tbuckley/cabot-search huggingface dataset:
Histone acetylation may suppress human glioma cell proliferation when p21WAF/Cip1 and gelsolin are induced
Authors: Hideki Kamitani, Seijiro Taniura, Kenji Watanabe, Makoto Sakamoto, Takashi Watanabe, Thomas Eling
Journal: Neuro-Oncology (2002)

Histone deacetylase inhibitors that increase histone acetylation on transformed cells are being investigated as unique anticancer drugs. The aim of this investigation was to evaluate an antiproliferative activity of the histone deacetylase inhibitors sodium butyrate (NaBT) and trichostatin A on 5 glioma cell lines, T98G, A172, U-87 MG, U-118 MG, and U-373 MG, with the examination of the altered expressions in p21 and gelsolin genes. Treatment with 5-mM NaBT and 40 ng/ml trichostatin A for 48 h caused more than a 50% growth inhibition in 5 cell lines as measured by cell proliferation assays. An increase in histone acetylation was confirmed in each cell line. After treatment with 5 mM NaBT, T98G, A172, and U118 cells undergo apoptosis as indicated by DNA ladder formation. Treatment with NaBT and trichostatin A also decreased DNA synthesis as examined by the fluorescence-activated cell sorting analysis in T98G and U87 cells. In addition to the suppression of cell growth, the up regulation of p21 and gelsolin expression was observed after treatment with NaBT, especially in T98G cells. Maximum expression of p21 and gelsolin was observed within 24 h after treatment. Results from our in vitro studies indicate that the treatment of human glioma cells with one of the histone deacetylase inhibitors suppresses cell growth with decreasing DNA synthesis and stimulates apoptosis, and that associated molecular mechanisms responsible for these effects include increased histone acetylation as well as enhanced expression of p21 and gelsolin.
Biceps femoris and semitendinosus—teammates or competitors? New insights into hamstring injury mechanisms in male football players: a muscle functional MRI study
Authors: Joke Schuermans, Damien Van Tiggelen, Lieven Danneels, Erik Witvrouw
Journal: British Journal of Sports Medicine (2014)

Background The hamstring injury mechanism was assessed by investigating the exercise-related metabolic activity characteristics of the hamstring muscles using a muscle functional MRI (mfMRI) protocol. Methods 27 healthy male football players and 27 football players with a history of hamstring injuries (recovered and playing fully) underwent standardised mfMR Imaging. The mfMRI protocol consisted of a resting scan, a strenuous bilateral eccentric hamstring exercise and a postexercise scan. The exercise-related T2 increase or the signal intensity shift between both scans was used to detect differences in metabolic activation characteristics (1) between the different hamstring muscle bellies and (2) between the injury group and the control group. Results A more symmetrical muscle recruitment pattern corresponding to a less economic hamstring muscle activation was demonstrated in the formerly injured group (p&lt;0.05). The injured group also demonstrated a significantly lower strength endurance capacity during the eccentric hamstring exercise. Conclusions These findings suggest that the vulnerability of the hamstring muscles to football-related injury is related to the complexity and close coherence in the synergistic muscle recruitment of the biceps femoris and the semitendinosus. Discrete differences in neuromuscular coordination and activity distribution, with the biceps femoris partly having to compensate for the lack of endurance capacity of the semitendinosus, probably increase the hamstring injury risk.
Bone Magnesium Pools in Uremia
Authors: Allen C. Alfrey, Nancy L. Miller
Journal: Journal of Clinical Investigation (1973)

Bone magnesium pools were studied in vitro in bone specimens obtained from control subjects, from patients with chronic renal failure before and after renal transplantation, and in a patient with chronic hypomagnesemia. 30% of bone magnesium is in a surface limited pool present either within the hydration shell or else on the crystal surface. The larger fraction of bone magnesium was shown not to be associated with bone matrix but rather to be an integral part of the bone crystal. With incineration this pool was mobilized at the same temperature that sudden enlargement of bone crystal size occurred. It is suggested that heating causes surface calcium to displace magnesium from the apatite crystal. Both magnesium pools are increased in patients with chronic renal failure. The major factor determining magnesium concentration in bone would appear to be the serum magnesium level. Following renal transplantation, in association with the fall in serum magnesium, surface magnesium was within the normal range; whereas, residual magnesium was not different from the other urenic bones. Both magnesium pools were significantly reduced in a patient with chronic hypomagnesemia. The in vitro studies would suggest that surface magnesium should rapidly reflect changes in serum magnesium levels, whereas, the deeper magnesium pool is probably deposited at time of bone formation with mobilization being dependent upon the resorptive processes. Since magnesium can influence crystal size and stability it seems possible that excess bone magnesium may play a role in renal osteodystrophy.
mRNA-Mediated Intron Losses: Evidence from Extraordinarily Large Exons
Authors: Deng-Ke Niu, Wen-Ru Hou, Shu-Wei Li
Journal: Molecular Biology and Evolution (2005)

Multicellular eukaryotes that have high intron density have their introns almost evenly distributed within genes, but unicellular eukaryotes that are generally intron poor have their introns asymmetrically distributed toward the 5' ends of genes. This was explained by homologous recombination of genomic DNA with the cDNA reverse transcribed from the 3' polyadenylated tail of spliced mRNA. This paper is to study whether mRNA-mediated intron losses have ever occurred in multicellular eukaryotes. If intron losses were mRNA-mediated, adjacent introns should be commonly lost together. A direct result is fusion of several previously adjacent exons and producing a large exon. We found that extraordinarily large exons (ELEs) are common not only in unicellular eukaryotes but also in multicellular eukaryotes. The percentage of genes having ELEs is negatively correlated with intron abundance. In addition, the number of lost introns estimated from the relative lengths of ELEs is negatively correlated with the number of extant introns. These results support mRNA-mediated intron losses in all eukaryotes. Moreover, we found that the ELEs of intron-common eukaryotes (with more than 0.5 intron per gene on average) are not only located at 3' ends but also at 5' ends and the middle of genes. This is contrary to what would be expected if the involved cDNAs were reverse transcribed from the 3' polyadenosine ends. A remarkable difference in intron distribution was revealed between intron-rare eukaryotes and intron-common eukaryotes. The intron-rare eukaryotes show very strong 5'-biased intron distribution, whereas the intron-common eukaryotes display even intron distribution or only weak 5'-biased distribution. We suspected that intron losses from 3' end of genes may be limited in intron-rare eukaryotes. The intron losses from intron-common eukaryotes should have other priming mechanism, like self-primed reverse transcription.
Lipopolysaccharide Interaction with Cell Surface Toll-like Receptor 4-MD-2
Authors: Sachiko Akashi, Shin-ichiroh Saitoh, Yasutaka Wakabayashi, Takane Kikuchi, Noriaki Takamura, Yoshinori Nagai, Yutaka Kusumoto, Koichi Fukase, Shoichi Kusumoto, Yoshiyuki Adachi, Atsushi Kosugi, Kensuke Miyake
Journal: The Journal of Experimental Medicine (2003)

Toll-like receptors (TLRs) are innate recognition molecules for microbial products, but their direct interactions with corresponding ligands remain unclarified. LPS, a membrane constituent of gram-negative bacteria, is the best-studied TLR ligand and is recognized by TLR4 and MD-2, a molecule associated with the extracellular domain of TLR4. Although TLR4-MD-2 recognizes LPS, little is known about the physical interaction between LPS and TLR4-MD-2. Here, we demonstrate cell surface LPS–TLR4-MD-2 complexes. CD14 greatly enhances the formation of LPS–TLR4-MD-2 complexes, but is not coprecipitated with LPS–TLR4-MD-2 complexes, suggesting a role for CD14 in LPS loading onto TLR4-MD-2 but not in the interaction itself between LPS and TLR4-MD-2. A tentative dissociation constant (Kd) for LPS–TLR4-MD-2 complexes was ∼3 nM, which is ∼10–20 times lower than the reported Kd for LPS–MD-2 or LPS–CD14. The presence of detergent disrupts LPS interaction with CD14 but not with TLR4-MD-2. E5531, a lipid A antagonist developed for therapeutic intervention of endotoxin shock, blocks LPS interaction with TLR4-MD-2 at a concentration 100 times lower than that required for blocking LPS interaction with CD14. These results reveal direct LPS interaction with cell surface TLR4-MD-2 that is distinct from that with MD-2 or CD14.
Liver lesion associated with gynaecological pathology
Authors: R. B. McCorry, R. O. Butcher, K. J. Moriarty
Journal: Gut (2009)

A young Caucasian woman was admitted with a 24 h history of right-sided, apical, pleuritic chest pain on a background of progressive dyspnoea and non-productive cough over several weeks. Physical examination recorded a heart rate of 130/min, blood pressure 120/75, temperature 37°C, respiratory rate 28/min, central cyanosis …
A new standardised and self-administered quality of life questionnaire specific to obstructive sleep apnoea
Authors: Y Lacasse
Journal: Thorax (2004)

<b>Background:</b> A short, standardised, self-administered quality of life questionnaire would be a useful addition to the outcome measures in obstructive sleep apnoea (OSA) research. A study was therefore undertaken to validate a new OSA specific self-administered questionnaire (the Quebec Sleep Questionnaire, QSQ) for use in clinical trials. <b>Methods:</b> This study followed a description of health related quality of life in patients with OSA. Construct validity and responsiveness were tested by comparing the baseline and changes in domain scores (daytime sleepiness, diurnal symptoms, nocturnal symptoms, emotions, social interactions) with those of questionnaires measuring related constructs (SF-36, Epworth Sleepiness Scale, Beck Depression Inventory, SCL-90, and Functional Outcomes in Sleep Questionnaire). <b>Results:</b> Sixty patients (48 men) of mean (SD) age 55 (10) years participated in the study. In the analysis of the discriminative function of the questionnaire, moderate to high correlations were found between the scores in each domain of the QSQ and the corresponding questionnaires. In the analysis of its evaluative function significant differences were found in score changes between patients who were treated and those who were not, and moderate to high correlations were seen between changes in scores in the QSQ and changes in the corresponding questionnaires. Most of these correlations met the a priori predictions made regarding their magnitude. <b>Conclusion:</b> The QSQ is a valid measure of health related quality of life in patients with OSA and is sensitive to treatment induced changes.
ADJUSTED DRUG TREATMENT IS SUPERIOR TO RENAL SYMPATHETIC DENERVATION IN PATIENTS WITH TRUE TREATMENT RESISTANT HYPERTENSION, A RANDOMIZED CLINICAL TRIAL
Authors: Fadl Elmula Mohamed Fadl Elmula, Pavel Hoffmann, Anne Cecilie Larstorp, Aud Hoieggen, Sverre Kjeldsen
Journal: Journal of the American College of Cardiology (2014)
Depression in Mothers
Authors: Sherryl H. Goodman
Journal: Annual Review of Clinical Psychology (2007)

Whether one takes a biological, psychological, or psychosocial perspective, depression in mothers raises concerns about risks for the development of psychopathology in the children. This review addresses the complexity of that risk and the essential role of development in a model that explains processes of transmission. This article addresses the following aims: (a) to provide convincing evidence that depression in mothers is an important topic for clinical psychologists; (b) to summarize current theoretical models of mechanisms of risk for the development of psychopathology in children of depressed mothers and the status of empirical support for those models; (c) to examine the theoretical bases and current status of evidence for moderators of this risk; (d) to argue for the advantages to be gained from a developmental psychopathology perspective on this topic; and (e) to point to future directions for theory, research, and practice.
Oral<i>N</i>‐acetylcysteine attenuates the rat pulmonary inflammatory response to antigen
Authors: S. Blesa, J. Cortijo, M. Mata, A. Serrano, D. Closa, F. Santangelo, J.M. Estrela, J. Suchankova, E.J. Morcillo
Journal: European Respiratory Journal (2003)

Oxidative stress is involved in the pathophysiology of inflammatory airway diseases including asthma; therefore, antioxidants might be of clinical benefit in asthma treatment. In the present study, the effects of N ‐acetylcysteine on sensitised brown Norway rats were examined. N ‐Acetylcysteine (3 mmol·kg body weight −1 administered orally) was given daily for 1 week before challenge and various antigen-induced pulmonary responses were studied. Antigen exposure increased lipid peroxidation in bronchoalveolar lavage fluid (BALF) and oxidised glutathione levels in lung tissue 2 h after challenge. Lung nuclear transcription factor‐κB‐binding activity was increased 2 h after challenge, and BALF tumour necrosis factor‐α and inducible nitric oxide synthase expression in lungs peaked 4 h after challenge. Expression of intercellular adhesion molecule‐1 and mucin MUC5AC was also increased 4 h after challenge. These changes in oxidant status, transcription factor activation, and inflammatory cytokine and gene expression were reduced by N ‐acetylcysteine. This thiol did not affect the immediate bronchospasm reaction to antigen in anaesthetised rats but inhibited airways hyperresponsiveness to 5‐hydroxytryptamine and the augmented eosinophil numbers in BALF, which appear 24 h after exposure of conscious rats to antigen aerosol, and abolished antigen-induced extravasation of Evans blue into BALF. These results indicate that oral N ‐acetylcysteine exerts an antioxidant protective effect and attenuates pulmonary inflammation in experimental asthma.
Anomalous origin of the right pulmonary artery from the ascending aorta associated with aortopulmonary window.
Authors: G Gula, C Chew, R Radley-Smith, M Yacoub
Journal: Thorax (1978)

A rare case of anomalous origin of the right pulmonary artery from the ascending aorta associated with an aortopulmonary window and severe pulmonary hypertension in a 13-year-old girl is reported. The window was closed using a Dacron patch and the continuity between the anomalous vessel and the main pulmonary artery was restored with a tubular Dacron graft. After operation the pulmonary pressure dropped to about one-half of the systemic pressure, and equal perfusion and ventilation of both lungs was demonstrated. Although early recognition and surgical treatment of this condition are mandatory to prevent the onset of irreversible pulmonary vascular disease, the presence of severe pulmonary hypertension did not contraindicate surgical correction in our patient.
IMMUNOLOGICAL AND BIOCHEMICAL STUDIES ON SERUM HAPTOGLOBIN
Authors: Bong-Sop Shim, Alexander G. Bearn
Journal: The Journal of Experimental Medicine (1964)

Antibody to purified type 1-1 human serum haptoglobin was obtained in rabbits. Using this antiserum it was demonstrated that the antigenic determinants of the haptoglobin molecule reside in both alpha- and beta-chains. No immunological difference between the normal alpha(1F)- and alpha(1S)-chains of haptoglobin could be detected. A number of healthy individuals whose haptoglobin pattern appeared normal by starch gel electrophoresis were shown to possess a haptoglobin which could be distinguished immunologically from the common haptoglobin types. These immunological atypical haptoglobins have been observed in individuals of types 1-1, 2-1, and 2-2. Combined immunological and chemical studies of purified haptoglobin have enabled the construction of a tentative model for the structure of human type 1-1 haptoglobin.
COMPARISON OF CAROTID ARTERY STENTING IN PATIENTS WITH SINGLE VERSUS BILATERAL CAROTID ARTERY DISEASE AND FACTORS AFFECTING OUTCOME
Authors: Josef Veselka, Petra Zimolova, Lucie Martinkovicova, Miloslav Spacek, Jiri Fiedler, David Zemanek, Petr Hajek, Martin Maly, Pavol Tomasov, David Tesar
Journal: Journal of the American College of Cardiology (2011)
Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at Risk for Diabetes
Authors: Anastassios G. Pittas, Jason Nelson, Joanna Mitri, William Hillmann, Cheryl Garganta, David M. Nathan, Frank B. Hu, Bess Dawson-Hughes
Journal: Diabetes Care (2012)

OBJECTIVE To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes. RESEARCH DESIGN AND METHODS Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying “lagged” covariates, as the mean of the previous and current visits at which diabetes status was assessed. RESULTS After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56–0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52–0.94) versus lifestyle arm (0.80; 0.54–1.17). CONCLUSIONS Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies.
Hyperaldosteronemia and Activation of the Epithelial Sodium Channel Are Not Required for Sodium Retention in Puromycin-Induced Nephrosis
Authors: Stéphane Lourdel, Johannes Loffing, Guillaume Favre, Marc Paulais, Antoine Nissant, Panos Fakitsas, Christophe Créminon, Eric Féraille, Franc[COMBINING CEDILLA]ois Verrey, Jacques Teulon, Alain Doucet, Georges Desche[Combining Circumflex Accent]nes
Journal: Journal of the American Society of Nephrology (2005)

Edema and ascites in nephrotic syndrome mainly result from increased Na<sup>+</sup> reabsorption along connecting tubules and cortical collecting ducts (CCD). In puromycin aminonucleoside (PAN)-induced nephrosis, increased Na<sup>+</sup> reabsorption is associated with increased activity of the epithelial sodium channel (ENaC) and Na<sup>+</sup>,K<sup>+</sup>-ATPase, two targets of aldosterone. Because plasma aldosterone increases in PAN-nephrotic rats, the aldosterone dependence of ENaC activation in PAN nephrosis was investigated. For this purpose, (<i>1</i>) the mechanism of ENaC activation was compared in nephrotic and sodium-depleted rats, and (<i>2</i>) ENaC activity in PAN-nephrotic rats was evaluated in the absence of hyperaldosteronemia. The mechanism of ENaC activation was similar in CCD from nephrotic and sodium-depleted rats, as demonstrated by (<i>1</i>) increased number of active ENaC evaluated by patch clamp, (<i>2</i>) recruitment of ENaC to the apical membrane determined by immunohistochemistry, (<i>3</i>) shift in the electrophoretic profile of γ-ENaC, and (<i>4</i>) increased abundance of β-ENaC mRNA. Corticosteroid clamp fully prevented all PAN-induced changes in ENaC but did not alter the development of a full-blown nephrotic syndrome with massive albuminuria, amiloride-sensitive sodium retention, induction of CCD Na<sup>+</sup>,K<sup>+</sup>-ATPase, and ascites. It is concluded that in PAN-nephrosis, (<i>1</i>) ENaC activation in CCD is secondary to hyperaldosteronemia, (<i>2</i>) sodium retention and induction of Na<sup>+</sup>,K<sup>+</sup>-ATPase in CCD are independent of hyperaldosteronemia, and (<i>3</i>) ENaC is not necessarily limiting for sodium reabsorption in the distal nephron.
Functional Reconstitution of Vascular Smooth Muscle Cells With cGMP-Dependent Protein Kinase I Isoforms
Authors: Robert Feil, Nicolai Gappa, Mark Rutz, Jens Schlossmann, Christine R. Rose, Arthur Konnerth, Sabine Brummer, Susanne Kühbandner, Franz Hofmann
Journal: Circulation Research (2002)

The cGMP-dependent protein kinase type I (cGKI) is a major mediator of NO/cGMP-induced vasorelaxation. Smooth muscle expresses two isoforms of cGKI, cGKIα and cGKIβ, but the specific role of each isoform in vascular smooth muscle cells (VSMCs) is poorly understood. We have used a genetic deletion/rescue strategy to analyze the functional significance of cGKI isoforms in the regulation of the cytosolic Ca 2+ concentration by NO/cGMP in VSMCs. Cultured mouse aortic VSMCs endogenously expressed both cGKIα and cGKIβ. The NO donor diethylamine NONOate (DEA-NO) and the membrane-permeable cGMP analogue 8-bromo-cGMP inhibited noradrenaline-induced Ca 2+ transients in wild-type VSMCs but not in VSMCs genetically deficient for both cGKIα and cGKIβ. The defective Ca 2+ regulation in cGKI-knockout cells could be rescued by transfection of a fusion construct consisting of cGKIα and enhanced green fluorescent protein (EGFP) but not by a cGKIβ-EGFP construct. Fluorescence imaging indicated that the cGKIα-EGFP fusion protein was concentrated in the perinuclear/endoplasmic reticulum region of live VSMCs, whereas the cGKIβ-EGFP protein was more homogeneously distributed in the cytoplasm. These results suggest that one component of NO/cGMP-induced smooth muscle relaxation is the activation of the cGKIα isoform, which decreases the noradrenaline-stimulated cytosolic Ca 2+ level.
Colon Cancer Screening: Tackling a Multifaceted Challenge
Authors: S. T. Hawley, J. E. Lafata
Journal: JNCI Journal of the National Cancer Institute (2014)

Correspondence to: Sarah T. Hawley, PhD, MPH, Departments of Medicine and Health Policy and Management, University of Michigan, Ann Arbor VA Healthcare System, Institute for Healthcare Policy and Innovation, North Campus Research Complex, 2800 Plymouth Road, 4th floor, Ann Arbor, MI 48109 (e-mail: sarahawl@umich.edu) or Jennifer Elston Lafata, PhD, School of Medicine and Massey Cancer Center, Virginia Commonwealth University, One Capital Square, 9th Floor, 830 East Main Street, PO Box 980149, Richmond, VA 23298-0149 (e-mail: jelstonlafat@vcu.edu).