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Biomedical subjects

I Sterzl

Publications and source records attributed to I Sterzl.

At least 19 recordsLinked to original sources
PubMed2000

Immunomodulatory 7-hydroxylated metabolites of dehydroepiandrosterone are present in human semen.

Seminal fluid represents a milieu enabling spermatozoa to break the ovum membrane and suppress its immune response and, at the same time, to protect male germ cells against infection. Among constituents of the seminal fluid, various steroids, including dehydroepiandrosterone (DHEA) and its sulphate, were detected. With respect to immunomodulatory and antioxidative properties of the latter steroid and its 7-hydroxylated metabolites, believed to be at least in some instances the locally active species, their presence in seminal fluid is of particular interest. Here for the first time unconjugated 3beta,7alpha-dihydroxy-5-androsten-17-one (7alpha-OH-DHEA) and its 7beta-hydroxyisomer have been detected and quantified in semen. Eight semen samples were extracted with diethyl ether and following evaporation and solvent partition both isomers were detected by gas chromatography-mass fragmentometry using the ions m/z 358 and 343 for quantification. Another portion was separated by HPLC and in the fractions corresponding to 7-OH-DHEA isomers the steroids were measured by recently developed specific radioimmunoassays (RIA). Mean concentrations of 7-OH-DHEA as measured by RIA amounted 5.75+/-1.29 and 5.39+/-0.75 nmol/l (mean+/-SEM) for 7alpha- and 7beta-OH-DHEA, respectively.

Adjuvants, Immunologic↗
PubMed2000

Occurrence of IgA and IgG autoantibodies to calreticulin in coeliac disease and various autoimmune diseases.

Calreticulin (CRT), a high-affintiy calcium binding protein and chaperone, was recently identified as one of the targets of autoantibodies in coeliac disease. We evaluated the level of IgA and IgG antibodies to CRT in sera from patients with coeliac disease and various autoimmune diseases. The level of antibodies to gliadin (shown previously to cross-react with CTR), isolated enterocytes and tissue transglutaminase were determined for comparison. The mean level of IgA antibodies to CRT was significantly higher (P< 0.001) in sera from coeliac patients with active disease (139.9+/-11.2 AU/+/-SE) than in healthy controls (20.9+/-1.7 AU). In sera of patients with systemic lupus erythematosus (SLE), insulin dependent diabetes mellitus (IDDM), multiple sclerosis (MS) and autoimmune thyroiditis (AT) or inflammatory bowel disease (IBD) the mean level (25.8+/-3.7 to 38.1+/-5.6 AU) did not exceed the cut-off value. A low level of these antibodies, however, was detected in some sera of patients with MS and IBD. The level of IgG anti-CRT antibodies was increased in coeliac patients (mean 125.4+/-8.0 AU, P< 0.001) when compared to that in healthy controls (33.9+/-2.3 AU). The IgG anti-CRT antibodies were also detected in about 30% of SLE patients sera (54.1+/-3.6 AU, P< 0.001), but the mean level reached only half that detected in coeliac patients.

Adolescent↗
PubMed2000

7-Hydroxydehydroepiandrosterone--a natural antiglucocorticoid and a candidate for steroid replacement therapy?

7-Hydroxylated metabolites of dehydroepiandrosterone (DHEA) are believed to be responsible for at least some immunomodulatory and antiglucocorticoid effects of DHEA and hence are considered candidates for hormone replacement therapy. Our experiments in vitro brought the evidence that 3beta, 7beta-dihydroxy-5-androsten-3-one (7beta-OH-DHEA), but not DHEA and its 7alpha-hydroxyisomer, could counteract the immunosuppressive effect of dexamethasone on the formation of plaques in culture of murine spleen lymphocytes. In another experiment, DHEA and after a 3-weeks pause 3beta-hydroxy-5-androstene-7,17-dione (7-oxo-DHEA) were applied transdermally to 6 male volunteers on 5 consecutive days. Blood levels of DHEA, its 7-hydroxylated metabolites, and in the first case also dehydroepiandrosterone sulphate (DHEAS), were measured before, during and one day after the end of treatment. Application of DHEA increased significantly not only DHEA and DHEAS, but also its both 7-hydroxyisomers. Application of 7-oxo-DHEA also led to a significant increase of both 7-hydroxyisomers of DHEA, with 7beta-OH-DHEA being the preferred metabolite the concentration of which was increased more than three times.

Administration, Cutaneous↗
PubMed1999

7Beta-OH-DHEA counteracts dexamethasone induced suppression of primary immune response in murine spleenocytes.

The effect of dexamethasone and of three potential antiglucocorticoids, namely dehydroepiandrosterone (DHEA) and its 7alpha-and 7beta-hydroxylated metabolites, on primary immune response has been studied by measuring the number of plaque forming cells (NPFC) and their viability in a cell culture of murine spleenocytes. As expected, dexamethasone suppressed considerably the NPFC as well as their viability. Surprisingly, DHEA as well as its 7alpha-hydroxylated metabolite decreased significantly the NPFC, while the effect of 7beta-hydroxy-DHEA was different: at low doses it decreased the NPFC, but this effect was less pronounced at higher concentrations. In addition, 7beta-hydroxy-DHEA was able to counteract the effect of dexamethasone on the NPFC. None of the natural steroids affected the cell viability.

Animals↗
PubMed1999

[Reactions to metals in patients with chronic fatigue and autoimmune endocrinopathy].

Our study was designed to assess the effect of heavy metals on the severity of fatigue in autoimmune thyroid disease associated with autoantibodies against other endocrine organs. We compared our data with those obtained from other groups of patients. A total of five groups of patients were examined by their medical history, dental examination, and using a modified test of blast transformation of metals (Melisa): a) 10 fatigues female patients with autoimmune thyroidism and polyglandular activation of autoimmunity, b) 12 fatigued patients with autoimmune thyroidism, c) 28 fatigued patients free of endocrinopathy, d) 22 professionals without evidence of autoimmunity, e) 13 controls, a population sample, the individuals did not complain of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. Fatigue regardless of the underlying disease is primarily associated with hypersensitivity to inorganic and organic mercury, nickel, and gold. The groups differed in their hypersensitivity to other metals. In the control group, hypersensitivity--mostly to cadmium and lead--was found in four of the examined individuals only. Statistical analysis of data obtained from professionals and controls revealed a higher incidence of positivity to organic and inorganic mercury and nickel in professionals.

Adult↗
PubMed1998

Effect of protein kinase inhibitors on primary antibody induction in tissue cultures.

The effects of protein-kinase-inhibitors (PKIs) on protein kinase C (PKCs) i.e., staurosporin, calphostin C, H-7, H-8, H-9, on phosphatidyl inositol 3-proteinkinase (PI3-K) i.e., wortmannin, and on protein tyrosine kinase (PTKs) i.e., genistein, herbimycin A, sanguinarin, lavendustin A and B were tested on the induction phase of the primary Ab-response in vitro. The inhibitory action of PKIs was the highest with herbimycin A, sanguinarin, H-9 and wortmannin. Although wortmannin inhibits the function of T-lymphocytes (Taub et al., 1997, Shi et al., 1997), we believe that this communication is the first report of PKIs immunosuppressive action on the inductive steps of Ab-formation.

Animals↗
PubMed1998

[The fatigue syndrome in autoimmune thyroiditis with polyglandular activation of autoimmunity].

The authors compared in a group of 118 patients with autoimmune thyroiditis and a positive antibody titre against ovaries the grade of fatigue with the presence of organ specific and non-specific autoantibodies in the peripheral blood stream, antibodies against EBV and CMV, immunoglobulin concentrations, biochemical parameters of the lipid metabolism, glucose tolerance, ion balance and melatonin and serotonin levels. Patients with autoimmune thyroiditis were differentiated according to the degree of fatigue into three groups: 38 with fatigue typical for CFS, 30 with occasional fatigue and 50 without the feeling of fatigue. Fatigue of the CSF type was characterized by a significantly higher incidence of autoantibodies against the adrenals and a higher cholesterol level. Increased fatigue of the patients was associated with a lower melatonin level, a higher serotonin level and a lower M/S ratio as compared with patients without fatigue. In other indicators no differences were found. Fatigue in CFS could be associated, similarly as in autoimmune endocrinopathies, with impaired immunoendocrine regulation. In autoimmune thyroiditis, regardless of the concomitant presence of fatigue, in addition to antibodies against thyroid peroxidase most frequently antibodies against the ovaries were detected.

Adult↗
PubMed1997

[Thyroid, ovarian and adrenal antibodies in female patients with autoimmune thyroiditis].

BACKGROUND: In patients with autoimmune thyroiditis confirmed by clinical and laboratory tests frequently complaints associated with ovarian disorders are encountered. In order to verify the polyclonal activation of the autoimmune response of patients with autoimmune thyroid disease the authors investigated the presence of autoantibodies against the thyroid and adrenals. METHODS AND RESULTS: 696 patients were selected (mean age 47.9 years) with autoimmune thyroiditis from a group of 1939 patients examined for the presence of antibodies against thyroid peroxidase (TPO). In these patients also the presence of antibodies against ovaries was assessed (in 183 women, i.e. 26.3%), the adrenals (zona glomerulosa in 136 women, i.e. 19.5%, zona fasciculata in 10 women, i.e. 1.4%, zona reticularis in 114 women, i.e. 16.4%) and the adrenal medulla in 46 women, i.e. 6.6%. The basic group was divided into two sub-groups depending on the presence of ovarian antibodies. In the group of 183 women with positive antibodies against the ovaries and TPO positivity against the zona glomerulosa was found in 93 women, i.e. 50.8%, the zona fasciculata in 7 women, i.e. 3.8%, the zona reticularis in 70 women, i.e. 38.3%, the adrenal medulla in 37% i.e. 20.2%. In the second group of 513 patients with positive TPO and negative antiovarian antibodies against the zona glomerulosa were found in 43 women, i.e. 8.4%, zona fasciculata in 3 women, i.e. 0.6%, zona reticularis in 44 women, i.e. 8.6% and against the adrenal medulla in 9 women, i.e. 1.8%. CONCLUSIONS: These results confirmed that in organ specific autoimmune thyroid disease also other autoantibodies against endocrine organs may be present, i.e. against the ovaries and adrenals. The relative frequency of a common finding of autoantibodies against organs which comprise steroid producing cells can be explained by the fact that for the ovaries and the adrenals a common antigen of steroid producing cells is typical.

Adrenal Glands↗
PubMed1997

The genetic basis of primary, predominantly specific immunodeficiencies.

The presented review lists primary immunodeficiencies which essentially involve a mutation in genes coding for functionally important molecules, membrane antigens (e.g., MHC), chains of lymphokine receptors, protein kinases of the signal cascade, transcription factors, and some important regulators of cellular metabolism. Mutations are expressed as early as during embryogenesis (lymphopoiesis-I) as well as during induction of the immune response by antigen ligand binding to cell receptors, TCR, BCR (immunopoiesis-II). Immunodeficiencies are classified by the stage of development (I) or immune response induction (II) in which they occur most markedly, even in clinical terms. It has been pointed out that the same autoactivation stimuli and mechanisms, allowing differentiation-maturation of cells during embryogenesis (action of stem cell factor (SFC), IL-3, IL-7, and activation cascade), serve even later as a functional prerequisite for an adaptive immune response to antigen. As a result, this attempt to classify primary immunodeficiencies by differentiation periods (when they become evident most markedly in terms of their function) has an inherent logical limitation. Some early mutations turn immediately lethal, some express themselves by blocking embryonic lymphopoiesis while other mutations do not become demonstrable until after cell stimulation by antigens. This explains why the developmental differentiation scheme is bound to turn, in the future, into an immunodeficiency classification by localization of gene mutations and their incidence in time, e.g., increased mutation incidence during proliferation following cell stimulation by antigen stimuli.

Animals↗
PubMed1996

[Endocrinopathy in the differential diagnosis of chronic fatigue syndrome].

Fatigue is a frequent and sometimes dominant symptom of some endocrinopathies. It may be associated with other symptoms which are included among the criteria of the chronic fatigue syndrome. These units are not always quite distinct and frequently endocrine diseases and chronic fatigue syndrome (CFS) overlap. From this ensue differential diagnostic problems and ideas on possible causal relations. The authors concentrate in articular on autoimmune endocrinopathies and the polyglandular autoimmune syndrome (APS) with emphasis on the necessity of an accurate endocrinological diagnosis, where is some patients with suspected CFS a defined endocrinopathy was revealed. Attention will be also paid to recent views on the possible participation of disorders of the hypothalamus-pituitary-adrenal axis in the etiopathogenesis of CFS where endocrine and immune regulation overlap and condition each other.

Autoimmune Diseases↗
PubMed1996

[Extra-thyroid autoantibodies in autoimmune thyroiditis].

Organ specific autoimmune diseases do not occur isolated. In the authors group of 4509 patients with confirmed autoimmune thyroiditis the authors investigated the frequency of extrathyroid organ specific and non-specific autoantibodies. The objective was to draw attention to other autoimmune diseases which may not yet be clinically manifest. The mutual positivity of antibodies against thyroid peroxidase (TPO) and antibodies against the adrenals was: in the zona glomerulosa 21.1%, in the zona fasciculata 3.0%, in the zona reticularis 19.5%, in the adrenal medulla 9.0%. The mutual positivity of antibodies against TPO and ovaries was 28.5%, testes 12.5%, parathyroid 10.2%, islets of Langerhans 8.2%, hair follicles 45.0%, cell nuclei 26.1%, mitochondria 3.1%, smooth muscles 2.4%, striated muscle 0.2%, and gastroparietal cells of the stomach 12.3%. These results draw attention to the importance of polyclonal activation of the autoimmune process in endocrinopathies and the necessity to assess extrathyroid autoantibodies in autoimmune thyroiditis.

Autoantibodies↗
PubMed1996

[Thyroglobulin and microsome autoantibodies and their clinical significance in adult type I diabetics].

In 34 patients with type 1 diabetes manifested in postadolescent age (mean age at time of diagnosis 25 years, 18 women and 16 men) after the establishment of the diagnosis perspectively the presence of antibodies against thyroglobulin and the microsomal fraction and their relation to affection of the thyroid gland was investigated. During an investigation of 20% of the patients the authors provided repeatedly evidence of the presence of both antibodies, in 23% repeatedly only against microsomes. In 21% some antibodies were detected only once. In the course of the investigation in 65% of the patients thyroid antibodies were found. The clinically most serious affection of the thyroid gland (from the sonographic an functional aspect) was found in groups 1 an 2, while in groups 3 and 4 in the majority of patients the thyroid gland was not affected. A different pathogenesis of the disease in the above groups is suggested in the areas of DR and DQ during HLA typing, the behaviour of other antibodies and differences in dermatoglyphic examinations. Moreover there is a high ratio of women in the first two groups (61%) and conversely of men in groups 3 and 4. In the discussion attention is drawn to the different course of diabetes in patients with thyroid autoimmunity.

Adult↗
PubMed1995

An increase in the blood thyroxine level after methylene blue in rats: the interaction with carbimazole.

Anterior pituitary (AP) weight, thyroid weight, the serum thyroxine (T4) level, the thyroid T4 and cAMP content, the serum TSH level and the TSH and cAMP content of the AP and thyroid were measured in control rats, rats given methylene blue (MB) in their food, rats given the thyroid-blocking agent carbimazole (CARB) and rats fed both MB and CARB. AP weight fell slightly after MB in both intact and CARB--fed animals. Thyroid weight rose strongly after CARB, MB partly inhibited this increase. The cAMP content of the thyroid rose after CARB; this increase was likewise blocked by MB, MB alone had no effect on the thyroid cAMP concentration. Previous observations showing that MB produced an increase in the blood T, were confirmed. The T4 level fell, of course, after CARB and the decrease was partly inhibited by MB. The T4 content of the thyroid also fell after CARB, this decrease was completely reversed by MB. The blood TSH level fell slightly after MB and rose 7--fold after a CARB blockade of the thyroid; this increase was completely inhibited by MB. The TSH content of the AP fell after MB in both intact and CARB--fed animals. The cAMP content of the AP fell after MB, it was unaffected by CARB. Thus, in some way, MB raised the blood thyroxine level in both intact and CARB--fed animals and strongly depressed the TSH content in the serum and the AP given alone or with CARB. The mechanism of this action should be a result of MB interaction in thyroid hormone metabolism and their binding activity on specific regulatory elements. It is a problem for future experiments.

Administration, Oral↗
PubMed1994

[Significance of determination of antibodies to TSH receptors (using TRAK) in the diagnosis and monitoring of therapy in endocrine orbital disease].

The elevated antibody level against receptors for TSH assessed by the commercial set TRAK (Henning Berlin) supports the diagnosis of endocrine orbitopathy (EO) which is important in more complicated cases with unilateral EO or EO in euthyroid or hypothyroid patients. During treatment of EO by elimination of the thyroid with radioiodine 131I (with or without previous thyroidectomy) a decline of originally high TRAK values to normal suggests successful elimination. Persistence of high TRAK values is associated with a poorer therapeutic effect of elimination and reasons for this should be sought. In four of 26 such patients the authors found radioiodine accumulation in the residual thyroid tissue, in 8 patients they found a non-accumulating residue by means of sonography. In 14 patients within two years after administration of the radioiodine elimination dose a residue of the thyroid gland was not found by scintigraphy nor by sonography. Improvement of the therapeutic effect occurred in one of these subjects with a drop of the TRAK value after the 30th month following elimination, in another female patient after a high diagnostic radioiodine dose. Improvement of the protrusion after radioiodine treatment with or without previous incomplete thyroidectomy and was recorded in 33 subjects where a drop of the originally high level of TRAK antibodies occurred was significantly greater than in subjects where the TRAK values did not decline.

Autoantibodies↗
PubMed1990

Morphological changes in the human thyroid gland cultivated in continual flow system.

In the present pilot study, the human thyroid gland tissue was cultivated under continuous culture conditions in the culture chambers of the ACUSYST-S system to determine morphological changes as well as the secretion of thyreoglobulin (Tgl) and thyroid hormones. After 24 hours of cultivation the follicular structure of the tissue was preserved in peripheral parts only, and there were regressive changes in the epithelium center. After 72 hours the regressive changes appeared in isolated follicles only; the size of the follicles increased, the height of the follicular epithelium decreased and there were macrophages present with phagocytized cell debris. After 144 hours disintegration of epithelia took place in the centre, while at the periphery the original follicles survived and very tiny new follicles formed, consisting of only 6 to 8 cells each and surrounding in section the homogeneous colloid. The parenchyma picture suggests a possibility of functional regeneration as an expression of adaptation to the conditions newly arisen during cultivation in a culture chamber. There was no significant influencing of the thyroid hormone secretion during cultivation. On the other hand, the Tgl secretion decreased throughout cultivation.

Culture Media↗