Search PubMed⌕ Search

Biomedical subjects

M Ekker

Publications and source records attributed to M Ekker.

54 records · Page 3Linked to original sources

Effects of ingested crude oil on thyroid hormones and on the mixed function oxidase system in ducks.

1. Ingestion of Statfjord A crude oil from the North Sea has no apparent effect on the metabolic rate of ducks (Jenssen, 1989). This may be because this particular oil does not affect plasma concentrations of thyroid hormones and enzyme activities in the mixed function oxidase (MFO) system of ducks. 2. To test this hypothesis, plasma concentrations of thyroid hormones (thyroxine and triiodothyronine), and levels of hepatic cytochrome P-450 and enzyme activities (NADPH cytochrome C reductase and GSH-S-transferase) in the MFO system were measured in domestic ducks (Anas platyrhynchos) which had ingested this crude oil. 3. Daily oral of 5 ml crude oil per kg body weight for 6 consecutive days resulted in a 53% increase in plasma triiodothyronine concentration and a 56% increase in the hepatic cytochrome P-450 level. The changes in these parameters were apparently not sufficient to cause any rise in metabolic heat production. 4. This apparent contradiction is probably because activation of the MFO-system is energetically inexpensive. Also, possible metabolic effects caused by increased plasma-triiodothyronine concentration and activation of the MFO-system may have been masked by an inhibitory effect of the crude oil on mitochondrial electrontransport and coupled phosphorylation.

Administration, Oral↗

Venous air embolism in swine: transport of gas bubbles through the pulmonary circulation.

The assumption that the lung is an effective filter for gas bubbles is of importance for certain occupations (e.g., divers, astronauts) as well as in the accomplishment of several medical procedures. The filtering capacity was tested in pigs by use of continuous air infusion into the right ventricle and a transesophageal echocardiographic transducer for detection of air in the left atrium. Twenty pigs, anesthetized with pentobarbital sodium and mechanically ventilated, were divided into groups that received air at infusion rates of 0.05 (group 1a, n = 7), 0.10 (group 2, n = 6), and 0.20 (group 3, n = 5) ml.kg-1.min-1. Two pigs served as controls. The breakthrough incidence was 0, 67, and 100%, respectively. Group 1a received a second infusion of 0.10 ml.kg-1.min-1 (group 1b, n = 7), and spillover of bubbles occurred in only 14% of these pigs. Infusion of gas caused a maximum increase in mean pulmonary arterial pressure (PAP) of 129 +/- 9% to 39.2 +/- 1.3 (SE) mmHg, with no significant difference between the groups. Breakthrough was observed only in animals with a dramatic reduction in mean arterial pressure and a PAP that returned to almost-normal values at spillover time. Our results suggest that the threshold value for breakthrough of air bubbles in pigs is reduced compared with that in dogs. The hemodynamic consequences at a given infusion rate are, however, greatly enhanced.

Animals↗

Arctic adaptation in whale hemoglobin: interplay of carbon dioxide and temperature in the oxygen unloading.

The functional properties of hemoglobin from the whale Balaenoptera acutorostrata have been characterized as a function of pH, CO2, organic phosphates and temperature. Carbon dioxide effect does not depend on the presence of organic phosphates such as 2,3-DPG and P6-inositol while it is strongly affected by temperature, so that at 37 degrees C it is completely abolished. This, together with the very small delta H of oxygen binding (delta H = -4 to -2 Kcal/mol of oxygen at pH 7.4) has been physiologically interpreted on the basis of the specific metabolic needs of fins and tail which are the place of a great muscular activity.

Adaptation, Physiological↗

Lactate does facilitate oxygen unloading from the hemoglobin of the whale, Balaenoptera acutorostrata, after diving.

The present study reports on a specific effect of lactate on the oxygen binding properties of the hemoglobin from the whale, Balaenontera acutorostrata. In fact 0.1 mM lactate may increase the amount of oxygen unloaded to the tissues as much as 30%. Under these conditions the Bohr shift, of the magnitude of about -1, does not alter the oxygen affinity, but plays an important role in the isohydric transport of carbon dioxide.

Animals↗

The activity of the mouse renin promoter in cells that do not normally produce renin is dependent upon the presence of a functional enhancer.

The expression of a hybrid gene containing the promoter region of the mouse Ren-1 or Ren-2 genes and the chloramphenicol acetyl transferase (CAT) gene coding region was analysed in five cell lines that do not normally express the renin gene. The renin promoter is inactive in each of these cell lines unless the SV40 enhancer is also present in the construct. In the latter case, transcription initiates at the normal renin start site. This is in contrast to the situation observed in lymphoid cells where the renin promoter is inactive even when coupled to a functional enhancer [(1987) EMBO J. 6, 1685-1690]. Furthermore, 5'-flanking sequences of Ren-2, placed upstream of the thymidine kinase or SV40 early region promoters do not alter the activity of these promoters in three different cell lines. The results suggest that, except for B cells, the renin promoter is not tissue-specific but that its lack of activity in cells that do not express the gene is not the result of repression but may be due to the absence in these cells of one or several trans-acting positive factors.

Animals↗

Determinant differences between the rabbit and mouse immunoglobulin kappa enhancers impair the activity of the rabbit enhancer in mouse myeloma cells.

Enhancer activity of the rabbit immunoglobulin kappa light chain gene intron conserved region (KICR) was examined in mouse myeloma cells using transient expression experiments. Compared to the homologous region of the mouse kappa light chain gene, the rabbit KICR shows nearly no stimulatory effect on expression of the indicator gene, cat. Experiments with mouse-rabbit chimeric KICRs indicated that differences in the region around the NF-kappa B binding site are responsible for the impaired activity of the rabbit KICR whereas mouse sequences covering the kappa E2 and kappa E3 motifs can be replaced by the equivalent rabbit fragment without affecting enhancer function. Creation of a perfect mouse NF-kappa B target sequence in the rabbit gene only partially restores enhancer activity. Furthermore, mouse and rabbit DNA fragments encompassing the NF-kappa B target sequence behave in an identical manner in an electrophoretic mobility shift assay. The results indicate species-related functional differences in the immunoglobulin kappa light chain gene enhancer and suggest that although the NF-kappa B binding site plays a crucial role in enhancer activity surrounding gene elements are also necessary for full enhancer effect.

Animals↗

Extra-renal transcription of the renin genes in multiple tissues of mice and rats.

Expression of the mouse renin genes (Ren-1 and Ren-2) and of the unique rat renin gene was determined in several extra-renal tissues of mice and rats by primer-directed enzymatic amplification of cDNAs. In addition to the adrenal glands, testis, and ovaries, renin transcripts are detected in the liver, whole brain, and hypothalamus and, at lower levels, in spleen, thymus, lung, and prostate. Expression of the rat renin gene correlates with that of the mouse Ren-1 gene with the notable exception of the submaxillary gland where renin transcripts are found only in mice. The levels of renin transcripts in the liver of females from both species are higher than in males. In mice, the relative levels of Ren-1 and Ren-2 transcripts vary widely in different tissues. These results support the hypothesis of a local renin-angiotensin system in multiple extra-renal sites and imply the existence of complex mechanisms of regulation of the renin gene, previously thought to be expressed in a tissue-specific manner.

Animals↗

Reduced amounts of S-adenosylmethionine decarboxylase in the adrenal glands of rats following administration of piribedil or 2-deoxyglucose.

The activity of S-adenosylmethionine decarboxylase (SAM-DC) is decreased in the adrenal gland of the rat following physical stress, metabolic stress or administration of dopamine agonists [M. Ekker and T. L. Sourkes, Endocrinology 120, 1299 (1987)]. Immunotitration studies with a serum directed against purified rat liver SAM-DC show that the reduction in activity of the enzyme following administration of 2-deoxyglucose or piribedil was paralleled by a decrease in the amount of immuno-reactive protein. There was no difference in the half-life of SAM-DC activity between piribedil-treated rats and controls. The properties of an extensively purified preparation of the adrenal enzyme resembled those of SAM-DC obtained from rat liver. It is suggested that the reduction in adrenal SAM-DC activity and protein content caused by stress is due to a reduction in the rate of synthesis of the enzyme.

Adenosylmethionine Decarboxylase↗

Structural analysis of 5'-flanking regions of rat, mouse and human renin genes reveals the presence of a transposable-like element in the two mouse genes.

The two renin genes of the mouse (Ren1 and Ren2) are expressed at different levels in the submaxillary gland (SMG). In contrast to mice, there is no detectable renin gene expression in the rat SMG. To determine the molecular basis for these different levels of renin expression, we have compared the 5'-flanking regions of the rat and mouse genes. The sequence of mouse, but not rat, genes reveals the presence in Ren1 and Ren2 of a large insertion, probably a new class of transposable elements. A second, apparently unrelated shorter insertion is present only in Ren2. Otherwise, the mouse and rat 5'-flanking sequences are well conserved and resemble the corresponding region of the human Ren gene, indicating that the insertions occurred after the separation of the rat and mouse species but before the duplication of the mouse Ren gene. We suggest that these structural differences may have a role in the differential expression of the Ren genes in mice and other animals.

Animals↗

A mouse renin promoter containing the conserved decanucleotide element binds the same B-cell factors as an authentic immunoglobulin heavy chain promoter.

A mouse renin-1 gene promoter fragment, normally inactive in B-cells, becomes a potent promoter in these cells after insertion of the highly conserved decanucleotide (dc/cd sequence) of immunoglobulin heavy and light chain promoters [(1987) EMBO J. 6, 1685-1690]. We observe retarded complexes of the same electrophoretic mobility when the cd-containing renin promoter fragment or an authentic immunoglobulin heavy chain promoter fragment is incubated with a nuclear extract from myeloma cells, suggesting that the renin promoter is activated due to its acquired ability to bind a B-cell-specific positive factor. No retarded complexes are observed with the original renin promoter fragment thus questioning the presence of a repressor as an explanation for its lack of activity in B-cells.

Animals↗

Developmental pattern of ornithine decarboxylase activity, S-adenosylmethionine decarboxylase, and polyamines of rat adrenal glands.

The concentrations of polyamines and the activities of ornithine decarboxylase (ODC) and of S-adenosylmethionine decarboxylase (SAM-DC) were measured in the adrenal glands of rats during development. Adrenal spermine content increases gradually during the first month of life whereas spermidine and putrescine decrease. A low spermidine/spermine ratio is obtained. The developmental pattern of adrenal SAM-DC resembles that of spermine content. The activity of adrenal ornithine decarboxylase increases after birth and attains a peak at 17 days of age. It declines sharply thereafter. Induction of adrenal ODC following the stress of immobilization is already observed in the rat at 4 days of age but the induction caused by maternal deprivation or cold exposure is obtained only at 17 days. The results suggest that the developmental pattern of ODC activity is independent of its responsivity to various stressors.

Adenosylmethionine Decarboxylase↗

Decreased activity of adrenal S-adenosylmethionine decarboxylase in rats subjected to dopamine agonists, metabolic stress, or bodily immobilization.

The activity of S-adenosylmethionine decarboxylase (SAM-DC) has been measured in the adrenal gland of rats given treatments that are known to result in increased activity of ornithine decarboxylase in this organ. In contrast to the effects of the dopamine agonists piribedil and apomorphine on the latter enzyme, the administration of these drugs caused decreases of SAM-DC in both parts of the gland. After piribedil the activity decreased rapidly to a minimum at 2-4 h, with recovery by 6 h. The stress of immobilization or the administration of insulin or 2-deoxyglucose (2-DG) also decreased adrenal SAM-DC activity. The results contrast with those observed in other rat tissues where SAM-DC is generally induced by treatments that induce ornithine decarboxylase. Denervation of the adrenal gland did not clearly affect the reduction in adrenomedullary SAM-DC after 2-DG. Hypophysectomy resulted in reduced SAM-DC activity in both adrenal medulla and cortex; the activity could be restored by giving the animals 2 IU ACTH daily for 4 days. These changes in activity were parallelled by changes in immunoreactive protein. 2-DG did not decrease SAM-DC in hypophysectomized rats receiving maintenance ACTH dosage. This indicates the presence of hormonal control over the activity of SAM-DC in the adrenal medulla and cortex. Acute administration of an additional 10 IU ACTH to hypophysectomized rats on maintenance dosage of ACTH resulted in decreased SAM-DC activity in both adrenal medulla and cortex. These decreases were not abolished by inhibition of corticosteroid synthesis with metopirone. PRL and GH had no significant effect on adrenal SAM-DC activity of hypophysectomized rats. The reduction of SAM-DC activity in both parts of the gland of hypophysectomized rats with administration of (Bu)2cAMP suggests that cAMP may mediate the decreases in SAM-DC caused by the above treatments.

Adenosylmethionine Decarboxylase↗

Increased activity of spermidine N1-acetyltransferase in the adrenal cortex of rats following administration of exogenous spermidine, carbamylcholine, 2-deoxyglucose and dopamine agonists.

The activity of N1-acetyltransferase was increased in the dissected adrenal cortex of the rat following a single administration of spermidine. The activity was maximal 6-8 h after the onset of treatment. The increase in enzyme activity was abolished when the rats were given cycloheximide 2 h after spermidine; this suggests that increased activity results from an augmentation in the synthesis of the enzyme. Adrenocortical spermidine N1-acetyltransferase was also induced by carbamylcholine, 2-deoxyglucose, apomorphine and piribedil, drugs that are known to cause induction of ornithine decarboxylase in that organ. Hypophysectomized rats showed reduced activity of spermidine N1-acetyltransferase when compared to sham-operated controls, and carbamylcholine no longer elicited an increase in enzyme activity in such animals. Adrenocortical spermidine N1-acetyltransferase activity of hypophysectomized rats is induced by corticotropin (ACTH). These results suggest a hormonal control over the activity of the enzyme in the adrenal cortex with ACTH acting as a mediator.

Acetyltransferases↗

Effects of alpha-difluoromethylornithine on polyamine biosynthesis and tyrosine hydroxylase induction in the adrenal gland of the rat subjected to stress or apomorphine.

Ornithine decarboxylase (ODC) and tyrosine hydroxylase (TH), the first enzymes in the polyamine and catecholamine biosynthetic pathways, respectively, are induced in the adrenal gland of the rat through the application of stressors or dopamine agonists. In the present work, following exposure of rats to cold, application of bodily restraint, or administration of apomorphine (APM), adrenal putrescine increased in proportion to the induction of ODC. Spermidine content increased by 60% after APM and about 30% after immobilization. Spermine was unaffected. To test whether the increases of ODC (and polyamines) are necessary to the slower and later induction of TH, induction of ODC in vivo was undertaken. alpha-Difluoromethylornithine (alpha-DFMO), an irreversible inhibitor of ODC, given orally or subcutaneously, almost completely abolished the induction of ODC by APM or immobilization, and inhibited the increase of putrescine in both cases, but did not affect spermidine after APM. Repeated administration of alpha-DFMO over several days did not affect the induction of adrenal TH. The results question whether increases of adrenal ODC activity and of putrescine are essential for the induction of TH in that gland.

Adrenal Glands↗

Differential effects of thioridazine, clozapine and metoclopramide on the induction of adrenomedullary enzymes by apomorphine.

The induction of two adrenomedullary enzymes, ornithine decarboxylase and tyrosine hydroxylase, by apomorphine was studied in rats receiving dopamine antagonists known to by specific in their site of action. Metoclopramide, a drug that acts predominantly on the A9 dopamine system, was effective in blocking the induction of the two enzymes by apomorphine. Thioridazine and clozapine, two antipsychotic drugs that act preferentially on the A10 dopamine systems, did not impair this induction and possibly potentiated it. The results suggest that the site of action of apomorphine responsible for the induction of adrenomedullary ornithine decarboxylase and tyrosine hydroxylase is located in the striatum.

Adrenal Medulla↗