SEARCH · Search PubMed

Results for “Biomarker development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed2002

Stress-induced premature senescence in BJ and hTERT-BJ1 human foreskin fibroblasts.

To test the involvement of the telomeres in the senescent phenotype, we used telomerase-immortalized human foreskin fibroblasts (hTERT-BJ1). We exposed hTERT-BJ1 and parental BJ cells to either UVB or H(2)O(2) subcytotoxic stress(es). Both cell lines developed biomarkers of replicative senescence: loss of replicative potential, increase in senescence-associated beta-galactosidase activity, typical senescence-like morphology, overexpression of p21(WAF-1) and p16(INK-4a), and decreased level of the hyperphosphorylated form of pRb. Telomere shortening was slightly higher under stress for both BJ and hTERT-BJ1 but still much lower than that reported for other cell lines. We conclude that pathways alternative to telomere shortening must cause the appearance of the senescence phenotype.

Cell Line↗

PubMed1996

Use of a specific zona pellucida (ZP) protein 3 antiserum as a clinical marker for human ZP integrity and function.

OBJECTIVE: To evaluate binding characteristics of a specific zona pellucida (ZP) protein 3 (ZP3) antiserum to human oocytes in order to determine its usefulness as a clinical marker for human ZP integrity and function and its correlation with IVF outcome. DESIGN: Prospectively designed, blinded, internally controlled study. SETTING: Tertiary care academic center. PATIENTS: Patients undergoing IVF therapy who had either total failed fertilization or partial fertilization were studied. INTERVENTIONS: Metaphase II oocytes showing absence of pronuclear formation were salt stored 48 hours after insemination and bisected into matching hemizonae using micromanipulation. One hemizona was incubated with AS ZP3-6 (an antiserum generated against a synthetic ZP3 peptide derived from an amino acid sequence that is highly conserved in the structure of ZP3), whereas the matching hemizona was incubated with AS ZP3-7, an antiserum detecting exclusively mouse ZP3 (internal, negative control). Antibody binding was visualized using the peroxidase-antiperoxidase method and diaminobenzidine as color reagent. RESULTS: A total of 104 unfertilized oocytes were evaluated. Analysis of variance showed a significant interaction between gamete factor groups (sperm and oocyte) and antiserum factor. Patients with oocyte factor had significantly lower mean staining scores for the AS ZP3-6-treated hemizonae than patients with sperm factor. CONCLUSIONS: These results demonstrate that anomalies of human ZP3 can be identified with AS ZP3-6 and that these ZP abnormalities correlate with fertilization failure during IVF treatment. Thus, this newly developed biomarker may be of clinical significance in the identification of oocyte defects that are associated with fertilization disorders and may help in the decision-making process in the IVF-assisted fertilization setting.

Adult↗

PubMed2003

Oxidative stress regulated genes in nigral dopaminergic neuronal cells: correlation with the known pathology in Parkinson's disease.

Oxidative stress (OS) is a primary pathogenic mechanism of nigral dopaminergic (DA) cell death in Parkinson's disease (PD). Oxidative damage, Lewy body formation and decreased mitochondrial complex I activity are the consistent pathological findings in PD. In nigral DA neurons, however, it is unknown whether any gene expressional changes induced by OS contribute to the typical PD pathology. Here, using microarray analysis, we identified several groups of genes in the nigral DA cell line, SN4741 [J. Neurosci. 19 (1999) 10; J. Neurochem. 76 (2001) 1010], that were regulated by OS. Approximately 36 significantly regulated genes that encode functional molecules of nuclear subunits of mitochondrial complex I, exocytosis and membrane trafficking proteins, markers for OS and oxidoreductases, regulatory molecules of apoptosis and unidentified EST clones were further analysed. OS modulated the expression of specific genes, of which physiological dysfunctions have been implicated in PD. For instance, the expression of the nuclear-encoded subunits of mitochondrial complex I, B8 and B17, were significantly down-regulated by OS, possibly contributing to selective defect in mitochondrial complex I activity in PD. Furthermore, syntaxin 8 and heme oxygenase-1 (HO-1) are most dramatically up-regulated by OS in DA cells. Syntaxin 8 is a SNARE protein, regulating lipid vesicle docking and fusion as well as early endosome membrane recycling. Lipid membranes are significantly oxidative-damaged in PD. HO-1 is an important cytoplasmic constituent of Lewy bodies, a pathological hallmark of idiopathic PD. Thus, our findings provide novel molecular probes that may be useful in unraveling the molecular mechanism(s) of OS-induced pathogenesis in PD. Further functional characterization of the affected genes including ESTs can help elucidate the underlying molecular pathology as well as develop biomarkers for monitoring degenerating DA neurons in PD.

Apoptotic Protease-Activating Factor 1↗

PubMedDate not supplied

Differential gene expression in chemically induced mouse lung adenomas.

Because of similarities in histopathology and tumor progression stages between mouse and human lung adenocarcinomas, the mouse lung tumor model with lung adenomas as the endpoint has been used extensively to evaluate the efficacy of putative lung cancer chemopreventive agents. In this study, a competitive cDNA library screening (CCLS) was employed to determine changes in the expression of mRNA in chemically induced lung adenomas compared with paired normal lung tissues. A total of 2555 clones having altered expression in tumors were observed following competitive hybridization between normal lung and lung adenomas after primary screening of over 160,000 clones from a mouse lung cDNA library. Among the 755 clones confirmed by dot blot hybridization, 240 clones were underexpressed, whereas 515 clones were overexpressed in tumors. Sixty-five clones with the most frequently altered expression in six individual tumors were confirmed by semiquantitative RT-PCR. When examining the 58 known genes, 39 clones had increased expression and 19 had decreased expression, whereas the 7 novel genes showed overexpression. A high percentage (>60%) of overexpressed or underexpressed genes was observed in at least two or three of the lesions. Reproducibly overexpressed genes included ERK-1, JAK-1, surfactant proteins A, B, and C, NFAT1, alpha-1 protease inhibitor, helix-loop-helix ubiquitous kinase (CHUK), alpha-adaptin, alpha-1 PI2, thioether S-methyltransferase, and CYP2C40. Reproducibly underexpressed genes included paroxanase, ALDH II, CC10, von Ebner salivary gland protein, and alpha- and beta-globin. In addition, CCLS identified several novel genes or genes not previously associated with lung carcinogenesis, including a hypothetical protein (FLJ11240) and a guanine nucleotide exchange factor homologue. This study shows the efficacy of this methodology for identifying genes with altered expression. These genes may prove to be helpful in our understanding of the genetic basis of lung carcinogenesis and in developing biomarkers for lung cancer chemoprevention studies in mice.

Adenoma↗

PubMed2003

Functional genomics as a window on radiation stress signaling.

Exposure to ionizing radiation, as well as other stresses, results in the activation of complex signal transduction pathways, which eventually shape the response of cells and organisms. Some of the important pathways responding to radiation include the ATM/P53 pathway, MAPK cascades and NF-kappaB activation, as well as signaling events initiated at the cell membrane and within the cytoplasm. Alterations in gene expression play roles both as intermediaries in signaling and as downstream effector genes. Differences in cell type, interindividual genetic differences and crosstalk occurring between signaling pathways may help to channel radiation stress signals between cell cycle delay, enhanced DNA repair, and apoptosis. These differences may in turn help determine the likelihood of late effects of radiation exposure, including carcinogenesis and fibrosis. The tools of the postgenomic era enable high-throughput studies of the multiple changes resulting from the interplay of radiation signaling pathways. Gene expression profiling, in particular shows great promise, both in terms of insight into basic molecular mechanisms and for the future hope of biomarker development and individual tailoring of cancer therapy.

Animals↗

PubMed2005

Diabesity: a polygenic model of dietary-induced obesity from ad libitum overfeeding of Sprague-Dawley rats and its modulation by moderate and marked dietary restriction.

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of a metabolic syndrome of diabesity comprised of age-related degenerative diseases and obesity in a outbred stock of Sprague-Dawley (SD) rats [Crl:CD (SD) IGS BR]. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights, carcass analysis, in-life data including estrous cyclicity, and histopathology were determined. At 6-7 weeks of age SD rats had 6% body fat. AL-feeding resulted in hypertriglyceridemia, hypercholesterolemia, and dietary-induced obesity (DIO) by study week 14, with 25% body fat that progressed to 36-42% body fat by 106 weeks. As early as 14 weeks, key biomarkers developed for spontaneous nephropathy, cardiomyopathy, and degenerative changes in multiple organ systems. Early endocrine disruption was indicated by changes in metabolic and endocrine profiles and the early development and progression of lesions in the pituitary, pancreatic islets, adrenals, thyroids, parathyroids, liver, kidneys, and other tissues. Reproductive senescence was seen by 9 months with declines in estrous cyclicity and pathological changes in the reproductive organs of both sexes fed AL or moderate DR, but not marked DR. The diabesity syndrome in AL-fed, DIO SD rats was readily modulated or prevented by moderate to marked DR. Moderate DR of balanced diets resulted in a better toxicology model by significantly improving survival, controlling adult body weight and obesity, reducing the onset, severity, and morbidity of age-related renal, endocrine, metabolic, and cardiac diseases. Moderate DR feeding reduces study-to-study variability, increases treatment exposure time, and increases the ability to distinguish true treatment effects from spontaneous aging. The structural and metabolic differences between the phenotypes of DIO and DR SD rats indicated changes of polygenic expression over time in this outbred stock. AL-overfeeding of SD rats produces a needed model of DIO and diabesity that needs further study of its patterns of polygenic expression and phenotype.

Aging↗

PubMed2006

Gene-gene, gene-environment & multiple interactions in colorectal cancer.

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.

Cocarcinogenesis↗

PubMed2006

Neurobiological correlates of acupuncture: November 17-18, 2005.

The "Neurobiological Correlates of Acupuncture" Conference was convened November 17-18, 2005 in Bethesda, Maryland. The conference was sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS). Its goals were to encourage exchange of ideas regarding the direction of neuroimaging in acupuncture research as well as to discuss some of the challenges in this field. The use of neuroimaging, a relatively recent advance in the study of acupuncture, holds the promise of localizing and characterizing brain activity associated with acupuncture interventions in real time and in a minimally invasive way. Among the main challenges to research into the biological mechanisms of acupuncture are the multiple treatment variables and the difficulties of selecting appropriate experimental controls. Despite these challenges, numerous findings from acupuncture neuroimaging experiments were presented and discussed at the conference on topics related to possible signaling networks, sham acupuncture controls, acupoint specificity, acupuncture analgesia, acupuncture-associated brain response, and the potential for using neuroimaging in conjunction with translational and clinical acupuncture research. Future directions in acupuncture neuroimaging research, as recommended by conference participants, should focus on (1) continuing exploration of acupuncture signaling networks; (2) establishing standards and recommendations for performing and reporting acupuncture neuroimaging results; (3) enabling data sharing in the acupuncture neuroimaging community; (4) gaining a better understanding of placebo and control groups in acupuncture neuroimaging experiments; and (5) developing biomarkers that relate to physiologically and/or clinically relevant acupuncture responses to neuroimaging results.

Acupuncture Therapy↗

PubMed2006

Optimized pH method for DNA elution from buccal cells collected in Whatman FTA cards.

DNA is the most accessible biologic material for obtaining information from the human genome because of its molecular stability and its presence in every nucleated cell. Currently, single nucleotide polymorphism genotyping and DNA methylation are the main DNA-based approaches to deriving genomic and epigenomic disease biomarkers. Upon the discontinuation of the Schleicher & Schuell IsoCode product (Dassel, Germany), which was a treated paper system to elute DNA from several biologic sources for polymerase chain reaction (PCR) analysis, a high-yielding DNA elution method was imperative. We describe here an improved procedure of the not fully validated Whatman pH-based elution protocol. Our DNA elution procedure from buccal cells collected in Whatman FTA cards (Whatman Inc., Florham Park, NJ) yielded approximately 4 microg of DNA from a 6-mm FTA card punch and was successfully applied for HLA-DQB1 genotyping. The genotypes showed complete concordance with data obtained from blood of the same subjects. The achieved high DNA yield from buccal cells suggests a potential cost-effective tool for genomic and epigenomic disease biomarkers development.

Alleles↗

PubMed2003

Monitoring human occupational and environmental exposures to polycyclic aromatic compounds.

Many research groups have been carrying out studies to develop biomarkers of exposure to polycyclic aromatic compounds (PACs) and apply these for human biomonitoring. The main objectives of the use of biomarkers are to determine specific occupational and environmental exposures to monitor the effectiveness of exposure controls and prediction of the risk of disease. This article presents a review of the literature in the field of biomarkers of human exposure to PACs and an evaluation of the relevant biomarkers for monitoring exposure to PACs in a range of exposure situations from coke ovens to bitumen handling and environmental exposures. For this evaluation, the relationships between external PAC exposures and the corresponding biomarker levels have been studied. The literature data indicate that urinary excretion of 1-hydroxypyrene correlates well with external PAC exposure and this compound appears to be a suitable marker for internal exposure to PACs. DNA adducts, mostly measured in white blood cells, do not show satisfactory correlations with exposure to PACs in a variety of workplace and exposure situations. It is not clear which factors are mainly responsible for this poor correlation. Micronuclei and sister chromatid exchanges measured in peripheral white blood cells are also unsatisfactory as biomarkers for PAC exposure. From the relatively limited data available, chromosome aberrations appear to show considerable promise as indicators of exposure to PACs. Because of their strong association with cancer, chromosome aberrations are considered suitable indicators of increased cancer risk arising from exposure to PACs.

Animals↗

PubMed2026

Causal relationships between oral-gut microbiome and bone neoplasm-related phenotypes: Insights from bidirectional Mendelian randomization.

The human oral and gut microbiota are the 4 largest microbial communities in the body and play crucial roles in maintaining homeostasis and influencing disease. Observational studies have suggested links between these microbiota and bone neoplasm-related phenotypes, but establishing causality has been challenging due to confounding factors and reverse causality. We conducted a bidirectional, 2-sample Mendelian randomization (MR) study to investigate evidence consistent with a potential causal association between the saliva and gut microbiota and various bone neoplasm-related phenotypes. Genetic instruments for saliva and gut microbiota were sourced from large genome-wide association studies. Inverse variance weighted was the primary MR method, supplemented by 4 other MR techniques. Sensitivity analyses, including MR-Egger regression, were performed to assess pleiotropy and heterogeneity. In the forward MR analysis, Veillonella parvula from the saliva microbiota was associated with a decreased risk of bone and connective tissue neoplasms (β: -0.236, 95% CI: [-0.275, -0.197], P = 8.20E-33). MR analyses identified genetically predicted associations between several microbial taxa and bone neoplasm-related phenotypes. Reverse MR analyses showed that genetic liability to bone neoplasm-related phenotypes was associated with variation in the composition of the oral (e.g., Order Bacteroidales, Rothia mucilaginosa) and gut microbiota (e.g., Class Methanobacteria, Genus Eubacterium oxidoreducens group). Sensitivity analyses confirmed the robustness of these findings, as no statistical evidence of substantial heterogeneity or directional horizontal pleiotropy was detected. This study provides genetic evidence supporting a bidirectional causal relationship between specific saliva and gut microbiota and bone neoplasm-related phenotypes. Our findings identify several microbial taxa as potential candidates for future biomarker development and therapeutic investigation in bone neoplasm-related phenotypes. However, these genetically informed associations require further mechanistic, experimental, and prospective clinical validation before clinical application.

Humans↗

PubMed2006

Mechanism of cerebral beta-amyloid angiopathy: murine and cellular models.

Cerebral amyloid angiopathy of the beta-amyloid type (Abeta-CAA) is a risk factor for hemorrhagic stroke and independently is believed to contribute to dementia. Naturally occurring animal models of Abeta-CAA are scarce and not well suited for the laboratory. To this end, a variety of transgenic mouse models have been developed that, similar to cerebral Abeta-amyloidosis in humans, develop either Abeta-CAA only or both Abeta-CAA and parenchymal amyloid, or primarily parenchymal amyloid with only scarce Abeta-CAA. The lessons learned from these mouse models are: i) Abeta-CAA alone is sufficient to induce cerebral hemorrhage and associate pathologies including neuroinflammation, ii) the origin of vascular amyloid is mainly neuronal, iii) Abeta-CAA results largely from impaired Abeta clearance, iv) a high ratio Abeta40:42 favors vascular over parenchymal amyloidosis, and v) genetic risk factors such as ApoE modulate Abeta-CAA and CAA-induced hemorrhages. Therapeutic strategies to inhibit Abeta-CAA are poor at the present time. Once Abeta-CAA is present current Abeta immunotherapy strategies have failed to clear vascular amyloid and even run the risk of serious side effects. Despite this progress in deciphering the pathomechanism of Abeta-CAA, with these first generation mouse models of Abeta-CAA, refining these models is needed and will help to understand the emerging importance of Abeta-CAA for dementia and to develop biomarkers and therapeutic strategies.

Amino Acid Sequence↗

PubMed2026

Metagenomic polymorphic toxin effector and immunity profiling predicts microbiome development and disease-related dysbiosis.

Bacteria use antagonistic interbacterial weapons, such as polymorphic toxin secretion systems (TSS), to compete for niches in the human gut microbiome. We hypothesized that TSS influence gut microbiome development and disease-related dysbiosis. We developed a bioinformatic marker gene approach (PolyProf) to quantify TSS including ~200 effector and immunity genes and applied it to ~15,000 publicly available human metagenomes. PolyProf alpha and beta diversity readily distinguished 12 different human disease states and enabled the construction of highly accurate linear regression classifier machine learning models. Elastic net machine learning models integrating bacterial taxonomy with PolyProf had strong predictive value for 12 disease states, outperforming models utilizing taxonomy alone. During microbiome development in the first year of life, PolyProf alpha diversity increases, and beta diversity becomes increasingly like the maternal microbiome, influenced by vertical transfer, delivery mode, and breastfeeding. PolyProf is related to strain sharing among adults through social interactions. In summary, TSS genes strongly correlate with microbiome development and interpersonal strain sharing, suggesting roles for interbacterial antagonism. Since PolyProf distinguishes diverse adult disease statuses, these dynamics may contribute to non-genetic inheritance.IMPORTANCEPrevious research has demonstrated that bacteria compete within the gut microbiome using toxin secretion systems (TSS). How TSS contribute to human microbiome development and the microbiome alterations observed in human diseases is not known. This study develops a new bioinformatic tool for profiling TSS-related genes in metagenomic data. Application of this approach to large-scale human fecal metagenomic data demonstrates the dynamic association of TSS during microbiome development, including the exchange of strains among social contacts. TSS gene abundance patterns are highly predictive of 12 disease states. This study advances the field by enabling TSS profiling in metagenomes and by identifying disease and microbiome development biomarkers that provide hypotheses for future mechanistic studies and may be useful for disease diagnosis.

Dysbiosis↗

PubMed2026

Programmed cell death and risk of diabetic retinopathy: a Mendelian randomization study.

BACKGROUND: Programmed cell death (PCD) plays an important role in diabetic retinopathy (DR); however, the underlying genetic mechanisms remain unclear. We used Mendelian randomization (MR) to investigate the causal relationships between PCD-related genes and DR. This study aimed to investigate the effects of PCD on the risk of DR by conducting MR analysis. METHODS: Summary statistics from gene expression quantitative trait loci (eQTL) studies (31,684 Europeans) were analyzed. Genetic instrumental variables were selected using cis-eQTL single-nucleotide polymorphisms (SNPs; P < 5 × 10- 8). Summary data-based MR (SMR) was employed to assess causal associations between PCD-related genes and DR, with three additional MR methods used for sensitivity testing. Bayesian colocalization was used to examine the shared regulatory mechanisms between PCD QTLs and DR risk loci. RESULTS: Sensitivity and colocalization analyses revealed six genes that affected DR: cathepsin H (CTSH), NAD(P)H: quinone oxidoreductase 1 (NQO1), tribbles pseudokinase 3 (TRIB3), and phosphoglycerate mutase 5 (PGAM5), which increased DR risk, and iron-responsive element binding protein 2 (IREB2) and tumor necrosis factor (TNF), which exhibited protective effects. Multivariate MR confirmed significant causal effects for CTSH, IREB2, and PGAM5 (p < 0.050). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (including 10 STRING-derived genes) revealed that 13 genes were enriched in necroptosis, apoptosis, mitophagy, and TNF signaling pathways in DR. CONCLUSIONS: This MR study supports the causal involvement of PCD in DR and identifies candidate genes (CTSH, IREB2, PGAM5, NQO1, TRIB3, and TNF) for therapeutic targeting or biomarker development in DR prevention or diagnosis.

Humans↗

PubMed2000

Exposure to hazardous substances and male reproductive health: a research framework.

The discovery in the mid-1970s that occupational exposures to pesticides could diminish or destroy the fertility of workers sparked concern about the effects of hazardous substances on male reproductive health. More recently, there is evidence that sperm quantity and quality may have declined worldwide, that the incidence of testicular cancer has progressively increased in many countries, and that other disorders of the male reproductive tract such as hypospadias and cryptorchidism may have also increased. There is growing concern that occupational factors and environmental chemical exposures, including in utero and childhood exposures to compounds with estrogenic activity, may be correlated with these observed changes in male reproductive health and fertility. We review the evidence and methodologies that have contributed to our current understanding of environmental effects on male reproductive health and fertility and discuss the methodologic issues which confront investigators in this area. One of the greatest challenges confronting researchers in this area is assessing and comparing results from existing studies. We elaborate recommendations for future research. Researchers in the field of male reproductive health should continue working to prioritize hazardous substances; elucidate the magnitude of male reproductive health effects, particularly in the areas of testicular cancer, hypospadias, and cryptorchidism; develop biomarkers of exposure to reproductive toxins and of reproductive health effects for research and clinical use; foster collaborative interdisciplinary research; and recognize the importance of standardized laboratory methods and sample archiving.

Biomarkers↗

PubMed2005

Acute ozone-induced differential gene expression profiles in rat lung.

Ozone is an oxidant gas that can directly induce lung injury. Knowledge of the initial molecular events of the acute O3 response would be useful in developing biomarkers of exposure or response. Toward this goal, we exposed rats to toxic concentrations of O3 (2 and 5 ppm) for 2 hr and the molecular changes were assessed in lung tissue 2 hr postexposure using a rat cDNA expression array containing 588 characterized genes. Gene array analysis indicated differential expression in almost equal numbers of genes for the two exposure groups: 62 at 2 ppm and 57 at 5 ppm. Most of these genes were common to both exposure groups, suggesting common roles in the initial toxicity response. However, we also identified the induction of nine genes specific to 2-ppm (thyroid hormone-beta receptor c-erb-A-beta; and glutathione reductase) or 5-ppm exposure groups (c-jun, induced nitric oxide synthase, macrophage inflammatory protein-2, and heat shock protein 27). Injury markers in bronchoalveolar lavage fluid (BALF) were used to assess immediate toxicity and inflammation in rats similarly exposed. At 2 ppm, injury was marked by significant increases in BALF total protein, N-acetylglucosaminidase, and lavageable ciliated cells. Because infiltration of neutrophils was observed only at the higher 5 ppm concentration, the distinctive genes suggested a potential amplification role for inflammation in the gene profile. Although the specific gene interactions remain unclear, this is the first report indicating a dose-dependent direct and immediate induction of gene expression that may be separate from those genes involved in inflammation after acute O3 exposure.

Administration, Inhalation↗

PubMed2005

Priority list of research areas for radiological nuclear threat countermeasures.

To help the nation prepare for the possibility of a terrorist attack using radiological and nuclear devices, the Office of Science and Technology Policy and the Homeland Security Council established an interagency working group. The working group deliberated on the research needs for radiological/ nuclear threat countermeasures and identified and prioritized 18 areas for further attention. The highest priorities were given to research on (1) radioprotectors for use prior to exposure; (2) therapeutic agents for postexposure treatment; (3) antimicrobial therapy for infections associated with radiation exposure; (4) cytokines and growth factors; (5) mechanisms of radiation injury at the molecular, cellular, tissue and organism levels; and (6) automation of biodosimetric assays. High priority was given to (1) developing biomarkers for biodosimetry; (2) enhancing training in the radiation sciences; (3) exploring the consequences of combined injury; (4) establishing a repository of information regarding investigational countermeasures; and (5) following the health of an exposed population to better prepare for subsequent events. The research areas that the committee felt required the attention of the radiation research community are described in this report in an effort to inform this community about the needs of the nation and to encourage researchers to address these critical issues.

Guidelines as Topic↗

PubMed2006

Proteomic analysis of urine in kidney transplant patients with BK virus nephropathy.

The differentiation of BK virus-associated renal allograft nephropathy (BKVAN) from acute allograft rejection (AR) in renal transplant recipients is an important clinical problem because the treatment can be diametrically opposite for the two conditions. The aim of this discovery-phase biomarker development study was to examine feasibility of developing a noninvasive method to differentiate BKVAN from AR. Surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry analysis was used to compare proteomic profiles of urine samples of 21 patients with BKVAN, 28 patients with AR (Banff Ia to IIb), and 29 patients with stable graft function. SELDI analysis showed proteomic profiles that were significantly different in the BKVAN group versus the AR and stable transplant groups. Peaks that corresponded to m/z values of 5.872, 11.311, 11.929, 12.727, and 13.349 kD were significantly higher in patients with BKVAN. Bioinformatics analyses allowed distinction of profiles of patients with BKVAN from patients with AR and stable patients. SELDI profiles also showed a high degree of reproducibility. Proteomic analysis of urine may offer a noninvasive way to differentiate BKVAN from AR in clinical practice. The identification of individual proteomic peaks can improve further the clinical utility of this screening method.

Adult↗