Search PubMed⌕ Search

Biomedical subjects

S Nielsen

Publications and source records attributed to S Nielsen.

At least 37 records · Page 2Linked to original sources
PubMed2004

Expression of aquaporin isoforms during human and mouse tooth development.

Previously, we described the development of hyaluronan (HA) deposition in human tooth germ tissues that are consistent with water transport in different stages of tooth development. The aquaporins (AQP) constitute a family of membrane water channels that are expressed in many organs. However, there are no data available about the expression pattern of aquaporin water channels in dental structures. In the present study we have characterised the expression of six different aquaporin isoforms (AQP1-5, AQP-9) in developing human and mouse tooth germs by immunohistochemistry using isoform specific antibodies. In the "bell stage" AQP1 was expressed in endothelial cells of small vessels whereas no other structures of the tooth primordial were labeled. AQP2, AQP3 and AQP9 immunoreactivity was not observed in tooth germs, whereas strong AQP4 and AQP5 expression was observed in dental lamina, inner enamel epithelium, stratum intermedium, stellate reticulum and the outer enamel epithelium. Oral epithelium also exhibited AQP4 and AQP5 immunolabeling. During development of the matrices of the dental hard tissues AQP4 and AQP5 immunostaining was observed in the odontoblasts and their processes, as well as in the secretory ameloblast and their apical processes. Immunolabeling controls were negative. In conclusion, AQP4 and AQP5 are expressed in tooth germ tissues in early development in cells that previously have been shown to express HA and/or CD44, indicating that AQP water channels may play a role for ECM hydration during tooth development.

Animals↗
PubMed2004

Results of the European Commission Marina II study: part II--effects of discharges of naturally occurring radioactive material.

Enhanced levels of naturally occurring radioactive materials (NORM) are produced through various industrial operations and may lead to discharges to the marine environment. A recent study, called MARINA II, carried out for the European Commission considered discharges of radionuclides from the NORM industries to north European marine waters and their consequences. There are two main sources that were considered in the study. The use of phosphogypsum during the production of phosphoric acid by the fertiliser industry and the pumping of oil and gas from the continental shelf in the North Sea which produces large quantities of water contaminated with enhanced levels of naturally occurring radionuclides. Discharges of alpha emitting radionuclides from these two industries have contributed significantly to the total input of alpha emitters to north European waters over the period 1981-2000 (data were not available prior to 1981). Discharges due to the use of phosphogypsum have declined since the early 1990s and are now very low. Discharges from the oil and gas industries stabilised in the second half of the 1990s and are now the major contributor to alpha discharges to the region. As most European countries do not report discharges of radioactivity with the water produced during extraction, there is considerable uncertainty in the discharges used in the study. The impact of the discharges has been estimated both in terms of the effect on non-human biota and the radiological impact for people. In the 1980s the radiation dose rates to marine biota in the region around a phosphate plant on the north-west coast of England were as high due to the discharges from the phosphate plant as those near to the Sellafield reprocessing plant due to its discharges. In recent years the additional dose to marine biota in this region due to the past NORM discharges is of the same order of magnitude as the natural background. The collective dose rate was estimated to determine the radiological impact on people. The peak collective dose rate from the NORM industries occurred in 1984 and was just over 600 manSv y(-1). The collective dose rate fell with time as discharges from the phosphate industry reduced and was estimated as under 200 manSv y(-1) in 2000.

Chemical Industry↗
PubMed2004

Results of the European Commission MARINA II study: part I--general information and effects of discharges by the nuclear industry.

From the collated data relevant to discharges by the nuclear industry, it results that the input of beta activity (excluding Chernobyl fallout and tritium) into the OSPAR region decreased by a factor of 4 from 1986 to 1991, reaching by this date the same level as in the early 1950s. Over the same period the discharges of the alpha activity into the OSPAR region also decreased by a factor 3, the same trend has been seen also for tritium. Since 1986 the effective dose to members of the critical group in the vicinity of Sellafield and Cap de La Hague was consistently below the ICRP and EU limit of 1 mSv per year to members of the general public. The overall radiological impact from nuclear industry on the population of the European Union from the OSPAR area has decreased from 280 manSv y(-1) in 1978 to 14 manSv y(-1) in 2000.

Environmental Monitoring↗
PubMed2004

Studies of mdx mice.

Cerebral water accumulation-clinically denoted as brain edema-is a potentially life threatening complication of almost every intracranial neuropathological state. The molecular membrane water channel aquaporin-4 (AQP4) has been shown to be present at the blood-brain barrier (BBB) where it plays pivotal role in the transport of water between the tissue water compartments of the brain. Accumulating evidence indicates that the blockade of AQP4 function at the BBB would be a new therapeutic approach to the treatment and prevention of brain swelling. The cytoskeletal protein dystrophin has been shown to be involved in the maintenance of the polarized expression of AQP4 at the BBB. In order to further elucidate the mechanisms responsible for the highly polarized AQP4 expression, we studied brain tissue water accumulation during induction of brain edema in dystrophin-null transgenic mice (mdx-bgeo) and control mice. Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null brains revealed a dramatic reduction of AQP4 in astroglial end-feet surrounding capillaries (BBB) and at the glia limitans (cerebrospinal fluid-brain interface). The AQP4 protein is mislocalized, because immunoblotting showed that the total AQP4 protein abundance was unaltered. Brain edema was induced by i.p. injection of distilled water and 8-deamino-arginine vasopressin. Changes in cerebral water compartments were assessed by diffusion-weighted MRI (DWI) with determination of the apparent diffusion coefficient (ADC). In dystrophin-null mice and control mice, ADC gradually decreased by 5-6% from baseline levels during the first 35 min, indicating the initial phase of intracellular water accumulation is similar in the two groups. At this point, the control mice sustained an abrupt, rapid decline in ADC to 58%+/-2.2% of the baseline at 52.5 min, and all of the animals were dead by 56 min. After a consistent delay, the dystrophin-null mice sustained a similar decline in ADC to 55%+/-3.4% at 66.5 min, when all of the mice were dead. These results demonstrate that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the BBB and cerebrospinal fluid-brain interface. Moreover, these results predict that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema.

Animals↗
PubMed2004

Sodium coupled bicarbonate transporters in the kidney, an update.

Recently five genes have been cloned, which code for sodium dependent bicarbonate transport proteins. These genes belong to the SLC4A gene family. This short review summarizes our knowledge of these gene products with respect to their renal distribution and function. The best characterized members are the SLC4A4 and SLC4A7. SLC4A4 codes for an electrogenic Na(+), HCO(3) (-)-cotransporter (NBCe1), which is present in the basolateral membranes of proximal tubules and is responsible for the bicarbonate efflux here, and thus about 80% of the renal bicarbonate reabsorption. SLC4A7 codes for an electroneutral NBC (called NBC3 and NBCn1), which is present basolaterally in the thick ascending limb and the distal part of the collecting ducts and in intercalated cells (either apically or basolaterally) in the connecting and collecting tubules. In the thick ascending limb NBCn1 may be important for NH(4) (+) reabsorption. SLCA5 codes for an electrogenic NBC (called NBC4 and NBCe2), which based on RT-PCR is located to the kidney but the exact localization awaits a good antibody. This is also the case for the SLC4A8 and SLC4A10 gene products, which are sodium dependent Cl(-), HCO(3) (-) exchangers. The recent development in this field substantially increases our understanding of the complex renal regulation of acid base status.

Acid-Base Equilibrium↗
PubMed2003

Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans.

Growth hormone (GH) and cortisol are important to ensure energy supplies during fasting and stress. In vitro experiments have raised the question whether GH and cortisol mutually potentiate lipolysis. In the present study, combined in vivo effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean males were examined four times over 510 min. Microdialysis catheters were inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of the thigh and abdomen. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of GH, insulin, and glucagon at baseline levels. At t = 150 min, administration was performed of NaCl (I), a 2 microg.kg(-1).min(-1) hydrocortisone infusion (II), a 200-microg bolus of GH (III), or a combination of II and III (IV). Systemic free fatty acid (FFA) turnover was estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose, insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II (0.50 +/- 0.08 microg/l, mean +/- SE). Peak levels during III and IV were approximately 9 microg/l. Cortisol levels rose to approximately 900 nmol/l in II and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased in response to both II and III. In IV, they were higher and equal to the isolated additive effects of the two hormones. In conclusion, we find that GH and cortisol stimulate systemic and regional lipolysis independently and in an additive manner when coadministered. On the basis of previous studies, we speculate that the mode of action is mediated though different pathways.

Abdomen↗
PubMed2003

A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells.

The choroid plexus epithelium of the brain ventricular system produces the majority of the cerebrospinal fluid and thereby defines the ionic composition of the interstitial fluid in the brain. The transepithelial movement of Na+ and water in the choroid plexus depend on a yet-unidentified basolateral stilbene-sensitive Na+-HCO3- uptake protein. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression in the choroid plexus of SLC4A10 mRNA, which encodes a stilbene-sensitive Na+-HCO3- transporter. Anti-COOH-terminal antibodies were developed to determine the specific expression and localization of this Na+-HCO3- transport protein. Immunoblotting demonstrated antibody binding to a 180-kDa protein band from mouse and rat brain preparations enriched with choroid plexus. The immunoreactive band migrated as a 140-kDa protein after N-deglycosylation, consistent with the predicted molecular size of the SLC4A10 gene product. Bright-field immunohistochemistry and immunoelectron microscopy demonstrated strong labeling confined to the basolateral plasma membrane domain of the choroid plexus epithelium. Furthermore, the stilbene-insensitive Na+-HCO3- cotransporter, NBCn1, was also localized to the basolateral plasma membrane domain of the choroid plexus epithelium. Hence, we propose that the SLC4A10 gene product and NBCn1 both function as basolateral HCO3- entry pathways and that the SLC4A10 gene product may be responsible for the stilbene-sensitive Na+-HCO3- uptake that is essential for cerebrospinal fluid production.

Animals↗
PubMed2003

Bending the primary cilium opens Ca2+-sensitive intermediate-conductance K+ channels in MDCK cells.

Increasing tubular fluid flow rate has previously been shown to induce K+ secretion in mammalian cortical collecting duct. The mechanism responsible was examined in the present study using MDCK cells as a model. The change in membrane potential difference (EM) of MDCK cells was measured with a fluorescent voltage-sensitive dye, DiBAC4(3), when the cell's primary cilium was continuously bent with a micropipette or by the flow of perfusate. Bending the cilium produced a hyperpolarization of the membrane that lagged behind the increase in intracellular Ca2+ concentration by an average of 36 seconds. Gd3+, an inhibitor of the flow-induced Ca2+ increase, prevented the hyperpolarization. Blocking K+ channels with Ba2+ reduced the flow-induced hyperpolarization, implying that it resulted from activation of Ca2+-sensitive K+ channels. Further studies demonstrated that the hyperpolarization was diminished by the blocker of Ca2+-activated K+ channels, charybdotoxin, whereas iberiotoxin or apamin had no effect, results consistent with the activation of intermediate-conductance Ca2+-sensitive K+ channels. RT-PCR analysis and sequencing confirmed the presence of intermediate-conductance K+ channels in MDCK cells. We conclude that the increase in intracellular Ca2+ associated with bending of the primary cilium is the cause of the hyperpolarization and increased K+ conductance in MDCK cells.

Animals↗
PubMed2003

Distribution of aquaporin water channels AQP1 and AQP5 in the ductal system of the human pancreas.

BACKGROUND: The exocrine pancreas secretes large volumes of isotonic fluid, most of which originates from the ductal system. The role of aquaporin (AQP) water channels in this process is unknown. METHODS: Expression and localisation of known AQP isoforms was examined in normal human pancreas, pancreatic adenocarcinoma, and pancreatic cell lines of ductal origin (Capan-1, Capan-2, and HPAF) using reverse transcriptase-polymerase chain reaction and immunohistochemistry. RESULTS: Messenger RNAs for AQP1, -3, -4, -5, and -8 were detected in normal pancreas and in pancreatic adenocarcinoma. The cell lines expressed AQP3, -4, and -5 but lacked AQP1 and AQP8. Immunohistochemistry of normal pancreas revealed that AQP1 is strongly expressed in centroacinar cells and in both the apical and basolateral domains of intercalated and intralobular duct epithelia. AQP1 expression declined with distance along the small interlobular ducts and was not detectable in larger interlobular ducts. AQP3 and AQP4 were not detectable by immunohistochemistry. AQP5 was observed at the apical membrane of intercalated duct cells and also in duct associated mucoid glands. AQP8 was confined to the apical pole of acinar cells. Both AQP1 and AQP5 were colocalised with cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of intercalated duct cells. CONCLUSIONS: AQP1 and AQP5 are strongly expressed in the intercalated ducts of the human pancreas. Their distribution correlates closely with that of CFTR, a marker of ductal electrolyte secretion. This suggests that fluid secretion is concentrated in the terminal branches of the ductal tree and that both AQP1 and AQP5 may play a significant role.

Adenocarcinoma↗
PubMed2003

Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis.

BACKGROUND AND AIM: Water retention is a major clinical problem in patients with liver cirrhosis. Recent research suggests that renal aquaporins may be pathophysiologically involved in this condition. The aim of the present cross sectional study of patients with liver cirrhosis was to determine if 24 hour urinary excretion of renal aquaporin 2 (AQP2) differed from that of healthy control subjects and if such excretion was related to the severity of liver disease and to the patient's water balance. RESULTS: Twenty four hour urinary excretion of AQP2 and free water clearance were measured in 33 stable cirrhosis patients on usual medication and in eight healthy subjects. AQP2 excretion, quantitated by immunoblotting, was eight times higher in cirrhosis patients than in controls (0.167 (0.270) U/day v 0.021 (0.017); p<0.05). Stratification according to clinical manifestations (Child- Pugh classes) revealed that it increased with the clinical severity of cirrhosis (class A 0.04 (0.04); class B 0.09 (0.16); class C 0.31 (0.35); p<0.05) but was not related to liver function, as measured by galactose elimination capacity. Excretion correlated inversely with free water clearance (rho=-0.57, p<0.01). It was higher in patients with oesophagogastric varices but not in those with ascites. Plasma vasopressin concentrations were not related to AQP2 excretion and there was no relation to dose or type of diuretic treatment. CONCLUSIONS: Urinary AQP2 excretion was increased in patients with cirrhosis. Moreover, urinary AQP2 excretion increased with severity of cirrhosis in parallel with impairment of free water clearance. This suggests a functional association between increased AQP2 excretion and increased renal reabsorption of water in cirrhosis.

Adult↗
PubMed2003

Sludge drying reed beds.

Sludge reduction occurs by dewatering (draining, evapotranspiration) and mineralization. Sludge from wastewater treatment plants (2,500-125,000 PE) is treated in sludge reed basin systems with 1-18 basins with loading rates of 25-2,200 tons dry matter/year for 10 years. In general, the sludge type is surplus activated sludge or a mix of mesophile digested sludge and surplus activated sludge. Dimensioning and design of reed basin systems for 10-year periods of operation depends on how the sludge is produced, rate of production (tons of dry matter/year), sludge type, quality and regional climate. Loading cycles are related to the sludge type and the age of the sludge reed systems. The period can be divided into a number of operating phases: commissioning, full operation, emptying and re-establishment of the system. Experience shows that efficiency makes special demands on the design of the systems and on the operational control in order to obtain a final dry matter content in the sludge residue of approximately 40% and the number of operating years. Sludge loadings with surplus activated sludge and surplus activated sludge mixed with anaerobically digested sludge amount to a maximum of 60 and 50 kg dry matter/m2 x year, respectively.

Biodegradation, Environmental↗
PubMed2002

Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans.

Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.

Abdomen↗
PubMed2002

Immunolocalization of electroneutral Na(+)-HCO cotransporters in human and rat salivary glands.

Patterns of salivary HCO secretion vary widely among species and among individual glands. In particular, virtually nothing is known about the molecular identity of the HCO transporters involved in human salivary secretion. We have therefore examined the distribution of several known members of the Na(+)-HCO cotransporter (NBC) family in the parotid and submandibular glands. By use of a combination of RT-PCR and immunoblotting analyses, the electroneutral cotransporters NBC3 and NBCn1 mRNA and protein expression were detected in both human and rat tissues. Immunohistochemistry demonstrated that NBC3 was present at the apical membranes of acinar and duct cells in both human and rat parotid and submandibular glands. NBCn1 was strongly expressed at the basolateral membrane of striated duct cells but not in the acinar cells in the human salivary glands, whereas little or no NBCn1 labeling was observed in the rat salivary glands. The presence of NBCn1 at the basolateral membrane of human striated duct cells suggests that it may contribute to ductal HCO secretion. In contrast, the expression of NBC3 at the apical membranes of acinar and duct cells in both human and rat salivary glands indicates a possible role of this isoform in HCO salvage under resting conditions.

Animals↗
PubMed2002

Urinary aquaporin-2 excretion in preterm and full-term neonates.

The study was undertaken to define the role of aquaporin-2 (AQP2) in renal concentrating performance by measuring urinary AQP2 excretion and urine osmolality in healthy preterm and full-term neonates during early postnatal life. Random urine samples were obtained from 9 full-term newborn infants (mean birth weight 3,218 g, mean gestational age 39.2 weeks) at postnatal ages of 1, 3 and 5 days. Five premature infants with a mean birth weight of 1,570 g and mean gestational age of 30.6 weeks were studied at the end of the 1st week and then weekly up to the 6th week. Urine osmolality (Knauer osmometer), creatinine (modified Jaffé's method) and AQP2 concentrations (radioimmunoassay) were measured. In full-term neonates, urinary AQP2 excretion showed no consistent changes over the age period studied, while urine osmolality decreased significantly with advancing age. In premature infants, urinary AQP2 excretion remained practically unchanged during the first 4 weeks followed by an abrupt increase thereafter. Urine osmolality did not follow the developmental pattern of AQP2 excretion; its mean values varied only from 78 +/- 39 to 174 +/- 146 mosm/l during the experimental period. It is concluded that during the early postnatal period, urinary AQP2 excretion does not serve as a direct marker of the renal action of AVP and the renal capacity to concentrate urine.

Aquaporin 2↗
PubMed2001

[Total knee arthroplasty with Boneloc cement. Clinical and radiological results].

INTRODUCTION: Fifty-five total knee prostheses cemented with Boneloc were assessed clinically and radiographically after a mean follow-up of 64 months. MATERIALS AND METHODS: At follow-up, 11 patients (12 TKR) were dead. One of these patients had both clinical and radiographic signs of loosening of the prosthesis, but was inoperable because of severe cardiopulmonary status. Seven patients (eight knees) refused assessment and two patients (two knees) have been reoperated. The mean duration of follow-up was 64 months (range, 44-97). RESULTS: The mean clinical knee score (the Hospital for Special Surgery) was 86 (range, 55-97). Overall, the result in 34 knees was excellent; in 14 good; in 5 fair, and in 2 poor. Forty-four prostheses (80 per cent) had no radiolucent lines (the Knee Society scoring system). The rest had radiolucent lines around the tibia component. Nine knees had non-progressive radiolucent lines, one moderate, and one a progressive radiolucency. Radiologically, the last knee was clearly loose, but the clinical result was still good. No correlation was found between the clinical and the radiological results (r = -0.02). There was a significant correlation between the follow-up time and the presence of radiolucency in TKR (r = 0.32, p = 0.02). DISCUSSION: The failure rate was 5.12% (four out of 78) within one to four years of the operation. The poor mechanical characteristics of the Boneloc cement indicate that all knees inserted with Boneloc cement should be followed up in order to detect failures early.

Aged↗