Hypoxia-inducible factor regulates alphavbeta3 integrin cell surface expression.

Hypoxia-inducible factor (HIF)-deficient placentas exhibit a number of defects, including changes in cell fate adoption, lack of fetal angiogenesis, hypocellularity, and poor invasion into maternal tissue. HIF is a heterodimeric transcription factor consisting of alpha and beta aryl hydrocarbon receptor nuclear translocator or ARNT) subunits. We used undifferentiated trophoblast stem (TS) cells to characterize HIF-dependent adhesion, migration, and invasion.

Associations among lead dose biomarkers, uric acid, and renal function in Korean lead workers.

Recent research suggests that both uric acid and lead may be nephrotoxic at lower levels than previously recognized. We analyzed data from 803 current and former lead workers to determine whether lead biomarkers were associated with uric acid and whether previously reported associations between lead dose and renal outcomes were altered after adjustment for uric acid. Outcomes included uric acid, blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, and urinary N-acetyl-ss-d-glucosaminidase (NAG) and retinol-binding protein.

Occupational lead exposure and longitudinal decline in neurobehavioral test scores.

Background: No previous longitudinal studies have compared and contrasted associations of blood lead and tibia lead with declines in cognitive function over the course of time in a large sample of subjects with current and past occupational exposure to inorganic lead.

Methods: From 1997 through 2001, we conducted a longitudinal study of 803 current and former lead workers in South Korea to evaluate effects on the central and peripheral nervous systems. Three study visits occurred during a mean follow-up duration of 2.

Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion.

The morphology and cytoskeletal structure of fibroblasts, endothelial cells, and neutrophils are documented for cells cultured on surfaces with stiffness ranging from 2 to 55,000 Pa that have been laminated with fibronectin or collagen as adhesive ligand. When grown in sparse culture with no cell-cell contacts, fibroblasts and endothelial cells show an abrupt change in spread area that occurs at a stiffness range around 3,000 Pa. No actin stress fibers are seen in fibroblasts on soft surfaces, and the appearance of stress fibers is abrupt and complete at a stiffness range coincident with that at which they spread.

Vitamin D receptor-deficient mice fail to develop experimental allergic asthma.

The active metabolite of vitamin D (1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))) is known to modulate the immune response in Th1 cell-directed diseases. To investigate the role of vitamin D in Th2 cell-directed diseases, experimental allergic asthma was induced in vitamin D receptor (VDR) knockout and in wild-type (WT) mice. As expected, WT mice developed symptoms of airway inflammation with an influx of eosinophils, elevated Th2 cytokine levels, mucous production, and airway hyperresponsiveness.

Death in the third dimension: apoptosis regulation and tissue architecture.

Tissue development, homeostasis and tumor pathogenesis all depend upon a complex dialogue between multiple cell types operating within a dynamic three-dimensional (3D) tissue extracellular matrix microenvironment. A major issue is whether the spatial organization of a cell within this 3D tissue microenvironment could modulate cell responsiveness to regulate cell fate decisions such as survival, and if so how. Classic developmental model systems and transgenic animals are instructive but pose special challenges for investigators conducting signaling studies and biochemical assays in tissues.

Burkholderia spp. alter Pseudomonas aeruginosa physiology through iron sequestration.

Pseudomonas aeruginosa and members of the Burkholderia cepacia complex often coexist in both the soil and the lungs of cystic fibrosis patients. To gain an understanding of how these different species affect each other's physiology when coexisting, we performed a screen to identify P. aeruginosa genes that are induced in the presence of Burkholderia: A random gene fusion library was constructed in P.

Watch thy neighbor: cancer is a communal affair.

Malignant transformation of an epithelium occurs within the context of a dynamically evolving tissue stroma that is composed of multiple cell types surrounded by an extracellular matrix. Because stromal-epithelial interactions regulate tissue homeostasis and can profoundly influence tumorigenesis it has been proposed that the stromal microenvironment is an epigenetic tumor modifier that can either positively or negatively regulate the malignant behavior of genetically aberrant cells. New work reported in this issue of Journal of Cell Science now provides compelling evidence that alterations in the stroma are necessary and also sufficient for induction of malignant behavior by genetically normal cells.

Autocrine laminin-5 ligates alpha6beta4 integrin and activates RAC and NFkappaB to mediate anchorage-independent survival of mammary tumors.

Invasive carcinomas survive and evade apoptosis despite the absence of an exogenous basement membrane. How epithelial tumors acquire anchorage independence for survival remains poorly defined. Epithelial tumors often secrete abundant amounts of the extracellular matrix protein laminin 5 (LM-5) and frequently express alpha6beta4 integrin.

Associations of renal function with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers.

We analyzed data from 798 lead workers to determine whether polymorphisms in the genes encoding delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR) were associated with or modified relations of lead exposure and dose measures with renal outcomes. Lead exposure was assessed with job duration, blood lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and tibia lead. Renal function was assessed with blood urea nitrogen (BUN), serum creatinine, measured creatinine clearance, calculated creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG), and retinol-binding protein.

Peroxisome proliferator-activated receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma.

Asthma is characterized by a predominant T(H)2 type immune response to airborne allergens. Controlling T(H)2 cell function has been proposed as therapy for this disease. We show here that ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)gamma significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease.

A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases.

The active form of vitamin D (1,25D3) suppressed the development of animal models of human autoimmune diseases including experimental inflammatory bowel disease (IBD). The vitamin D receptor (VDR) is required for all known biologic effects of vitamin D. Here we show that VDR deficiency (knockout, KO) resulted in severe inflammation of the gastrointestinal tract in two different experimental models of IBD.

Summary of historical beryllium uses and airborne concentration levels at Los Alamos National Laboratory.

Beryllium operations and accompanying medical surveillance of workers at Los Alamos National Laboratory began in the 1940s. In 1999 a Former Workers Medical Surveillance Program that includes screening for chronic beryllium disease was initiated. As part of this program, historical beryllium exposure conditions were reconstructed from archived paper and electronic industrial hygiene data sources to improve understanding of past beryllium uses and airborne concentration levels.

Associations of lead biomarkers with renal function in Korean lead workers.

Aims: To compare associations of lead biomarkers with renal function in current and former lead workers.

Methods: Cross sectional analysis of first year results from a longitudinal study of 803 lead workers and 135 controls in South Korea. Clinical renal function was assessed by blood urea nitrogen (BUN), serum creatinine, and measured and calculated creatinine clearance.

The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells.

Vitamin D is a potent immune system regulator. The active form of vitamin D (1,25(OH)(2)D(3)) suppresses the development of animal models of human autoimmune diseases. 1,25(OH)(2)D(3) decreased the proliferation of all T helper (h) cells and decreased the production of IFN-gamma, IL-2, and IL-5.

Alpha 6 beta 4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of alpha 3 beta 1 integrin.

Growth factor-induced cell migration and proliferation are essential for epithelial wound repair. Cell migration during wound repair also depends upon expression of laminin-5, a ligand for alpha 6 beta 4 integrin. We investigated the role of alpha 6 beta 4 integrin in laminin-5-dependent keratinocyte migration by re-expressing normal or attachment-defective beta 4 integrin in beta 4 integrin null keratinocytes.

Strength-based assessment of African-American adolescents with behavioral disorders.

The study examined consistencies and differences between 60 parents and their adolescent children with behavioral problems when rating the adolescents' strengths. The parents and teenagers agreed on most of the strength categories of the Behavior and Emotional Rating Scale. However, caretakers rated the adolescents as more involved in family life, while the adolescents rated themselves as more involved in school activities.

An assessment of water quality, physical habitat, and biological integrity of an urban stream in Wichita, Kansas, prior to restoration improvements (phase I).

Urban development alters the natural hydrological conditions of many streams and rivers often resulting in the degradation of water quality, physical habitat, and biotic integrity of lotic systems. Restoration projects attempt to improve and maintain the ecological integrity of urban streams; however, few projects have quantified improvements to stream ecology following implementation of restoration measures. This paper summarizes pre-restoration data collected as part of an urban stream restoration project on Gypsum Creek in Wichita, Kansas.

Alternative therapies for traditional disease states: osteoarthritis.

Americans spend more on natural remedies for osteoarthritis than for any other medical condition. In treating osteoarthritis, glucosamine and chondroitin sulfate, two of the molecular building blocks found in articular cartilage, are the most commonly used alternative supplements. In randomized trials of variable quality, these compounds show efficacy in reducing symptoms, but neither has been shown to arrest progression of the disease or regenerate damaged cartilage.

Genes for chlorogenate and hydroxycinnamate catabolism (hca) are linked to functionally related genes in the dca-pca-qui-pob-hca chromosomal cluster of Acinetobacter sp. strain ADP1.

Hydroxycinnamates are ubiquitous in the environment because of their contributions to the structure and defense mechanisms of plants. Additional plant products, many of which are formed in response to stress, support the growth of Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca-pca-qui-pob chromosomal cluster.

The organizing principle: microenvironmental influences in the normal and malignant breast.

The current paradigm for cancer initiation and progression rests on the groundbreaking discoveries of oncogenes and tumor suppressor genes. This framework has revealed much about the role of genetic alterations in the underlying signaling pathways central to normal cellular function and to tumor progression. However, it is clear that single gene theories or even sequential acquisition of mutations underestimate the nature of the genetic and epigenetic changes in tumors, and do not account for the observation that many cancer susceptibility genes (e.

Development of a medical examination program for former workers at a Department of Energy national laboratory.

Background: As a part of the U.S. Department of Energy (DOE) Former Workers' Medical Surveillance Program, a Needs Assessment was conducted at Los Alamos National Laboratory (LANL).

beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium.

Tumor cells can evade chemotherapy by acquiring resistance to apoptosis. We investigated the molecular mechanism whereby malignant and nonmalignant mammary epithelial cells become insensitive to apoptosis. We show that regardless of growth status, formation of polarized, three-dimensional structures driven by basement membrane confers protection to apoptosis in both nonmalignant and malignant mammary epithelial cells.

Interleukin-2 is one of the targets of 1,25-dihydroxyvitamin D3 in the immune system.

Interleukin (IL)-2 knockout (KO) mice, which spontaneously develop symptoms of inflammatory bowel disease similar to ulcerative colitis in humans, were made vitamin D deficient (D-) or vitamin D sufficient (D+) or were supplemented with 1,25-dihydroxyvitamin D(3) (1,25D3). 1,25-Dihydroxyvitamin D3 supplementation, but not vitamin D supplementation, reduced the early mortality of IL-2 KO mice. However, colitis severity was not different in D-, D+, or 1,25D3 IL-2 KO mice.