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      • SCIE

        Maintained ENaC trafficking in aldosterone-infused rats during mineralocorticoid and glucocorticoid receptor blockade.

        Nielsen, Jakob,Kwon, Tae-Hwan,Frokiaer, Jorgen,Knepper, Mark A,Nielsen, Soren American Physiological Society 2007 American Journal of Physiology Vol.292 No.1

        <P>Aldosterone induces redistribution of epithelial sodium channel (ENaC) to the apical plasma membrane from intracellular vesicles in renal connecting tubule (CNT) and cortical collecting duct (CCD). The role of the classical mineralocorticoid receptor (MR) in ENaC trafficking is still debated. We examined whether the MR antagonist spironolactone affects ENaC regulation in the kidney cortex of aldosterone-infused rats. Aldosterone infusion for 7 days resulted in a plasma aldosterone concentration in the high physiological range (3 to 4 nM). Aldosterone infusion decreased plasma K(+) concentration compared with untreated control rats. Cotreatment with spironolactone completely blocked the aldosterone-induced decrease in plasma K(+). Immunoblotting and immunohistochemistry showed increased protein abundance of Na-K-ATPase alpha(1)-subunit and NCC in the kidney cortex, in response to aldosterone infusion that was blocked by spironolactone. In contrast, aldosterone-induced redistribution of ENaC subunits from the cytoplasm to the apical plasma membrane domain in CNT and CCD was unaffected by spironolactone. Immunoblotting of alphaENaC showed increased protein abundance in aldosterone-infused rats that was not blocked by spironolactone treatment. To exclude possible glucocorticoid receptor (GR)-mediated effects of aldosterone, we treated aldosterone-infused rats with both spironolactone and the GR antagonist RU486. Combined MR and GR blockade prevented neither ENaC trafficking nor the upregulation of alphaENaC protein abundance in aldosterone-infused rats. We provide new evidence for ENaC trafficking occurring independent of MR and GR activation in aldosterone-infused rats.</P>

      • KCI등재

        Effects of Thiazide on the Expression of TRPV5, Calbindin-D28K, and Sodium Transporters in Hypercalciuric Rats

        장혜련,허남주,김효상,Soren Nielsen,오윤규,나기영,주권욱,한진석,김세중,이정환,전은실 대한의학회 2009 Journal of Korean medical science Vol.24 No.-

        TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague- Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin- D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats.

      • SCOPUSKCI등재

        International Repercussions of Source-based Capital Income Taxation

        ( Thomas Alslev Christensen ),( Soren Bo Nielsen ) 세종대학교 경제통합연구소 1995 Journal of Economic Integration Vol.10 No.1

        The paper is concerned with international effects of source-based capital income taxation in a large economy. We derive, within the context of a two-country overlapping generations model in continuous time, the implications of such taxation for the world interest rate and for investment, consumption, saving and external balances at home and abroad. Furthermore, we argue that higher source-based taxes will hurt foreigners alive at the time of the policy change, whereas future citizens abroad stand to benefit. Finally, the effects of source- and residence-based taxes are compared.

      • SCOPUSKCI등재

        Regulation of aquaporin-2 in the kidney: A molecular mechanism of body-water homeostasis

        ( Tae Hwan Kwon ),( Jorgen Frokiær ),( Soren Nielsen ) 대한신장학회 2013 Kidney Research and Clinical Practice Vol.32 No.3

        The kidneys play a key role in the homeostasis of body water and electrolyte balance. Aquaporin-2 (AQP2) is the vasopressin-regulated water-channel protein expressed at the connecting tubule and collecting duct, and plays a key role in urine concentration and body-water homeostasis through short-term and long-term regulation of collecting duct water permeability. The signaling transduction pathways resulting in the AQP2 trafficking to the apical plasma membrane of the collecting duct principal cells, including AQP2 phosphorylation, RhoA phosphorylation, actin depolymerization, and calcium mobilization, and the changes of AQP2 abundance in water-balance disorders have been extensively studied. Dysregulation of AQP2 has been shown to be importantly associated with a number of clinical conditions characterized by body-water balance disturbances, including hereditary nephrogenic diabetes insipidus (NDI), lithium-induced NDI, electrolytes disturbance, acute and chronic renal failure, ureteral obstruction, nephrotic syndrome, congestive heart failure, and hepatic cirrhosis. Recent studies exploiting omics technology further demonstrated the comprehensive vasopressin signaling pathways in the collecting ducts. Taken together, these studies elucidate the underlying molecular mechanisms of body-water homeostasis and provide the basis for the treatment of bodywater balance disorders.

      • Impact of spar-nacelle-blade coupling on the edgewise response of floating offshore wind turbines

        Dinh, Van-Nguyen,Basu, Biswajit,Nielsen, Soren R.K. Techno-Press 2013 Coupled systems mechanics Vol.2 No.3

        The impact of spar-nacelle-blade coupling on edgewise dynamic responses of spar-type floating wind turbines (S-FOWT) is investigated in this paper. Currently, this coupling is not considered explicitly by researchers. First of all, a coupled model of edgewise vibration of the S-FOWT considering the aerodynamic properties of the blade, variable mass and stiffness per unit length, gravity, the interactions among the blades, nacelle, spar and mooring system, the hydrodynamic effects, the restoring moment and the buoyancy force is proposed. The aerodynamic loads are combined of a steady wind (including the wind shear) and turbulence. Each blade is modeled as a cantilever beam vibrating in its fundamental mode. The mooring cables are modeled using an extended quasi-static method. The hydrodynamic effects calculated by using Morison's equation and strip theory consist of added mass, fluid inertia and viscous drag forces. The random sea state is simulated by superimposing a number of linear regular waves. The model shows that the vibration of the blades, nacelle, tower, and spar are coupled in all degrees of freedom and in all inertial, dissipative and elastic components. An uncoupled model of the S-FOWT is then formulated in which the blades and the nacelle are not coupled with the spar vibration. A 5MW S-FOWT is analyzed by using the two proposed models. In the no-wave sea, the coupling is found to contribute to spar responses only. When the wave loading is considered, the coupling is significant for the responses of both the nacelle and the spar.

      • SCOPUSKCI등재

        장기 복막투석 동물 모델에서 물수송체의 역할

        박민선(MS Park),차정호(JH Cha),김진(J Kim),(Soren Nielsen) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.2

        N/A Sufficient fluid removal is vital to renal replace-ment therapy in end-stage renal failure patients. Aquaporins are integral membrane proteins and the primary water channels that allow water transport only. Type 1, 3 and 4 aquaporins were found in peritoneal capillary walls and peritoneal mesothelial cells. Approximately 5096 of total amount of free water transported during peritoneal dialysis is through aquaporins. Ultrafiltration failure and fluid overload are found in some of long-term continous ambulatory peritoneal dialysis(CAPI3) patients and are major causes of withdrawl from CAPD. Long- term use of high glucose containing dialysis solutions, and functional and morphological changes of aquaporins were suggested as possible mechanisms of ultrafiltration failure. However, a direct relation between alterations of aquaporins in the peritoneum and ultrafiltration failure in long-term CAPD has not been reported yet. In this study peritoneal aquaporins and ultrafiltration were evaluated after long-term peritoneal exposure to high glucose containing dialy- sis solutions in rats. Sprague-Dawley rats with normal kidney func- tions were used. Twenty five milliliter of 4.25% glucose containing dialysis solutions were injected into the peritoneal cavity twice a day for 12 weeks in 13 rats(dialysis-group). The other 13 rats were used without intraperitoneal injection as controls (control-group). One rat from each group died during the study was excluded. After 12 weeks of intraperitoneal injection, a 2 hour peritoneal transport study was done in 9 rats from each group. To calculate intraperitoneal fluid absorption rate, (131)I labelled human serum albumin(RISA) was used as a volume marker. Mesenteries were taken from the remaining three rats from each group for immuno-histochemistry for aquaporin type l. Intraperitoneal volume after 2 hour dialysis was significantly lower in dialysis-group than in control-group(33.7±3.6 vs 39.4±6.1mL, p<0,05). The peri- toneal fluid absorption rate was significamtly higher in dialysis-group than in contml-group(0,070±0.051 vs 0.049±0.016 mL/min, p<0.05). Dg'P> srxlium was signifieantly higher in dialysis-group than in con- trol-group(0.890±0.014 vs 0.856±0.038, p<0.05).D₂P₂urea and D2/D0 glucose did not differ between the two groups. Immunohistochemistry revealed that aquaporin type 1 was strongly stained in the me-sentery capillary walls in control-group, while it was almost disappeared in dialysis-group. In conclusion, long-term use of high glucose containing dialysis solutions decreased aquaporin type 1 population in the peritoneum and ultrafil-tration volume. Increased peritoneal fluid absorption rate is also in part responsible for decreased ultra- filtration volume after long-term use of dialysie solutions.

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