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Biomedical subjects

W Greil

Publications and source records attributed to W Greil.

At least 37 records · Page 2Linked to original sources

Further evidence for the presence of thyroxine binding globulin-like protein in human breast adipose tissue. Deiodination of thyroxine and triiodothyronine by the microsomal fraction.

The object of the study was to obtain information on how adipose tissue of normal subjects processes thyroid hormones. L-125I-thyroxine(125I-T4) is bound by the cytosol fraction of normal human female breast adipose tissue with high affinity. Computer analysis of the binding data revealed the presence of two saturable systems with Kd values of 3.9 and 29.1 nM and binding capacities of 1.7 and 8.7 pmol/mg of cytosol protein, respectively; a third binding system was non-saturable. The binding of the iodothyronines to the cytosol fraction indicated that L-triiodothyronine (T3) possessed two-fold higher affinity as compared to L-thyroxine (T4) whereas other iodothyronines had relative affinities of less than 3%. Binding of 125I-T4 was optimal at pH 7.0 and was sensitive to the action of pronase and neuraminidase. Affinity chromatography of the cytosol fraction using T3-epoxy-sepharose 6B and con A-sepharose 4B, yielded a 125I-T4 binding component that was purified 150-fold. Isoelectric focusing of the purified fraction yielded six major brands of protein which had pI values comparable to those of human serum thyroxine-binding-globulin (TBG); however, the pattern of separation was different. Incubation of the fraction with 125I-T4 followed by isoelectric focusing and autoradiography revealed that the protein bands bound radioactivity. The microsomal fraction of the adipose tissue deiodinated 125I-T4 to L-125I-triiodothyronine (125I-T3) to an extent of 0-0.8 fmol/(mg of protein X min) which corresponded to about 0.2%; T4 was not deiodinated to L-3,3',5'-triiodothyronine (r-T3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Lithium dosage in the elderly. A study with matched age groups.

Lithium dosage was examined in 3 age groups (less than or equal to 45 years, 46-64 years, greater than or equal to 65 years) of 78 inpatients, matched on relevant variables. Although mean steady-state lithium plasma levels showed no essential differences, mean daily lithium doses were significantly lower in the elderly. The ratio of weight-related lithium dose to plasma level showed a 36% decline with age (0.58, 0.46 and 0.37 1/kg, P less than 0.0001, analysis of variance). Comparing different decades this ratio, indicating the dose required for a certain plasma level, displayed a clear-cut decrease at 50 years. This may be caused by age-related changes in apparent volume of distribution and/or in elimination half-life of lithium, the latter being the consequence of age-related decrease of glomerular filtration rate.

Age Factors

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

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

Tiapride: effects on tardive dyskinesia and on prolactin plasma concentrations.

In a placebo-controlled double-blind crossover study of 21 patients chronically treated with neuroleptics and suffering from tardive dyskinesia, tiapride (600 mg/day, mean plasma level: 682 ng/ml) exhibited a transient efficacy during 12 weeks of treatment, most distinct in the 6th week (p less than 0.01). Tiapride induced an increase of prolactin plasma levels, on the average, from 1,195 to 2,179 microIU/ml (p less than 0.01). Tiapride was well tolerated. Increase of parkinsonism was only mild and not significant. The results underline the difficulty in treating tardive dyskinesia and, thus, confirm the importance of prevention.

Aged

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

[Additional treatment to lithium prophylaxis of affective psychoses (author's transl)].

Ten endogenous-depressive patients under lithium maintenance therapy participated in a group behaviour therapy program for the modification of behavioural problems that are typical for this group of patients. The problem intensity as measured individually through a "problem barometer" as well as the score on the Pt-scale of the MMPI were reduced significantly over the ten treatment sessions. Concurrently, patients' self image regarding depressive components and social resonance improved. The effects were still present after a 3-month follow-up period. It is concluded that in lithium treated patients behaviour therapy methods can be used in the modification of typical behaviour disorders.

Adult

Prepartation of soluble chromatin and specific chromatin fractions with restriction nucleases.

By digestion of rat liver nuclei with EndoR HaeIII, EndoR EcoRI, and EndoR Bam and subsequent lysis of the nuclei approx. 90%, 40%, and 45%, respectively, of the chromatin were solubilized. The plateau values of solubilization are in agreement with a model in which the chromatin strands are crosslinked and/or attached to a supporting structure. The distribution of DNA lengths in the soluble and insoluble chromatin fractions were determined. According to digestion experiments with restriction nucleases rat liver DNA contains highly repetitive sequences, some of which are arranged in tandem repeats of 95 and 380 nucleotide pairs, respectively. With EndoR EcoRI chromatin containing the repetitive RNA was preferentially solubilized and, by subsequent sucrose gradient centrifugation, purified to about 90%. The useful properties of chromatin prepared by the specific action of restriction nucleases are discussed.

Animals

Studies on the lithium transport across the red cell membrane. I. Li+ uphill transport by the Na+-dependent Li+ counter-transport system of human erythrocytes.

Li+ net-transfer across cell membranes was studied on human erythrocytes and ghosts preloaded with 1-2 mM Li+ and incubated in saline media of varying composition at initial thermodynamic equilibrium for Li+. The following results were obtained: 1. Li+ is extruded from glycolyzing erythrocytes against an electrochemical gradient until a steady-state Li+ distribution is established after 24-28 h. 2. The initial rate of Li+ extrusion is not altered by ouabain or by reduction of ATP levels to less than 25% of the normal value. 3. Replacement of external Na+ by K+ or choline+ abolishes the establishment of an electrochemical Li+ gradient. 4. The Li+ distribution ratio Lie+/Lii+ increases proportional to the ratio Nae+/Nai+ at constant extravellular K+ concentrations. 5. In ghost suspension an uphill Li+ transport is driven by an oppositely directed Na+ gradient. The direction of the Li+ uphill transport can be reversed by reversing the Na+ gradient. From the results it is concluded that the Li+ uphill transport across human red cell membranes is mediated by a Na+-dependent Li+ counter-transport system. This system is not inhibited by ouabain and does not appear to be identical to the Na+-Na+ exchange system described by Garrahan and Glynn.

Adenosine Triphosphate

Nuclease digestion in between and within nucleosomes.

In the course of digestions of rat liver nuclei with micrococcal nuclease the size of the nucleosomal DNA is shortened by 50-60 nucleotide pairs from starting lengths of about 200, 400, 600, 800, etc. nucleotide pairs in the monomeric and oligomeric nucleosomes, respectively. Acid soluble DNA material is created relatively slowly as compared to the rate of formation of subnucleosomal material. More DNA with lengths in between the 200, 400, etc. nucleotide pairs of nucleosomal DNA is formed when digestions with micrococcal nuclease are carried out at 0 to 10 degrees C compared to 40 degrees C. With DNAase II, on the other hand, formation of a 200 nucleotide pair pattern is favoured at the low temperatures. Apparently, the accessibility of potential cleavage sites in between and within nucleosomes depends strongly on the conditions of digestion. Possible reasons for this dependence are discussed.

Animals

[Direct quantitative measurement of tremor: first results of a new mesuring procedure in patients under lithium therapy].

The use of a new piezoresistive minature accelerometer as part of an electronic measurement system for the direct quantification of human finger tremor in physical units is described. The system was designed to yield digital values for the mean tremor amplitude in a given period of time. Reliability coefficients were computed for a smaple of 34 patients under lithium therapy. Coefficients ranged between 0.75 and 0.94 for test-retest intervals between 30 min and several days. Some of the usual indirect methods for the assessment of tremor showed very low correlations to the true tremor amplitude and seemed to be only of limited usefulness. It was further demonstrated that situational factors play a dominant role independently of the particular method of measurement.

Fingers

[The distribution of lithium between erythrocytes and plasma: in vitro studies on the transport of lithium in human erythrocytes].

Distribution ratiors of intracellular lithium (Lii) and extracellular Li (Lie) were determined in vitro after incubation of Li-free or Li-loaded red cells in media containing varying Li-concentrations (37 degrees C, pH 7.4). The distribution ratios Lii/Lie obtained in vitro after 24 h of incubation corresponded to those found in vivo. The results indicate that Li can be extruded from red cells against an electrochemical gradient. This Li extrusion is inhibited by replacing extracellular Na+ with K+ or choline+, but is not affected by ouabain or by glucose depletion.

Biological Transport, Active