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Biomedical subjects

H Perrild

Publications and source records attributed to H Perrild.

At least 19 recordsLinked to original sources
PubMed1992

Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man.

To assess the regional changes in cerebral blood flow, 10 healthy volunteers were given 400 micrograms thyrotropin-releasing hormone iv in a double-blind, randomized, cross-over study. Regional cerebral blood flow was determined simultaneously in two slices of the brain, using a single photon emission computerized tomograph and inhalation of 133Xe. Thyrotropin-releasing hormone caused a significant mean increase of 3.7% (range -8.8-22.7) in blood flow in a region consistent with the left thalamus compared to placebo (3.2% decrease). In 25 other regions no significant change was detected. The thalamic region has previously been shown to be a region especially affected by thyrotropin-releasing hormone in animal studies. The thyrotropin-releasing hormone injection was followed by a minor rise in systemic blood pressure, but not a rise that could affect the cerebral blood flow. The effect of thyrotropin-releasing hormone on the regional cerebral blood flow in the thalamic region was much lower compared to changes found in sedated animals given a hundredfold higher dose of thyrotropin-releasing hormone.

Adult↗
PubMed1992

Intracellular pH regulation in human thyrocytes: evidence of both Na+/H+ exchange and Na(+)-dependent Cl-/HCO3- exchange.

The present study was undertaken to investigate the regulation of intracellular pH in human thyroid epithelial cells and to characterize the kinetics of the acid-extruding processes operating in the absence and presence of HCO3-, Na+ and Cl-. A dynamic technique of dual excitation microfluorimetry and the pH-sensitive fluorescent probe 2',7'-bis-(2-carboxyethyl)-5(and-6)-carboxyfluorescein was employed. The intracellular pH was 7.01 +/- 0.27 (n = 29) and 6.94 +/- 0.25 (n = 54) in the absence and presence of HCO3- respectively. Both in the absence and presence of HCO3-, the recovery from intracellular acid loads was not only due to an Na+/H+ exchange, but also to an Na(+)-dependent HCO3-/Cl- exchange. In alkaline conditions caused by NH4Cl pulsing, an HCO3-/Cl- exchange was also found. The cells in HCO3- responded with a wide range of maximal hydrogen efflux rates in experiments where cells were either pretreated with 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid or incubated with amiloride. The heterogeneity might be due to subpopulations of thyrocytes in different metabolic states or at different points in the cell cycle. It is concluded that recovery from intracellular acidification in human thyroid cells is due to both Na+/H+ exchange and Na(+)-dependent Cl-/HCO3- exchange even in nominally HCO3(-)-free conditions, and that recovery from intracellular alkalinization is due to a Cl-/HCO3- exchange which needs to be characterized further.

Bicarbonates↗
PubMed1991

The thyroid function and size in healthy man during 3 weeks treatment with beta-adrenoceptor-antagonists.

The influence of beta-adrenoceptor antagonists on serum TSH level (supersensitive method) and thyroid volume has not previously been studied. Thirty-two young non-smoking males were treated for 3 weeks with either atenolol 50 mg (b.i.d.), metoprolol 100 mg (b.i.d.) or propranolol 80 mg (b.i.d.) in a placebo controlled study. After 1 week, median serum TSH level increased in the atenolol (from 1.76 (range: 0.96-4.04) to 2.25 (range: 1.11-4.22) mU/l, P less than 0.05) and propranolol (from 1.91 (range: 0.90-3.83) to 2.44 (range: 0.75-6.30) mU/l, P less than 0.05) treated groups. After 3 weeks, median serum TSH reached pretreatment level in the atenolol treated, whereas median serum TSH decreased compared to pretreatment values in the propranolol treated (1.68 (range: 0.68-3.62) mU/l, P less than 0.05). Except for a slight increase in the atenolol treated group, no changes in median thyroid volume was seen after 3 weeks. The changes in serum TSH or thyroid volume were not related to changes in the concentrations of thyroid hormones, or of a magnitude likely to interfere with the clinical evaluation of thyroid function.

Adrenergic beta-Antagonists↗
PubMed1991

Serum bone Gla protein (BGP) during treatment of hyperthyroidism and hypothyroidism. A longitudinal study.

Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (BGP) was measured before and with initially 2 weeks, later 4-8 weeks intervals for 20-58 weeks during treatment of patients with hyperthyroidism (n = 10) and hypothyroidism (n = 4). Biochemical euthyroidism was obtained in the hyperthyroid patients after a median of 3 weeks (range 1-8 weeks), and in the hypothyroid patients after a median of 17 weeks (range 10-27 weeks). Serum BGP levels closely followed the thyroid state, being high respectively low in the hyperthyroid and hypothyroid state and reaching a stable plateau just at the time biochemical euthyroidism was obtained. These data suggest that osteoblastic activity is enhanced in hyperthyroidism and reduced in hypothyroidism, and that normalization occurs in close conjunction with the normalization of the thyroid state, without any delay, indicating a direct effect on the function of the excisting osteoblasts by the thyroid hormones.

Aged↗
PubMed1991

Acupuncture in the treatment of Graves' ophthalmopathy. A blinded randomized study.

Seventeen patients with Graves' ophthalmopathy, all euthyroid for at least one year, were included in a blinded trial to test the effect of acupuncture twice a week during two months on the eye disease, assessed by an ophthalmologist and computed tomography of the eye muscle volume. No significant change was found in eye muscle volume, Hertel measure, palpebral aperture, intraocular pressure, Hess chart, nor was there any statistically significant improvement of the irritative conjunctival symptoms.

Acupuncture Therapy↗
PubMed1991

Influence of interleukin 6 on the function of secondary cultures of human thyrocytes.

Interleukin 6 has been suggested as second mediator of the effects of interleukin 1 in some cell systems. Interleukin 1 has previously been shown to inhibit the function of human thyrocytes in secondary cultures. We have therefore studied the influence of interleukin 6 (10(-1)-5.10(7) U/l) on the function of thyroid cells. Recombinant interleukin 6 slightly inhibited the production of cAMP, but failed to influence the production of thyroglobulin or the DNA content. Endotoxins (lipopolysaccharides from Salmonella abortus equi or Yersinia enterocolitica) had only a slightly inhibitory effect on thyroid cell functions, and the effect of interleukin 6 could not by itself be explained by endotoxin contamination. The effect of interleukin 6 did not mimic effects on thyroid cells afforded by recombinant interleukin 1 alpha and 1 beta. Furthermore, antibodies to interleukin 6 were not able to inhibit the interleukin 1 beta-induced inhibition of thyroid cell functions. In conclusion, it is unlikely that interleukin 6 by itself mediates the biological effects of interleukin 1 on human thyroid cells.

Antibodies↗
PubMed1990

Acute beta-blockade changes the extracellular distribution of thyroid hormones.

The acute (within hours) changes in the concentrations of T4, T3, reverse-T3 (rT3) and T3 resin uptake test (T3RU) were studied in 31 hyperthyroid patients for 4 h after po treatment with either acebutolol, oxprenolol, pindolol or timolol. In 21 of the patients, the changes were compared to changes in the serum concentrations of alpha 2-macroglobulin (a macromolecule) and two middle-sized molecules; thyroid hormone-binding globulin (TBG) and albumin in order to calculate the changes in extracellular distribution of the thyroid hormones and to distinguish between changes due to a changed metabolism and changes due to a changed distribution of the thyroid hormones. Acebutolol, oxprenolol and timolol caused a decrease in serum T3 after 1/2 h, and acebutolol and oxprenolol also a decrease in rT3 after 1/2 - 1 h, the changes reversed within 2 h. A concomitant decrease in serum albumin and TBG suggests a change in the extracellular distribution of middle-sized molecules to which thyroid hormones are attached, as an explanation of the acute decrease (1 h) of the thyroid hormones. The small and insignificant change in alpha 2-macroglobulin indicates that the changes are mainly extravascular, but the difference of alpha 2-macroglobulin changes between the drugs (acebutolol/timolol vs pindolol/oxprenolol) could depend on the intrinsic sympathomimetic activity of the drugs.

Acebutolol↗
PubMed1990

Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment.

Thyroid function was investigated in 100 manic-depressive patients. Goiter was more common in patients treated with lithium for 1-5 years (44%) or more than 10 years (50%) than in patients who never received lithium (16%). Smoking contributed significantly to thyroid size and goiter. In nonsmoking patients, ultrasonically determined thyroid volume was significantly related to treatment duration. The mechanism behind this increased thyroid volume is unclear, as most patients had normal serum thyrotropin levels and no thyroid autoimmunity. Subclinical or overt hypothyroidism was found in 4% and 21% of patients treated for 1-5 and more than 10 years, respectively. Since few hypothyroid patients had autoimmunity or goiter, lithium may affect the thyroid gland directly.

Adult↗
PubMed1990

Bone Gla protein and sex hormone-binding globulin in nontoxic goiter: parameters for metabolic status at the tissue level.

Several patients with nontoxic goiter have reduced serum TSH levels, as measured with new sensitive assays. Whether this is a sign of subclinical hyperthyroidism, thus having the potential of adverse effects on different organs with time, is not known. We have measured serum levels of 2 markers of thyrometabolic status at the tissue level, bone gamma-carboxyglutamic acid-containing protein (BGP), reflecting the function of osteoblasts, and sex hormone-binding globulin (SHBG), reflecting the function of hepatocytes, in 44 patients (41 women and 3 men) with nontoxic goiter (11 diffuse and 33 nodular goiters; serum T4, T3, free T4, and free T3 levels had been normal and stable for at least 0.5 yr). Serum TSH levels ranged from normal to unmeasurably low values (less than 0.05 mU/L). Serum TSH levels correlated negatively to serum BGP levels (r = -0.60; P less than 0.001). Due to the postmenopausal surge in serum BGP levels, premenopausal women (n = 21) were tested separately without changing the significance (r = -0.53; P less than 0.02). Expressing serum BGP values as a percentage of the mean value in control subjects of the same age and sex did not change the correlation (r = -0.63; P less than 0.001). Six patients had serum BGP levels above the normal range, and patients with reduced serum TSH levels (less than 0.45 mU/L; n = 12) had significantly enhanced serum BGP levels [median, 1.53 nmol/L (range, 1.02-4.24) vs. 1.23 nmol/L (0.62-3.71); P less than 0.05]. Serum TSH also correlated negatively to serum SHBG levels (r = -0.56; P less than 0.001; women alone: r = -0.58; P less than 0.001). Eight patients had serum SHBG levels above the normal range, and patients with reduced serum TSH levels had significantly enhanced serum SHBG levels, expressed as a percentage of the mean control value for the relevant sex [203% (range, 75-288) vs. 120% (42-317); P less than 0.01]. It is concluded that the lower serum TSH levels in patients with nontoxic goiter, the higher are serum BGP and SHBG levels. This suggests a progressively generalized (not only pituitary) tissue overexposure to thyroid hormones, the lower the serum TSH levels. Therefore, the finding of a reduced serum TSH level in patients with nontoxic goiter might reflect supraphysiological levels of T4 and/or T3, which could possibly be harmful.

Adult↗
PubMed1990

Different effects of thyroid disease on serum levels of procollagen III N-peptide and hyaluronic acid.

Serum levels of procollagen III N-peptide (PIIINP) and hyaluronic acid (HA) reflect secretion of procollagen III and HA from fibroblasts, a cell type sensitive to thyroid hormones. Serum PIIINP and HA concentrations were measured in different thyroid function states, the former by two different assays, one detecting intact and aggregated PIIINP (PIIINP assay) and another detecting low mol wt degradation products of PIIINP as well (Fab-PIIINP assay). Two thirds of 28 hyperthyroid patients had elevated serum PIIINP values (mean, 192% in the PIIINP assay and 243% in the Fab-PIIINP assay) compared to age- and sex-matched controls (P less than 0.001). Normalization was seen after medical treatment (n = 16). In contrast, serum HA levels increased from 49 +/- 30 to 68 +/- 37 ng/mL (P less than 0.01) when a euthyroid state was achieved. Hypothyroid patients (n = 23) had increased serum HA levels (mean, 162%; P less than 0.05), which normalized after L-T4 treatment (71 +/- 50 before and 41 +/- 20 ng/mL after treatment (n = 16; P less than 0.02). L-T4 treatment also increased serum PIIINP levels significantly. Subjects with familial dysalbuminemic hyperthyroxinemia (n = 8), representing a situation with elevated circulating levels of T4 due to enhanced protein binding, and patients with nontoxic goiter with serum TSH levels ranging from 3.6-0.05 mU/L had normal serum levels of PIIINP and HA. Our data suggest that the secretion of procollagen III and that of HA from fibroblasts are influenced differently by thyroid hormones, since the secretion of procollagen III seems enhanced by thyroid hormones, whereas the secretion of HA seems reduced. Neither euthyroidism with enhanced serum T4 levels (familial dysalbuminemic hyperthyroxinemia) nor euthyroidism with reduced serum TSH levels (nontoxic goiter) seems associated with alterations at the connective tissue level.

Adolescent↗
PubMed1990

Differential effects of interleukin 1 alpha and 1 beta on cultured human and rat thyroid epithelial cells.

The effects of human recombinant interleukin 1 alpha (20 pg/1-2 micrograms/l) and 1 beta (200 pg/1-20 micrograms/l) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1 beta (20 ng/1-20 micrograms/l), but not by interleukin 1 alpha. None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.

Animals↗
PubMed1989

Acute in vitro thyrotropin regulation of lysosomal enzyme activity in the thyroid follicular cell.

The acute effect of a physiological concentration (1 mU/l) of thyrotropin (TSH) on the activity of four lysosomal enzymes in the thyroid follicular lining cell has been studied by quantitative cytochemical techniques. N-acetyl-beta-glucosaminidase (NAG) activity was increased by 14% after 10 min TSH stimulation and NAG and beta-galactosidase activities were increased by 24% and 25% respectively (P less than 0.05) after 20 min stimulation and by 40% and 45% (P less than 0.05) respectively after 30 min stimulation with TSH, indicating an early processing of these carbohydrate residues in thyroglobulin. Acid phosphatase activity, an acid hydrolase unrelated to the hydrolysis of thyroglobulin, was unchanged 30 min after TSH stimulation. Leucyl-beta-naphthylaminidase (LNA) activity changed biphasically with peak activities of 7 and 25 min possibly representing an early fusion of endocytotic vesicles and lysosomes and later the release process of the thyroid hormones. The changes in LNA activity and thus membrane permeability were not reflected in the other enzyme activities studied. This may indicate that the TSH regulation of lysosomal enzyme activities could be independent to the endocytotic process, which is known to involve fusion of lysosomes and endocytotic vesicles. In conclusion we have demonstrated for the first time with physiological concentrations of TSH a specific acute regulation of some lysosomal enzyme activities which may be involved in thyroglobulin processing. Further, these effects may be independent of the changes in lysosomal membrane permeability due to formation of secondary lysosomes.

Acetylglucosaminidase↗
PubMed1989

Differential effect of continuous administration of beta-adrenoceptor antagonists on antipyrine and phenytoin clearance.

1. Antipyrine (1000 mg orally) clearance was studied 3 days before treatment with either atenolol (50 mg twice daily), metoprolol (100 mg twice daily), propranolol (80 mg twice daily) or placebo, and at day 5 and 18 during treatment. Phenytoin (100 mg intravenously) clearance was measured on days 0, 7 and 21 during treatment. 2. Antipyrine clearance was decreased by about 20% after 5 days of treatment with either propranolol or atenolol and this decrease persisted after 18 days of treatment. Antipyrine clearance did not change during treatment with either metoprolol or placebo. Phenytoin clearance did not change during any of the treatments.

Adrenergic beta-Antagonists↗
PubMed1989

Changes in serum phosphate during beta-blockade in healthy men are not due to changes in the renal handling of phosphate.

Serum parathyroid hormone (PTH), phosphate, ionized calcium, magnesium, alkaline phosphatase and creatinine and the urinary excretion of phosphate and creatinine were studied after 1 and 3 weeks beta-blockade in 32 young healthy men given either atenolol at 50 mg, metoprolol at 100 mg, propranolol at 80 mg or placebo twice a day. After 1 week treatment serum phosphate (mean (range] increased in the propranolol-treated subjects (1.17 (0.99-1.30) to 1.32 (1.08-1.71) mmol l-1 (P = 0.03), minor changes were found in the atenolol and the metoprolol-treated subjects but not in the placebo group. Serum phosphate was unchanged compared to pretreatment values after 3 weeks. Renal clearance and urinary excretion of phosphate and creatinine was unchanged after both 1 and 3-weeks treatment. Serum PTH, ionized calcium, magnesium and alkaline phosphatase were unchanged in all groups, whereas serum urate and creatinine increased in the metoprolol-treated subjects after both 1 and 3 weeks.

Adult↗
PubMed1989

Characterization of the natural killer cell activity in Hashimoto's and Graves' diseases.

Natural killer (NK) cell activity and blood mononuclear cell subpopulations were characterized in patients with Hashimoto's thyroiditis (n = 11), Graves' disease (n = 20), non-toxic goitre (n = 10) and in normal controls (n = 22). NK cell activity against K 562 target cells and the capability of IFN-alpha, Il-2, and indomethacin to enhance NK cell activity in vitro did not differ significantly between the groups. The percentages of large granular lymphocytes, CD5+, CD4+, CD8+ and CD16+ cells were normal in patients with non-toxic goitre, Hashimoto's and Graves' diseases. There was no correlation between NK cell activities and TgAb, MAb and TSAb. Although NK cell activity is suppressed in several autoimmune diseases, NK cell function is normal in patients with autoimmune thyroid disorders.

Adult↗
PubMed1989

Parkinson's disease and autoimmunity.

Sera from 22 patients with Parkinson's disease were tested for autoantibodies in 11 different assays, including a test for autoantibodies directed against determinants in the pituitary gland. All patients were tested twice with a 12-month interval between tests. No pituitary autoantibodies were detected. The other autoantibodies investigated were found in low frequencies and in low titers. Our data supports the view that the pathogenesis of Parkinson's disease is not autoimmune.

Adult↗
PubMed1989

Suppressed natural killer cell activity in patients with euthyroid Graves' ophthalmopathy.

The purpose of the present study was to determine whether patients with euthyroid Graves' exophthalmopathy have an impaired NK cell function compared to patients with Graves' hyperthyroidism and healthy controls. The NK cell activity measured against K562 target cells was significantly suppressed (p less than 0.01) in patients with euthyroid Graves' ophthalmopathy, whereas the NK cell activity of patients with Graves' hyperthyroidism was not. Although interferon-alpha, interleukin-2 and indomethacin significantly enhanced (p less than 0.01) the NK cell activity in all three groups, none of these agents fully restored the defective NK cell activity in euthyroid Graves' ophthalmopathy. The concentrations in the blood of large granular lymphocytes and CD16 positive cells did not differ between the three groups, furthermore an immunosuppressive serum factor was not detected. The number of effector/target cell conjugates did not differ between patients and controls, whereas the interferon-alpha induced production of a soluble natural killer cytotoxic factor (NKCF) with specificity for NK sensitive target cells was suppressed in patients with Graves' euthyroid ophthalmopathy. We conclude that one of the mechanisms underlying the defective NK cell activity in patients with euthyroid ophthalmopathy may be an impairment of the release of NKCF from the NK cells.

Adolescent↗