Genetic bases of estrogen-induced tumorigenesis in the rat: mapping of loci controlling susceptibility to mammary cancer in a Brown Norway x ACI intercross.

Exposure to estrogens is associated with an increased risk of breast cancer. Our laboratory has shown that the ACI rat is uniquely susceptible to 17beta-estradiol (E2)-induced mammary cancer. We previously mapped two loci, Emca1 and Emca2 (estrogen-induced mammary cancer), that act independently to determine susceptibility to E2-induced mammary cancer in crosses between the susceptible ACI rat strain and the genetically related, but resistant, Copenhagen (COP) rat strain.

Genetic bases of renal agenesis in the ACI rat: mapping of Renag1 to chromosome 14.

Unilateral renal agenesis (URA) is a common developmental defect in humans, occurring at a frequency of approximately 1 in 500-1,000 births. Several genetic syndromes include bilateral or unilateral renal agenesis as an associated phenotype. However, URA frequently occurs in individuals not afflicted by these syndromes and is often asymptomatic.

Substrate mineralization stimulates focal adhesion contact redistribution and cell motility of bone marrow stromal cells.

Understanding the mechanisms of substrate based control of cell function is critical to the design of biomaterials. Cells interact with their extracellular matrix through cell adhesion contacts. We have previously described the self assembly of bone-like mineral onto an organic template and have shown that these biomimetic surfaces lead to an increased volume fraction of bone regenerated in vivo.

Nurses' reflections on pain management in a nursing home setting.

Achieving optimal and safe pain-management practices in the nursing home setting continues to challenge administrators, nurses, physicians, and other health care providers. Several factors in nursing home settings complicate the conduct of clinical process improvement research. The purpose of this qualitative study was to explore the perceptions of a sample of Colorado nursing home staff who participated in a study to develop and evaluate a multifaceted pain-management intervention.

Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: Evidence for disease-associated changes.

Abnormalities of the anterior cingulate cortex have previously been described in schizophrenia, major depressive disorder and bipolar disorder. In this study 2-DE was performed followed by mass spectrometric sequencing to identify disease-specific protein changes within the anterior cingulate cortex in these psychiatric disorders. The 2-DE system comprised IPGs 4-7 and 6-9 in the first, IEF dimension and SDS-PAGE in the second dimension.

Activation of MAPKs in thrombin-stimulated ventricular myocytes is dependent on Ca2+-independent PLA2.

Thrombin stimulation of isolated rabbit ventricular myocytes activates a membrane-associated, Ca(2+)-independent PLA(2) (iPLA(2)) that selectively hydrolyzes plasmalogen phospholipids and results in increased production of arachidonic acid and lysoplasmenylcholine. To determine whether MAPK regulates myocardial iPLA(2) activity, we isolated ventricular myocytes from rabbit heart by collagenase digestion and pretreated them with MAPK inhibitors before stimulating them with thrombin. Pretreatment with PD-98059 to inhibit p42/44 MAPK or SB-203580 to inhibit p38 MAPK had no significant effect on thrombin-stimulated, membrane-associated iPLA(2) activity.

Linking nursing home working conditions to organizational performance.

Exploring selected working conditions and performance in nursing homes suggests that high and low performers can be determined based on both quantitative and qualitative findings.

Genetic mapping of Eutr1, a locus controlling E2-induced pyometritis in the Brown Norway rat, to RNO5.

In certain rat strains, chronic estrogen administration can lead to pyometritis, an inflammation of the uterus accompanied by infection and the accumulation of intraluminal pus. In this article, we report that the Brown Norway (BN) rat is highly susceptible to pyometritis induced by 17beta-estradiol (E2). The susceptibility of the BN rat to E2-induced pyometritis appears to segregate as a recessive trait in crosses to the resistant August x Copenhagen Irish (ACI) strain.

Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its phosphorylation and persistent activation.

Transcription factor NF-kappaB governs the expression of multiple genes involved in cell growth, immunity, and inflammation. Nuclear translocation of NF-kappaB is regulated from the cytoplasm by IkappaB kinase-beta (IKKbeta), which earmarks inhibitors of NF-kappaB for polyubiquination and proteasome-mediated degradation. Activation of IKKbeta is contingent upon signal-induced phosphorylation of its T loop at Ser-177/Ser-181.

Perceptions of the role of the hospital palliative care team.

Aim: The aim of this study was to understand staff perceptions of the role of the hospital palliative care team and to identify knowledge and confidence levels of general staff caring for patients with palliative care needs.

Method: A survey questionnaire tool was used with a response rate of 51 per cent. Participants included nurses, health care assistants and doctors.

Positive regulation of IkappaB kinase signaling by protein serine/threonine phosphatase 2A.

Transcription factor NF-kappaB plays a key regulatory role in the cellular response to pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF). In the absence of TNF, NF-kappaB is sequestered in the cytoplasm by inhibitory IkappaB proteins. Phosphorylation of IkappaBby the beta-catalytic subunit of IKK, a multicomponent IkappaB kinase, targets the inhibitor for proteolytic destruction and facilitates nuclear translocation of NF-kappaB.

The role of proteomics in investigating psychiatric disorders.

Proteomics is the study of protein expression and function on a genome-wide scale and its application in psychiatric research is relatively new. As protein expression is the mediator of genetic vulnerabilities, it is critical that this area is explored further to increase our understanding of psychiatric disease and reveal potential new treatments.

Genetic bases of estrogen-induced pituitary tumorigenesis: identification of genetic loci determining estrogen-induced pituitary growth in reciprocal crosses between the ACI and Copenhagen rat strains.

Estrogens stimulate proliferation and enhance survival of the prolactin (PRL)-producing lactotroph of the anterior pituitary gland and induce development of PRL-producing pituitary tumors in certain inbred rat strains but not others. The goal of this study was to elucidate the genetic bases of estrogen-induced pituitary tumorigenesis in reciprocal intercrosses between the genetically related ACI and Copenhagen (COP) rat strains. Following 12 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), pituitary mass, an accurate surrogate marker of absolute lactotroph number, was increased 10.

Genetic determination of susceptibility to estrogen-induced mammary cancer in the ACI rat: mapping of Emca1 and Emca2 to chromosomes 5 and 18.

Hormonal, genetic, and environmental factors play major roles in the complex etiology of breast cancer. When treated continuously with 17beta-estradiol (E2), the ACI rat exhibits a genetically conferred propensity to develop mammary cancer. The susceptibility of the ACI rat to E2-induced mammary cancer appears to segregate as an incompletely dominant trait in crosses to the resistant Copenhagen (COP) strain.

Orthostatic modification of ventilatory dynamic response to carbon dioxide perturbations.

In order to determine whether changes in ventilatory control contribute to the observed decrease in arterial partial pressure of carbon dioxide (PaCO(2)) during head up tilt, we assessed ventilatory dynamic sensitivity to changes in PaCO(2) during supine and 70 degrees passive head up tilt. In 24 adult normals, we stimulated the ventilatory control system by switching inspired CO(2) between room air and room air+5% CO(2) in a pseudo random binary sequence. A Box-Jenkins model was used to compute ventilatory response to CO(2).

Pain assessment practices with nursing home residents.

The purpose of this research was to describe the kinds of pain assessments nursing home staff use with nursing home residents and the characteristics and behaviors of residents that staff consider as they assess pain. Twenty-one focus groups were held in 12 nursing homes. Nurses and other nursing home staff attended the focus groups.

Differential responses in three thalamic nuclei in moderately disabled, severely disabled and vegetative patients after blunt head injury.

In vivo imaging techniques have indicated for many years that there is loss of white matter after human traumatic brain injury (TBI) and that the loss is inversely related to cognitive outcome. However, correlated, quantitative evidence for loss of neurons from either the cerebral cortex or the diencephalon is largely lacking. There is some evidence in models of TBI that neuronal loss occurs within the thalamus, but no systematic studies of such loss have been undertaken in the thalamus of humans after blunt head injury.

Optimization of the first dimension for separation by two-dimensional gel electrophoresis of basic proteins from human brain tissue.

A major cause of poor resolution in the alkaline pH range of two-dimensional electrophoresis (2-DE) gels is unsatisfactory separation of basic proteins in the first dimension. We have compared methods for the separation of basic proteins in the isoelectric focusing dimension of human brain proteins. The combined use of anodic cup-loading and the hydroxyethyldisulphide containing solution (DeStreak) produced better resolution in both analytical and micropreparative protein loaded 2-DE gels than the other methods investigated.

Phase II study of low-dose topotecan in myelodysplastic syndromes: a Hoosier Oncology Group (HOG) study.

Topotecan has demonstrable activity in high-risk MDS and CMMoL. However, the significant toxicity of topotecan administered at a dose of 2mg/m2 i.v.

The role of certified nursing assistants in nursing homes.

Unlabelled: OBJECTIVE Pilot study to examine the experiences of the certified nursing assistants (CNAs) in Colorado nursing homes.

Background Data: CNAs provide 80% to 90% of the care to residents in nursing homes. Their reported turnover rate is as high as 400% in some studies, and the potential pool of CNAs is dwindling.

Signal-induced ubiquitination of I kappaB Kinase-beta.

Initiation of the genetic programs for inflammation and immunity involves nuclear mobilization of transcription factor NF-kappaB. This signal-dependent process is controlled in part by the beta-catalytic subunit of IkappaB kinase (IKKbeta), which marks IkappaBalpha and other cytoplasmic inhibitors of NF-kappaB for proteolytic destruction. The catalytic activity of IKKbeta is stimulated by pathologic and physiologic inducers of NF-kappaB, such as the Tax oncoprotein and proinflammatory cytokines.

Protein kinase Calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes.

NF-kappaB is an ubiquitous transcription factor that is a key in the regulation of the immune response and inflammation. T-cell receptor (TCR) cross-linking leads to NF-kappaB activation, an IkappaB kinase (IKK)-dependent process. However, the upstream kinases that regulate IKK activity following TCR activation remain to be fully characterized.

Rat strain specific attenuation of estrogen action in the anterior pituitary gland by dietary energy restriction.

The purpose of this study was to compare the effects of a 40% restriction of dietary energy consumption, relative to that consumed by rats allowed to feed ad libitum, on the ability of 17beta-estradiol (E2) to induce pituitary tumorigenesis in two inbred rat strains, ACI and Copenhagen (COP), which are very closely related genetically. Ovary-intact ACI and COP rats were fed either a control or an energy-restricted diet beginning at 8 wk of age. Continuous treatment with E2, released from subcutaneous Silastic tubing implants, was initiated at 9 wk of age and the animals were killed 12 wk later.

In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase.

Transcription factor NF-kappaB plays a pivotal regulatory role in the genetic programs for cell cycle progression and inflammation. Nuclear translocation of NF-kappaB is controlled by an inducible protein kinase called IKK, which earmarks cytoplasmic inhibitors of NF-kappaB for proteolytic destruction. IKK contains two structurally related catalytic subunits termed IKKalpha and IKKbeta as well as a noncatalytic subunit called IKKgamma/NEMO.