Biomedical subjects

R Hoermann

Publications and source records attributed to R Hoermann.

At least 19 recordsLinked to original sources

PubMed2003

Impact of smoking on the response to treatment of thyroid associated ophthalmopathy.

BACKGROUND: In patients with Graves' disease, smoking considerably increases the incidence and severity of thyroid associated ophthalmopathy (TAO). The authors sought to determine if smoking also influences the course of TAO during treatment, and the efficacy of therapy. METHODS: 41 smokers and 19 non-smokers with moderate untreated TAO were included in this prospective study. All patients were treated with steroids and, 6 weeks after the beginning of drug therapy, with orbital irradiation. Follow up was performed 1.5, 4.5, 7.5, and 12 months after the beginning of the study. Proptosis, clinical activity score (CAS), and motility were evaluated. The extent of smoking was derived from the concentration of the haemoglobin adduct N-2-hydroxyethylvaline (HEV), a parameter of long term smoking. RESULTS: There was no difference in the clinical manifestations of TAO between smokers and non-smokers at the beginning of treatment. However, CAS decreased (p<0.05) and motility improved (p<0.02) significantly faster and to a greater extent in non-smokers than smokers. Inverse correlations between the CAS decrease and the HEV levels observed 4.5 and 7.5 months after the beginning of treatment and between the improvement of motility and the HEV levels after 1.5, 4.5, and 7.5 months indicated a dose dependence. Mean HEV levels did not vary much during the follow up period and were significantly different in smokers (mean 5.4 (SD 2.7) micro g/l) and non-smokers (mean 1.8 (1.3) micro g/l; p<0.01). CONCLUSION: Smoking influences the course of TAO during treatment in a dose dependent manner. The response to treatment is delayed and considerably poorer in smokers.

Adolescent↗

PubMed2003

Tumor- and pregnancy-derived isoforms of human chorionic gonadotropin: biological and diagnostic relevance.

OBJECTIVES: Human chorionic gonadotropin (hCG) and hCG variants are of high clinical importance for the diagnosis of pregnancy, monitoring of abnormal and ectopic pregnancies, testing for Down's syndrome or monitoring therapy of hCG-secreting malignancies. In serum and urine, hCG appears in microheterogeneous isoforms with respect to protein backbone structure and the extent of glycosylation. The present study reports on the identification, immunological characterization, biological activity of glycosylation isoforms of pregnancy (preg) and tumor-derived (tu) hCG, and the impact of glycosylation on diagnostic immunoassays. METHODS: Twenty-two urinary preg- and tu-hCG isoforms were separated by preparative isoelectrofocusing (hCG-pI variants) and characterized by Western blot. Number, topography and accessibility pattern of epitopes on their surface was evaluated by two-site radioimmunoassays using 14 different monoclonal antibodies (mabs). Binding of hCG isoforms to four different LH/CG receptors was investigated in radioreceptor assays, and their biological activity determined by measuring cAMP elevation. RESULTS: All 22 hCG glycosylation variants appeared immunologically intact: each isoform, even when highly acidic, expressed all 14 surface epitopes which were arranged in a topographical manner indistinguishable from crude hCG. hCG isoforms were able to bind to four different receptor variants, with slightly varying affinities, but orientations indistinguishable from each other as shown by identical epitope accessibility patterns. Each of the hCG-pI variants was able to activate the LH/CG-Rs, but with varying reactivities. CONCLUSIONS: We conclude that in contrast to deglycosylated hCG, all hCG glycosylation isoforms investigated act as receptor agonists. Moreover, there is no overspecificity of mabs to certain hCG isoforms due to carbohydrate variability that exclude others from diagnostic measurement.

Adult↗

PubMed2002

Maturation of thyroidal dendritic cells in Graves' disease.

Because thyroidal dendritic cells (t-DC) may be implicated in the pathogenesis of Graves' disease (GD), we compared t-DC in thyroid sections of patients with GD (n = 15) and control patients with toxic (TG; n = 12) or non-toxic goitre (NG; n = 12). Goitres in GD, but not TG or NG, were populated with three discernible t-DC phenotypes. (i) Immature t-DC (major histocompatibility complex (MHC) II+/CD40-/CD80-) were located perifollicularly (95% of the patients with GD, but only 55% of TG and 51% of NG patients); numbers of such t-DC were significantly elevated in GD (P < 0.001). (ii) Partially matured CD80+ t-DC were present in connective tissue (73% of the patients) and focal interstitial clusters (40% of the patients). In 53% of the patients with GD, single as well as clustered interstitial t-DC expressed CD40. (iii) However, phenotypically mature t-DC (MHC II+/CD40+/CD80+/RFD1+) were only present in clusters and colocalized with activated CD4+/MHC class II+ T-helper (Th) cells. Expression of CD54 and CD83 did not significantly differ among the groups. The phenotype of intrathyroidal DC in GD thus supports their role as potential (co)stimulators of thyroid autoimmunity.

Adult↗

PubMed2002

Immunological and biological activity of different commercial preparations of human chorionic gonadotropin.

In vitro immunological and biological activity of four commercially available preparations of human chorionic gonadotropin (hCG) for clinical use (Predalon(R): hCG-A, Primogonyl(R): hCG-B, Choragon(R): hCG-C and Pregnisin(R): hCG-D) were examined. The methods used include immunoassay, cAMP production in Chinese hamster ovary (CHO) cells and structural analysis of hCG with high performance liquid chromatography (HPLC). There were remarkable differences in immunological activities among preparations. hCG-D had the highest concentration of free hCGbeta. In CHO cells, production of cAMP with hCG-C was significantly higher than that with other preparations. Analyses in HPLC showed similar pattern in hCG-C and a standard preparation of hCG (CR 123). The highest immunological activity in hCG-A could be attributed to the presence of nicked form of hCG in this preparation. Various hCG components in preparation may explain these differences.

Animals↗

PubMed2002

Long-term follow-up of thyroid nodule growth.

Benign thyroid nodules are common in iodine deficient countries. Although many recent studies have addressed the molecular basis and short-term outcome of treatment in nodular thyroid disease, data on the long-term follow-up of thyroid nodule growth are widely lacking. The aim of the present study was to evaluate the long-term behaviour of benign thyroid nodules growth. We followed 109 consecutive patients seen at yearly intervals in our Outpatient Clinic for at least 3 years (range 3-12 years, mean 4.9 +/- 2.6 years) presenting with 139 benign nodules in uni- or multinodular goiters. The size of the nodules and thyroid glands was analysed retrospectively. The study included a spectrum of benign thyroid nodules, 86 functioning and 53 non-functioning. 27 patients were treated with levothyroxine, 8 with iodide and 16 with a combination of both. 58 patients were not treated mainly because of thyroid functional autonomy. Patients with overt hyperthyroidism or suspected malignancy by fine-needle aspiration were excluded from the study. The nodules and glands were assessed by ultrasonography at yearly intervals and documented by photoprints. Relevant growth was defined as an increase in nodule volume of at least 30%. For statistical analyses, Cox Proportional Hazard Model and life-table analyses according to Kaplan-Meier were performed. Most thyroid nodules grew slowly but continuously during follow-up. After about 3 years, half of the nodules had increased their volume by at least 30%. Growth of the nodules was significantly faster than of the corresponding thyroid glands (p < 0.0001). Age and sex of the patients and size or function of the nodules at initial presentation were not significantly related to their growth. Suppression of TSH did not affect growth of the nodules irrespective of the source of thyroid hormones, endogenous or by administration of levothyroxine. In conclusion, benign thyroid nodules have a slow intrinsic growth potential, which is apparently higher than that of the non-nodular tissue. In this study, not only nodular but even non-nodular goiter growth continues in the majority of patients. Exogeneous factors, including therapy with levothyroxine and/or iodide, appear to have little effect on the growth behaviour.

Adolescent↗

PubMed2002

Human chorionic gonadotropin exhibits normal biological activity in patients with recurrent pregnancy loss.

To test the hypothesis that the structural abnormality of human chorionic gonadotropin (hCG) may induce recurrent pregnancy loss, we examined the biological activity of hCG in pregnant women with a history of repeated miscarriages (n = 44). Pregnant women without a history of miscarriage (n = 85) were included as controls. Serum hCG, estradiol (E2) and progesterone levels were found to be significantly lower in the pregnancy loss group. There was no difference in serum thyroid hormone levels. Sera from both groups of women were then incubated with Chinese hamster ovary (CHO) cells transfected with hCG/luteinizing hormone receptor (CHO-hCG/LHr) or human thyroid stimulating hormone receptor (CHO-hTSHr). Biological response to hCG in women with recurrent pregnancy loss was identical to that of women in the control group in both CHO-hCG/LHr and CHO-hTSHr cells. When sera were subjected to high performance liquid chromatography, no difference in hydrophobicity was observed between control and patients groups. The structure of the hCG molecule and its biological activity in women with a history of recurrent pregnancy loss are apparently not different from those in women with normal pregnancy. Lower serum progesterone and E2 levels in the patient group can be explained by lower serum hCG levels in these women. Intrinsic gonadotropic and thyrotropic activities of the hCG molecule appear to play no major role in recurrent pregnancy loss.

Abortion, Habitual↗

PubMed2001

Posterior retroperitoneoscopic adrenalectomy: lessons learned within five years.

Posterior retroperitoneoscopic adrenalectomy is one of the new endoscopic methods in endocrine surgery. In a prospective clinical study 142 posterior retroperitoneoscopic adrenalectomies (72 right, 70 left) were performed in 130 patients (52 males, 78 females, age 49.1 +/- 14.9 years). Indications were primary adrenal tumors (unilateral, n = 118; bilateral, n = 2), adrenal metastases (n = 2), and bilateral ACTH-dependent hyperplasias (n = 10). Tumor size ranged from 0.5 to 7.0 cm (mean 2.7 +/- 1.4 cm). Partial adrenalectomies were performed in 39 patients. Conversion to open posterior adrenalectomy was necessary in five patients and seven procedures (5%). Intraoperative and postoperative complications were minor and occurred in 5% and 13%, respectively. Mortality was zero. Operating time was 101 +/- 39 minutes (range 35-285 minutes) and depended on tumor type (pheochromocytoma versus others; p < 0.01), tumor size (< 3 vs. > or = 3 cm; p < 0.05), gender (p < 0.05), and extent of resection (partial versus complete, p < 0.05. Twenty-three adrenalectomies (17%) were performed within 1 hour or less. Blood loss was 54 +/- 72 ml. Consumption of analgesics was low (mean 6 mg piritramide postoperatively). Median duration of hospitalization was 3 days. Posterior retroperitoneoscopic adrenalectomy is a safe method that has become a standard procedure in endocrine surgery.

Adenoma↗

PubMed1999

Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease.

Detection of autoantibodies to the TSH receptor (TSH-R) in Graves' disease has found widespread use in clinical routine and is performed mostly by commercial RRAs measuring TSH binding inhibitory activity. We report in this study on a second generation TSH binding inhibitory assay using the human recombinant TSH-R with two major improvements: 1) superior diagnostic sensitivity for Graves' disease, and 2) for the first time, nonradioactive and radioactive coated tube (CT) technology. Full-length human recombinant TSH-R was expressed in the K562 leukemia cell line and grown in suspension at a high density. A murine monoclonal antibody was selected for binding to the native TSH-R without interfering with autoantibodies or TSH and was coated to polystyrene tubes. After detergent extraction, TSH-R was affinity immobilized on antibody-coated tubes. The binding of TSH to the TSH-R could be demonstrated by the addition of 125I- or acridinium ester-labeled bovine TSH, and this binding could be inhibited by sera from patients with Graves' disease up to 95%. Subsequently, these novel assays, a CT RRA and a CT luminescence receptor assay, were compared to the conventional RRA based on porcine antigen in a blinded clinical multicenter trial. Sera from 328 patients with Graves' disease (86 untreated, 116 treated, and 126 in remission) and 520 controls (comprised of healthy blood donors and patients with autoimmune diseases or goiter) were tested in all 3 assays. Receiver-operating characteristic plot analysis resulted in a specificity of 99.6% with a sensitivity of 98.8% for both CT assays, compared to 99.6% specificity and 80.2% sensitivity for the conventional RRA (P < 0.001). In all 3 groups of patients with Graves' disease, the 2 CT assays were significantly more sensitive for the disease than the conventional assay, without loss of specificity in the control groups. This increase in sensitivity and the nonradioactive or radioactive CT format constitute a significant improvement over the currently available assays.

Adolescent↗

PubMed1998

T3-release from autonomously functioning thyroid nodules in vitro.

Toxic thyroid nodules have been shown to be of clonal origin. In a portion of them, point mutations affecting either the gene of the TSH receptor (TSHr) or the alpha-subunit of stimulating G-protein, consecutively leading to enhanced cAMP levels, which may enhance growth or functional activity of the thyrocyte or both, were recently found. To complement these studies, we evaluated hormone response (i.e. T3 release) in vitro from tissues derived from toxic thyroid nodules as compared directly to the surrounding paranodular tissues as well as tissues derived from euthyroid goiter and from patients with Graves' disease. Experiments were conducted in the presence and absence of bTSH or Graves' immunoglobulines. Tissues obtained during surgery were incubated over 5 h, followed by equilibrium dialysis for 24 h, and determination of free T3 in an aliquot by RIA. Basal T3 release in nodular tissues (n = 10) was significantly higher (median: 7.3 ng/l) compared to paranodular tissues (3.2 ng/l; P < 0.01), tissues derived from euthyroid goiter (1.3 ng/l; n = 12; P < 0.001) and thyroid tissues derived from patients with Graves' disease (2.5 ng/l; n = 6; P < 0.001). Upon stimulation with bTSH (1 IU/l), median T3 concentrations markedly increased to 11.5 ng/l (P < 0.05), 7.3 ng/l (P < 0.05), 4.2 ng/l (P < 0.01) and 3.2 ng/l (P = N.S.), respectively. Stimulation over basal values was 1.6-fold in nodular tissues, 2.3-fold in paranodular tissues, 3.2-fold in euthyroid goiter and 1.3-fold in Graves' disease. In toxic thyroid nodules basal hormone-releasing activities were stimulated by fifteen out of twenty (75%) Graves' sera tested. For comparison, stimulation in other tissues occurred in 45% (paranodular), 80% (euthyroid goiter) and 35% (Graves' disease), respectively. In conclusion, tissue derived from toxic thyroid nodules exhibits enhanced basal hormone release as compared to both, the surrounding paranodular tissues and tissues from euthyroid goiter in vitro, which may reflect constitutional activation of TSHr, alpha-subunit of stimulating G-protein or other so far unknown intermediate by point mutations affecting the respective genes. Hyperactivities in toxic thyroid nodules may be even further enhanced by external stimulators such as TSH or TSH receptor antibodies. The first stimulator may have clinical relevance in patients with toxic thyroid nodules and not yet suppressed TSH; the latter could play a role in the rare Marine Lenhart syndrome.

Adult↗

PubMed1998

Course of thyroid nodules.

Thyroid nodules are present in up to 30% of the German population. The causative role of iodine deficiency which is still endemic in this country has long been established. Recent progress has shed some light on the pathogenesis of nodular thyroid disease which still remains less well understood than goitrogenesis. Most thyroid nodules appear to be of clonal origin. Functional abnormalities have been related to alterations within the TSH signaling cascade, particularly mutations in the TSH receptor and stimulating G-protein-alpha-subunit. Proliferation which is dissociable from thyroid function has been linked to genetic differences of the thyroid cells themselves and growth factors being partly overexpressed by thyroid nodules. Data regarding the correlation of the molecular characteristics to the clinical behavior and growth potential have not yet been elucidated. On the other hand, there are only a few clinical studies that have addressed the long-term natural history of thyroid nodules. From these studies at least it appears that thyroid nodules tend to grow slowly and their increase in size may even by modern ultrasonography technique become apparent only after several years. Those in vitro and in vivo observations have important implications for the planning of therapeutical trials. Studies have focused so far mainly on short term effects of different therapeutic regimens such as iodine or levothyroxine. However, pathophysiological considerations and clinical observation would encourage studies over more prolonged periods of time.

Germany↗

PubMed1998

Pre-evaluation and system optimization of the Elecsys thyroid electrochemiluminescence immunoassays.

We present the results of a pre-evaluation of the thyroid function test free thyroxine, free triiodothyronine and third generation TSH using the Elecsys electrochemiluminescence immunoassay system. A collaborative field study between the development center of the manufacturer and a clinical chemistry laboratory addressed the reliability and comparability of the new Elecsys assays to established methods under clinical laboratory conditions using samples from routine in vitro thyroid testing. Preliminary (reference) formulations of the reagents and several electrochemiluminescent pilot models were used for assay measurements, either in the company's research center or in the clinical setting. The new thyroid assays were compared with the respective Enzymun-Test assays, performed on the ES300 automated immunoassay analyzer. A WHO standard was used for standardization of TSH, whereas an equilibrium dialysis method was applied for free triiodothyronine. The free thyroxine assay was standardized against the Enzymun-Test free thyroxine assay, which had previously been calibrated against equilibrium dialysis. The aim of this field study was to support the optimization of the technology used for Elecsys in an early stage of development and thereby prepare the ground for the adaptation of the immunoassays to the final Elecsys 2010 random access analyzer. A subsequent multicenter evaluation demonstrated that the requirements of routine thyroid testing in terms of reliability were fulfilled by the system.

Electrochemistry↗

PubMed1997

Beta-human choriogonadotropin therapy and HIV-related Kaposi's sarcoma.

Recently, two clinical trials demonstrated an antitumour effect of systemic high-dose beta-hCG therapy and of different regimens of local beta-hCG injections in AIDS-related Kaposi's sarcoma. We report the efficacy and safety of subcutaneous beta-hCG treatment (low-dose (2500-25000 IU/day) or high dose (25000-100000 IU/day)) in eight patients with advanced HIV disease in whom systemic chemotherapy and radiation were contraindicated or had failed. During therapy, serum hCG-concentrations as well as LH and FSH were measured. In the low-dose regimen one partial response was achieved. In the high-dose regimen, one patient maintained his response without further improvement. Three patients had stable disease and four patients disease progression. Serious side effects related to beta-hCG therapy were not observed. In conclusion, systemic beta-hCG-therapy for Kaposi's sarcoma is safe but associated with regression only in a minority of patients with advanced HIV-disease.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Cholesterol 7 alpha-hydroxylase activity in hypothyroidism and hyperthyroidism in humans.

Alterations of serum cholesterol levels are well recognized findings in hypothyroidism and hyperthyroidism. It remains unclear, whether thyroid hormones may affect serum concentrations of cholesterol through changes in the activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolic conversion of cholesterol to bile acids. We determined serum concentrations of the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one, which reflects cholesterol 7 alpha-hydroxylase activity in the liver, in 19 patients with hypothyroidism and in 10 patients with hyperthyroidism before and after treatment, respectively. In patients with hypothyroidism, serum concentrations of cholesterol and LDL-cholesterol decreased by 33% (p < 0.0005) and 39% (p < 0.0005), respectively, after replacement therapy with thyroid hormones. In contrast, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one (21.7 +/- 15.8 ng/ml vs 24.5 +/- 18.1 ng/ml before treatment, n.s.) as well as serum HDL-cholesterol were unchanged during substitution therapy. In patients with hyperthyroidism, serum concentrations of cholesterol and LDL-cholesterol increased by 27% (p < 0.01) and 39% (p < 0.01) after antithyroid treatment, respectively. Again, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one did not change significantly during treatment (15.8 +/- 12.6 ng/ml vs 14.7 +/- 8.1 ng/ml before treatment, n.s.). These findings indicate that in humans, thyroid hormones influence serum lipid concentrations by other mechanisms than by affecting the activity of cholesterol 7 alpha-hydroxylase.

Adenoma↗

PubMed1997

Regulation of intercellular adhesion molecule-1 expression in human thyroid cells in vitro and human thyroid tissue transplanted to the nude mouse in vivo: role of Graves' immunoglobulins and human thyrotropin receptor.

To further explore a potential role for the human TSH receptor (hTSHR) in the propagation of thyroid autoimmune disease, we examined immunomodulatory effects in response to its stimulation by Graves' Igs both in human thyroid tissue transplanted to the nude mouse and in primary cultures of human thyrocytes. We injected nude mice bearing transplants derived from normal human thyroid with protein A-Sepharose-purified Graves' IgGs (0.05-1 mg) on 2 days and assessed, in addition to functional stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by transplant thyrocytes. In parallel to functional stimulation, as demonstrated by thyroid follicular cell hypertrophy in the transplants and increased T4 production, Graves' IgGs induced a marked dose-dependent expression of ICAM-1 by transplanted thyrocytes, which exceeded that of a continuous interferon-gamma infusion (200 IU/24 h) for 2 days. Normal IgGs were ineffective. Bovine TSH (bTSH) had little effect by itself, but did enhance interferon-gamma-induced ICAM-1 expression. To assess the specificity of their effects, experiments with Graves' IgGs were conducted in the presence and absence of a selective hTSHR antagonist (asialoagalacto-hCG). Asialoagalacto-hCG nearly completely abolished the stimulatory effect of Graves' IgGs on ICAM-1 expression and significantly reduced the combined bTSH/interferon-gamma effect. It failed, however, to affect interferon-gamma action. In vitro studies using human thyroid cells in primary culture confirmed the in vivo observations, treatment with saline resulted in 14% of cells expressing ICAM-1, with pooled normal IgGs (500 mg/L) in 18% and with Graves' IgGs (patient A, 448 mg/L; patient B, 260 mg/L) in 78% and 51%, respectively. Upon exposure to Graves' IgGs (90 mg/L) plus asialo-hCG(350 mg/L), 25% of the cells stained positively for ICAM-1, 29% to bTSH (10 IU/L), 31% to recombinant human TSH (10 IU/L), and 84% to interferon-gamma (10 IU/mL). In conclusion, stimulation of human thyroid cells, either transplanted to the nude mouse in vivo or studied under in vitro conditions, with Igs derived from patients with Graves' disease increased the expression of ICAM-1 on the surface of the cells. The action appears to be specific and mediated by the hTSHR. This particular property of TSHR autoantibodies may be of pathophysiological relevance in Graves' disease, as it may assist in targeting the autoimmune attack and in promoting lymphocyte recruitment to the thyroid gland.

Animals↗

PubMed1996

Immunochemical mapping of gonadotropins.

As a glycoprotein hormone, human chorionic gonadotropic (hCG) is not a single molecular entity but this term rather comprises an array of molecular variants such as hCG, hCG beta, hCGn, hCG beta n, hCG beta cf, -CTPhCG, hCG beta CTP, deglyhCG, asialohCG, hCGav and the closely related molecules hLH, hLH beta and hLH beta ef. The advent of monoclonal antibodies (MCA), the availability of ultrasensitive detection systems and the recent determination of the crystal structure of hCG, made it possible to design special purpose diagnostic and clinical research immunoassays for hCG-like molecules. For more than a decade we and others have tried to refine epitope maps for hCG and related molecules by means of a large panel of MCA, naturally occurring metabolic variants of hCG (hCGn, hCG beta, hCG alpha, hCG beta cf, hCG beta CTP), homologous hormones and subunits of various species (e.g. hLH, hLH beta, hFSH, hTSH, oLH, rLH beta), chemically modified molecules (deglyhCG, asialohCG, tryptic and chymotryptic hCG beta and hCG alpha fragments) and synthetic peptides (octapeptides and longer). It appeared that all epitopes on molecular hCG-variants recognized by our MCA are determined by the protein backbone. Except for the two major epitopes on hCG beta CTP and parts of two antigenic domains on hCG alpha, epitopes on hCG-derived molecules are determined by the tertiary and quarternary structure. Operationally useful descriptive epitope maps were designed including information on assay suitability of antigenic determinants. On this basis we established ultrasensitive time-resolved fluoroimmuno-assays for hCG, hCG and hCGn, hCG beta and hCG beta n and hCG beta cf, hCG alpha and additional assays recognizing different spectra of hCG-variants. Such assay have been applied by us and others to the detection of pregnancy, early pregnancy loss, choriocarcinoma, testicular cancer, other cancers and prenatal diagnosis. However, as the molecular structure of many epitopes utilized in immunoassays of different laboratories was not resolved, comparability of results was not satisfactory. Consequently, attempts were made to compare schematic epitope maps from different research institutions. The situation has been much improved by solving the three-dimensional (3D) structure of hCG. It has been shown that hCG is a member of the structural superfamily of cystine knot growth factors like NGF, PDGF-B and TGF-beta. Each of its subunits is stabilized in its topology by three disulfide bonds forming a cystine knot. Moreover, it turned out that the disulfide bridges in their majority have previously been wrongly assigned. Computer molecular modeling of crystallographic coordinates of hCG and subsequent selective combined--PCR-based and immunological--mutational analyses of hCG beta expressed via the transmembrane region of a MHC molecule made it possible to more precisely localize epitopes on hCG-derived molecules. Although the entire surface of hCG has to be regarded as potentially immunogenic there seems to be hot spots where epitopes are clustered in antigenic domains. These are located on the first and third loops protuding from the cystine knots of both subunits and are possibly centered around the knot itself. Ultimate answers on epitope localizations will be given by the crystal structure determination of hCG complexed with different Fabs.

Amino Acid Sequence↗

PubMed1996

Posterior retroperitoneoscopy as a new minimally invasive approach for adrenalectomy: results of 30 adrenalectomies in 27 patients.

Posterior retroperitoneoscopic adrenalectomy is a new minimally invasive method. It represents an alternative to conventional open procedures and laparoscopic techniques. Between July 1994 and November 1995 a total of 30 retroperitoneoscopic adrenalectomies were performed on 27 patients. In 24 patients, unilateral tumors were seen (size 1-7 cm): seven Cushing adenomas, five Conn adenomas, seven pheochromocytomas, four hormonally inactive tumors, one cyst. Three patients suffered from Cushing syndrome with bilateral adrenal gland hyperplasias (two inoperable pituitary gland tumors, one bronchial carcinoid with ACTH secretion). The operations were carried out in prone position. After balloon dilatation of the retroperitoneum and creation of a pneumoperitoneum the preparation of the adrenal gland was performed via three trocar sites positioned below the 12th rib. Twenty-five adrenalectomies were completed endoscopically, and five times (among four patients) conversion to the conventional posterior technique was necessary. The average operating time of complete endoscopic adrenalectomies was 124 minutes (45-225 minutes); blood loss was 10 to 120 ml. With minimal need for postoperative analgesia (average dosage 7.9 mg of piritramide), mobilization and adequate food uptake were possible on the day of operation. The posterior retroperitoneoscopic adrenalectomy is a relatively fast, safe method, with the advantages of the posterior open approach and minimally invasive surgery. It therefore represents an important addition to adrenal gland surgery.

Adenoma↗

PubMed1996

Enhanced functional activity in thyroid adenomas in vitro.

The majority of thyroid adenomas have been shown to be of clonal origin. In a portion of them, somatic or germline point mutations leading to altered TSH receptor or Gs alpha-proteins have been found. The constitutive activation of these proteins consecutively stimulate cAMP-levels. Expression of the TSH receptor mutants in mammalian cells leads to increased cAMP-production compared to cells transfected with the wild type receptor. Presently, the role of these mutations in the development and growth of such tumours is still unclear. In our own investigations we made an attempt to evaluate the functional significance of these observations. In nodular tissue derived from patients with functioning autonomous adenoma we found significantly higher basal and TSH stimulated thyroid hormone releasing activity than in the surrounding paranodular tissue and in thyroid tissue derived from patients with euthyroid goiter. These findings indicate a functional relevance of constitutively activated intracellular signal transducing cascade in thyroid adenomas that may lead to hyperthyroidism in the presence or absence of external thyroid stimulators.

Adenoma↗

PubMed1996

Stimulation of thyroidal and extrathyroidal thyrotropin receptors.

TSH receptor plays a pivotal role in the regulation of thyroid function and is intimately involved in the pathogenesis of common thyroid disorders. A lack of specificity and absence of down regulation upon stimulation renders the human TSH receptor susceptible to exogenous overstimulation, which forms the basis of hyperthyroidism in TSHoma, Graves' disease and gestational thyrotoxicosis. Further, TSH receptor activation in the absence of exogenous stimulators due to the expression of endogenously active mutant receptors has recently been described, and may in part account for hyperthyroidism in autonomously functioning thyroid nodules. Signal bifurcating by coupling of TSH receptor to different G proteins may be a likely mechanism to explain the multitude of distinct effects caused by TSH receptor activation including mainly hormone production and growth promotion. Also, TSH receptor appears to mediate immunological stimulation, its activation by TSH R Ab inducing expression of adhesion molecules and HLA class II antigens on thyrocytes. Increasing evidence suggests that TSH receptor is not restricted to thyroid and may be expressed in extrathyroidal tissues with a potential role in the pathogenesis of Graves' orbitopathy.

Humans↗