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Linköping, Sweden

Kagedal K.,Prince of Wales Medical Research Institute | Kim W.S.,Prince of Wales Medical Research Institute | Kim W.S.,University of New South Wales | Appelqvist H.,Experimental Pathology | And 9 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2010

The Niemann-Pick type C1 (NPC1) protein mediates the trafficking of cholesterol from lysosomes to other organelles. Mutations in the NPC1 gene lead to the retention of cholesterol and other lipids in the lysosomal compartment, and such defects are the basis of NPC disease. Several parallels exist between NPC disease and Alzheimer's disease (AD), including altered cholesterol homeostasis, changes in the lysosomal system, neurofibrillary tangles, and increased amyloid-beta generation. How the expression of NPC1 in the human brain is affected in AD has not been investigated so far. In the present study, we measured NPC1 mRNA and protein expression in three distinct regions of the human brain, and we revealed that NPC1 expression is upregulated at both mRNA and protein levels in the hippocampus and frontal cortex of AD patients compared to control individuals. In the cerebellum, a brain region that is relatively spared in AD, no difference in NPC1 expression was detected. Similarly, murine NPC1 mRNA levels were increased in the hippocampus of 12-month-old transgenic mice expressing a familial AD form of human amyloid-beta precursor protein (APP) and presenilin-1 (APP/PS1tg) compared to 12-month-old wild type mice, whereas no change in NPC1 was detected in mouse cerebellum. Immunohistochemical analysis of human hippocampus indicated that NPC1 expression was strongest in neurons. However, in vitro studies revealed that NPC1 expression was not induced by transfecting SK-N-SH neurons with human APP or by treating them with oligomeric amyloid-beta peptide. Total cholesterol levels were reduced in hippocampus from AD patients compared to control individuals, and it is therefore possible that the increased expression of NPC1 is linked to perturbed cholesterol homeostasis in AD. © 2010 Elsevier B.V. All rights reserved. Source


Nubile M.,University of Chieti Pescara | Curcio C.,University of Chieti Pescara | Lanzini M.,University of Chieti Pescara | Calienno R.,University of Chieti Pescara | And 4 more authors.
Ophthalmic Research | Year: 2013

Aim: Ultraviolet (UV) B irradiation induces gene expression that leads to skin cancer. Among the transcription factors induced by UVB radiation exposure, the cyclic AMP response element-binding protein (CREB) is significant. Since several factors downstream of CREB signaling are known to be involved in pterygium pathogenesis, we investigated CREB expression in pterygial and human conjunctival tissues to evaluate if a similar expression pattern is present. Moreover, we analyzed the correlation with CREB expression and other known pterygium markers. Methods: Primary pterygium samples and normal bulbar conjunctivas surgically removed were analyzed. Formalin-fixed, paraffin-embedded tissues were stained by immunohistochemistry with anti-CREB, anti-vimentin, anti-ki-67, anti-survivin, anti-MMP7, anti-p63, anti-cyclin D1, or anti-p53 antibodies. Results: 94.4% of pterygium samples were positive for CREB with a significant difference compared to the control group (p = 0.002). The staining was localized in the epithelium and absent in the stroma. An increased expression was found for cyclin D1 (p = 0.019), ki-67 (p = 0.005), vimentin (p = 0.003), survivin (p < 0.001), p63 (p = 0.003), and MMP7 (p = 0.002). CREB expression showed a significant correlation with cyclin D1 (ρ = 0.49; p = 0.035), ki-67 (ρ = 0.61; p = 0.007), and p53 (ρ = 0.57; p = 0.013) in pterygium. Conclusions: These results permit to hypothesize that CREB is involved in pterygium pathogenesis. Since various molecules have been discovered to inhibit CREB, these data could be of interest for pterygium treatment. Copyright © 2013 S. Karger AG, Basel. Source


Bergfors E.,Research and Development Unit in Local Health Care | Lundmark K.,Experimental Pathology | Kronander U.N.,Linkoping University
BMJ Case Reports | Year: 2013

A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations. Source


Baroud M.,Experimental Pathology | Araj G.F.,American University of Beirut | Matar G.M.,Experimental Pathology | Matar G.M.,American University of Beirut
International Arabic Journal of Antimicrobial Agents | Year: 2011

The CTX-M type enzymes have become the most prevalent extended spectrum β-lactamases (ESBLs) worldwide. Among the CTX-M type enzymes, CTX-M-15 is the most widespread and has been reported from all continents. It has been recovered from diferent Enterobacteriaceae and has been isolated from both community and hospital acquired infections. This review primarily highlights the prevalence of CTX-M-15 in addition to other ESBLs in the Middle East. Detection of any type of ESBL is of importance in therapeutic treatment.© Under License of Creative Commons Attribution 3.0 License. Source


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.98K | Year: 1996

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