| 1. |
- Hagleitner, M M, et al.
(författare)
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Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
- 2008
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Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244. ; 45:2, s. 93-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients. OBJECTIVE: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients. METHODS: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors. Results and CONCLUSIONS: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.
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| 2. |
- Hulten, MA, et al.
(författare)
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On the origin of trisomy 21 Down syndrome
- 2008
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Ingår i: Molecular cytogenetics. - : Springer Science and Business Media LLC. - 1755-8166. ; 1, s. 21-
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Rosengren, B., et al.
(författare)
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Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by a Western diet
- 2006
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Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636. ; 26:7, s. 1579-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the distribution of group V secretory phospholipase A2 (sPLA2) in human and mouse lesions and compare its expression by human vascular cells, its activity toward lipoproteins, and the interaction with arterial proteoglycans (proteoglycans) with those of sPLA2-IIA. In addition, we also investigated the effect of a Western diet and lipopolysaccharide challenge on the aortic expression of these enzymes in mouse models. METHODS AND RESULTS: Immunohistochemistry showed sPLA2-V in human and mouse lesions to be associated with smooth muscle cells and also surrounding foam cells in lipid core areas. mRNA of the enzyme was expressed in human lesions and human vascular cells, supporting the immunohistochemistry data. sPLA2-V but not sPLA2-IIA was active on lipoproteins in human serum. The association with proteoglycans enhanced 2- to 3-fold sPLA2-V activity toward low-density lipoproteins but not that of the group IIA enzyme. Experiments in mouse models showed that treatment with a Western diet induced expression of sPLA2-V but not that of sPLA2-IIA in aorta. On the other hand, lipopolysaccharide-induced acute inflammation augmented the expression of sPLA2-IIA but not that of sPLA2-V. CONCLUSIONS: These results indicate that these phospholipases could have different roles in atherosclerosis.
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| 4. |
- Bartels, E. D., et al.
(författare)
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Endothelial lipase is highly expressed in macrophages in advanced human atherosclerotic lesions
- 2007
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Ingår i: Atherosclerosis. - 0021-9150.
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial lipase (EL) is expressed in endothelial cells, and affects plasma lipoprotein metabolism by hydrolyzing phospholipids in HDL. To determine the cellular expression of EL mRNA and protein in human atherosclerotic lesions, we performed in situ hybridization and immunohistochemical studies on sections of carotid endarterectomy specimens from patients with symptomatic cerebrovascular disease. In each of eight patients, EL mRNA and/or protein were seen in areas between the necrotic core and the fibrotic cap where they colocalized with LPL and macrophage-specific CD68. Moreover, there was a positive association between the expression of EL mRNA and CD68 mRNA in plaques from 26 patients. The impact of differentiation from monocytes into macrophages, and subsequently foam cells (by incubation with acetylated LDL) on expression was studied using THP-1 monocytes and primary human monocytes. EL mRNA expression increased markedly when either type of monocytes was differentiated into macrophages. Upon further differentiation into foam cells EL mRNA decreased whereas protein levels remained high compared to monocytes. In conclusion, macrophages in advanced human atherosclerotic lesions display high levels of EL expression, and the level of EL expression varies greatly during transformation of blood monocytes into foam cells.
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| 5. |
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| 6. |
- Boström, Pontus, 1982, et al.
(författare)
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Hypoxia converts human macrophages into triglyceride-loaded foam cells.
- 2006
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 26:8, s. 1871-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Atherosclerotic lesions have regions that are hypoxic. Because the lesion contains macrophages that are loaded with lipid, we investigated whether hypoxia can influence the accumulation of lipids in these cells. METHODS AND RESULTS: Exposure of human macrophages to hypoxia for 24 hours resulted in an increased formation of cytosolic lipid droplets and an increased accumulation of triglycerides. Exposure of the macrophages to oxidized low-density lipoprotein (oxLDL) increased the accumulation of cytosolic lipid droplets because of an increase in cellular cholesterol esters. The accumulation of lipid droplets in oxLDL-treated cells was further increased after hypoxia, caused by an increased level of triglycerides. Expression analyses combined with immunoblot or RT-PCR demonstrated that hypoxia increased the expression of several genes that could promote the accumulation of lipid droplets. Hypoxia increased the mRNA and protein levels of adipocyte differentiation-related protein (ADRP). It is well known that an increased expression of ADRP increases the formation of lipid droplets. Hypoxia decreased the expression of enzymes involved in beta-oxidation (acyl-coenzyme A synthetase and acyl-coenzyme A dehydrogenase) and increased the expression of stearoyl-coenzyme A desaturase, an important enzyme in the fatty acid biosynthesis. Moreover, exposure to hypoxia decreased the rate of beta-oxidation, whereas the accumulation of triglycerides increased. CONCLUSIONS: The results demonstrate that exposure of human macrophages to hypoxia causes an accumulation of triglyceride-containing cytosolic lipid droplets. This indicates that the hypoxia present in atherosclerotic lesions can contribute to the formation of the lipid-loaded macrophages that characterize the lesion and to the accumulation of triglycerides in such lesions.
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| 7. |
- Delaini, G G, et al.
(författare)
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Is an ileal pouch an alternative for patients requiring surgery for Crohn's proctocolitis?
- 2005
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Ingår i: Techniques in coloproctology. - : Springer Science and Business Media LLC. - 1123-6337 .- 1128-045X. ; 9:3, s. 222-4
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Tidskriftsartikel (refereegranskat)abstract
- Most surgeons consider Crohn's colitis to be an absolute contraindication for a continent ileostomy, due to high complication and failure rates. This opinion may, however, be erroneous. The results may appear poor when compared with those after pouch surgery in patients with ulcerative colitis (UC), but the matter may well appear in a different light if the pouch patients are compared with Crohn's colitis patients who have had a proctocolectomy and a conventional ileostomy.We assessed the long-term outcomes in a series of patients with Crohn's colitis who had a proctocolectomy and a continent ileostomy (59 patients) or a conventional ileostomy (57 patients). The median follow-up time was 24 years for the first group and 27 years for the second group.The outcomes in the two groups of patients were largely similar regarding both mortality and morbidity; the rates of recurrent disease and reoperation with loss of small bowel were also similar between groups.The possibility of having a continent ileostomy, thereby avoiding a conventional ileostomy-even if only for a limited number of years--may be an attractive option for young, highly motivated patients.
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| 8. |
- Delaini, G G, et al.
(författare)
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The ileoanal pouch procedure in the long-term perspective: a critical review.
- 2005
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Ingår i: Techniques in coloproctology. - : Springer Science and Business Media LLC. - 1123-6337 .- 1128-045X. ; 9:3, s. 187-92
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Tidskriftsartikel (refereegranskat)abstract
- An ileo-pouch anal anastomosis (IPAA) has become the gold standard procedure for ulcerative colitis and familial adenomatous polyposis. Clinical results on the pelvic pouch procedure have often been encouraging; when confronted with the different surgical options, the majority of patients select IPAA as the best operation. However, even if IPAA is a great innovation, it is by no means the first choice for all patients. For patients old enough to join in a responsible discussion, the pros and cons of the various operations must be carefully described; the choice of surgical procedure must meet the patient's wishes and appear soundly based to the surgeon. The young age of most patients has to be considered and a long follow-up time is required to establish whether and, if so, to what extent the operation may adversely impact the patient's continence, sex life, fertility, and quality of life. The risk of cancer transformation in the residual rectal mucosa in the muscular or columnar cuff is another important factor that may influence the eventual decision. This article critically reviews our experience and the literature.
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