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https://www.readbyqxmd.com/read/28102076/kinobead-and-single-shot-lc-ms-profiling-identifies-selective-pkd-inhibitors
#1
Martin Golkowski, Rama Subba Rao Vidadala, Chloe K Lombard, Hyong Won Suh, Dustin J Maly, Shao-En Ong
ATP-competitive protein kinase inhibitors are important research tools and therapeutic agents. Because there are >500 human kinases that contain highly conserved active sites, the development of selective inhibitors is extremely challenging. Methods to rapidly and efficiently profile kinase inhibitor targets in cell lysates are urgently needed to discover selective compounds and to elucidate the mechanisms of action for polypharmacological inhibitors. Here, we describe a protocol for microgram-scale chemoproteomic profiling of ATP-competitive kinase inhibitors using kinobeads...
January 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#2
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28098745/effect-of-freeze-dried-allograft-bone-with-human-basic-fibroblast-growth-factor-containing-a-collagen-binding-domain-from-clostridium-histolyticum-collagenase-on-bone-formation-after-lumbar-posterolateral-fusion-surgery-in-rats
#3
Gen Inoue, Kentaro Uchida, Osamu Matsushita, Hisako Fujimaki, Wataru Saito, Masayuki Miyagi, Hiroyuki Sekiguchi, Nozomu Nishi, Seiji Ohtori, Mizuki Yogoro, Masashi Takaso
STUDY DESIGN: An experimental study. OBJECTIVE: To evaluate the effectiveness of freeze-dried bone allograft (FDBA) with basic fibroblast growth factor (bFGF) fused with the polycystic kidney disease domain (PKD) and the collagen-biding domain (CBD) of Clostridium histolyticum collagenase, for the acceleration of lumbar posterolateral fusion in rats. SUMMARY OF BACKGROUND DATA: Reports indicate bFGF is an effective growth factor with osteogenic potential for promoting bone regeneration, although its efficiency decreases rapidly following its diffusion in body fluid from the host site...
January 16, 2017: Spine
https://www.readbyqxmd.com/read/28077787/androgen-suppresses-protein-kinase-d1-expression-through-fibroblast-growth-factor-receptor-substrate-2-in-prostate-cancer-cells
#4
Liyong Zhang, Zhenlong Zhao, Shuping Xu, Manuj Tandon, Courtney R LaValle, Fan Deng, Q Jane Wang
In prostate cancer, androgen/androgen receptor (AR) and their downstream targets play key roles in all stages of disease progression. The protein kinase D (PKD) family, particularly PKD1, has been implicated in prostate cancer biology. Here, we examined the cross-regulation of PKD1 by androgen signaling in prostate cancer cells. Our data showed that the transcription of PKD1 was repressed by androgen in androgen-sensitive prostate cancer cells. Steroid depletion caused up regulation of PKD1 transcript and protein, an effect that was reversed by the AR agonist R1881 in a time- and concentration-dependent manner, thus identifying PKD1 as a novel androgen-repressed gene...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28049233/baseline-cardiovascular-characteristics-of-adult-patients-with-chronic-kidney-disease-from-the-korean-cohort-study-for-outcomes-in-patients-with-chronic-kidney-disease-know-ckd
#5
Hyoungnae Kim, Tae Hyun Yoo, Kyu Hun Choi, Kook Hwan Oh, Joongyub Lee, Soo Wan Kim, Tae Hee Kim, Suah Sung, Seung Hyeok Han
Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). We report the baseline cardiovascular characteristics of 2,238 participants by using the data of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) study. The cohort comprises 5 subcohorts according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), polycystic kidney disease (PKD), and unclassified. The average estimated glomerular filtration rate (eGFR) was 50...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28049232/baseline-general-characteristics-of-the-korean-chronic-kidney-disease-report-from-the-korean-cohort-study-for-outcomes-in-patients-with-chronic-kidney-disease-know-ckd
#6
Eunjeong Kang, Miyeun Han, Hyunsuk Kim, Sue Kyung Park, Joongyub Lee, Young Youl Hyun, Yong Soo Kim, Wookyung Chung, Hyo Jin Kim, Yun Kyu Oh, Curie Ahn, Kook Hwan Oh
The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28049203/the-involvement-of-protein-kinase-d-in-t-cell-induced-mast-cell-activation
#7
Pazit Salamon, Irit Shefler, Alon Y Hershko, Yoseph A Mekori
BACKGROUND: It has recently been reported that mast cells (MC) can be activated to degranulate and release certain cytokines in response to direct physical contact with activated but not resting T cells or their membranes. The MAPK family members ERK and p38 were found to participate. In this work, we further characterize the signaling events involved in this novel pathway of activation. METHODS: Human MC were stimulated by activated T cell membranes (T*m). Phosphorylation of kinases was assessed by Western blotting...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28032559/bradykinin-stimulates-protein-kinase-d-mediated-colonic-myofibroblast-migration-via-cyclooxygenase-2-and-heat-shock-protein-27
#8
Eric Chu, Shyla Saini, Tiegang Liu, James Yoo
BACKGROUND: Inflammatory bowel disease is characterized by episodic intestinal injury and repair. Myofibroblasts are gastrointestinal tract stromal cells that regulate the reparative process and are known targets of inflammatory mediators including bradykinin (BK). However, the mechanisms through which inflammation regulates myofibroblast-induced wound healing remain incompletely understood. Here, we demonstrate, for the first time, that BK stimulates myofibroblast migration through protein kinase D (PKD)-mediated activation of the cyclooxygenase-2 (COX-2) and heat shock protein 27 (Hsp27) pathways...
October 20, 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/28025160/characterisation-of-arginase-paralogues-in-salmonids-and-their-modulation-by-immune-stimulation-infection
#9
Ottavia Benedicenti, Tiehui Wang, Eakapol Wangkahart, Douglas J Milne, Jason W Holland, Catherine Collins, Christopher J Secombes
In this study we show that four arginase isoforms (arg1a, arg1b, arg2a, arg2b) exist in rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). We have characterised these molecules in terms of a) sequence analysis, b) constitutive expression in different tissues, and modulated expression following c) stimulation of head kidney macrophages in vitro, or d) vaccination/infection with Yersinia ruckeri and e) parasite infection (AGD caused by Paramoeba perurans and PKD caused by Tetracapsuloides bryosalmonae)...
December 23, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28018471/paroxysmal-kinesigenic-dyskinesia-in-a-patient-with-a-prrt2-mutation-and-centrotemporal-spike-discharges-on-electroencephalogram-case-report-of-a-10-year-old-girl
#10
Sun Young Seo, Su Jeong You
Coexistence of paroxysmal kinesigenic dyskinesia (PKD) with benign infantile convulsion (BIC) and centrotemporal spikes (CTS) is very rare. A 10-year-old girl presented with a 3-year history of frequent attacks of staggering while laughing and of suddenly collapsing while walking. Interictal electroencephalogram (EEG) revealed bilateral CTS, but no changes in EEG were observed during movement. The patient's medical history showed afebrile seizures 6 months after birth, while the family history showed that the patient's mother and relatives on the mother's side had similar dyskinesia...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/28017639/selective-coupling-of-the-s1p3-receptor-subtype-to-s1p-mediated-rhoa-activation-and-cardioprotection
#11
Bryan S Yung, Cameron S Brand, Sunny Y Xiang, Charles B B Gray, Christopher K Means, Hugh Rosen, Jerold Chun, Nicole H Purcell, Joan Heller Brown, Shigeki Miyamoto
Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P1, S1P2, and S1P3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to Gq. We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD...
December 23, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28007903/autophagy-activators-suppress-cystogenesis-in-an-autosomal-dominant-polycystic-kidney-disease-model
#12
Ping Zhu, Cynthia J Sieben, Xiaolei Xu, Peter C Harris, Xueying Lin
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2 It is one of the most common heritable human diseases with eventual development of renal failure; however, effective treatment is lacking. While inhibition of mechanistic target of rapamycin (mTOR) effectively slows cyst expansions in animal models, results from clinical studies are controversial, prompting further mechanistic studies of mTOR-based therapy. Here, we aim to establish autophagy, a downstream pathway of mTOR, as a new therapeutic target for PKD...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27993381/dietary-salt-restriction-is-beneficial-to-the-management-of-autosomal-dominant-polycystic%C3%A2-kidney-disease
#13
Vicente E Torres, Kaleab Z Abebe, Robert W Schrier, Ronald D Perrone, Arlene B Chapman, Alan S Yu, William E Braun, Theodore I Steinman, Godela Brosnahan, Marie C Hogan, Frederic F Rahbari, Jared J Grantham, Kyongtae T Bae, Charity G Moore, Michael F Flessner
The CRISP study of polycystic kidney disease (PKD) found that urinary sodium excretion associated with the rate of total kidney volume increase. Whether sodium restriction slows the progression of Autosomal Dominant PKD (ADPKD) is not known. To evaluate this we conducted a post hoc analysis of the HALT-PKD clinical trials of renin-angiotensin blockade in patients with ADPKD. Linear mixed models examined whether dietary sodium affected rates of total kidney volume or change in estimated glomerular filtration rate (eGFR) in patients with an eGFR over 60 ml/min/1...
February 2017: Kidney International
https://www.readbyqxmd.com/read/27934598/human-embryonic-stem-cells-derived-from-abnormal-blastocyst-donated-by-polycystic-kidney-syndrome-patient
#14
Qi Ouyang, Xiaoying Zhou, Jing Chen, Juan Du, Guangxiu Lu, Ge Lin, Yi Sun
Human embryonic stem cell (hESC) line chHES-468 was derived from abnormal blastocyst donated by polycystic kidney syndrome (PKD) patient after preimplantation genetic diagnosis (PGD) treatment. DNA sequencing analysis confirmed that chHES-468 cell line carried a heterozygous mutation, c.10526_10527delAG, of PKD1. Characteristic tests proved that the chHES-468 cell line presented typical markers of pluripotency and had the capability to form the three germ layers both in vitro and in vivo.
November 5, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27921040/new-insights-into-the-molecular-mechanisms-targeting-tubular-channels-transporters-in-pkd-development
#15
REVIEW
Ming Wu, Shengqiang Yu
BACKGROUND: Autosomal dominant polycystic kidney disease (PKD) or autosomal recessive PKD is caused by a mutation in the PKD1, PKD2 or PKHD1 gene, which encodes polycystin-1, polycystin-2 or fibrocystin, respectively. Embryonic and postnatal mutation studies show that transport or channel function is dysregulated before the initiation of cystogenesis, suggesting that the abnormality of transport or channel function plays a critical role in the pathology of PKD. SUMMARY: Polycystin-2 by itself is a calcium-permeable cation channel, and its channel function can be regulated by polycystin-1 or fibrocystin...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27921038/the-clinical-manifestation-and-management-of-autosomal-dominant-polycystic-kidney-disease-in-china
#16
REVIEW
Cheng Xue, Chen-Chen Zhou, Ming Wu, Chang-Lin Mei
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease characterized by progressive enlargement of renal cysts. The incidence is 1-2‰ worldwide. Mutations in two genes (PKD1 and PKD2) cause ADPKD. Currently, there is no pharmaceutical treatment available for ADPKD patients in China. Summary: This review focused on advances in clinical manifestation, gene diagnosis, risk factors, and management of ADPKD in China. There is an age-dependent increase in total kidney volume (TKV) and decrease in renal function in Chinese ADPKD patients...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27909846/benzimidazole-inhibitors-of-protein-kinase-ck2-potently-inhibit-the-activity-of-atypical-protein-kinase-rio1
#17
Konrad Kubiński, Maciej Masłyk, Andrzej Orzeszko
Benzimidazole derivatives of 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) comprise the important class of protein kinase CK2 inhibitors. Depending on the structure, benzimidazoles inhibit CK2 with different selectivity and potency. Besides CK2, the compounds can inhibit, with similar activity, other classical eukaryotic protein kinases (e.g. PIM, DYRK, and PKD). The present results show that a majority of the most common CK2 inhibitors can affect the atypical kinase Rio1 in a nanomolar range. Kinetic data confirmed the mode of action of benzimidazoles as typical ATP-competitive inhibitors...
December 1, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27871768/red-cell-pyruvate-kinase-deficiency-in-spain-a-study-of-15-cases
#18
Laura Montllor, María Del Mar Mañú-Pereira, Esther Llaudet-Planas, Pilar Gómez Ramírez, Julián Sevilla Navarro, Joan Lluís Vives-Corrons
BACKGROUND AND OBJECTIVE: Pyruvate kinase deficiency (PKD) is a rare, inherited disease causing chronic hemolysis and anemia of varying intensity. The genetic heterogeneity of PKD is high and, to this day, over 240 different mutations have been identified. PATIENTS AND METHODS: 15 unrelated patients affected by PKD have been studied. PKLR gene sequencing was performed by SANGER, including the determination of promoter regions, exonic, intronic flanking and 3'UTR...
January 6, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/27862246/a-retrospective-analysis-of-mortality-in-captive-pygmy-hippopotamus-choeropsis-liberiensis-from-1912-to-2014
#19
Gabriella L Flacke, Suzana Tkalčić, Beatrice Steck, Kristin Warren, Graeme B Martin
The pygmy hippopotamus (Choeropsis liberiensis) is an IUCN Red List Endangered species (CITES Appendix II) that has been housed in zoological collections since 1912. As wild populations continue to decline throughout the species' range, successful ex situ breeding and management, including an understanding of morbidity and mortality, are of utmost importance. This study is the first comprehensive review of mortality data from the captive population since 1982 and significantly expands on previous analyses. We solicited necropsy reports from 129/187 zoological institutions worldwide that currently or previously held pygmy hippos and received data for 404 animals (177 ♂, 220 ♀, 7 undermined sex), representing 43% of pygmy hippos that have died in captivity...
November 2016: Zoo Biology
https://www.readbyqxmd.com/read/27853247/six2crefrs2%C3%AE-knockout-mice-are-a-novel-model-of-renal-cystogenesis
#20
Pawan Puri, Daniel Bushnell, Caitlin M Schaefer, Carlton M Bates
Six2cre-mediated deletion of Frs2α (Six2creFrs2αKO), a major fibroblast growth factor receptor (Fgfr) docking protein in mouse nephron progenitors results in perinatal renal hypoplasia; however, postnatal Six2creFrs2αKO kidneys develop cysts. We sought to determine the pathogenesis of Six2creFrs2αKO cyst formation. We performed histological assays, Western blots, and quantitative PCR (qPCR). While embryonic day (E) 18.5 Six2Frs2αKO kidneys were hypoplastic and not cystic, postnatal day (P) 7 mutants had proximal tubular-derived cysts that nearly replaced the renal parenchyma by P21...
November 17, 2016: Scientific Reports
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