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A Kurylowicz,
Y Hiromatsu,
B Jurecka-Lubieniecka,
D Kula,
M Kowalska,
M Ichimura,
H Koga,
H Kaku,
E Bar-Andziak, J Nauman,
B Jarzab,
R Ploski,
T Bednarczuk
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ABSTRACT: Recently, a functional polymorphism in the NFKB1 gene promoter (-94ins/del ATTG) has been identified and associated with chronic inflammatory diseases. The aim of this study was to analyze the association of NFKB1 polymorphism with susceptibility to and phenotype of Graves' disease (GD). The initial case-control association study, performed in a Polish-Warsaw cohort (388 GD patients and 688 controls), was followed by the two replication studies performed in Polish-Gliwice and Japanese-Kurume cohorts (198 GD patients and 194 controls, and 424 GD patients and 222 controls, respectively). The frequency of the -94del ATTG (D) allele was increased in GD compared to controls in Warsaw cohort. This finding was replicated in Gliwice cohort. Combining both Polish-Caucasian cohorts showed that the NFKB1 polymorphism was significantly associated with susceptibility to GD with a codominant mode of inheritance (P=0.00005; OR=1.37 (1.18-1.60)). No association with GD was found in Japanese cohort. However, subgroup analysis in Japanese GD patients revealed a correlation between the NFKB1genotype and the development of ophthalmopathy (P=0.009; OR=1.49 (1.10-2.01)), and the age of disease onset (P=0.009; OR=1.45 (1.09-1.91)). Our results suggest that NFKB1 -94ins/del ATTG polymorphism may be associated with susceptibility to and/or phenotype of GD.
Genes and Immunity 11/2007; 8(7):532-8. · 3.87 Impact Factor
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ABSTRACT: Susceptibility to Graves' disease (GD) is determined by multiple environmental and genetic factors, which are not fully understood. Because of the autoimmune etiology of the disease, recent reports describing the development of GD during long-term immunosuppressive treatment seem quite surprising. We report a second case of GD in a 17-yr old patient, treated with cyclosporin A and prednisone, after liver transplantation. The development of GD despite adequate immunosuppressive therapy may suggest that this patient had a genetic predisposition to autoimmunity and severe immunoregulatory defects. We analyzed the HLA-DRB1 alleles and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphism (A/G) at position 49 in exon 1. The patient had the HLA-DRB1*03 allele which is known to confer susceptibility to GD. Further studies are necessary to identify genes that may predispose patients specifically to GD during immunosuppressive therapies.
Journal of endocrinological investigation 04/2003; 26(3):257-60. · 1.57 Impact Factor
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ABSTRACT: The purpose of this study was to compare thyroid hormone metabolism between non-cancerous tumor-surrounding human kidney tissues and renal clear cell carcinomas (RCCC). The material consisted of samples taken from 10 RCCC patients of both sexes and three grades of differentiation, G1 to G3. We showed that, similar to rat tissue, type I 5' monodeiodinase (5'DI) expression is heterogeneous within the human kidney. We also found a poor correlation between 5'DI activity and mRNA level in non-cancerous tumor-surrounding tissue suggesting significant post-transcriptional regulation of 5'DI expression by an unidentified process in the human kidney. In all RCCC tissues both 5'DI activity and mRNA levels were undetectable. This suggests either loss of human 5'DI gene expression during neoplastic transformation or the origination of RCCC from a tubular cell type that does not express 5'DI.
Journal of endocrinological investigation 05/2001; 24(4):253-61. · 1.57 Impact Factor
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ABSTRACT: Human renal clear cell carcinoma (RCCC) accounts for up to 2% of human cancers. To find out if thyroid hormone (T3) and its receptors (TRs) play a role in tumorigenesis of RCCC, the expression of TRs was evaluated on mRNA and protein level. It was found that TRalpha (both alpha1 and alpha2) mRNA amount was significantly decreased in tumors while compared with healthy kidney tissue, and this decrease was deepest in G1 (well differentiated) RCCCs. In contrast, TRalpha1 protein was 1.6x overexpressed in tumors. TRbeta1 mRNA amount was overexpressed in 30% and significantly decreased in 70% of examined tumors. On the protein level, TRbeta1 amount was 1.7x lower in tumors than in healthy controls.
Cancer Letters 08/2000; 155(2):145-52. · 4.24 Impact Factor
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ABSTRACT: Autoantibodies reacting with extracellular matrix proteins have been extensively studied in various autoimmune connective tissue diseases. Because of the possibility that such antibodies may play a role in orbital connective tissue inflammation in thyroid-associated ophthalmopathy (TAO), we studied the humoral immune response against specific extracellular matrix (ECM) proteins, namely: collagen types I, III, IV, V (CI, CIII, CIV, CV), fibronectin (FN), and laminin (LM). Anti-ECM antibodies of immunoglobulin G (IgG), IgA, and IgM classes were determined by enzyme linked immunosorbent assay (ELISA). Overall, sera from 50% of patients with TAO contained antibodies reactive against one or more ECM proteins, compared to 27% with Graves' disease (GD) without evident eye involvement, 28% with Hashimoto's thyroiditis (HT), and 9% of normal subjects. Serum anti-CI, anti-CIII, anti-CV and anti-LM levels were significantly (p<0.05) higher in patients with TAO than in normals. Anti-CI, anti-CV and anti-LM reactivity was antigen-specific in most TAO sera, while anti-CIII antibodies cross-reacted with other antigens. Anti-collagen antibodies were mainly of the IgG class. To determine the structural epitopes of these proteins, we performed immunoblotting studies on cyanogenbromide (CNBr)-derived peptides of CI and CV. While sera from 9 of 10 patients with TAO reacted with CI peptides, the response was polyclonal and uniform in all patients. However, only 2 of 10 TAO sera reacted with CV peptides. In conclusion, our study suggests that a variety of ECM proteins (CI, CV, LM) may be secondary autoantigens that are recognized by antibodies in TAO. While these antibodies appear to react with epitopes expressed on both native and denatured proteins, and may therefore have the potential to bind to ECM in vivo, their pathogenic role in TAO remains unknown.
Thyroid 03/1999; 9(3):289-95. · 4.79 Impact Factor
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ABSTRACT: Although thyroid-associated ophthalmopathy (TAO) is now generally accepted as an autoimmune inflammatory disorder of the extraocular muscles and the orbital connective tissue, its aetiopathogenesis remains poorly understood. Recent data indicate that impaired interactions between T cells and extracellular matrix (ECM) proteins may play an important role in development and maintaining of an inflammatory process. We report here results of the study focusing on interactions between T lymphocytes and collagen-I (Coll-I), collagen-IV (Coll-IV), fibronectin (FN), laminin (LM) in patients with TAO. Using a standard peripheral blood mononuclear cells (PBMC) proliferation assay, we observed a markedly enhanced T cell response to Coll-I in patients with active TAO (mean SI=4.5). The proliferatory response to Coll-I was significantly greater (Wilcoxon test; p < 0.001) than in normal subjects (mean SI=1.88), patients with stable TAO (mean SI=2.05) and patients with thyroid autoimmune diseases (AITD) without ophthalmopathy (mean SI=2.49). PBMC stimulation by Coll-I is likely to be antigen-dependent requiring engagement of the T cell receptor with collagen peptides, rather than mediated via integrins. The percentage of circulating CD29+ (beta1 integrin chain) T cells was not increased in patients with active TAO. Additionally in the assay of costimulation of CD3-mediated proliferation, we found that peripheral blood T cells from patients with TAO and AITD were costimulated only by FN. On the other hand a markedly enhanced costimulation of CD3-mediated proliferative responses by Coll-I, Coll-IV, FN and LM were observed in a retrobulbar T cell line. We conclude that abnormalities in T cell interactions with ECM proteins, especially Coll-I may play a role in the pathogenesis of TAO.
Autoimmunity 02/1998; 27(4):221-30. · 2.47 Impact Factor
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ABSTRACT: In Graves' disease an increased immunological activity against glycoconjugate antigens is observed. Since gangliosides seem to be important for thyroid stimulation we searched for the presence of antiganglioside antibodies in Graves' patients sera by the immunoenzymatic method. Antibodies against some of 12 different gangliosides used in this study were found in 22% of the patients. However, in most cases the titer of antiganglioside antibodies was very low. Only the serum from one patient reacted with FucGM1 ganglioside at the dilution up to 1:1300. Anti-FucGM1 antibodies were present in serum samples of this patient taken before and during the treatment when she was hyper-hypo- and euthyroid. The lack of relation of the anti-FucGM1 antibody titer to the thyroid status of this patient, and the very low titer of antiganglioside antibodies in sera of some other patients, suggest that the presence of these antibodies has no close connection to the thyroid disease.
Autoimmunity 02/1994; 18(2):149-52. · 2.47 Impact Factor
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ABSTRACT: The results of study concerning iodine deficiency among children attending primary schools in Warsaw and Ciechanów voivodships have been presented. The study was a part of a nationwide program on iodine prophylactics and incidence of goiter in Poland. Altogether 675 children, 356 girls and 319 boys of age between 6 and 13 years, were included into the study. Of these, 337 inhibited urban, and 338 rural areas. The presence of goiter was found in 48.6% of the studied population. In 60% of the affected children the degree of thyroid enlargement was small (IB). The incidence of goiter was higher in rural than in urban children and higher in girls than in boys. In above 90% goiter was of the diffuse type. In almost 65% of cases the diagnosis of goiter by palpation was confirmed by ultrasonography. The urinary concentration of iodine was low in 85% of the children studied. This was true for 88% of children with goiter and for 83% of children with normal size of the thyroid. Only 12% of the children studied used iodinated salt in the diet. The use of iodinated salt was more popular among urban children than among the rural ones. Low urinary concentration of iodine was found both in children not consuming and in the majority of those consuming iodinated salt. The individual iodine prophylactics had no effect on the incidence of goiter. The results obtained indicate the presence of iodine deficiency in the studied region suggesting urgent need for informative action explaining the existing situation and necessity of undertaking the widespread and effective prophylactic measures.
Endokrynologia Polska 02/1993; 44(3):287-96. · 1.24 Impact Factor
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ABSTRACT: The mechanism of thyroxine uptake by human adipocyte precursors has been studied in primary culture. Also the rates of transport of this hormone into the isolated cells of adipose tissue were compared for lean and obese subjects. It was demonstrated that thyroxine transport into the human adipocyte precursor cells is an active, energy-dependent process characterized by very low rate (Km = 10 pmol/l, Vmax = 8 fmol FT4/10(6) cells/min.). By comparing the rates of thyroxine transport into the precursor cells of adipocytes isolated from adipose tissue of lean and obese subjects it was possible to demonstrate a clear tendency to the lowered rate of transport of thyroxine to the cells in obesity. The results of this study suggest that the lowered rate of thyroxine transport to preadipocytes and adipocytes observed in obesity may significantly influence the metabolic state of these cells.
Endokrynologia Polska 02/1992; 43(1):13-21. · 1.24 Impact Factor
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Experimental and clinical endocrinology 06/1991; 97(2-3):173-8.
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Experimental and clinical endocrinology 06/1991; 97(2-3):202-5.
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Endokrynologia Polska 02/1989; 40(5):263-9. · 1.24 Impact Factor
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Endokrynologia Polska 02/1988; 39(2):59-66. · 1.24 Impact Factor
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Endokrynologia Polska 02/1988; 39(1):41-7. · 1.24 Impact Factor
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Radiobiologia, radiotherapia 02/1987; 28(5):570-4.
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ABSTRACT: Pure adrenergic beta-action, brought about by long-term adrenaline + regitine application in rats, was able to increase liver T4-5'-deiodinase activity for 8 h (Nauman et al. 1984a). Long-term isoprenaline application without alpha-blocking yielded contrary results. One of the compensatory mechanism to be probably blamed could have been the very high endogenous adrenaline-levels (Porta et al. 1985). Simultaneous treatment with isoprenaline and alpha-methyltyrosinemethylester did not settle the problem since even then deiodinase activity was still drastically decreased. Two more components have been found which could very well be the reason for that "paradox beta-action" in vivo, namely very low glucose and insulin levels, both of which are known to influence deiodinase activity. In vivo--contrary to in vitro--it is seemingly not possible that catecholaminergic beta-action could increase the peripheral production of T3 unless general alpha-blocking took place.
Experimental pathology 02/1987; 31(3):179-83.
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Endokrynologia Polska 02/1986; 37(4):143-52. · 1.24 Impact Factor
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ABSTRACT: Male Sprague-Dawley rats were treated during 20 h with subcutaneously implanted tablets (controlled release systems) containing either adrenaline (A), noradrenaline (NA), isoprenaline (ISO) or just placebos. Levels of the exogenously administered catecholamines (CA) in plasma and liver homogenate were significantly higher than in controls throughout the test time. During NA application endogeneous A and dopamine (DA) plasma values rose considerably, while ISO application enhanced endogenous NA and A levels. Adrenaline application increased NA and DA plasma levels. Several possibilities for this phenomenon are discussed, and it is concluded that previous papers dealing with observations of long term action of CA's should be reevaluated unless the influence of the artificially given CA on the elevation of endogenous CA's has been already taken into consideration.
Experimental pathology 02/1985; 28(3):181-6.
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ABSTRACT: Antibodies that reacted with plasma membranes of human eye muscle but showed no binding to plasma membranes of human skeletal muscle were identified in serum of patients with Graves' ophthalmopathy. Rabbit antithyroglobulin serum at a dilution of 1 X 10(-3) to 20 X 10(-3) had no effect on the binding of these antibodies to eye muscle membrane antigens. There was no correlation between antihuman eye muscle plasma membrane antibodies and antihuman thyroid membrane antibodies or antibodies against thyroglobulin. It is suggested that specific antibodies against eye muscle membranes are present in Graves' ophthalmopathy and that this disease might represent a distinct autoimmune disorder.
British medical journal (Clinical research ed.) 02/1985; 290(6463):191-2.
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ABSTRACT: Especially coated adrenaline tablets (A) or placebo tablets (P) which release linearly the hormone were implanted in male Wistar rats. Six hours later animals were sacrificed and kinetic parameters of T3-125I binding to nuclear receptor, intracellular distribution of endogenous T3 and activities of alfa-GPD and ME were investigated. The association constant values (Ka) of nuclear receptor were increased after pretreatment with 7.5, 15 and 45 mg A tablets and were 1.07, 1.35 and 1.48 X 10(9) M-1 vs 0.85 X 10(8) M-1 value seen after P. The maximal binding capacity (MBC) values decreased after pretreatment with the same doses of A and were 0.044, 0.036 and 0.025 pmol T3/100 micrograms DNA vs. 0.065 pmol T3/100 micrograms DNA in P pretreated. Adrenaline pretreatment significantly increased the amount of endogenous T3 present in liver nuclei while the amount of T3 present in cytosol decreased. Activity of mitochondrial alfa-GPD was increased after 15 and 45 mg of A. Significant rise of activity of cytosol ME was seen only after pretreatment with 45 mg of A.
Hormone and Metabolic Research 11/1984; 16(10):521-4. · 2.19 Impact Factor
