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H Rasmussen

Publications and source records attributed to H Rasmussen.

At least 91 records · Page 5Linked to original sources
PubMed1992

Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study.

The aim of the study was to investigate the effect of 25 micrograms 17 beta-estradiol administered as a small vaginal tablet (Vagifem, Novo Nordisk A/S) on the symptoms of the vagina related to atrophy. The study was designed as a double-blind randomized placebo controlled study running for 12 weeks. The women were treated once daily for 2 weeks with the active or the placebo tablet. During the subsequent 10 weeks the women were treated twice a week. One hundred and sixty-four women were included. Ten dropped out for minor reasons, most of these due to lack of effect in the placebo group. In the Vagifem group 78.8% were suffering from moderate to severe atrophy of the vagina, compared with 81.9% in the placebo group. After 2 weeks the percentages were 14.3 and 35.3, respectively. After 12 weeks of treatment, 10.7% in the Vagifem group compared with 29.9% in the placebo group had moderate to severe atrophy (P less than 0.0001). A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia. After 12 weeks of treatment, a significant improvement was found in the Vagifem group (P less than 0.002). Before treatment 53.1% in the treatment group and 41.0% in the placebo group were suffering from urological symptoms. After 2 weeks, 60.5% of the women in the Vagifem group underwent a change for the better compared to 35.3% in the placebo group. After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8% and 32.4%. In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the postmenopausal urogenital symptoms related to atrophy.

Administration, Intravaginal↗
PubMed1992

Signal transduction mechanisms involved in carbachol-induced aldosterone secretion from bovine adrenal glomerulosa cells.

In cultured bovine adrenal glomerulosa cells, diacylglycerol content remains elevated for up to 75 min following the removal of angiotensin II. This maintained increase could provide a mechanism by which angiotensin II pretreatment may prime cells to secrete aldosterone in response to the calcium channel agonist Bay K 8644. In the present study we find that carbachol failed both to produce this persistent diacylglycerol elevation and to exert a priming effect. In addition, because carbachol was also a less potent activator of phospholipase D than angiotensin II, our results implicate phospholipase D in the maintained increase in diacylglycerol content observed following stimulation with and removal of angiotensin II. Carbachol also elicited changes in the radiolabeled levels of both myristate- and arachidonate-containing diacylglycerol. However, the rapid decline in diacylglycerol content following carbachol removal resembled the rapid fall in arachidonate-diacylglycerol; we therefore proposed that the diacylglycerol species generated with carbachol stimulation contains predominantly arachidonic acid. In summary, our results suggest that prolonged elevations in diacylglycerol content following removal of hormones such as angiotensin II, as well as the identity of the diacylglycerol species itself, may be important in the regulation of cellular responses.

Aldosterone↗
PubMed1992

Immunocytochemical localization of alpha-protein kinase C in rat pancreatic beta-cells during glucose-induced insulin secretion.

To investigate the role of protein kinase C (PKC) in the regulation of insulin secretion, we visualized changes in the intracellular localization of alpha-PKC in fixed beta-cells from both isolated rat pancreatic islets and the pancreas of awake unstressed rats during glucose-induced insulin secretion. Isolated, perifused rat islets were fixed in 4% paraformaldehyde, detergent permeabilized, and labeled with a mAb specific for alpha-PKC. The labeling was visualized by confocal immunofluorescent microscopy. In isolated rat pancreatic islets perifused with 2.75 mM glucose, alpha-PKC immunostaining was primarily cytoplasmic in distribution throughout the beta-cells. In islets stimulated with 20 mM glucose, there was a significant redistribution of alpha-PKC to the cell periphery. This glucose-induced redistribution was abolished when either mannoheptulose, an inhibitor of glucose metabolism, or nitrendipine, an inhibitor of calcium influx, were added to the perifusate. We also examined changes in the intracellular distribution of alpha-PKC in the beta-cells of awake, unstressed rats that were given an intravenous infusion of glucose. Immunocytochemical analysis of pancreatic sections from these rats demonstrated a glucose-induced translocation of alpha-PKC to the cell periphery of the beta-cells. These results demonstrate that the metabolism of glucose can induce the redistribution of alpha-PKC to the cell periphery of beta-cells, both in isolated islets and in the intact animal, and suggest that alpha-PKC plays a role in mediating glucose-induced insulin secretion.

Animals↗
PubMed1992

Ca(2+)-cyclic AMP interactions in sustained cellular responses.

As early as 1970 it was apparent that the cyclic AMP (cAMP) and Ca2+ messenger systems often interact to regulate cellular responses. Work over the past 20 years has greatly expanded our knowledge of these interactions, and has shown that these signalling systems interact in complex ways to regulate sustained cellular responses such as aldosterone secretion, smooth muscle contraction and insulin secretion. The latter system is considered in detail because it illustrates several types of interactions, both positive and negative, which help to determine the normal response of beta-cells to physiological stimuli, and how abnormalities in secretory patterns can develop as a consequence of the prolonged stimulation of a messenger system.

Animals↗
PubMed1991

Influence of staurosporine on glucose-mediated and glucose-conditioned insulin secretion.

The effect of staurosporine, a putative inhibitor of protein kinase C (PKC), on insulin secretion induced by glucose and 4-methyl-2-oxopentanoate (KIC) was examined. In addition, the effects of staurosporine on the actions of other agonists, for which glucose acts as a conditional modifier, were also examined. At 20 nM, staurosporine caused a marked inhibition of second-phase insulin secretion, whether it was stimulated by 10 mM- or 20 mM-glucose, by 15 mM-KIC, or by carbachol or tolbutamide in islets co-perifused with 7.0 mM-glucose. In each case, the second-phase secretory response was inhibited by 70-85%. In contrast, in all cases there was no effect of staurosporine on the magnitude of the first phase of insulin secretion, nor on the time course of first-phase secretion, except when glucose alone was the secretagogue. With either 10 mM- or 20 mM-glucose, the peak of the first phase of insulin secretion was delayed. Staurosporine does not alter glucose metabolism, or the ability of glucose to activate phosphoinositide hydrolysis or to cause the translocation of alpha-PKC to the membrane. These findings support the concept that PKC activation plays an important role in fuel-induced or fuel-conditioned insulin secretion.

Alkaloids↗
PubMed1991

Effects of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on islet-cell responsiveness.

Collagenase-isolated rat islets were labelled for 2 h in myo-[2-3H]inositol solution supplemented with 2.75 mM-glucose. The phorbol ester phorbol 12-myristate 13-acetate (PMA; 0.1 or 1 microM) was also present in some experiments. After labelling, islets were washed and then perifused in 2.75 mM-glucose to establish basal [3H]inositol-efflux and insulin-secretory rates. Subsequently, the responses of these islets to stimulation with various agonists were assessed. Inositol phosphate accumulation was measured at the termination of the perifusion. In separate experiments, the cellular location of protein kinase C (PKC) after PMA pretreatment was measured by quantitative immunoblotting of membrane and cytosolic fractions. The following observations were made. (1) Labelling in 0.1-1 microM-PMA had no deleterious effect on total [3H]inositol incorporation during the 2 h labelling period. However, islets labelled for 2 h in 1 microM-PMA were unable to respond, in terms of increases in insulin release, to a 1 microM-PMA stimulus during the subsequent perifusion. (2) As compared with the responses of control islets labelled in 2.75 mM-glucose alone, islets labelled in the additional presence of 1 microM-PMA displayed a significant impairment in phosphoinositide (PI) hydrolysis, but an enhancement of both first-and second-phase insulin secretion, in response to subsequent 20 mM-glucose stimulation. (3) Decreasing extracellular Ca2+ level to 0.1 mM and including the Ca(2+)-channel antagonist nitrendipine (0.5 microM) along with 1 microM-PMA during the [3H]inositol-labelling period did not alter the response of the islets to the subsequent addition of 20 mM-glucose. Glucose-induced PI hydrolysis was still inhibited and 20 mM-glucose-induced insulin release was still enhanced. (4) A markedly amplified and sustained insulin-secretory response to 200 microM-tolbutamide in the presence of 2.75 mM-glucose was also obtained from 1 microM-PMA-pretreated islets. This contrasts sharply with the small and transient response to tolbutamide noted in control islets. (5) When present only during the perifusion phase of the experiments, nitrendipine (0.5 microM) abolished the amplified insulin-secretory responses to both 20 mM-glucose and 200 microM-tolbutamide noted in PMA-pretreated islets. (6) Prior labelling in 1 microM-PMA dramatically amplified the insulinotropic effect of 25 mM-K+ or 5 microM-A23187 stimulation. The amplified insulin-secretory response to K+, but not to A23187, was abolished by inclusion of nitrendipine during the perifusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

[Inguinal hernia with acute acalculous cholecystitis].

The presence of an inflamed gall bladder in an inguinal hernia has not been described previously. As in the case here, most pathological processes in hernias are found in old and frequently mentally reduced patients. It is therefore important to be alert to changes in the symptomatology in particularly large inguinal hernias in this group of patients.

Acute Disease↗
PubMed1991

Cell cycle-dependent coupling of the calcitonin receptor to different G proteins.

Calcitonin is a calcium regulating peptide hormone with binding sites in kidney and bone as well as in the central nervous system. The mechanisms of signal transduction by calcitonin receptors were studied in a pig kidney cell line where the hormone was found to regulate sodium pumps. Calcitonin receptors activated the cyclic adenosine monophosphate (cAMP) or the protein kinase C (PKC) pathways. The two transduction pathways required guanosine triphosphate (GTP)-binding proteins (G proteins) (the choleratoxin sensitive Gs and the pertussis toxin sensitive Gi, respectively) and led to opposite biological responses. Moreover, selective activation of one or the other pathway was cell cycle-dependent. Therefore, calcitonin may induce different biological responses in target cells depending on their positions in the cell cycle. Such a modulation of ligand-induced responses could be of importance in rapidly growing cell populations such as during embryogenesis, growth, and tumor formation.

Adenylyl Cyclases↗
PubMed1991

Angiotensin-II-induced changes in diacylglycerol levels and their potential role in modulating the steroidogenic response.

Angiotensin-II (Ang II) not only increases aldosterone secretion from bovine adrenal glomerulosa (AG) cells, but also primes these cells to respond to a subsequent challenge with the calcium channel agonist Bay K 8644. In cultured AG cells we investigated the hypothesis that this priming effect was the result of a persistent elevation in diacylglycerol (DAG) content. Ang II elicited an increase in DAG content, which was maintained for up to 75 min after the removal of Ang II, an effect which could underlie the ability of Ang II to prime the cells to respond to Bay K 8644. We then investigated the possibility that the DAG found in bovine AG cells consists of multiple species and the potential relationship of the species to the persistent elevation. We found that [3H]arachidonate and [14C]myristate were differentially incorporated into phospholipids, with approximately 80-85% of the latter radiolabel contained in phosphatidylcholine. Ang II elicited increases in the levels of both arachidonate- and myristate-containing DAG. The subsequent addition of an Ang II antagonist resulted in a rapid decrease in [3H]arachidonate-labeled DAG levels, but a much slower decline in myristate-containing DAG. These results suggest that the species of DAG generated in response to hormonal stimulation may be important in determining the speed with which this signal is terminated. Ang II also stimulated the release of water-soluble [3H]choline metabolites, in particular choline and phosphorylcholine, from prelabeled cells. These results indicate that 1) various DAG species exhibit different turnover rates; and 2) perhaps as a result of this disparity, the increase in DAG induced by an agonist may persist for a considerable period of time after the removal of the agonist or the inhibition of its action.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Parathyroid hormone modulates angiotensin II-induced aldosterone secretion from the adrenal glomerulosa cell.

The effect of PTH on aldosterone secretion from isolated bovine adrenal glomerulosa cells was examined. PTH binding was autoradiographically localized to the adrenal cortex, suggesting a specific effect. This binding of PTH was displaceable by cold PTH, but not by ACTH. No binding was observed in the adrenal medulla. In addition, PTH was shown to stimulate aldosterone secretion in a dose-dependent manner and to potentiate aldosterone secretion in response to angiotensin-II, such that PTH (10(-9)M) elevated the secretory rate from 58.6 +/- 6.8 to 110.9 +/- 19 pg/min.million cells in the presence of 10 nM angiotensin-II. The magnitude of the synergism between the two hormones depended on the concentrations of PTH and angiotensin-II as well as the time during which aldosterone secretion was measured. Within the first 15 min of stimulation, PTH increased the sensitivity to angiotensin-II, shifting the Ka for activation from 1.0 to 0.3 nM. In contrast, between 30-45 min of angiotensin-II stimulation, PTH elevated the maximal secretory response to angiotensin-II from 109 +/- 3.4 to 219 +/- 13.3 pg/min.million cells. By itself PTH elicited only a small increase in the intracellular Ca2+ concentration, as measured by aequorin luminescence in glomerulosa cells. In cells pretreated with angiotensin-II or 15 mM potassium, the intracellular calcium response to PTH was markedly potentiated. PTH was also found to cause a small increase in the cellular cAMP content. Thus, PTH stimulates aldosterone secretion from adrenal glomerulosa cells, both alone and in combination with angiotensin-II.

Adrenal Cortex↗
PubMed1990

Protein kinase C translocation in intact vascular smooth muscle strips.

Using intact muscle strips from the bovine carotid artery, the time course of translocation of protein kinase C (PKC) from the cytosol to the membrane fraction was measured in response to various agonists that induce contractile responses. PKC activity was assessed by Ca2+/phospholipid-dependent phosphorylation of histone. Exposure of the muscle strips to phorbol ester (12-deoxyphorbol 13-isobutyrate) induced a rapid and sustained translocation of PKC from the cytosol to the membrane fraction, and a slowly developing but sustained contractile response. Histamine induced a comparable initial translocation of PKC to the membrane which then decreased somewhat to a stable plateau significantly above basal values. Histamine also led to a rapid and sustained increase in tension. Angiotensin I, which caused a rapid but transient contraction, induced a rapid initial translocation of PKC to the membrane. The membrane-associated PKC then declined to a stable plateau significantly lower than that seen after a histamine-induced response, and only slightly above the basal value. Endothelin, which induced a sustained contraction, caused a sustained translocation of PKC from the cytosol to the membrane. In contrast, although exposure to 35 mM-KCl induced a rapid and sustained contraction, it caused only a transient translocation of PKC; the membrane-associated PKC returned to its basal value within 20 min. These results demonstrate that PKC in intact smooth muscle can be rapidly translocated to the membrane and remains membrane-bound during sustained phorbol ester- or agonist-induced contractions, but that such a sustained translocation of PKC does not occur during prolonged stimulation with KCl.

Angiotensin II↗
PubMed1990

Effect of buffer systems and pHi on the measurement of [Ca2+]i with fura 2.

The fluorescent probe, fura 2, is widely used to measure agonist-induced changes in intracellular calcium concentration ([Ca2+]i) in cultured cells. However, in many instances, the results obtained in the same cell type have differed from one study to the next. The possibility that such differences might be due to experimental conditions was examined by using fura 2 in four different cell types responding to appropriate agonists when the cells were incubated in either CO2/HCO3-- or HEPES-buffered media. Examined were: 1) the response of rat glomerular mesangial cells to arginine vasopressin, 2) the response of vascular smooth muscle cells to angiotensin II, 3) the response of adrenal glomerulosa cells to angiotensin II, and 4) the response of hypothalamic cells to insulin-like growth factor-1. In each cell type there was a significant difference in the pattern of agonist-induced change in [Ca2+]i when HEPES vs. CO2/HCO3- was used as the buffer system: in HEPES buffer, agonist addition led to a transient rise in [Ca2+]i followed by a fall to a sustained plateau 27 to 34 nM higher than the original basal value, whereas in CO2/HCO3- buffer, agonist addition led to an identical transient increase in [Ca2+]i followed by a fall to a value within 10 nM or less of the preagonist level. The plateau value of [Ca2+]i in the different buffers was examined in relationship to known differences in intracellular pH (pHi). It was found that measurements of [Ca2+]i with fura 2 were influenced by shifts in pHi that occur when cells are incubated in either HEPES-buffered or CO2/HCO3- media of differing pHo values. However, at any given value of pHi, the apparent [Ca2+]i measured in cells incubated in HEPES-buffered media was slightly higher than in cells incubated in CO2/HCO3- buffered media.

Adrenal Medulla↗
PubMed1990

Glucose-induced translocation of protein kinase C in rat pancreatic islets.

The role of protein kinase C (PKC) as a mediator of glucose-induced insulin secretion has been a subject of controversy. Glucose-induced translocation of PKC has not been reported, and the relevant PKC isoenzymes in islets have not been identified. To address these issues, we developed specific antibodies to the alpha, beta, and gamma isoenzymes of PKC. Western blots of homogenates of freshly isolated rat islets probed with these antibodies revealed that the major isoenzyme present is alpha-PKC. Islets were perifused for 15 min with either 2.75 mM glucose, 20 mM glucose, 20 mM glucose plus 30 mM mannoheptulose, 15 mM alpha-ketoisocaproate, or alpha-ketoisocaproate plus mannoheptulose. Quantitative immunoblotting of membrane and cytosol fractions showed that alpha-PKC translocated from the cytosol to the membrane in freshly isolated rat islets stimulated with either 20 mM glucose or 15 mM alpha-ketoisocaproate. Both the secretory response and the translocation of alpha-PKC were blocked by the addition of mannoheptulose, an inhibitor of glucose metabolism, in islets stimulated with glucose but not in islets stimulated with alpha-ketoisocaproate. These results support a role for alpha-PKC in mediating glucose-induced insulin secretion in pancreatic islets.

Amino Acid Sequence↗
PubMed1990

Interactions between Ca2+ and cAMP messenger system in regulation of airway smooth muscle contraction.

Cholinergic stimuli acting via muscarinic receptors stimulate airway smooth muscle to contract and beta-adrenergic stimuli induce it to relax. Cholinergic agonists stimulate intracellular Ca2+ release and Ca2+ influx, and beta-adrenergic agonists stimulate adenosine 3',5'-cyclic monophosphate (cAMP) production. Since it was found that cAMP alters cholinergic agonist-induced changes in cellular Ca2+ metabolism, it was postulated that cAMP brought about a relaxation of this smooth muscle primarily by altering Ca2+ metabolism. More recently, it has become clear that when cholinergic agonists, as well as histamine and serotonin, act, the hydrolysis of polyphosphoinositols is stimulated, diacylglycerol production is increased, and coordinated changes in Ca2+ metabolism and protein kinase function occur. These agonists also act to inhibit adenylate cyclase activity. Conversely, it has been found that in the absence of agonist activation, cAMP increases Ca2+ influx without stimulating contraction and that in the presence of muscarinic agonists, it acts to inhibit polyphosphoinositide hydrolysis. In addition, cAMP has been shown to alter the state of phosphorylation of a number of cellular proteins, an effect that is independent of any effect on cellular Ca2+ metabolism. Based on these newer data, an expanded model of Ca2(+)-cAMP interactions in the regulation of airway smooth muscle tone is presented. A key feature of this model is the operation of dual, reciprocal inhibitory signals by which the Ca2+ and cAMP messenger systems modulate each other's expression.

Animals↗