PubMed Health⌕ Search

Biomedical subjects

L Kayser

Publications and source records attributed to L Kayser.

At least 37 records · Page 2Linked to original sources
PubMed1993

Multivesicular bodies in HEp-2 cells are maturing endosomes.

Conventional fluorescence microscopy of fixed HEp-2 cells as well as video microscopy of living cells incubated with transferrin-Texas Red (Tf-TxR) for < 60 min revealed distinct punctuate endosomal structures. Quantitative ultrastructural analysis using horseradish peroxidase (HRP) and cationized gold as tracers showed that spherical multivesicular bodies (MVBs) were the predominant endocytic compartments in HEp-2 cells and that MVBs within 60 to 90 min matured into lysosomes still containing internal vesicles. The number of labeled MVBs increased continuously from 2.5 min to 30 min of tracer incubation. However, when the cells were pulsed for 5 min followed by 10 or 25 min chases, the number of labeled MVBs corresponded to that obtained after 5 min of continuous incubation. The diameter of labeled MVBs was largely constant with time, but the number of internal MVB vesicles increased. Thus, early or newly formed MVBs contained few internal vesicles, whereas late MVBs, that is to say, MVBs that have existed for some period of time, contained numerous internal vesicles, and finally a mixture of membranous material or myelin figures and vesicles. It is thus in principle possible to distinguish between early and late MVBs in HEp-2 cells on the basis of morphology. However, the difference in number of internal vesicles applies only to the entire MVB population; after only 2.5 to 5 min of incubation, MVBs with numerous internal vesicles could also be reached by internalized tracer. Concomitant with the gradual changes in morphology, the MVBs also showed a characteristic change in content of marker proteins as detected by immunogold labeling on ultracryosections. Hence, early MVBs with relatively few internal vesicles and typically reached by internalized tracers within 5 min contained transferrin receptors (TfRs). By contrast, MVBs with many internal vesicles and labeled after 60 min of incubation contained mannose-phosphate receptors (MPRs), and the MVBs with distinct membranous material or myelin figures in addition to the internal vesicles were enriched in the lysosome membrane protein lamp-1. Thus, there seems to be a gradual maturation of MVBs in HEp-2 cells.

Carcinoma, Squamous Cell↗
PubMed1992

Effects of human anti-IL-1 alpha autoantibodies on receptor binding and biological activities of IL-1.

Immunoglobulin G (IgG) antibodies to interleukin 1 alpha (IL-1 alpha) are frequently found in the sera of healthy human individuals. The effects of these autoantibodies on receptor binding and biological activities of human IL-1 were tested. Using the murine T-lymphocyte line NOB-1, human thyrocytes and human foreskin fibroblasts, the antibodies competitively inhibited the biological activity of human recombinant IL-1 alpha (rIL-1 alpha). The degree of inhibition correlated with 125I-rIL-1 alpha binding to IgG in different immunoglobulin preparations and in individual sera. These antibodies also neutralized the IL-1 activity of isolated membrane fragments and lysates of human blood monocytes activated by lipopolysaccharide. In contrast, the supernatant IL-1 activity was not affected. Stronger inhibition of biological activity and cell binding of 125I-rIL-1 alpha was obtained with NOB-1 cells than with human thyrocytes. The antibodies failed to interfere with the biological activity of rIL-1 beta. It is concluded that IgG autoantibodies of IL-1 alpha in the sera of healthy humans selectively inhibit the biological activity of the soluble and membrane-associated forms of IL-1 alpha in vitro, and that the degree of biological inhibition afforded by these antibodies depends upon the target cell.

Animals↗
PubMed1992

A substantial part of GLUT-1 in crude membranes from muscle originates from perineurial sheaths.

The distribution of GLUT-1 and GLUT-4 in cryosections of rat skeletal muscles was investigated immunocytochemically. Intense labeling of GLUT-1 was found in the perineurial sheaths of intramuscular nerves, whereas only a very faint signal was associated with the sarcolemma, and labeling of extraneural vessels was not detectable. The majority of the GLUT-4 reactivity was located at the periphery of muscle cells in nonuniform patches, and GLUT-4 was absent in vessels and nerves. In sections of femoral nerve GLUT-1 was confined to the perineurial sheath and endoneurial vessels. The contribution of GLUT-1 from intramuscular perineurial sheaths to total GLUT-1 in a muscle was determined from immunoblots of crude membranes isolated from mixtures of homogenates of excised nerves and muscles. The recovery of GLUT-1 increased linearly with the amount of nerve added, and it was calculated that GLUT-1 from intramuscular perineurial sheaths accounted for approximately 60% of the GLUT-1 content in a membrane fraction from soleus muscle or red gastrocnemius. The remaining 40% of GLUT-1 is likely to originate from the sarcolemma.

Animals↗
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

[Occurrence of hypophosphatemia in a Danish hospital population].

Hypophosphataemia is a potentially dangerous condition which may be present but unrecognized in prolonged periods. The incidence of hypophosphataemia among patients in a Danish hospital population was determined retrospectively by registering the number of blood samples with low serum phosphate values (less than or equal to 0.6 mmol l/l) in a Danish university hospital during a period without and in a period with an open casualty department. Case reports from patients with low serum phosphate values were reviewed with the object of revealing the causes of the hypophosphataemia and possible symptoms which might be related to the hypophosphataemic condition. A total of 192 patients were found with serum phosphate values less than or equal to 0.6 mmol/l but only 15 patients with severe hypophosphataemia (serum phosphate less than or equal to 0.3 mmol/l). No relationship between the serum phosphate concentration and the symptoms could be demonstrated. The commonest causes of hypophosphataemia were gastrointestinal loss and parenteral infusion of fluids. Quoting of low serum phosphate measurement is not recommended unless this analysis has been specially requested as the majority of cases even of severe hypophosphataemia are self-limiting and do not produce symptoms.

Denmark↗
PubMed1991

Quantitative cytochemical demonstration of intracellular thyroglobulin in cultured human thyrocytes. Effects of fixatives, TSH and interleukin-1 beta.

A quantitative immunocytochemical method is described for measuring intracellular thyroglobulin in human thyrocytes grown in monolayer, based on the imidazole-enhanced 3,3'-diaminobenzidine/peroxidase reaction. The influence of ten different fixatives on the content of thyroglobulin immobilized on nitrocellulose filters and in single cells and the influence of thyrotropin and interleukin-1 beta (IL-1 beta) on the amount of intracellular thyroglobulin were evaluated. The most suitable fixatives for single cells were 2% carbodiimide, Lison's 'Gendre fluid' and 2 or 4% paraformaldehyde, whereas Bouin, Carnoy A and B, formalin-calcium and Lillie's formaldehyde-acetic acid-alcohol fixative all resulted in reduction of intracellular thyroglobulin. Two per cent glutaraldehyde caused a considerable reduction (p less than 0.0001). Nitrocellulose filters were not suitable for evaluation of the fixatives, since the results did not correspond to those obtained with single cells. Thyrotropin (1 U/l) increased intracellular thyroglobulin, whereas addition of interleukin-1 beta to the culture medium for three days caused a dose-dependent reduction with a plateau level at 2 x 10(-6) gl-1 (10(4) U/l) of interleukin-1 beta. It is concluded that changes in intracellular thyroglobulin concentration caused by either thyrotropin or IL-1 beta can be quantified under experimental circumstances where samples for measurements of thyroglobulin-mRNA or extracellular thyroglobulin are difficult or impossible to obtain.

Cells, Cultured↗
PubMed1991

Interleukin-1 receptors on human thyroid cells and on the rat thyroid cell line FRTL-5.

Cellular binding of interleukin-1 (IL-1) was tested on monolayers of human thyrocytes in secondary culture, on long-term cultures of human thyrocytes, and on the rat thyroid cell line FRTL-5. The human thyrocytes in secondary culture showed specific binding of human 125I-rIL-1 alpha. Scatchard plots of data obtained at 4 degrees C indicated the presence of a single population of receptors with a Kd of 30 to 170 pM and 2,000 to 6,000 receptors per cell. Incubation at room temperature resulted in internalization of the receptor-ligand complex. Parallel experiments were performed with the IL-1 receptor-positive murine T-cell lines EL-4 and NOB-1. The IL-1 receptors on these cells had Kd values one fifth to one tenth those on human thyroid cells in secondary culture. Both rIL-1 alpha and rIL-1 beta inhibited 125I-rIL-1 alpha binding to human thyrocytes and the murine T cells. In contrast to the cells in secondary culture, there was no specific binding of 125I-rIL-1 alpha to long-term cultivated human thyroid cells or to the FRTL-5 cells. We concluded that recently described differences in the response to IL-1 of different thyroid cell culture systems are most likely caused by differences in expression of IL-1 receptors.

Animals↗
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

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↗
PubMed1991

Interleukin-6 production by thyroid epithelial cells. Enhancement by interleukin-1.

Interleukin-1 is a potent inhibitor of thyroglobulin and cAMP production in human thyroid cells and the inhibitory effect is enhanced by tumor necrosis factor-alpha and interferon-gamma. In the present study secondary cultures of human thyroid cells produced interleukin-6 and the production was significantly increased after exposure of the cells to recombinant interleukin-1 alpha and -1 beta. This increase was dose-dependent and concomitant of the IL-1 induced decrease in cAMP and thyroglobulin production. Both tumor necrosis factor-alpha and -beta also augmented interleukin-6 production, but less potently than interleukin-1. Interferon-gamma did not affect the production of interleukin-6. The rat thyroid cell line FRTL-5 produced interleukin-6 spontaneously, and the production was enhanced after addition of recombinant interleukin-1 beta. A pathogenetic role of interleukin-6 in autoimmune thyroid disease is suggested.

Animals↗
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

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

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↗
PubMed1988

Three-week beta-adrenergic blockade does not impair or improve general intellectual function in young healthy males.

The widespread use of beta blockers in treatment of both cardiovascular and nonvascular conditions has generated interest in changes in functions of the central nervous system during treatment. We studied the effect of 3 weeks of beta blockade on learning and memory ability, concentration, and verbal abstraction in 32 young normotensive healthy men. We chose healthy males to exclude the possible influence of changes related to a hypertensive state. Subjects were randomized into a 3-week treatment protocol with either atenolol 50 mg X 2 (cardioselective, hydrophilic), metoprolol 100 mg X 2 (cardioselective, lipophilic), propranolol 80 mg X 2 (noncardioselective, lipophilic), or placebo X 2. Each subject underwent two neuropsychological testing sessions. We found no significant enhancement or impairment of intellectual or psychomotor performances after the 3-week treatment with beta-adrenergic-blocking agents compared to a placebo-treated control group. Differences in pharmacokinetic profiles of the drugs (e.g., central nervous system penetrability, lipophilicity, or membrane-stabilizing effect) did not influence the test outcome. Antihypertensive treatment with beta blockers over a prolonged period does not affect young peoples' learning and memory abilities or reasoning powers, nor their ability to concentrate and perform psychometric tasks.

Adrenergic beta-Antagonists↗
PubMed1987

Serum phosphate increase during short-term beta-adrenoceptor blockade in thyrotoxicosis.

We studied the changes in blood plasma electrolytes during acute and short-term treatment with four different beta-adrenergic-blocking agents in 31 patients with hyperthyroidism. Serum phosphate increased during the first four hours and remained elevated after one week both after cardioselective (acebutolol) and non-cardioselective (oxprenolol, pindolol and timolol) beta-blockade (p less than 0.05). Albumin decreased after four hours but no change was found after one week. Serum creatinine increased after one week in the acebutolol-treated group, while sodium, potassium and albumin-corrected calcium in serum did not change. The hyperphosphatemic effect may be due to blockade of beta 1-adrenoceptors, since the effect of the cardioselective acebutolol was no less than that of the non-cardioselective beta-adrenoceptor blockers.

Acebutolol↗