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Biomedical subjects

J de Koning

Publications and source records attributed to J de Koning.

At least 91 records · Page 5Linked to original sources

The involvement of ovarian factors in maintaining the pituitary glands of female rats in a state of low LH responsiveness to LHRH.

The effects of discontinuation and restoration of ovarian influences on the pituitary LH response to LHRH in vitro were investigated. When female rat pituitary glands taken on day 2 of dioestrus were incubated with LHRH the release of LH was low during the first hour (lag phase response) and afterwards a progressive, protein synthesis-dependent increase took place (second phase response), this being the self-priming action of LHRH. Short-term discontinuation (less than 1 day) of ovarian influences on the rat pituitary gland in vivo (ovariectomy) or in vitro (incubation in medium only) resulted in an increased LHRH-induced LH response during the lag phase. The biphasic LH response or the self-priming action of LHRH disappeared completely after long-term discontinuation of ovarian influences on the pituitary gland, LH release being at its maximum from the start of the incubation. The biphasic response was reinstated when ovaries were implanted under the kidney capsules of ovariectomized rats. Auto-implantation of an ovary into the spleen immediately after bilateral ovariectomy did not, however, prevent the disappearance of the LHRH self-priming action. Ovarian activity responsible for the presence of the low LH response during the lag phase was thus effectively removed by the liver, but inhibin-like activity suppressing serum FSH levels remained present. Silicone elastomer implants (s.c.) containing oestradiol-17 beta, implanted for 4 weeks, did not reverse the loss of the biphasic LH response to LHRH. It is concluded that liver-labile factors released by the ovaries keep the pituitary gland in a state of low responsiveness to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Levels of LH-releasing hormone in hypophysial stalk plasma during an oestrogen-stimulated surge of LH in ovariectomized rats.

Treatment of ovariectomized rats with 50 micrograms oestradiol benzoate, followed by 20 micrograms oestradiol benzoate 3 days later, induced surges of LH and FSH on the day following the second injection with oestradiol benzoate. During this surge of gonadotrophins, which was not blocked by the anaesthetic required to collect hypophysial stalk blood, increased hypophysial stalk plasma levels of immunoreactive LHRH were noted. Furthermore, the levels of LHRH in hypophysial portal blood were found to fluctuate. Measurement of LHRH in a pool of portal plasma revealed similar results when determined by radioimmunoassay and by a sensitive in-vitro bioassay. To mimic the observed release of LHRH during the surge of gonadotrophins, LHRH was infused, either systemically or directly into a long portal vessel, into oestrogen-treated, ovariectomized rats which had their endogenous release of LHRH blocked by pentobarbitone. An infusion of LHRH into the jugular vein, resulting in peripheral levels of LHRH which were somewhat lower than those measured in hypophysial stalk plasma, caused a surge of FSH similar to that found in rats used for collection of hypophysial stalk blood. When compared with the values in the latter animals, however, the levels of LH became two to four times higher by this infusion of LHRH. When LHRH was infused directly into a long portal vessel to mimic the observed secretion rate of LHRH during the oestrogen-stimulated surge of gonadotrophins, then the surges of LH and FSH were lower than those observed in the rats used for collection of stalk blood.

Animals↗

Effects of ovarian inhibin on pulsatile release of gonadotrophins and secretion of LHRH in ovariectomized rats: evidence against a central action of inhibin.

Intraperitoneal administration of bovine follicular fluid (bFF) decreased plasma concentrations of FSH in ovariectomized rats after 2-3 h, while plasma LH and prolactin were unaffected. In untreated ovariectomized animals the concentrations of these hormones were found to show pulsatile variations. Concomitant occurrence of peak values of LH and FSH was found in about 40% of the pulses. No pulses of FSH were observed after i.p. treatment with bFF or partly purified preparations of inhibin from bFF, but the pulsatile release of LH and prolactin remained similar. Infusion of bFF into the lateral ventricle of the brain did not alter the concentrations of FSH, whereas administration of bFF into the pituitary gland diminished the plasma concentrations of FSH. Anaesthesia (urethane plus xylazine) did not prevent the occurrence of the pulses of FSH and LH, but it reduced the pulse amplitude and clearance. During this anaesthesia, the concentrations of LHRH in the hypophysial stalk plasma decreased by 30% after administration of bFF, but did not alter after treatment with partly purified preparations of inhibin. It is concluded that the inhibin-like activity in bFF suppresses pulsatile FSH secretion in ovariectomized rats by an action on the pituitary gland, but has no effect on the pulsatile release of LH and prolactin.

Animals↗

Patterns of LH and FSH in men during high-frequency blood sampling.

The aim of the study was to test the hypothesis that in serial determinations of concentrations of LH and FSH involving blood samples taken every minute, the observed pulses of LH and FSH which last less than 3-4 min might not be a physiological phenomenon but part of the 'noise' of the radioimmunoassay or blood-sampling technique. Blood was sampled every minute for a period of 90 min in six men. During the first 45 min, blood was sampled by means of vacuum tubes only. During the second 45 min, sampling took place with a syringe via a rubber stopper, either using a tourniquet (n = 3) or flushing the cannula with heparinized saline. Three criteria were used to identify variations in the patterns of LH and FSH as true hormonal changes. First, a threshold was used which had to be exceeded by the difference between nadir and maximum values before a pulse could be identified. An average of approximately six pulses per 90 min was found in both the LH and FSH series. The majority of these pulses lasted less than 3-4 min. In two subjects, larger LH pulses of longer duration were measured. Secondly, differences between duplicate measurements of nadir and/or maximum values of more than one-third of the amplitude of a pulse were considered unacceptable. This involved about 75% of the pulses. Thirdly, the reproducibility of the hormone variations was estimated. In one subject, concentrations of LH were measured four times in four separate assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Acute leukemia in Fanconi's anemia. Report of a patient and review of the literature].

A case is reported of a 7 years old boy with Fanconi's Anemia (FA). The aplastic anemia has been treated with androgens. Six years after the confirmation of the diagnosis FA a (pre-)leukemia occurred. Because of the known complications of cytostatics in FA and the bad prognosis, the leukemia has not been treated. The boy died 4 months later. An overview of the literature shows 31 patients with acute non-lymphocytic leukemia in FA, of which the clinical course, chromosomal investigations and therapy are discussed.

Acute Disease↗

Comparison of the time courses of luteinizing hormone (LH) secretion rates during continuous stimulation by LH-releasing hormone (LH-RH) in vivo and in vitro.

The patterns of LH secretion during constant stimulation of the pituitary glands of estradiol-treated ovariectomized rats with a maximally stimulating amount of LH-RH in vivo and in vitro correspond with each other qualitatively and quantitatively. In vitro the changes with time of the LH secretion rate are somewhat retarded, especially the occurrence of desensitization.

Animals↗

Determination of permeabilities for two gases from recording the partial pressure of one gas.

When a flexible diffusion layer separates two closed gas chambers containing different mixtures of several gases, the different permeabilities of the layer for these gases lead to differences in the total gas pressures of the two chambers resulting in bulging of the layer and consequent changes in the chamber volumes. Application of the gas laws to binary gas mixtures provides two equations relating the partial pressure changes of one gas in any of the two chambers to the partial pressure difference between the two chambers across the layer. This permits the calculation of the two unknown factors, permeability (or Krogh's diffusion coefficient) of the layer for the measured gas and the permeability ratio of the two gases. Thus the permeabilities of both gases can be determined from recording the partial pressure of one of the gases only. We filled the gas chambers with different mixtures of oxygen and a second gas (nitrogen or carbon dioxide) at atmospheric pressure, closed the chambers, and measured the diffusion of the gases across thin (12-500 microns) layers of various materials by recording the oxygen partial pressure in both chambers with polarographic oxygen electrodes. Permeabilities of these layers for oxygen and the other gas were determined for plastic layers (MEM213, Silastic, Teflon), as well as water and methemoglobin solutions either in a fluid layer or soaked in Millipore filters. The data agreed well with those obtained from other studies in most cases.

Gases↗

The effect of different photoperiods on the methylating capacity of the pineal gland of adult, male golden hamsters, with special reference to 5-methoxyindoles.

Testes weight, plasma FSH and LH concentration and pineal methylating capacity were compared in hamsters housed under either long (LD14:10) or short (LD8:16) photoperiods. Hamsters housed for 14 weeks under short photoperiod showed gonadal atrophy, which was complete after 6 weeks. Also plasma FSH and LH concentration showed a marked decline after transfer to short photoperiod. However, after 14 weeks the concentration of FSH and LH as well as testes weight increased again. Under both photoperiods day/night rhythms in plasma FSH and LH concentration were measured. Under both light regimes the concentrations did not show significant differences. Under long as well as short photoperiods in the pineal gland of animals no significant differences were found in the daily synthesis of various MI tested. Only the synthesis of ML was significantly higher in the pineal of hamsters housed under short photoperiod. The function of this higher synthesis of ML remains unknown. Although the maxima of the rhythm for the various MI found under different LD regimes did not differ in magnitude or duration, their location in respect to the onset of darkness was different. It is suggested that this specific location is of more physiological importance than the quantity or duration of synthesis, concentration or release of MI. At the moment the day/night rhythms were determined there were indications that recrudescence of the testes had already started. It is suggested that this recrudescence is responsible for the fact that no differences in the synthesis of MI were found comparing the influence of both photoperiods. After 14 weeks of exposure to short photoperiod, aML synthesis was, in contrast to the synthesis of the other MI, (not significantly) higher under LD8:16. Moreover, opposite results for aMT and aML synthesis during darkness were found. It is suggested that the ratio of synthesis of these compounds is of physiological significance.

5-Methoxytryptamine↗

Diagnosis of Lyme disease by demonstration of spirochetes in tissue biopsies.

In 14 patients with Lyme disease skin biopsies, synovial specimens and a lymphnode showed lymphohistiocytic infiltrates, often perivascular. Obliterative alterations of blood vessels and fibrinoid were characteristic for infection of synovium. Spirochetes were demonstrated in all specimens by the Bosma-Steiner silver impregnation method. Spirochetes were localized in dermal papilles and subepidermal zones of skin sections of ECMA, in lymph vessels and collagen fibres. In synovia of patients with arthritis the spirochetes were found beneath the synovial lining cells and perivascularly. In the lymphnode of a patient with arthritis and lymphadenitis the spirochetes were localized in and round the blood vessels and in the lymph vessels.

Adolescent↗

Short-term pituitary desensitization to LH-RH after pulsatile LH-RH in the ovariectomized rat: an in vivo experiment.

The development of acute insensitivity of pituitary LH secretion to LH-RH after a short exposure to LH-RH is described. In the first experiment, ovariectomized (OVX), phenobarbital-pretreated rats were given pulses of LH-RH (1.25 or 6.25 ng/100 g body weight (b.w.), intravenously). In rats given 1.25 ng at time 0, 6.25 ng at 60 min, 1.25 ng at 80 min and 1.25 ng at 120 min, there was a substantial increase in plasma LH after the first two injections, no increase after the third injection and a relatively small increase after the fourth one. In other rats treated identically but not given a 1.25-ng dose at 80 min, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after the 1.25-ng dose given at time 0. If the 1.25-ng LH-RH pulses given at times 0 and 80 min were replaced by a rat pituitary extract, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after administration of pituitary extract. In the second experiment, OVX phenobarbital-pretreated rats were given 1.25 ng LH-RH/100 g b.w. at t = 0. They were then divided into three groups, each receiving 1.25, 3.75 or 6.25 ng LH-RH/100 g b.w. at t = 60 min. Each of these three groups was again divided into three groups which received 1.25 ng LH-RH/100 g b.w. at 80, 100 or 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Divergent effects on LH and FSH synthesis and release from intact female rat pituitary glands in vitro by methylxanthines, cyclic AMP derivatives and sodium fluoride.

FSH release from the female rat pituitary gland consists of an LH-like, LRH-dependent component and an autonomous, inhibin-sensitive component. It was investigated whether cyclic AMP mediated FSH release. BrcAMP, theophylline, MIX or NaF stimulated LH release but inhibited FSH release and synthesis. Although dbcAMP had no inhibitory effect on FSH release, it partly reversed the inhibitory action of theophylline. In view of previous and the present results it is concluded that cyclic AMP may mediate the LRH-dependent LH and FSH release and, through a separate pathway, may mediate the inhibition of autonomous FSH release by the ovarian protein inhibin.

1-Methyl-3-isobutylxanthine↗

[The effect of lowering the hematocrit on polycythemia and thrombocytopenia in congenital cyanotic heart defect].

The clinical history of a 15 year old girl with Down's syndrome and a complete atrioventricular septal defect undergoing blood-letting and plasma administration as a palliative treatment of polycythaemia and thrombocytopenia. A clear clinical improvement and a rapid increase of the thrombocyte count has been observed. The palliative treatment has to be continued with intervals after the therapeutic trial.

Adolescent↗

Comparison between the biological effects of LH-RH and buserelin on the induction of LH release from hemi-pituitary glands of female rats in vitro.

The biological effects of LH-RH and the agonist [D-Ser(But)6-des Gly10]-LH-RH(1-9)-ethylamide (buserelin) were compared during 8 h of incubation with female rat hemi-pituitary glands. Similar dose-response relationships were found for LH-RH and buserelin as concerns the release of luteinizing hormone (LH) by pituitary glands from intact and ovariectomized rats. Also the LH secretion patterns from glands of intact rats were similar: an initial low response was followed by a fast increase (priming effect) after which the response declined again (desensitization). In a subsequent experiment pituitary glands from ovariectomized rats were first exposed to LH-RH or buserelin for 4 h and then further incubated in medium only. After discontinuation of the stimuli the rate of LH release decreased in all cases, but this decrease was significantly greater when the glands had been exposed to LH-RH. Short-term (1/2, 1 or 2 h) exposures to LH-RH or buserelin followed by an intervening period (1 1/2, 1 or 0 h, respectively) of incubation in medium only resulted in an almost similar, significant increase in the subsequent protein synthesis-independent LH response to LH-RH (priming effect). Only preincubation with LH-RH for 2 h was significantly more effective. The results demonstrate equal intrinsic activities for LH-RH and buserelin. Differences in the biopotencies for LH-RH and buserelin in vivo and in vitro may occur only after discontinuation of the external stimuli.

Animals↗

The HLA-system in immune thrombocytopenic purpura: its relation to the outcome of therapy.

The distribution of HLA-A, -B, -C and -DR antigens was investigated in 154 patients with immune thrombocytopenia (99 adults and 55 children). An increased frequency of HLA-Bw56 (a split of HLA-Bw22) was found both in the adults (RR = 4.30) as well as in the children (RR = 7.91). Differences in HLA antigen distributions have also been analysed in patient subgroups with a good and a bad response to corticosteroids and splenectomy. The frequency of HLA-DR4 was low in those patients with a good response to prednisone as compared with those with a poor response. The opposite was found in splenectomized patients. In 22 patients who did not respond to splenectomy, LB4 (a local split of HLA-DR4) was completely absent. These results suggest that HLA-DR4 (LB4) may be a predictive marker for therapy in ITP patients, i.e. a bad response to corticosteroids and a favourable outcome of splenectomy. However, none of the differences were significant after correction was made for the number of antigens tested.

Adolescent↗

Long-term follow-up study of 168 patients with immune thrombocytopenia. Implications for therapy.

A total of 168 patients (90 adults, 78 children) with immune thrombocytopenia (ITP) and a median follow-up of 75 months were treated with a sequential regimen of corticosteroids (n = 125), splenectomy (n = 83) and immunosuppressives (n = 25). In 43 patients an observation period of a minimum of 1 month preceded the therapy. It is concluded that: (i) withholding therapy in the expectation of spontaneous recovery is at least in children justified in case of limited bleeding tendency; (ii) corticosteroids should be limited in adults to a maximum of 3 weeks and in children to a maximum of 6 weeks; (iii) if corticosteroids fail, splenectomy remains the therapy of choice, especially in patients aged less than or equal to 30 years, and should be performed within 6 months after diagnosis; (iv) after failure of the aforementioned forms of therapy, there is rarely a beneficial effect of treatment with azathioprine and vincristine; (v) no reaction to any form of therapy can be followed by an acceptable long-term outcome.

Adolescent↗

Effect of inhibin-like activity on LH-RH-stimulated release of FSH by pituitary glands from female rats in vitro.

During long-term incubation of pituitary glands from intact female rats in the presence of inhibin-like activity, LH-RH-stimulated release of FSH becomes inhibited after 4 h of incubation. However, at the same time inhibition of basal FSH release is included. Therefore, glands were at first incubated for 4 h in the presence of inhibin-like activity to block basal release completely and thereafter LH-RH was added to the medium. It was found that LH-RH still could stimulate FSH release, despite the continuous presence of inhibin-like activity. This means that LH-RH-stimulated release of FSH could be investigated separately from basal release. Using this way of incubation, it was found that part of the action of LH-RH on FSH release was independent of protein synthesis. Also part of LH-RH-stimulated FSH release was independent of the presence of extracellular Ca2+. Furthermore it was found that LH-RH, when added after 4 h of incubation did stimulate FSH synthesis, in the presence as well as absence of inhibin-like activity. The present results indicate that LH-RH-stimulated release of FSH is not affected by inhibin-like activity. Complete inhibition of basal release and synthesis of FSH does not prevent LH-RH from stimulating FSH release and synthesis. It is suggested that two separate releasing mechanisms for FSH could exist in the pituitary gland.

Animals↗