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T Nilsson

Publications and source records attributed to T Nilsson.

At least 217 records · Page 12Linked to original sources
PubMed1988

A proposal for the site and mechanism of redox-linked proton translocation in cytochrome c oxidase.

In this paper, we present a detailed mechanistic model for the redox-linked proton pump of cytochrome c oxidase. Using the spectroscopic properties of CuA, we have constructed a molecular orbital model for the electronic structure of the CuA site. One prediction of this model is that a ligand rearrangement should occur upon reduction of CuA. We further describe a detailed mechanism for proton pumping which utilizes this redox-linked CuA ligand rearrangement as its central feature. The turnover cycle of this proton pump model is then discussed in terms of the theoretical thermodynamic and kinetic requirements of a redox-linked proton pump.

Binding Sites↗
PubMed1988

Urodynamic evaluation of calcified bilharzial bladders.

The functioning of 100 bladders with bilharzial calcification has been urodynamically studied and compared to 30 non-bilharzial healthy males of the same age group. Uroflowmetry, fluid cystometry and pressure flow studies were performed in all bilharzial and control patients. No significant urodynamic differences were found between the bilharzial patients and the control group except that bilharzial patients showed residual urine (mean 100 ml) and delayed first sensation (mean 250 ml). Cystoscopy and multiple deep bladder biopsies were conducted in all bilharzial patients. Histology showed that bladder calcification involves mainly the mucosa and submucosal layers. It was only occasionally that calcified ova were seen in the muscle layers. Since the bladder muscles are largely intact, it is not surprising that the detrusor function is normal even though the bilharzial bladder wall is severely calcified.

Calcinosis↗
PubMed1988

Chronic urinary schistosomiasis: patterns of abnormalities in radionuclide Tc-99 m DTPA diuretic renogram.

The aim of this study was to describe the abnormal morphological and functional patterns observed in radionuclide diuretic renograms (RDR) in patients with chronic urinary schistosomiasis. A retrospective analysis of RDR for 92 patients was made. It revealed the following abnormalities: A) Morphological changes observed in the images: Pelvicalyceal retention of tracer (and dilatation) was seen in 68% of kidneys. Calyceal retention alone was seen in 5% and pelvic retention alone in 9%. An atrophic kidney was noted in 5%, nephropathic pattern in 3% and normal kidneys in 10%. Ureteric retention of tracer was seen in 64% of ureters. This was frequently associated with pelvicalyceal retention (61%) and this abnormality was bilateral in 44% of the urinary systems. B) Functional changes observed in the time activity curves: Non-obstructive delayed excretion was noted in 71% of kidneys. An obstructed kidney pattern nonresponsive to lasix was seen in 12%, plateau curve due to nephropathic kidney in 3% and atrophic kidney pattern in 4% of kidneys.

Adult↗
PubMed1988

Bowel preparation prior to colonoscopy using a limited intake of electrolyte solution for cleansing. A comparison between peroral and rectal intestinal lavage evaluated through degree of cleansing, acceptability by the patient and nursing time involved.

In a randomised single-blind study, peroral intestinal cleansing was compared with rectal lavaging in 55 completed colonscopies. After rapid oral intake of 1.5 l cold (5-7 degrees C) electrolyte solution, a better cleansing of colon was observed than after rectal lavage. A majority of patients preferred this method. More than one hour per patient of the nurses' time was saved in the electrolyte solution group. The amount of electrolyte solution used was less than in previous studies. It did not result in undesirable fluid retention in the colon. No serious side effects were observed, and only minor changes in the patients' weight and plasma osmolality occurred in the electrolyte solution group.

Administration, Oral↗
PubMed1987

Characterization of the inositol 1,4,5-trisphosphate-induced Ca2+ release in pancreatic beta-cells.

Pancreatic beta-cells isolated from obese-hyperglycaemic mice released intracellular Ca2+ in response to carbamoylcholine, an effect dependent on the presence of glucose. The effective Ca2+ concentration reached was sufficient to evoke a transient release of insulin. When the cells were deficient in Ca2+, the Ca2+ pool sensitive to carbamoylcholine stimulation was equivalent to that released by ionomycin. Unlike intact cells, cells permeabilized by high-voltage discharges failed to generate either inositol 1,4,5-triphosphate (InsP3) or to release Ca2+ after exposure to carbamoylcholine. However, the permeabilized cells released insulin sigmoidally in response to increasing concentrations of Ca2+. Also in the absence of functional mitochondria these cells exhibited a large ATP-dependent buffering of Ca2+, enabling the maintenance of an ambient Ca2+ concentration corresponding to about 150 nM even after several additional pulses of Ca2+. InsP3, maximally effective at 6 microM, promoted a rapid and pronounced release of Ca2+. The InsP3-sensitive Ca2+ pool was rapidly filled and lost its Ca2+ late after ATP depletion. The transient nature of the Ca2+ signal was not overcome by repetitive additions of InsP3. It was possible to restore the response to InsP3 after a delay of approx. 20 min, an effect which had less latency after the addition of Ca2+. These latter findings argue against degradation and/or desensitization as factors responsible for the transiency in InsP3 response. It is suggested that Ca2+ released by InsP3 is taken up by a part of the endoplasmic reticulum (ER) not sensitive to InsP3. On metabolism of InsP3, Ca2+ recycles to the InsP3-sensitive pool, implying that this pool indeed has a very high affinity for the ion. The presence of functional mitochondria did not interfere with the recycling process. The ER in pancreatic beta-cells is of major importance in buffering Ca2+, but InsP3 only modulates Ca2+ transport for a restricted period of time following immediately upon its formation. Thereafter the non-sensitive part of the ER takes over the continuous regulation of Ca2+ cycling.

Animals↗
PubMed1987

Extracellular Ca2+ induces a rapid increase in cytoplasmic free Ca2+ in pancreatic beta-cells.

Using pancreatic beta-cells isolated from obese hyperglycemic mice, it was demonstrated that the addition of 5 mM extracellular Ca2+ evoked a rapid and transient increase in cytoplasmic free Ca2+ concentration ([Ca2+]i). The effect remained in the presence of D-600. Extracellular Ca2+ did not raise [Ca2+]i subsequent to emptying the inositol 1,4,5-trisphosphate (InsP3) sensitive pool by carbamylcholine stimulation, indicating that the pool released by extracellular Ca2+ is of similar origin. Stimulation with extracellular Ca2+ was accompanied by a pronounced insulin release. Our results suggest that the Ca2+-induced rise in [Ca2+]i is mediated through the formation of InsP3, a mechanism that might operate also in other types of cells.

Animals↗
PubMed1987

Cadmium-induced insulin release does not involve changes in intracellular handling of calcium.

A possible interaction between Cd2+ and Ca2+ as a component in Cd2+-induced insulin release was investigated in beta cells isolated from obese hyperglycemic mice. The glucose stimulated Cd2+ uptake was dependent on the concentration of sugar. This uptake was sigmoidal with a Km for glucose of about 5 mM and was suppressed by both 50 microM of the voltage-activated Ca2+ channel blocker D-600 and 12 mM Mg2+. In the presence of 8 mM glucose 5 microM Cd2+ evoked a prompt and sustained stimulatory response, corresponding to about 3-fold of the insulin release obtained in the absence of the ion. Whereas 5 microM Cd2+ was without effect on the glucose-stimulated 45Ca efflux in the presence of extracellular Ca2+, 40 microM inhibited it. At a concentration of 5 microM, Cd2+ had no effect on the resting membrane potential or the depolarization evoked by either glucose or K+. In the absence of extracellular Ca2+ there was only a modest stimulation of 45Ca efflux by 5 microM Cd2+. Studies of the ambient free Ca2+ concentration maintained by permeabilized cells also indicate that 5 microM Cd2+ do not mobilize intracellularly bound Ca2+ to any great extent. On the contrary, at this concentration, Cd2+ even suppressed inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. The present study suggests that Cd2+ stimulates insulin release by a direct mechanism which does not involve an increase in cytoplasmic free Ca2+ concentration.

Animals↗
PubMed1987

Inhibition of ATP-regulated K+ channels precedes depolarization-induced increase in cytoplasmic free Ca2+ concentration in pancreatic beta-cells.

The effects of glucose, diazoxide, K+, and tolbutamide on the activity of K+ channels, membrane potential, and cytoplasmic free Ca2+ concentration were investigated in beta-cells from the Uppsala colony of obese hyperglycemic mice. With [K+]e = [K+]i = 146 mM, it was demonstrated that the dominating channel at the resting potential is a K+ channel with a single-channel conductance of about 65 picosiemens and a reversal potential of about +70 mV (pipette potential). This channel is characterized by complex kinetics with openings grouped in bursts. The channel was completely inhibited by 20 mM glucose in intact cells or by intracellularly applied Mg-ATP (1 mM). The number of active channels was markedly reduced already by 5 mM glucose. However, the single channel current of the channels remaining active was unaffected, indicating no major depolarization. To evoke a substantial depolarization of the membrane and thereby action potentials, a total block in channel activity was necessary. This could be achieved either by increasing the concentration of glucose to 20 mM or by combining 5 mM glucose with 100 microM tolbutamide. In both cases, the effect was counteracted by the hyperglycemic sulfonamide diazoxide. The effects on single channel activity were paralleled by changes in membrane potential and cytoplasmic free Ca2+ concentration, also when the latter measurements were performed at room temperature. The transient increase in the number of active channels and the resulting hyperpolarization observed after raising the glucose concentration to 20 mM probably reflected a drop in cytoplasmic ATP concentration. It is suggested that ATP works as a key regulator of the beta-cell membrane potential and thereby the opening of voltage-activated Ca2+ channels.

Adenosine Triphosphate↗
PubMed1987

Are the alpha 2-adrenoceptors in the noradrenaline cell body region of physiological significance?

Preganglionic stimulation of the cervical sympathetic increased the content of 3,4-dihydroxyphenylacetic acid (DOPAC) in the superior cervical ganglion of rats treated with the dopamine beta-hydroxylase inhibitor FLA-63. It also increased and decreased the concentrations of dopamine and noradrenaline, respectively, in the salivary gland. The effects were partially inhibited by the alpha 2-adrenoceptor agonist clonidine via a yohimbine-sensitive mechanism. The alpha 2-adrenoceptor antagonist yohimbine by itself did not enhance the stimulation-evoked increase in ganglionic DOPAC, but it markedly potentiated the stimulation-evoked changes in dopamine and noradrenaline in the salivary gland. The results indicate that there are inhibitory alpha 2-adrenoceptors both in the somatodendritic and in the axon terminal region of the noradrenaline neurons but that only the alpha 2-receptors of the axon terminals are physiologically stimulated.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Hydroxyurea treatment of myeloproliferative disorders. Macro-megaloblastic blood and bone marrow changes.

Blood and bone marrow changes induced by continuous low-dose hydroxyurea treatment are described. A linear increase in mean red cell volume was observed after onset of therapy. The entire normocyte population was replaced by abnormally large erythrocytes within 150 days. The bone marrow morphology changed in megaloblastic direction. Bone marrow iron stores and number of sideroblasts increased, findings compatible with ineffective erythropoiesis. Serum folate and cobalamin levels remained normal. These morphologic changes might cause confusion when examining blood or bone marrow samples from patients treated with hydroxyurea.

Bone Marrow↗
PubMed1986

Galanin inhibits glucose-stimulated insulin release by a mechanism involving hyperpolarization and lowering of cytoplasmic free Ca2+ concentration.

The intrapancreatic neuropeptide galanin has been demonstrated to lower plasma insulin levels in vivo. The effects of this peptide on insulin secretion, cytoplasmic free Ca2+ concentration and membrane potential have now been studied in vitro. Glucose-stimulated insulin secretion was inhibited by galanin under these conditions, indicating a direct effect of the peptide on the beta-cells. The neuropeptide reversed both the increase in membrane potential and cytoplasmic free Ca2+ in response to glucose stimulation. At a non-stimulatory concentration of the sugar, galanin induced a slight hyperpolarization without any effect on cytoplasmic free Ca2+. Galanin did not affect K+-induced increase in cytoplasmic free Ca2+, excluding a direct inhibitory effect on the voltage-activated Ca2+ channels. The results indicate that galanin inhibition of glucose-stimulated insulin release involves hyperpolarization with a subsequent decrease in cytoplasmic free Ca2+.

Animals↗
PubMed1986

Accumulation of cadmium in pancreatic beta cells is similar to that of calcium in being stimulated by both glucose and high potassium.

The transport of Cd2+ and the effects of this ion on secretory activity and metabolism were investigated in beta cell-rich pancreatic islets isolated from obese-hyperglycemic mice. The endogenous cadmium content was 2.5 mumol/kg dry wt. After 60 min of incubation in a Ca2+-deficient medium containing 2.5 microM Cd2+ the islet cadmium content increased to 0.18 mmol/kg dry wt. This uptake was reduced by approx. 50% in the presence of 1.28 mM Ca2+. The incorporation of Cd2+ was stimulated either by raising the concentration of glucose to 20 mM or K+ to 30.9 mM. Whereas D-600 suppressed the stimulatory effect of glucose by 75%, it completely abolished that obtained with high K+. Only about 40% of the incorporated cadmium was mobilized during 60 min of incubation in a Cd2+-free medium containing 0.5 mM EGTA. It was possible to demonstrate a glucose-induced suppression of Cd2+ efflux into a Ca2+-deficient medium. Concentrations of Cd2+ up to 2.5 microM did not affect glucose oxidation, whereas, there was a progressive inhibition when the Cd2+ concentration was above 10 microM. Basal insulin release was stimulated by 5 microM Cd2+. At a concentration of 160 microM, Cd2+ did not affect basal insulin release but significantly inhibited the secretory response to glucose. It is concluded that the beta cell uptake of Cd2+ is facilitated by the activation of voltage-dependent Ca2+ channels. Apparently, the accumulation of Cd2+ mimics that of Ca2+ also involving a component of intracellular sequestration promoted by glucose.

Animals↗
PubMed1986

Stimulation of insulin release by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate in the clonal cell line RINm5F despite a lowering of the free cytoplasmic Ca2+ concentration.

The effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) on the handling of Ca2+ and insulin release were investigated in the clonal insulin-producing cell line RINm5F. The presence of the phorbol ester lowered the free cytoplasmic Ca2+ and suppressed the increase obtained by depolarization with high concentrations of K+. Despite the lowering in cytoplasmic Ca2+ by TPA, there was a concomitant stimulation of insulin release indicating that one feature of protein kinase C activation is to make the secretory system more sensitive to Ca2+. Furthermore, there was no interaction of TPA with the mechanisms responsible for inositol 1,4,5-tris(phosphate) induced Ca2+ release or Ca2+ uptake in permeabilized cells. Although TPA slightly depolarized the RINm5F cells there was no interference with K+-induced depolarization. It is suggested that an additional effect of protein kinase C activation in these cells, is to stimulate the extrusion of Ca2+ over the plasma membrane.

Animals↗
PubMed1986

Assay characteristics and fibrin affinity of plasminogen activators of the intrinsic fibrinolytic system.

Plasminogen activators (PA) in the euglobulin fraction of dextran sulfate activated plasma (DS-EF) were assayed on fibrin plates. Activity related to tissue plasminogen activator (t-PA) or urokinase (u-PA) was quantified by antiserum inhibition. The DS-EF contained 30% t-PA, 30% u-PA and 40-50% activity unrelated to t-PA or u-PA. The latter was completely inhibited by 1.7 mumol/1 C1-inhibitor (C1INH), the two former were less sensitive. Addition of flufenamate to the DS-EF (DS-EF/Fluf) from normal and two factor XII (F XII)-deficient plasmas increased their activities to the same high level. More than 50% of the activity was unrelated to t-PA or u-PA, 30-40% was u-PA and 5-10% t-PA related. After addition of fibrinogen to DS-EF/Fluf and clotting with thrombin, the remaining solution contained only about 30% of the total activity, including less than 10% u-PA. The epsilon-aminocaproic acid inhibition pattern obtained with the DS-EF was uniform, and thus different from the biphasic pattern obtained with the low fibrin affinity PA, two-chain urokinase. Thus, both the plasma u-PA and the major unidentified PA in plasma have affinity for fibrin.

Adult↗
PubMed1986

Structural and functional dissection of an MHC class I antigen-binding adenovirus glycoprotein.

The early transmembrane glycoprotein E19 of adenovirus-2 binds to class I antigens of the major histocompatibility complex (MHC). The association is initiated in the endoplasmic reticulum of infected cells and abrogates the intracellular transport of the class I molecules. To examine which parts of the E19 molecule are responsible for the association with the class I antigens and which parts confine the protein to the endoplasmic reticulum we have constructed a series of mutated E19 genes, which have been expressed in an improved mammalian expression vector. By various manipulations the membrane anchoring and the cytoplasmic domains were removed from the protein. The biosynthesis of the mutant protein was examined. All mutant proteins were secreted from the cells suggesting that the transmembrane and/or cytoplasmic portions of the E19 molecule are responsible for its confinement to the endoplasmic reticulum. The ability to associate with class I antigens was retained by the lumenal domain of the E19 protein.

Adenovirus Early Proteins↗
PubMed1986

Stereological estimates of nuclear volume correlated with histopathological grading and prognosis of bladder tumour.

The aim of this retrospective study is to provide morphometric data which make grading of urinary bladder tumours objective and reproducible by stereological estimation of nuclear volume using the principle of estimating of the volume of particles of arbitrary shape. The study includes 92 specimens: 12 from normal bladder mucosa, and 80 from bladder tumours (15 grade I, 45 grade II, 19 grade III and one grade IV according to Bergkvist et al. 1965). After standard fixation, embedding, sectioning and hematoxylin-eosin staining, an unbiased estimate of the mean volume of nuclei sampled with a change proportional to the volume: (Formula: see text) was calculated. Here l0 is the length of the intercept through a test point hitting a nucleus measured in a random direction through the test point. The weighted means of nuclear volume in bladder tumours are spread over a wide range and show a strong correlation with the Bergkvist grade. Moreover, the relationship between the weighted mean volume of nuclei in bladder tumours and the prognosis is very good. Only one of 35 patients with a mean nuclear volume below 300 micron 3 died of bladder cancer whereas 18 of 19 patients with a mean nuclear volume above 500 micron 3 developed invasives tumours or died of their disease. This simple and fast estimate of nuclear volume seems to provide objective data of high prognostic value.

Adult↗