A5023291748- Hormonal Regulation and Hypertension
- Adrenal and Paraganglionic Tumors
- Adrenal Hormones and Disorders
- Pituitary Gland Disorders and Treatments
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Neuroendocrine Tumor Research Advances
- Cancer, Hypoxia, and Metabolism
- Ion Transport and Channel Regulation
- Thyroid Cancer Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Pharmacogenetics and Drug Metabolism
- Growth Hormone and Insulin-like Growth Factors
- IgG4-Related and Inflammatory Diseases
- COVID-19 Clinical Research Studies
- Hormonal and reproductive studies
- Thyroid Disorders and Treatments
- Apelin-related biomedical research
- Bone health and osteoporosis research
- Sexual Differentiation and Disorders
- Renal and related cancers
- Glaucoma and retinal disorders
- Connective tissue disorders research
- SARS-CoV-2 and COVID-19 Research
- Estrogen and related hormone effects
- Long-Term Effects of COVID-19
Kyoto Medical Center
2014-2024
University of Michigan
2015-2024
Brigham and Women's Hospital
2017
Harvard University
2017
Laboratoire d’immunologie intégrative du cancer
2016
Akashi Medical Center
2016
Sapporo City General Hospital
2016
National Kyushu Medical Center
2016
Matsuyama Red Cross Hospital
2016
Kitasato University
2016
Significance Primary aldosteronism (PA) represents the most common adrenal disease and cause of secondary hypertension. However, little is known regarding cellular origins. Recently, subcapsular aldosterone-producing cell clusters (APCCs) were observed in normal adrenals. We hypothesize that APCCs are a contributor to PA. Here, we characterized APCC transcriptome show CYP11B2 expression increased compared with rest cortex. also many harbor adenoma (APA)-related ion channels/pumps ( ATPase,...
Somatic mutations have been identified in aldosterone-producing adenomas (APAs) genes that include KCNJ5, ATP1A1, ATP2B3, and CACNA1D. Based on independent studies, there appears to be racial differences the prevalence of somatic KCNJ5 mutations, particularly between East Asians Europeans. Despite high cardiovascular disease mortality blacks, no studies focusing APAs this population. In present study, we investigated genetic characteristics blacks using a CYP11B2 (aldosterone synthase)...
Somatic mutations have been identified in more than half of aldosterone-producing adenomas (APAs) through mutation hotspot sequencing. The underlying pathogenesis inappropriate aldosterone synthesis the remaining population is still unknown. To investigate prevalence and spectrum somatic APAs using an synthase (CYP11B2) immunohistochemistry (IHC)‒guided next-generation sequencing (NGS) approach. Formalin-fixed paraffin-embedded adrenal tissue from white American patients with primary...
Background: Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, influence on physiology is not well understood. Methods: The relationship between age adrenal synthase (CYP11B2) expression was evaluated in 127 normal glands from deceased kidney donors (age, 9 months to 68 years). Following immunohistochemistry, CYP11B2-expressing area areas abnormal foci cells, called aldosterone-producing cell clusters, were analyzed. In a...
Aldosterone-producing adenoma (APA) cause primary aldosteronism-the most frequent form of secondary hypertension. Somatic mutations in genes coding for ion channels and ATPases are found APA aldosterone-producing cell clusters. We investigated the genetic, cellular, molecular heterogeneity different structures adrenals with APA, to get insight into mechanisms driving their development investigate clinical biochemical correlates. Genetic analysis clusters, nodules was performed adrenal...
Although primary aldosteronism (PA) is the most common cause of endocrine hypertension, histopathological methods to reveal presence and sites aldosterone overproduction remain be established. The objective study was investigate significance immunohistochemical staining detect CYP11B2 CYP11B1 in adrenal tissue patients with PA. Thirty-two PA who underwent unilateral adrenalectomy were studied. Immunohistochemical performed using anti-CYP11B2 anti-CYP11B1 antibodies on paraffin-embedded...
Driver somatic mutations for aldosterone excess have been found in ≈90% of aldosterone-producing adenomas (APAs) using an synthase (CYP11B2)-guided sequencing approach. In the present study, we identified a novel CACNA1H mutation (c.T4289C, p.I1430T) APA without any currently known aldosterone-driver CYP11B2 immunohistochemistry-guided whole exome sequencing. The gene encodes voltage-dependent T-type calcium channel alpha-1H subunit. Germline variants this are as cause familial...
We are witnessing a revolution in our understanding of primary aldosteronism (PA). In the past 2 decades, we have learned that PA is highly prevalent syndrome largely attributable to pathogenic somatic mutations, contributes cardiovascular, metabolic, and kidney disease, when recognized, can be adequately treated with widely available mineralocorticoid receptor antagonists and/or surgical adrenalectomy. Unfortunately, rarely diagnosed, or treated, mainly because lack awareness education....
Although confirmatory testing to verify aldosterone excess is a key step in the diagnosis of primary aldosteronism (PA), there no consensus as whether it always needed and which tests need be performed.The objective this study was investigate diagnostic significance PA.In group A, 120 hypertensive patients who had positive case detection using renin ratio (ARR) were subjected at least one test: captopril challenge test (CCT), furosemide upright (FUT), or saline infusion (SIT). Among 57...
The use of next-generation sequencing has resulted in the identification recurrent somatic mutations underlying primary aldosteronism (PA). However, significant gaps remain our understanding relationship between tumor aldosterone synthase (CYP11B2) expression and mutation status.The objective study was to investigate CYP11B2 aldosterone-driver gene heterogeneity.Fifty-one adrenals from 51 PA patients were studied. Immunohistochemistry for performed. Aldosterone-producing adenomas with...
Summary Objective Correct subtyping of primary aldosteronism ( PA ) is essential for good surgical outcomes. Adrenal vein sampling AVS and/or computed tomography CT are used subclassification. Clinical biochemical improvement after surgery, however, not always achieved in patients with presumed unilateral . We aimed to identify the pitfalls subclassification leading treatment failures. Patients and Design retrospectively studied 208 who underwent adrenal a tertiary referral centre, between...
A subtype prediction score for primary aldosteronism has not yet been developed and validated using a large dataset. This study aimed to develop validate new compare it with existing scores multicenter database.In total, 1936 patients were randomly assigned the development validation datasets, constituting 1290 646 patients, respectively. Three generated or without confirmatory tests, logistic regression analysis. In dataset, compared receiver operating characteristic curve, net...
Cosyntropin [ACTH (1-24)] stimulation during adrenal vein (AV) sampling (AVS) enhances the confidence in success of AV cannulation and circumvents intraprocedure hormonal fluctuations. Cosyntropin's effect on primary aldosteronism (PA) lateralization, however, is controversial.To define major patterns time-dependent their determinants, after cosyntropin AVS.We retrospectively studied patients with PA who underwent AVS before, 10, 20 minutes between 2009 2018. Unilateral (U) or bilateral (B)...
Abstract Context Results of previous studies demonstrated clear racial differences in the prevalence somatic mutations among patients with aldosterone-producing adenoma (APA). For instance, those East Asian countries have a high KCNJ5, whereas other aldosterone-driving genes are rare. Objectives To determine mutation Japanese APA using an aldosterone synthase (CYP11B2) immunohistochemistry (IHC)-guided sequencing approach. Method Patients unilateral form primary aldosteronism who underwent...
To evaluate the prevalence of dyslipidemia in population Hashimoto thyroiditis, we reviewed medical records on consecutive 1181 cases with adult thyroiditis and 830 were adopted for study. First, serum TSH level increased free T4 decreased, slightly but significantly, increasing age. There significant positive correlations between levels lipid parameters such as total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), non-HDL-C LDL-C/HDL-C ratio (L/H). In...
In the adrenal gland, neuroendocrine cells that synthesize catecholamines and epithelial produce steroid hormones are united beneath a common organ capsule to function as single stress-responsive organ. The functional anatomy of hormone–producing cortex catecholamine-producing medulla is ill defined at level small molecules. Here, we report comprehensive high-resolution mass spectrometry imaging (MSI) map normal human gland. A large variety biomolecules was accessible by matrix-assisted...
Abstract Somatic mutations driving aldosterone production have been identified in approximately 90% of aldosterone-producing adenomas (APAs) using an synthase (CYP11B2) immunohistochemistry (IHC)-guided DNA sequencing approach. In the present study, CYP11B2-guided whole-exome (WES) and targeted amplicon sequencing, we detected 2 somatic variants CLCN2 APAs that were negative for currently known aldosterone-driver mutations. The gene encodes voltage-gated chloride channel ClC-2. germline...
Co-secretion of cortisol and aldosterone can be observed in adrenal adenomas. The aim this study was to investigate the molecular characteristics a co-existing aldosterone- cortisol-producing adenoma (CPA) same patient.Two different adenomas within gland from 49-year-old female patient with primary aldosteronism (PA) Cushing's syndrome (CS) were studied. Multiple formalin-fixed paraffin-embedded tumor blocks used for analysis. Immunohistochemistry (IHC) performed using specific antibody...
Abstract Context and Objective Posture-responsive posture-unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in 90% APAs. This study was designed characterize the biochemical, histopathologic, genetic properties these 2 types APA. Methods Plasma levels aldosterone hybrid steroids (18-oxocortisol 18-hydroxycortisol) were measured by liquid chromatography-tandem mass...