University of Arkansas for Medical Sciences

About: University of Arkansas for Medical Sciences is a education organization based out in Little Rock, Arkansas, United States. It is known for research contribution in the topics: Population & Health care. The organization has 14077 authors who have published 26012 publications receiving 973592 citations. The organization is also known as: UAMS.

PTEN Mutation Spectrum and Genotype-Phenotype Correlations in Bannayan-Riley-Ruvalcaba Syndrome Suggest a Single Entity With Cowden Syndrome

Abstract: Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in BRR. The partial clinical overlap in these two syndromes is exemplified by the hallmark features of BRR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in BRR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in BRR. In this study, constitutive DNA samples from 43 BRR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and BRR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR cases. Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family ( P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of BRR ( P = 0.113). Comparisons between BRR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and BRR when compared with BRR alone ( P = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and BRR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance.

Radiation-related heart disease: current knowledge and future prospects.

Abstract: INTRODUCTIONIt has been recognized since the 1960s that the heart may bedamaged by substantial doses of radiation [>30 Gray (Gy)],such as used to occur during mantle radiotherapy for Hodg-kin lymphoma. During the last few years, however, evidencethat radiation-related heart disease (RRHD) can occur fol-lowing doses below 20 Gy has emerged from several inde-pendent sources. Those sources include studies of breastcancer patients who received mean cardiac doses of 3 to 17Gy when given radiotherapy following surgery and studiesof survivors of the atomic bombings of Japan who receiveddoses of up to 4 Gy.At doses above 30 Gy, an increased risk of RRHD can be-comes apparent within a year or two of exposure, and the riskincreases with higher radiotherapy dose, younger age at irra-diation, and the presence of conventional risk factors. Atlower doses, the typical latency period is much longer andis often more than a decade. The nature and magnitude ofthe risk following lower doses is not well characterized,and it is not yet clear whether there is a threshold dose belowwhich there is no risk.The evidence regarding RRHD comes from several differ-ent disciplines. The present review brings together informa-tion from pathology, radiobiology, cardiology, radiationoncology, and epidemiology; it summarizes current knowl-edge, identifies gaps in that knowledge, and outlines somepotential strategies for filling them.CURRENT KNOWLEDGEPathologyThe pathological expressions of RRHD documented fol-lowing therapeutic irradiation can be broadly reduced tofour conditions: pericarditis, pericardial fibrosis, diffusemyocardial fibrosis, and coronary artery disease (CAD)(1, 2). Radiation may also cause valvular disease, althoughtheevidence for this isnotasstrong.None of these conditionsis specific to radiation.Radiation-related pericarditis is characterized by an exu-date of a variable amount of protein-rich fluid within thepericardial sac (pericardial effusion). Rapid accumulationof this fluid can, in rare cases, cause potentially fatal cardiactamponade. Almost invariably, fibrin accumulates on the

Overweight and Obesity: Prevalence, Consequences, and Causes of a Growing Public Health Problem.

Abstract: This review considers a variety of perspectives on overweight and obesity (OW/obesity), including measurement and classification; prevalence and changes in prevalence in recent years; genetic, biological, medical, individual, and social correlates of OW/obesity; and treatment approaches. Despite increased attention, OW/obesity is escalating in prevalence worldwide, and the causes are exceedingly complex. A range of innovative studies, including basic research on gut microflora, dietary composition, pharmacologic interventions, and surgical procedures, is generating findings with potential for future prevention and treatment of OW/obesity. Social system changes such as school programs and the awareness of the roles of personal, family, health provider, and cultural experiences related to OW/obesity have also gained traction for vital prevention and treatment efforts over the past decade.

Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients

Abstract: Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important regulators of immune responses in cancer and have been directly implicated in promotion of tumor progression. However, the heterogeneity of these cells and lack of distinct markers hampers the progress in understanding of the biology and clinical importance of these cells. Using partial enrichment of PMN-MDSC with gradient centrifugation we determined that low density PMN-MDSC and high density neutrophils from the same cancer patients had a distinct gene profile. Most prominent changes were observed in the expression of genes associated with endoplasmic reticulum (ER) stress. Surprisingly, low-density lipoprotein (LDL) was one of the most increased regulators and its receptor oxidized LDL receptor 1 OLR1 was one of the most overexpressed genes in PMN-MDSC. Lectin-type oxidized LDL receptor 1 (LOX-1) encoded by OLR1 was practically undetectable in neutrophils in peripheral blood of healthy donors, whereas 5-15% of total neutrophils in cancer patients and 15-50% of neutrophils in tumor tissues were LOX-1+. In contrast to their LOX-1- counterparts, LOX-1+ neutrophils had gene signature, potent immune suppressive activity, up-regulation of ER stress, and other biochemical characteristics of PMN-MDSC. Moreover, induction of ER stress in neutrophils from healthy donors up-regulated LOX-1 expression and converted these cells to suppressive PMN-MDSC. Thus, we identified a specific marker of human PMN-MDSC associated with ER stress and lipid metabolism, which provides new insight to the biology and potential therapeutic targeting of these cells.