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Biomedical subjects

J Kunert-Radek

Publications and source records attributed to J Kunert-Radek.

At least 37 records · Page 2Linked to original sources

Effects of calcitonin and calcitonin gene-related peptide on 3H-thymidine incorporation into DNA of rat thyroid lobes in vitro.

The effects of a 4 h incubation of rat thyroid lobes, in the presence of calcitonin (CT) and calcitonin gene-related peptide (CGRP) on the incorporation of 3H-thymidine into DNA, were investigated. In other groups the thyroid lobes were incubated during exposure to CT and thyrotropin (TSH), and to CGRP together with TSH. All concentrations of CT (10(-6)-10(-8) M) revealed a tendency towards lowering 3H-thymidine uptake, but the effect was not statistically significant. The influence of CGRP was dose-dependent; the lowest concentration of CGRP (10(-9) M) significantly enhanced DNA synthesis in the incubated rat thyroids; an intermediate dose of the peptide (10(-8) M) had no effect, while the highest concentration of CGRP (10(-7) M) decreased 3H-thymidine incorporation. Calcitonin (10(-7) M), as well as CGRP (10(-8) M), suppressed the stimulatory effect of TSH on 3H-thymidine incorporation.

Animals

Stimulation of rat pituitary tumoral cell proliferation in vitro by tetra- and pentagastrin.

The effects of the active gastrin fragments, penta- and tetragastrin on the incorporation of tritiated thymidine into the rat pituitary tumoral cells were investigated in vitro. The significant stimulation of 3H-thymidine incorporation was observed as an effect of the investigated substances. The putative role of gastrin as an autocrine growth factor active in pituitary tumorigenesis was discussed.

Animals

Inhibitory effect of thyrotropin releasing hormone on spontaneous proliferation of mouse spleen lymphocytes in vitro.

The effects of thyrotropin releasing hormone (TRH) and of TRH-like tripeptide pGlu-His-Gly-OH (colon mitosis inhibitor, CMI) on spontaneous proliferation of murine splenocytes were investigated in vitro. The 3H-thymidine incorporation into splenocyte DNA was used as an index of proliferation. It was found that TRH suppressed the proliferation of splenocytes. In contrast, CMI was ineffective by itself but used together with TRH blocked the effect of the latter.

Amino Acid Sequence

Inhibitory effect of bombesin and SMS 201-995 on DNA synthesis in the rat thyroid lobes incubated in vitro.

The effects of 4-h incubation in the presence of bombesin on the incorporation of [3H]-thymidine into DNA of the rat thyroid lobes, collected from animals treated in vivo with a long-acting somatostatin analog (SMS 201-995) or with 0.9% NaCl, were investigated. It was shown that not only in vivo injections of SMS 201-995, but also, unexpectedly, in vitro incubation with bombesin inhibited [3H]-thymidine incorporation. The two examined substances did not reveal any additive action in their inhibitory effects on the thyroid growth.

Animals

Inhibitory effect of porphyrins on the proliferation of mouse spleen lymphocytes in vitro.

The influence of various porphyrins (deuteroporphyrin IX, mesoporphyrin IX, protoporphyrin IX, hematoporphyrin) and two related compounds (hemin, biliverdin) on the spontaneous proliferation of mouse spleen lymphocytes has been estimated in vitro by the 3H-thymidine uptake assay. It has been found that porphyrins (endogenous ligands for the mitochondrial benzodiazepine receptor) produce a concentration-dependent inhibition of 3H-thymidine incorporation into the DNA of these cells. Metalloporphyrin-hemin has been observed to evoke a weak inhibitory effect, in a high concentration (10(-4)M), whereas biliverdin, a porphyrins degradation product, was inactive in the same experimental conditions. Those findings indicate that endogenous porphyrins, presumably acting through the mitochondrial benzodiazepine receptor, could regulate the proliferation of mouse spleen lymphocytes in vitro.

Animals

Effects of metoclopramide on rat spleen lymphocyte proliferation.

The effect of metoclopramide on proliferation of spleen lymphocytes in rats was examined. The rate of [3H]thymidine incorporation into DNA was used as an index of lymphocytes proliferation. It was shown that the incorporation of [3H]thymidine into DNA of spleen lymphocytes in the rats treated with metoclopramide was significantly higher than that in the control group. The effects of various concentrations of prolactin and metoclopramide on [3H]thymidine uptake by DNA of spleen lymphocytes was also studied in vitro. It was shown that: 1, Prolactin, at the concentration of 1 and 0.1 ng/ml significantly increased [3H]thymidine incorporation into DNA of spleen lymphocytes. Metoclopramide in all the examined concentrations also caused a significant proliferogenic effect on lymphocytes.

Animals

Somatostatin analog (SMS 201-995) inhibits the basal and angiotensin II-stimulated 3H-thymidine uptake by rat adrenal glands.

The effects of a long-acting somatostatin analog SMS 201-995 injections on the basal and angiotensin II-stimulated [3H]-thymidine uptake by the rat adrenal glands incubated in vitro were examined. It was shown that SMS 201-995 significantly inhibited the [3H]-thymidine uptake and, additionally, suppressed the stimulatory effect of a single angiotensin II injection.

Adrenal Glands

Effects of calcium channel modulators on the proliferation of mouse spleen lymphocytes in vitro.

The effects of nimodipine (voltage-dependent calcium channel blocker), CGP 28392 and BAY K 8644 (novel dihydropyridine derivatives that are considered as calcium entry stimulators) on the spontaneous proliferation of mouse spleen lymphocytes were studied in vitro. [3H]-thymidine incorporation into DNA of lymphocytes was used as an sensitive index of the cell proliferation. It has been found that nimodipine (10(-4) M-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose dependent fashion with ED50 value of 2.4 x 10(-5) M. Unexpectedly, CGP 28392 (10(-4) M-10(-7) M) acts as a calcium entry blocker and produces a strong inhibitory effect on lymphocyte proliferation (ED50-2 x 10(-5) M). BAY K 8644 at a high concentration (10(-4) M) also has an inhibitory effect but at a lower concentration (10(-6) M-10(-10) M) significantly increased [3H]-thymidine uptake and abolished the inhibitory effect of nimodipine. This effect of nimodipine was also reversed by 5 x 10(-3) M calcium chloride. These findings indicate that calcium channel modulators can regulate the proliferation of mouse spleen lymphocytes in vitro.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Hydrocortisone inhibits the basal and angiotensin II-stimulated proliferation of rat adrenocortical cells in organ culture.

The present study has been to test the effect of hydrocortisone (HC) on the mitotic incidence in adrenocortical cells of organ-cultured rat adrenal explants during a 24-hour incubation with or without angiotensin II (ANG). It was shown that HC significantly decreased the mean mitotic activity rate (MMAR) of adrenocortical cells in organ culture. That decrease concerned all the three cortical zone vs respective controls. In turn, ANG markedly increased the MMAR of the zona glomerulosa cells, when compared to the values recorded in controls, while there were no changes of the MMAR of the zona glomerulosa in the adrenal explants incubated with joint exposure to HC and ANG. The obtained results indicate that HC exhibits an inhibitory effect on the adrenocortical cell proliferation, which may suggest that arachidonic acid metabolites play an important role in the process of adrenocortical hyperplasia, their participation in the ANG-induced zona glomerulosa cell proliferation being strongly assumed.

Adrenal Cortex

Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro.

The effects of 2 specific calcium channel blockers, verapamil and nimodipine, on the proliferation of human glioma tumour cells were investigated in vitro. Tumour tissues for primary cell cultures were obtained bioptically from 3 patients with the histopathological diagnosis of glioblastoma. The [3H]-thymidine incorporation into glioma tumour cells DNA was used as a sensitive index of the cell proliferation. It was found that verapamil (10(-4)-10(-5) M) and nimodipine (10(-4)-10(-6) M) significantly inhibited the [3H]-thymidine uptake in a dose-related manner. The inhibitory effect of both calcium channel antagonists was reversed by simultaneous addition of calcium chloride (5 x 10(-3) M). These results indicate that verapamil and nimodipine may exert an antiproliferative effect on glioma cells growth acting through a blockade of specific voltage-dependent calcium channels.

Calcium

Influence of melatonin and N-acetylserotonin on the cyclic AMP concentration in the rat thyroid lobes incubated in vitro.

Effects of melatonin and N-acetylserotonin on the cyclic AMP (cAMP) concentration in the organ-cultured rat thyroid gland were investigated. Exposure of the thyroid explants to melatonin (10(-8) M) resulted in a decrease of cAMP levels. Melatonin at higher concentrations (10(-7) M and/or 10(-6) M) failed to influence the thyroid cAMP level. N-acetylserotonin (10(-6) M), like melatonin in the lowest concentration employed, reduced cAMP concentrations in the thyroid explants when compared with controls. Unexpectedly, melatonin (at a concentration of 10(-7) M) added to the incubation medium with TSH (60 mU/ml), decreased the cAMP concentration in the thyroid compared with the group exposed to melatonin (10(-7) M) alone.

Animals

Increased 3H-thymidine incorporation into DNA of organ-cultured adrenal explants from rats injected with corticotropin and/or cysteamine.

The effect of a single injection of cysteamine /CySH/ - a sulfhydryl substance, known to deplete tissue content of somatostatin /SS/ - on 3H-thymidine incorporation into DNA of rat adrenal explants incubated in vitro was investigated. It was shown that: 1/ Single in vivo injection of ACTH or of CySH increased 3H-thymidine incorporation into DNA of the organ-cultured adrenals, 2/ Dexamethasone reduced the 3H-thymidine uptake, but that decrease did not attain statistical significance versus controls.

Adrenal Glands

Effect of benzodiazepines on the proliferation of mouse spleen lymphocytes in vitro.

The effect of several benzodiazepines (clonazepam, diazepam, Ro 5-4864, Ro 15-1788) and two pineal gland indoleamines (N-acetylserotonin, melatonin) on the spontaneous proliferation of mouse spleen lymphocytes was estimated in vitro by the 3 H-thymidine uptake assay. It was found that diazepam and Ro 5-4864 (a selective peripheral-type benzodiazepine receptor ligand) produced the concentration-dependent inhibition of 3 H-thymidine incorporation into the DNA of these cells. Ro 15-1788, a specific central-type receptor ligand, evoked a slight inhibitory effect in a high concentration (10(-4) M), whereas clonazepam did not produce any significant inhibition. When Ro 5-4864 was tested in combination with diazepam, the inhibition of lymphocyte proliferation did not exceed the effect of diazepam given alone. Ro 15-1788 was unable to reverse the inhibitory action of diazepam in the same experimental conditions. Melatonin and its precursor N-acetylserotonin tested in the concentration range of 10(-4)-10(-8) M had no significant influence on the spleen lymphocyte DNA replication in our assay system. These data suggest that diazepam inhibition of lymphocyte proliferation is mediated by peripheral-type sites. Additionally, the fact that melatonin and N-acetylserotonin were unable to affect 3 h-thymidine incorporation argues against any benzodiazepine receptor mediated effect of pineal indoleamines on a cellular proliferation.

Animals

Inhibition of cell proliferation of human gliomas by benzodiazepines in vitro.

The effects of several benzodiazepines (diazepam, clonazepam, Ro 15-1788 and Ro 5-4864) on cell proliferation of 2 human gliomas were estimated in vitro by means of [3H]-thymidine uptake assay. It was found that all tested benzodiazepines suppressed [3H]-thymidine incorporation into the DNA of glioma cells, the effects being stronger in case of peripheral-type benzodiazepine receptor ligands. The results indicated that benzodiazepines might exert an antiproliferative action on glioma tumour cells growth.

Astrocytoma

Influence of somatostatin and epidermal growth factor (EGF) on the proliferation of follicular cells in the organ-cultured rat thyroid.

The effects of somatostatin (SS), epidermal growth factor (EGF), as well as interactions among SS, EGF, and TSH in their action on the proliferation of thyroid follicular cells (TFC) in organ culture were investigated. It was shown that (1) SS (10(-7) M) decreased significantly the mean mitotic activity rate (MMAR) of TFC; (2) SS (10(-7) M) suppressed the mitogenic TSH action on the TFC proliferation; and (3) TSH, as well as EGF, caused an elevation of MMARs of TFC, the effect of TSH, however, being much stronger than that of EGF. The acquired data suggest that SS, most probably by paracrine interaction, may inhibit the mitotic activity of TFC. The mitogenic effect of EGF, a potent mitogen for TFC in cell culture, is not so strongly expressed in organ culture.

Animals

Somatostatin suppression of meningioma cell proliferation in vitro.

Considering the presence of a stereospecific receptor for somatostatin (SST) in human meningioma cells and the possible involvement of this neuropeptide in the growth control of certain meningioma cell lines, the effects of SST on the proliferation of human meningioma cells in vitro was investigated. Tumour tissues for primary cell cultures were obtained surgically from 2 women with histopathological diagnosis of meningothelial meningioma. The incorporation of [3H]-thymidine into meningioma cells DNA was measured as an index of the cells proliferation. It was shown that SST (10(-7)-10(-5) M) significantly inhibited the [3H]-thymidine incorporation. The results have indicated that SST may have an antiproliferative effects on the meningioma tumour cells in vitro.

Adult

Immunomodulatory action of somatostatin.

The influence of somatostatin (SST) on spontaneous proliferation and cyclic AMP level in mouse spleen lymphocytes and on inhibition of human leukocyte migration was studied. The rate of [3H]thymidine incorporation was used as an index of proliferation. It was found that lower concentrations of SST/10(-9) and 10(-8)M, inhibited the splenocyte proliferation. In contrast, a higher SST concentration, 10(-7)M, exerted a stimulatory effect. SST in concentrations from 10(-9) to 10(-6)M did not influence cyclic AMP levels in mouse splenocytes; a significant decrease of cyclic AMP was found after the exposure to superactive SST analog RC-102-2H in concentrations 10(-8) and 10(-7)M. SST, 10(-7)M, and RC-102-2H, 10(-7)M, significantly enhanced the migration inhibition of human leukocytes induced by the exposure of leukocytes to cardiac antigen or phytohemagglutinin. The data provide evidence for an immunomodulatory action of SST.

Adjuvants, Immunologic