tbuckley/cabot-search huggingface dataset:
Incidence and Clinical Relevance of Slow Ventricular Tachycardia in Implantable Cardioverter-Defibrillator Recipients
Authors: Nicolas Sadoul, Ralph Mletzko, Frédéric Anselme, Robert Bowes, Wolfgang Schöls, Claude Kouakam, Gaëlle Casteigneau, Raffaele Luise, Nicolas Iscolo, Etienne Aliot
Journal: Circulation (2005)

Background— This study aims to assess the incidence and clinical relevance of slow ventricular tachycardia (VT) and the effectiveness and/or deleterious effects of antitachycardia pacing in slow VT in implantable cardioverter-defibrillator recipients. Methods and Results— This multicenter prospective randomized study included 374 patients (326 men) without prior history of slow VT (&lt;148 bpm) implanted with a dual-chamber implantable cardioverter-defibrillator. Patients had a 3-zone detection configuration: a slow VT zone (101 to 148 bpm), a conventional VT zone (&gt;148 bpm), and a ventricular fibrillation zone. Patients were randomized to a treatment group (n=183) with therapy activated in the slow VT zone or a monitoring group (n=191) with no therapy in the slow VT zone. During follow-up (11 months), 449 slow VTs occurred in 114 patients (30.5% slow VT incidence); 181 VTs (54 patients) occurred in the monitoring group; 3 were readmitted to the hospital; and lightheadedness and palpitations occurred in 4 and 250 (60 patients) in the treatment group treated by antitachycardia pacing (89.8% success rate) and shock delivery (n=2). There were 10 crossovers from the monitoring to treatment group and 3 crossovers from the treatment to monitoring group ( P =0.09). Quality of life scores were not different between groups. Conclusions— Slow VT incidence (&lt;150 bpm) is high (30%) in implantable cardioverter-defibrillator recipients without prior history of slow VT, has limited clinical relevance, and is efficiently and safely terminated by antitachycardia pacing.
Heterogeneous phenotypes of expression of the NKB1 natural killer cell class I receptor among individuals of different human histocompatibility leukocyte antigens types appear genetically regulated, but not linked to major histocompatibililty complex haplotype.
Authors: J E Gumperz, N M Valiante, P Parham, L L Lanier, D Tyan
Journal: The Journal of Experimental Medicine (1996)

Natural killer (NK) cells that express the NKB1 receptor are inhibited from killing target cells that possess human histocompatibility leukocyte antigen (HLA) B molecules bearing the Bw4 serological epitope. To investigate whether NKB1 expression is affected by HLA type, peripheral blood lymphocytes of 203 HLA-typed donors were examined. Most donors had a single population of NKB1+ cells, but some had two populations expressing different cell surface levels of NKB1, and others had no detectable NKB1+ cells. Among the donors expressing NKB1, both the relative abundance of NKB1+ NK cells and their level of cell surface expression varied substantially. The percentage of NKB1+ NK cells ranged from 0 to >75% (mean 14.7%), and the mean fluorescence of the positive population varied over three orders of magnitude. For each donor, the small percentage of T cells expressing NKB1 (usually <2%), had a pattern of expression mirroring that of the NK cells. NKB1 expression by NK and T cells remained stable over the 2-yr period that five donors were tested. Patterns of NKB1 expression were not associated with Bw4 or Bw6 serotype of the donor or with the presence of any individual HLA-A or -B antigens. Cells expressing NKB1 are often found in donors who do not possess an appropriate class I ligand, and can be absent in those who express Bw4+ HLA-B antigens. Family studies further suggested that the phenotype of NKB1 expression is inherited but not HLA linked. Whereas identical twins show matching patterns of NKB1 expression, HLA-identical siblings can differ in NKB1 expression, and conversely, HLA-disparate siblings can be similar. Thus NKB1 expression phenotypes are tightly regulated and extremely heterogeneous, but not correlated with HLA type.
Attitudes to participation in a lung cancer screening trial: a qualitative study
Authors: Deesha Patel, Ajiri Akporobaro, Nyasha Chinyanganya, Allan Hackshaw, Clive Seale, Stephen G Spiro, Chris Griffiths
Journal: Thorax (2011)

<h3>Background</h3> Earlier diagnosis of lung cancer is key to reducing mortality. New evidence suggests that smokers have negative attitudes to screening and participation in lung cancer screening trials is poor (&lt;1 in 6 of those eligible). Understanding participation is important since uptake in screening trials is likely to predict uptake in screening programmes. A qualitative study of people accepting and declining participation in the Lung-SEARCH screening trial was conducted. Two questions were addressed: Are the screening methods offered acceptable to patients? Why do some people take part and others decline? <h3>Methods</h3> The qualitative study used semi-structured interviews with 60 respondents from three groups: (a) trial participants providing an annual sputum sample; (b) trial participants with a sputum sample showing abnormal cytology and thus undergoing annual CT scanning and bronchoscopy; and (c) those declining trial participation. <h3>Results</h3> Most respondents (48/60, 80%) viewed sputum provision, CT scanning and bronchoscopy as largely acceptable. Those declining trial participation described fear of bronchoscopy, inconvenience of travelling to hospitals for screening investigations and perceived themselves as having low susceptibility to lung cancer or being too old to benefit. Patients declining participation discounted their risk from smoking and considered negative family histories and good health to be protective. Four typological behaviours emerged within those declining: 'too old to be bothered', 'worriers', 'fatalists' and 'avoiders'. <h3>Conclusion</h3> Sputum provision, CT scanning and bronchoscopy are largely acceptable to those participating in a screening trial. However, the decision to participate or decline reflects a complex balance of factors including acceptability and convenience of screening methods, risk perception, altruism and self-interest. Improving practical and changing cognitive aspects of participation will be key to improving uptake of lung cancer screening.
Role for Peroxisome Proliferator-Activated Receptor α in Oxidized Phospholipid–Induced Synthesis of Monocyte Chemotactic Protein-1 and Interleukin-8 by Endothelial Cells
Authors: Hans Lee, Weibin Shi, Peter Tontonoz, Shirley Wang, Ganesamoorthy Subbanagounder, Catherine C. Hedrick, Susan Hama, Christine Borromeo, Ronald M. Evans, Judith A. Berliner, Laszlo Nagy
Journal: Circulation Research (2000)

Abstract —The attraction, binding, and entry of monocytes into the vessel wall play an important role in atherogenesis. We have previously shown that minimally oxidized/modified LDL (MM-LDL), a pathogenically relevant lipoprotein, can activate human aortic endothelial cells (HAECs) to produce monocyte chemotactic activators. In the present study, we demonstrate that MM-LDL and oxidation products of 1-palmitoyl-2-arachidonyl- sn -glycero-3-phosphocholine (PAPC) activate endothelial cells to synthesize monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8). Several lines of evidence suggest that this activation is mediated by the lipid-dependent transcription factor peroxisome proliferator-activated receptor α (PPARα), the most abundant member of the PPAR family in HAECs. Treatment of transfected CV-1 cells demonstrated activation of the PPARα ligand-binding domain by MM-LDL, Ox-PAPC, or its component phospholipids, 1-palmitoyl-2-oxovalaroyl- sn -glycero-phosphocholine and 1-palmitoyl-2-glutaroyl- sn -glycero-phosphocholine; these lipids also activated a consensus peroxisome proliferator-activated receptor response element (PPRE) in transfected HAECs. Furthermore, activation of PPARα with synthetic ligand Wy14,643 stimulates the synthesis of IL-8 and MCP-1 by HAECs. By contrast, troglitazone, a PPARγ agonist, decreased the levels of IL-8 and MCP-1. Finally, we demonstrate that unlike wild-type endothelial cells, endothelial cells derived from PPARα null mice do not produce MCP-1/JE in response to Ox-PAPC and MM-LDL. Together, these data demonstrate a proinflammatory role for PPARα in mediation of the activation of endothelial cells to produce monocyte chemotactic activity in response to oxidized phospholipids and lipoproteins.
Evidence for carrier-mediated chloride/bicarbonate exchange in canalicular rat liver plasma membrane vesicles.
Authors: P J Meier, R Knickelbein, R H Moseley, J W Dobbins, J L Boyer
Journal: Journal of Clinical Investigation (1985)

To determine whether anion exchangers might play a role in hepatic bile formation, we looked for the presence of Cl-:OH- and Cl-:HCO3- exchange in highly purified canalicular (c) and basolateral (bl) rat liver plasma membrane (LPM) vesicles. In cLPM vesicles, a pH gradient (7.7 in/6.0 out) stimulated 36Cl- uptake twofold above values obtained during pH-equilibrated conditions (7.7 in = out). When 50 mM HCO3- was also present inside the vesicles, the same pH gradient (7.7 in/6.0 out) resulted in Cl- uptake to levels fourfold above pH- and HCO3--equilibrated controls and two- to threefold above Cl- equilibrium (overshoot). Initial rates of both pH and HCO3- gradient-stimulated Cl- uptake were completely inhibited by 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). A valinomycin-induced K+ diffusion potential (inside positive) also stimulated Cl- uptake in cLPM, but this conductive Cl- pathway was insensitive to DIDS. The DIDS-sensitive, pH and HCO3- gradient-stimulated Cl- uptake demonstrated: saturation with Cl- (Km approximately 6.3 mM; Vmax approximately 51 nmol X mg-1 X min-1); partial inhibition by bumetanide (26%), furosemide (33%), probenecid (37%), and 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (49%); cis-inhibition by chloride and nitrate but not by sulfate and various organic anions, and independence from the membrane potential. These data demonstrate the presence of an electroneutral Cl-:OH- and Cl-:HCO3- exchanger in rat liver canalicular membranes that favors Cl-:HCO3- exchange. In contrast, no evidence was found for the presence of a Cl-:HCO3- (OH-) exchange system in blLPM vesicles. Furthermore, neither blLPM nor cLPM vesicles exhibited Na+-stimulatable Cl- uptake, indicating the absence of a NaCl co-transport system in either LPM subfraction. These findings are consistent with a functional role for a Cl-:HCO3- (OH-) exchanger in canalicular bile formation.
Phosphorylation of the F <sub>1</sub> F <sub>o</sub> ATP Synthase β Subunit
Authors: Lesley A. Kane, Matthew J. Youngman, Robert E. Jensen, Jennifer E. Van Eyk
Journal: Circulation Research (2009)

We previously discovered several phosphorylations to the beta subunit of the mitochondrial F(1)F(o) ATP synthase complex in isolated rabbit myocytes on adenosine treatment, an agent that induces cardioprotection. The role of these phosphorylations is unknown.The present study focuses on the functional consequences of phosphorylation of the ATP synthase complex beta subunit by generating nonphosphorylatable and phosphomimetic analogs in a model system, Saccharomyces cerevisiae.The 4 amino acid residues with homology in yeast (T58, S213, T262, and T318) were studied with respect to growth, complex and supercomplex formation, and enzymatic activity (ATPase rate). The most striking mutant was the T262 site, for which the phosphomimetic (T262E) abolished activity, whereas the nonphosphorylatable strain (T262A) had an ATPase rate equivalent to wild type. Although T262E, like all of the beta subunit mutants, was able to form the intact complex (F(1)F(o)), this strain lacked a free F(1) component found in wild-type and had a corresponding increase of lower-molecular-weight forms of the protein, indicating an assembly/stability defect. In addition, the ATPase activity was reduced but not abolished with the phosphomimetic mutation at T58, a site that altered the formation/maintenance of dimers of the F(1)F(o) ATP synthase complex.Taken together, these data show that pseudophosphorylation of specific amino acid residues can have separate and distinctive effects on the F(1)F(o) ATP synthase complex, suggesting the possibility that several of the phosphorylations observed in the rabbit heart can have structural and functional consequences to the F(1)F(o) ATP synthase complex.
The C677T Methylenetetrahydrofolate Reductase Gene Mutation in Hemodialysis Patients
Authors: HIDEKI KIMURA, FUMITAKE GEJYO, SATORU SUZUKI, RYOICHI MIYAZAKI
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Hyperhomocysteinemia, which results from renal impairment, may promote arteriosclerosis and glomerulosclerosis. The combined effect of renal failure and a common mutation (C677T) in the methylenetetrahydrofolate reductase gene that leads to serum homocysteine elevations in dialysis patients was investigated. Genotypes were determined at this locus in 545 dialysis patients and 676 healthy subjects, and serum concentrations of total homocysteine and folate were measured in a subgroup of 464 patients. Multiple regression analysis showed that the TT genotype and low serum folate concentration were independent positive predictors of the serum total homocysteine concentration. The negative slope of a regression line relating homocysteine and folate concentrations was significantly steeper for patients with the TT genotype than for other genotypes. Patients with the TT genotype were significantly younger at the time of the study (54.8 ± 12.9 versus 59.6 ± 12.3 yr; P &lt; 0.0001) and at initiation of dialysis (46.6 ± 16.2 versus 51.2 ± 15.9 yr; P &lt; 0.02) than those with other genotypes. In patients who were older at the time of the study or at initiation of dialysis, the prevalence of the TT genotype was lower than in control subjects. In the middle quartiles (37.1 to 63.0 yr) for age at the start of dialysis, the prevalence of the TT genotype was lower in patients with a longer duration of dialysis. In this cross-sectional study, genotype and serum total homocysteine concentration were not independent risk factors for vascular disease in dialysis patients. These results indicate that the methylenetetrahydrofolate reductase mutation is a significant independent predictor for serum total homocysteine concentration.
Ultrasound aids in diagnosis and severity assessment of hidradenitis suppurativa
Authors: N.L. Kelekis, E. Efstathopoulos, A. Balanika, T.N. Spyridopoulos, A. Pelekanou, T. Kanni, A. Savva, E. Brountzos, E.J. Giamarellos-Bourboulis
Journal: British Journal of Dermatology (2010)
Maintenance Treatment for Patients With Bipolar I Disorder: Results From a North American Study of Quetiapine in Combination With Lithium or Divalproex (Trial 127)
Authors: Trisha Suppes, Eduard Vieta, Sherry Liu, Martin Brecher, Björn Paulsson
Journal: American Journal of Psychiatry (2009)

The authors evaluated the efficacy and safety of quetiapine plus lithium or divalproex in the prevention of recurrent mood events in patients with stabilized bipolar I disorder.A total of 1,953 patients received open-label quetiapine (400-800 mg/day in flexible, divided doses) with either lithium or divalproex (target serum concentrations 0.5-1.2 meq/liter and 50-125 microg/ml, respectively) for up to 36 weeks. After at least 12 weeks of clinical stability, 628 patients were randomly assigned to double-blind treatment with quetiapine or placebo, in combination with lithium or divalproex, for up to 104 weeks. The primary efficacy measure was time to recurrence of any mood event (mania, depression, or a mixed episode).Fewer patients in the quetiapine group experienced a mood event compared with the placebo group (20.3% versus 52.1%). The hazard ratio for time to recurrence of a mood event was 0.32. Hazard ratios were similar for mania and depression events (0.30 and 0.33, respectively). Sedation, weight increase, and hypothyroidism occurred more frequently in the quetiapine group, as did discontinuations due to adverse events. The incidence and incidence density of a single emergent blood glucose value > or =126 mg/dl were higher in the quetiapine group (12.6% versus 5.4%; 18.44 versus 9.56 patients per 100 patient-years). Adverse events were generally consistent with the known tolerability profile of quetiapine.In patients stabilized on quetiapine plus lithium or divalproex, continued treatment was associated with a significant risk reduction in the time to recurrence of any mood event compared with placebo and lithium or divalproex.
Chromosome Size in Diploid Eukaryotic Species Centers on the Average Length with a Conserved Boundary
Authors: X. Li, C. Zhu, Z. Lin, Y. Wu, D. Zhang, G. Bai, W. Song, J. Ma, G. J. Muehlbauer, M. J. Scanlon, M. Zhang, J. Yu
Journal: Molecular Biology and Evolution (2011)

Understanding genome and chromosome evolution is important for understanding genetic inheritance and evolution. Universal events comprising DNA replication, transcription, repair, mobile genetic element transposition, chromosome rearrangements, mitosis, and meiosis underlie inheritance and variation of living organisms. Although the genome of a species as a whole is important, chromosomes are the basic units subjected to genetic events that coin evolution to a large extent. Now many complete genome sequences are available, we can address evolution and variation of individual chromosomes across species. For example, "How are the repeat and nonrepeat proportions of genetic codes distributed among different chromosomes in a multichromosome species?" "Is there a general rule behind the intuitive observation that chromosome lengths tend to be similar in a species, and if so, can we generalize any findings in chromosome content and size across different taxonomic groups?" Here, we show that chromosomes within a species do not show dramatic fluctuation in their content of mobile genetic elements as the proliferation of these elements increases from unicellular eukaryotes to vertebrates. Furthermore, we demonstrate that, notwithstanding the remarkable plasticity, there is an upper limit to chromosome-size variation in diploid eukaryotes with linear chromosomes. Strikingly, variation in chromosome size for 886 chromosomes in 68 eukaryotic genomes (including 22 human autosomes) can be viably captured by a single model, which predicts that the vast majority of the chromosomes in a species are expected to have a base pair length between 0.4035 and 1.8626 times the average chromosome length. This conserved boundary of chromosome-size variation, which prevails across a wide taxonomic range with few exceptions, indicates that cellular, molecular, and evolutionary mechanisms, possibly together, confine the chromosome lengths around a species-specific average chromosome length.
Specialist palliative care in dementia
Authors: Julian C Hughes, Louise Robinson, Ladislav Volicer
Journal: BMJ (2005)

Specialised units with outreach and liaison are needed 

I n its latest report on palliative care, the health committee of the House of Commons recorded the Department of Health's admission that the lack of palliative care for patients without cancer was the greatest inequity of all.1 In the United Kingdom, people die in hospices almost solely from cancer, although it accounts for only 25% of all deaths.1 w1 Yet patients dying from dementia have been shown to have healthcare needs comparable to those of cancer patients.2

The palliative care approach provides appropriate control of symptoms, emphasises overall quality of life, takes a holistic approach, involves the patient and the family in decisions, and fosters good supportive communication between all concerned.w2 Hence, it equates to person centred care in dementia.w3 w4 Evidence suggests a palliative care approach in dementia is favoured by formal and informal carers.3 The wishes of patients themselves, however, are hardly known—although preliminary results show high rates of satisfaction …
Accurate Discrimination of Barrett's Esophagus and Esophageal Adenocarcinoma Using a Quantitative Three-Tiered Algorithm and Multimarker Real-time Reverse Transcription-PCR
Authors: Michael Mitas, Jonas S. Almeida, Kaidi Mikhitarian, William E. Gillanders, David N. Lewin, Demetri D. Spyropoulos, Loretta Hoover, Amanda Graham, Tammy Glenn, Peter King, David J. Cole, Robert Hawes, Carolyn E. Reed, Brenda J. Hoffman
Journal: Clinical Cancer Research (2005)

Abstract Esophageal adenocarcinoma (EA) is increasing faster than any other cancer in the U.S. In this report, we first show that EA can be distinguished from normal esophagus (NE) and esophageal squamous cell carcinoma by plotting expression values for EpCam, TFF1, and SBEM in three-dimensional Euclidean space. For monitoring progression of Barrett's esophagus (BE) to EA, we developed a highly sensitive assay for limited quantities of tissue whereby 50 ng of RNA are first converted to cDNA using 16 gene-specific primers. Using a set of training tissues, we developed a novel quantitative three-tiered algorithm that allows for accurate (overall accuracy = 61/63, 97%) discrimination of BE versus EA tissues using only three genes. The gene used in the first tier of the algorithm is TSPAN: samples not diagnosed as BE or EA by TSPAN in the first tier are then subjected to a second-tier analysis using ECGF1, followed by a third-tier analysis using SPARC. Addition of TFF1 and SBEM to the first tier (i.e., a five-gene marker panel) increases the overall accuracy of the assay to 98% (62/63) and results in mean molecular diagnostic scores (± SD) that are significantly different between EA and BE samples (3.19 ± 1.07 versus −2.74 ± 1.73, respectively). Our results suggest that relatively few genes can be used to monitor progression of BE to EA.
Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia
Authors: Jun Ooi, Tohru Iseki, Satoshi Takahashi, Akira Tomonari, Kashiya Takasugi, Yoko Shimohakamada, Toshiki Yamada, Koji Ishii, Nobuhiro Ohno, Fumitaka Nagamura, Kaoru Uchimaru, Arinobu Tojo, Shigetaka Asano
Journal: Blood (2003)
Effect of Alterations of Coronary Blood Flow on the Oxygen Consumption of the Nonworking Heart
Authors: Richard L. Kahler, Eugene Braunwald, Leslie L. Kelminson, Laurence Kedes, Charles A. Chidsey, Stanton Segal
Journal: Circulation Research (1963)

The effect of varying CBF and myocardial O 2 delivery on MV O O2 was studied in 23 experiments. In 14 of the experiments an isolated dog heart was perfused, while in the others the heart of a dog, whose systemic circulation was maintained on cardiopulmonary bypass, was studied. The ventricles were kept empty, developed no pressure and performed no external work, while their temperature was held constant. CBF and myocardial O 2 delivery were controlled by pumping blood into the coronary arteries, total coronary venous return was collected from the right side of the heart and MV O O2 , was calculated during a steady state by the Fick principle. Myocardial anoxia was avoided by maintaining the coronary venous O 2 content above 4 vol % and myocardial O 2 extraction below 78%. A comparison of MV O O2 at two levels of CBF (and O 2 delivery) was made in 42 instances, and in 32 of them 11 MV increased substantially as CBF was elevated, or vice versa. The ten exceptions all occurred when O 2 delivery greatly exceeded MV O O2 with O 2 extraction ratios below 35%. The fundamental mechanisms responsible for these findings are not clear, but a number of possible explanations are discussed.