Janusz Nauman

Lymphoid tyrosine phosphatase (PTPN22/LYP) variant and Graves' disease in a Polish population: association and gene dose-dependent correlation with age of onset.

Objective  Susceptibility to Graves’ disease (GD) is to a significant extent determined by genetic factors of which the best known are those associated with the HLA and the CTLA4 locus. Recently, two studies on British Caucasians reported that a single nucleotide polymorphism, 1858 C>T in PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which is a negative regulator of T‐cell activation, increases the risk of GD. The purpose of our study was to investigate whether the PTPN22‘T’ allele is associated with GD and/or its subsets, defined by clinical or genetic parameters, in a Polish population.

Total and Free Triiodothyronine in Human Serum

A reliable method has been developed for the determination of total serum T3, dialyzable fraction (DFT3), and absolute concentration of free T3 (AFT3). Total T3 values (mean +/- SD) were: healthy euthyroid subjects, 0.33 +/- 0.07 mug per 100 ml; hyperthyroid patients, 0.71 +/- 0.1 mug per 100 ml; hypothyroid, 0.10 +/- 0.03 mug per 100 ml. Values (mean +/- SD) for DFT3 in these groups were 0.46 +/- 0.14%, 0.78 +/- 0.17%, and 0.16 +/- 0.08%, respectively. Calculated values for AFT3 were: 1.51 +/- 0.4 mmug per 100 ml, 5.00 +/- 0.6 mmug per 100 ml and 0.24 +/- 0.1 mmug per 100 ml, respectively. Dilution of serum before dialysis lowered estimated DFT3 values. Enrichment of serum with labeled T3 in the range examined did not affect DFT3. However, DFT3 was increased by addition of Merthiolate to serum in concentration 1: 10,000 due to displacement of T3 from thyroxine-binding globulin to albumin. The data suggest that triiodothyronine may play a considerably more important role in normal and pathological physiology, as evidenced by kinetic analysis using these data. A metabolic role for T3 equal to that of T4 is indicated.

Expression of thyroid hormone receptors is disturbed in human renal clear cell carcinoma

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.

T-Cell–Mediated Immunity in Thyroid-Associated Ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) is considered to be an autoimmune inflammatory disorder of the extraocular muscles and the orbital fat/connective tissue. Recent studies analyzing T cells infiltrating retrobulbar tissues generated important insights into the immunopathogenesis of TAO. The present review focuses on advances in our understanding of mechanisms responsible for the autoimmune inflammation in TAO, especially T cell migration to the inflammatory site, T cell activation by autoantigens and costimulatory signals and their cytokine profile. The elucidation of these processes might lead to the development of novel therapeutic strategies directed against autoreactive T cells.

Interleukin‐13 gene polymorphisms in patients with Graves’ disease

objective  In patients with Graves’ disease (GD), an elevation of serum immunoglobulin E (IgE) has been recently reported to be associated with the severity of hyperthyroidism and ophthalmopathy. Interleukin 13 (IL‐13) is a major cytokine involved in IgE synthesis and therefore may be a potential candidate gene contributing to the development of GD or influencing the clinical course of the disease.

Vitamin D Receptor Binding to DNA Is Altered without the Change in Its Expression in Human Renal Clear Cell Cancer

Vitamin D co-regulates cell proliferation, differentiation and apoptosis, the processes that are disturbed in cancer tissues. It acts through the vitamin D nuclear receptor (VDR) that binds to DNA in the regulatory sequences of the target genes. As the kidney is one of the key organs for vitamin D metabolism and action, we analyzed VDR expression and its DNA binding activity in human renal clear cell cancer. 24 tumors, 24 controls that were excised from the opposite pole of the same kidney and 7 controls originating from kidneys without cancer were examined. Independently of tumor grading neither Northern blots nor immunoblotting demonstrated statistically significant differences of the mean VDR mRNA and protein amounts, respectively, in the cancer as compared to both control types. In contrast, the amount of VDR-DNA complexes was lower in 52.2% of the tumors in comparison to their corresponding controls. After normalization against VDR receptor protein amount in 34.8% of the tumors VDR-DNA binding was at least 3–4 times weaker than in the controls. However, the expression of vitamin D-dependent P21 gene on the mRNA level was not decreased in these cancers. It remains to be elucidated if altered VDR function due to its impaired binding to DNA contributes to the process of tumorigenesis, and what potential vitamin D-dependent mechanisms are involved in this process.

Autoantibodies of IgM and IgG Class Against Eye Muscle Antigens in Patients with Graves Ophthalmopathy

The presence of autoantibodies /aab/ reacting with microsomal membrane1 or plasma membrane /AEMA/2 eye muscle antigens have been recently reported in Graves ophthalmophathy /GO/.The significance of humoral mediated immunity in GO was further supported by studies in which correlation between presence and development of ophthalmopathy and titer of anti membrane autoantibodies were established.3,4

Humoral Immunity in Graves Ophthalmopathy

There is a growing evidence that several autoantibodies might be generated in Graves ophthalmopathy (1–7) and result in diversiform clinical picture and course of the disease.