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B S Jensen

Publications and source records attributed to B S Jensen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Na+-K+-2Cl- cotransport in Ehrlich cells: regulation by protein phosphatases and kinases.

To identify protein kinases (PK) and phosphatases (PP) involved in regulation of the Na+-K+-2Cl- cotransporter in Ehrlich cells, the effect of various PK and PP inhibitors was examined. The PP-1, PP-2A, and PP-3 inhibitor calyculin A (Cal-A) was a potent activator of Na+-K+-2Cl- cotransport (EC50 = 35 nM). Activation by Cal-A was rapid (<1 min) but transient. Inactivation is probably due to a 10% cell swelling and/or the concurrent increase in intracellular Cl- concentration. Cell shrinkage also activates the Na+-K+-2Cl- cotransport system. Combining cell shrinkage with Cal-A treatment prolonged the cotransport activation compared with stimulation with Cal-A alone, suggesting PK stimulation by cell shrinkage. Shrinkage-induced cotransport activation was pH and Ca2+/calmodulin dependent. Inhibition of myosin light chain kinase by ML-7 and ML-9 or of PKA by H-89 and KT-5720 inhibited cotransport activity induced by Cal-A and by cell shrinkage, with IC50 values similar to reported inhibition constants of the respective kinases in vitro. Cell shrinkage increased the ML-7-sensitive cotransport activity, whereas the H-89-sensitive activity was unchanged, suggesting that myosin light chain kinase is a modulator of the Na+-K+-2Cl- cotransport activity during regulatory volume increase.

Animals↗
PubMed1998

Characterization of the cloned human intermediate-conductance Ca2+-activated K+ channel.

The human intermediate-conductance, Ca2+-activated K+ channel (hIK) was identified by searching the expressed sequence tag database. hIK was found to be identical to two recently cloned K+ channels, hSK4 and hIK1. RNA dot blot analysis showed a widespread tissue expression, with the highest levels in salivary gland, placenta, trachea, and lung. With use of fluorescent in situ hybridization and radiation hybrid mapping, hIK mapped to chromosome 19q13.2 in the same region as the disease Diamond-Blackfan anemia. Stable expression of hIK in HEK-293 cells revealed single Ca2+-activated K+ channels exhibiting weak inward rectification (30 and 11 pS at -100 and +100 mV, respectively). Whole cell recordings showed a noninactivating, inwardly rectifying K+ conductance. Ionic selectivity estimated from bi-ionic reversal potentials gave the permeability (PK/PX) sequence K+ = Rb+ (1.0) > Cs+ (10.4) >> Na+, Li+, N-methyl-D-glucamine (>51). NH+4 blocked the channel completely. hIK was blocked by the classical inhibitors of the Gardos channel charybdotoxin (IC50 28 nM) and clotrimazole (IC50 153 nM) as well as by nitrendipine (IC50 27 nM), Stichodactyla toxin (IC50 291 nM), margatoxin (IC50 459 nM), miconazole (IC50 785 nM), econazole (IC50 2.4 microM), and cetiedil (IC50 79 microM). Finally, 1-ethyl-2-benzimidazolinone, an opener of the T84 cell IK channel, activated hIK with an EC50 of 74 microM.

Azepines↗
PubMed1997

Hypertonicity enhances expression of functional Na+/K+/2Cl- cotransporters in Ehrlich ascites tumour cells.

Ehrlich cells exposed to a hypertonic medium for five hours respond by an increased expression of Na+/K+/2Cl- cotransport proteins as estimated from immunoprecipitations using polyclonal anti-cotransporter antibodies. The 3.4-fold increase in cotransport expression is followed by a concomitant 2.6-fold increase in the maximal bumetanide-sensitive K+ influx during regulatory volume increase, indicating a 2.6-fold increase in the number of functional cotransporters in the plasma membrane.

Animals↗
PubMed1997

Effect of verapamil in intermittent claudication A randomized, double-blind, placebo-controlled, cross-over study after individual dose-response assessment.

BACKGROUND: The calcium antagonist verapamil is a vasodilator drug that has been shown to increase oxygen extraction of ischemic tissues in coronary and peripheral vascular disease. METHODS AND RESULTS: Since the balance between the positive and the negative effects of vasodilation may be delicate in ischemic diseases a dose-response study (dose range, 120 to 480 mg) was established to determine optimal, individual dosages of slow-release verapamil in 44 patients with stable intermittent claudication (Fontaine classification stage II) with respect to walking capacity. A randomized, double-blind, placebo-controlled, cross-over study (4 weeks) was performed to assess clinical and hemodynamic effects of verapamil. The optimal daily dose of verapamil on maximal walking ability was 120 (8 patients), 240 (8 patients), 360 (14 patients), and 480 mg (14 patients). Walking distances were measured at a metronome-controlled speed of 60 steps per minute on level surface. Optimal individual doses of verapamil increased mean pain-free walking distance by 29% from 44.9 to 57.8 meters (P < .01) and maximal walking distance by 49% from 100.7 to 149.8 meters (P < .001) compared with placebo. The increase in maximal walking distance correlated positively only with initial systolic ankle pressure (r = .49, P < .001) and ankle/brachial pressure index (r = .37, P < .013). Verapamil had no effect on systolic ankle pressure, ankle/brachial pressure index, peripheral leg temperature, or blood pressure, which suggests that the drug may have extrahemodynamic effects, possibly brought about through improved oxygen metabolism. CONCLUSIONS: Verapamil showed significant clinical benefits in patients with moderate intermittent claudication in this short-term study. Individual optimization of drug dosage should be considered an option both in trials and in the clinical setting in these patients.

Aged↗
PubMed1996

Occlusion of K+ in the Na+/K+/2Cl- cotransporter of Ehrlich ascites tumor cells.

Proteins of n-octyl glucoside solubilized membrane vesicles derived from Ehrlich ascites tumor cells can occlude 86Rb+.K+ displaces 86Rb+ and it is assumed that 86Rb+ can be used as a tracer to measure K+ occlusion. The following observations indicate that the Na+/K+/2Cl- cotransporter is responsible for this occlusion: (1) Na+ does not compete for the K+ binding site, but rather stimulates 86Rb+ occlusion. (2) K+ occlusion saturates with increasing [Na+] and [K+], the respective K0.5 values being 50 +/- 7 microM for Na+ and 371 +/- 63 microM for K+. (3) Preincubation with 1 mM ouabain does not inhibit 86Rb+ occlusion, arguing against the Na+/K+-ATPase as being responsible for the occlusion. This notion is supported by the K0.5 value for K+ being higher than reported for Na+/K+-ATPase and by the stimulatory effect of Na+. (4) The K+ occlusion is sensitive to [Cl-], and the occluded ion is protected by the presence of bumetanide during cation exchange chromatography. Our results suggest that occlusion measurements of substrate ions could be a profitable way to study the ion binding mechanism(s) of the Na+/K+/2Cl- cotransporter.

Animals↗
PubMed1996

[Occupational environment in veterinary clinics].

In veterinary clinics many drugs and materials are handled, for instance antibiotics, disinfectants and anaesthetic gases. The staff is in close contact with various animal species and performs surgical and obstetrical operations as well as post mortem examinations. X-ray is used widely. Some investigations have indicated, that the working environment has incurred little attention. For example, X-ray equipment has been found defective and air-extraction insufficient in connection with anaesthesias. Consequently the potential for work-related health problems is obvious. The few epidemiologic investigations done indicate an increased frequency of toxic and allergic skin diseases, asthma and certain infections such as ornithosis. As general prophylaxis, better arrangement of the clinics, alterations of drug administration forms and use of gloves and other protective devices are recommended. It is concluded, that the existing knowledge about the working environment in Danish veterinary clinics is scarce, that it may imply health risks, and that further investigation of the question is needed.

Animals↗
PubMed1995

Two subsites in the binding domain of the acetylcholine receptor: an aromatic subsite and a proline subsite.

The ligand binding site of the nicotinic acetylcholine receptor (AcChoR) is localized in the alpha-subunit within a domain containing the tandem Cys-192 and -193. By analyzing the binding-site region of AcChoR from animal species that are resistant to alpha-neurotoxins, we have previously shown that four residues in this region, at positions 187, 189, 194, and 197, differ between animals sensitive (e.g., mouse) and resistant (e.g., mongoose and snake) to alpha-bungarotoxin (alpha-BTX). In the present study, we performed site-directed mutagenesis on a fragment of the mongoose AcChoR alpha-subunit (residues 122-205) and exchanged residues 187, 189, 194, and 197, either alone or in combination, with those present in the mouse alpha-subunit sequence. Only the mongoose fragment in which all four residues were mutated to the mouse ones exhibited alpha-BTX binding similar to that of the mouse fragment. The mongoose double mutation in which Leu-194 and His-197 were replaced with proline residues, which are present at these positions in the mouse AcChoR and in all other toxin binders, bound alpha-BTX to approximately 60% of the level of binding exhibited by the mouse fragment. In addition, replacement of either Pro-194 or -197 in the mouse fragment with serine and histidine, respectively, markedly decreased alpha-BTX binding. All other mutations resulted in no or just a small increase in alpha-BTX binding. These results have led us to propose two subsites in the binding domain for alpha-BTX: the proline subsite, which includes Pro-194 and -197 and is critical for alpha-BTX binding, and the aromatic subsite, which includes amino acid residues 187 and 189 and determines the extent of alpha-BTX binding.

Amino Acid Sequence↗
PubMed1994

Activation of protein kinase C during cell volume regulation in Ehrlich mouse ascites tumor cells.

We have previously demonstrated that in Ehrlich cells a bumetanide-sensitive Na+,K+,2Cl- cotransporter is activated during regulatory volume decrease after cell shrinkage (hypertonic conditions) as well as during the late phase of regulatory volume decrease (hypotonic conditions). It is, however, quiescent under isotonic conditions. Using a protein kinase C assay system (Amersham, UK) it is here demonstrated that hypertonic cell shrinkage results in an increase in protein kinase C activity to 174% within the first minute, concomitant with the activation of the Na+,K+,2Cl- cotransporter. Hypotonic cell swelling results in a late activation of protein kinase C concomitant with a late activation of the Na+,K+,2Cl- cotransporter. The activation of protein kinase C during hypertonic as well as hypotonic conditions is inhibited by H-7. The more specific protein kinase C inhibitor chelerythrine inhibited protein kinase C as well as the Na+,K+,2Cl- cotransporter to the same extent as did H-7. These results indicate the involvement of protein kinase C in the regulation of the Na+,K+,2Cl- cotransporter in Ehrlich ascites tumor cells during cell volume regulation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Na+, K+, Cl- cotransport and its regulation in Ehrlich ascites tumor cells. Ca2+/calmodulin and protein kinase C dependent pathways.

Net Cl- uptake as well as unidirectional 36Cl influx during regulatory volume increase (RVI) require external K+. Half-maximal rate of bumetanide-sensitive 36Cl uptake is attained at about 3.3 mM external K+. The bumetanide-sensitive K+ influx found during RVI is strongly dependent on both Na+ and Cl-. The bumetanide-sensitive unidirectional Na+ influx during RVI is dependent on K+ as well as on Cl-. The cotransporter activated during RVI in Ehrlich cells, therefore, seems to transport Na+, K+ and Cl-. In the presence of ouabain and Ba+ the stoichiometry of the bumetanide-sensitive net fluxes can be measured at 1.0 Na+, 0.8 K+, 2.0 Cl- or approximately 1:Na, 1:K, 2:Cl. Under these circumstances the K+ and Cl- flux ratios (influx/efflux) for the bumetanide-sensitive component were estimated at 1.34 +/- 0.08 and 1.82 +/- 0.15 which should be compared to the gradient for the Na+, K+, 2Cl- cotransport system at 1.75 +/- 0.24. Addition of sucrose to hypertonicity causes the Ehrlich cells to shrink with no signs of RVI, whereas shrinkage with hypertonic standard medium (all extracellular ion concentrations increased) results in a RVI response towards the original cell volume. Under both conditions a bumetanide-sensitive unidirectional K+ influx is activated. During hypotonic conditions a small bumetanide-sensitive K+ influx is observed, indicating that the cotransport system is already activated. The cotransport is activated 10-15 fold by bradykinin, an agonist which stimulates phospholipase C resulting in release of internal Ca2+ and activation of protein kinase C. The anti-calmodulin drug pimozide inhibits most of the bumetanide-sensitive K+ influx during RVI. The cotransporter can be activated by the phorbol ester TPA. These results indicate that the stimulation of the Na+, K+, Cl- cotransport involves both Ca2+/calmodulin and protein kinase C.

Animals↗
PubMed1990

Kits for the diagnosis of infectious mononucleosis compared with the Paul-Bunnell test.

We compared the results obtained with six different test kits for infectious mononucleosis with those obtained with the Paul-Bunnell test. The investigation was carried out in one laboratory using 149 selected pools of patient sera. Each pool was tested three times with the Paul-Bunnell test and once with each kit. The results obtained with the kits were grouped according to the titre found with the Paul-Bunnell test. The percentage of positive results within each group was calculated for each kit. The Paul-Bunnell titre, which would have classified 50% of the specimens as positive, was estimated for each kit and this was designated the 50% cut off value. In general, there was good agreement. However, false positive test results were found rather frequently with one kit (19%) and the 50% cut off values differed. One kit showed a 50% cut off value at about 8, another at about 16, and the rest at between 16 and 32. We suggest the introduction of improved internal quality control combined with external quality assessment.

Antibodies, Heterophile↗
PubMed1989

[Prognosis after surgery of infrarenal abdominal aortic aneurysm].

During the period from January 1972 to September 1984, 285 patients were admitted and treated operatively for abdominal aortic aneurysm (AAA). At operation a non-ruptured AAA was found in 177 patients and a ruptured AAA in 108 patients. Advanced age and reduced renal function were found by employment of Cox's regression analysis to influence the peroperative and postoperative mortalities. The commonest cause of postoperative death was renal failure both in cases of non-ruptured and ruptured AAA. The commonest causes of late deaths were coronary occlusion, malignant disease, cerebral haemorrhage and haemorrhage from the anastomosis.

Aged↗
PubMed1989

The natural history of abdominal aortic aneurysm.

The outcome of 65 patients with unoperated abdominal aortic aneurysms (AAA) were reviewed in order to evaluate the natural history and "quality of life". An estimated cumulative life-table was constructed. Of the 65 patients admitted to the department (from 1972 to 1984), 52 were discharged from the hospital and not operated on because of concurrent medical disorders. These patients were divided into two groups: 34 with asymptomatic AAA on admission to the department and 18 with symptoms. During follow-up, 38 patients died, 71% in the asymptomatic and 78% in the symptomatic group. Less than 50% of all the patients died of concurrent disease. Of the patients in the asymptomatic group with a small aneurysm, 38% died of rupture of AAA. As AAA is a disease with a high mortality, the co-existent medical disorders must be very "serious" if the patient is not to be offered an operation. Even small, asymptomatic AAAs may rupture and should be operated on. No factor seemed to predict the natural history for the individual patient. A score system, for example, the "Boston score", is recommended. This would facilitate good objective assessment of the patients entering into future studies and the evaluation of "survival curves" will improve.

Aged↗
PubMed1985

Spontaneous progression of valvular aortic stenosis.

In 11 adult patients with isolated valvular aortic stenosis, the progression of the disease was assessed by two heart catheterisations without intervening aortic valve surgery. Four patients had bicuspid valves, whereas the remaining seven were considered to have acquired aortic stenosis. Significant differences between the two catheterisations were found for left ventricular peak systolic pressure (LVPSP), left ventricular aortic mean pressure gradient (LV-AO gradient), and for aortic valve area (OA). The rate of progression varied considerably. In one case the pressure gradient increased 43 mm Hg in 68 months, whereas in another case it remained almost unchanged for 103 months. One patient developed aortic valve regurgitation. ECG, chest X-ray and phonocardiography gave only poor estimates of the degree of progression. Thus having established a mild aortic stenosis at heart catheterisation, recatheterisation usually remains necessary to give the final indication for operation.

Adolescent↗