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B L Jensen

Publications and source records attributed to B L Jensen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of dietary salt on adrenomedullin and its receptor mRNAs in rat kidney.

There is accumulating evidence that adrenomedullin (ADM) is involved in the control of salt and water homeostasis. ADM is considered to act primarily in a paracrine fashion, and since the kidneys are target organs for ADM, we investigated the localization and regulation of ADM and ADM receptor (ADM-R) mRNAs in the kidney. mRNAs for ADM and ADM-R were colocalized in renal vessels, glomeruli, and inner medullary collecting ducts. ADM mRNA was also detected in proximal tubules, whereas ADM-R mRNA was found in distal convoluted tubules. By ribonuclease protection assay, the abundance of ADM mRNA was fourfold higher in cortex than in outer medulla and papilla. In isolated glomeruli, ADM mRNA was threefold higher compared with cortex. Conversely, ADM-R mRNA was fourfold higher in papilla than in renal cortex. This distribution of mRNAs for ADM and ADM-R suggests a cortical source of ADM and a preferential action of ADM in the papilla. Ten days of feeding a low-salt (0.02%) or a high-salt diet (4%) did not change ADM mRNA or ADM-R mRNA in any kidney zone.

Adrenomedullin↗
PubMed1998

Chloride regulates afferent arteriolar contraction in response to depolarization.

-Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-induced contraction in isolated perfused rabbit afferent arterioles. In 70% of vessels examined, K+-induced contraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl- (30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel antagonist diltiazem (10(-6) mol/L) abolished K+-induced contractions. Bicarbonate did not modify the sensitivity to chloride. Norepinephrine (10(-6) mol/L) induced full contraction in depolarized vessels even in the absence of chloride. Iodide and nitrate were substituted for chloride with no inhibitory effect on K+-induced contraction. Approximately 30% of the vessels constricted in response to K+ in the absence of chloride. This response was reversibly blocked by the alpha1-blocker phentolamine (PA) (10(-5) mol/L) and, with PA present, the dependence on chloride was similar to the above series. The results show that K+-induced contraction of smooth muscle cells in the afferent arteriole is highly sensitive to chloride, whereas neurotransmitter release and ensuing contraction is not dependent on chloride. Thus, there are different activation pathways for depolarizing vasoconstrictors and for the sympathetic nervous system in renal afferent arterioles. This could be of physiological relevance for the resetting of afferent arteriolar sensitivity during changes in salt intake.

Animals↗
PubMed1997

Resistance of human breast-cancer cells to the pure steroidal anti-estrogen ICI 182,780 is not associated with a general loss of estrogen-receptor expression or lack of estrogen responsiveness.

To elucidate the mechanisms responsible for the development of anti-estrogen resistance, we have cloned and established 3 stable ICI-182,780-resistant sub-lines, MCF-7/182R-1, MCF-7/182R-6 and MCF-7/182R-7 from the estrogen-receptor(ER)-positive and estrogen-responsive human breast-cancer MCF-7 cell line by long-term treatment with 10(-7) M ICI 182,780. The ICI-182,780-resistant MCF-7 sub-lines express ER, but compared with MCF-7 cells the level is significantly lower in all 3 sub-lines. In the MCF-7 cell line we find that ER expression is regulated by estrogen and anti-estrogens at the transcriptional and post-transcriptional level. This is in contrast to the ICI-182,780-resistant sub-lines, in which we find very little hormonal effects on the ER mRNA expression level. The resistant sub-lines also deviate from parent characteristics by the complete lack of expression of progesterone receptor even when grown in the presence of estradiol. All 3 resistant sub-lines have a lower basal expression of cathepsin-D mRNA comparable with the lower ER expression, but, in contrast, they have higher basal expression of the pS2 mRNA than the parent MCF-7 cell line. Although there are different basal expression levels of the pS2 and cathepsin-D genes, the resistant sub-lines behave like the parent MCF-7 cell line with respect to the hormonal regulation of both genes. The estrogen receptors in the resistant sub-lines have also maintained wild-type characteristics with respect to estrogen and anti-estrogen regulation of the estrogen-regulated proteins procathepsin D, alpha1-antitrypsin and a 42-kDa protein. The resistant cells require estrogen for growth in athymic nude mice. Our results clearly demonstrate that the ER in the resistant sub-lines have a normal function for most parameters investigated, supporting our earlier observation that only wild-type ER protein is expressed in these cells. The few observed differences in ER function between the parent MCF-7 cell line and the resistant sub-lines are not likely to be responsible for the ICI-182,780-resistant phenotype.

Animals↗
PubMed1997

Giant renin secretory granules in beige mouse renal afferent arterioles.

The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige mice with that of control (NMRI) mice. Immunohistochemistry with an antibody specific for renin revealed intense staining of the juxtaglomerular part of the afferent arterioles in both strains of mice. Plasma renin concentrations were higher in the controls than in the beige mice (4.4+/-0.6 vs 2.5+/-0.3 mGoldblatt units/ml). The total volume of renin granules per afferent arteriole was similar in the two mice strains (1114 microm3 in the controls and 1507 microm3 in the beige mice). The total number of renin granules per arteriole as assessed by stereological techniques was about 1900 in controls (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable tool in the study of renin release.

Animals↗
PubMed1997

Differential regulation of renal cyclooxygenase mRNA by dietary salt intake.

Experiments were done to investigate the influence of dietary salt intake on renal cyclooxygenase (COX) I and II mRNA levels. To this end rats were fed either a low NaCl diet (LS; 0.02% NaCl wt/wt) or a high NaCl diet (HS diet; 4% NaCl wt/wt) for 5, 10 and 20 days. After 10 days Na excretion differed 760-fold, plasma renin activity and renin mRNA were increased eight- and threefold in LS compared to HS animals. Total renal COX I mRNA decreased 50% following the LS diet and did not change after the HS diet. Conversely, COX II mRNA declined after HS intake and transiently increased after salt depletion. COX I and II mRNAs were unevenly distributed along the cortical-medullary axis with ratios of the cortex:outer medulla:papilla of 1:3:23 and 1:1:2, respectively. Cortical COX mRNAs were inversely regulated by salt intake with eightfold changes in COX II. Conversely, in medullary zones, COX I mRNA correlated directly with salt intake. We conclude that dietary salt intake influences renal cyclooxygenase mRNAs zone-specifically with opposite responses between cortex and medulla. Cortical COX II-mediated prostaglandin formation is probably important in low salt states whereas medullary COX I-produced prostaglandins seem to be more important for renal adaptation to a high salt intake.

Animals↗
PubMed1997

Chloride is essential for contraction of afferent arterioles after agonists and potassium.

A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses to norepinephrine, angiotensin II (ANG II), and potassium were measured after chloride depletion and compared with controls. Chloride depletion did not change arteriolar diameters, but the response to norepinephrine was markedly reduced when chloride was substituted with gluconate (n = 6) or isethionate (n = 6). Reintroduction of chloride fully restored the sensitivity to norepinephrine. Contractions after ANG II and potassium were totally abolished in the absence of chloride (n = 6). In additional experiments (n = 7), the arteriolar contraction to 100 mM potassium was abolished only 1 min after removal of extracellular chloride. We conclude that norepinephrine and ANG II use different mechanisms for contraction and that extracellular chloride is essential for contraction in afferent arterioles after activation of voltage-dependent calcium channels. We suggest that a chloride influx pathway is activated concomitantly with the voltage-dependent calcium channel to allow chloride influx to compensate for the cation influx.

Angiotensin II↗
PubMed1997

Adrenomedullin stimulates renin release and renin mRNA in mouse juxtaglomerular granular cells.

The recently discovered peptide adrenomedullin (AM) alters blood pressure through effects on the resistance vessels. Moreover, AM modifies the secretion of corticotropin and aldosterone and could thereby indirectly influence blood pressure through the renin-angiotensin-aldosterone system. Although plasma AM and renin concentration have been found to directly correlate, a causal linkage between AM and renin has not been shown. The present study tested the influence of AM on renin secretion and renin gene expression by renal juxtaglomerular granular cells. Prominent expression and release of AM by vascular structures has been reported; therefore, we investigated the local expression of AM in juxtaglomerular structures. Renin release from isolated perfused rat kidneys was dose-dependently increased by AM (1 to 30 nmol/L), whereas renal perfusate flow rate increased up to 17% at a constant perfusion pressure of 100 mm Hg. In primary cultures of mouse granular cells, AM augmented renin release, renin mRNA accumulation, and cAMP production in a dose- and time-dependent manner (threshold values in the range 10 pmol/L to 1 nmol/L). By reverse transcription-polymerase chain reaction, significant expression of the AM gene was detected in microdissected rat glomeruli with afferent arterioles and in primary cultures of mesangial and granular cells. We conclude that AM is expressed in juxtaglomerular structures and that it has a direct stimulatory effect on renin secretion and renin mRNA abundance by receptors on juxtaglomerular cells, possibly through increases in cAMP. AM could act as an autocrine/paracrine stimulatory factor in the control of renin secretion and renin gene expression.

Adrenomedullin↗
PubMed1996

Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles.

Calcium-activated chloride channels have been proposed to control renin release from juxtaglomerular cells and to be involved in the excitation-contraction coupling of the renal afferent arteriole. The hypothesis was tested on renin release from rat glomeruli and in microperfused rabbit afferent arterioles with the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Renin secretion was equally enhanced by omission of extracellular calcium and by addition of 0.5 mM DIDS. The inhibitory effect of calcium was blocked by DIDS. The stimulatory effects of low calcium [with or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate. Norepinephrine (5 x 10(-7)-1 x 10(-6) M) and angiotensin II (1 x 10(-8)-10(-6) M) evoked reversible and dose-dependent contractions of microperfused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the basal diameter of the arterioles but strongly inhibited the response to angiotensin II and attenuated the duration of the contractile response to norepinephrine. The results support the hypothesis that DIDS-sensitive calcium-activated chloride channels are involved in regulation of renin release and in the afferent arteriolar contraction after angiotensin II but do not play a pivotal role in the response to norepinephrine.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1996

Prostaglandins stimulate renin secretion and renin mRNA in mouse renal juxtaglomerular cells.

This study examined 1) effects of prostaglandins (PG) on renin secretion and renin gene expression from isolated juxtaglomerular granular cells and 2) expression of cyclooxygenases in juxtaglomerular structures. Incubation of granular cell cultures with PGE2, -I2, -F2 alpha, and thromboxane B2 identified PGI2 and PGE2 as stimulators of renin secretion; the effects were dose and time dependent. PGE2 also increased renin mRNA accumulation time and dose dependent. PGE2 and PGI2 activated adenylate cyclase concentration dependent in granular cells. PGE2 stimulations of renin secretion and renin mRNA were nonadditive to those of forskolin and were inhibited by endothelin. The findings are compatible with cellular actions through adenosine 3',5'-cyclic monophosphate (cAMP). On total RNA harvested from whole kidneys, from microdisected glomeruli with attached afferent arterioles and from mesangial cells in primary culture, reverse transcription-polymerase chain reaction revealed significant expression of cyclooxygenase I and II. By direct interaction with PG receptors on renal juxtaglomerular cells, PGE2 and PGI2 can act as potent and rapid stimulators of renin secretion and renin mRNA probably through cAMP-dependent pathways.

Adenylyl Cyclases↗
PubMed1994

Renin release from permeabilized juxtaglomerular cells is stimulated by chloride but not by low calcium.

The intracellular concentrations of calcium and chloride have been suggested to be involved in the control of renin secretion from juxtaglomerular (JG) cells. We have tested these propositions on permeabilized JG cells. Rat glomeruli with attached JG cells were isolated by the magnetic iron technique, superfused, and permeabilized by 20 microM digitonin for 12 min. The calcium concentration was varied with Ca ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) buffers [0 (5 MM EGTA without calcium), 17, 73, 170, 440, or 700 nM and 1.5, 15 or 150 microM]. These maneuvers had no effect on renin release, while 1.5 mM calcium caused a stimulation, which was not inhibited by 50 mM sucrose. Isosmotic increases in the chloride concentration to 25, 60, and 132 mM resulted in prompt stimulations of renin release. Similarly, iodide and nitrate stimulated renin release. We conclude that renin release from permeabilized JG cells is unaffected by calcium concentrations in the nano- and micromolar range, while the release is stimulated by chloride or other permeant anions. We suggest that in intact JG cells an increase in calcium inhibits renin release through activation of chloride channels followed by a drop in the intracellular chloride concentration. The stimulation caused by the high calcium concentration may be a toxic effect or may be due to stimulation of the fusion between granules and cell membrane in a way analogous to other secretory cells.

Animals↗
PubMed1993

Osmotically sensitive renin release from permeabilized juxtaglomerular cells.

Renin secretion from juxtaglomerular (JG) cells is sensitive to external osmolality in a way that has been suggested to depend either on cellular volume or on effects on secretory granules. To distinguish between these possibilities, a technique for permeabilization of JG cell membranes was developed. Rat glomeruli with attached JG cells were isolated and permeabilized by 20 microM digitonin for 12 min and followed by continuous exposure to 2 microM digitonin. Experiments on proximal tubules showed that cellular volume was unaffected by changes in external sucrose concentration after a similar permeabilization procedure. With permeabilized JG cells the following changes in osmolality were tested (in mM sucrose): +90 (n = 6), +60 (n = 5), +30 (n = 6), +15 (n = 6), -15 (n = 5), -30 (n = 6), -60 (n = 6), and -90 (n = 6). With nonpermeabilized cells similar experiments were done with changes of +90 (n = 7), +30 (n = 4), -30 (n = 4), and -90 (n = 6) mM sucrose. Increases in osmolality caused inhibition of renin release, whereas decreases stimulated secretion. Within +/- 10% variations in osmolality there were no differences between the responses in permeabilized and intact cells, whereas the responses with larger changes were less in the permeabilized cells. Increase or decrease in urea concentration by 30 mM did not affect renin release. Thus water fluxes can influence renin release by a mechanism that is independent of cell volume.

Animals↗
PubMed1992

Dental treatment strategies in cleidocranial dysplasia.

Based on the findings of our recent longitudinal study on the abnormalities of the dentition in cleidocranial dysplasia (CCD), a hypothesis has been proposed, which makes it possible to predict time of onset of formation of supernumerary teeth and their location in the jaws. It was found that a diagnosis should be made early so that formation of supernumerary teeth can be diagnosed and early intervention undertaken. It should be possible to diagnose supernumerary incisors at about 5-7 years of age and supernumerary canines and premolars a few years later. When root length of the normal permanent teeth has reached about one third of its final length, the overlying supernumerary teeth should be removed, together with overlying bone and primary teeth. In regions where no supernumerary teeth are formed, eruption may also be improved by removal of the primary teeth and surgical exposure of the underlying permanent teeth. Conventional orthodontic treatment and eventually autotransplantation of teeth may still be necessary in the future, but it can be anticipated that the new strategy, with much earlier intervention, will materially reduce the extent of surgical and orthodontic interventions, which have previously been of extremely long duration, tedious to the patients and often of limited success.

Adolescent↗
PubMed1992

Involvement of chloride in renin secretion from isolated rat glomeruli.

The sensitivity of renin release to changes in anion and calcium concentrations was assessed in superfused rat glomeruli with attached juxtaglomerular cells. Isosmotic substitution of Cl-with gluconate (1/12, 1/6, 1/3, 2/3, or total exchange), isethionate (15 or 101 mM), or sulfate (10 mM) inhibited renin release reversibly. Substitution of Cl- with nitrate (101 mM) stimulated renin secretion. Substitution with iodide (15 or 101 mM) had no consistent effect. The stimulation induced by calcium-free solutions was high in May and low in September. In the absence of chloride, the response to calcium-free solution was inhibited similarly all year. In May reintroduction of calcium and chloride stimulated renin release, suggesting that releasable renin had been stockpiled during the exposure to calcium-free solution. In September reintroduction of calcium and chloride inhibited renin release. It is concluded that the renin secretory process has a demand for permeant anions. The stimulation caused by low external calcium involves at least two mechanisms: one is anion sensitive, powerful, varies with the season, and includes a recruitment phenomenon; another is anion insensitive and weak.

Animals↗
PubMed1992

HIV-2 infection in Denmark.

A collection of 3019 selected serum samples (ss), comprising 329 ss from intravenous drug abusers, 558 ss from homosexual men, 682 samples from persons attending a STD clinic, 100 ss from individuals of African origin, 300 ss from sexual contacts to Africans, 650 ss from Danish blood donors who resided in Africa greater than 2 years prior to donating the ss, and 400 ss with equivocal antibody reactions in an HIV-1 Western blot was tested for antibodies against HIV-2 by in-house HIV-2 ELISA and Western blot. Four ss were positive for antibodies against HIV-2. Three of the ss originated from West African men, the fourth belonged to the spouse of one of these men. Three of the samples presented with an uncharacteristic reaction in a HIV-1 Western blot. The study indicates that HIV-2 infection is not yet widespread in Denmark and that it remains closely related to West Africa.

Africa, Western↗
PubMed1992

HIV infection among intravenous drug users in Copenhagen.

From October 1985 until the end of December 1986, 439 intravenous drug users (IVDU) presented themselves at the outpatient venereal disease clinic of Copenhagen for an HIV-test. HIV-antibodies were found in 53 out of 272 men (19.5%) and in 25 of 167 women (15.0%), giving an overall prevalence of 17.8%. Risk factors for HIV were the length of drug abuse (p less than 0.05) and having injected drugs within the last six months before testing (p less than 0.005). HIV-antibodies were found in 18 of 90 women (20%) and in three of 20 men (15%), who had a history of a past or ongoing life as a prostitute. The IVDU in this study have been chosen as a cohort and recalled for an ongoing follow-up study focusing on drug and sexual behaviour in relation to the initial HIV-test result.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Cellular and intrarenal aspects of renin secretion].

Renin is synthesized, stored and excreted from cells (JG cells) localized in the afferent glomerular arteriole. Preprorenin is formed first by biosynthesis. After splitting off of the pre-fraction, glycosylering and passage through the Golgi apparatus, prorenin, which is biologically inactive, may be excreted immediately or be stored in secretory granules where activation occurs by splitting off of the pro-fraction. Excretion of the secretory granules is regulated and takes place by exocytosis. Important intracellular signal molecules include, inter alii, calcium which is inhibitory and cyclic AMP which stimulates release. In addition, osmotic water movements also play an important role. The physiological regulatory mechanisms include 1) a baroreceptor: lowered perfusion pressure to the kidney stimulates release of renin, 2) a tubular signal: decrease in Cl(-)-concentration at the macula densa stimulates release of renin, 3) the nerve supply of the kidney which stimulates directly via beta-receptors on the JG cells and also indirectly via alpha-adrenergic influence on haemodynamic and tubular resorption and 4) local and circulating hormones, particularly angiotensin II and prostaglandins.

Calcium↗