tbuckley/cabot-search huggingface dataset:
An Outbreak of Multidrug-Resistant &lt;EMPH TYPE="ITAL"&gt;Acinetobacter baumannii&lt;/EMPH&gt; Associated With Pulsatile Lavage Wound Treatment
Authors: Lisa L. Maragakis
Journal: JAMA (2004)

Pulsatile lavage is a high-pressure irrigation treatment used increasingly in a variety of health care settings to debride wounds. Infection control precautions are not routinely used during the procedure and are not included in pulsatile lavage equipment package labeling.To investigate an outbreak of multidrug-resistant Acinetobacter baumannii and to test the hypothesis that pulsatile lavage wound treatment was the mode of transmission for the organism.Outbreak case-control investigation including case identification, review of medical records, environmental cultures, and pulsed-field gel electrophoresis.A 1000-bed tertiary care hospital in Baltimore, Md, during September and October 2003.The investigation included 11 patients infected or colonized with multidrug-resistant A baumannii. Seven of these patients met the case definition for the case-control study and were compared with 28 controls randomly selected from a list of inpatients without multidrug-resistant A baumannii who had a wound care consultation.Infection or colonization with multidrug-resistant A baumannii.Eleven patients had cultures that grew multidrug-resistant A baumannii during the outbreak period. Of the 10 health care-associated cases, 8 had received pulsatile lavage treatment. One strain of multidrug-resistant A baumannii was recovered from all 6 pulsatile lavage patients who had isolates available for pulsed-field gel electrophoresis analysis and from multiple surfaces in the wound care area. Six of 7 cases (86%) were treated with pulsatile lavage vs 4 of 28 controls (14%) (odds ratio, 36; 95% confidence interval, 2.8-1721; P<.001). These results confirm that pulsatile lavage was a significant risk factor for acquisition of multidrug-resistant A baumannii.Transmission was apparently caused by dissemination of multidrug-resistant A baumannii during the pulsatile lavage procedure, resulting in environmental contamination. Appropriate infection control precautions should be used during pulsatile lavage therapy and should be included in pulsatile lavage equipment labeling.
Susceptibility of Various Strains of Mice to Urethan-Induced Lung Tumors and Depressed Natural Killer Cell Activity&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: E Gorelik, R B Herberman
Journal: JNCI Journal of the National Cancer Institute (1981)

Inbred A/J, CBA/J, and C57BL/6 mice at age 7-8 weeks were inoculated with 1 mg urethan/g body weight. Three months later, 13.2, 1.8, and 0.1 tumors per lung were found in these mice, respectively. Cytotoxicity by spleen cells of normal and urethan-treated mice was analyzed in a 4-hour 51Cr release assay against YAC-1 cells. During the first 2 weeks after treatment, urethan strongly suppressed the cytotoxicity by spleen cells of A/J mice but had relatively little effect on the reactivity of spleen cells of CBA/J mice. Natural killer (NK) activity was not suppressed in urethan-treated C57BL/6 mice. The effect of urethan on natural in vivo antitumor resistance in the lungs was studied by measurement of elimination from the lungs of [125I]-deoxyuridine-labeled YAC-1 cells. Urethan caused profound and sustained suppression of in vivo NK reactivity in the lungs of A/J mice, had only a transient effect on CBA/J mice, and had no detectable effect on C57BL/6 mice. The differences in the effects of urethan on the natural antitumor resistance in the three strains of mice could not be attributed to a generally greater susceptibility of A/J mice to inhibition of NK activity, since cyclophosphamide (0.15 mg/g) equally suppressed the clearance from the lungs of the radiolabeled tumor cells in A/J, CBA/J, and C57BL/6 mice. These results indicate a positive correlation between susceptibility of A/J, CBA/J, and C57BL/6 mice to urethan-induced lung carcinogenesis and inhibition of in vitro and in vivo natural cell-mediated cytotoxicities and support the hypothesis that NK cells play a role in resistance to urethan-induced lung carcinogenesis.
APOE4 enhances age-dependent decline in cognitive function by down-regulating an NMDA receptor pathway in EFAD-Tg mice
Authors: De-shan Liu, Xiao-dong Pan, Jing Zhang, Hui Shen, Nicole C Collins, Arron M Cole, Kevin P Koster, Manel Ben Aissa, Xiao-man Dai, Meng Zhou, Leon M Tai, Yuan-gui Zhu, Mary Jo LaDu, Xiao-chun Chen
Journal: Molecular Neurodegeneration (2015)

Alzheimer’s disease (AD) causes progressive loss of memory and cognition, exacerbated by APOE4, the greatest genetic risk factor for AD. One proposed mechanism for apolipoprotein E (apoE) effects on cognition is via NMDAR-dependent signaling. APOE genotype-specific effects on this pathway were dissected using EFAD-transgenic (Tg) mice (5xFAD mice, that over-express human amyloid-beta (Aβ) via 5 familial-AD (FAD) mutations, and express human apoE), and 5xFAD/APOE-knockout (KO) mice. Previous data from EFAD-Tg mice demonstrate age-dependent (2-6 months), apoE-specific effects on the development of Aβ pathology. This study tests the hypothesis that apoE4 impairs cognition via modulation of NMDAR-dependent signaling, specifically via a loss of function by comparison of E4FAD mice with 5xFAD/APOE-KO mice, E3FAD and E2FAD mice. Using female E2FAD, E3FAD, E4FAD and 5xFAD/APOE-KO mice aged 2-, 4-, and 6-months, the Y-maze and Morris water maze behavioral tests were combined with synaptic protein levels as markers of synaptic viability. The results demonstrate a greater age-induced deficit in cognition and reduction in PSD95, drebrin and NMDAR subunits in the E4FAD and 5xFAD/APOE-KO mice compared with E2FAD and E3FAD mice, consistent with an apoE4 loss of function. Interestingly, for NMDAR-mediated signaling, the levels of p-CaMK-II followed this same apoE-specific pattern as cognition, while the levels of p-CREB and BDNF demonstrate an apoE4 toxic gain of function: E2FAD > E3FAD > 5xFAD/APOE-KO > E4FAD. These findings suggest that compared with E2FAD and E3FAD, E4FAD and 5xFAD/APOE-KO mice exhibit enhanced age-induced reductions in cognition and key synaptic proteins via down-regulation of an NMDAR signaling pathway, consistent with an apoE4 loss of function. However, levels of p-CREB and BDNF, signaling factors common to multiple pathways, suggest a gain of toxic function. Publications in this field present contradictory results as to whether APOE4 imparts a loss or gain of function. As with the results reported herein, the overall effect of APOE4 on a given CNS-specific measure will be the product of multiple overlapping mechanisms. Thus, caution remains critical in determining whether APOE gene inactivation or therapies that correct the loss of positive function related to apoE4, are the appropriate therapeutic response.
Current Development of Clinical Inhibitors of Poly(ADP-Ribose) Polymerase in Oncology
Authors: Kapila Ratnam, Jennifer A. Low
Journal: Clinical Cancer Research (2007)

Abstract Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that signals the presence of DNA damage by catalyzing the addition of ADP-ribose units to DNA, histones, and various DNA repair enzymes and by facilitating DNA repair. PARP has been gaining increasing interest as a therapeutic target for many diseases and especially for cancer. Inhibition of PARP potentiates the activity of DNA-damaging agents, such as alkylators, platinums, topoisomerase inhibitors, and radiation in in vitro and in vivo models. In addition, tumors with DNA repair defects, such as those arising from patients with BRCA mutations, may be more sensitive to PARP inhibition. At least five different companies have now initiated oncology clinical trials with PARP inhibitors, ranging in stage from phase 0 to phase 2. This review summarizes the preclinical and clinical data currently available for these agents and some of the challenges facing the clinical development of these agents.
Rapid Creation of Forward-Genetics Tools for C. briggsae Using TALENs: Lessons for Nonmodel Organisms
Authors: Qing Wei, Yongquan Shen, Xiangmei Chen, Yelena Shifman, Ronald E. Ellis
Journal: Molecular Biology and Evolution (2013)

Although evolutionary studies of gene function often rely on RNA interference, the ideal approach would use reverse genetics to create null mutations for cross-species comparisons and forward genetics to identify novel genes in each species. We have used transcription activator-like effector nucleases (TALENs) to facilitate both approaches in Caenorhabditis nematodes. First, by combining golden gate cloning and TALEN technology, we can induce frameshifting mutations in any gene. Second, by combining this approach with bioinformatics we can predict and create the resources needed for forward genetic analysis in species like Caenorhabditis briggsae. Although developing genetic model organisms used to require years to isolate marker mutations, balancers, and tools, with TALENs, these reagents can now be produced in months. Furthermore, the analysis of nonsense mutants in related model organisms allows a directed approach for making these markers and tools. When used together, these methods could simplify the adaptation of other organisms for forward and reverse genetics.
International Union of Pharmacology. LXIX. Status of the Calcitonin Gene-Related Peptide Subtype 2 Receptor
Authors: Debbie L. Hay, David R. Poyner, Remi Quirion
Journal: Pharmacological Reviews (2008)

Historically, calcitonin gene-related peptide (CGRP) receptors have been divided into two classes, CGRP<sub>1</sub> and CGRP<sub>2</sub>. After the cloning of calcitonin receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs), it became clear that the CGRP<sub>1</sub> receptor was a complex between CLR and RAMP1. It is now apparent that the CGRP<sub>2</sub> receptor phenotype is the result of CGRP acting at receptors for amylin and adrenomedullin. Accordingly, the term "CGRP<sub>2</sub>" receptor should no longer be used, and the "CGRP<sub>1</sub>" receptor should be known as the "CGRP" receptor.
GI Stromal Tumors: 15 Years of Lessons From a Rare Cancer
Authors: Angela Cioffi, Robert G. Maki
Journal: Journal of Clinical Oncology (2015)

A confluence of factors, most prominently the recognition of GI stromal tumor (GIST) as a specific sarcoma subtype and the availability of imatinib, led to the "Big Bang" of GIST therapy (ie, the successful treatment of the first patient with GIST with imatinib in 2000). The trail blazed by imatinib for chronic myelogenous leukemia and GIST has become a desired route to regulatory approval of an increasing number of oral kinase inhibitors and other novel therapeutics. In this review, the status of GIST management before and after GIST's "Big Bang" and new steps being taken to further improve on therapy are reviewed.
Trends in Cancer Mortality in 15 Industrialized Countries, 1969-1986
Authors: D. G. Hoel, D. L. Davis, A. B. Miller, E. J. Sondik, A. J. Swerdlow
Journal: JNCI Journal of the National Cancer Institute (1992)

Assessing trends in cancer provides a means for gauging progress against the disease, estimating future demands for care and treatment, and suggesting clues about shifting causal factors that may account for the more recent changes.This study was designed to evaluate trends in the major sites of cancer associated with high mortality rates in 15 industrialized countries. To highlight differences among regions, we grouped these countries into six geographic areas: United States, Eastern Europe, Western Europe, East Asia, Oceania, and Nordic countries. In addition, cancer mortality trends in these regions were compared with incidence patterns in the United States.Data provided by the World Health Organization were used to evaluate age-specific mortality trends from 1969 through 1986 for lung, breast, prostate, stomach, and colorectal cancers and for all other sites considered as a group. We also assembled and analyzed data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for the same sites and age groups from 1973 through 1986.Over the period 1969 through 1986, recorded cancer mortality in persons aged 45 years and older in the six regions studied has increased for lung, breast, and prostate cancers in most age groups, while the decline in stomach cancer mortality is substantial. The increase in lung cancer deaths in men aged 45-54 years has slowed greatly or reversed in all areas except Eastern Europe and East Asia. Trends for intestinal cancer vary by age and region. For all other sites considered as a group, increases have occurred for persons older than 64 years in most regions. In Eastern Europe, there are disturbingly high rates and rapid increases for several of the major forms of cancer in persons aged 45-54 years. In general, trends for cancer incidence in the United States parallel those for mortality. For intestinal cancer, however, incidence has increased while mortality has declined.The trends we report cannot be explained solely by changes in cigarette smoking or aging. Other causes of changes in cancer incidence and mortality need to be determined.The increasing and decreasing trends in mortality from and incidence of cancer that we found are important for health care planning and may also suggest opportunities for research in cancer prevention.
COMPARISON OF ECCENTRIC HAMSTRING STRENGTH AND INJURY RATES BETWEEN PROFESSIONAL AND SEMI-PROFESSIONAL AUSTRALIAN FOOTBALLERS
Authors: S Duhig
Journal: British Journal of Sports Medicine (2014)

Background Hamstring strain injuries (HSI) are the most common injury within Australian football with reports showing no decrease in incidence over two decades. Objective To compare differences of HSIs and eccentric hamstring strength, using a field-based testing device, between elite and sub-elite Australian footballers. Design A prospective cohort study. Setting 2 football teams were involved in the study with data collected at their respective club. The first team competes in the elite Australian Football League (AFL) whilst the other competes in the sub-elite North East Australian Football League (NEAFL). Participants 82 Australian footballers, 41 footballers from a sub-elite NEAFL team and 41 footballers from an elite AFL team participated in the study. Risk factor assessment The teams were tested during their preseason, with each footballer performing 3 repetitions of the Nordic hamstring exercise on a field-based testing device. Between limb imbalance and absolute strength were the independent variables. Main outcome measurements The dependent variable was the HSI rates, each team was required to record all injuries for the subsequent ‘home and away’ season. Results Although not statistically significant, e lite AFL players displayed slightly higher average peak torques for the left limb (+17.5N, P=.113) and right limb (+21.1N, P=.09). No difference was observed for between limb imbalance (P=.408) between elite and sub-elite players. However, elite players sustained 3 times more HSIs (9 vs. 3) and missed a greater number of games as a result (28 vs. 6). Conclusion Minimal differences were observed between strength and between limb strength imbalances, however, a 60% increase in HSIs was observed in the elite group. We propose that the strength levels displayed within the AFL and additional study is required to assess whether the elite level has higher physical demands and thus requiring greater strength.
Vitamin E Reduces the Uptake of Oxidized LDL by Inhibiting CD36 Scavenger Receptor Expression in Cultured Aortic Smooth Muscle Cells
Authors: Roberta Ricciarelli, Jean-Marc Zingg, Angelo Azzi
Journal: Circulation (2000)

Background —Vitamin E is well known as an antioxidant, and numerous studies suggest that it has a preventive role in atherosclerosis, although the mechanism of action still remains unclear. Methods and Results —The original aim of this study was to establish whether α-tocopherol (the most active form of vitamin E) acts at the earliest events on the cascade of atherosclerosis progression, that of oxidized LDL (oxLDL) uptake and foam-cell formation. We show here that the CD36 scavenger receptor (a specific receptor for oxLDL) is expressed in cultured human aortic smooth muscle cells (SMCs). Treatment of SMCs and HL-60 macrophages with α-tocopherol (50 μmol/L, a physiological concentration) downregulates CD36 expression by reducing its promoter activity. Furthermore, we find that α-tocopherol treatment of SMCs leads to a reduction of oxLDL uptake. Conclusions —This study indicates that CD36 is expressed in cultured human SMCs. In these cells, CD36 transports oxLDL into the cytosol. α-Tocopherol inhibits oxLDL uptake by a mechanism involving downregulation of CD36 mRNA and protein expression. Therefore, the beneficial effect of α-tocopherol against atherosclerosis can be explained, at least in part, by its effect of lowering the uptake of oxidized lipoproteins, with consequent reduction of foam cell formation.
Downregulation of c-MYC Protein Levels Contributes to Cancer Cell Survival under Dual Deficiency of Oxygen and Glucose
Authors: Hiroaki Okuyama, Hiroko Endo, Tamaki Akashika, Kikuya Kato, Masahiro Inoue
Journal: Cancer Research (2010)

The c-MYC protein participates in energy-consuming processes such as proliferation and ribosome biosynthesis, and its expression is often dysregulated in human cancers. Cancer cells distant from blood vessels in solid tumors are in short supply of oxygen and nutrition yet can adapt to the microenvironment and survive under metabolic stress. The role and regulation of c-MYC protein in the tumor microenvironment of limited energy sources are poorly understood. Here, we show that c-MYC protein levels in cancer cells are strikingly reduced in the area distant from the blood vessels in vivo and also under oxygen- and glucose-deprived conditions in vitro. The rapid reduction of c-MYC protein levels requires low levels of both oxygen and glucose, and under these conditions, downregulation is mainly achieved by enhanced degradation. Suppression of c-MYC protein levels by small hairpin RNA decreases the necrotic cell death induced by oxygen and glucose deprivation. Thus, the environmental milieu regulates c-MYC protein levels, and downregulation of c-MYC might be a strategy for cancer cells to survive under conditions of limited energy sources.
THE PURIFICATION AND PARTIAL CHARACTERIZATION OF SEVERAL FORMS OF HOG RENIN SUBSTRATE
Authors: Leonard T. Skeggs, Kenneth E. Lentz, Harry Hochstrasser, Joseph R. Kahn
Journal: The Journal of Experimental Medicine (1963)

Hog renin substrate has been separated into three major (A, B, and C) and two minor forms (D and E) by DEAE cellulose chromatography. Two of the major forms (B and C) have been further fractionated into two additional types (1 and 2) by countercurrent distribution. The purification of substrates A, C(1), and C(2) has been completed. Analysis shows that all three are glycoproteins with molecular weights of about 57,000, and have similar amino acid compositions. Differences exist in the sialic acid, glucosamine, and neutral hexose content, which may account for different physical properties. All the forms of the substrates are attacked by renin at similar rates, and appear to yield the same angiotensin I.
Antipsychotic Drug Use and Mortality in Older Adults with Dementia
Authors: Sudeep S. Gill, Susan E. Bronskill, Sharon-Lise T. Normand, Geoffrey M. Anderson, Kathy Sykora, Kelvin Lam, Chaim M. Bell, Philip E. Lee, Hadas D. Fischer, Nathan Herrmann, Jerry H. Gurwitz, Paula A. Rochon
Journal: Annals of Internal Medicine (2007)

Background: Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety. Objective: To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality. Design: Population-based, retrospective cohort study. Setting: Ontario, Canada. Patients: Older adults with dementia who were followed between 1 April 1997 and 31 March 2003. Measurements: The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Two pairwise comparisons were made: atypical versus no antipsychotic use and conventional versus atypical antipsychotic use. Groups were stratified by place of residence (community or long-term care). Propensity score matching was used to adjust for differences in baseline health status. Results: A total of 27 259 matched pairs were identified. New use of atypical antipsychotics was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling cohort (adjusted hazard ratio, 1.31 [95% CI, 1.02 to 1.70]; absolute risk difference, 0.2 percentage point) and the long-term care cohort (adjusted hazard ratio, 1.55 [CI, 1.15 to 2.07]; absolute risk difference, 1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal rates of censoring over time may have affected these results. Relative to atypical antipsychotic use, conventional antipsychotic use was associated with a higher risk for death at all time points. Sensitivity analysis revealed that unmeasured confounders that increase the risk for death could diminish or eliminate the observed associations. Limitations: Information on causes of death was not available. Many patients did not continue their initial treatments after 1 month of therapy. Unmeasured confounders could affect associations. Conclusions: Atypical antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia. The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics.