Long-term outcomes after ARDS.

Early reports of late outcomes among survivors of ARDS indicated that most patients improved dramatically after their intensive care unit stay, and few lived with residua of their once-severe pulmonary injury. Over the last decade, a collection of new studies with improved methodology and novel questions has improved our understanding of life after ARDS. After reviewing these newer investigations in the context of previously published literature, we have drawn several preliminary conclusions: (1) Long-term survival after hospital discharge is unaffected by ARDS, but is strongly affected by ARDS risk factor and comorbidities.

Expression of cellular prion protein in the frontal and occipital lobe in Alzheimer's disease, diffuse Lewy body disease, and in normal brain: an immunohistochemical study.

Cellular prion protein (PrP(c)) is a glycoprotein expressed at low to moderate levels within the nervous system. Recent studies suggest that PrP(c) may possess neuroprotective functions and that its expression is upregulated in certain neurodegenerative disorders. We investigated whether PrP(c) expression is altered in the frontal and occipital cortex in two well-characterized neurodegenerative disorders--Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD)--compared with that in normal human brain using immunohistochemistry and computerized image analysis.

Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia.

Background: The orbitofrontal cortex is involved in the monitoring of reward and in judgement. Lesion studies and functional neuroimaging investigations implicate this region in affective disorders, and altered neuronal and glial cell composition have been observed in this region in subjects with major depressive disorder (MDD).

Aims: Stereologically based investigation of caudal orbitofrontal cortex (cOFC), in 60 postmortem brains from four groups of 14 subjects each with bipolar disorder (BPD), schizophrenia and MDD.

Death rounds: end-of-life discussions among medical residents in the intensive care unit.

Purpose: We introduced "Death Rounds," a monthly discussion of the issues and emotions surrounding the care of dying patients, into the intensive care unit (ICU) rotations for medical house staff. We surveyed participating residents to evaluate their satisfaction with these discussions.

Subjects And Methods: Death Rounds occurred at university-based teaching hospitals in Seattle, Washington and Salt Lake City, Utah, between October 2000 and March 2002.

Myt1 family recruits histone deacetylase to regulate neural transcription.

The myelin transcription factor 1 (Myt1) gene family is comprised of three zinc finger genes [Myt1, Myt1L (Myt1-Like) and NZF3] of the structurally unique CCHHC class that are expressed predominantly in the developing CNS. To understand the mechanism by which this family regulates neural differentiation, we searched for interaction partners. In both yeast and a mammalian two-hybrid system, Myt1 and Myt1L interacted with Sin3B, a protein that mediates transcriptional repression by binding to histone deacetylases (HDACs).

Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype.

Objective: Epstein-Barr virus (EBV) is hypothesized to play a role in the development of systemic lupus erythematosus (SLE). Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important in regulating T cell-mediated immunity, encompassing the first line of response to viral infections, and genetic variation in CTLA-4 has been associated with SLE. This study examined the seroprevalence of EBV in a population-based study of SLE patients from the southeastern United States, and potential interactions with CTLA-4 polymorphisms were assessed.

Cyclooxygenase-2 functions as a downstream mediator of lysophosphatidic acid to promote aggressive behavior in ovarian carcinoma cells.

Elevated levels of the bioactive lipid lysophosphatidic acid (LPA) are detectable in the majority of patients with both early- and late-stage ovarian cancer, suggesting that LPA promotes early events in ovarian carcinoma dissemination. LPA contributes to the development, progression, and metastasis of ovarian cancer in part by inducing the expression of genes that contribute to proliferation, survival, or invasion, including cyclooxgenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2). We have previously shown that LPA promotes proMMP-2 activation and MMP-2-dependent migration and invasion in ovarian cancer cells.

Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses.

Systemic sclerosis (SSc; scleroderma) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain IL-10 genotypes are risk factors for the development of SSc and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese SSc patients and controls were genotyped for three loci: -3575, -2849, and -2763.

Intrinsic positive end-expiratory pressure in Acute Respiratory Distress Syndrome (ARDS) Network subjects.

Objective: We tested the hypothesis that subjects randomized to the 6 mL/kg predicted body weight tidal volume study group of the National Institutes of Health Acute Respiratory Distress Syndrome (ARDS) Network study had higher levels of intrinsic positive end-expiratory pressure (PEEP) than subjects randomized to the 12 mL/kg predicted body weight tidal volume study group.

Design: Secondary analysis of a subgroup from a randomized controlled trial.

Setting: Hospitals located in San Francisco, CA, and Seattle, WA.

Practice changes in glycemic management and outcomes in coronary artery bypass surgery patients.

This study aims to evaluate whether a quality improvement initiative in hyperglycemia management could result in substantiated practice changes and improved outcomes for coronary artery bypass surgery patients. Retrospective chart review and analysis of 103 randomly selected patients hospitalized for coronary artery bypass surgery was used. After the glycemia awareness initiative, the perioperative use of intravenous insulin infusion therapy increased in the total population (P = .

CTLA-4 gene polymorphisms and systemic lupus erythematosus in a population-based study of whites and African-Americans in the southeastern United States.

Cytotoxic lymphocyte antigen-4 (CTLA-4) plays an important role in regulating T cell activation, and may help to limit T cell response under conditions of inflammation. Genetic variability in CTLA-4 has been implicated in the development of several autoimmune diseases. Some studies have described associations between CTLA-4 polymorphisms and systemic lupus erythematosus (SLE), but findings have been inconsistent.

Roles of mitogen activated protein kinases and EGF receptor in arsenite-stimulated matrix metalloproteinase-9 production.

The dermatotoxicity of arsenic is well established and epidemiological studies identify an increased incidence of keratinocytic tumors (basal cell and squamous cell carcinoma) associated with arsenic exposure. Little is known about the underlying mechanisms of arsenic-mediated skin carcinogenesis, but activation of mitogen-activated protein (MAP) kinases and subsequent regulation of downstream target genes may contribute to tumor promotion and progression. In this study, we investigated activation of the extracellular signal regulated kinase (ERK) and the stress-associated kinase p38 by arsenite in HaCat cells, a spontaneously immortalized human keratinocyte cell line.

Expression of a catalytically inactive transmembrane protein tyrosine phosphatase epsilon (tm-PTP epsilon) delays optic nerve myelination.

Reversible tyrosine phosphorylation is integral to the process of oligodendrocyte differentiation. To interfere with the subset of the phosphorylation cycle overseen by protein tyrosine phosphatase epsilon (PTP epsilon) in oligodendrocytes, we applied a substrate-trapping approach in the development of transgenic mice overexpressing a catalytically inactive, transmembrane PTP epsilon-hemaglutinin (tm-PTP epsilon-HA) from the dual promoter element of the gene encoding the myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). Transgene expression peaked during the active myelinating period, at 2-3 weeks postnatal.

Developmental transcription factor slug is required for effective re-epithelialization by adult keratinocytes.

During re-epithelialization of cutaneous wounds, keratinocytes recapitulate several aspects of the embryonic process of epithelial-mesenchymal transition (EMT), including migratory activity and reduced intercellular adhesion. The transcription factor Slug modulates EMT in the embryo and controls desmosome number in adult epithelial cells, therefore, we investigated Slug expression and function during cutaneous wound re-epithelialization. Slug expression was elevated in keratinocytes bordering cutaneous wounds in mice in vivo, in keratinocytes migrating from mouse skin explants ex vivo, and in human keratinocytes at wound margins in vitro.

Cell density and cortical thickness in Heschl's gyrus in schizophrenia, major depression and bipolar disorder.

There is evidence that the superior temporal gyrus and Heschl's gyrus within it are implicated in schizophrenia. We investigated neuronal and glial cell density and cortical thickness within Heschl's gyrus, using the optical disector to estimate cell density within cortical layers 3 and 5 in tissue derived postmortem from people with diagnoses of major depressive disorder, schizophrenia and bipolar disorder, compared with normal controls (n=15 per group). No significant difference in neuronal or glial cell density or in cortical thickness was observed between the groups; our findings therefore provide no support for the presence of cellular pathology within Heschl's gyrus in schizophrenia.

Transgene dispersal through pollen.

Techniques used for the transfer of novel genes into host plant genomes have created new possibilities for crop improvement. The implementation of transgenic crop species into agriculture has introduced the possibility of transgene escape into the environment via pollen dispersal. Although the movement of pollen is a critical step in transgene escape, there is currently no system to monitor transgenic pollen movement under field conditions.

Oxidative stress and apoptosis in metal ion-induced carcinogenesis.

Epidemiological evidence suggests that exposure to certain metals causes carcinogenesis. The mechanisms of metal-induced carcinogenesis have been pursued in chemical, biochemical, cellular, and animal models. Significant evidence has accumulated that oxidative stress may be a common pathway in cellular responses to exposure to different metals.

Arsenite causes DNA damage in keratinocytes via generation of hydroxyl radicals.

Arsenic is an environmental and occupational toxin. Dermatologic toxicities due to arsenic exposure are well-documented and include basal cell and squamous cell carcinomas. However, the mechanism of arsenic-induced skin cancer is not well-understood.

Id2 is a primary partner for the E2-2 basic helix-loop-helix transcription factor in the human placenta.

We screened a term placental cDNA library by the yeast two-hybrid approach with Id2, a negative regulator of basic helix-loop-helix (bHLH) factors. Of the clones obtained, approximately one-third were the E2-2 bHLH transcription factor. Id2 and E2-2 were shown to interact in direct two-hybrid assays in yeast cells, as well as immunoprecipitation assays in mammalian cells.

Barriers to providing lung-protective ventilation to patients with acute lung injury.

Objective: No studies have explored the barriers to implementing lung-protective ventilation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Our objective was to identify barriers to using lung-protective ventilation in patients with ALI/ARDS.

Design: Survey with content analysis of open-ended responses.

Myelin transcription factor 1 (Myt1) modulates the proliferation and differentiation of oligodendrocyte lineage cells.

Myelin transcription factor 1 (Myt1) is a zinc finger DNA-binding protein that is expressed in neural progenitors and oligodendrocyte lineage cells. This study examines the role of Myt1 in oligodendrocyte lineage cells by overexpressing putative functional domains, a four-zinc finger DNA-binding region (4FMyt1) or a central protein-protein interaction domain (CDMyt1), without the predicted transcriptional activation domain. In the presence of mitogens, overexpression of 4FMyt1 inhibited proliferation of oligodendrocyte progenitors, but not cell types (astrocytes and NIH3T3 cells) lacking endogenous Myt1.

Effect of acute lung injury and acute respiratory distress syndrome on outcome in critically ill trauma patients.

Objective: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known to be associated with increased mortality and costs in trauma patients. We estimated the independent impact of these conditions on mortality and cost, beyond the severity of injury with which they are correlated.

Design: One-year prospective cohort.

Ethnic differences in cytotoxic T lymphocyte associated antigen 4 genotype associations with systemic sclerosis.

Objective: To determine the role of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) genetic polymorphisms in susceptibility to systemic sclerosis (SSc, scleroderma).

Methods: The study population consisted of 293 African American and Caucasian patients with SSc and matched controls. Subjects were genotyped for allelic determinants at 4 polymorphic sites: 3 in the promoter region (positions -318, -1661, -1722) and one in the first exon (position +49) of the CTLA-4 gene, using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods.