Top PDF Peripheral blood signatures of lead exposure.

Peripheral blood signatures of lead exposure.

Peripheral blood signatures of lead exposure.

BLLs directly is the most common method of determining blood Pb concentration. BLL is a measure of circulating Pb and does not measure total Pb stored in the body. Nor does it measure the effects of current or cumulative Pb exposure. Pb is also known to impair heme biosynthesis. Therefore, an alternative method to screen for Pb exposure is to measure the level of erythrocyte protoporphyrin (EPP) or zinc protoporphyrin (ZPP), which is an early and reliable indicator of impaired heme biosynthesis. This method is not sensitive enough to be used to screen children, but can be used in monitoring occupationally exposed adults and can reflect average Pb exposure over a period of a few weeks. Our approach, as outlined in Figure 1, was to measure global gene expression in the blood of mice exposed to lead acetate via their drinking water and to generate a signature based on the genes most highly correlated with the exposure. Our hypotheses were that 1) PBC gene expression signatures would be good indicators of low-level Pb exposure which is not associated with observable effects, but contributes to negative health outcomes, and 2) PBC gene expression signatures may reflect past exposures, representing an opportunity to characterize an individual’s exposure history and its relationship to current health issues and future health risks. We report robust and dose-specific blood-based signatures of Pb exposure. The low-level Pb signature is particularly promising because it represents an estimated BLL of 3.3 m g/dL, which is well below the 10 m g/dL level for children set by the CDC. It is also below the lower limits of detection for the EPP and ZPP tests. The ability to detect such low-level Pb exposure could allow researchers Figure 2. Transcriptional changes following exposure and recovery. A) Schematic of experimental design, in which mice were exposed to lead via drinking water over the course of two weeks at which time a blood sample was collected. Then the lead source was removed and the mice had a two-week recovery period before a second blood collection. B) The x-axis represents the 250 probes in the low-dose lead signature, ordered from lowest to highest average expression value relative to controls. The y-axis represents the normalized average signal intensity of the probe across the samples. The blue field represents the mean signal intensity of the signature probes in mice exposed to low-dose lead, normalized by subtracting the mean values in the control mice. The magenta field represents the mean signal intensity of the same signature probes after the two-week recovery period and normalized against controls. C) A comparison of the gene expression signature in mice following two weeks of exposure to high- dose lead (blue) and then two weeks of recovery (magenta).
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Autonomic function evaluation in an intermittent lead exposure animal model

Autonomic function evaluation in an intermittent lead exposure animal model

Abstract — Lead (Pb) is a toxic metal , which widespread use has resulted in environmental contamination, human exposure and significant public health problems. The autonomic nervous system, being a homeostatic controller, is impaired in acute and chronic lead exposure. In fact, sympathoexcitation associated to hypertension and tachypnea has been described together with baroreflex and chemoreflex dysfunction. However, up to date, no studies described the autonomic effects of an intermittent low- level lead exposure. In the present work, we addressed in vivo, autonomic behaviour in rats under chronic Pb exposure (control) and in rats under intermittent Pb exposure. For that, arterial blood pressure (BP) and ECG were recorded in 28 weeks old animal and low frequencies (LF) and high frequencies (HF) were determined (to estimate sympathetic and parasympathetic activities) using FisioSinal software with Wavelet module. Our preliminary results depict that intermittently lead-exposed rats show a significant decrease in systolic BP, without significant changes on LF, HF and LF/HF bands, when compared to chronically Pb- exposed rats.
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Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures

Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures

Microarray Analysis: We performed statistical power and sample size calculations for the microarray profiling of whole blood using the sample size estimation tool implemented in Partek genomics Suite [31, 32]. To detect a low fold-change of 1.3-fold at a p-value <0.005 that we would accept for a biological signal or biomarker gene at a power of 85%, a sample size of 45 samples per group for whole blood is necessary. Therefore, we were more than adequately powered even for the Discovery cohort used in this study. None of the samples were excluded based on the standard Affymetrix Quality Control metrics and by Principal Components Analysis plots derived in Partek Genomics Suite. Class comparisons were performed using a 1-way ANOVA model using the Method of Moments [33]. The one-way ANOVA that we employed to detect differentially expressed genes is also robust and tolerates reasonable levels of experimental data variance. Moreover, the danger of violating the normal distributions corresponds with the possibility to detect false positives, which we have controlled for with a stringent False Discovery Rate (FDR) of <5%. Class predictions were performed with the Support Vector Machines (SVM) algorithm. To correct for the possibility of over-fitting of the predictors, we used the bootstrapping method of Harrell et al. where the original data set is sampled 500 times with replacement and the Area Under the
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Peripheral blood mononuclear cells isolation

Peripheral blood mononuclear cells isolation

Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, Elejalde), RAB27A (GS2) or MLPH (GS3) genes. Typical features of all three subtypes of this disease include pigmentary dilution of the hair and skin and silvery-gray hair. Whereas the GS3 phenotype is restricted to the pigmentation dysfunction, GS1 patients also show primary neurological impairment and GS2 patients have severe immunological deficiencies that lead to recurrent infections and hemophagocytic syndrome. We report here the diagnosis of GS2 in 3-year-old twin siblings, with silvery-gray hair, immunode- ficiency, hepatosplenomegaly and secondary severe neurological symptoms that culminated in multiple organ failure and death. Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. A homozygous nonsense mutation, C-T transition (c.550C>T), in the coding region of the RAB27A gene, which leads to a premature stop codon and prediction of a truncated protein (R184X), was found. In patient mononuclear cells, RAB27A mRNA levels were the same as in cells from the parents, but no protein was detected. In addition to the case report, we also present an updated summary on the exon/intron organization of the human RAB27A gene, a literature review of GS2 cases, and a complete list of the human mutations currently reported in this gene. Finally, we propose a flow chart to guide the early diagnosis of the GS subtypes and Chédiak-Higashi syndrome.
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Socially Responsive Toxicology; Looking Outside the Windows of Medical Wards: A Tale of Lead Exposure

Socially Responsive Toxicology; Looking Outside the Windows of Medical Wards: A Tale of Lead Exposure

Although reducing the number of individuals whose BLL exceeds the level at which chelation therapy is required would yield cost savings, it is much smaller than the savings that would be expected as a result of reducing the lead-related IQ loss in the general population, which affects many more people (Figure 2). Similar arguments could be made in regard to other measures that should be taken in cases with high BLL, including follow-up blood lead monitoring, neurodevelopmental monitoring, abdominal X ray, other laboratory works and recommended education.
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Characterization of CD8+ T-CELL populations of the human peripheral blood

Characterization of CD8+ T-CELL populations of the human peripheral blood

memory cells. How these long-lasting memory cells generated and selected during the primary immune response is an issue difficult to address directly. However, several lines of evidence allowed the envisagement of a model to explain T-cell memory generation in humans (Sallusto et al., 2004; Sprent and Tough, 2001). According to this model, memory formation is a rather complex mechanism largely dependent upon multiple factors, such as the density of antigen, TCR affinity, local contact with particular cytokines and the nature of the APC. As discussed above, these factors establish the strength of stimulation that lymphocytes receive and determine their fate. Hierarchical activation thresholds are thought to progressively drive naïve T cells to proliferate, acquire fitness, differentiate and ultimately die by AICD (Figure 9a). As cytokine stimulation and encounter of T cells with APCs are probabilistic events that vary throughout the immune response, lymphocytes participating in the same response will receive different degrees of stimulation. This can lead to the arrest of primed T cells in different stages of the activation pathway, in addition to lymphocytes that have reached fully differentiation. In the early stages of the immune response, rapid replication of the pathogen ensures continuous entry of large numbers of activated APCs into the T-cell zones of the secondary lymphoid organs. Consequently, there is a huge density of APCs carrying high doses of antigen and co-stimulatory molecules, and secreting large amounts of cytokines. T cells can thus rapidly accumulate signals that enable them to become fit, proliferate and be converted into fully differentiated effector cells. At later stages of the response, elimination of the pathogen at the site of infection by effector cells reduces inflow of antigen-laden APC into the T-cell zones. Under these conditions, T-cell interaction with diminishing numbers of antigen-bearing APCs exhausts the capacity of APCs to produce stimulatory cytokines (Langenkamp et al., 2000). The exhausted APCs continue to elicit T-cell proliferation but cytokine production by T cells and formation of fully differentiated effector cells are reduced. Therefore, polarized cells would develop as the result of prolonged exposure to antigen, whereas non-polarized cells would arise by default when antigen is limiting (Iezzi et al., 2001; Langenkamp et al., 2002). This spectrum can be simply resolved into distinct subsets of T CM and T EM surviving
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Lead concentrations in the blood of children from pottery-making families exposed to lead salts in a Mexican village

Lead concentrations in the blood of children from pottery-making families exposed to lead salts in a Mexican village

zinc protoporphyrin, and delta-aminolevulinic acid found in the blood and urine of Tonala children from pottery-making families points to considerable lead exposure [r]

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Systemic signature of the lung response to respiratory syncytial virus infection.

Systemic signature of the lung response to respiratory syncytial virus infection.

Interferon-regulated responses appear to be part of the innate response to viral and to some extent to bacterial pathogens. Zaas et al. [9] reported whole-blood gene expression signatures in response to RSV, rhinovirus, and influenza, in a cohort of healthy adult volunteers. These healthy volunteers all showed mild symptoms upon RSV infection. Viral infection signatures allowed to accurately discriminate viral infections from bacterial infections (Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli) or uninfected controls, but were mutually very comparable. Of the genes reported in at least one of their viral top-30 signatures, twelve were also regulated in our blood data (Cxcl10, Gbp1, H28/ Ifi44l, Herc5, Ifi27, Ifi44, Ifit1, Ifit2, Ifit3, Ly6e, Socs1, Stat1), again including mostly interferon responsive genes. Of these, Gbp1 was only present in the RSV signature. Ramilo et al. [10] described classifiers to distinguish between pediatric patients with acute influenza, S. pneumoniae, S. aureus, or E. coli infection. Their influenza classifier genes showed mostly IFN regulated genes, several of which (Ifi44, G1p2, Oas1, Zbp1) showed overlap with our signature. By contrast, in their classifiers to distinguish bacterial infections from influenza or between different bacterial infections, practically no IFN regulated genes were found and only Stat1 overlapped with our blood signature. Predominantly IFN regulated signatures were also reported by Thach et al. [11] in basic military trainees with adenoviral febrile respiratory illness. Additionally, IFN responses were found in peripheral blood of cynomolgus macaques after smallpox infection [21]. Taken together, these studies show the role of interferon responsive Figure 2. Functional enrichment for lung, lymph node, and blood responses. Nodes represent tissue responses (pink), shared primary response (red), GO/UniProt functional terms (yellow) and immune cell type (light blue). Edges represent significant (p,0.01) enrichment (dark blue) or a subset relation (gray).
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Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease.

Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease.

To date, the underlying mechanisms involved in the association between ApoE protein and AD are uncertain. ApoE is an important modulator of plasma lipid metabolism and cholesterol homeostasis [10]. Previous studies showed that disturbances in cholesterol metabolism may influence synapse formation, function and stability. ApoE also serves as essential component in cholesterol delivery to neurons [37]. A lower level of plasma ApoE may impair the normal physiological functions of ApoE, contributing to cognitive decline and degeneration of CNS. Besides, ApoE is suggested to bind Ab and promote its clearance and degradation, which is a decisive event in the pathogenesis of AD. A lower ApoE level may reduce the efficiency of Ab clearance, and lead to the pathogenesis of AD [38]. Cramer et al. demonstrated that Ab plaque and cognitive function were rapidly ameliorated in AD mouse models after treatment by an agonist that regulates ApoE expression [39]. In line with our results, many of those studies that did not meet the strict inclusion criteria for the meta-analysis also found a positive association between lower ApoE levels and AD. Van Vliet P et al. reported that offspring
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Induction of interleukin-10 by HIV antigens in peripheral mononuclear cells of health care workers after occupational exposure to HIV-1-positive blood

Induction of interleukin-10 by HIV antigens in peripheral mononuclear cells of health care workers after occupational exposure to HIV-1-positive blood

The role of IL-10 in HIV-1 infection remains controversial. It is likely that, by down-regulating proinflammatory cytokines, IL-10 inhibits HIV-1 replication. It was ob- served that IL-10 is produced during HIV-1 infection and that IL-10 inhibits viral repli- cation in macrophages in vitro (8,11,12). On the other hand, the enhancement of virus replication is also attributed to IL-10 (9). It has been suggested that, in amounts not large enough to inhibit TNF- α , IL-10 may in- crease virus replication. Moreover, it has also been shown that IL-10 may be impor-

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Perspective on Lead Toxicity, a Comparison between the United States and Iran

Perspective on Lead Toxicity, a Comparison between the United States and Iran

Environmental exposure to lead occurs via several sources and can impact the entire population; however, children are much more susceptible to its toxic effects. As such, the majority of US public health initiatives have focused on the reduction of pediatric lead exposure [3]. Symptomatic lead poisoning was first reported in the US in 1917 and became more commonly recognized during the mid-20th century. It was also during this time that chelation therapy for lead toxicity was being developed and refined [4]. The neurocognitive sequelae of lead exposure in symptomatic children was readily apparent, but it was not until the 1970s that the more subtle effects of subclinical exposure were noted [5]. Because of the profound neurocognitive effects of lead, the US Centers for Disease Control (CDC) made formal recom- mendations for lead screening in children as well as defined a “normal” blood lead level (BLL). The recom- mendations for the upper limit of blood lead concentra- tions has been revised several times over the subsequent decades based on emerging toxicity data. For example, in the 1960s, the CDC defined a toxic BLL as greater than 60 μg/dL, but this was decreased over subsequent decades to 10 μg/dL [6,7]. In 2012, in response to new evidence that neurocognitive effects could occur even with BLLs less than 10 μg/dL, the CDC has now defined
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Int. Arch. .  vol.17 número1

Int. Arch. . vol.17 número1

The present study was performed in children with a history of lead exposure, which indicates an initial lead concentration higher than the maximum limit of blood lead considered acceptable (10 μg/dL) (2). Follow-up measurements of blood lead level in the 20 children demonstrated a reduction in the median blood lead concentration over the period of the 4 analyses: the median lead concentration level was almost 15 μg/dL in the first and second collections, but was below 10 μg/dL in third and fourth collections (Figure 1). This result was obtained from the establishment and execution of actions that aimed to reduce the lead exposure of the population in the contaminated area, through the complete recovery of the soil, underground and surface waters, and vegetation.
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Ciênc. saúde coletiva  vol.11 número1

Ciênc. saúde coletiva vol.11 número1

Abstract Lead concentration in whole blood (Blood-Pb) is the primary biomarker used to monitor exposure to this metallic element. How- ever, the difficulty in assessing the exact nature of Pb exposure is dependent not so much on prob- lems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments. If we are to differen- tiate more effectively between Pb that is stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of in- ternal Pb dose has yet been accepted by the scien- tific community as a reliable substitute for a Blood-Pb measurement. This review focuses on the limitations of biomarkers of Pb exposure, and the need to improve the accuracy of their measure- ment. We present here only the traditional analyt- ical protocols in current use and we attempt to as- sess the influence of confounding variables on Blood-Pb levels. Finally, we discuss the interpreta- tion of Blood-Pb data with respect to both exter- nal and endogenous Pb exposure, past or recent exposure, as well as the significance of lead deter- minations in human specimens including hair, nails, saliva, bone, blood, urine, feces, and exfoli- ated teeth.
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Determination of Lead in Human Calculi and Its Effects on Renal Function of Lead Occupational Workers

Determination of Lead in Human Calculi and Its Effects on Renal Function of Lead Occupational Workers

Seventy five samples of renal and eighteen samples of supra gingival calculi of lead recycling workers were collected over the period of seven years (2008-2014) and studied for the accumulation of lead. The results were compared with those of non exposed subjects. The lead content of calculi was investigated for its dependence on type and composition of calculi, blood lead, job status and duration of exposure. The effect of blood lead and renal calculi was also investigated in relation to kidney function of respective subjects. The mean lead levels of various types of calculi were found to follow the order as phosphate > oxalate > urate .> cystine while single principal group of supra gingival calculi resulted in lower levels of metal. The lead content of calculi positively correlated with phosphate content of both of the renal (r = 0.655) and supra gingival calculi (r= 0.866). Impaired renal function was more pronounced in active workers and depended on blood lead levels in addition to presence of metal in renal calculi.
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Effects of lead exposure on the concentration of cadmium, selenium and values of morphology in the blood

Effects of lead exposure on the concentration of cadmium, selenium and values of morphology in the blood

Stę- żenie kadmu we krwi wykazało ujemną korelację ze stężeniem selenu w surowicy, co zostało potwierdzo- ne również w opracowaniach przez innych badaczy w przypadku narażenia zawodowego[r]

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Can blood gene expression predict which patients with multiple sclerosis will respond to interferon?

Can blood gene expression predict which patients with multiple sclerosis will respond to interferon?

The most commonly used disease- modifying therapies are interferon β (IFNβ) [2] and glatiramer acetate [2,3]. Despite initial excitement, these therapies have benefi cial effects in some, but not all, patients [2,3]. Because of the potential favorable effects of these therapies, it has been suggested that they should be initiated as early as possible to maximize neuroprotection [4]. Additionally, it has been recommended that patients should be monitored closely to determine whether and when it is necessary to modify treatment in order to maximize the benefi t [5]. The recommended monitoring is based on annual rate of relapses, neurological deterioration, and evidence of disease activity on brain magnetic resonance imaging scans. However, given the destructive nature of the disease, if we rely solely on clinical or radiological manifestations (such as a relapse or a new lesion on a scan) to determine a patient’s response to therapy, we will probably be responding too late.
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Diverse radiofrequency sensitivity and radiofrequency effects of mobile or cordless phone near fields exposure in Drosophila melanogaster.

Diverse radiofrequency sensitivity and radiofrequency effects of mobile or cordless phone near fields exposure in Drosophila melanogaster.

Methods/Results: Two experiments have been designed and performed in the same laboratory conditions. Insect cultures were exposed to the near field of a 2G mobile phone (the GSM 2G networks support and complement in parallel the 3G wide band or in other words the transmission of information via voice signals is served by the 2G technology in both mobile phones generations) and a 1880 MHz cordless phone both digitally modulated by human voice. Comparison with advanced statistics of the egg laying of the second generation exposed and non-exposed cultures showed limited statistical significance for the cordless phone exposed culture and statistical significance for the 900 MHz exposed insects. We calculated by physics, simulated and illustrated in three dimensional figures the calculated near fields of radiation inside the experimenting vials and their difference. Comparison of the power of the two fields showed that the difference between them becomes null when the experimental cylinder radius and the height of the antenna increase.
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Mott Cells in the Peripheral Blood of a Patient with Dengue Fever

Mott Cells in the Peripheral Blood of a Patient with Dengue Fever

1. Jego G, Robillard N, Puthier D, Amiot M, Accard F, Pineau D, Bataille R, Pellat-Deceunynck C. Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells. Blood 1999;94:701-712. 2. Thai KT, Wismeijer JA, Zumpolle C, de Jong MD, Kersten MJ,

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CIGARETTE SMOKING IN SCHIZOPHRENIC PATIENTS THAT ARE CURRENTLY TREATED IN A MEXICAN HOSPITAL

CIGARETTE SMOKING IN SCHIZOPHRENIC PATIENTS THAT ARE CURRENTLY TREATED IN A MEXICAN HOSPITAL

Although direct memory (the i rst presentation of words – A1) increased, other cognitive parameters deteriorated. We observed a statistically signii cant decrease in verbal learning (i fth presentation of words – A5). If prior to working at the site, the average memorized words were (M ± SD) 10,43 ± 2,09, after working at the Shelter the same variable was 9,86 ± 1,70 words (p <0,01). Particularly relevant seemed the deterioration of short-term verbal memory (word list reps A6) and the increased proactive interference effect of verbal information (number of repeated words list B); such as, the preservation of material degradation under the inl uence of information that has been previously memorized and which tend to interfere. In other words, after working at the Shelter people developed learning barriers caused by the exposure to information learned in the past. However, the effect of retroactive interference of verbal information (difference of repeated word lists A5 and A6 (A5-A6); i.e. the preservation of material degradation under the inl uence of learning or manipulation with further information, which might interfere, decreased.
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Intraclonal diversity in a Sezary syndrome with a differential response to 2‐deoxycoformycin of the two lymphoma cell populations

Intraclonal diversity in a Sezary syndrome with a differential response to 2‐deoxycoformycin of the two lymphoma cell populations

typic enumeration of peripheral blood lymphocytes at diagnosis and at different times during follow-up after starting treat- ment with 2-DCF. The WBC counts (– –) and the lymphocyte counts (–d–) counts are shown in the upper panel. The lower panel shows the relative representation of large abnormal CD4 + Sezary T cells (red bars), small abnormal CD4 + Sezary T cells (green bars) and small normal residual CD4 + plus CD8 + T lymphocytes (black bars), as the percentage of total peripheral blood T cells. Dot plots in the top of the upper panel represent the SSC/FSC distribution of peripheral blood cells as well as the percentage of each cell population among total white blood cells from the sample (for key, see Fig 1).
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