseases. Glasgow, UK; 20160626-30.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Serotyping of Streptococcus pneumoniae (pneumococcus) is required to monitor epidemiological trends following introductions of pneumococcal conjugate vaccines. However, new techniques are needed to lower the costs and work-load for obtaining pneumococcal serotype information, especially in low-income settings. Here, we validated a modified protocol of sequetyping for S. pneumoniae serotype identification. Methods: Forty-six strains of S. pneumoniae, isolated from blood cultures at the Sahlgrenska University Hospital, Gothenburg, Sweden, were analyzed. Serotypes of the strains were identified by Sanger sequencing of the regulatory gene cpsB of the capsulation locus of S. pneumoniae, using a modification of an earlier protocol (Leung et. al. 2012). To increase the coverage of the 1,000 bp sequence length of the cpsB gene, two additional sequencing primers in the central region of the gene were designed. The sequences were compared to available reference sequences, using the NCBI BLAST function. The results were compared to those obtained by multiplex qPCR, modified from a protocol published by the U.S. Centres of Disease Control and Prevention, and with the results obtained by gel diffusion and/or Quellung reactions, performed by the Public Health Agency of Sweden. Results: In total, 22 different serotypes/serotype groups were acquired by sequetyping of the 46 isolates. Contrary to the 74% of isolates that were serotyped/serotype grouped by qPCR, sequetyping could identify the serotype/serotype group in 98% of the isolates. Of the serotypes correctly identified by sequetyping, 32% were identified to a single serotype, whereas in 68% of the isolates, a single serotype could not be assigned. The serotype groups that could not be differentiated further included 6A/6B/6C/6D and 9A/9V. Conclusion: Sequetyping is a sensitive technique for serotype identification. However, in many cases, the difference between serotypes is detected in only one or two base-pairs, or the sequences are identical, making a definitive serotype identification difficult. To obtain serotype results in these cases, additional PCRs for differentiating particular serotypes/groups are required.
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| 1007. |
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| 1008. |
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| 1009. |
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| 1010. |
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