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I Sterzl

Publications and source records attributed to I Sterzl.

At least 19 recordsLinked to original sources

Immunomodulatory effects of Bacillus firmus on mouse peritoneal cells in vitro.

The effect of nonpathogenic G+ bacterium B. firmus (BF) on stimulation of mouse peritoneal cells in vitro was evaluated by testing nitric-oxide-synthesis induction and cytokine formation. The reactivity was compared of peritoneal cells from two inbred mouse strains, C57B1/6 and BALB/c, which differ in their immunological reactivity. Peritoneal macrophages from C57B1/6 produced more nitric oxide after a 1-d cultivation with inactivated BF than those of BALB/c mice. In both strains, production can be further increased by adding exogenous IFN-gamma to the culture. There were no significant differences between peritoneal cells of these two mouse strains in cytokine production after optimal in vitro stimulation with BF. BF effectively activated peritoneal cells for the production of TNF-alpha, IL-1beta and IL-10, delipidated bacterium (DBF) being more efficient than BF in induction of IL-10 and TNF-alpha. On the other hand, BF had only small effect on IFN-gamma production and no detectable effect on IL-12 production. Macrophage activation by BF/DBF can represent one of the mechanisms responsible for previously described immunomodulatory activity of BF.

Animals↗

Immunological profiles of patients with chronic myeloid leukaemia. I. State before the start of treatment.

In view of the increasing interest in the immunotherapy of CML it seems highly desirable to broaden the present knowledge on the immune reactivity of CML patients. A group of 24 patients and 24 healthy controls were studied for the total of 15 immunological parameters, including the prevalence of antibodies against human herpesviruses and papillomaviruses. To clearly discriminate between changes associated with the disease and those induced by the therapy, all patients were enrolled prior to the start of any anti-leukaemic therapy. Statistically significant differences between patients and controls were found in the levels of IgA, C4 component of complement, CRP and IL-6, the production of Th1 cytokines in stimulated CD3 cells and the E. coli stimulatory index. The analysis of the interrelationship between the results obtained in the individual patients presented some unexpected findings, such as the lack of correlation between the CRP and IL-6 levels. It will be the purpose of a follow-up to determine whether and how the immune status of the patients prior to the treatment correlates with their response to therapy and how the individual immunological profiles change in the course of the disease. These observations will be utilized in the future immunotherapeutic studies to constitute the vaccine- and placebo-treated groups.

Adult↗

[Thyroid autoimmunity in adults with diabetes mellitus type 1. Own experience gained by 11-year monitoring].

The results of study on thyroid autoimmunity and its clinical importance gained during 11-year follow-up of 47 adults with type 1 diabetes mellitus (DM1) are presented. The study proved the preponderance of women among subject affected with thyroid autoimmunity, the autoantibodies against thyroid gland (T-Ab) were significantly more often detected in women compared to men (68% vs. 32%, p < 0.05). Also, serious forms of thyroid autoimmunity manifested with persistence of both T-Ab, faster development of subclinical hypothyroidism (TSH > 4.5 mIU/l in 100% within 4 years after first detection of T-Ab positivity, and within 8 years after DM1 manifestation, respectively), and diffuse hypoechogenic pattern at thyroid gland ultrasonography (USG) were significantly more often observed in women compared to men (45% vs. 12%, p < 0.01). These patients often had small thyroid gland (77% of subjects had volume below 25th percentile of control subjects at the 11th year of follow-up) and presence of thyreopathy in the first degree relatives. No difference between men and women was observed in persistence of thyroid peroxidase autoantibodies (anti-TPO) solely (20% vs. 23%); milder clinical course of thyroid disease was observed in these subjects (the fist detection of TSH > 4.5 mIU/l in the 9th year of follow-up). These patients had varied findings at USG examination with focally/diffuse hypoechogenic/ non-homogenous thyroid gland, and 50% of subjects had thyroid gland volume above 95th percentile in the 11th year of follow-up. Among subjects without thyroid autoimmunity men prevailed (68% vs. 32% women, p < 0.01), and in the 11th year of follow-up the USG finding was often abnormal (thyroid gland volume above 95th percentile of the controls in more than 60% of subjects, trend towards nodulisation). Except for 1 subject, TSH did not exceed 4.5 mIU/l. These results obtained from the Czech population constitute the basis for our recommendation to screen regularly markers of thyroid autoimmunity in patients with DM1. Ultrasonographic examination, that is able to detect sings of thyroid immunopathy in many subjects before first manifestation of T-Ab, is the most sensitive according to both our experience and the published data. For clinical practice, determination of TSH once a year in all DM1 subjects, and of anti-TPO in DM1 women in fertile age is recommended. Ultrasonographic examination should be carried out in case of pathologic results of these tests.

Adult↗

[Autoimmune thyroiditis--selected etiopathogenic mechanisms].

Autoimmune thyroiditis occurs as organ specific autoimmune disease not only as an isolated impairment of thyroid gland, but also linked to many autoimmune endocrinopathies. Genetic predisposition in the area of HLA antigens was followed up by patients with autoimmune thyroiditis diagnosed in this way and it appeared that genetic predisposition in isolated autoimmune thyroiditis is different when compared to the occurrence linked to endocrine polyglandular disease. In selected groups of patients with autoimmune disease also the influence of extraneous factors on the development of the autoimmune process was followed up, namely the influence of heavy metals and the influence of infectious agent--Helicobacter pylori. These factors have a different character of activation of autoimmune thyroiditis too, depending on the character of its manifestation as isolated disorder or in link to autoimmune polyglandular syndrome type II, or in link to the group of polyglandular activation of autoimmunity. To conclude, this study leads to the assumption, that autoimmune thyroiditis is a set of clinical syndromes that depends on the activation of the autoimmune process, rather than a strictly genetically and epigenetically characterized nosological unit.

Adult↗

[Is decreased thyroid echogenity a good indicator of thyroid autoimmune disorder?].

INTRODUCTION: Thyroid gland with mildly decreased or significantly decreased echogenity is indicating possible autoimmune disorder even before first symptoms, i.e. change in laboratory tests measuring the level of thyroid hormones and antibodies to thyroid antigens occur. TARGET: to consider changes in thyroid gland echogenity suspecting thyroid autoimmune disorder and to determine antibodies to thyroid antigens in the respective type of thyroid echogenity (increased, normal, mildly decreased or significantly decreased) to consider the activity of autoimmune thyropathies related to echogenity and to compare these factors. METHODS: Echogenity of the thyroid gland was examinated in randomly selected population (n = 1 055, 360 male, 695 female) in 11 regions of the Czech republic, all presented with urinary iodine concentration > 100 microg/L of urine. The echogenity was determined in 4-level scale as increased (1), normal (0), mildly decreased (-1) and significantly decreased (-2). Texture of thyroid was evaluated in 2-level scale as homogenous or non-homogenous. For the evaluation of the relation between echogenity type (1 to -2) and TgAb, and between the type of echogenity and TOPAb frequence analysis (logarithm-linear modules) was used, i.e. the complete module was compared with the measured values. RESULTS: The selected adults (695 female, 360 male) with urinary iodine concentration > 100 microg/L of urine presented with increased echogenity in 2 females (0.28%) and 1 male (0.28%), normal echogenity in 281 females (40.42%) and 206 males (57.22%), mildly decreased echogenity in 288 females (41.43%) and 128 males (35.56%) and significantly decreased echogenity in 124 females (17.84%) and 25 males (6.95%). The biggest group, both in males and in females, presented with normal and mildly decreased echogenity. Homogenous thyroid gland structure was found in 223 females (32.08%) and 220 males (61.11%). Non-homogenous texture was found in 472 females (67.92 %) and 140 males (38.89%). Frequence analysis both in males and in females was focused on: 1. relation between the echogenity (ECHO) and TgAb: in females with positive TgAb (14.23%), significant relation to ECHO can be seen (p < 0,0001), in contradiction to males; 2. relation between the echogenity (ECHO) and TPOAb: this relation is very significant both in males and in females (p < 0.0001); 3. mutual relation between TgAb and TPOAb: both in males and in females very significant (p < 0.0001); positive relation between antibodies can be seen. Positive presence of antibodies can be found less frequent, negative presence of both antibodies is more frequent; 4. relation between the echogenity, TgAb and TPOAb: no statistic significance was found. CONCLUSION: Homogenous thyroid gland structure was mainly found in males and, on the contrary, non-homogenous structure in females. In 52.7% of adults with significantly decreased echogenity, autoimmune disorder was confirmed in laboratory tests at the same time. With echogenity increasing, TgAb and TPOAb decreased, vice versa. Sonography, evaluating decreased echogenity, can be an early indicator of serious thyropathies before function parameters and clinical symptoms appear. Detected risky adults with sonographic signs of autoimmune disorder have to be monitored and respective treatment considered and started at the very first occurence of positive antibodies even if the function is still normal.

Adult↗

Differences in type I diabetes mellitus of young adults with and without thyroid autoimmunity.

This work was intended to study if the coexistence of thyroid and Langerhans islets autoimmunity is associated with a different nature and course of diabetes in young adult diabetic patients. We followed the laboratory and clinical course of diabetes and the thyroid gland status of 47 young adults with Type I diabetes over a 9-year period starting from the onset of diabetes (ranging from 18 to 35 years of age). The patients were divided into subgroup I (with thyroid peroxidase and thyroglobulin antibodies, n = 13), subgroup II (thyroid peroxidase antibody only, n = 10), and subgroup III (without thyroid autoimmunity, n = 24). Out of the 22 females followed, 10 (46 %) and 5 (23 %) were in subgroups with thyroid autoimmunity (TA), I and II, respectively. On the contrary, out of the 25 men followed, 17 (68 %) were in group III. Within the 9 years, insulin secretion nearly ceased (C-peptide < 0.03 nmol/L) in all of the patients of subgroup I and 70 % of subgroup II, but only in 46 % of patients in subgroup III (I : II p < 0.01, I : III, p < 0.01, II : III, p < 0.05). The cumulative incidence of antiGAD > 1 U/mL (CIS, RIA) in subgroup I was higher (92 %) than in subgroups II (80 %) and III (53 %); I : III, p < 0.05. The cumulative incidence of tyrosine phosphatase antibodies (anti-IA2, BRAHMS, RIA) was insignificantly higher in subgroups I and II when compared with subgroup III (62 %, 60 %, and 42 %). The study of organ-specific and systemic autoantibodies showed their highest cumulative incidence in subgroup I, i.e., in patients with the most expressed manifestations of TA and the lowest one in subgroup III, i.e., diabetic patients without TA. Our results suggest that overall thyroid autoimmunity in young adult patients with Type I diabetes was associated not only with female gender, but also with more pronounced Langerhans islets autoimmunity and significantly faster cessation of endogenous insulin secretion; it was associated with therapeutical doses of insulin as well.

Adolescent↗

Immune response after adjuvant mucosal immunization of mice with inactivated influenza virus.

Satisfactory mucosal immunity in the respiratory tract is very important for protection against influenza. It can be achieved only by mucosal immunization. Mucosal vaccination with inactivated influenza virus may not be sufficiently effective and suitable adjuvants are therefore sought. We tested intratracheal immunization of mice with inactivate B type influenza virus in a mixture with formolized G+ bacterium Bacillus firmus, whose adjuvant effects have previously been documented in another system. The treatment resulted in a marked increase of both systemic and mucosal antibody response in IgG and IgA classes. Stimulation of T lymphocytes after adjuvant immunization was very mild, no proliferation taking place after specific stimulation with antigen in vitro. However, slightly increased systemic (spleen) and local (lungs) production of cytokines without perceptible Th1/Th2 polarization was determined. B. firmus is an efficient adjuvant in respiratory tract immunization while with subcutaneous immunization it lowers the antibody response.

Adjuvants, Immunologic↗

Thyroid autoantibodies and their clinical relevance in young adults with type 1 diabetes during the first 12 yr after diabetes onset.

In order to obtain prospective data on occurrence of thyroid autoantibodies [against thyroid peroxidase (antiTPO) and against thyroglobulin (antiTgl)] and their clinical relevance, we followed up on 109 young adults with Type 1 diabetes for 12 yr after diabetes onset. The patients were divided into subgroup I [positivity of both thyroid autoantibodies (T-Ab); 25%, women predominantly], subgroup II (isolated antiTPO positivity only, 26%, men and women equally) and subgroup III (thyroid autoimmunity not present, 49%, men mainly). Cumulative incidence of T-Ab during the 12 yr of follow-up was 51% with predominance of women over men (65% vs 38%, p<0.01). At the time of the first T-Ab detection, an ultrasonography pattern of a hypoechogenic thyroid gland was noted in 59% of subgroup I patients and in 25% of subgroup II patients (p<0.05). At the same time, TSH>4.5 mlU/I was shown in 30 and 7% of patients of subgroups I and II, respectively (p<0.05). In the patients with the repeated positivity of both T-Ab (subgroup I) subclinical hypothyroidism developed in all patients within 4 yr after the first detection of T-Ab. On the contrary, the clinical course in patients with isolated antiTPO positivity (subgroup II) was milder with 11% developing subclinical hypothyroidism within 4 yr after the first antiTPO detection (p<0.001). The data shed new light on the relative diagnostic value of thyroid antibodies, ultrasonography and functional examination for an early detection of thyroid autoimmunity of adult diabetic patients.

Adolescent↗

Serum levels of IGF-I, HGF, TGFbeta1, bFGF and VEGF in thyroid gland tumors.

IGF-I, HGF, TGFbeta1, bFGF and VEGF are involved in the pathogenesis of thyroid gland tumors and their growth. We decided to find whether changes in the production of these cytokines by thyroid tumor cells are reflected by changes of their peripheral blood. Using ELISA kits, we measured the concentrations of growth factors in the peripheral blood serum in 28 patients with thyroid gland tumors (14 adenomas, 14 papillary carcinomas) and compared these concentrations with those in healthy people. We found significantly lower serum levels of IGF-I in patients with thyroid adenoma compared to the healthy population. Serum levels of HGF and bFGF were significantly higher in patients with thyroid adenoma and papillary carcinoma compared with those in healthy subjects. Serum concentrations of TGFbeta1 and VEGF were not significantly different in any groups of investigated subjects. Changes in the production of these cytokines by thyroid gland tumor cells are reflected in their peripheral blood levels, but these levels also depend on a number of other physiological and pathological processes in the organism. However, significant differences of HGF and bFGF serum levels can be explained by their very high production by thyroid tumor cells and by their strong effect on the follicular and endothelial cell proliferation.

Adenoma↗

HLA antigen expression in autoimmune endocrinopathies.

The HLA allelic frequency was determined in three groups of autoimmune endocrinopathies: A) 30 patients with autoimmune thyroiditis, B) 20 patients with polyglandular activation of autoimmunity, and C) 10 patients with the autoimmune polyglandular syndrome type II. The groups were defined by the clinical state and serological parameters. Healthy blood donors of Caucasian population from the US database of HLA frequencies served as the controls. In group A, a higher occurrence of HLA-A24 (21.7 %) was found as compared to group B (5.0 %) and to the controls (8.5 %), of HLA-B27 (15.0 %) and of HLA-DR-11 (20 %) as compared to the controls (4.2 % and 8.5 %). In group B, a higher occurrence of HLA-A3 (25.0 %) was found as compared to group A (10 %) and to the controls (11.8 %), and of HLA-B8 (22.5 %) as compared to group A (8.3 %) and to the controls (8.6 %). In this group the occurrence of HLA-DR3 (30.0 %) was higher as compared to group A (10.0 %) and to the controls (9.8 %) and of HLA-B8 (30.0 %) as compared to group A (8.3 %) and to the controls (8.6 %). Genetic markers indicate a similarity of groups B and C. Patients in these groups could be at different stages of the same disease, however, some distinctions between them lead us to consider the possibility whether different epigenetic factors could extend the difference between these groups in the course of clinical development.

Adrenal Glands↗

Anti-GAD-positive patients with type 1 diabetes mellitus have higher prevalence of autoimmune thyroiditis than anti-GAD-negative patients with type 1 and type 2 diabetes mellitus.

The aim of our study was to evaluate antibodies against thyroglobulin (anti-TG) and thyroid peroxidase (anti-TPO) - markers of autoimmune thyroiditis - in several groups of adult patients with type 1 and type 2 diabetes mellitus (DM). We were particularly interested whether the presence of thyroid antibodies is related to the positivity of glutamic acid decarboxylase antibodies (anti-GAD). We found elevated anti-GAD in 46 % (97/210) patients with type 1 DM. All patients with type 2 diabetes were anti-GAD-negative. At least one thyroid antibody (anti-TG and/or anti-TPO) was found in 30 % (62/210) patients with type 1 DM and 27 % (22/83) type 2 diabetes patients. The patients with type 1 DM were further grouped according to their anti-GAD status. The anti-GAD-positive patients had a higher prevalence of anti-TG antibodies than the anti-GAD-negative patients (25 % vs. 12 %, p=0.03) as well as anti-TPO antibodies (32 % vs. 12 %, p<0.001). At least one thyroid antibody was detected in 39 % (38/97) of anti-GAD-positive but only in 21 % (24/113) of anti-GAD-negative patients with type 1 DM (p=0.006). No significant difference in the frequency of thyroid antibodies was found between anti-GAD-negative patients with type 1 and type 2 DM (21 % vs. 27 %, p=0.4). The groups with or without thyroid antibodies in both type 1 and type 2 diabetic patients did not differ in actual age, the age at diabetes onset, duration of diabetes, body mass index or HbA1c level. Patients with elevated thyroid antibodies had significantly higher levels of TSH than those without thyroid antibodies (1.86 vs. 3.22 mIU/l, p=0.04 in type 1 DM; 2.06 vs. 4.89 mIU/l, p=0.003 in type 2 DM). We conclude that there is a higher frequency of thyroid-specific antibodies in anti-GAD-positive adult patients with type 1 DM than in anti-GAD-negative patients or in patients with type 2 DM. Patients with or without thyroid antibodies do not differ in age, DM onset and duration, BMI or HbA1c. Thyroid antibodies-positive patients have higher levels of thyroid stimulating hormone (TSH).

Adolescent↗

Comparison of cytokine levels in sera of patients with autoimmune endocrinopathies.

Autoimmune endocrinopathies can be divided according to the presence of organ specific autoantibodies and according to the clinical manifestations into isolated autoimmune endocrinopathies, autoimmune polyglandular syndromes (APS) and polyglandular activation of autoimmunity (PAA). Many factors take part in the development of the autoimmune disease: predominantly a genetic predisposition, environmental etiologic causes and dysregulation in the microenvironment of the target organ. Until now it is not completely clear, if manifestations of the clinical disease depend primarily upon external factors and the degree of regulation mechanism disorder (e.g. in Th1/Th2 regulation) or upon the different genetic predisposition. In this work we compared the levels of Th1 and Th2 lymphocyte cytokines in peripheral blood in three groups of patients: group A of 30 patients with autoimmune thyroiditis, group B of 25 patients with PAA, and group C of 10 patients with APS type II. From group of Th1 cytokines IL-2 and IFN-gamma were detected, whereas from group of Th2 cytokines IL-4 and IL-10 were determined by ELISA kit. We did not find any differences in the concentrations of IL-2, IFN-gamma, IL-4 and IL-10 among the groups of patients with autoimmune endocrinopathies.

Autoimmune Diseases↗

[Specific mucosal immunity in the female reproductive tract: protection against infectious diseases and regulation of fertility (part 2)].

Immune mediated defense against pathogenic microorganisms and maintenance of immune tolerance to allogeneic antigens of sperm and fetus are main function of female reproductive tract mucosal immune system. Specific mechanisms concerning development of mucosal vaccines to sexually transmitted diseases and the immune regulation of fertility are reviewed in this article.

Animals↗

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↗

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↗

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↗