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Biomedical subjects

K Horn

Publications and source records attributed to K Horn.

At least 109 records · Page 6Linked to original sources
PubMed1985

Involvement of cyclic AMP, iodide and metabolites of arachidonic acid in the regulation of cell proliferation of isolated porcine thyroid follicles.

Experiments with primary cultures of isolated porcine thyroid follicles were performed in serum-free well-defined medium to investigate different pathways that may be involved in the regulation of thyroid cell growth. The incorporation of [3H]thymidine into DNA within 72 h was about 25-fold with fetal calf serum (FCS, 1%), 20-fold with epidermal growth factor (EGF, 1 ng/ml) and 3.5-fold with insulin (10 micrograms/ml) as compared to controls. Bovine TSH significantly reduced the basal and insulin-induced growth rate at concentrations of 10(-6) to 10(-4) U/ml and 10(-4) U/ml, respectively. Forskolin stimulated cyclic AMP accumulation in thyroid cells and significantly reduced FCS-, EGF- or insulin-induced growth. In contrast, a 2- to 7-fold increase in FCS-, insulin- or EGF-induced growth rate was found, when cyclic AMP formation was inhibited by 2',5'-dideoxyadenosine (DDA). Iodide was stimulatory at low concentrations (1 microM) and inhibitory at higher concentrations (40-80 microM) on FCS-induced growth rate. The inhibitory effect of iodide was blocked by propylthiouracil (PTU), indicating that an iodinated compound is responsible for this effect. Indomethacin, a cyclooxygenase inhibitor, did not inhibit EGF- and insulin-induced growth up to a concentration of 100 microM. However, nordihydroguaiaretic acid (NDGA) and BW-755C, which are lipoxygenase inhibitors, strongly inhibited the growth of thyroid cells at micromolar concentrations. These data clearly show that (1) bovine TSH is not a growth factor for isolated thyroid cells in vitro, (2) thyroid cell proliferation, induced by FCS, EGF and insulin is under negative control of cyclic AMP. (3) Iodide controls dose-dependently thyroid cell growth by iodinated metabolites, probably modulating 2 different pathways: (a) at low iodide concentrations, an iodinated compound enhances the growth rate by inhibition of cyclic AMP formation, and (b) at high concentrations, iodide diminishes the growth rate by inhibiting the response to growth factors. (4) Metabolite(s) of lipoxygenase appear to be involved in intracellular signal transduction evoked by growth factors in thyroid cells.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Preparation of porcine thyroid follicles with preserved polarity: functional and morphological properties in comparison to inside-out follicles.

One of the main problems in establishing isolated thyroid follicles in vitro is their tendency to form inside-out follicles. The reason for this change in polarity is unknown. We describe here a method for the preparation of stable thyroid follicles with preserved polarity for at least 6 days. Isolated follicles were obtained by infusion of collagenase (1.5 mg/ml) dissolved in minimal essential medium into the artery of intact thyroid glands. The morphological and functional properties of these follicles were compared to inside-out follicles. These inside-out follicles were obtained by digestion of minced thyroid tissue in a collagenase (1 mg/ml) solution. The polarity of follicles was proved by morphological criteria. Follicles with preserved polarity did not change polarity for at least 6 days in the presence of 1% or 5% fetal calf serum. As the culture conditions for both preparation methods were identical, we conclude that the preparation method rather than the culture condition is responsible for the preservation of cell polarity of isolated thyroid follicles in our system. Increases in cyclic AMP levels induced either by bovine thyrotropin (10(-3) U/ml) or by isoproterenol (10(-6) M) as well as iodide uptake and organification were rapid and significant in right-side-right follicles but not in inside-out follicles. Therefore the TSH receptor and the beta-adrenergic receptor appear to be exclusively located at the basal membrane of follicular cells. In addition, iodide uptake apparently is unidirectional.

Animals↗
PubMed1985

Advantages of sensitive assays for thyrotropin in the diagnosis of thyroid disorders.

Using two new immunoradiometric assays for thyrotropin, we measured thyrotropin levels in serum of patients suffering from various clinically and biochemically diagnosed thyroid disorders, and in healthy controls. A thyroliberin stimulation test was performed in all patients and controls. Thyrotropin levels were measured using a solid phase IRMA in 339 patients and a coated tube sandwich assay in 152 patients. The lower limits of detection of 0.1 mU/1 (solid phase IRMA) and 0.02 mU/1 (coated tube sandwich assay) as well as the specificity of these two assays were superior to those of conventional thyrotropin assays. Basal thyrotropin values were clearly different between euthyroid controls and patients non responding to thyroliberin stimulation. However, the values for these two groups overlapped those for patients showing a subnormal increase upon stimulation with thyroliberin. The thyroliberin stimulation test in patients with autonomous adenomas, together with the measurement of thyrotropin using these sensitive assays, provides additional information in the low range below 1.0 mU/1,i.e. below the lower limit of detection of conventional double antibody radioimmunoassays.

Adenoma↗
PubMed1985

Characterization of microheterogeneity of human thyroglobulin from different thyroid disorders.

Human thyroglobulin (Tg) was isolated to apparent purity from various thyroid tissue samples obtained after surgery. Iodine and iodothyronine content of Tg was determined. Isoelectric focussing (IEF) was performed on thin layer agarose gels. Tg revealed a microheterogeneity of 6 bands in the range between pH 4.2 and 4.6. The intensity of the single bands depended on the iodothyronine content of Tg. With increasing degree of iodination, the bands with a lower pI (pI 4.35, 4.40) became more prominent, whereas the bands with higher pI (pI 4.55, 4.60) diminished. This typical change in microheterogeneity pattern could be confirmed by kinetic in vitro iodination and consecutive iodothyronine formation of low iodinated Tg (0.05% iodine). After in vitro desialylation, the bands shifted to a higher pH range (pH 4.60 to pH 4.90), but no reduction of the number of bands occurred. Even in desialylated Tg microheterogeneity is still dependent on iodine content. These results suggest, that the microheterogeneity of Tg is influenced, but not caused by different iodine and NANA content. Different polypeptide composition may be responsible for the microheterogeneity of Tg. In thyroid diseases without disturbance in Tg synthesis (endemic, diffuse and nodular goitre, Graves' disease) variations in relative intensity of single bands could be related to differences in iodine content. In thyroid cyst fluid and cold nodules in addition to low iodinated Tg, further bands were found with pI-values comparable to desialylated Tg.

Adenoma↗
PubMed1985

Detection of thyroid disorders by use of basal thyrotropin values determined with an optimized "sandwich" enzyme immunoassay.

To measure the concentrations of thyrotropin (thyroid-stimulating hormone), we used the components of a commercially available two-step "sandwich" enzyme immunoassay (Enzymun-Test TSH, Boehringer Mannheim) based on the specific binding of the beta-subunit of thyrotropin by monoclonal antibodies coated on polystyrene tubes. By modifying the original assay protocol, we lowered the limit of detection to 0.18 milli-int. units/L, using a total incubation period of 22 h. With this modification we could differentiate between patients responsive to administration of thyroliberin (thyrotropin-releasing factor) and those who were non-responders, by measuring only the basal concentration of thyrotropin. Furthermore, we demonstrated a correlation between the basal concentration of thyrotropin and its increase after administration of thyroliberin (r = 0.77, n = 48).

Evaluation Studies as Topic↗
PubMed1985

[Methods and clinical evaluation of a new enzyme immunologic method for determination of thyroxin binding globulin (TBG) and T4/TBG quotient: a multicenter study].

A heterogeneous enzyme immunoassay for the determination of thyroxine binding globulin (TBG) was developed and assessed in clinical trials in 12 laboratories. The assay is based on the competition principle and employs plastic tubes coated with goat anti-TBG. CV's between 1.4-8.9% for intra-assay precision and 2.9-8.6% for inter-assay precision were found over the concentration range of 4-40 mg/l TBG. In comparative studies using highly purified TBG as standard, values with Enzymun-Test TBG were found to be on average 30% lower than those obtained by various TBG-RIAs. A broad-base study, to determine reference values, was carried out on a group of control persons 18 to 50 years old without previous history of thyroid disease. This study revealed a median of 14.33 mg/l TBG, with 95% of all values between 9.6 and 18.5 mg/l TBG. The median in women of 14.5 mg/l TBG was significantly higher than in men (13.4 mg/l TBG). TBG values in hyperthyroid patients were within the reference range while those in hypothyroid individuals were elevated. Highly elevated TBG values were seen in women receiving oestrogen (median: 22.2 mg/l TBG) and in pregnant women (median: 28.5 mg/l TBG). The T4/TBG ratios made it possible to distinguish between euthyroid, hyperthyroid and hypothyroic subjects (median: 4.9, 11.3 and 1.0, respectively). These ratios were significantly lower in pregnant women (median: 3.1) than in the control persons.

Anticoagulants↗
PubMed1985

[Psychosocial counseling in pediatric practice--report of experiences].

The authors report on the activities of a female consultant with psychosocial orientation acting within the framework of a practising lady paediatrician's medical activities. The paediatrician refers patients or families to the social sciences consultant who studied paedagogics, sociology and psychology and who is so to say part of the paediatric consultation work. This amounts to an approach to an integrated type of treatment. It is an attempt to extend the old therapeutic concept of "disease", which has been mainly directed at cure and at treating the human organism, via practical interaction between various fields of human activity. Paediatric medicine lends itself quite easily to such an approach on the basis of experience collected in the course of time. The authors give a systematised description of the consultant practice, showing the boundary-lines of competencies. A few practical cases are outlined. The authors consider this set-up as an attempt to effect structural improvements of general medical care.

Child↗
PubMed1984

[Is fractionation of serum bilirubin useless?].

The validity of fractionation of serum bilirubin into direct and indirect fractions for differentiation of haemolytic and hepatobiliary hyperbilirubinaemia was assessed in 20 patients with haemolysis and 72 patients with hepatobiliary diseases. The groups varied significantly regarding the ratio of direct and total bilirubin (0.45 +/- 0.24 vs. 0.58 +/- 0.18, P less than 0.005). Due to the frequency distribution between both groups in each patient there was an a-priori probability of haemolysis of 22% and of hepatobiliary disease of 78%. Fractionation increased the probability of correct diagnosis from 22% to 55% and from 78% to 91%. Exclusion of patients with a total bilirubin of more than 3 mg/dl (51 mumol/l) increased the probability from 26% to 80% and from 74% to 86%. Thus fractionation of serum bilirubin is a considerable gain for the diagnosis of haemolysis, particularly in relatively low total bilirubin. The more frequent hepatobiliary diseases can be better diagnosed using other laboratory methods. Thus fractionation is useful only when a hepatobiliary disease has been established as unlikely beforehand.

Anemia, Hemolytic↗