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P Thomopoulos

Publications and source records attributed to P Thomopoulos.

At least 55 records · Page 3Linked to original sources
PubMed1984

Inhibition of transferring binding and iron uptake of hematopoietic cell lines by phorbol esters.

Phorbol esters inhibit cell growth and the binding of transferrin to receptors on K 562, HL 60 and U 937 human leukemic cell lines. Exposure of these cells to 12-0-tetradecanoyl phorbol-13-acetate (TPA) at 37 degrees C results in a 40% reduction of the specific binding of 125I-transferrin, which is apparent within 15 min. Half-maximal inhibition occurs at about 1 nM. Other tumor promoting phorbol esters also inhibit 125I-transferrin binding in a dose-dependent manner which parallels their known promoting activity in vivo. TPA reduces the number of transferrin receptors, and does not alter the degradation or the internalization of transferrin. In addition, TPA inhibits iron uptake by these cell lines. These effects are specific, since phorbol esters do not affect either cell growth or the binding of transferrin to Friend erythroleukemia cells and Raji cell line. On the basis of these findings it is suggested that the inhibition of transferrin binding may represent one of the mechanisms by which phorbol esters affect the growth and the differentiation of hematopoietic cell lines.

Biological Transport↗
PubMed1984

Effects of sodium ipodate and propylthiouracil in athyreotic human subjects, role of triiodothyronine and pituitary thyroxine monodeiodination in thyrotrophin regulation.

To investigate the respective role of triiodothyronine (T3) and thyroxine (T4) in the regulation of TSH secretion, we studied the action of sodium ipodate and propylthiouracil (PTU) in 11 athyreotic patients. The LT4 replacement dose was adjusted to obtain, in each patient, a normal basal TSH level and a normal TSH response to TRH. In the 5 ipodate-treated patients (single 6 g oral dose), the mean serum T3 level fell by 64% below the baseline value and serum rT3 rose 180% above the baseline. The free T4 index (FT4I) did not change whereas the mean serum TSH concentration increased 280% above baseline values. In the 6 PTU-treated patients (250 mg orally every 6 h for 10 days), serum T3 levels fell 33%, serum rT3 increased up to 82% and the FT4I did not change. The mean serum TSH concentration increased 68% above the baseline value. Thus, the mean percentage increase in serum TSH was less in PTU- than in ipodate-treated patients (68% vs 280%). Statistical analysis of the correlation between the serum T3 decrease (delta T3) and the serum TSH (delta TSH) increase demonstrated that for the same T3 diminution, the ipodate-treated group displayed higher increase of TSH than the PTU-treated patients. In the rat, PTU interferes with the 5'-deiodination of T4 in the liver and kidney but not in the pituitary, while ipodate appears to have the same effect in all tissues. If this holds true for human subjects, our data strongly suggest that circulating T4 (through its intrapituitary conversion to T3) shares with serum T3 the capacity to regulate TSH secretion in man.

Adult↗
PubMed1984

Effect of phorbol esters on iron uptake in human hematopoietic cell lines.

We have investigated the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on iron uptake into human hematopoietic cell lines K562, U937, and HL-60. TPA inhibited both cell growth and iron uptake by these cell lines. This effect was rapid, which is typical of phorbol esters which are biologically active, and it occurred at very low concentrations of TPA. This effect of TPA was dependent upon an inhibition of the transferrin-binding capacity as estimated on intact cells. However, experiments with transferrin binding on cell samples dissolved in 1% Triton X-100 showed that TPA-treated cells exhibited a transferrin-binding capacity similar to that of control cells. On the basis of this result, it is suggested that TPA modified a part of transferrin receptors present in the cells; as a result of this modification, these receptors became unavailable for binding transferrin, but they remained physically present in the cell. Other compounds capable of inducing the differentiation of leukemic cells, such as dimethyl sulfoxide, butyrate, retinoic acid, and 1 alpha,25-dihydroxy-vitamin D3, did not acutely inhibit iron uptake. We also investigated the effect of TPA on transferrin receptors in a cellular system in which phorbol esters stimulate cell proliferation. At 16 X 10(-9) M, TPA markedly stimulated the proliferation of T-lymphocytes. However, in spite of this marked stimulation of cell proliferation, TPA-stimulated lymphocytes exhibited a transferrin-binding capacity much inferior to cells stimulated by other mitogens, such as phytohemagglutinin.

Biological Transport↗
PubMed1983

Erythroid properties of K562 cells. Effect of hemin, butyrate and TPA induction.

Two sublines of the human leukemia cell line K562 including the original cell line and three clones have been investigated for their erythroid features. All of them produce embryonic and fetal hemoglobins, glycophorin A, spectrin and true acetylcholinesterase, but to a varying extent among the cell lines. The Hb and glycophorin contents were correlated in the different K562 cell lines, whereas acetylcholinesterase was independently expressed from these two other erythroid markers. Hb accumulation is enhanced by exposure of the cells to 100 microM hemin without a significant modification of the expression of the other erythroid markers. Butyrate greatly increased the activity of acetylcholinesterase, slightly enhanced the production of hemoglobin, but did not modify the expression of glycophorin and spectrin. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced an almost complete disappearance of glycophorin, reduced the synthesis of Hb by K562 cells and also abolished the action of hemin on Hb accumulation. Therefore, all the different K562 cell lines exhibit clear erythroid features including acetylcholinesterase. Butyrate or hemin did not induce terminal differentiation of K562 cells, whereas TPA significantly diminished the erythroid phenotype.

Acetylcholinesterase↗
PubMed1983

Urinary free corticoids: an evaluation of their usefulness in the diagnosis of Cushing's syndrome.

We evaluated the usefulness of measurement of urinary free corticoids (UFC) in the diagnosis of hypercorticism. One hundred and thirty patients with features suggestive of Cushing's syndrome were examined. Twenty-six patients were proved to have Cushing's syndrome. The remaining 104 patients were considered not to have this disease on the basis of other investigations, and were designated as 'suspected patients'. UFC and 17-hydroxycorticosteroids were measured in all these patients in the basal state and on the 5th day of a low-dose-dexamethasone suppression test (3 mg/day for 5 days). UFC values of patients with Cushing's syndrome were well above 125 micrograms/24 h in the basal state and higher than 10 micrograms/24 h during the suppression test. UFC values of 'suspected patients' were between 20 and 125 micrograms/24 h in the basal state and below 10 micrograms/24 h during the suppression test. It can be concluded that the measurement of UFC in the basal state and on the 5th day of a suppression test is not only a very sensitive but also a specific method for the diagnosis of Cushing's syndrome.

17-Hydroxycorticosteroids↗
PubMed1983

The number of the Trf receptors on human hematopoietic cell lines is influenced by membrane phospholipids.

The effect of phospholipases and of inhibitors of phospholipases on the binding of 125I-Trf to human hematopoietic cell lines was investigated. The results showed that incubation of the cells with phospholipases or inhibitors of phospholipases elicited a significant reduction of the Trf binding. This phenomenon was related to a reduction of Trf binding sites without affecting the affinity of the receptors for Trf. These results suggest that the phospholipids of the cell membrane may modulate the binding of transferrin to its receptor.

Acetophenones↗
PubMed1983

[Modulation of the expression of transferrin receptors by iron, hemin and protoporphyrin IX].

The expression of transferrin receptors in human leukemic cell lines was investigated. Our results have clearly shown that heme, iron and protoporphyrin-IX may modulate the expression of Trf receptors: iron and heme induce a decrease in the number of Trf receptors; in contrast protoporphyrin-IX elicited a significant increase in the number of Trf receptors. On the basis of these data we suggest that the intracellular concentration of iron, heme and protoporphyrin-IX may represent the main factor involved in the regulation of the expression of Trf receptors.

Animals↗
PubMed1982

Inhibition of insulin receptor binding by phorbol esters.

Phorbol esters inhibit the binding of insulin to its receptors on U-937 monocyte-like and HL-60 promyelocytic leukemia human cell lines. Within 20-30 min, exposure of these cells to 12-O-tetradecanoylphorbol 13-acetate (TPA) at 37 degrees C results in a 50% reduction of the specific binding of 125I-insulin. Half-maximal inhibition occurs at 1 nM TPA. Other tumor-promoting phorbol esters also inhibit 125I-insulin binding in a dose-dependent manner which parallels their known promoting activity in vivo. TPA does not alter the degradation of the hormone nor does it induce any shedding of its receptors in the medium. The effect of phorbol esters is dependent on temperature and cell type. It is less prominent at 22 degrees C than at 37 degrees C. It is reversible within 2 h at 37 degrees C. TPA reduces the binding of insulin predominantly by increasing its dissociation rate. This effect results in an accelerated turnover of the hormone on its receptors.

Animals↗
PubMed1981

Receptors for insulin-like peptides (ILAs) in rat reticulocytes and erythrocytes.

Rat reticulocytes possess receptors for an insulin-like somatomedin peptide ILAs. At 20 C, pH 7.4 and 10(8) cells per ml, the binding of 125I-ILAs reached a steady-state at 120 min. Binding was partially reversible at 20 C and totally reversible at 37 C. Insulin did not compete with ILAs at concentrations as high as 10 microgram/ml. Insulin-like growth factor II (IGF II) competed with the same potency as ILAs itself, while insulin-like growth factor I (IGF I) was five times less potent. The optimum pH for 125I-ILAs binding was 8.5. Mature erythrocytes possessed seven times less binding sites than reticulocytes. These data suggest that the somatomedins might mediate the effect of growth hormone on erythropoiesis.

Animals↗
PubMed1981

False hyperthyrotropinemia induced by heterophilic antibodies against rabbit serum.

A case of false hyperthyrotropinemia was investigated. The serum of the patient contained heterophilic antibodies against rabbit immunoglobulins secondary to immunization with rabbit serum. Some vaccines against viral or bacterial diseases contain animal serum capable of inducing heterophilic antibodies in man. This technical problem can be prevented by the routine addition of control rabbit serum or immunoglobulins to the TSH RIA.

Animals↗
PubMed1981

Embryonic and fetal hemoglobin synthesis in K562 cell line.

K562 cell line was grown in liquid suspension and in plasma clot cultures. Morphological studies revealed the presence of a minority of cells, which were identified as erythroblasts. However, the majority of the cells remained unidentified. Biochemical studies confirmed the synthesis of hemoglobin by K562 cells. The pattern of hemoglobin (Hb) production was of the embryonic type, with the presence of small amount of fetal Hb. The addition of several inducers, like Epo and butyrate, was unable to modify the pattern of Hb production of K562. In contrast, the addition of hemin increased the synthesis of Hb and stimulated the synthesis of fetal Hb and probably adult Hb.

Butyrates↗
PubMed1981

[Dopamine and pituitary hormones. Physiology and pathology (author's transl)].

Dopamine regulates the secretion of pituitary hormones: it inhibits permanently the production of prolactin and blocks the gonadotrophins and the thyroid-stimulating hormone. It stimulates inconstantly the secretion of growth hormone and it does not control corticotropin. Dopamine agonists and antagonists are currently used in the investigation and the treatment of hyper-prolactinemia and acromegaly.

Acromegaly↗
PubMed1981

Excess alpha chains are lost from beta-thalassemic reticulocytes by proteolysis.

During incubation of reticulocytes from patients with beta-thalassemia, after labeling of the hemoglobin with radioactive amino acids, the excess alpha chains are gradually lost from the cells. The aim of this study was to investigate the mechanism of this phenomenon. A system was developed in which reticulocytes from beta-thalassemia patients are labeled with [3H]leucine, washed several times in nonradioactive medium, and then incubated in the same medium containing puromycin added in order to stop further protein synthesis. The results have clearly shown that excess alpha chains are gradually degraded by proteolysis. N-ethylmaleimide or epsilon-aminocaproic acid inhibited the proteolysis of free alpha chains. The addition of either ATP or hemin did not change the rate of alpha chain degradation. The time required to degrade 50% of the pool of free alpha chains was directly dependent on the initial value of this pool. This finding suggests the absence of a significant individual variation in the ability to proteolyse free alpha chains.

Adenine↗