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Biomedical subjects

H A Drexhage

Publications and source records attributed to H A Drexhage.

At least 19 recordsLinked to original sources
PubMed1992

Interactions between the immune system and the thyroid. Regulatory networks in health and disease.

Hashimoto's thyroiditis, primary myxedema and Graves' disease are thyroid disease that are due to autoimmune reactions towards thyroidal antigens such as thyroid peroxidase (TPO), thyroglobulin (Tg) and the TSH receptor. Thyrocyte destruction in Hashimoto's thyroiditis and primary myxedema is caused by TPO- and Tg-specific lymphocytes and autoantibodies, thyrocyte stimulation in Graves' disease is caused by antibodies stimulating the TSH receptor, thyroid atrophy in primary myxedema is caused by antibodies blocking the TSH receptor, or a yet unknown thyroid growth receptor. The above listed thyroid autoimmune diseases are familial (genetically determined), and due to defects in the immunoregulatory mechanisms that should normally control excessive thyroid autoimmune reactivity. This control towards thyroidal antigens (tolerance) can be broken by professional antigen presenting cells, such as the dendritic cells. It is now known that thyroid autoimmune diseases are indeed initiated by dendritic cells: dendritic cells are present in low number in normal thyroids, but accumulate very early in thyroids that are later affected by thyroid autoimmune disease. Dendritic cells are also present in the normal anterior pituitary and in this gland they are known as the (folliculo) stellate cells, the regulators of growth and function of the surrounding pituitary-endocrine cells. It is discussed whether the influx and clustering of dendritic cells in the thyroid observed during early autoimmune thyroid disease is meant for the regulation of growth and function of the thyrocytes thus linking a putative early endocrine disturbance to the initiation of thyroid autoimmune disease.

Autoimmunity↗
PubMed1991

Reversible thyroid dysfunction during treatment with GM-CSF.

To investigate whether autoimmunity against thyroid antigens is induced or exacerbated by granulocyte-macrophage colony-stimulating factor, thyroid function and thyroid autoantibodies were studied in 14 patients with advanced breast cancer and 11 with soft-tissue sarcoma who received several cycles of doxorubicin and cyclophosphamide plus GM-CSF 250 micrograms/m2 intravenously daily for 10 days in every 21 day cycle. All patients had normal thyroid function before treatment. In 2 patients with pre-existing thyroid antibodies, thyroid dysfunction developed but disappeared after cessation of GM-CSF. No other autoimmune abnormalities appeared. Stimulation of antigen-presenting cells by GM-CSF may bring about this phenomenon.

Adult↗
PubMed1991

Defects in monocyte polarization and dendritic cell clustering in patients with Graves' disease. A putative role for a non-specific immunoregulatory factor related to retroviral p15E.

A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent infections of the respiratory tract and in various types of malignancies. These impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; less than 25 kDa) circulating in the serum of the patients. The factor, which seems to be a non-specific immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenic retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendritic cells of Graves' patients, monocytes were isolated from the peripheral blood and dendritic cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogeneic lymphocytes. A defective fMLP-induced monocyte polarization was found (16 vs 37% in healthy controls), whereas the dendritic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of less than 25 kDa prepared from the serum of Graves' patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E-like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendritic cell clustering.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Morphological, immunohistochemical and functional homologies between pituitary folliculo-stellate cells and lymphoid dendritic cells.

Lymphoid dendritic cells and pituitary folliculo-stellate cells have many morphological and immunocytochemical characteristics in common. They both have a stellate morphology, they are specifically detected by the presence of MHC class II determinants as well as the Ca(2+)-binding protein S100, they also produce the cytokine interleukin 6. A panel of monoclonal antibodies directed against murine and rat macrophages and/or dendritic cells was used to study the presence of dendritic and folliculo-stellate cells in the mouse and rat anterior pituitary. In the mouse pituitary stellate cells are detected with a monoclonal antibody against the dendritic cell aminopeptidase, but these cells display no S100 protein immunoreactivity. In the rat pituitary there were many S100 protein positive folliculo-stellate cells as well as a few macrophage-like cells, whereas stellate cells that express MHC class II markers were found in both mouse and rat anterior pituitaries. The present data suggest of a homology between lymphoid dendritic cells and pituitary folliculo-stellate cells, or at least a subgroup of the latter cells.

Animals↗
PubMed1990

Comparison of placebo with L-thyroxine alone or with carbimazole for treatment of sporadic non-toxic goitre.

The efficacy of treatment with TSH-suppressive doses of L-thyroxine (T4, 2.5 micrograms/kg body weight daily) either alone or combined with carbimazole (CBZ, 40 mg daily) was studied in 78 patients with sporadic non-toxic goitre in a prospective placebo-controlled double-blind randomised clinical trial. Treatment was given for 9 months, with 9 months of follow-up. A response to treatment as measured by ultrasonography was found in 58% of the T4 group, in 35% of the T4/CBZ group, and in 5% of the placebo group. The mean (SEM) decrease of thyroid volume at 9 months in the responders was 25% (2). After discontinuation of treatment, thyroid volume increased in the responders and had returned to base-line values after 9 months of follow-up. In the placebo group mean thyroid volume had increased by 6% (4) at 4 months, 20% (7) at 9 months, and 27% (8) at 18 months. The findings show that untreated sporadic non-toxic goitre continues to increase in size; T4 is effective in the treatment of the disorder; and the addition of CBZ has no therapeutic advantage.

Adult↗
PubMed1990

Immunosuppressive retroviral-related factors in sera of patients with head and neck cancer.

The chemotactic responsiveness of mononuclear phagocytes has often been found defective in patients with various malignancies. We have previously reported a defective chemotactic responsiveness in patients with head and neck cancer. Low-molecular-weight factors (LMWFs) have been isolated from tumors and can be held responsible for the inhibitory effect on monocyte chemotactic responsiveness. It is an intriguing new finding that these LMWFs can be neutralized by antibodies reactive to P15E, a structural envelope protein of murine leukemia retroviruses. In this report we describe a relatively easy and rapid method for the detection of immunosuppressive P15E-like factors in the sera of patients with head and neck cancer. The test is based on the monocyte polarization assay. Although only nine head and neck cancer patients were included in this study, the findings indicate that the test might be of value for clinical application. An early detection of a recurrence after treatment might be possible by the finding of a reappearance of the P15E-like factors in patients' sera during follow-up.

Aged↗
PubMed1990

Dendritic cells and class II MHC expression on thyrocytes during the autoimmune thyroid disease of the BB rat.

The BB rat is a well-established model for spontaneous thyroid autoimmune disease. Since antigen presentation in thyroid autoimmunity is still a matter of debate, we studied the presence of antigen-presenting dendritic cells in the thyroid of the BB/O rat during the development of the disease in relation to the presence of other leucocytes and the aberrant expression of class II MHC determinants by thyrocytes. Thyroid glands, as well as thyroid-draining lymph nodes, were investigated in enzyme histochemistry and immune histochemistry. The appearance of anti-colloid antibodies in the circulation at 6 weeks of age was accompanied by an increase in the weight of the thyroid-draining cervical lymph nodes, which contained many anti-thyroglobulin-producing plasma cells. The only noteworthy event in the thyroid gland in this early stage of the disease was an increase in the number of dendritic cells. T cells, B cells, and plasma cells were virtually absent from the thyroid, and thyrocytes were invariably negative for class II MHC determinants. Only after 18 weeks of age, when large accumulations of dendritic cells, B lymphocytes, and T lymphocytes were seen in 40% of the BB thyroids, could some class II MHC positive thyroicytes be observed. At this stage the thyroid also contained some anti-thyoglobulin-producing plasma cells. Our observations suggest that dendritic cells play a role in antigen presentation in the early stages of the thyroid autoimmune response.

Animals↗
PubMed1990

Beneficial effects of the thymic hormone preparation thymostimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis. A double-blind cross-over trial on improvements in monocyte polarization and clinical effects.

Twenty patients with chronic purulent rhinosinusitis were treated with TP-1 (Serono; 1 mg/kg body weight), in a double-blind cross-over trial. TP-1 was administered by daily i.m. injections for the first 14 days followed by two injections/week for 6 further weeks. The patients were immunologically special in that they had defects in their cell-mediated immune system. Fourteen showed a decreased chemotactic responsiveness of their peripheral blood monocytes as measured in the polarization assay. This defective function can probably be ascribed to the presence in serum of low molecular weight factors (LMWFs; less than 25 kD). As reported earlier, this factor shows a structural homology to the envelope protein of murine and feline leukaemia virus (P15E). Thirteen patients showed a defective delayed-type hypersensitivity (DTH) skin test reactivity towards candidin and/or streptokinase-streptodornase (Sk/Sd) antigen, 14 had a defective MIF production from their peripheral blood lymphocytes towards candidin, Sk/Sd and/or Haemophilus influenzae antigen. Eighteen patients completed the TP-1 trial and showed clinical improvements: 12 out of 15 were feeling better during TP-1 therapy and the nasal mucosa showed on inspection absent mucopurulent secretion in 13 patients. Positive bacterial culture rates for the nose decreased from 14 out of 16 to five out of 15. Placebo treatment had no significant effects. The clinical improvements were accompanied by a better performance of the cell-mediated immune system; the most significant effects were recorded in the monocyte polarization assay. The suppressive P15E-like LMWFs in serum clearly decreased during TP-1 treatment. In vitro TP-1 neutralized the immunosuppressive effect of the LMWFs. The restoring effects of TP-1 on monocyte polarization and its neutralizing activity of P15E-like LMWFs could explain the beneficial effects of thymic hormone treatment reported in adults with clinical signs of immunodeficiency in the presence of a full T cell repertoire.

Adult↗
PubMed1990

A delayed-type hypersensitivity skin-test system using the insulinoma cell line RINm5F to monitor beta cell-specific cellular autoimmune reactivity in the spontaneously diabetic BB/O rat.

Islet-specific autoimmune reactivity (humoral and cell-mediated) is the basis for the insulitis process of type I diabetes mellitus. In this report a delayed-type hypersensitivity (DTH) skin test was used to monitor the presence of an islet-specific cell-mediated autoimmune component in BB/O rats. The BB/O rat is a strain characterized by the spontaneous development of type I diabetes. Intact RINm5F cells as well as a RINm5F cell membrane preparation were used as DTH skin test antigens. Rats of different ages and disease stages were tested in the ear with the insulinoma cell line and its cell membrane preparation. As control antigens, the fibroblast cell line 3Y1 and a cell membrane preparation made thereof were used. The DTH reaction system showed a positive cell-mediated reactivity in BB/O rats for membrane-bound RINm5F cell antigens, and not for the control fibroblast 3Y1 cell membrane determinants. The true DTH character of the skin test was established by the time-course of the reaction (maximum at 24 h), the histopathology (infiltration by dendritic cells, lymphocytes and macrophages), and the possibility to transfer the reaction with spleen cells and lymph node cells. The DTH test towards RINm5F cells showed the highest prevalence of positivity (100%) in BB/O rats around the onset of diabetes (3 weeks before to 3 weeks after the onset of glucosuria). The prevalence of DTH positivity was 56% in the period of more than 3 weeks before the onset of glucosuria. In BB/O rats with a duration of glucosuria of more than 3 weeks, the prevalence of positivity was around 60-70%.

Age Factors↗
PubMed1990

Sexual precocity induced by ovarian follicular cysts. Is autoimmunity involved?

A 2-year-old girl presented with gonadotrophin-independent precocious puberty due to ovarian follicles. Central precocious puberty was excluded by several GnRH-tests and overnight LH sampling. There were no signs of McCune-Albright syndrome. An ovarian tumour was excluded by laparotomy and biopsies. Abdominal sonography demonstrated follicles occurring mostly in the left, sometimes in the right, ovary. Immunoglobulin G (IgG) purified from the patient's serum was capable of stimulating DNA synthesis in granulosa cells of rat ovarian segments kept in organ culture. Since FSH had a similar in-vitro action it is hypothesized that this patient's IgG mimics the action of FSH.

Animals↗
PubMed1990

T-cellular immune reactions (in macrophage inhibition factor assay) against Mycobacterium paratuberculosis, Mycobacterium kansasii, Mycobacterium tuberculosis, Mycobacterium avium in patients with chronic inflammatory bowel disease.

A mycobacterial aetiology has been suggested for Crohn's disease. A slow growing mycobacterium, biochemically and genetically identical to M paratuberculosis, the causative agent of enteritis in ruminants (Johne's disease), has been isolated from gut specimens of patients affected by Crohn's disease. If M paratuberculosis or other mycobacteria play a role in the pathogenesis of Crohn's disease, then patients may have been sensitised to these mycobacteria or show an anergy immune reaction. We therefore investigated the T-cell mediated immune response to sonicates of M paratuberculosis, M kansasii, M avium, and M tuberculosis in 35 patients with Crohn's disease, 28 with ulcerative colitis, and 25 controls using a macrophage inhibition factor assay on peripheral blood lymphocytes. Two types of reaction patterns were identified--that is, 'responders' (subjects with a macrophage inhibition factor assay in which a dose response relation was present and a percentage of inhibition exceeding 20%), and 'non-responders'. There was no significant difference in the prevalence of responders (59%-80%) and non-responders (20%-41%) to these mycobacteria between the group of Crohn's disease, ulcerative colitis, and control group. We found also that a large proportion of controls showed T-cell immunisation to the mycobacteria which supports the contention that the antigens are practically commensal. Our results do not support the proposed involvement of mycobacteria in the pathogenesis of Crohn's disease.

Adult↗
PubMed1990

Deoxyribonucleic acid cytophometry on rat ovarian follicles kept in organ culture: the effects of gonadotropins and plasma from normal, hypergonadotropic menopausal, and hypogonadotropic women.

Pituitary FSH as well as urinary FSH were found to be potent stimulators of in vitro granulosa cell DNA synthesis in Wistar rat ovarian segments kept in organ culture. Optimal responses were reached at the highest concentration used (pituitary FSH, 5 mU/mL: urinary FSH, 50 mU/mL). hCG also appeared to be a potent stimulator (optimal response, 5 mU/mL). LH showed no stimulating effect, but the hormone had a potentiating effect on FSH-induced DNA synthesis. Plasma samples of five normally menstruating women obtained at different stages of the follicular phase were also added to the rat ovarian culture system. All samples stimulated DNA synthesis, but the plasma samples obtained in the late follicular phase showed stronger growth responses, reaching optimal values at lower concentrations compared to the potency of plasma obtained in the early follicular phase (10(-3)-10(-5) vs. 10(-2)-10(-3) mL, respectively). The strong bioeffect of late follicular phase plasma could partly be explained by the potentiating effects of plasma LH on FSH-induced DNA synthesis. When plasma samples of five hypergonadotropic amenorrheic women were added to the culture system, 4 stimulated DNA synthesis moderately, with an optimal growth response at plasma concentrations of 10(-4)-10(-3) mL. When 10 plasma samples of hypogonadotropic amenorrheic women were added to the culture system, 8 had no effect on DNA synthesis, and clear discrepancies were evident between the low to absent ovarian growth potential of the plasma and the practically normal immunoreactive plasma FSH measured by RIA and immunoradiometric assay. These discrepancies may be the effect of nonimmune or immune factors interfering with FSH-induced growth or the effect of molecular changes in the FSH molecule (isoforms).

Adrenocorticotropic Hormone↗
PubMed1990

Chromatographically purified immunoglobulin G of endemic and sporadic goiter patients stimulates FRTL5 cell growth in a mitotic arrest assay.

A strain of differentiated rat thyroid cells (FRTL5) in continuous culture was used to study the presence of thyroid growth-promoting immunoglobulins (TGI) in the serum of patients with endemic and sporadic euthyroid goiters. To identify true in vitro cell proliferation a microscopic mitotic arrest assay was used. Immunoglobulins G (IgGs) were prepared with QAE-Sephadex A-50 or protein-A-Sepharose. A positive growth stimulation index was found in IgG preparations of 65 of 71 patients with endemic goiter and in 9 of 14 IgG preparations of patients with sporadic goiter. IgG preparations of 15 control subjects from an area where endemic goiter due to iodine deficiency does not occur and of 18 subjects without iodine deficiency and without thyroid enlargement living in the endemic area did not stimulate FRTL5 cell growth. FRTL5 cell growth stimulation with IgGs of these euthyroid goiter patients could only be detected when IgG was tested in combination with a small dose of TSH. Immunoprecipitation with polyclonal and monoclonal antihuman IgG was able to abolish the growth-promoting effects. In 32 blinded samples the Feulgen cytobiochemical assay, formerly used to detect TGI, was compared with the FRTL5 mitotic arrest assay. The two methods showed similar results. Our observations of chromatographically purified IgG promoting thyroid cell proliferation in vitro provide good evidence that IgG was responsible for thyroid cell growth in vitro and suggest that autoimmune growth mechanisms may be involved in the pathogenesis of both endemic and sporadic goiters.

Adult↗
PubMed1990

A diminished adherence of blood lymphocytes of patients with thyroid autoimmune disease to high endothelial venules in the thyroid and the thyroid-draining lymph nodes.

The function of high endothelial venules (HEVs), present in the T-cell area of lymphoid tissue is to attract lymphocytes to secondary lymphoid organs ("homing"). In Graves' disease, sporadic goitre and lymphocytic thyroiditis HEVs develop in the thyroid. To study the "homing" of peripheral blood lymphocytes (PBL) of healthy individuals and thyroid patients to the thyroid area we studied the adherence of PBL of such individuals to HEVs present in Hashimoto's goitres and to HEVs in thyroid draining lymph nodes. A modification of the in vitro "homing assay" described by Stamper and Woodruff (J Exp Med 144: 823) was used. The number of PBL of patients with Graves' disease which adhered to thyroidal and thyroid-draining lymphnode HEVs was significantly (p less than or equal to 0.001, Wilcoxon test) less than that of healthy control PBL's; in the case of thyroid HEVs 12 (mean, sd 8, n = 18) patient lymphocytes adhered to 35 HEVs vs 19 (mean, sd 7, n = 16) healthy control lymphocytes; in the case of thyroid lymphnode HEVs 20 (mean, sd 12, n = 15) patient lymphocytes adhered vs 35 (mean, sd 9, n = 9) healthy control lymphocytes. PBL of a few sporadic goitre (n = 5) and atrophic lymphocytic thyroiditis (n = 2) patients also showed a diminished adherence to thyroidal HEVs. We also studied the homing capability of lymphocyte suspensions isolated from the thyroid glands of three Graves' disease patients; these infiltrated cells showed a normal adherence pattern to thyroidal HEVs. We favour the idea that the data should be explained by a redistribution of lymphocytes possessing "thyroid-specific-homing-receptors" from the circulation to the thyroid area in patients with thyroid autoimmune disease.

Adolescent↗
PubMed1990

Thyroid growth stimulating immunoglobulins in sporadic and endemic colloid goitre.

Several methods have been described to measure immunoglobulins stimulating the growth of thyroid cells in vitro, the so called Thyroid Growth stimulating Immunoglobulins (TGI). The methods make use of either Ig-stimulated guinea pig thyroid (organ) cultures (the cytochemical bioassays; growth is measured via Feulgen-densitometry or pentose shunt analysis), the culture of Ig-stimulated rat or porcine thyroid follicles (growth is measured via 3H-thymidine incorporation), or of Ig-stimulated rat FRTL-5 cells (growth is measured via 3H-thymidine incorporation, or counting the number of mitoses in arrest). The various methods have now been validated: (a) the data obtained with TGI preparations in the Feulgen Cytochemical Bioassay (CBA's) correlate well with those obtained in the FRTL-5 mitosis arrest assay with the same TGI preparations, (b) the growth stimulation can not be ascribed to hormonal contaminations of the used Ig preparations, since protein A-sepharose purified IgG is active in the assays and since anti human IgG's neutralize the growth stimulating effects of the preparations. Using the assays TGI has been found positive in goitrous Graves patients, in sporadic goitre patients and in endemic goitre patients. Particularly, patients complaning of recurrent goitre after thyroidectomy or with recent goitre growth are TGI positive. TGI occurs in sporadic goitre in the absence of TSH-receptor antibodies. The autoimmune-prone animal model of the BB rat also proved to be TGI-positive; the animal shows an increased thyroid glandular weight. Both the histomorphology of human goitres as well as the goitre of the BB rat indicate that the dendritic cell plays a prominent role in initiating the thyroid autoimmune reaction.

Animals↗
PubMed1989

Endemic cretinism: possible role for thyroid autoimmunity.

Thyroid atrophy, rather than goitre, is a characteristic feature of myxoedematous cretinism but its cause and nature are unknown. In this study, purified IgG fractions of serum from patients with myxoedematous endemic cretinism inhibited thyrotropin-induced DNA synthesis in guineapig thyroid segments in a sensitive cytochemical bioassay. IgG from patients with euthyroid neurological endemic cretinism or from normal subjects did not inhibit thyroid growth. Furthermore, in myxoedematous subjects, the presence of the thyroid-growth-blocking immunoglobulins showed a positive relation with thyroid atrophy found on ultrasound. These findings provide a pathogenic basis for the variable clinical expression of endemic cretinism.

Adolescent↗
PubMed1989

Autoimmune involvement in Cushing syndrome due to primary adrenocortical nodular dysplasia.

Cushing syndrome due to primary adrenocortical nodular dysplasia was diagnosed in two patients, aged 3 years 9 months and 9.5 years. Subsequently, adrenalectomy was performed and followed by steroid replacement. In both cases, the adrenals were normal or only slightly enlarged and showed adrenocortical nodular dysplasia histologically. Small lymphocytic infiltrates consisting of T-cells and class II MHC positive macrophages were present in adrenal specimens of both the patients. Samples of protein A sepharose purified serum immunoglobulins from both children stimulated adrenocortical DNA synthesis and cortisol production in cultured guinea-pig adrenal segments in vitro in a dose dependent fashion. Adrenal stimulating immunoglobulins were also demonstrated in serum specimens of both patients' mothers. However, none of them had overt signs of adrenal disease. Our data support the view that autoimmune mechanisms may be involved in primary adrenocortical nodular dysplasia.

Adrenal Cortex↗