tbuckley/cabot-search huggingface dataset:
Treatment Goals of Pulmonary Hypertension
Authors: Vallerie V. McLaughlin, Sean Patrick Gaine, Luke S. Howard, Hanno H. Leuchte, Michael A. Mathier, Sanjay Mehta, Massimillano Palazzini, Myung H. Park, Victor F. Tapson, Olivier Sitbon
Journal: Journal of the American College of Cardiology (2013)
Intrarenal vascular effects of [des-Asp1] angiotensin I and angiotensin III in the dog.
Authors: S L Britton, W H Beierwaltes, M J Fiksen-Olsen, J C Romero
Journal: Circulation Research (1979)

We determined the effects of direct renal intra-arterial injections of [des-Asp^angiotensin I (0.2-3.2 pg) and angiotensin HI (0.00625-0.1 fig) on renal blood flow in 10 dogs anesthetized with pentobarbitaL Both [des-Asp*]angiotensin I and angiotensin HI caused dose-dependent decreases in renal blood flow.The decreases in ipsilateral renal blood flow occurred in the absence of alterations in systemic arterial pressure and flow to the contralateral kidney, suggesting that the response was a local event.The renovascular responses to [des-Asp'jangiotensin I were greatly attenuated during the intravenous administration of SQ 20881, a synthetic peptide that competitively inhibits angiotensin converting enzyme., SQ 20881 did not alter the vasoconstrictor responses to angiotensin EH, angiotensin n, or norepinephrine.[Ue'jAngiotenain HI (an angiotensin HI antagonist) abolished decreases in renal blood flow produced by [des-Asp'langiotenflin L, angiotensin H angiotensin HL and angiotensin I, whereas the response to norepinephrine was unchanged.These results suggest that the decrease in renal blood flow produced by [des-Asp'Jangiotensin I is due to its local enzymatic conversion to angiotensin HI.About 7% of [des-Asp'Jangiotensin I is converted to angiotensin HI during one transit through the kidney.Circ Res 44:666-671, 1979IT HAS BEEN demonstrated recently that [des-Asp'jangiotensin LI (angiotensin III) is as potent as angiotensin II in decreasing renal blood flow, and it was hypothesized that the local production of angiotensin HI occurs at the level of the renal arteriolar receptor (Freeman et aL, 1975).Data are available to support the existence of two pathways for the generation of angiotensin HI: the first from angiotensin II by the cleavage of the N-terminal aspartic acid through the action of aminopeptidases (Glenner et al., 1962;Regoli et al.,
Human Neutrophil Peptides and Phagocytic Deficiency in Bronchiectatic Lungs
Authors: Stefanos Voglis, Kieran Quinn, Elizabeth Tullis, Mingyao Liu, Melanie Henriques, Celia Zubrinich, Oscar Peñuelas, Holman Chan, Frances Silverman, Vera Cherepanov, Neil Orzech, Aye Aye Khine, André Cantin, Arthur S. Slutsky, Gregory P. Downey, Haibo Zhang
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: A well-known clinical paradox is that severe bacterial infections persist in the lungs of patients with cystic fibrosis (CF) despite the abundance of polymorphonuclear neutrophils (PMN) and the presence of a high concentration of human neutrophil peptides (HNP), both of which are expected to kill the bacteria but fail to do so. The mechanisms remain unknown.Objectives: This study examined several possible mechanisms to understand this paradox.Methods: PMN were isolated from sputum and blood of subjects with and without CF or non-CF bronchiectasis for phagocytic assays. HNP isolated from patients with CF were used to stimulate healthy PMN followed by phagocytic tests.Measurements and Main Results: PMN isolated from the sputum of the bronchiectatic patients display defective phagocytosis that correlated with high concentrations of HNP in the lung. When healthy PMN were incubated with HNP, decreased phagocytic capacity was observed in association with depressed surface Fcγ RIII, actin-filament remodeling, enhanced intracellular Ca2+, and degranulation. Treatment of PMN with an intracellular Ca2+ blocker or α1-proteinase inhibitor to attenuate the activity of HNP largely prevented the HNP-induced phagocytic deficiency. Intratracheal instillation of HNP in Pallid mice (genetically deficient in α1-proteinase inhibitor) resulted in a greater PMN lung infiltration and phagocytic deficiency compared with wild-type mice.Conclusions: HNP or PMN alone exert antimicrobial ability, which was lost as a result of their interaction. These effects of HNP may help explain the clinical paradox seen in patients with inflammatory lung diseases, suggesting HNP as a novel target for clinical therapy.
Intermittent KoldBlue cryotherapy of 3×10 min changes mid-portion Achilles tendon microcirculation
Authors: Karsten Knobloch, Ruth Grasemann, Marcus Spies, Peter M Vogt
Journal: British Journal of Sports Medicine (2006)

Neovascularisation and microcirculatory changes have been reported in Achilles tendinopathy. Cryotherapy and compression, as part of a rest, ice, compression and elevation regimen, are shown to decrease pain and improve function. However, the microcirculatory changes following a given dosage of cryotherapy on mid-portion Achilles tendon remain unclear.Prospective clinical cohort study, level of evidence 2.30 people (12 males, 33 (SD 12) years, body mass index 25.6 (5.3) kg/m2) were included in the cohort. 3x10 min KoldBlue ankle-cooling bandages were applied and microcirculation of Achilles tendon mid-portion was real-time and continuously assessed using a laser-Doppler-spectrophotometry system (O2C, Germany).Superficial capillary blood flow was reduced from 42 to 6, 5 and 3 relative units (rU) in the first, second and third cryotherapy periods, respectively (-65%, p = 0.001), with no significant capillary hyperaemia. Deep capillary tendon blood flow was reduced from 180 to 82, 53 and 52 rU (-71%, p = 0.001) within 6-9 min of application without hyperaemia. Superficial tendon oxygen saturation dropped significantly from 43% to 26%, 18% and 11% (p = 0.001) after repetitive cryotherapy, with persisting increase of tendon oxygenation during rewarming (51%, 49% and 54%, p = 0.077) up to 27% of the baseline level. At 8 mm tendon depth, cryotherapy preserved local oxygenation. Relative postcapillary venous tendon filling pressures were favourably reduced from 41 (11) to 31, 28 and 26 rU (-36%, p = 0.001) superficially and from 56 (11) to 45, 46 and 48 rU (-18%, p = 0.001) in deep capillary blood flow during cryotherapy, facilitating capillary venous clearance.Intermittent cryotherapy of 3x10 min significantly decreases local Achilles tendon mid-portion capillary blood flow by 71%. Within 2 min of rewarming, tendon oxygen saturation is re-established following cryotherapy. Postcapillary venous filling pressures are reduced during cryotherapy, favouring capillary venous outflow of the healthy Achilles tendon.
Aberrant CBFA2T3B gene promoter methylation in breast tumors.
Authors: Anthony J Bais, Alison E Gardner, Olivia LD McKenzie, David F Callen, Grant R Sutherland, Gabriel Kremmidiotis
Journal: Molecular Cancer (2004)

The CBFA2T3 locus located on the human chromosome region 16q24.3 is frequently deleted in breast tumors. CBFA2T3 gene expression levels are aberrant in breast tumor cell lines and the CBFA2T3B isoform is a potential tumor suppressor gene. In the absence of identified mutations to further support a role for this gene in tumorigenesis, we explored whether the CBFA2T3B promoter region is aberrantly methylated and whether this correlates with expression. Aberrant hypo and hypermethylation of the CBFA2T3B promoter was detected in breast tumor cell lines and primary breast tumor samples relative to methylation index interquartile ranges in normal breast counterpart and normal whole blood samples. A statistically significant inverse correlation between aberrant CBFA2T3B promoter methylation and gene expression was established. CBFA2T3B is a potential breast tumor suppressor gene affected by aberrant promoter methylation and gene expression. The methylation levels were quantitated using a second-round real-time methylation-specific PCR assay. The detection of both hypo and hypermethylation is a technicality regarding the methylation methodology.
Primary Defects in β-Cell Function Further Exacerbated by Worsening of Insulin Resistance Mark the Development of Impaired Glucose Tolerance in Obese Adolescents
Authors: Anna M.G. Cali, Chiara Dalla Man, Claudio Cobelli, James Dziura, Aisha Seyal, Melissa Shaw, Karin Allen, Shu Chen, Sonia Caprio
Journal: Diabetes Care (2008)

OBJECTIVE—Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing prevalence among obese adolescents. The purpose of this study was to determine the natural history of progression from normal glucose tolerance (NGT) to IGT in obese adolescents. RESEARCH DESIGN AND METHODS—We determined the evolution of β-cell function, insulin sensitivity (SI), and glucose tolerance in a multiethnic group of 60 obese adolescents over the course of approximately 30 months. Each subject underwent three serial 3-h oral glucose tolerance tests. Dynamic, static, and total β-cell responsivity (Φd, Φs, and Φtot, respectively) and Si were assessed by oral C-peptide and glucose minimal models. The disposition index (DI), which adjusts insulin secretion for Si, was calculated. RESULTS—At baseline, all 60 subjects had NGT. Seventy-seven percent (46 subjects) maintained NGT over the three testing periods (nonprogressors), whereas 23% (14 subjects) developed IGT over time (progressors). At baseline, percent fat and BMI Z score were comparable between the groups. Fasting plasma glucose, 2-h glucose, glucose area under the curve at 180 min, and Φd were significantly different between the two groups at baseline, whereas Si was comparable between the two groups. Over time, although Si remained unchanged in nonprogressors, it steadily worsened by ∼45% (P &amp;gt; 0.04) in progressors. β-Cell responsivity decreased by 20% in progressors, whereas it remained stable in nonprogressors. The DI showed a progressive decline in progressors compared with a modest improvement in nonprogressors (P = 0.02). CONCLUSIONS—Obese adolescents who progress to IGT may manifest primary defects in β-cell function. In addition, progressive decline in Si further aggravates β-cell function, contributing to the worsening of glucose intolerance.
Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial
Authors: Ira M Jacobson, Gregory J Dore, Graham R Foster, Michael W Fried, Monica Radu, Vladimir V Rafalsky, Larysa Moroz, Antonio Craxi, Monika Peeters, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Guy De La Rosa, Ronald Kalmeijer, Jane Scott, Rekha Sinha, Maria Beumont-Mauviel
Journal: The Lancet (2014)
Body composition in ileostomy patients with and without ileal resection.
Authors: J C Cooper, A Laughland, E J Gunning, L Burkinshaw, N S Williams
Journal: Gut (1986)

Body composition was measured in 24 patients who had previously undergone proctocolectomy and ileostomy. One group (control group) had undergone resection of only small amounts of terminal ileum (median 4 cm), the other group of patients (resected group) had undergone resection of greater lengths of small bowel (median 54 cm). These values of body composition were then compared with predicted values in normal subjects. Proctocolectomy and ileostomy without ileal resection did not significantly affect body weight, or the body contents of fat or water, but led to a reduction in total body nitrogen and total body potassium, suggesting a reduction in fat free mass. A modest resection of the terminal ileum undertaken during the course of proctocolectomy decreased body weight largely because of a reduction in body fat. None of the ileostomy patients was found to be dehydrated.
SAD: A Presynaptic Kinase Associated with Synaptic Vesicles and the Active Zone Cytomatrix that Regulates Neurotransmitter Release
Authors: Eiji Inoue, Sumiko Mochida, Hiroshi Takagi, Susumu Higa, Maki Deguchi-Tawarada, Etsuko Takao-Rikitsu, Marie Inoue, Ikuko Yao, Kosei Takeuchi, Isao Kitajima, Mitsutoshi Setou, Toshihisa Ohtsuka, Yoshimi Takai
Journal: Neuron (2006)
Immunotherapy: An Iron Oxide Nanocarrier Loaded with a Pt(IV) Prodrug and Immunostimulatory dsRNA for Combining Complementary Cancer Killing Effects (Adv. Healthcare Mater. 7/2015)
Authors: Javier Hernández‐Gil, Macarena Cobaleda‐Siles, Aintzane Zabaleta, Luca Salassa, Javier Calvo, Juan C. Mareque‐Rivas
Journal: Advanced Healthcare Materials (2015)

Micelles filled with iron oxide nanoparticles (IONPs) with a size suitable for effective lymphatic delivery are loaded with a cisplatin Pt(IV) prodrug and a immunostimulatory dsRNA (poly (I:C)) to provide targeted chemoimmunotherapy. On page 1034, J. C. Mareque-Rivas and colleagues show that, compared to the free drugs, the poly (I:C)-Pt(IV)-IONPs exhibit greatly enhanced cancer cell killing properties and ability to activate dendritic cells.
NHS could face even tougher targets on efficiency and productivity
Authors: A. O'Dowd
Journal: BMJ (2010)

The NHS in England may have to make productivity and efficiency savings even higher than the £15bn (€17bn; $22bn) to £20bn currently set by the government, MPs have been told.

Experts on economic and health policy have warned that the health service is facing a “massive” step up in the level of efficiency savings it must meet over the next few years and that these could increase even more.

The parliamentary health select committee held a one-off evidence session on 25 March for its inquiry into value for money in the NHS.

MPs asked the witnesses what state they expected the NHS’s finances to be in over the next parliamentary period.

John Appleby, chief economist at …
Epistasis between mouse Klra and major histocompatibility complex class I loci is associated with a new mechanism of natural killer cell–mediated innate resistance to cytomegalovirus infection
Authors: Marie-Pierre Desrosiers, Agnieszka Kielczewska, J-C Loredo-Osti, Sonia Girard Adam, Andrew P Makrigiannis, Suzanne Lemieux, Trung Pham, Melissa B Lodoen, Kenneth Morgan, Lewis L Lanier, Silvia M Vidal
Journal: Nature Genetics (2005)
Androgen Receptor Controls <i>EGFR</i> and <i>ERBB2</i> Gene Expression at Different Levels in Prostate Cancer Cell Lines
Authors: Jean-Christophe Pignon, Benjamin Koopmansch, Gregory Nolens, Laurence Delacroix, David Waltregny, Rosita Winkler
Journal: Cancer Research (2009)

EGFR or ERBB2 contributes to prostate cancer (PCa) progression by activating the androgen receptor (AR) in hormone-poor conditions. Here, we investigated the mechanisms by which androgens regulate EGFR and ERBB2 expression in PCa cells. In steroid-depleted medium (SDM), EGFR protein was less abundant in androgen-sensitive LNCaP than in androgen ablation-resistant 22Rv1 cells, whereas transcript levels were similar. Dihydrotestosterone (DHT) treatment increased both EGFR mRNA and protein levels and stimulated RNA polymerase II recruitment to the EGFR gene promoter, whereas it decreased ERBB2 transcript and protein levels in LNCaP cells. DHT altered neither EGFR or ERBB2 levels nor the abundance of prostate-specific antigen (PSA), TMEPA1, or TMPRSS2 mRNAs in 22Rv1 cells, which express the full-length and a shorter AR isoform deleted from the COOH-terminal domain (ARDeltaCTD). The contribution of both AR isoforms to the expression of these genes was assessed by small interfering RNAs targeting only the full-length or both AR isoforms. Silencing of both isoforms strongly reduced PSA, TMEPA1, and TMPRSS2 transcript levels. Inhibition of both AR isoforms did not affect EGFR and ERBB2 transcript levels but decreased EGFR and increased ERBB2 protein levels. Proliferation of 22Rv1 cells in SDM was inhibited in the absence of AR and ARDeltaCTD. A further decrease was obtained with PKI166, an EGFR/ERBB2 kinase inhibitor. Overall, we showed that ARDeltaCTD is responsible for constitutive EGFR expression and ERBB2 repression in 22Rv1 cells and that ARDeltaCTD and tyrosine kinase receptors are necessary for sustained 22Rv1 cell growth.
Bone formation and resorption of highly purified β-tricalcium phosphate in the rat femoral condyle
Authors: Naoki Kondo, Akira Ogose, Kunihiko Tokunaga, Tomoyuki Ito, Katsumitsu Arai, Naoko Kudo, Hikaru Inoue, Hiroyuki Irie, Naoto Endo
Journal: Biomaterials (2005)
Enhanced Redundancy in Akt and Mitogen-activated Protein Kinase-induced Survival of Malignant<b><i>versus</i></b>Normal Prostate Epithelial Cells
Authors: Aarti R. Uzgare, John T. Isaacs
Journal: Cancer Research (2004)

Activation of the downstream akt and mitogen-activated protein kinases is associated with development and progression of prostate cancer to the lethal androgen-independent state. However, the causal role of these downstream kinases in androgen-independent prostate cancers is unknown. In this study, activation and requirements of akt and mitogen-activated protein kinase (erk, p38, and jnk) signaling for the survival and proliferation of five malignant human cell lines encompassing the spectrum of androgen-independent prostate cancers was compared with the activation and requirements in normal prostate epithelial cells. Using Western blotting with phospho-antibodies, we detected differential activation in exponentially growing, growth factor-deprived, and restimulated cultures of malignant versus normal cells. The inhibition of erk, p38, jnk, and akt with U0126, SB203580, SP600125, and Akt inhibitor, respectively, document that normal cells require simultaneous erk and jnk signaling for survival, plus akt signaling for proliferation. In malignant cells, however, only jnk inhibition as monotherapy produces a consistent apoptotic response, although the combinatorial inhibition of jnk, erk, p38 plus akt results in statistically enhanced apoptosis. These results demonstrate that prostate cancer progression to a lethal androgen-independent state involves the acquisition of an enhanced redundancy in downstream survival signaling.
Phylogenetically and spatially conserved word pairs associated with gene-expression changes in yeasts
Authors: Derek Y Chiang, Alan M Moses, Manolis Kellis, Eric S Lander, Michael B Eisen
Journal: Genome biology (2003)

Transcriptional regulation in eukaryotes often involves multiple transcription factors binding to the same transcription control region, and to understand the regulatory content of eukaryotic genomes it is necessary to consider the co-occurrence and spatial relationships of individual binding sites. The determination of conserved sequences (often known as phylogenetic footprinting) has identified individual transcription factor binding sites. We extend this concept of functional conservation to higher-order features of transcription control regions. We used the genome sequences of four yeast species of the genus Saccharomyces to identify sequences potentially involved in multifactorial control of gene expression. We found 989 potential regulatory 'templates': pairs of hexameric sequences that are jointly conserved in transcription regulatory regions and also exhibit non-random relative spacing. Many of the individual sequences in these templates correspond to known transcription factor binding sites, and the sets of genes containing a particular template in their transcription control regions tend to be differentially expressed in conditions where the corresponding transcription factors are known to be active. The incorporation of word pairs to define sequence features yields more specific predictions of average expression profiles and more informative regression models for genome-wide expression data than considering sequence conservation alone. The incorporation of both joint conservation and spacing constraints of sequence pairs predicts groups of target genes that are specific for common patterns of gene expression. Our work suggests that positional information, especially the relative spacing between transcription factor binding sites, may represent a common organizing principle of transcription control regions.
The effect of rugby shoulder padding on peak impact force attenuation
Authors: D A Harris, I R Spears
Journal: British Journal of Sports Medicine (2010)

The introduction of shoulder pads has coincided with a rise in shoulder impact injuries in the game of rugby. In this study, the effect of shoulder pads on impact force attenuation was quantified.Four different commercially available shoulder pads were tested for material properties. Hard and soft objects were dropped from predetermined heights onto a force plate imparting peak impact forces of 500, 1000 and 1500 N. The pads were then placed on the plate and subjected to 10 repeated impacts for each pad and drop height.Institutional laboratory setting.Peak force attenuation, expressed as the percentage reduction of peak force when compared with the no-pad condition, was calculated. Time to peak impact, expressed as the percentage increase of time to peak impact when compared with the no-pad condition, was calculated.All pads were found to reduce peak impact force and increase time to peak impact. Results varied between 1% and 70%, depending on the drop height and properties of the impactor. The best performing pad was the thickest, and all pads were best able to attenuate force under hard-object impacts particularly for the lower loads.Although several limitations exist to laboratory-based studies such as these, the inconsistencies in force attenuation were nonetheless disappointing. The pads appear to ''bottom out'' under higher-impact loads and therefore offer little protection when the athlete may need it most.
Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study
Authors: Alfred I. Neugut, Grace Clarke Hillyer, Lawrence H. Kushi, Lois Lamerato, Nicole Leoce, S. David Nathanson, Christine B. Ambrosone, Dana H. Bovbjerg, Jeanne S. Mandelblatt, Carol Magai, Wei Yann Tsai, Judith S. Jacobson, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2012)

Purpose For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. Patients and Methods We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years. Results Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor– and progesterone receptor–negative status) were associated with increased chemotherapy initiation. Conclusion Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.