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- Lilja, I, et al.
(författare)
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Presence of group IIa secretory phospholipase A(2) in mast cells and macrophages in normal human ileal submucosa and in Crohn's disease
- 2000
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 38:12, s. 1231-1236
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Tidskriftsartikel (refereegranskat)abstract
- Secretory group IIa phospholipase A(2) (PLA(2)-II) is an important regulator of proinflammatory lipid mediator production and may play a role in ileal inflammation in Crohn's disease. The enzyme has previously only been detected in epithelial Paneth cells. However, one characteristic feature of Crohn's disease is the transmural inflammation. Full thickness ileal sections from nine patients with Crohn's disease, and histologically normal sections from patients with colonic cancer (n=7) and chronic severe constipation (n=1) as controls, were used in this study. PLA(2)-II-positive cells were detected by immunofluorescence and in situ hybridization. Metachromatic staining and esterase staining were used to identify mast cells and macrophages, respectively. It was shown that mast cells and macrophages in the ileal submucosa in both patients and controls showed positive PLA(2)-II staining. The number of PLA(2)-II-labeled cells that did not react with metachromasia, e.g. macrophages, was significantly greater in inflamed Crohn's disease compared to controls. This is, to our knowledge, the first study that has described the presence in healthy, while presence and upregulation of PLA(2)-II-positive cells in inflamed human ileal submucosa. Our findings suggest a proinflammatory potential for secretory PLA(2)-II in submucosa, while proinflammatory stimulation of mast cells and macrophages in vitro has shown that the enzyme is responsible for delayed prostaglandin formation.
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| 3. |
- Lindvall, O, et al.
(författare)
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Cell therapy and transplantation in Parkinson's disease
- 2001
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : De Gruyter. - 1434-6621 .- 1437-4331. ; 39:4, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted human fetal dopamine neurons can reinnervate the striatum in patients with Parkinson's disease (PD). Recent findings using positron emission tomography indicate that the grafts are functionally integrated and restore dopamine release in the patient's striatum. The grafts can exhibit long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. About two-thirds of grafted patients have shown clinically useful, partial recovery of motor function. The major obstacle for the further development of this cell replacement strategy is that large amounts of human fetal mesencephalic tissue are needed for therapeutic effects. Stem cells hold promise as a virtually unlimited source of self-renewing progenitors for transplantation. The possibility to generate dopamine neurons from such cells is now being explored using different approaches. However, so far the generated neurons have survived poorly after transplantation in animals.
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| 4. |
- Olofsson, A., et al.
(författare)
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Amyloid : Morphology and Toxicity
- 2002
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 40:12, s. 1266-1270
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Tidskriftsartikel (refereegranskat)abstract
- We have expressed transthyretin (TTR) mutants which have significantly destabilised tetramers that aggregate into amyloid fibrils via a series of intermediates. We used atomic force microscopy to follow the morphology of aggregates during fibril formation. Initially, amorphous aggregates are formed that subsequently mature into fibrillar structures. This observation is interpreted as an optimisation of beta-strand registers. The rate of aggregation and maturation is highly temperature-dependent suggesting that entropic forces significantly contribute to stability. In addition, we identified a correlation between the presence of early formed aggregates of TTR and cytotoxicity. The toxic response was mediated via an apoptotic mechanism. The fact that early formed amorphous aggregates, but not more mature fibrils, exert a toxic response suggests that the rate of fibril formation may be a critical parameter. We propose that a slow rate of aggregation facilitates an increased concentration of a toxic intermediate.
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| 5. |
- Pavlou, AK, et al.
(författare)
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Sniffing out the truth: Clinical diagnosis using the electronic nose
- 2000
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 38:2, s. 99-112
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Tidskriftsartikel (refereegranskat)abstract
- Recently the use of smell in clinical diagnosis has been rediscovered due to major advances in odour sensing technology and artificial intelligence (AI). It was well known in the past that a number of infectious or metabolic diseases could liberate specific odours characteristic of the disease stage. Later chromatographic techniques identified an enormous number of volatiles in human clinical specimens that might serve as potential disease markers. "Artificial nose" technology has been employed in several areas of medical diagnosis, including rapid detection of tuberculosis (TB), Helicobacter pylori (HP) and urinary tract infections (UTI). Preliminary results have demonstrated the possibility of identifying and characterising microbial pathogens in clinical specimens. A hybrid intelligent model of four interdependent "tools", odour generation "kits", rapid volatile delivery and recovery systems, consistent low drift sensor performance and a hybrid intelligent system of parallel neural networks (NN) and expert systems, have been applied in gastric, pulmonary and urine diagnosis. Initial clinical tests have shown that it may be possible in the near future to use electronic nose technology not only for the rapid detection of diseases such as peptic ulceration, UTI, and TB but also for the continuous dynamic monitoring of disease stages. Major advances in information and gas sensor technology could enhance the diagnostic power of future bio-electronic noses and facilitate global surveillance models of disease control and management.
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