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Sensitive Biomarker (sensitive + biomarker)
Selected AbstractsSomatic mutant frequency at the HPRT locus in children associated with a pediatric cancer cluster linked to exposure to two superfund sitesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2005Pamela M. Vacek Abstract The somatic mutant frequency (Mf) of the hypoxanthine phosphoribosyl transferase (HPRT) gene has been widely used as a biomarker for the genotoxic effects of exposure but few studies have found an association with environmental exposures. We measured background Mfs in 49 current and former residents of Dover Township, New Jersey, who were exposed during childhood to industrially contaminated drinking water. The exposed subjects were the siblings of children who developed cancer after residing in Dover Township, where the incidence of childhood cancer has been elevated since 1979. Mfs from this exposed group were compared to Mfs in 43 age-matched, presumably unexposed residents of neighboring communities with no known water contamination and no increased cancer incidence. Statistical comparisons were based on the natural logarithm of Mf (lnMF). The mean Mf for the exposed group did not differ significantly from the unexposed group (3.90 × 10,6 vs. 5.06 × 10,6; P = 0.135), but unselected cloning efficiencies were higher in the exposed group (0.55 vs. 0.45; P = 0.005). After adjustment for cloning efficiency, lnMf values were very similar in both groups and age-related increases were comparable to those previously observed in healthy children. The results suggest that HPRT Mf may not be a sensitive biomarker for the genotoxic effects of environmental exposures in children, particularly when substantial time has elapsed since exposure. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] Subcellular cadmium distribution, accumulation, and toxicity in a predatory gastropod, Thais clavigera, fed different preyENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2006Ma-Shan Cheung Abstract Bioaccumulation and toxicity of Cd were investigated in a marine predatory whelk, Thais clavigera, after being fed with the rock oyster, Saccostrea cucullata, or the herbivorous snail, Monodonta labio, for up to four weeks. The oysters and snails had different subcellular Cd distributions and concentrations in their bodies given their different metal-handling strategies and were exposed to dissolved Cd for two weeks before being fed to the whelks. After four weeks of dietary exposure, the Cd body concentrations in T. clavigera increased from 3.1 ,g/g to between 22.9 and 41.8 ,g/g and to between 22.7 and 24.1 ,g/g when they were fed with oyster and snail prey, respectively. An increasing proportion of Cd was found to be distributed in the metallothionein (MT)-like proteins and organelle fractions, whereas the relative distribution in the metal-rich granules fraction decreased when the whelks were fed Cd-exposed prey. At the highest Cd dosage, more Cd was distributed in the pool of metal-rich granules when the whelks were fed the oysters than when they were fed the snails. Among all the biomarkers measured (MT induction, condition index, lipid peroxidation, and total energy reserve including carbohydrate, lipid, and protein), only MT showed a significant difference from the control treatments, and MT was the most sensitive biomarker for dietary Cd exposure. No toxicity was found in the whelks fed different Cd-exposed prey as revealed by various biomarkers at the different biological levels. Our results imply that metal fractionation in prey can alter the subsequent subcellular metal distribution in predators and that dietary Cd toxicity to the whelks was low, even when the accumulated Cd body concentrations were high. [source] Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects,ANNALS OF NEUROLOGY, Issue 4 2009Leslie M. Shaw PhD Objective Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods Amyloid-, 1 to 42 peptide (A,1,42), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and A,1,42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. Results CSF A,1,42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for A,1,42, t-tau, and APO,4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/A,1,42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation The CSF biomarker signature of AD defined by A,1,42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009 [source] Two Brothers with Myocardial Infarction in the Absence of Atherosclerotic Coronary Artery Disease: Spontaneous Coronary Thrombosis: Case Reports of Two BrothersCLINICAL CARDIOLOGY, Issue 12 2009Jamal Hussain MD Myocardial infarction in the absence of significant atherosclerotic coronary artery disease is not uncommonly encountered in clinical practice. This has been more often seen with the current sensitive biomarker assays for myocardial necrosis. Acute illnesses, spontaneous coronary dissection, sepsis, pulmonary embolism and coagulation disorders are some of the common clinical situation where elevated cardiac markers are noted. We describe two brothers presenting with acute myocardial infarction due to thrombus without any obvious cause. Copyright © 2009 Wiley Periodicals, Inc. [source] Inflammation and the etiology of type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2006Åke Sjöholm Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-,. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis. Copyright © 2005 John Wiley & Sons, Ltd. [source] | |||||||||||||