Reduced hippocampal functional connectivity in Alzheimer disease.

Objective: To determine if functional connectivity of the hippocampus is reduced in patients with Alzheimer disease.

Design: Functional connectivity magnetic resonance imaging was used to investigate coherence in the magnetic resonance signal between the hippocampus and all other regions of the brain.

Participants: Eight patients with probable Alzheimer disease and 8 healthy volunteers.

NF-kappaB activation as a key mechanism in ethanol-induced disruption of the F-actin cytoskeleton and monolayer barrier integrity in intestinal epithelium.

Intestinal barrier disruption has been implicated in several intestinal and systemic disorders including alcoholic liver disease (ALD). Using monolayers of intestinal (Caco-2) cells, we showed that ethanol (EtOH) disrupts the barrier integrity via destabilization of the cytoskeleton. Because proinflammatory conditions are associated with activation of NF-kappa B (NF-kappaB), we hypothesized that EtOH induces disruption of cytoskeletal assembly and barrier integrity by activating NF-kappaB.

DNA damage, superoxide, and mutant K-ras in human lung adenocarcinoma cells.

DNA single-strand breaks (quantitative comet assay) were assessed to indicate ongoing genetic instability in a panel of human lung adenocarcinoma cell lines. Of these, 19/20 showed more DNA damage than a nontransformed cell line from human peripheral lung epithelium, HPL1D. DNA damage was significantly greater in those derived from pleural effusates vs those from lymph node metastases.

Use of herbal preparations in the treatment of oxidant-mediated inflammatory disorders.

Complementary and alternative medicine (CAM) use has increased in popularity in recent years and herbal therapy alone is now a billion dollar market. For centuries herbs have been used as food and for medicinal purposes. Various herbs have been identified as possessing anti-inflammatory and antioxidative properties, and they are currently being used to treat inflammatory disorders as well as those caused by reactive oxygen species (ROS).

Reduced immunostaining for c-kit receptors in mucosal mast cells in inflammatory bowel disease.

Background And Aim: The deleterious effects of stress in inflammatory bowel disease (IBD) have been attributed to activation of the brain-gut axis (BGA) and its end effectors, mast cells (MC). We previously showed that cold pressor stress test (CPT) results in increased activation and degranulation (but not increased proliferation) of mucosal MC, mitochondrial damage to epithelial cells and mucosal protein oxidation in both healthy controls and IBD patients. These changes are more marked in IBD patients.

Role of Nrf2 in protection against intracerebral hemorrhage injury in mice.

Nrf2 is a key transcriptional factor for antioxidant response element (ARE)-regulated genes. While its beneficial role has been described for stroke, its contribution to intracerebral hemorrhage (ICH)-induced early brain injury remains to be determined. Using wild-type (WT) and Nrf2 knockout (Nrf2(-/-)) mice, the role of Nrf2 in ICH induced by intracerebral injection of collagenase was investigated.

Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: stress, intestinal hyperpermeability and inflammation.

Mast cells (MC) are pivotal elements in several physiological and immunological functions of the gastro-intestinal (GI) tract. MC translate the stress signals that has been transmitted through brain gut axis into release of proinflammatory mediators that can cause stimulation of nerve endings that could affect afferent nerve terminals and change their perception, affect intestinal motility, increase intestinal hyperpermeability and, in susceptible individuals, modulate the inflammation. Thus, it is not surprising that MC are an important element in the pathogenesis of inflammatory bowel disease and non inflammatory GI disorders such as IBS and mast cell enterocolitis.

Symmetric division of cancer stem cells--a key mechanism in tumor growth that should be targeted in future therapeutic approaches.

As cancer stem cells (SCs) drive tumor growth, it is only through the elimination of those cancer SCs that a pharmacologic cure can be attained. To study ways to develop drugs that target cancer SC, we investigated changes in cellular mechanisms and kinetics that occur in SC populations during colorectal cancer (CRC) development. We used computer modeling to determine which changes could give rise to exponential increases in both SC and non-SC populations in CRC.

Evidence for non-chemical, non-electrical intercellular signaling in intestinal epithelial cells.

Synchrony between mechanically separated biological systems is well known. We posed the question: can cells induce synchronous behavior in neighboring cells which are mechanically separated and which cannot communicate via chemical or electrical mechanisms. Caco-2 cell cultures were divided into three groups.

The VHA New England Medication Error Prevention Initiative as a model for long-term improvement collaboratives.

Background: Quality improvement collaboratives (QICs) are a widely applied strategy for implementing change in health care organizations. Alternative collaborative methodologies were compared to gain insight into the elements important for QIC success.

Methods: A modified version of a previously described QIC evaluation tool was used to assess the methods and characteristics of the Medication Error Prevention Initiative (MEPI) and to compare MEPI with two other long-term ongoing QICs--the Vermont-Oxford Network's Neonatal Intensive Care QIC and the Northern New England Cardiovascular Disease Study Group, and the shorter-term Breakthrough Series QICs of the Institute for Healthcare Improvement (IHI).

Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling.

Inflammatory bowel disease (IBD) affects more than 1 million Americans with more than 30,000 new cases diagnosed each year. IBD increases patient morbidity and susceptibility to colorectal cancer, yet its etiology remains unknown. Current models identify two key determinants of IBD pathogenesis: hyperpermeability of the gut epithelial barrier to bacterial products and an abnormal immune response to these products.

Transcriptional interference among the murine beta-like globin genes.

Mammalian beta-globin loci contain multiple genes that are activated at different developmental stages. Studies have suggested that the transcription of one gene in a locus can influence the expression of the other locus genes. The prevalent model to explain this transcriptional interference is that all potentially active genes compete for locus control region (LCR) activity.

Effects of selenium supplementation on expression of glutathione peroxidase isoforms in cultured human lung adenocarcinoma cell lines.

Selenium is an essential nutrient, a component of several anti-oxidant enzymes, and a possible factor in cancer risk, including lung cancer. We determined the subtoxic range of selenium concentration (as sodium selenite) required to increase and maintain the expression of anti-oxidant selenoproteins gluthathione peroxidases GPX1 and GPX4 at a constant level in cultures of human lung adenocarcinoma cell lines (H460, H1703 and H1944) and in HPL1D, a non-transformed lung epithelial cell line. Selenium dose-dependently increased GPX1 protein expression 1.

Multidetector computed tomography pulmonary angiogram in the assessment of myocardial infarction.

Purpose: The objective of this study is to evaluate the effectiveness of nonelectrocardiographic gated multidetector computed tomography (MDCT) performed for the purpose of assessment of pulmonary embolus in the evaluation of myocardial infarction (MI).

Methods: We retrospectively evaluated 147 consecutive patients who had a computed tomography angiogram for pulmonary embolus on a 16-detector MDCT. Of this cohort, we determined 11 patients to have acute MIs based on electrocardiogram, positive troponin levels, and clinical findings and history.

Absence of the apolipoprotein E epsilon4 allele is associated with working memory impairment in Parkinson's disease.

The apolipoprotein E (APOE) epsilon4 allele has been associated with an increased risk of Alzheimer's disease (AD) and weaker episodic memory among elderly. Although this APOE allele has been linked to earlier onset of Parkinson's disease (PD), an association with dementia in PD has been only inconsistently demonstrated. Given the heterogeneity of cognitive impairment patterns in PD, this study sought to determine whether an association exists between APOE genotype and specific cognitive deficits in PD.

Resolution of common dietary sugars from probe sugars for test of intestinal permeability using capillary column gas chromatography.

Background: The most widely accepted method for the evaluation of intestinal barrier integrity is the measurement of the permeation of sugar probes following an oral test dose of sugars. The most-widely used sugar probes are sucrose, lactulose, mannitol and sucralose. Measuring these sugars using a sensitive gas chromatographic (GC) method, we noticed interference on the area of the lactulose and mannitol peaks.

PKCdelta clustering at the leading edge and mediating growth factor-enhanced, but not ecm-initiated, dermal fibroblast migration.

We have previously shown that the immobilized extracellular matrices (ECMs) initiate cell migration and soluble growth factors (GFs) further enhance ECM-initiated cell migration. GFs alone cannot initiate cell migration. To further investigate the specificity of the two signaling mechanisms, we focused on the protein kinase C (PKC) family genes in primary human dermal fibroblasts (DFs).

Mechanical thrombectomy following intravenous thrombolysis in the treatment of acute stroke.

Background: The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment.

Objectives: To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study.

Deletion of the core region of 5' HS2 of the mouse beta-globin locus control region reveals a distinct effect in comparison with human beta-globin transgenes.

The beta-globin locus control region (LCR) is a large DNA element that is required for high-level expression of beta-like globin genes from the endogenous mouse locus or in transgenic mice carrying the human beta-globin locus. The LCR encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors. These HSs each contain a core of a few hundred base pairs (bp) that has most of the functional activity and exhibits high interspecies sequence homology.

Do men believe that physically attractive women are more healthy and capable of having children?

The purpose of this research was to test the hypothesis that men view physical attractiveness as an index of a woman's health and her capacity to have children. 21 men and 26 women from an introductory psychology course were shown photographs from 1972 of men and women college students, judged in 2002 to be attractive or unattractive. Subjects were asked to rate the photographed individuals' current health, the probability that they were married, the probability that they had children, and whether they had reproductive problems.

Quality of life in Essential Tremor Questionnaire (QUEST): development and initial validation.

Background/objective: Essential tremor (ET) can diminish functioning and quality of life (QOL) but generic QOL measures may be relatively insensitive to ET and its therapies. We sought to develop an ET-specific measure that might be more sensitive, acceptable to patients, relatively brief, and easily used.

Design/methods: A sample of 200 patients (average age 70 years, range 30-91; average disease duration 15 years) rated the extent to which tremor impacts a function or state, tremor severity in various body parts, perceived health, and overall QOL.

Heightened responses to stressors in patients with inflammatory bowel disease.

Objectives: Several studies suggest that stressful situations (stressors) worsen the course of inflammatory bowel disease (IBD), but the mechanism is not known. Based on several lines of evidence, we hypothesized that psychosocial stress activates the brain-gut axis (BGA) and mucosal mast cells (MC), and activated MC produce proinflammatory cytokines. To test this hypothesis, we determined whether stressor-induced activation of BGA is exaggerated in IBD patients.