scholarly journals Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas

2015 ◽  
Vol 22 (5) ◽  
pp. 735-744 ◽  
Author(s):  
Tobias Åkerström ◽  
Holger Sven Willenberg ◽  
Kenko Cupisti ◽  
Julian Ip ◽  
Samuel Backman ◽  
...  

Aldosterone-producing adenomas (APAs) are found in 1.5–3.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the KCNJ5 gene. More recently, somatic mutations in CACNA1D, ATP1A1 and ATP2B3, also important for membrane potential/intracellular Ca2+ regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in CACNA1D in 3.0% (one novel mutation), ATP1A1 in 6.1% (six novel mutations) and ATP2B3 in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in CACNA1D, ATP1A1 and ATP2B3 were operated at an older age, were more often male and had tumors that were smaller than those in patients with KCNJ5 mutated tumors. Microarray transcriptome analysis segregated KCNJ5 mutated tumors from ATP1A1/ATP2B3 mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene NPNT, in ATP1A1/ATP2B3 mutated tumors compared to KCNJ5 mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential/intracellular Ca2+ levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration.

2020 ◽  
Vol 16 (3) ◽  
pp. 208-222
Author(s):  
Miglena Smerikarova ◽  
Stanislav Bozhanov ◽  
Vania Maslarska

Background: Sartans are mostly used as a part of combination with additional medicines in the therapy of essencial hypertension. Preferred combinations are ARB and thiazide diuretics (Hydrochlorothiazide (HCT) and Chlorthalidone (CHL)) or ARB and calcium antagonists. The number of sartans mostly prescribed by specialists is only seven - Candesartan (CDS), Eprosartan (EPS), Irbesartan (IBS), Losartan (LOS), Olmesartan (OMS), Telmisartan (TMS) and Valsartan (VLS). Methods: The widespread use of sartans in the treatment of hypertension requires reliable methods of analysis. Bulk drugs and pharmaceutical preparations should be analyzed to ensure the quality of the medicinal products reaching patients. On the other hand, the analysis of drugs in biological fluids aims to trace and improve patient care by adjusting the therapeutic doses of drugs. According to our knowledge, a review devoted to the analysis of sartans was published in 2014. Results: Spectral methods are widely used in the analysis of bulk drugs and pharmaceutical dosage forms due to their relatively simple procedures, low reagent and sample consumption, speed, precision and accuracy combined with accessibility and comparatively low cost of common apparatus. Many papers for determination of sartans in bulk drugs and pharmaceutical preparations based on liquid chromatographic techniques were published in the available literature. Among these methods, HPLC takes the leading place but UPLC and HPTLC are also present. Conclusion: The widespread use of sartans in the treatment of hypertension requires reliable methods of analysis. Bulk drugs and pharmaceutical preparations should be analyzed to ensure the quality of the medicinal products reaching patients. On the other hand, the analysis of drugs in biological fluids aims to trace and improve patient care by adjusting the therapeutic doses of drugs. Since 2014, many articles have been published on the sartans analysis and this provoked our interest to summarize the latest applications in the analysis of sartans in pharmaceutical formulations and biological media. Articles published from 2014 to 2018 are covered.


Author(s):  
Roman David Bülow ◽  
Daniel Dimitrov ◽  
Peter Boor ◽  
Julio Saez-Rodriguez

AbstractIgA nephropathy (IgAN) is the most common glomerulonephritis. It is characterized by the deposition of immune complexes containing immunoglobulin A (IgA) in the kidney’s glomeruli, triggering an inflammatory process. In many patients, the disease has a progressive course, eventually leading to end-stage kidney disease. The current understanding of IgAN’s pathophysiology is incomplete, with the involvement of several potential players, including the mucosal immune system, the complement system, and the microbiome. Dissecting this complex pathophysiology requires an integrated analysis across molecular, cellular, and organ scales. Such data can be obtained by employing emerging technologies, including single-cell sequencing, next-generation sequencing, proteomics, and complex imaging approaches. These techniques generate complex “big data,” requiring advanced computational methods for their analyses and interpretation. Here, we introduce such methods, focusing on the broad areas of bioinformatics and artificial intelligence and discuss how they can advance our understanding of IgAN and ultimately improve patient care. The close integration of advanced experimental and computational technologies with medical and clinical expertise is essential to improve our understanding of human diseases. We argue that IgAN is a paradigmatic disease to demonstrate the value of such a multidisciplinary approach.


Author(s):  
Curtis L Simmons ◽  
Laura K Harper ◽  
Kathryn J Holst ◽  
Nathan J Brinkman ◽  
Christine U Lee

Abstract Buffered lidocaine is a local anesthetic option during percutaneous needle-directed procedures in the breast. At our institution, sodium bicarbonate (the buffer) is dispensed in volumes that frequently lead to medical waste and shortages. In this study, we describe how moving the buffering of lidocaine from the procedure room to our clinical hospital pharmacy results in a reduction in costs and improves satisfaction across the breast radiology department. While cost savings are difficult to tease out in practices that opt for bundled payments, we were able to access pricing and supply data and coordinate with our pharmacy to change our practice. Making these changes saves our practice $26 000 a year and allows us to continue to offer buffered lidocaine even during sodium bicarbonate shortages. This manuscript describes how these changes came about and their economic impact.


2021 ◽  
pp. 036354652110086
Author(s):  
Prem N. Ramkumar ◽  
Bryan C. Luu ◽  
Heather S. Haeberle ◽  
Jaret M. Karnuta ◽  
Benedict U. Nwachukwu ◽  
...  

Artificial intelligence (AI) represents the fourth industrial revolution and the next frontier in medicine poised to transform the field of orthopaedics and sports medicine, though widespread understanding of the fundamental principles and adoption of applications remain nascent. Recent research efforts into implementation of AI in the field of orthopaedic surgery and sports medicine have demonstrated great promise in predicting athlete injury risk, interpreting advanced imaging, evaluating patient-reported outcomes, reporting value-based metrics, and augmenting the patient experience. Not unlike the recent emphasis thrust upon physicians to understand the business of medicine, the future practice of sports medicine specialists will require a fundamental working knowledge of the strengths, limitations, and applications of AI-based tools. With appreciation, caution, and experience applying AI to sports medicine, the potential to automate tasks and improve data-driven insights may be realized to fundamentally improve patient care. In this Current Concepts review, we discuss the definitions, strengths, limitations, and applications of AI from the current literature as it relates to orthopaedic sports medicine.


2021 ◽  
Vol 7 (15) ◽  
pp. eabe8978
Author(s):  
Álvaro Herrero-Navarro ◽  
Lorenzo Puche-Aroca ◽  
Verónica Moreno-Juan ◽  
Alejandro Sempere-Ferràndez ◽  
Ana Espinosa ◽  
...  

Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yu-Liang Jiang ◽  
Xiao-Dong Xu ◽  
Bai-Rong Li ◽  
En-Da Yu ◽  
Zi-Ye Zhao ◽  
...  

Abstract Objective To report Peutz–Jeghers syndrome (PJS) cases with non-definitive clues in the family or personal history and finally diagnosed through pathological examination and STK11 gene mutation test. Clinical presentation and intervention PJS was suspected in 3 families with tortuous medical courses. Two of them had relatives departed due to polyposis or colon cancer without pathological results, and the other one had been diagnosed as hyperplastic polyposis before. Diagnosis of PJS was confirmed by endoscopy and repeated pathological examinations, and the STK11 mutation test finally confirmed the diagnosis at genetic level, during which 3 novel mutation were detected (536C > A, 373_374insA, 454_455insGGAGAAGCGTTTCCCAGTGTGCC). Conclusion Early diagnosis of PJS is important and may be based on a family history with selective features among family members, and the pathological information is the key. The novel mutations also expand the STK11 variant spectrum.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wiruntita Chankeaw ◽  
Sandra Lignier ◽  
Christophe Richard ◽  
Theodoros Ntallaris ◽  
Mariam Raliou ◽  
...  

Abstract Background A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle. Results In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process. Conclusion The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.


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