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Biomedical subjects

J Nauman

Publications and source records attributed to J Nauman.

At least 19 recordsLinked to original sources

Development of Graves' disease in a patient under immunosuppressive therapy after liver transplantation.

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.

Adolescent↗

Iodine-induced hyperthyroidism--an epidemiological survey several years after institution of iodine prophylaxis in Poland.

In 1997, the obligatory model of iodine prophylaxis was introduced in Poland in order to correct the existing status of mild and/or moderate iodine deficiency. In order to monitor possible side-effects of increased iodine supply, studies on iodine-induced hyperthyroidism were initiated by establishing several regional registers of hyperthyroidism. In the present paper, the results of a two-year monitoring (2000-2001) have been summarized. There are no epidemiological data on hyperthyroidism prior to starting the iodine prophylaxis, but the obtained current data are comparable to observations in other countries, made after iodine supplementation. The incidence of iodine-induced hyperthyroidism did not exceed the acceptable level, thus confirming--together with previous observations on the effectiveness of iodine prophylaxis--the adequacy of applied dose of KI (30 microg/kg NaCl), used for salt iodization in Poland.

Adult↗

Type I 5'-iodothyronine deiodinase activity and mRNA are remarkably reduced in renal clear cell carcinoma.

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.

Adenocarcinoma, Clear Cell↗

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.

Adenocarcinoma, Clear Cell↗

Randomized comparison of intranasal and transdermal estradiol.

OBJECTIVE: To compare the efficacy and patient acceptability of intranasal versus transdermal 17 beta-estradiol (E2) delivery systems for postmenopausal symptoms. METHODS: Postmenopausal women were randomly assigned to intranasal 17 beta-E2, 300 microg daily (n = 176) or transdermal 17 beta-E2 (delivering 50 microg/day), two patches per week (n = 185) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12. Patient acceptability was compared by patient choice of administration route and by questionnaire at week 16. RESULTS: Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12. Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups (P <.001). The difference between groups in the Kupperman Index score of -0.5 +/- 0.9 (95% confidence interval -2.3, 1.3) was within the predetermined interval of equivalence. Both therapies were well tolerated with similar adverse event rates, except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 (7.2%) than with the patch (15.5%, P =.02). Sixty-six percent of patients chose to continue the intranasal therapy and 34% the transdermal therapy (P <.001). Satisfaction was greater with intranasal therapy at week 16 (P <.001). CONCLUSION: Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles. Intranasal therapy was the patients' choice for long-term treatment.

Administration, Cutaneous↗

Autoantibodies reactive with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy.

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.

Adolescent↗

T cell interactions with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy.

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.

Adolescent↗

Exercise and exhaustion effects on glycogen synthesis pathways.

Female Sprague-Dawley rats were infused with [1-13C]glucose to measure the effect of endurance training and the effect of various metabolic conditions on pathways of hepatic glycogen synthesis. Four metabolic states [sedentary (S), trained (T), sedentary exhausted (SE), and trained exhausted (TE)] were studied. T and TE rats were trained on a motor-driven treadmill (30 m/min, 15% grade, 1.0 h/day, 5 days/wk) for 8-10 wk. After a 24-h fast, SE and TE rats were run to exhaustion (sedentary average = 78 min, trained average = 155 min) at a training pace and immediately infused with labeled glucose for 2 h. S and T rats were infused after a 24-h fast. After infusion, tissues were removed and glycogen was isolated and hydrolyzed to glucose. The glucose was measured for distribution of 13C by using nuclear magnetic resonance. Glycogen was synthesized predominantly by the indirect pathway for all metabolic states, indicating that infused glucose was first metabolized primarily in the peripheral tissue. The direct-pathway utilization was greater in rested S than in rested T animals (30 vs. 14%); however, for exhausted animals, the trained use of the direct pathway was greater (22 vs. 9%). Both TE and rested T animals utilize the indirect pathway a comparable amount. Sedentary animals, on the other hand, dramatically decreased utilization of the direct pathway, with exhaustive exercise changing from 30 to 9%. The results indicate that endurance training modifies glucose utilization during glycogen synthesis after fasting and exhaustive exercise.

Animals↗

Immunocytochemical staining with monoclonal antibody MoAb47 in the diagnosis of thyroid neoplasms (preliminary communication).

The study is aimed at the estimation of diagnostic value of immunocytochemical (ICH) staining with MoAb47 of cytological material from thyroid nodules obtained by FNAB with emphasis on a precise distinction between benign and malignant follicular tumours. Monoclonal antibody 47 has very strong avidity to thyroperoxidase (TPO) from normal thyrocytes and from benign thyroid lesions. Binding of MoAb47 with TPO from thyroid carcinoma cells is null or very weak. We report the results of ICH staining in 34 cases of "cold" or quickly growing thyroid nodules, most of them solitary. Cytological diagnosis was thyroid carcinoma in 4 cases, microfollicular neoplasm in 7 and different benign lesions in 23. As expected in carcinomas the ICH staining was negative and the presence of cancer was histopathologically proved in 3 already operated on patients. In all follicular tumours staining with MoAb47 was positive and in 5 surgically treated cases postoperative examination identified benign follicular adenoma. Smears from colloidal nodules, cystic and degenerative lesions stained positively with MoAb47. In our opinion staining of cytological material with MoAb47 may improve the diagnosis of thyroid nodules.

Adolescent↗

Determination of the glycogen synthesis pathway by 13C nuclear magnetic resonance analysis.

The level of hepatic glycogen synthesized directly from glucose was measured in rats with [1-13C]glucose. The nuclear magnetic resonance (NMR) spectrum of glucose was used to measure the distribution of the 13C label from C1 to the other carbons. Female Sprague-Dawley rats were surgically implanted with catheters in the left carotid artery and the right jugular vein, followed by a 3-day recovery period and a 24-hour fast to deplete liver glycogen. A 2-hour infusion of the fasted animal with [1-13C]glucose was immediately followed by the removal of blood and liver tissue. The liver was divided into the right, left, caudate, and medial lobes, and then freeze-clamped in liquid nitrogen and stored at -80 degrees C. The 13C NMR glucose spectra were obtained from glycogen that was isolated from each liver lobe and hydrolyzed to glucose with amyloglucosidase. Spectra were obtained at 50.3 MHz in a narrow-bore Gemini 200-MHz NMR spectrometer (Varian, Palo Alto, CA). The distribution of 13C onto glucose carbons was measured from these spectra, and the percent direct pathway was calculated to be 29% +/- 2.5%. Metabolic variation for the synthesis of glycogen within the liver was determined by measuring the direct pathway contribution in each of the four liver lobes. Percent direct pathway values were similar (P > .05) in right (35% +/- 4.9%), left (26% +/- 5.1%), medial (25% +/- 4.9%), and caudate (27% +/- 5.6%) lobes. For some of the animals, the direct pathway was determined by infusion with [6-13C]glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Incidental presence of antibodies against gangliosides in Graves' disease.

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.

Autoantibodies↗

Principles, main goals and methods of the nationwide program: "investigations on iodine deficiency and model of iodine prophylaxis in Poland".

The main reasons to start investigations on IDD in Poland as a nationwide project of the Ministry of Health and Welfare sponsored by the State Committee For Scientific Research and Foundation for Polish Science were: cessation of iodizing of kitchen salt in Poland in 1980, increase of the incidence of goitre in the population and hyperthyrotropinemia in newborns, results of the survey undertaken after Chernobyl disaster indicating an increase of goiter incidence (Nauman et al.) and results of the pilot study (Gutekunst, Gembicki, Kinalska and Rybakowa) indicating an increase of thyroid volume and diminishing of iodine excretion in urine of children in Kraków, Białystok ad Poznań regions. Therefore the main goals of the project were as follows: to evaluate IDD in Poland on the population basis, to map goiter incidence and iodine deficiency in geographic areas, to evaluate a voluntary model of iodine prophylaxis in Poland (20 mg of KI/kg of salt). The investigations were carried out in 19330 children (48.7% of boys and 51.3% for girls) in age group 6-13 years, attending 111 coeducational randomly selected schools from all the country. This number represents 0.35% of children subpopulation in the above age-groups. For practical purposes local coordinating centers at the relevant Departments of Endocrinology and Board of Coordinators were set up. The programme of survey included: filling the questionnaire by children's parents, thyroid palpation and classification according to WHO and ICCIDD criteria, thyroid volume determination by means of ultrasonograph Kontron Sigma 1 L with linear transducer 7.5 MHz, determination of iodine in casual morning urine sample using Sandell and Kalthoff method. Determination of iodine concentration in urine was performed in each case of goiter and in the same number of children without goiter. The results were segregated according to coordinating centers and according to 6 geographical areas of the country. The results were calculated according to the descriptive statistics using Student's test, Chi-square test F-test and Leven's test. The results segregated according to geographic areas were tested by means of analysis of variance using the linear model. The final results of the programme are presented in the next papers.

Adolescent↗

Iodine intake and goiter incidence among schoolchildren living in Warsaw Region (Warsaw and Ciechanów Voivodships--Warsaw coordinating center).

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.

Adolescent↗

Uptake of thyroxine by cultured human adipocyte precursors isolated from lean and obese subjects.

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.

Adipocytes↗

[Study of the effects of some prophylactic measures and radiological contamination in Poland after the Czernobyl accident; Introduction to the research program MZ-XVII].

An aim of the introduction is to remained the scale of radiological contamination in Poland after the accident in the Czernobyl Power Station, the evaluation of findings which led to prophylactic administration of potassium iodide first in part of Poland and later Country-wide. The introduction gives also the history of Research Programme MZ-XVII and its implementation in several regions of Poland. The main aims of the Programme were: 1. Estimation of radioiodine dose accumulated in thyroids of children, youths and adults who lived in different parts of Poland and evaluation whether these doses could lead to the development of thyroid disorders. 2. Evaluation of thyroid function in those exposed to radioiodine in different trimesters of preneonatal life, who were born euthyroid and who were given potassium iodine in first days of life. 3. Evaluation of efficacy of single dose of potassium iodide and estimation of possible intrathyroid and extrathyroid side-effects after prophylactic iodide administration. The foundations of the Programme and Centers involved in its implementation are also specified.

Adolescent↗