| 1. |
- Mørk, Cato, et al.
(författare)
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Microvascular arteriovenous shunting is a probable pathogenetic mechanism in erythromelalgia
- 2000
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 114:4, s. 643-646
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Tidskriftsartikel (refereegranskat)abstract
- Erythromelalgia is a condition consisting of red, warm, and burning painful extremities. Symptoms are relieved by cold and aggravated by heat. A wide variety of etiologic conditions can cause erythromelalgia, but one common pathogenetic mechanism, microvascular arteriovenous shunting, has been hypothesized. The aim of this study was to test this hypothesis. Quantification of skin microvascular perfusion using laser Doppler perfusion imaging and skin temperature at rest and after central body heating was performed in 14 patients with erythromelalgia and 11 controls. Attacks of erythromelalgia were induced in eight patients after heat provocation. In the plantar region of the foot, the location of numerous anatomical arteriovenous shunts, these patients significantly increased the skin perfusion as compared with asymptomatic patients with erythromelalgia and controls. In the dorsal region with few arteriovenous shunts no significant differences between the groups were demonstrated. The results show a relation between clinical symptoms and increased perfusion in the region of numerous anatomical arteriovenous shunts, and support the hypothesis of increased thermoregulatory arteriovenous shunt flow during attacks in primary erythromelalgia.
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| 2. |
- Allhorn, Maria, et al.
(författare)
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Heme-Scavenging Role of alpha1-Microglobulin in Chronic Ulcers.
- 2003
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 121:3, s. 640-646
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Tidskriftsartikel (refereegranskat)abstract
- Chronic venous ulcers are characterized by chronic inflammation. Heme and iron, originating from blood cell hemolysis as well as extravascular necrosis, have been implicated as important pathogenic factors due to their promotion of oxidative stress. It was recently reported that the plasma and tissue protein alpha1-microglobulin is involved in heme metabolism. The protein binds heme, and a carboxy-terminally processed form, truncated alpha1-microglobulin, also degrades heme. Here, we show the presence of micromolar levels of heme and free iron in chronic leg ulcer fluids. Micromolar amounts of alpha1-microglobulin was also present in the ulcer fluids and bound to added radiolabeled heme. Truncated alpha1-microglobulin was found in the ulcer fluids and exogenously added alpha1-microglobulin was processed into the truncated alpha1-microglobulin form. Histochemical analysis of chronic wound tissue showed the presence of iron deposits, heme/porphyrins in infiltrating cells basement membranes and fibrin cuffs around vessels, and alpha1-microglobulin ubiquitously distributed but especially abundant in basement membranes around vessels and at fibrin cuffs. Our results suggest that alpha1-microglobulin constitutes a previously unknown defense mechanism against high heme and iron levels during skin wound healing. Excessive heme and iron, which are not buffered by alpha1-microglobulin, may underlie the chronic inflammation in chronic ulcers.
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| 3. |
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| 4. |
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| 5. |
- Andersson, Ann-Catrin, et al.
(författare)
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Elevated levels of the human endogenous retrovirus ERV3 in human sebaceous glands
- 1996
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 106:1, s. 125-128
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Tidskriftsartikel (refereegranskat)abstract
- ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. Long terminal repeat-envelope (env) gene spliced mRNAs of 9 and 3.5 kb are widely expressed in human tissues and cells, but gag-pol mRNAs have not been found. Furthermore, the env gp70 gene contains an open reading frame throughout its length. The highest expression of ERV3 mRNA detected so far is in placenta and the lowest in choriocarcinoma cell lines. We have previously shown that the human monoblastic cell line U-937 and some normal and neoplastic tissues also express high levels of ERV3 env message by Northern blot analysis; however, this method does not distinguish between mRNA expression in different cell types in tissues. In this report, we have studied the ERV3 mRNA expression in specific cell types of human skin by in situ hybridization. We found high levels expression of ERV3 env mRNA in human sebaceous glands in normal skin and dermoid cysts of the ovary. In all glands, the expression is maximal in the periphery of the lobule and ceases towards the center in the region of characteristic holocrine secretion. Since it is known that the regulation of sebaceous glands is primarily via steroid hormones, particularly androgens, it is possible that expression of ERV3 is hormone dependent.
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| 6. |
- Busch, Christer, et al.
(författare)
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Expression of Cellular Retinoid-Binding Proteins During Normal and Abnormal Epidermal Differentiation
- 1992
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 99:6, s. 795-802
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Tidskriftsartikel (refereegranskat)abstract
- Retinoids have important roles in growth and differentiation of epidermal cells. We have analyzed the expression of two intracellular retinoid-binding proteins, the cellular retinol-binding protein type I and the cellular retinoic acid - binding protein type I, during normal and abnormal epidermal differentiation. Both proteins were found to be expressed in normal epidermis with increasing expression from basal layer towards superficial layers. In psoriatic lesions, a hyperproliferative condition of the skin, the epidermal expression of cellular retinol-binding protein I was induced, whereas expression of cellular retinoic acid-binding protein I was sharply down-regulated. This and other features of psoriatic lesions indicate that down-regulation of cellular retinoic acid - binding protein I expression might cause aberrant retinoid-regulated gene expression in skin. In basal and squamous cell carcinomas, cellular retinoic acid - binding protein I expression was down-regulated, whereas cellular retinol-binding protein I was expressed. Apart from epidermal cells, a mesenchymal, dendritic cell-type, strongly expressing cellular retinoic acid-binding protein I, was identified in the dermis. In several hyperproliferative conditions of the skin, including psoriasis, and squamous and basal cell carcinomas, this cell type was abundant. These results have implications for the role of retinoids in normal and abnormal epidermal differentiation and suggest that part of the phenotype of psoriasis is due to inappropriate metabolism of retinoic acid in skin.
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| 7. |
- Schmitt-Egenolf, Marcus, et al.
(författare)
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Familial juvenile onset psoriasis is associated with the human leukocyte antigen (HLA) class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303 : a population- and family-based study
- 1996
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Ingår i: Journal of Investigative Dermatology. - : Nature Publishing Group. - 0022-202X .- 1523-1747. ; 106:4, s. 711-714
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Tidskriftsartikel (refereegranskat)abstract
- To further evaluate the nature of the HLA association with psoriasis, HLA haplotypes of 60 patients with type 1 (early onset, positive family history) and 30 patients with type II (late onset, no family history) psoriasis were investigated by polymerase chain reaction sequence-specific oligonucleotide hybridization (HLA class II) and serology (HLA class I). Ethnically matched blood donors (146) served as controls. In type I, but not type II psoriasis, the Caucasian HLA extended haplotype (EH) Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303 named according to the B allele EH-57.1 was highly significantly overrepresented (p cor= 0.00021). This particular EH was present in 35% of type I psoriatics but only 2% of controls. EH-57.1+ individuals therefore carry a 26 times higher risk of developing type I psoriasis than individuals who are EH-57.1-negative Further analysis of individual HLA alleles revealed that within EH-57.1, HLA class I antigens (Cw6-B57) were associated to a much higher extent with type I psoriasis than the HLA class II alleles (DRB1*0701-DQA1*0201-DQB1* 0303). Pedigree analysis of three multiply affected families over three generations revealed a cosegregation of disease with EH-57.1. These results strongly suggest that a gene for familial psoriasis is associated with the class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303.
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| 8. |
- Schmitt-Egenolf, Marcus, et al.
(författare)
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Oligonucleotide typing reveals association of type I psoriasis with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype
- 1993
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Ingår i: Journal of Investigative Dermatology. - : Nature Publishing Group. - 0022-202X .- 1523-1747. ; 100:6, s. 749-752
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Tidskriftsartikel (refereegranskat)abstract
- Although the pathogenesis of psoriasis is still a matter of debate, there are several lines of evidence supporting the concept of this disease being immunologically mediated with T cells playing a crucial role. Because a considerable portion of the cellular infiltrate in psoriasis consists of activated T-helper cells, expression of HLA class II antigens might be of particular importance for the understanding of its pathogenesis. Therefore, we investigated the HLA type of patients with type I (early onset, positive family history) and type II (late onset, no family history) psoriasis by means of serology (n = 89) and genotyping using sequence-specific oligonucleotide probes (n = 64). Serologic analysis of class I documented the association of type I psoriasis with HLA-Cw6, -B13, and -B57, whereas type II psoriasis showed a weaker correlation with HLA-Cw2 and -B27. Genotyping using SSO for class II detected the elevation of the HLA-DRB1*0701/2 allele frequency from 13% in normal population to 36% in type I, but only to 15% in type II psoriatics. Moreover, positive correlations with type I psoriasis were detected for HLA-DQA1*0201 and HLA-DQB1*0303. The HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype was found exclusively in type I psoriasis. This is the first report documenting the association of distinct HLA class II alleles with type I psoriasis as detected on the DNA level, an approach both more specific and more sensitive when compared to serology.
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| 9. |
- Schmitt-Egenolf, Marcus, et al.
(författare)
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Type I and type II psoriasis show a similar usage of T-cell receptor variable regions
- 1991
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Ingår i: Journal of Investigative Dermatology. - : Nature Publishing Group. - 0022-202X .- 1523-1747. ; 97:6, s. 1053-1056
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Tidskriftsartikel (refereegranskat)abstract
- In nonpustular psoriasis, principally two forms can be distinguished [Christophers E. Henseler T: Patient subgroups and the inflammatory pattern in psoriasis. Acta Dermatol Venereol 69(suppl 151):88-92, 1989): Type I frequently shows positive family history, linkage disequilibrium for human leucocyte antigens (HLAs) Cw6, B13 and Bw57 as well as an early onset. Type II manifests itself around the 5th decade, it is more frequently than normal associated with Cw2 and B27. In the light of this association with HLAs an autoimmune pathogenesis has been discussed. In order to investigate the pathogenetic function of T cells we obtained biopsies from patients with type I (n = 10) and type II (n = 10) psoriasis. Three-step peroxidase staining was performed using a panel of monoclonal antibodies directed against five variable (V) regions of the beta chain (V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12) and one of the alpha chain (V alpha 2) of the T cell receptor (TCR). Positive or negative selection of a particular TCR V region could not be detected in the demonstrable repertoire. Furthermore, the usage of the V regions under investigation revealed a similar pattern in the two forms of psoriasis.
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| 10. |
- Vahlquist, Anders, et al.
(författare)
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Increased concentrations of 3,4-didehydroretinol and retinoic acid-binding protein (CRABPII) in human squamous cell carcinoma and keratoacanthoma but not in basal cell carcinoma of the skin
- 1996
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 106:5, s. 1070-1074
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Tidskriftsartikel (refereegranskat)abstract
- Retinoids are biologic response modifiers that are present in normal skin and may possibly be perturbed in carcinogenesis. To examine this possibility in human skin, we analyzed vitamin A and cytosolic retinoid binding proteins (cellular retinol binding protein and cellular retinoic acid binding protein [CRABP]) in a total of 38 non-melanoma skin tumors and 25 healthy skin samples using high performance liquid chromatography, radioligand electrophoresis, and reverse transcriptase-polymerase chain reaction. The mean +/- SEM retinol concentration was normal in basal cell carcinoma (0.60 +/- 0.10 microM) and seborrheic keratosis (0.47 +/- 0.07 microM), but increased in keratoacanthoma (1.60 +/- 0.41 microM) and squamous cell carcinoma (1.17 +/- 0.28 microM) (p < 0.05 for both). Also, the concentrations of 3,4-didehydroretinol, a major vitamin A metabolite produced in human skin, were markedly elevated (6-7 times normal) in keratoacanthoma and squamous cell cancer. All types of tumors showed moderately increased levels of cellular retinol binding protein. In addition, keratoacanthoma and squamous cell cancer showed markedly increased levels (6-7 times normal) of CRABPII protein. Transcriptional activity of the CRABPII gene was demonstrated in both normal and neoplastic epidermis, but clear CRABPI mRNA expression was found only in basal cell carcinoma. The data indicate that characteristic perturbations of the vitamin A and retinoid binding protein levels occur in squamous cell-derived skin tumors, but whether these reflect intrinsic errors in retinoid metabolism or are secondary to abnormal cellular differentiation is unknown.
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