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Arthritis Rheum. 2002 Sep;46(9):2465-75.
Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age.

Bardos T, Zhang J, Mikecz K, David CS, Glant TT.

University of Pecs, Pecs, Hungary.

OBJECTIVE: To describe and characterize a novel inflammatory toe disease with severe bone destruction that developed spontaneously in "humanized" (HLA transgenic) mice lacking their own major histocompatibility complex (MHC). METHODS: We studied 5 different HLA transgenic mouse lines (HLA-DR2.Ab(0), DR3.Ab(0), DR4.Ab(0), DQ6.Ab(0), and DQ8.Ab(0)) in similar genetic background for an extended period of time (>14 months). Clinical, radiologic, and histologic abnormalities were monitored, and the MHC-related major immunologic parameters in affected and resistant mice were compared. RESULTS: Animals of 4 transgenic lines (HLA-DR2.Ab(0), DR4.Ab(0), DQ6.Ab(0), and DQ8.Ab(0)) developed severe toe inflammation accompanied by progressive bone resorption, hyperkeratosis, alopecia, loss of nails, and shortening and thickening of the distal phalanges. HLA-DR3.Ab(0) transgenic mice were resistant to inflammation. The disease manifested only at advanced ages (6 months or older) and affected 70-100% of the mice, with a female preponderance. The clinical signs and the radiographic and histopathologic features of the affected toes were not similar to those of any disease previously described in mice but did resemble those described for human psoriatic arthritis (PsA). Mice from the 4 susceptible lines expressed lower levels of the HLA transgene and exhibited significantly fewer CD4+ cells in the peripheral blood and reduced natural killer cell activity compared with mice from the resistant HLA-DR3.Ab(0) line. CONCLUSION: This novel, spontaneously developing PsA-like toe disease in MHC-manipulated mice seems to be related to the absence of endogenous MHC class II. Replacement with HLA transgene expression that is insufficient (or no replacement at all) may result in imbalanced MHC class I and class II functions and lead to development of the disease.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12355495&dopt=Abstract




Acta Diabetol. 2002 Sep;39(3):111-5.
Family history and risk of type 1 diabetes mellitus.

Sipetic S, Vlajinac H, Kocev N, Marinkovic J, Radmanovic S, Denic L.

Institute of Epidemiology, School of Medicine, Belgrade University, Visegradska 26, 11000 Belgrade, Yugoslavia.

The aim of the study was to evaluate association of type 1 diabetes in children and adolescents with positive family history of type 1 diabetes, type 2 diabetes, and thyroid, adrenal, rheumatic, allergic, celiac and some other diseases. A case-control study was conducted in Belgrade. The case group comprised 105 subjects < or = 16 years old who were for the first time hospitalized because of type 1 diabetes during the period 1994-1997. For each case, two controls were chosen among children and adolescents treated for skin diseases. Cases and controls were individually matched by age (+/- one year), sex and place of residence (all were from Belgrade). In the statistical analyses we used chi(2)-test, Fisher's exact test and univariate and multivariate logistic regressions. According to multivariate logistic regression analysis, risk of type 1 diabetes was significantly associated with a positive family history for type 1 diabetes (OR = 4.04; 95% CI, 2.31-7.07), allergic diseases (OR = 3.32; 95% CI, 1.63-6.76), celiac and Crohn's diseases (OR = 11.02; 95% CI, 1.14-106.89) and other diseases (thrombocytopenia, alopecia areata, psoriasis, chronic uveitis and pernicious anemia; OR = 3.63; 95% CI, 1.05-12.48).

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12357294&dopt=Abstract

uab.es

This study determined the frequency of occurrence and the mean number of 'flame follicles' per skin section and assessed their diagnostic significance in cutaneous biopsies of Shar-pei dogs. The number of 'flame follicles' per section was recorded in skin sections from 42 Shar-pei dogs, of which 40 had non-neoplastic skin disease and non-atrophic dermatoses and 2 had healthy skin. Forty-two skin sections from dogs of different breeds served as control specimens, 28 of which were examples of non-neoplastic and non-atrophic dermatoses and 14 were from dogs with healthy skin. Differences among groups were analysed by means of the unpaired Student's t-test. It was concluded that 'flame follicles' were more frequent and found in significantly higher numbers in the Shar-pei group when compared with the control group suggesting that 'flame follicles' in skin sections from Shar-pei dogs do not have the same diagnostic significance as in other breeds.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12358610&dopt=Abstract













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