bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of Neuronal Nitric Oxide Synthase in the Rat Remnant Kidney
Authors: ROCZNIAK AGNES , FRYER JAMES N. , LEVINE DAVID Z. , BURNS KEVIN D. 
Published: April 2021

Abstract.
Chronic renal failure is associated with disturbances in nitric oxide (NO) production. This study was conducted to determine the effect of 5/6 nephrectomy (5/6 Nx) on expression of intrarenal neuronal nitric oxide synthase (nNOS) in the rat. In normal rat kidney, nNOS protein was detected in the macula densa and in the cytoplasm and nuclei of cells of the inner medullary collecting duct by both immunofluorescence and electron microscopy. Western blot analysis revealed that 2 wk after 5/6 Nx, there were significant decreases in nNOS protein expression in renal cortex (sham: 95.42 ± 15.60 versus 5/6 Nx: 47.55 ± 12.78 arbitrary units, P < 0.05, n = 4) and inner medulla (sham: 147.70 ± 26.96 versus 5/6 Nx: 36.95 ± 17.24 arbitrary units, P < 0.005, n = 8). Losartan treatment was used to determine the role of angiotensin II (AngII) AT1 receptors in the inhibition of nNOS expression in 5/6 Nx. Losartan had no effect on the decreased expression of nNOS in the inner medulla, but partially increased nNOS protein expression in the cortex of 5/6 Nx rats. In contrast, in sham rats losartan significantly inhibited nNOS protein expression in the cortex (0.66 ± 0.04-fold of sham values, P < 0.05, n = 6) and inner medulla (0.74 ± 0.12-fold of sham values, P < 0.05, n = 6). nNOS mRNA was significantly decreased in cortex and inner medulla from 5/6 Nx rats, and the effects of losartan on nNOS mRNA paralleled those observed on nNOS protein expression. These data indicate that 5/6 Nx downregulates intrarenal nNOS mRNA and protein expression. In normal rats, AngII AT1 receptors exert a tonic stimulatory effect on expression of intrarenal nNOS. These findings suggest that the reduction in intrarenal nNOS expression in 5/6 Nx may play a role in contributing to hypertension and altered tubular transport responses in chronic renal failure.
Parathyroid Hormone-Related Protein (107-139) Stimulates Interleukin-6 Expression in Human Osteoblastic Cells
Authors: DE MIGUEL FERNANDO , MARTINEZ-FERNANDEZ PILAR , GUILLEN CARLOS , VALIN ALVARO , RODRIGO ANA , MARTINEZ MARIA EUGENIA , ESBRIT PEDRO 
Published: April 2021

Abstract.
The N-terminal region of both parathyroid hormone (PTH) and PTH-related protein (PTHrP) binds to the same PTH/PTHrP receptor in osteoblasts. However, C-terminal PTHrP (107-139) inhibits growth and various functions of osteoblasts and osteoclasts apparently through PTHrP-specific receptors. PTH (1-34) and PTHrP (1-34) rapidly induce interleukin-6 (IL-6) expression by osteoblasts. The aim of the present study was to assess the effects of PTHrP (107-139) on IL-6 gene expression and secretion by osteoblastic cells from human trabecular bone (hOB). Using reverse transcription followed by PCR, it was found that IL-6 mRNA was twofold maximally increased by either PTHrP (1-34) or PTHrP (107-139), at 10 nM, over basal within 1 to 2 h in hOB cells. This effect of PTHrP (107-139), and that of PTHrP (1-34), were abolished by the transcription inhibitor actinomycin D. Meanwhile, puromycin, a protein synthesis inhibitor, superinduced IL-6 expression in the presence or absence of each PTHrP peptide. Both PTHrP (1-34) and PTHrP (107-139), but not PTHrP (38-64), stimulated IL-6 secretion to the hOB cell-conditioned medium at 24 h, dose dependently. In addition, this maximal stimulatory effect (twofold over basal) was similar with each PTHrP peptide alone, and not additive when added together. PTHrP (107-139) stimulation of mRNA and protein in hOB cells was abolished by bisindolylmaleimide I, a protein kinase C inhibitor, but not by either adenosine 3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS), or N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89), two protein kinase A inhibitors. These results indicate that C-terminal PTHrP, like its N-terminal domain, induces IL-6 production by human osteoblastic cells. This effect of both PTHrP regions could provide a mechanism to modulate bone turnover.
Ambulatory Blood Pressure and Left Ventricular Mass in Normotensive Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: VALERO F. ALFREDO , MARTINEZ-VEA ALBERTO , BARDAJÍ ALFREDO , GUTIERREZ CRISTINA , GARCIA CARMEN , RICHART CRISTOBAL , OLIVER JESUS A. 
Published: April 2021

Abstract.
Higher left ventricular mass (LVM) has been found in early stages of autosomal dominant polycystic kidney disease (ADPKD). The mechanisms involved in the increase of LVM are unknown. To investigate whether LVM in ADPKD may be influenced by abnormal diurnal BP variations, the 24-h ambulatory BP profile was analyzed in a group of young normotensive ADPKD patients. Ambulatory BP monitoring and two-dimensional echocardiography were performed in 26 young normotensive ADPKD with normal renal function and in 26 healthy control subjects. LVM index was higher in ADPKD patients than in controls (90.8 ± 19.6 g/m2
versus 73.9 ± 16.1 g/m2, P = 0.001). Average 24-h and daytime systolic, diastolic, and mean BP were similar in both groups. Nighttime diastolic and mean BP, but not systolic BP, were greater in ADPKD patients. The average and percent nocturnal decrease of systolic BP was lower in ADPKD patients than in control subjects (10.0 mmHg [-3 to 24] versus 15.5 mmHg [-4 to 31], P = 0.009, and 9.0% [-2 to 22] versus 14.2% [-2 to 25], P = 0.016, respectively). On the basis of their profile BP patterns, 54% of ADPKD subjects and 31% of controls were classified as nondippers (P = 0.092). There were no differences between dippers and nondippers in left ventricular wall thickness, chamber dimensions, and mass indexes. In ADPKD patients, simple regression analysis showed that LVM index was correlated with 24-h, daytime, and nighttime systolic BP. On multiple regression analysis, the 24-h systolic BP was the only variable linked to LVM index. It is concluded that young normotensive ADPKD patients have higher LVM that is closely related to the ambulatory systolic BP. The nocturnal fall in BP is attenuated in these patients, although it is not associated with the higher LVH that they present.
Effect of Histamine H2-Receptor Antagonist on the Phosphorus-Binding Abilities of Calcium Carbonate and Calcium Lactate in Hemodialysis Patients
Authors: TAKAHASHI NORIHIRO , SHOJI TETSUO , MATSUBARA KEISUKE , HITOMI HIROFUMI , HASHIMOTO MAYUKO , KIYOMOTO HIDEYASU , UCHIDA KOICHI , MIKI SHIGEHIRO , HIROHATA MAMORU , ISHIZU TSUTOMU , AKIYAMA KENJI , MIZUSHIGE KATSUFUMI , MATSUO HIROHIDE , YUASA SHIGEKAZU 
Published: April 2021

Abstract.
The effect of histamine H2-receptor antagonist (famotidine) on the phosphorus-binding abilities of calcium carbonate and calcium lactate were examined in 13 chronic hemodialysis patients. In seven patients receiving calcium carbonate, famotidine (20 mg/d) was given because of gastroduodenal disorders, and calcium carbonate was replaced with calcium lactate as a phosphorus binder after 4 wk of treatment with famotidine. With the 4-wk administration of famotidine accompanied by calcium carbonate, the serum phosphorus level increased from 6.3 ± 0.9 to 7.1 ± 0.5 mg/dl (P < 0.05). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly when compared to that before substitution (6.3 ± 0.2 and 6.0 ± 0.9 mg/dl after 4 and 8 wk of substitution, respectively), despite continued administration of famotidine. Serum calcium, creatinine, alkaline phosphatase, high sensitive parathyroid hormone, blood urea nitrogen, arterial blood pH, and bicarbonate were not significantly altered during the trial period. In six control patients treated with calcium carbonate alone, there were no statistical changes in serum calcium and phosphorus levels after substitution of calcium lactate for calcium carbonate. These results suggest that famotidine significantly affects the phosphorus-binding ability of calcium carbonate, but not that of calcium lactate. A careful observation of changes in the serum phosphorus level should be required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphorus binder in such hemodialysis patients.
Plasma Total Homocysteine and Hemodialysis Access Thrombosis
Authors: SHEMIN DOUGLAS , LAPANE KATE L. , BAUSSERMAN LINDA , KANAAN ELIAS , KAHN SEWELL , DWORKIN LANCE , BOSTOM ANDREW G. 
Published: April 2021

Abstract.
Mild hyperhomocysteinemia, a putative risk factor for atherothrombotic cardiovascular disease morbidity and mortality, may contribute to the excess incidence of atherothrombotic outcomes in the dialysis-dependent end-stage renal disease population. Hemodialysis access (fistula or graft) thrombosis is an unfortunately common and costly morbidity in this patient population. In this study, using a prospective design, the potential relationship between baseline nonfasting, predialysis plasma total homocysteine (tHcy) levels and vascular access-related morbidity was examined in a cohort of 84 hemodialysis patients with a fistula or prosthetic graft as their primary hemodialysis access. Vascular access thrombotic episodes were recorded over a subsequent 18-mo follow-up period. Forty-seven patients (56% of the total) had at least one access thrombosis during the 18-mo follow-up period (median follow-up, 13 mo; rate, 0.6 events per patient-year of follow-up). Proportional hazards modeling revealed that each 1 μM/L increase in the tHcy level was associated with a 4.0% increase in the risk of access thrombosis (95% confidence interval, 1.0 to 6.0%, P = 0.008). This association persisted after adjustment for type of access (fistula versus graft), age, gender, time on dialysis, diabetes, smoking, hypertension, nutritional status, urea reduction ratio, dyslipidemia, and the presence of previous vascular disease. Elevated tHcy levels appear to confer a graded, independent increased risk for hemodialysis access thrombosis. A randomized, controlled trial examining the effect of tHcy-lowering intervention on hemodialysis access thrombosis appears to be justified.
Growth Plate Cartilage Formation and Resorption Are Differentially Depressed in Growth Retarded Uremic Rats
Authors: COBO ANGELES , LÓPEZ JOSÉ , CARBAJO EDUARDO , SANTOS FERNANDO , ALVAREZ JESÚS , FERNÁNDEZ MARTA , WERUAGA ANA 
Published: April 2021

Abstract.
To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF). NX rats were growth retarded and severely uremic. Growth plate height (mean ± SD) was much greater (P < 0.05) in NX (868.4 ± 85.4 μm) than SAL (570.1 ± 93.5 μm) and SPF (551.9 ± 99.7 μm) rats as a result of a higher (P < 0.05) hypertrophic zone (661.0 ± 89.7 versus 362.8 ± 71.6 and 353.0 ± 93.9 μm, respectively). The increased size of the growth plate was associated with a greater number of chondrocytes and modifications in their structure, particularly in the hypertrophic zone adjacent to bone. In this zone, chondrocytes of NX animals were significantly (P < 0.05) smaller (12080.4 ± 1158.3 μm3) and shorter (34.1 ± 2.5 μm) than those of SAL (16302.8 ± 1483.4 μm3 and 37.8 ± 2.0 μm) and SPF (14465.8 ± 1521.0 μm3 and 36.3 ± 1.8 μm). The interface between the growth plate cartilage and the metaphyseal bone appeared markedly irregular in NX rats. Kinetics of chondrocytes was also modified (P < 0.05) in the NX rats, which had lower cell turnover per column per day (5.4 ± 0.9), longer duration of hypertrophic phase (89.0 ± 15.2 h), and reduced cellular advance velocity (7.4 ± 2.2 μm/h) compared with SAL (8.0 ± 1.6, 32.1 ± 6.7 h, and 11.3 ± 2.7 μm/h) and SPF (7.2 ± 1.1, 34.8 ± 5.1 h, and 10.1 ± 2.5 μ/h). Cell proliferation was no different among the three groups. Because the growth plates of SPF and SAL rats were substantially not different, modifications observed in the NX rats cannot be attributed to the nutritional deficit associated with renal failure. These findings indicate that chronic renal failure depresses both the activity of the growth plate cartilage by altering chondrocyte hypertrophy and the replacement of cartilage by bone at the metaphyseal end. The two processes are differentially depressed since cartilage resorption is more severely lowered than cartilage enlargement and this leads to an accumulation of cartilage at the hypertrophic zone.
Directed Membrane Transport Is Involved in Process Formation in Cultured Podocytes
Authors: SIMONS MATIAS , SAFFRICH RAINER , REISER JOCHEN , MUNDEL PETER 
Published: April 2021

Abstract.
Mature glomerular visceral epithelial cells, or podocytes, are unique cells with a complex cell architecture. Characteristically, they possess a highly branched array of major processes and foot processes, which are essential for glomerular filtration in the kidney. A podocyte cell line with the potential to exhibit many features of differentiated podocytes, particularly the formation of cell processes, was recently established. In this study, it is shown that directed membrane transport is involved in process formation in cultured podocytes. The well-characterized vesicular stomatitis virus G was used as a marker protein for the biosynthetic pathway in these cells. It seems that newly synthesized vesicular stomatitis virus G is preferentially delivered into the cell processes of the podocytes, where it is colocalized with known regulators of vesicular transport from the Golgi apparatus to the plasma membrane, such as the small GTPase rab8 and the sec6/sec8 complex. To determine the role of vesicular transport in process formation, cells were treated with brefeldin A, a drug that disrupts the trafficking of post-Golgi transport vesicles. As a result, the podocytes reversibly lost their ability to form processes. These findings suggest that podocytes are dependent on a constant fresh source of lipids and proteins to form their processes.
Quantitative Trait Loci for Blood Pressure Exist Near the IGF-1, the Liddle Syndrome, the Angiotensin II-Receptor Gene and the Renin Loci in Man
Authors: NAGY ZSUZSANNA , BUSJAHN ANDREAS , BÄHRING SYLVIA , FAULHABER HANS-DIETER , GOHLKE HANS-RÜDIGER , KNOBLAUCH HANS , ROSENTHAL MAGDA , MÜLLER-MYHSOK BERTRAM , SCHUSTER HERBERT , LUFT FRIEDRICH C. 
Published: April 2021

Abstract.
Blood pressure (BP) is heritable and finding quantitative trait loci that influence BP is an important step in identifying genes responsible for BP regulation. Sixty-six pairs of dizygotic (DZ) twin subjects and their parents were used in a sib-pair analysis to look for linkage of selected candidate genes to the quantitative trait BP. Microsatellite markers were tested in the vicinity of the gene loci for insulin-like growth factor-1 (IGF-1), Liddle syndrome, autosomal-dominant hypertension with brachydactyly, angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, renin, and lipoprotein lipase. BP was measured in a standardized manner. Heart size was determined echocardiographically. Significant linkage was found at the IGF-1, Liddle syndrome, and AT1 receptor gene for systolic BP. Linkage for diastolic BP was found at the autosomal-dominant hypertension with brachydactyly locus. Both systolic and diastolic BP were linked to the renin gene locus. The linkage was most consistent for the IGF-1 gene locus and systolic BP. Linkage was also found between the IGF-1 gene locus and posterior cardiac wall thickness, septal thickness, and left ventricular mass index. It is suggested that these quantitative trait loci may be important for the subsequent detection of allelic variants for elevated BP. Furthermore, these results linking the IGF-1 gene locus to both BP and cardiac dimensions underscore the importance of the IGF-1 gene as a candidate gene for cardiovascular disease.
Developmental Expression of Protein Phosphatase 2A in the Kidney
Authors: EVERETT ALLEN D. , XUE CHUN , STOOPS TAMARA 
Published: April 2021

Abstract.
Although a number of growth and transcription factors are known to regulate renal growth and development, the signal transduction molecules necessary to mediate these developmental signals are relatively unknown. Therefore, the activity and mRNA and protein expression of the signal transduction molecule protein phosphatase 2A (PP2A) were examined during rat kidney development. Northern analysis of total kidney RNA or Western analysis of kidney protein homogenates from embryonic day 15 to 90-d-old adults demonstrated developmental regulation of the catalytic, major 55-kD B regulatory subunit and A structural subunit with the highest levels of expression in late embryonic and newborn kidneys. Similarly, okadaic acid-inhibitable phosphatase enzyme activity was highest in the embryonic and newborn kidney. To map cell-specific expression of PP2A in the developing kidney, in situ hybridization with a catalytic subunit digoxigenin-labeled cRNA was performed on embryonic day 20 and newborn kidneys. PP2A was found predominately in the nephrogenic cortex and particularly in the developing glomeruli and nonbrush border tubules in the embryonic day 20 and newborn kidneys. Similarly, immunocytochemistry with a specific PP2A catalytic subunit polyclonal anti-peptide antibody demonstrated catalytic subunit protein particularly concentrated in the podocytes of glomeruli in the newborn kidney. In the adult kidney, PP2A protein was no longer detectable except in the nuclei of distal tubular cells. Therefore, the developmental regulation of PP2A activity and protein during kidney development and its mapping to the nephrogenic cortex, developing glomeruli, and tubules suggests a role for PP2A in the regulation of nephron growth and differentiation.
Role of Reactive Oxygen Metabolites in Organophosphate-Bidrin-Induced Renal Tubular Cytotoxicity
Authors: POOVALA VANDANA S. , HUANG HONG , SALAHUDEEN ABDULLA K. 
Published: April 2021

Abstract.
Due to low toxicity to nontarget species and rapid degradation after its application, organophosphate (OP) remains a widely used class of pesticide. Suicidal or accidental overdose of OP can result in acute tubular necrosis. Experimental evidence shows little correlation between the renal tubular necrosis and the degree of OP-induced acetylcholinesterase inhibition, the main mechanism of OP's toxicity, suggesting the involvement of alternate mechanisms. Since reactive oxygen species (ROS) are known mediators of many toxin-induced renal injuries, this study was conducted to investigate whether ROS play a role in Bidrin® (BD)-induced renal tubular epithelial cell (LLC-PK1) toxicity. BD is an OP insecticide formulation with dicrotophos as the active ingredient. LLC-PK1 cell death, determined by lactate dehydrogenase (LDH) release (% of total), rose concentration- and time-dependently after exposure of the cells to 1000, 1250, 1500, 1750, and 2000 ppm of BD for 6, 12, 24, and 48 h. Antioxidants 2-methylaminochroman (2-MAC; 0.3 to 2.5 μM) and desferrioxamine (DFO; 0.25 to 2 mM) reduced cell damage induced by 1250 ppm of BD over a 24-h incubation in a concentration-related manner. The greatest reductions in % LDH were produced by DFO 2 mM and 2-MAC 2.5 μM, both significantly lower than BD alone. H2O2 levels (μmol/mg protein per h) were significantly elevated after exposure to 1250 ppm of BD. Significantly increased malondialdehyde formation (nmol/mg protein) compared with control was also found in BD-exposed cells indicating enhanced lipid peroxidation. Malondialdehyde generation was significantly suppressed by 2-MAC and DFO. These results demonstrate that the organophosphate BD can cause direct tubular cytotoxicity, and implicate, at least in part, a role for ROS and accompanying lipid peroxidation in cytotoxicity. Based on these direct in vitro findings, it is hypothesized that, besides hypotension that often accompanies OP intoxication, OP-induced oxidative stress at the tubular level may play a role in the pathogenesis of acute tubular necrosis.
Analysis of IgA1 O-Glycans in IgA Nephropathy by Fluorophore-Assisted Carbohydrate Electrophoresis
Authors: ALLEN ALICE C. , BAILEY ELAINE M. , BARRATT JONATHAN , BUCK KATHARINE S. , FEEHALLY JOHN 
Published: April 2021

Abstract.
Abnormal O-glycosylation of IgA1 may contribute to pathogenic mechanisms in IgA nephropathy (IgAN). Observations of altered lectin binding to IgA1 in IgAN suggest that the O-glycan chains may be undergalactosylated, but precise structural definition of the defect has proved technically difficult, and it remains unconfirmed. This is the first study using fluorophore-assisted carbohydrate electrophoresis (FACE) to analyze IgA1 O-glycans in IgAN and controls. IgA1 was purified from serum, and the intact O-glycans were released by hydrazinolysis at 60°C. After re-N-acetylation, the glycans were fluorophore-labeled and separated by polyacrylamide gel electrophoresis. Sequential exoglycosidase digestions of IgA1 allowed identification of the different O-glycan bands on FACE gels, and their relative frequencies in IgA1 samples were measured by ultraviolet densitometry. Lectin binding of the IgA1 samples was also measured. In some patients with IgAN, FACE analysis demonstrated a significant increase in the percentage of IgA1 O-glycan chains consisting of single N-acetyl galactosamine (GalNAc) units rather than the more usual galactosylated and sialylated forms. This finding was confirmed using both desialylated IgA1 and enzymatically released O-glycans. Good correlation was also found between O-glycan agalactosylation on FACE analysis and IgA1 lectin binding in IgAN, supporting the value of lectins as tools for detection of this abnormality. This is the first study in which all of the predicted O-glycan forms of IgA1 have been analyzed simultaneously, and demonstrates that in IgAN, the IgA1 O-glycan chains are truncated, with increased terminal GalNAc. This abnormality has the potential to significantly affect IgA1 behavior and handling with pathogenic consequences in IgAN.