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Biomedical subjects

J de Koning

Publications and source records attributed to J de Koning.

At least 109 records · Page 6Linked to original sources

LH-RH and dopamine levels in hypophysial stalk plasma and their relationship to plasma gonadotrophins and prolactin levels in male rats bearing a prolactin- and adrenocorticotrophin-secreting pituitary tumor.

The present study was concerned with the effects of a transplantable pituitary tumor secreting prolactin (PRL) and adrenocorticotrophin (ACTH) on the levels of LH and FSH in peripheral plasma and on the hypothalamic release of LH-RH and dopamine in the male rat. Male rats of the same age not inoculated with the tumor served as controls. Hypophysial stalk blood was collected from urethane-anesthetized rats 4-5 weeks after tumor inoculation to measure their LH-RH and dopamine content. A peripheral blood sample was withdrawn from the animals just before sectioning the hypophysial stalk to measure their content of LH, FSH and PRL. It was found that in the tumor-bearing rats the levels of PRL increased 17-fold, whereas plasma levels of LH and FSH decreased by 45 and 70% respectively, when compared with the control rats. In the tumor-bearing rats, the secretion rate of dopamine in hypophysial stalk plasma increased from 1.4 to 4.1 ng/h, whereas the secretion rate of LH-RH decreased from 122 to 61 pg/h. However, when at the time of tumor inoculation adrenalectomy was performed, the tumor did not decrease plasma levels of LH and FSH and the secretion of LH-RH into hypophysial stalk blood any longer. The effect of the tumor on hypothalamic dopamine secretion was, however, still present in the adrenalectomized rats. It is concluded that the effect of the PRL- and ACTH-secreting pituitary tumor on plasma levels of LH and FSH requires the presence of the adrenal gland and that this effect is mediated through an inhibition of the hypothalamic release of LH-RH. Furthermore, this tumor increases the hypothalamic release of dopamine independent of the presence of the adrenal gland.

Adrenocorticotropic Hormone↗

Effect of pre-treatment of long-term ovariectomized rats with anti-LRH on the response of the pituitary gland in vitro to the analogue of LRH D-ser-(tBu)6-des-gly10-ethylamide-LRH (Buserelin).

Ovariectomized rats were injected iv with an antiserum against LRH or normal rabbit serum. Anti-LRH caused a decrease of plasma LH and FSH. After 24 or 48 h, the rats were decapitated and the pituitary glands incubated in the presence of an analogue of LRH which reacts minimally with anti-LRH (Buserelin). Pre-treatment with anti-LRH caused an increased response of pituitary LH release to Buserelin. Similar results were obtained with regard to FSH. In this case, however, basal release of FSH was lowered by pre-treatment with anti-LRH. Pituitary LH and FSH contents were not affected by anti-LRH, but synthesis of LH and FSH in vitro was smaller than in control glands obtained from rats pre-treated with normal rabbit serum.

Animals↗

Studies on the mechanism of the selective suppression of plasma levels of follicle-stimulating hormone in the female rat after administration of steroid-free bovine follicular fluid.

Steroid-free bovine follicular fluid (bFF) selectively suppresses the plasma levels of FSH in the female rat, demonstrating that bFF contains inhibin-like material. The present study was concerned with the effects of bFF on the hypothalamic release of LH releasing hormone (LH-RH) into hypophysial stalk blood and on the metabolic clearance rates of gonadotrophins. The metabolic clearance rates of FSH, LH and prolactin were determined after a single injection of and during a constant infusion with adenohypophysial extract. Similar results were obtained with both methods, and treatment with bFF did not alter the metabolic clearance rates of FSH, LH and prolactin. Anaesthesia with urethane, used for surgery involved in the collection of hypophysial stalk blood, did not interfere with the effect of bFF on plasma levels of FSH. The administration of bFF did not change the hypothalamic content of LH-RH, but caused a 30% decrease in the levels of LH-RH in hypophysial stalk plasma. However, a fraction isolated from bFF, which contained 20 times more inhibin-like activity per mg protein than bFF, did not alter the hypothalamic release of LH-RH into the hypophysial portal blood while this fraction was effective in specifically suppressing the plasma levels of FSH. It was concluded that the inhibin-like activity in bFF does not suppress the plasma levels of FSH by affecting its plasma clearance or by influencing the hypothalamic release of LH-RH, but that it has a direct effect on the adenohypophysis in inhibiting the release of FSH. Besides the inhibin-like activity, bFF also contains another factor which can decrease the levels of LH-RH in hypophysial stalk plasma.

Animals↗

Early detection of hemorrhagic hypovolemia by muscle oxygen pressure assessment: preliminary report.

Skeletal muscle PO2 was studied during graded hemorrhagic shock in Labrador dogs by means of a polarographic needle PO2 electrode. Compared to hemodynamic, blood gas, biochemical, and hematologic variables, a shift to the left of the cumulative histogram of skeletal muscle PO2 was the earliest and most sensitive indicator of impaired skeletal muscle oxygenation. The mean arterial blood pressure and the mean of the medians of the skeletal muscle PO2, respectively, were as follows: during the control period 125 and 38.1 mm Hg, during the imminent shock period 143 and 24.5 mm Hg, and during the shock period 89 and 5.1 mm Hg. This electrode is suitable for clinical use.

Animals↗

Release of LH in vitro from anterior pituitary glands of ovariectomized rats by LRH or elevated potassium concentration after pre-treatment with oestradiol benzoate in vivo.

Pituitary glands from ovariectomized rats which had been pre-treated with oestradiol benzoate (OeB) or solvent oil were incubated in Krebs-Ringer bicarbonate buffer with glucose containing either LRH (1000 ng/ml) or a high K+ concentration (50 mM). OeB (7 micrograms sc) or oil was injected at 2.5 or 6.5 h before the beginning of the incubation experiment or during the three preceding days (three daily injections). Depending upon the period during which the pituitary glands had been exposed to OeB LH release induced by LRH was inhibited (negative effect of OeB) or augmented (positive effect). When the glands were incubated in medium containing high K+, only the negative effect of OeB pre-treatment was seen. It is concluded that that part of LRH-induced LH release which is mimicked by high K+ is involved in the negative effect of OeB, but not in its positive effect.

Animals↗

Release and synthesis of FSH by pituitary glands of female rats in vitro.

Anterior hemi-pituitary glands from intact female and ovariectomized (OVX) rats were incubated with or without a maximally effective dose of LRH. During an 8 h incubation, LRH-stimulated release of FSH by pituitary glands from intact rats was biphasic: an initial slow rate of release and, from 2 to 8 h, an enhanced rate of release. Basal release was low up to 4 h, after which a marked increase of the rate of release was measured: from 6 to 8 h there was no difference between the rates of basal and LRH-stimulated release. Basal and LRH-stimulated release of FSH by pituitary glands from OVX rats were high and approximately constant during an 8 h incubation. Both basal and LRH-stimulated release by glands from intact as well as OVX rats were protein synthesis dependent. During the incubations as LRH-independent synthesis is involved, either directly or indirectly, in increasing the rate of basal release of FSH after 4 h. A comparison of release and synthesis of FSH with those of LH reveals characteristic differences.

Animals↗

Time course of inhibition of synthesis and basal release of FSH from pituitary glands of female rats by bovine follicular fluid in vitro.

Inhibin-like activity in steroid-free bovine follicular fluid (bFF) is demonstrated using an in vitro technique with hemi-pituitary glands from intact female (second day of dioestrus) and ovariectomized rats: synthesis as well as basal release of FSH, but not of LH, are inhibited profoundly. The results confirm and extend data from other investigators on the action of inhibin-like material. The effect of the inhibin-like activity is shown to be reversible, as synthesis and the rise of basal release are restored when bFF is withdrawn from the incubation medium. Synthesis of FSH seems to be inhibited earlier than basal release, and it is suggested that the inhibin-like material acts only directly on FSH synthesis. Some possibilities of the mechanisms of action of inhibin-like activity are discussed.

Animals↗

[Factors determining the prognosis of leukemia].

The prognostic factors of acute leukemia in children are described. The maintenance of the first complete remission is the principal aim of treatment. Initial high leucocyte counts over 50 x 10(9)/l and leukemic infiltration of the central nervous system and the testis are poor prognostic signs. The morphological classification of acute lymphoblastic leukemia versus acute non-lymphoblastic leukemia is more important than the differentiation in lymphoblastic types. Immunological characterisation as a B-cell leukemia seems to hold a poor prognosis. Cell replication rate, chromosomal studies and HLA typing are of growing importance but should not influence the choice of therapy at this moment. Sex, race and age of onset are factors, reported to be of importance, are worth to be studied more intensively in connection to the other factors. The quality of the results in trials and in different centres urge to a multi-variate analysis of the data in order to prevent unreliable conclusions.

Age Factors↗

Oxygen transport and the function of myoglobin. Theoretical model and experiments in chicken gizzard smooth muscle.

We studied the steady-state oxygen transfer across thin layers of respiring chicken gizzard smooth muscle and compared three models for oxygen consumption with respect to their influence on the facilitation of oxygen diffusion by myoglobin. These models assumed zero-order, Michaelis-Menten or exponential kinetics. The transport equation was solved for these models with simultaneous oxygen facilitation assuming chemical equilibrium between oxygen and myoglobin. Experimental flux data were obtained in two situations: a) high oxygen pressure throughout the layer of tissue providing maximum oxygen consumption and oxygen permeability, and b) anoxic conditions in part of the layer and with submaximal oxygen consumption and desaturation of myoglobin. Measurements in the presence of functional myoglobin were compared with data obtained after abolishing the transport function of myoglobin by application of 1 kPa carbon monoxide. It was found that oxygen consumption interferes with the facilitation effect. The oxygen pressure at half maximum oxygen consumption in the Michaelis-Menten model was 0.3 +/- 0.1 (S.E) kPa. The facilitation of the oxygen transport by myoglobin was 50 to 100% of the maximum value to be expected on the basis of the prevailing myoglobin concentration.

Amobarbital↗

Dopaminergic and adrenergic effects on plasma LH levels in rats with hypothalamic islands.

In female rats hypothalamic islands were prepared by making a cut around the mediobasal hypothalamus. Three weeks later the rats were ovariectomized. Two weeks after ovariectomy, part of the animals showed elevated blood LH levels with oscillations, although the mean LH levels were significantly lower than in sham-operated ovariectomized animals. There was a significant correlation between the occurrence of elevated blood LH levels after ovariectomy and the inclusion of at least part of the suprachiasmatic nucleus within the islands. Nor-adrenaline content of the hypothalamus was decreased significantly, but there was no significant change in hypothalamic dopamine content. Injection of doses of apomorphine, ranging form 2.5 microgram/kg to 25 mg/kg sc into island-bearing and sham-operated animals caused a dose-dependent decrease of plasma LH. However, the magnitude of the decrease was smaller in rats with hypothalamic islands than in controls. Even the highest doses of apomorphine did not decrease plasma LH further than to about 100 ng of LH-RP-1/ml. Phenoxybenzamine (10 and 40 mg/kg ip) and phentolamine (20 mg/kg ip) caused a decrease of plasma LH in ovariectomized control rats, but in ovariectomized rats with hypothalamic islands these drugs caused an increase. Clonidine (100 microgram/kg sc followed by 100 microgram/kg ip) had no effect in ovariectomized control rats, but in ovariectomized rats with a hypothalamic island an increase was induced. These results may have been caused by an increased sensitivity of hypothalamic alpha-receptors resulting from severing afferent noradrenergic fibres.

Animals↗

Dependence on protein synthesis of the N6-monobutyryl cyclic AMP plus theophylline mediated release of luteinizing hormone induced by luteinizing hormone releasing hormone from rat pituitary glands in vitro.

The involvement of cyclic AMP in the action of LH releasing hormone (LH-RH) on LH secretion was studied by incubating pituitary glands from adult female rats on day 2 of dioestrus with 1 mN-N6-monobutyryl cyclic AMP (mbcAMP) and 10 mM-theophylline for periods of up to 10 h. This treatment induced a pattern of LH release similar to that observed in the presence of a low concentration of LH-RH (0.1 ng LH-RH/ml), i.e. an initial 4 h period during which the release of LH was minimal was followed subsequently by an increased rate of release. In this system inhibition of protein synthesis by cycloheximide (25 microgram/ml) did not impair the initial response of the pituitary tissue but the increase in the rate of LH release during the second phase of the response was blocked. Preincubation with mbcAMP and theophylline increased the responsiveness of the pituitary tissue to LH-RH. This action could be prevented by including cycloheximide during the preincubation period, whereas addition of this drug during the incubation with LH-RH no longer impaired the increased responsiveness. The size of the sensitizing action of mbcAMP and theophylline mediated through the induction of protein synthesis was comparable with that of a high concentration of LH-RH. From the absence of a significant change in total LH during the preincubation period, it was concluded that the increased responsiveness was not the result of newly synthesized LH. The present results suggest a role or roles for cyclic AMP in the secretion of LH induced by LH-RH. Besides an effect on the formation of a factor related to the synthesis of protein, other than LH which has a permissive role in the acute release of LH, cyclic AMP might also be concerned in the secretion process through a pathway which does not involve synthesis of protein.

Animals↗

Colony forming units in culture in childhood aplastic anemia.

The results of the determination of the numbers of colony forming units in culture of the bone marrow of 17 children with aplastic anaemia before and after bone marrow transplantation, of 4 children with antilymphocyte globulin and of 16 children treated conventionally are presented. In the aplastic phase the number of C.F.U.-C. was very low to zero. After successful transplantation the number of bone marrow C.F.U.-C. rose but did not become normal. After antilymphocyte globulin and conventional therapy the number of bone marrow C.F.U.-C. remained low, even when a restoration of the haematological values in the peripheral blood took place.

Anemia, Aplastic↗

Erythrocyte superoxide dismutase deficiency in Fanconi's anaemia established by two independent methods of assay.

Erythrocyte superoxide dismutase (SOD; E.C.1.15.1.1) levels were quantitated in human haemolysates, both by an immunological technique and by an activity assay. The erythrocyte SOD activity level in a group of seven Fanconi's anaemia patients was significantly decreased (27%, on the average) compared to a control group of nineteen healthy individuals. The fact that both the activity per antigenic unit and the electrophoretic mobility of the erythrocyte SOD was normal indicates that the deficiency in these Fanconi's anaemia patients is most probably not due to a mutation in the structural gene for the enzyme but more likely due to a disturbed mechanism regulating the SOD level in the erythrocyte.

Anemia, Aplastic↗