tbuckley/cabot-search huggingface dataset:
Anaerobic performance and metabolism of the hyperthyroid heart
Authors: Ruth A. Altschuld, Alan Weiss, Fred A. Kruger, Arnold M. Weissler
Journal: Journal of Clinical Investigation (1969)

Anaerobically periused hearts from rats with experimentally induced hyperthyroidism exhibited accelerated deterioration of pacemaker activity and ventricular performance. The diminished anaerobic performance of hyperthyroid hearts was associated with decreased adenosine triphosphate (ATP) levels and a reduced rate of anaerobic glycolysis as reflected in decreased lactic acid production during 30 min of anoxic perfusion.Studies on whole heart homogenates demonstrated inhibition at the phosphofructokinase (PFK) step of the glycolytic pathway. Such inhibition was not demonstrated in the hyperthyroid heart cytosol. It is postulated that an inhibitor of PFK which resides dominantly in the particulate fraction is probably responsible for the diminished anaerobic glycolysis and performance of the hyperthyroid heart.
Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: systematic review and meta-analyses
Authors: David Oliver, James B Connelly, Christina R Victor, Fiona E Shaw, Anne Whitehead, Yasemin Genc, Alessandra Vanoli, Finbarr C Martin, Margot A Gosney
Journal: BMJ (2006)

<b>Objectives</b> To evaluate the evidence for strategies to prevent falls or fractures in residents in care homes and hospital inpatients and to investigate the effect of dementia and cognitive impairment. <b>Design</b> Systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression to investigate the effects of dementia and of study quality and design. <b>Data sources</b> Medline, CINAHL, Embase, PsychInfo, Cochrane Database, Clinical Trials Register, and hand searching of references from reviews and guidelines to January 2005. <b>Results</b> 1207 references were identified, including 115 systematic reviews, expert reviews, or guidelines. Of the 92 full papers inspected, 43 were included. Meta-analysis for multifaceted interventions in hospital (13 studies) showed a rate ratio of 0.82 (95% confidence interval 0.68 to 0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies) the rate ratio for hip fractures was 0.67 (0.46 to 0.98), but there was no significant effect on falls and not enough studies on fallers. For all other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication review in hospital) meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment. <b>Conclusion</b> There is some evidence that multifaceted interventions in hospital reduce the number of falls and that use of hip protectors in care homes prevents hip fractures. There is insufficient evidence, however, for the effectiveness of other single interventions in hospitals or care homes or multifaceted interventions in care homes.
Molecular and cellular aspects of endometrial receptivity
Authors: H M Beier, K Beier-Hellwig
Journal: Human Reproduction Update (1998)

Endocrine and paracrine controls regulate the endometrium during the luteal phase of the cycle to permit implantation. Part of this differentiation process is the production of a specific secretion which fills the intrauterine cavity and glandular lumen. Its molecular composition originates from the gland secretion, from transudations from stroma, from the endometrial blood vessels, and last, but not least, from cellular components of apoptotic and exfoliated cells. We have studied the secretions of all phases during the menstrual cycle using patterns evaluated by SDS-PAGE, by laser densitometry or Western blots. Uterine secretion electrophoresis (USE) permits detailed analyses of the intrauterine micromilieu and allows clinical assessment of the receptive stage of endometrium during the luteal phase. Several individual protein bands have been defined as characteristic markers for such receptive pattern. We have isolated and identified the molecular structure of several of these proteins, e.g. histones, cyclophilin, transthyretin, haptoglobin and uteroglobin. Investigations on the endocrine regulation of these proteins, were carried out on the uterine secretions of patients treated with progesterone antagonists (mifepristone and onapristone). The results demonstrate how progesterone-dependent components produce a receptive pattern, which can serve as a useful and precise marker in the clinical diagnosis of the luteal phase. Essential progesterone-dependent components differentiating during the luteal phase may provide new targets for contraceptive interventions by preventing the physiological changes typical of receptivity.
Heart mitochondria: gates of life and death
Authors: A. B. Gustafsson, R. A. Gottlieb
Journal: Cardiovascular Research (2007)

Mitochondria are important generators of energy, providing ATP through oxidative phosphorylation. However, mitochondria also monitor complex information from the environment and intracellular milieu, including the presence or absence of growth factors, oxygen, reactive oxygen species, and DNA damage. Mitochondria have been implicated in the loss of cells in various cardiac pathologies, including ischaemia/reperfusion injury, cardiomyopathy, and congestive heart failure. The release of factors such as cytochrome c, Smac, Omi/Htr2A, and AIF from mitochondria serves to activate a highly complex and regulated cell death program. Furthermore, mitochondrial calcium overload might trigger opening of the mitochondrial permeability transition pore, causing uncoupling of oxidative phosphorylation, swelling of the mitochondria due to influx of water, and rupture of the mitochondrial outer membrane. In this review, we discuss the role of mitochondria in the control of cell death in cardiac myocytes.
Human papillomavirus type 16 DNA in anal cancers from six different countries.
Authors: J H Scholefield, I B Kerr, N A Shepherd, K J Miller, R Bloomfield, J M Northover
Journal: Gut (1991)

An association between anal squamous cell carcinoma and human papillomavirus (HPV) type 16 DNA has been documented in the UK. If HPV type 16 is an important aetiological factor in the development of this tumour it would be expected to occur in anal cancer tissues from other parts of the world. In this study a series of 173 anal squamous cell carcinoma tissue samples from five centres around the world have been examined by DNA hybridisation for HPV type 16 DNA sequences. HPV type 16 DNA was found in 50 of 173 (29%) of these. The prevalence of HPV associated anal squamous cell carcinoma was significantly lower in tissue from India and South Africa than in the Swiss, Polish, or Brazilian samples. HPV associated anal squamous cell carcinoma does occur in other countries and further investigations of the prevalence of these tumours in association with other HPV types are required.
Cell adhesion and migration are regulated at distinct stages of thymic T cell development: the roles of fibronectin, VLA4, and VLA5.
Authors: L Crisa, V Cirulli, M H Ellisman, J K Ishii, M J Elices, D R Salomon
Journal: The Journal of Experimental Medicine (1996)

T cell development in the thymus requires the establishment of stable interactions with cell-selecting elements such as the cortical epithelium followed by a regulated movement of selected progenitors to the medulla. Cell adhesion and migration are mediated by integrins in a number of biological systems though little is known regarding their function in the thymus. We demonstrated previously that immature CD3loCD69lo double positive human thymocytes adhere avidly to FN via the integrin, VLA4. We now demonstrate that the interaction of mature CD3hiCD69hi thymic subsets with FN triggers migration rather than firm adhesion. Migration requires the engagement of VLA4 in cooperation with VLA5 and both receptors regulate the persistence and directionality of movement. While migration capability is linked to maturation state, ligand concentration determines the efficiency of migration. In fact, FN and the alternatively spliced CS1 site are predominant in the thymic medulla, suggesting an instructive role of this ECM protein in vivo. Our studies identify a novel VLA4 and VLA5/FN-mediated pathway likely to be involved in regulating cell traffic between the cortex and medulla of the thymus. Moreover, the data provides evidence that VLA4 exists in at least two functional states at distinct stages of T cell development. While different states of VLA4 activation have been described on cell lines, this represents the first evidence supporting a biological significance for this integrin property.
The effects of short-term venous congestion on forearm venous volume and reactive hyperemia blood flow in human subjects.
Authors: R Zelis, R Capone, E Mansour, J M Field
Journal: Circulation (1978)

Congestive heart failure is associated with a reduction in limb venous volume at an effective venous pressure of 30 mm Hg (VV[30]). Further, an attenuated arteriolar dilation in response to a metabolic stimulus has been demonstrated. It was the purpose of this study to determine to what extent the chronic elevation in venous pressure seen in heart failure might explain these abnormalities of the limb circulation. Ten normal human volunteers were subjected to venous congestion of one arm for three hours at 70 mm Hg. A mercury-in-rubber strain gauge plethysmograph was used to measure forearm VV [30] and forearm blood flow at rest after release of five minutes of arterial occlusion (the reactive hyperemia response). Congestion reduced VV [30] 22%, resting forearm blood flow 49% and peak reactive hyperemia blood flow 25%. Thus, chronic venous congestion per se may significantly reduce limb venous volume as well as resting and reactive hyperemia blood flow.
Origin and behaviour of emphysematous bullae.
Authors: M D Morgan, C W Edwards, J Morris, H R Matthews
Journal: Thorax (1989)

Giant emphysematous bullae are believed to produce symptoms of pulmonary compression and collapse by containing gas under pressure that has been generated through valvular feeding airways. To examine this hypothesis, we have measured oxygen and carbon dioxide tensions (PO2, PCO2) in four patients and pressure within the bullae in three patients immediately before surgery. During spontaneous tidal respiration PO2 in the bulla was higher than arterial PO2 but did not rise as fast during the breathing of oxygen. The intra-bulla pressure during inspiration was negative (-5.5 to -19 cm H2O) and similar to pleural pressure in phase and degree. During intermittent positive pressure ventilation in two patients airway pressures were transmitted to the bulla with the development of a positive end expiratory pressure within the bulla. Histological examination of the walls of the bullae in the four patients and adjacent lung tissue in an additional patient failed to identify any valvular mechanism. The available information suggests that bullae develop after retraction and collapse of surrounding lung away from a region of weakness.
Antitumor Activity of a Boiled Scallop Extract: Brief Communication 2
Authors: Takuma Sasaki, Nobuo Takasuka, Noriko Abiko
Journal: JNCI Journal of the National Cancer Institute (1978)

A fraction from a boiled scallop extract modified by a sonication procedure exhibited marked antitumor activity when it was injected intradermally into either ICR or C3H/He mice that had been given sc implants of sarcoma 180 and Ehrlich carcinoma. The active moiety was heat-stable and noncytotoxic. In contrast, preparations from raw scallop showed lower antitumor activity and were heat-labile.
Variation in alternative splicing across human tissues
Authors: Gene Yeo, Dirk Holste, Gabriel Kreiman, Christopher B Burge
Journal: Genome biology (2004)

Abstract Background Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues. Conclusions This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis -regulatory elements and trans -acting factors likely to have important roles in tissue-specific AS in human cells.
Roles of peroxiredoxin II in the regulation of proinflammatory responses to LPS and protection against endotoxin-induced lethal shock
Authors: Chul-Su Yang, Dong-Seok Lee, Chang-Hwa Song, Se-Jin An, Shengjin Li, Jin-Man Kim, Cuk Seong Kim, Dae Goon Yoo, Byeong Hwa Jeon, Hee-Young Yang, Tae-Hoon Lee, Zee-Won Lee, Jamel El-Benna, Dae-Yeul Yu, Eun-Kyeong Jo
Journal: The Journal of Experimental Medicine (2007)

Mammalian 2-Cys peroxiredoxin II (Prx II) is a cellular peroxidase that eliminates endogenous H(2)O(2). The involvement of Prx II in the regulation of lipopolysaccharide (LPS) signaling is poorly understood. In this report, we show that LPS induces substantially enhanced inflammatory events, which include the signaling molecules nuclear factor kappaB and mitogen-activated protein kinase (MAPK), in Prx II-deficient macrophages. This effect of LPS was mediated by the robust up-regulation of the reactive oxygen species (ROS)-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and the phosphorylation of p47(phox). Furthermore, challenge with LPS induced greater sensitivity to LPS-induced lethal shock in Prx II-deficient mice than in wild-type mice. Intravenous injection of Prx II-deficient mice with the adenovirus-encoding Prx II gene significantly rescued mice from LPS-induced lethal shock as compared with the injection of a control virus. The administration of catalase mimicked the reversal effects of Prx II on LPS-induced inflammatory responses in Prx II-deficient cells, which suggests that intracellular H(2)O(2) is attributable, at least in part, to the enhanced sensitivity to LPS. These results indicate that Prx II is an essential negative regulator of LPS-induced inflammatory signaling through modulation of ROS synthesis via NADPH oxidase activities and, therefore, is crucial for the prevention of excessive host responses to microbial products.
Amyloid-β Peptide Induces Mitochondrial Dysfunction by Inhibition of Preprotein Maturation
Authors: Dirk Mossmann, F.-Nora Vögtle, Asli Aras Taskin, Pedro Filipe Teixeira, Julia Ring, Julia M. Burkhart, Nils Burger, Catarina Moreira Pinho, Jelena Tadic, Desiree Loreth, Caroline Graff, Friedrich Metzger, Albert Sickmann, Oliver Kretz, Nils Wiedemann, René P. Zahedi, Frank Madeo, Elzbieta Glaser, Chris Meisinger
Journal: Cell Metabolism (2014)
On Colles' Fracture of the Radius, and its Treatment
Authors: J. A. Macdonald
Journal: BMJ (1873)

lungs were sound.She had taken a great variety of tonics and seda.tives, but had become worse.The patient was seen in consultation with Mr. White, who, at my request, gave a full trial to conium, but without any benefit ensuing.She took five drachms or more of the succus three times a day.Subsequently, she had a fortnight's trial of one of Pulvermacher's large chains; but this was equally inefficacious.In Case i, the tremor could be arrested by an effort of volition ; in Case iv, it could not; in Case iii, it was aggravated.In Case II, it could be arrested in one arm, but not in the other.Some sensory dis- order was present in Cases iii and iv, but scarcely at all in the others.The affinity of the disorder with chorea was very evident in Case II ; in fact, I have no doubt the condition was essentially identical with the choreic; but some slight modification of the state of the nerve-cells rendered the symptoms different.The circumstance that Case iiI gained two stone in weight during his illness is noteworthy.I sup- pose the exhaustion of nerve-fore induced asthenic obesity, just as an acute illness may do during the period of convalescence.It is also remarkable that his abdomen lessened in size considerably as he im- proved-probably from the intestinal muscles regaining their tone and preventing the accumulation of flatus.The alternation of the limb- affection with impairment of speech (vocal) in Case II is good evidence of the purely neurotic character of the disorder.
Effect of a Lung Protective Strategy for Organ Donors on Eligibility and Availability of Lungs for Transplantation
Authors: Luciana Mascia, Daniela Pasero, Arthur S. Slutsky, M. Jose Arguis, Maurizio Berardino, Salvatore Grasso, Marina Munari, Silvia Boifava, Giuseppe Cornara, Francesco Della Corte, Nicoletta Vivaldi, Paolo Malacarne, Paolo Del Gaudio, Sergio Livigni, Elisabeth Zavala, Claudia Filippini, Erica L. Martin, Pier Paolo Donadio, Ilaria Mastromauro, V. Marco Ranieri
Journal: JAMA (2010)

Many potential donor lungs deteriorate between the time of brain death and evaluation for transplantation suitability, possibly because of the ventilatory strategy used after brain death.To test whether a lung protective strategy increases the number of lungs available for transplantation.Multicenter randomized controlled trial of patients with beating hearts who were potential organ donors conducted at 12 European intensive care units from September 2004 to May 2009 in the Protective Ventilatory Strategy in Potential Lung Donors Study. Interventions Potential donors were randomized to the conventional ventilatory strategy (with tidal volumes of 10-12 mL/kg of predicted body weight, positive end-expiratory pressure [PEEP] of 3-5 cm H(2)O, apnea tests performed by disconnecting the ventilator, and open circuit for airway suction) or the protective ventilatory strategy (with tidal volumes of 6-8 mL/kg of predicted body weight, PEEP of 8-10 cm H(2)O, apnea tests performed by using continuous positive airway pressure, and closed circuit for airway suction).The number of organ donors meeting eligibility criteria for harvesting, number of lungs harvested, and 6-month survival of lung transplant recipients.The trial was stopped after enrolling 118 patients (59 in the conventional ventilatory strategy and 59 in the protective ventilatory strategy) because of termination of funding. The number of patients who met lung donor eligibility criteria after the 6-hour observation period was 32 (54%) in the conventional strategy vs 56 (95%) in the protective strategy (difference of 41% [95% confidence interval {CI}, 26.5% to 54.8%]; P <.001). The number of patients in whom lungs were harvested was 16 (27%) in the conventional strategy vs 32 (54%) in the protective strategy (difference of 27% [95% CI, 10.0% to 44.5%]; P = .004). Six-month survival rates did not differ between recipients who received lungs from donors ventilated with the conventional strategy compared with the protective strategy (11/16 [69%] vs 24/32 [75%], respectively; difference of 6% [95% CI, -22% to 32%]).Use of a lung protective strategy in potential organ donors with brain death increased the number of eligible and harvested lungs compared with a conventional strategy.clinicaltrials.gov Identifier: NCT00260676.
Suppression of Tumor Formation by a Cyclooxygenase-2 Inhibitor and a Peroxisome Proliferator-Activated Receptor γ Agonist in an <i>In vivo</i> Mouse Model of Spontaneous Breast Cancer
Authors: Aladdin Mustafa, Warren D. Kruger
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Activation of COX-2 and inhibition of PPARγ have been observed in human and animal models of breast cancer. Both inhibition of COX-2 and activation of PPARγ can inhibit proliferation of breast cancer cells in vitro. Here, we examine the effects of the COX-2 inhibitor celecoxib and the PPARγ agonist N-(9-fluorenyl-methyloxycarbonyl)-l-leucine (F-L-Leu) on mouse breast tumor cells in vitro and in vivo. Experimental Design: We created and characterized a mouse mammary adenocarcinoma cell (MMAC-1) line from C3 (1)-SV40 tumor antigen mice to study COX-2 and PPARγ expression and response to celecoxib and F-L-Leu in vitro. To study the in vivo effects, C3 (1)-SV40 tumor antigen mice were given either control diet or diets containing three different concentrations of celecoxib and F-L-Leu as well as a combination of both agents. Mice were then followed for tumor formation up to 1 year. Results: MMAC-1 cells express both COX-2 and PPARγ mRNA and exhibited cooperative growth inhibition with a combination of celecoxib and F-L-Leu. In mice, the median age of death due to mammary tumors was significantly delayed in celecoxib-treated animals at all three concentrations but was not significantly affected by F-L-Leu treatment alone. A combination of celecoxib and F-L-Leu was significantly more effective than celecoxib alone. Conclusions: Our findings suggest that a combination of a COX-2 inhibitor and PPARγ agonist can delay breast cancer in a mouse model and suggest that these agents should be studied in the context of human populations with high breast cancer risk.