bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine Regulates Renal Nitric Oxide Production in Hypothyroid Rats
Authors: FRANCO MARTHA , TAPIA EDILIA , MARTÍNEZ FLAVIO , DAVILA MA. EUGENIA , GRIMALDO JUANA INÉS , MEDINA KLELIA , HERRERA-ACOSTA JAIME 
Published: April 2021

Abstract.
In the hypothyroid kidney, exogenous adenosine (ADO) produces vasodilation and restores renal function to near-normal values. This study evaluates whether this response is mediated by nitric oxide synthesis stimulated by adenosine. GFR and urinary excretion of NO2
-/NO3
- (UNO2
-/NO3
-) were measured in normal (NL) and hypothyroid (HTX) rats under basal conditions and during infusion of: intra-aortic ADO, intravenously, 1,3-dipropyl-8p-sulfophenylxanthine (DPSPX), 8-cyclopentyl-1,3-dipropyl xanthine (DPCPX), N
ω-nitro-L-arginine methylester (L-NAME) + ADO, L-NAME + PSPX, L-NAME + DPCPX, and intrarenal (IR) ADO or DPCPX + IR ADO. Intra-aortic ADO induced a fall in GFR and increased UNO2
-/NO3
- slightly in NL rats; in HTX rats, both GFR and UNO2
-/NO3
- increased significantly. DPSPX and DPCPX increased UNO2
-/NO3
- excretion in NL animals with minor changes in GFR; the blockers increased both GFR and UNO2
-/NO3
- in HTX rats. L-NAME completely blocked the increase in NO2
-/NO3
- induced by ADO, DPSPX, and DPCPX. The intrarenal infusion of ADO at 1, 10, and 35 nmol/kg per min progressively decreased GFR with a slight increase in UNO2
-/NO3
- in NL rats; in the HTX, GFR increased with the highest dose and UNO2
-/NO3
- progressively increased. DPCPX prevented the fall in GFR induced by intrarenal ADO in NL rats, with no further changes in UNO2
-/NO3
-; in HTX rats, intrarenal ADO under A1 blockade further increased GFR and UNO2
-/NO3
-. Arterial and venous ADO concentrations were lower in the HTX rats. In the HTX kidney, NO production was stimulated by ADO, most likely through activation of A2 or A3 receptors, whereas A1 receptors had an inhibitory effect. Thus, ADO receptors are involved in the regulation of kidney function in pathophysiologic conditions.
Reduction in Glomerular Heparan Sulfate Correlates with Complement Deposition and Albuminuria in Active Heymann Nephritis
Authors: RAATS C. J. ILSE , LUCA MARIKEN E. , BAKKER MARINKA A. H. , VAN DER WAL ANNEMIEKE , HEERINGA PETER , VAN GOOR HARRY , VAN DEN BORN JACOB , DE HEER EMILE , BERDEN JO H. M. 
Published: April 2021

Abstract.
In a time-study of active Heymann nephritis, the expression of agrin, the main heparan sulfate proteoglycan in the glomerular basement membrane, was analyzed in relation to deposition of IgG and complement in the glomerular capillary wall and the development of albuminuria. Binding of IgG autoantibodies to the glomerular capillary wall could be detected from 2 wk onward, followed by activation of complement after 6 wk. Progressive albuminuria developed from 6 wk onward to a level of 274 ± 68 mg/18 h at week 12. The staining intensity for the agrin core protein decreased slightly, and the staining intensity for the heparan sulfate stubs that were still attached to the core protein after heparitinase digestion remained normal. From week 6 onward, however, a progressive decrease was seen in the staining of two monoclonal antibodies (mAb) directed against different epitopes on the heparan sulfate polysaccharide side chain of agrin (to 35 and 30% of the control level, respectively, at week 12, both mAb P = 0.016). Moreover, albuminuria was inversely correlated with heparan sulfate staining as revealed by these antibodies (r
s = -0.82 and r
s = -0.75, respectively, both mAb P < 0.0001). This decrease in heparan sulfate staining was due to a progressive reduction of glomerular heparan sulfate content to 46 and 32% of control level at week 10 and week 12 of the disease, respectively, as measured biochemically. It is speculated that the observed decrease in glomerular heparan sulfate in active Heymann nephritis is due to complement-mediated cleavage of heparan sulfate, resulting in an increased permeability of the glomerular basement membrane to macromolecules.
Is 100KF an Isoform of Hemopexin? Immunochemical Characterization of the Vasoactive Plasma Factor 100KF
Authors: CHEUNG PO KAM , STULP BEN , IMMENSCHUH STEPHAN , BORGHUIS THEO , BALLER JULIUS F. W. , BAKKER WINSTON W. 
Published: April 2021

Abstract.
The human vasoactive plasma factor 100KF has been proposed to play a role in minimal change disease in relapse. Since preliminary data suggested similarity between 100KF and the human plasma glycoprotein hemopexin (Hx), this study was conducted to compare 100KF with purified Hx for sequence homology, immunostaining properties in Western and dot-blot assays, ability to affect glomerular ecto-ATPase and glomerular polyanions in vitro, as well as their glomerular permeability increasing effect following alternate perfusion into the rat kidney ex vivo. 100KF was purified from normal pooled plasma according to standard chromatographic techniques, and from the same batch Hx was prepared using affinity chromatography. A second batch of Hx was prepared directly from human serum according to a standard protocol. (For comparison, additional Hx samples obtained from other centers were also included in the study.) The results show: (1) 100% homology of 100KF with plasma Hx after internal sequence analysis; (2) positive staining of the eluate with both monoclonal and polyclonal anti-Hx IgG as well as anti-100KF IgG in dot-blot assays, and similar bands on Western blotting using the same antibodies; (3) affection of glomerular polyanions and glomerular ecto-ATPase after incubation of kidney tissue with either 100KF or Hx (1.5 respectively 1.0 mg/ml; 1.0 h, 37°C), as detected by computerized histochemical quantification; and (4) significant enhancement of urinary protein leakage after Hx perfusion followed by diluted rat serum into the rat kidney ex vivo (Hx: 210.65 ± 49.79 μg protein leakage per min versus heat-inactivated Hx control: 112.2 ± 49.18 μg per min [both n = 6]). From these data and from the observation that both Hx and 100KF activity can be inhibited by serine protease inhibitors but not by broad spectrum collagenase inhibitors, it is concluded that Hx may be closely related or identical to the active moiety of 100KF.
Renin Inhibition Improves Pressure Natriuresis in Essential Hypertension
Authors: PAASSEN PIETER VAN , ZEEUW DICK DE , JONG PAUL E. DE , NAVIS GERJAN 
Published: April 2021

Abstract.
Pressure natriuresis (PN), i.e., a rise in renal sodium excretion in response to a higher BP, is involved in long-term BP regulation. PN is blunted in essential hypertension, but the mechanism is unknown. This study assessed the role of the renin-angiotensin-aldosterone system (RAAS) in PN in eight essential hypertensive men from the individual correlations between spontaneous fluctuations in BP and time corresponding changes in sodium excretion (collected at 2- and 4-h intervals for 48 h), during strict sodium balance, without treatment, and during renin inhibition (remikiren, 600 mg oral compound). Without treatment, daily values for mean arterial pressure were 109.5 ± 1.9 and 107 ± 1.9 mmHg, for urinary sodium excretion were 37.2 ± 2.8 and 42.0 ± 2.8 mmol/24 h, and for plasma renin activity were 2.34 ± 0.48 and 2.23 ± 0.44 nmol/L per h, respectively, for two consecutive days. During remikiren treatment, mean arterial pressure was 101.9 ± 1.7 and 100.8 ± 1.7 mmHg (P < 0.05, versus baseline). Urinary sodium excretion was 39.3 ± 3.7 and 45.2 ± 5.3 mmol/24 h (not significant versus baseline), and plasma renin activity was 0.79 ± 0.11 and 0.82 ± 0.13 nmol/L per h (P < 0.05 versus baseline). During remikiren treatment, BP correlated positively with sodium excretion in all patients but in only three of eight patients without treatment. The slope of the regression equation was steeper during remikiren treatment in seven of eight patients. Thus, the relationship between BP and natriuresis was more readily apparent during RAAS blockade, suggesting that RAAS activity blunts PN in hypertensive patients. Improved PN may contribute to the hypotensive effect of RAAS blockade and to maintenance of sodium balance at a lower BP level without volume expansion.
Development of Autosomal Recessive Polycystic Kidney Disease in BALB/c-cpk/cpk Mice
Authors: RICKER JUSTIN L. , GATTONE VINCENT H. , CALVET JAMES P. , RANKIN CAROLYN A. 
Published: April 2021

Abstract.
Autosomal recessive polycystic kidney disease (ARPKD) is a rare but devastating inherited disease in humans. Various strains of mice that are homozygous for the cpk gene display renal pathology similar to that seen in human ARPKD. The PKD progresses to renal insufficiency, azotemia, and ultimately a uremic death by approximately 3 wk of age. This study characterizes PKD in mice that are homozygous for the cpk gene on a BALB/c inbred mouse background. The BALB/c-cpk/cpk murine model displays renal as well as extrarenal pathology similar to that found in human ARPKD. The renal pathology includes the well-characterized early proximal tubule and, later, massive collecting duct cysts. The extrarenal defects in this murine model include common bile duct dilation, intrahepatic biliary duct cysts with periductal hyperplasia, and pancreatic dysplasia with cysts. Renal mRNA expression of c-myc, a proto-oncogene, and clusterin (SGP-2), a marker associated with immature collecting ducts, decreases during normal development but is upregulated in murine ARPKD. Expression of epidermal growth factor (EGF) mRNA is significantly diminished, whereas EGF receptor mRNA is upregulated in the BALB/c-cpk/cpk kidney compared with phenotypically normal littermates. To determine whether the altered EGF expression contributes to the development of PKD, neonatal mice were treated with exogenous EGF (1 μg/g body wt injected subcutaneously on postnatal days 3 through 9). EGF treatment reduced the relative kidney weight and common bile duct dilation and downregulated renal expression of clusterin and EGF receptor. However, exogenous EGF did not affect the degree of renal failure, the pancreatic pathology, or the misregulated renal expression of c-myc. In summary, the present study characterizes the renal and extrarenal pathology in the BALB/c-cpk/cpk murine model of ARPKD. Renal mRNA expression of EGF is diminished in this mouse model. EGF treatment did not prevent renal failure but ameliorated pathologic changes in the kidney and the biliary ducts of the BALB/c-cpk/cpk mouse.
Renal Epithelium Is a Previously Unrecognized Site of HIV-1 Infection
Authors: BRUGGEMAN LESLIE A. , ROSS MICHAEL D. , TANJI NOZOMU , CARA ANDREA , DIKMAN STEVEN , GORDON RONALD E. , BURNS GODFREY C. , D'AGATI VIVETTE D. , WINSTON JONATHAN A. , KLOTMAN MARY E. , KLOTMAN PAUL E. 
Published: April 2021

Abstract.
The striking emergence of an epidemic of HIV-related renal disease in patients with end-stage renal disease provided the rationale for the exploration of whether HIV-1 directly infects renal parenchymal cells. Renal glomerular and tubular epithelial cells contain HIV-1 mRNA and DNA, indicating infection by HIV-1. In addition, circularized viral DNA, a marker of recent nuclear import of full-length, reverse-transcribed RNA, was detected in the biopsies, suggesting active replication in renal tissue. Infiltrating infected leukocytes harbored more viral mRNA than renal epithelium. Identification of this novel reservoir suggests that effectively targeting the kidney with antiretrovirals may be critical for patients who are seropositive with renal disease. Thus, renal epithelium constitutes a unique and previously unrecognized cell target for HIV-1 infection.
Calcemic Activity of 19-Nor-1,25(OH)2D2 Decreases with Duration of Treatment
Authors: BROWN ALEX J. , FINCH JANE , TAKAHASHI FUMIAKI , SLATOPOLSKY EDUARDO 
Published: April 2021

Abstract.
19-Nor-1,25(OH)2D2 (19-norD2) has been shown to suppress parathyroid hormone effectively, but with lower calcemic activity than 1,25(OH)2D3. The present study investigated potential mechanisms to explain the reduced calcemic response to 19-norD2. Tissue localization of [3H]19-norD2 or[3H]1,25(OH)2D3 after a single injection was not different. Intestinal calcium absorption and bone mobilization, measured in vitamin D-deficient rats 24 h after single injections of 60 or 600 pmol of 19-norD2 or 1,25(OH)2D3, were enhanced to a similar degree by the two compounds. However, when normal rats were treated every other day with 240 pmol of 19-norD2 or 1,25(OH)2D3, increases in serum calcium were identical 24 h after the first injection but diverged thereafter with significantly lower serum calcium in the 19-norD2-treated rats by 5 d. Intestinal calcium absorption and bone calcium mobilization were reassessed in vitamin D-deficient rats after seven daily injections of 600 pmol of 19-norD2 or 1,25(OH)2D3, and both parameters were significantly lower in the 19-norD2-treated rats. Pharmacokinetic analysis after seven daily injections of 600 pmol of 19-norD2 or 1,25(OH)2D3 showed similar localization to the intestine and bone. In addition, intestinal vitamin D receptor levels were not different after 1 wk of treatment with 19-norD2 or 1,25(OH)2D3. In conclusion, the low calcemic activity of 19-norD2 seems to be due to an acquired, postreceptor resistance of the intestine and bone to chronic treatment with the analog.
Glomerular Permselectivity at the Onset of Nephropathy in Type 2 Diabetes Mellitus
Authors: LEMLEY KEVIN V. , BLOUCH KRISTINA , ABDULLAH ISHA , BOOTHROYD DEREK B. , BENNETT PETER H. , MYERS BRYAN D. , NELSON ROBERT G. 
Published: April 2021

Abstract.
The development of microalbuminuria in individuals with type 2 diabetes mellitus is associated with a 10-fold increase in the risk of progression to overt nephropathy and eventual end-stage renal failure. The present study reports long-term (up to 8 yr) follow-up of 43 Pima Indians with type 2 diabetes detected on screening to have microalbuminuria. The natural history of albuminuria in these individuals included progression to overt proteinuria (urinary albumin excretion ≥ 300 mg/d) in half of the participants by 7 yr of follow-up. The size selectivity of the glomerular barrier was also investigated using dextran sieving and pore theory. Whereas a comparison group of macroalbuminuric Pima Indians had an excess of large pores that served as a macromolecular “shunt,” individuals with microalbuminuria had a shunt size no different from long-term diabetic, normoalbuminuric control subjects. An abrupt transition from little or no relationship to a highly significant and positive relationship between increasing albuminuria and shunt size occurred at an albumin-to-creatinine ratio of approximately 3000 mg/g. Shunt size in macroalbuminuric individuals correlated with the extent of foot process broadening. Podocyte foot processes in microalbuminuric participants were not different from those in control subjects. In conclusion, although microalbuminuria in type 2 diabetic Pima Indians often heralds progressive glomerular injury, it is not the result of defects in the size permselectivity of the glomerular barrier but rather of changes in either glomerular charge selectivity or tubular handling of filtered proteins or of a combination of these two factors.
Effects of Growth Hormone on Leptin Metabolism and Energy Expenditure in Hemodialysis Patients with Protein-Calorie Malnutrition
Authors: GARIBOTTO GIACOMO , BARRECA ANTONINA , SOFIA ANTONELLA , RUSSO RODOLFO , FIORINI FULVIO , CAPPELLI GIORGIO , CAVATORTA FOSCO , CESARONE ARIANNA , FRANCESCHINI ROBERTO , SACCO PAOLO , MINUTO FRANCESCO , BARRECA TOMASO 
Published: April 2021

Abstract.
The relationships among growth hormone (GH), leptin, and resting energy expenditure (REE) are not understood. It has been reported that in malnourished hemodialysis patients, GH increases muscle protein synthesis, a process that requires energy. The present study evaluated the arterial levels and the forearm exchange of leptin, as well as the REE of the same patients during their participation in the same study, in four sequential 6-wk periods: I, baseline; II, GH treatment; III, washout; and IV, GH + intradialytic parenteral nutrition. During periods II and IV, patients received GH (5 mg three times per week). REE rose by 5% in period II, declined during period III, and rose by 7% during period IV. Basal leptin levels were low (2.0 ± 0.19 ng/L). Insulin and leptin levels, as well as leptin release from the forearm, were unchanged during periods I through III but rose (+ 36%; P < 0.05) during period IV. Changes in arterial leptin were directly related to changes in forearm leptin release (P < 0.002), indicating a role of leptin production by peripheral tissues on leptinemia. Changes in leptin release were directly related to insulin (P < 0.001) and, less consistently, to insulin-like growth factor-binding protein-1 levels (P < 0.02). Similarly, variations in leptin levels were directly related to insulin (P < 0.01). Variations in REE were not related to variations in leptin or insulin levels but to changes in muscle protein synthesis (P < 0.025). The data show that in malnourished hemodialysis patients, treatment with GH is not invariably associated with an increase in leptin production. An increase in leptin release by peripheral tissues and leptin levels occurs only in the setting of hyperinsulinemia. The increase in REE that is induced by treatment with GH is not dependent on changes in leptin but is largely accounted for by the energy cost of the stimulation of muscle protein synthesis.
Detection of Na+ Transporter Proteins in Urine
Authors: McKEE J. ANDREW , KUMAR SHAILESH , ECELBARGER CAROLYN A. , FERNÁNDEZ-LLAMA PATRICIA , TERRIS JAMES , KNEPPER MARK A. 
Published: April 2021

Abstract.
Previous studies have established that the vasopressin-regulated water channel of the collecting duct, aquaporin-2, is excreted in the urine, providing a means for assessment of regulation and dysregulation of aquaporin-2 in humans. This article addresses the hypothesis that membrane transporters from upstream nephron segments are normally detectable in urine. The experiments employed rabbit polyclonal antibodies against the major Na transporters of the proximal tubule (the type 3 Na-H exchanger [NHE3]), the thick ascending limb of Henle's loop (the bumetanide-sensitive Na-K-2Cl cotransporter [NKCC2]), and the distal convoluted tubule (the thiazide-sensitive Na-Cl cotransporter [NCC]) in immunoblotting experiments. All three of these transporters were readily detectable as high molecular weight complexes present in lowdensity membrane fractions from urine of normal rats. Cross linking studies of NHE3, NKCC2, and NCC revealed that high molecular weight complexes are normally present in renal tissue. The molecular weights of the complexes in urine matched those of the cross-linked complexes in native kidney tissue. The presence in urine of integral membrane proteins representative of each nephron segment raises the possibility that limited or comprehensive proteomic analysis of urine samples may be useful in clinical settings.
Glomerular Expression of Dystroglycans Is Reduced in Minimal Change Nephrosis But Not in Focal Segmental Glomerulosclerosis
Authors: REGELE HEINRICH M. , FILLIPOVIC EDITH , LANGER BRIGITTE , POCZEWKI HELGA , KRAXBERGER ILSE , BITTNER REGINALD E. , KERJASCHKI DONTSCHO 
Published: April 2021

Abstract.
Extensive flattening of podocyte foot processes and increased permeability of the glomerular capillary filter are the major pathologic features of minimal change nephrosis (MCN) and focal segmental glomerulosclerosis (FSGS). Adhesion proteins anchor and stabilize podocytes on the glomerular basement membrane (GBM), and presumably are involved in the pathogenesis of foot process flattening. Thus far, α3 β1-integrin was localized to basal cell membrane domains. In this report, α- and β-dystroglycan (DG) were detected at precisely the same location by immunoelectron microscopy, and the presence of α- and β-DG chains was confirmed by immunoblotting on isolated human glomeruli. Because the major DG binding partners in the GBM (laminin, agrin, perlecan), and the intracellular dystrophin analogue utrophin are also present in glomeruli, it appears that podocytes adhere to the GBM via DG complexes, similar to muscle fibers in which actin is linked via dystrophin and DG to the extracellular matrix. As with muscle cells, it is therefore plausible that podocytes use precisely actin-guided DG complexes at their “soles” to actively govern the topography of GBM matrix proteins. Expression of the α/β-DG complex was reported to be reduced in muscular dystrophies, and therefore a search for similar pathologic alterations in archival kidney biopsies from patients with MCN (n = 16) and FSGS (n = 8) was conducted by quantitative immunoelectron microscopy. The density of α-DG on the podocyte's soles was significantly reduced to 25% in MCN, whereas it was not different in normal kidneys and FSGS. The expression of β-DG was reduced to >50% in MCN, and was slightly increased in FSGS. Levels of DG expression returned to normal in MCN after steroid treatment (n = 4). Expression of β1-integrin remained at normal levels in all conditions. These findings point to different potentially pathogenic mechanisms of foot process flattening in MCN and FSGS.
GNSS for Quasi-Real-Time Earthquake Source Determination in Eastern Tibet: A Prototype System toward Early Warning Applications
Authors: Shan Xinjian , Li Yanchuan , Wang Zhenjie , Yin Hao , Liu Xiaodong , Liu Yunhua , Zhang Guohong , Zhang Yingfeng , Qu Chunyan 
Published: April 2021

AbstractActive crustal deformation of the Tibetan plateau results in destructive continental earthquakes and is therefore the focus of intense research interest. Increases in the numbers of Global Navigation Satellite System (GNSS) networks and stations deployed in Tibet are allowing for the characterization of crustal deformation during different phases of the earthquake cycle. Here, we present the status of a “seismic + high-rate GNSS” network deployed in eastern Tibet, including its data streams and data processing system, with the goal of supporting quasi-real-time earthquake source determination. Furthermore, we use this network to test a prototype earthquake early warning (EEW) system using data from the 2008 Mw 7.9 Wenchuan earthquake, the 2011 Mw 9.0 Tohoku earthquake, and 2200 synthetic earthquakes with moment magnitudes ranging from 6.5 to 7.5 on the southern Longmen Shan fault and Anninghe fault. The results show that our current methodology could respond to moderate-to-large earthquakes (magnitude 7+) within tens of seconds after the origin time, with implications for EEW applications in China.