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At least 307 records · Page 17Linked to original sources
PubMed2005

Genetics, genomics and proteomics in atherosclerosis research.

Atherosclerosis and its clinical manifestations are the leading cause of death in Western countries. Atherosclerosis is a multifactorial disease characterized by endothelial dysfunction, smooth muscle cell (SMC) proliferation and migration, inflammation, lipid and matrix accumulation and thrombus formation. Multiple genetic and environmental features and interactions between these factors influence the disease process. To understand fundamental pathobiological mechanisms in atherogenesis and to develop and target new therapies, information on genetic factors (atherogenetics), gene expression patterns (atherogenomics) and protein expression patterns (atheroproteomics) are needed. This review will summarize current knowledge in these areas of atherosclerosis research with a special emphasis on microarray technology.

Atherosclerosis↗
PubMed1995

Establishment of a human hepatic adenosquamous carcinoma cell line (KMC-2) and its response to cytokines.

A human hepatic adenosquamous carcinoma cell line (KMC-2) was established from a serially transplanted tumor in nude mice (nuKMC-2), which originated from human cholangio-cellular carcinoma and showed histological alteration from adenocarcinoma to squamous cell carcinoma (SCC) along with serial transplantation. KMC-2 cells in monolayer culture proliferated in a sheet-like arrangement with a population doubling time of 29.5 h, whereas the cells in 0.1% collagen gel embedded culture formed a compact and tubular structure with the population doubling time of 35.4 h. The cells secreted carbohydrate antigen 19-9 (CA19-9), tissue polypeptide antigen and SCC-related antigen. The back-transplanted nude mouse tumor exhibited morphologic features of adenosquamous carcinoma resembling those in the original nude mouse tumor. IFN-alpha, IFN-gamma and TNF-alpha suppressed cell proliferation significantly. Functionally, IFN-gamma significantly suppressed CA19-9 secretion, and conversely promoted SCC-related antigen secretion. These findings suggest that KMC-2 is the first human hepatic adenosquamous carcinoma cell line primarily originated from adenocarcinoma; the environmental factors, such as the presence of extracellular matrix and the cytokines influenced the growth, morphology and function of KMC-2.

Animals↗
PubMed1986

Gross and microscopic lesions in the female SENCAR mouse skin and lung in tumor initiation and promotion studies.

The skin and lung tissues from SENCAR mice used as part of the Environmental Protection Agency's (EPA's) Carcinogenesis Testing Matrix were examined. This study included SENCAR mice used in three different short-term bioassay protocols in which the skin papilloma assay was used to identify initiators, promoters, and complete carcinogens. Also included were the pathology findings from SENCAR mice used in the combined bioassay in which the skin assay and the lung adenoma assay were conducted simultaneously. The gross and microscopic features of treatment-associated and spontaneous lesions of the skin and lung of the SENCAR mouse used in these studies are defined and the lesions most commonly observed are described. Generally, gross observations and microscopic findings in both the skin and lung tissues were poorly correlated. Although there are several definite criteria on which gross interpretations of the various skin and lung lesions can be made, with the exception of pedunculated squamous cell papillomas and the classic squamous cell carcinomas, the various lesion types had a wide variety of clinical presentations that severely compromised the accuracy of gross diagnosis. Further, in the case of benign skin neoplasms, malignant transformation of these tumors most often occurred at the base of the lesion and was initially hidden from gross observation. As a result, approximately 50% of the neoplasms interpreted clinically as benign tumors (papillomas and keratoacanthomas) were actually malignant neoplasms. Moreover, many lesions determined grossly to be nontumorous were in fact found to be neoplastic when examined microscopically. The SENCAR mouse was found to be more responsive in the lung adenoma assay than other strains examined with exception of the Strain A. Although accurate interpretation of the lung lesions in the SENCAR was compromised by nonneoplastic treatment-associated and/or spontaneous lesions, the feasibility of using the SENCAR skin and lung as target tissues in two-stage combined carcinogenesis studies merits further consideration.

Animals↗
PubMed1994

GABA-induced chemokinesis and NGF-induced chemotaxis of embryonic spinal cord neurons.

During CNS development, neuroblasts proliferate within germinal zones of the neuroepithelium, and then migrate to their final positions. Although many neurons are thought to migrate along processes of radial glial fibers, increasing evidence suggests environmental factors also influence nerve cell movement. Extracellular matrix molecules are thought to be involved in guiding neuronal migration, and molecules such as NGF and GABA exert trophic effects on immature neurons. The nature of the signals that initiate and direct neuroblast migration, however, is unknown. In vitro, NGF and GABA promote neurite outgrowth from cultured cells, and NGF induces axonal chemotaxis (directed migration along a chemical gradient). At earlier developmental stages, these molecules could influence neuroblast movement. Therefore, we investigated whether these molecules induce embryonic neuronal migration. Using an in vitro microchemotaxis assay, we show that rat embryonic spinal cord neurons migrate toward picomolar NGF and femtomolar GABA beginning at embryonic day 13 (E13). Cells exhibit chemotactic responses to NGF while GABA stimulates chemokinesis (increased random movement). GABA effects are mimicked by muscimol and inhibited by bicuculline and picrotoxin, suggesting GABA motility signals are mediated by GABA receptor proteins. Expression of GABA receptors by embryonic cord cells has been previously reported (Mandler et al., 1990; Walton et al., 1993). We used polymerase chain reaction analysis to demonstrate the presence of NGF and trk mRNA in E13 and E14 cord cells, indicating the cells express message for both NGF and high-affinity NGF receptors. Immunohistochemistry of E13 spinal cord sections indicates that NGF and GABA colocalize in fibers close to the target destinations of migrating neurons, suggesting diffusible gradients of these molecules provide chemoattractant signals to migratory cells. Thus, in vitro, neuroblast migration is induced by specific signaling molecules that are present in the developing spinal cord, and may stimulate migration of embryonic neurons prior to synaptogenesis.

Animals↗
PubMed1990

Extracellular matrix from normal but not Steel mutant mice enhances melanogenesis in cultured mouse neural crest cells.

The Steel mutation is a non-cell-autonomous defect in mice that affects the development of several stem cell populations, including germ cells, hematopoietic cells, and neural crest-derived pigment cells. To characterize the environmental lesion caused by the Steel mutation, we have compared the ability of normal and mutant extracellular matrix material to support the differentiation of normal mouse neural crest cells in vitro. Extracellular matrix deposited by cultured skin cells isolated from normal fetuses enhanced melanogenesis by crest cells over that observed on plastic substrata. In contrast, matrix material produced by Steel-Dickie (Sld) fetal skin cells failed to enhance melanogenesis. Adrenergic differentiation by neural crest-derived cells was promoted equally by both normal and mutant extracellular matrix compared to control substrata. We conclude that the environmental defect in mutant embryos selectively affects a melanogenic subpopulation of neural crest cells and resides, at least in part, in the extracellular matrix.

Animals↗
PubMed1990

Critical appraisal of two methods for determining aluminum in blood samples.

We report two methods for determining aluminum concentrations in blood. Method 1, proposed for routine monitoring of patients with chronic renal failure, includes a collection procedure that can be adopted by any renal dialysis unit, with a minimum of sample contamination. Plasma samples are diluted fourfold with HNO3/Triton X-100 matrix modifier. Method 2 is proposed for determining aluminum concentrations in patients with normal renal function, e.g., in drug studies and environmental monitoring. Samples are diluted with an equal volume of Mg(NO3)2 matrix modifier and atomized from a L'vov platform. By either method, analytical recovery of aluminum added to serum ranged between 92% and 105% throughout the linear calibration range. The reference interval (mean +/- SD) for aluminum in 22 healthy subjects by method 2 was 0.044 +/- 0.030 mumol/L.

Aluminum↗
PubMed1999

Structure/function/activity relationships in marine snow. Current understanding and suggested research thrusts.

Marine snow and marine snow components contribute to the mucilage phenomenon in the northern Adriatic Sea. Of special relevance is the matrix material, composed of extracellular polymeric substances, which are packaged into fibrils of colloidal dimensions. These 0.005 micron diameter fibrils are physical units of mucilage which can be visualized by transmission electron microscopy (TEM). They form polymer bridges between the various biotic and mineral components of marine snow, creating three-dimensional networks which affect floc porosity, density and settling behaviour. Recent observations of the matrix by TEM reveal complex fibril-delimited channels and capillary systems which partially traverse marine snow flocs and which are postulated to play roles in anomalous settling. Considering the marine snow floc as a microecosystem, the relationships between ultrastructure, chemistry and environmental properties are being explored. On the assumption that colloidal matrix materials, including those released into the bulk water, might provide advance information on anomalous floc behaviour, two new methods are recommended for monitoring the northern Adriatic Sea. One is a technique for chemical quantification of colloidal organic carbon. The other uses TEM, applied to water fractions derived from cascade ultracentrifugation, to estimate fibril quantities as a proportion of colloidal organic carbon.

Chemical Phenomena↗
PubMedDate not supplied

Genetic and environmental components of adolescent adjustment and parental behavior: a multivariate analysis.

Adolescent adjustment measures may be related to each other and to the social environment in various ways. Are these relationships similar in genetic and environmental sources of covariation, or different? A multivariate behavior-genetic analysis was made of 6 adjustment and 3 treatment composites from the study Nonshared Environment in Adolescent Development, using 674 same-sex adolescent sibling pairs aged 9-11. Cholesky decompositions of the total covariance matrix yielded additive and nonadditive genetic, and shared and nonshared environmental matrices. Factor analyses led to 3 factors for all but shared environment. The first 2 factors resembled Neuroticism and Extraversion factors typically found for personality; the third factor, parental monitoring and control, appeared to have different associations in different matrices.

Adolescent↗
PubMed1999

Improving protein identification from peptide mass fingerprinting through a parameterized multi-level scoring algorithm and an optimized peak detection.

We have developed a new algorithm to identify proteins by means of peptide mass fingerprinting. Starting from the matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) spectra and environmental data such as species, isoelectric point and molecular weight, as well as chemical modifications or number of missed cleavages of a protein, the program performs a fully automated identification of the protein. The first step is a peak detection algorithm, which allows precise and fast determination of peptide masses, even if the peaks are of low intensity or they overlap. In the second step the masses and environmental data are used by the identification algorithm to search in protein sequence databases (SWISS-PROT and/or TrEMBL) for protein entries that match the input data. Consequently, a list of candidate proteins is selected from the database, and a score calculation provides a ranking according to the quality of the match. To define the most discriminating scoring calculation we analyzed the respective role of each parameter in two directions. The first one is based on filtering and exploratory effects, while the second direction focuses on the levels where the parameters intervene in the identification process. Thus, according to our analysis, all input parameters contribute to the score, however with different weights. Since it is difficult to estimate the weights in advance, they have been computed with a generic algorithm, using a training set of 91 protein spectra with their environmental data. We tested the resulting scoring calculation on a test set of ten proteins and compared the identification results with those of other peptide mass fingerprinting programs.

Algorithms↗
PubMed2006

Evidence in favor of the contribution of genes involved in the maintenance of the extracellular matrix of the arterial wall to the development of intracranial aneurysms.

Intracranial aneurysm is probably a complex disease with both genetic and non-genetic or environmental risk factors contributing to the etiology of the disease. A disruption of the extracellular matrix (ECM) of the arterial wall is a likely factor in the pathogenesis of intracranial aneurysms. We analyzed 44 potential candidate genes involved in the maintenance of the integrity of the ECM in 382 Dutch Caucasian patients with intracranial aneurysms and 609 Dutch Caucasian controls for 384 tag single nucleotide polymorphisms (SNPs) using the GoldenGate assay on an Illumina BeadStation 500 GX. We identified SNPs that were associated with intracranial aneurysms (P<0.01) in six of these 44 genes: serpine1 (SERPINE1, P=0.0008), transforming growth factor beta induced (TGFBI, P=0.0026), perlecan (HSPG2, P=0.0044), fibronectin (FN1, P=0.0069), fibrillin 2 (FBN2, P=0.0077) and alpha 1 type IV collagen (COL4A1, P=0.0087). In a second independent cohort of 310 Dutch Caucasian intracranial aneurysm patients and 336 Dutch Caucasian controls, the association for the HSPG2 gene [combined odds ratio (OR) 1.33, 95% confidence interval (CI) 1.13-1.57, P=6 x 10(-4)] was replicated. The population attributable risk (PAR) for this SNP is 19%. Combining the two cohorts still showed association for the SERPINE1 (combined OR 1.27, 95% CI 1.07-1.50, P=0.004, PAR 6%), FBN2 (combined OR 1.37, 95% CI 1.07-1.75, P=0.01, PAR 3%) and COL4A1 (combined OR 1.22, 95% CI 1.05-1.42, P=0.007, PAR 7%) genes. These PARs are likely to be overestimates as they are calculated from the joint analyses combining stages 1 and 2 of our association study. Our findings indicate that variation in genes involved in the maintenance of the integrity of the ECM of the arterial wall plays a role in susceptibility to intracranial aneurysms. These findings further support our hypothesis that diminished maintenance of the ECM of the arterial wall is important in the development of intracranial aneurysms.

Extracellular Matrix↗
PubMed2006

Salmonella produces an O-antigen capsule regulated by AgfD and important for environmental persistence.

In this study, we show that Salmonella produces an O-antigen capsule coregulated with the fimbria- and cellulose-associated extracellular matrix. Structural analysis of purified Salmonella extracellular polysaccharides yielded predominantly a repeating oligosaccharide unit similar to that of Salmonella enterica serovar Enteritidis lipopolysaccharide O antigen with some modifications. Putative carbohydrate transport and regulatory operons important for capsule assembly and translocation, designated yihU-yshA and yihVW, were identified by screening a random transposon library with immune serum generated to the capsule. The absence of capsule was confirmed by generating various isogenic Deltayih mutants, where yihQ and yihO were shown to be important in capsule assembly and translocation. Luciferase-based expression studies showed that AgfD regulates the yih operons in coordination with extracellular matrix genes coding for thin aggregative fimbriae and cellulose. Although the capsule did not appear to be important for multicellular behavior, we demonstrate that it was important for survival during desiccation stress. Since the yih genes are conserved in salmonellae and the O-antigen capsule was important for environmental persistence, the formation of this surface structure may represent a conserved survival strategy.

Bacterial Capsules↗
PubMedDate not supplied

Analytical applications of flow injection with chemiluminescence detection--a review.

This paper reviews the literature on analytical applications of flow injection (FI) techniques with chemiluminescence (CL) detection from 1995-1999. The focus is on the application of FI-CL to the quantitative determination of specific analytes in real sample matrices. Therefore, entries have been tabulated under the most appropriate application area, ie pharmaceutical, environmental, foods and beverages and biomedical, as defined by the matrix that has been analysed. Each table lists analytes alphabetically and gives details of the exact sample matrix, the limit of detection (as reported in the original paper) and comments on the CL reaction used.

Environmental Pollutants↗
PubMed1999

Determination of the instrumental detection limits of commercial nonylphenol ethoxylates with a wide range of molecular masses using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Recent interest in the environmental fate and impact of nonylphenol ethoxylates (NPEs) has necessitated the need for the development of specific, and yet efficient, analytical methodologies for their detection. Using seventeen commercial NPEs, all having the general formula 4-(C(9)H(19))-C(6)H(4)-(OCH(2)CH(2))(n)-OH, we have established minimum concentrations at which matrix-assisted laser desorption ionization (MALDI)/time-of-flight (TOF)/mass spectrometry (MS) can be used in their detection. The NPEs were dissolved in an acetonitrile/tetrahydrofuran (3:1) solvent system prior to mixing with the matrix (alpha-cyano-4-hydroxycinnamic acid, dissolved in acetonitrile/tetrahydrofuran) solution, and the resulting MALDI-TOF mass spectra produced mostly sodiated molecules [M + Na](+).For the NPEs in which the major components contain three to ten ethoxy units, the sodiated molecules were detected at a minimum analyte concentration of 10 &mgr;g/L, whereas those in which the major components contain eight to fifteen ethoxy units were detected at a minimum concentration of 30 &mgr;g/L. Those NPEs containing oligomers in excess of twenty ethoxy units were only detectable at much higher concentration. For examples, Surfonic(R) N-300, N-400, N550, N-700, N-800, and N-1000 had detection limits of (&mgr;g/L): 1000, 1600, 2000, 2600, 3500 and 4500, respectively. These variations in instrumental detection limits must be considered when analyzing environmental samples for the presence of nonylphenol ethoxylates. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1998

Dust in the wind.

Explore the source record for details and available documents.

Aerosols↗
PubMed2002

Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault.

The acquisition of an androgen-independent phenotype by prostate cancer cells is presently a death sentence for patients. In order to have a realistic chance of changing this outcome, an understanding of what drives the progression to androgen independence is critical. We review here a working hypothesis based on the position that the development of androgen-independent epithelial cells is the result of a series of cellular and molecular events within the whole tissue that culminates in the loss of normal tissue-maintained growth control. This tissue includes the epithelial and stromal cells, the supporting extracellular matrix and circulating hormones. This review discusses the characteristics of these malignant cells, the role of stromal cells involved in growth and the differentiation of epithelial cells, and the role of the extracellular matrix as a mediator of the phenotypes of stromal and epithelial cells. In addition, environmental, neuroendocrine and immune factors that may contribute to disturbance of the fine balance of the epithelial-stromal-extracellular matrix connection are considered. While the goal of many therapeutic approaches to prostate cancer has been androgen ablation or targeting the androgen receptor (AR) of epithelial cells, these therapies become ineffective as the cells progress beyond dependence on androgen for growth control. Twenty years ago Sir David Smithers debated that cancer is the result of loss of tolerance within tissues and the organizational failure of normal growth-control mechanisms. This is precipitated by prolonged or abnormal demands for regeneration or repair, rather than of any inherent disorder peculiar to each of the individual components involved. He wrote "It is not the cell itself that is disorderly, but its relationship with the rest of the tissue". We have gained significantly large amounts of precise data on the effects of androgenic ablation on cancerous prostate cells and on the role of the AR in prostate cancer. The need has come to compile this information towards a perspective of dysregulation of tissue as a whole, and to develop experimental systems to address this broader perspective to find and develop therapies for treatment and prevention.

Androgens↗
PubMed1982

Environmental factors affecting neural crest differentiation: melanocyte differentiation by crest cells exposed to cell-free (deoxycholate-extracted) dermal mesenchyme matrix.

Deoxycholate-extracted, cell-free matrices were prepared from primary explants or dispersed cell cultures of embryonic avian dermis, ectoderm, gut mesenchyme, endoderm, pharynx, or umbilical artery. Neural crest cells in association with matrices from dermal explants or monolayers formed melanocytes after six days. Crest cells in association with matrices from all other tissues or grown on plastic did not form melanocytes. It is concluded that a deoxycholate-resistant structural component of the dermal extracellular matrix induces melanocyte differentiation.

Animals↗
PubMed2004

Regulation of endothelial cell function BY FAK and PYK2.

Endothelial cells form a continuous single layer lining throughout the vascular tree. Such positioning allows the endothelium to monitor numerous environmental signals within the blood vessel, including blood composition, structural matrix, and blood flow dynamics. Following signal integration, endothelial cells then induce context-specific changes in vessel properties. The nonreceptor tyrosine kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2) are activated by integrins, growth factors, and mechanical stimuli, suggesting a potentially important role in the integration of environmental stimuli. This review will explore the current understanding of FAK and Pyk2 signaling in endothelial regulation of vascular function.

Animals↗
PubMed2026

Meta-analysis of source identification and apportionment in soil: A systematic review of analytical procedures, receptor modeling, and environmental applications.

Soil pollution poses significant risks to ecosystems and human health, necessitating accurate source identification and apportionment to guide mitigation strategies. This systematic review evaluates the application of Positive Matrix Factorization (PMF) and other receptor models in soil pollution studies, focusing on analytical procedures, tracer indicators, and environmental applications. This review aims to provide a comprehensive framework for conducting soil source apportionment studies, aiding policymakers in designing effective, region-specific environmental management strategies by compiling global trends and methodological insights. The study addresses sampling protocols, emphasizing representativeness and quality control. Data from 500 peer-reviewed publications highlight the dominance of research in China, Eastern Europe, and South Asia, with agricultural soils being the most frequently studied. Key findings reveal that traffic emissions (20.8 %) and industrial activities (19.4 %) are the primary global contributors to soil contamination, with regional variations such as coal combustion in cold climates and agricultural inputs in developing regions. Policy recommendations include stricter industrial regulations, sustainable agricultural practices, and targeted remediation efforts based on source-specific risks.

Soil Pollutants↗