Alpha2beta1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis.

Background: Ovarian cancer is characterized by a wide-spread intra-abdominal metastases which represents a major clinical hurdle in the prognosis and management of the disease. A significant proportion of ovarian cancer cells in peritoneal ascites exist as multicellular aggregates or spheroids. We hypothesize that these cellular aggregates or spheroids are invasive with the capacity to survive and implant on the peritoneal surface.

Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease.

Objectives: Matrix metalloproteinases (MMPs) are plausible candidates for prediction of unstable coronary syndromes. We hypothesised that the MMP-3 polymorphism (- 1171, 5A/6A) would relate to coronary plaque characteristics and unstable clinical presentation.

Methods And Results: Forty patients with de novo presentation of coronary artery disease (CAD) were classified into unstable coronary syndrome (n=19) or stable angina pectoris (n=21).

Antiinflammatory effects of the cyclopentenone isoprostane 15-A(2)-IsoP in human gestational tissues.

Proinflammatory prostaglandins and cytokines are involved in the initiation of human labor and delivery. Although cyclopentenone prostaglandins regulate the formation of these prolabor mediators via nuclear factor-kappaB (NF-kappaB) and/or peroxisome proliferator-activated receptor-gamma, recent evidence suggests that they do not exist in vivo. Cyclopentenone isoprostanes (IsoPs), which are highly reactive structural isomers of bioactive cyclopentenone prostaglandins, do exist physiologically and have been shown to inhibit the inflammatory response in macrophages.

Advanced glycation endproducts mediate pro-inflammatory actions in human gestational tissues via nuclear factor-kappaB and extracellular signal-regulated kinase 1/2.

Processes of human labour include increased oxidative stress, formation of inflammatory mediators (e.g. cytokines) and uterotonic phospholipid metabolites (e.

Why do membranes rupture at term? Evidence of increased cellular apoptosis in the supracervical fetal membranes.

Objective: Reduced tensile strength of the human fetal membranes overlying the cervix has previously been identified. We used transcervical application of Bonney's blue dye, before the onset of term labor to identify the supracervical membranes for analysis after elective cesarean section delivery. We hypothesized that pro- and antiapoptotic proteins, which are representative of both the extrinsic and intrinsic pathways, would be expressed differentially in the supracervical membranes compared with membranes taken from distal sites.

Pharmacist-managed vaccination program increased influenza vaccination rates in cardiovascular patients enrolled in a secondary prevention lipid clinic.

Study Objectives: To determine whether a vaccination program in a pharmacist-managed secondary prevention lipid clinic increased influenza immunization rates in a high-risk population, and whether age or gender disparity existed among those vaccinated.

Design: Retrospective chart review.

Setting: Large, multispecialty, group practice.

Mitogen-activated protein kinase proteins regulate LPS-stimulated release of pro-inflammatory cytokines and prostaglandins from human gestational tissues.

The role of pro-inflammatory cytokines and prostaglandins in human labour is well established. Many of the mRNAs stabilised by the MAPK pathway encode inflammatory mediators, suggesting that this kinase pathway plays a major role in the regulation of inflammation. The aim of this study was to determine if the MAPK pathway regulates the inflammatory response in human gestational tissues.

Socioeconomic consequences of mercury use and pollution.

In the past, human activities often resulted in mercury releases to the biosphere with little consideration of undesirable consequences for the health of humans and wildlife. This paper outlines the pathways through which humans and wildlife are exposed to mercury. Fish consumption is the major route of exposure to methylmercury.

Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome.

TREX1 constitutes the major 3'-->5' DNA exonuclease activity measured in mammalian cells. Recently, biallelic mutations in TREX1 have been shown to cause Aicardi-Goutieres syndrome at the AGS1 locus. Interestingly, Aicardi-Goutieres syndrome shows overlap with systemic lupus erythematosus at both clinical and pathological levels.

Identification of differentially regulated proteins in a patient with Leber's Congenital Amaurosis--a proteomic study.

Background: To identify the pattern of protein expression in the retina from a patient with Leber's Congenital Amaurosis (LCA) secondary to a mutation in the AIPL1 gene. The retina from one eye of a patient with LCA and 7 control eyes were studied. The tissue was subjected to high resolution two-dimensional gel electrophoresis, image analysis and mass spectrometry, in an effort to identify differentially regulated proteins.

Effect of high oxygen on placental function in short-term explant cultures.

Ex situ culture of human gestational tissues has been routinely used as a model to investigate tissue function. The objective of this study was to determine the effect of varying oxygen concentrations on human term placental explants over a 24-h time period. Specifically, the effect of incubating placental explants in oxygen concentrations of 8%, 21% or 95% on tissue viability, metabolism and cell death was measured by assessing glucose consumption, lactate production, release of lactate dehydrogenase, parathyroid hormone-related protein (PTHrP), tumour necrosis factor-alpha (TNF-alpha) and 8-isoprostane, immunoreactivity for cleaved-caspase-9 and immunohistochemistry for the caspase-3-cleaved cytokeratin-18 neoepitope, M30.

Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer: NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition.

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be upregulated in ovarian cancer cells. In this study, we report that the expression of immunoreactive NGAL (irNGAL) in ovarian tumors changes with disease grade and that this change is reflected in the concentration of NGAL in peripheral blood. A total of 59 ovarian tissues including normal, benign, borderline malignant and grades 1, 2 and 3 malignant were analyzed using immunohistochemistry.

Proteomic analysis and characterisation of human cervico-vaginal fluid proteins.

Aim: Cervico-vaginal fluid (CVF) may provide insight into the biochemical pathways of human reproduction and parturition. The aim of this study was to establish a 2-D electrophoretic map of human CVF in healthy, pregnant women at term.

Methods: CVF was collected, concentrated and processed by routine 2-D polyacrylamide gel electrophoresis using pH 4-7-immobilised pH gradient strips and 8-16% gradient polyacrylamide gels.

Identification of bactenecin-1 in cervicovaginal fluid by two-dimensional electrophoresis in an ovine model of preterm labour.

Preterm labour is a major problem in obstetrics. Timely intervention with available treatments is hampered by the lack of a reliable test of imminent preterm delivery. Current methods of diagnosis are based on the detection of breakdown products of foetal membranes or structural changes to the cervix when preterm labour is well established.

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: a validated genetic association study.

Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI).

Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study.

The renin-angiotensin system is a key regulator of blood pressure (BP), with inhibitors of angiotensin-converting enzyme (ACE) used clinically to treat hypertension and other cardiovascular conditions. ACE2 is a newly identified member of this system, which converts angiotensin II to angiotensin, and of which the occurrence in plasma has not been investigated. The aim of this study was to determine the heritability of circulating ACE, ACE2, and neprilysin (NEP), which may also be a regulator of BP, in a family study, and to determine covariates that contribute to the variation in plasma activity.

The role of disease burden measures in future estimates of endemic waterborne disease.

The 1996 Safe Drinking Water Act amendments require the US Environmental Protection Agency and the Centers for Disease Control and Prevention to develop a national estimate of the occurrence of waterborne infectious disease that is attributable to public drinking water systems in the United States. Much of the information for developing the national estimate will be derived from epidemiologic data, and the primary outcome of this effort will be an estimate of the number of cases of gastrointestinal illness. While quantifying the number of these cases provides some measure of waterborne disease impact, the usefulness of this measure may be limited because the full spectrum of societal impact also involves consideration of the additional effects of these diseases such as hospitalization costs and lost productivity.

The role and regulation of the nuclear factor kappa B signalling pathway in human labour.

Within the discipline of reproductive biology, our understanding of one of the most fundamental biological processes is lacking--the cellular and molecular mechanisms that govern birth. This lack of understanding limits our ability to reduce the incidence of labour complications. The incidence of labour complications including: preterm labour; cervical incompetence; and post-date pregnancies has not diminished in decades.

Microdissection-based high-resolution genomic array analysis of two patients with cytogenetically identical interstitial deletions of chromosome 1q but distinct clinical phenotypes.

We describe two boys with cytogenetically identical interstitial deletions in the q42.11-q42.13 region of the long arm of chromosome 1 detected by high-resolution G-banding analysis.

Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline.

Objective: The study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension.

Study Design: Forty children, undergoing cardiopulmonary bypass and at risk for pulmonary hypertension, were randomized to receive 5 perioperative doses (1.9 g/m2 per dose) of either oral citrulline or placebo.

Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells.

The incidence of hormone-related diseases such as prostatic, breast, ovarian, and endometrial cancer is lower in Asian populations compared to Western countries. High consumption of soybean products that are rich in phytoestrogens, predominantly genistein, is postulated to be responsible for the lower incidence of hormone-related disease, although the mechanism through which this effect might be mediated is unclear. In this study, microarray analysis was used to identify the changes in gene expression elicited by treatment of the human endometrial cancer cell line, Ishikawa, with genistein at both physiologically achievable and supraphysiological concentrations.

A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses.

Background: Teriflunomide, a dihydro-orotate dehydrogenase inhibitor, has immunomodulatory effects, including the ability to suppress experimental allergic encephalomyelitis. In this randomized, double-blind, placebo-controlled Phase II study, the authors examined the safety and efficacy of oral teriflunomide in multiple sclerosis (MS) with relapses.

Methods: Patients (n = 179) with relapsing-remitting MS (n = 157) or secondary progressive MS with relapses (n = 22) were randomized to receive placebo, teriflunomide 7 mg/day, or teriflunomide 14 mg/day for 36 weeks.

Advanced techniques in placental biology -- workshop report.

Major advances in placental biology have been realized as new technologies have been developed and existing methods have been refined in many areas of biological research. Classical anatomy and whole-organ physiology tools once used to analyze placental structure and function have been supplanted by more sophisticated techniques adapted from molecular biology, proteomics, and computational biology and bioinformatics. In addition, significant refinements in morphological study of the placenta and its constituent cell types have improved our ability to assess form and function in highly integrated manner.

Ventricular enlargement in MS: one-year change at various stages of disease.

Objectives: To investigate ventricular enlargement (VE) over 1 year at three different stages of multiple sclerosis (MS).

Methods: A semi-automated technique for measuring VE was applied to MRI scans in 26 patients with clinically isolated syndromes (CIS) suggestive of MS, 30 with early relapse-onset MS of 1 year duration, 41 with established relapsing remitting (RR) MS, and 23 with secondary progressive (SP) MS.

Results: VE at 1 year was seen in early MS (median increase 0.

Protein profiling the effects of in vitro hyperoxic exposure on fetal rabbit lung.

The aim of this study was to test the hypothesis that acute in vitro exposure of prematurely delivered fetal rabbit lungs to hyperoxic conditions will induce the expression of an adaptive cassette of proteins that mediates antioxidant and inflammatory processes. To test this hypothesis, ex situ fetal rabbit lung explants were prepared from New Zealand white rabbits delivered by cesarean section on day 29 of gestation and incubated under air (21% O2; 5% CO2) or hyperoxic (95% O2; 5% CO2) atmospheres. Total tissue protein was extracted following incubation and subjected to 2-DE.