tbuckley/cabot-search huggingface dataset:
Rates of DNA change and phylogeny from the DNA sequences of the alcohol dehydrogenase gene for five closely related species of Hawaiian Drosophila.
Authors: R G Rowan, J A Hunt
Journal: Molecular Biology and Evolution (1991)

The sequence of 1.6 kb of DNA surrounding the alcohol dehydrogenase (Adh) gene from five species of the Planitibia subgroup of the Hawaiian picture-winged Drosophila, with estimated divergence times of 0.4-5.1 Myr, has been determined. The gene trees which were found by using the sequence divergence from different regions of the sequences are generally in accord with the phylogeny proposed for these species when chromosomal inversions and island of origin are used. One of the species (D. picticornis) appears to be more distant from the other species in this group than they are from a member of the Grimshawi group (D. affinidisjuncta) which is chromosomally more distant. Two of the species (D. differens and D. plantibia) show heterogeneity in the nucleotide changes in the Adh coding region, heterogeneity which is interpreted to be due to a gene conversion or recombination after hybridization between the two species. The minimal rate of nucleotide substitution of synonymous nucleotides and of nontranscribed nucleotides downstream from the coding region is estimated as 1.5 x 10(-8) and 1.1 x 10(-8) substitutions/nucleotide/year, respectively. This rate is two to three times the maximal rate estimated for mammalian synonymous substitutions.
Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma
Authors: Qiang Gao, Xiao-Ying Wang, Shuang-Jian Qiu, Ichiro Yamato, Masayuki Sho, Yoshiyuki Nakajima, Jian Zhou, Bai-Zhou Li, Ying-Hong Shi, Yong-Sheng Xiao, Yang Xu, Jia Fan
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The aberrant expression of programmed cell death 1 ligands 1 and 2 (PD-Ls) on tumor cells dampens antitumor immunity, resulting in tumor immune evasion. In this study, we investigated the expression of PD-Ls in human hepatocellular carcinoma (HCC) to define their prognostic significance after curative surgery. Experimental Design: Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B+ cytotoxic and FoxP3+ regulatory T cell infiltration on tissue microarrays containing 240 randomly selected HCC patients who underwent surgery. The results were further verified in an independent cohort of 125 HCC patients. PD-Ls expression on HCC cell lines was detected by Western blot assay. Results: Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence. No correlation was found between PD-Ls expression and granzyme B+ lymphocyte infiltration, whereas a significant positive correlation was detected between PD-Ls expression and FoxP3+ lymphocyte infiltration. In addition, tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence. The prognostic value of PD-L1 expression was validated in the independent data set. Conclusion: Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against this fatal malignancy.
miR-34a as part of the resistance network in chronic lymphocytic leukemia
Authors: Thorsten Zenz, Julia Mohr, Eric Eldering, Arnon P. Kater, Andreas Bühler, Dirk Kienle, Dirk Winkler, Jan Dürig, Marinus H. J. van Oers, Daniel Mertens, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2008)
Metabolic Fate of Chylomicron Phospholipids and Apoproteins in the Rat
Authors: Alan R. Tall, Peter H. R. Green, Robert M. Glickman, John W. Riley
Journal: Journal of Clinical Investigation (1979)

To study the metabolic fate of chylomicron phospholipid and apoproteins, 15 mg of doubly labeled ([3H]leu, [32P]phospholipid) rat mesenteric lymph chylomicrons were injected as an intravenous bolus into conscious rats. The specific radioactivity, composition, pool size, and morphology of the plasma lipoproteins were determined after 2-60 min. After injection of chylomicrons, there was a rapid transfer of radioactivity into high density lipoproteins (HDL). At peak specific activity in HDL (2-5 min), 35% of injected apoprotein and 25% of phospholipid radioactivity were recovered in HDL (d 1.063-1.21 g/ml), with smaller recoveries in other lipoproteins and liver. There was an initial rapid rise of 32P specific activity in HDL and d 1.02-1.063 lipoproteins (low density lipoproteins [LDL]), but whereas LDL specific activity subsequently converged with that of d < 1.02 lipoproteins, HDL specific activity decayed more rapidly than LDL or d < 1.02 lipoproteins.
Oxidant-antioxidant balance in alveolar macrophages from newborn rats
Authors: C Delacourt, MP d'Ortho, I Macquin-Mavier, S Pezet, B Housset, C Lafuma, A Harf
Journal: European Respiratory Journal (1996)

An oxidant-antioxidant imbalance in neonatal alveolar macrophages (AMs) may contribute to the increased susceptibility to lung injury described in the neonatal period. We therefore evaluated oxygen radical production by rat AMs at various postnatal ages, and measured in parallel cellular antioxidant enzyme activities. AMs were obtained by bronchoalveolar lavage from rats aged &lt; 24 h, 21 days and 5 weeks, and results were compared to those obtained with adult rat AMs. Intracellular production of oxygen radical species, estimated fluorometrically using 2',5'-dichlorofluorescein diacetate as the substrate, was significantly reduced in neonates as compared with adults, both in the presence and in the absence of cell stimulation with phorbol myristate acetate (PMA) or opsonized zymosan. A similar pattern was observed for the extracellular release of oxygen radical species, evaluated by lucigenin-enhanced chemiluminescence (CL) or peroxidase-catalysed CL oxidation of luminol: peak CL values measured after cell stimulation with PMA or opsonized zymosan remained significantly lower for AMs from newborn rats than for AMs from adults. By contrast, high values for antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) in AMs were demonstrated in newborns as compared to adults. We conclude that high antioxidant activity in rat AMs after birth may be at least partly responsible for the low production of oxygen metabolites observed during the same period.
A Phase II Pharmacodynamic Study of Erlotinib in Patients with Advanced Non–Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy
Authors: Enriqueta Felip, Federico Rojo, Martin Reck, Astrid Heller, Barbara Klughammer, Gemma Sala, Susana Cedres, Sergio Peralta, Heiko Maacke, Dorothee Foernzler, Marta Parera, Joachim Möcks, Cristina Saura, Ulrich Gatzemeier, José Baselga
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non–small cell lung cancer patients refractory to platinum-based chemotherapy. Experimental Design: Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment. Results: Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease ≥12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit. Conclusion: In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.
Improvement of asthma control by a concomitant therapy with cineole
Authors: Heinrich Worth
Journal: European Respiratory Journal (2011)

With its proven mucolytic and anti-inflammatory effects it is hypothesized that cineole, the main constituent of eucalyptus oil, improves asthma control. In a double blind, placebo controlled multi-centre-study 247 patients with symptomatic asthma were randomly administered 3x200 mg of cineole (n: 126;mean age, 52.3 years) or a placebo (n:121;mean age,53.5 years), per day as a concomitant therapy over 6 months.  The combined primary outcome measures, which were implemented as a multiple criteria testing process were: improvement of FEV1, asthma symptoms and quality of life (AQLQ). Secondary outcome measures included changes in hypersecretion, various respiratory symptoms, and the use of ICS.   Results:  1.Patients treated with cineole showed significantly more improvements to the multiple testing criteria (i.e. improvement of FEV1,p=0.0398; mean improvement of AQLQ, p=0.0475; symptom score of nocturnal asthma, p=0.0325) as compared to placebo group, (p= 0,0027, Wei Lachin test).  2. Secondary outcome measures supported these findings showing reduced dyspnea and cough as well as overall better health condition amongst the cineole treatment group.  3. Adverse events were comparable in both groups.   Conclusion:  Concomitant therapy using cineol can lead to improvement in asthma symptoms, lung function and quality of life. This study underlines the fact that cineole actively controls airway inflammation in patients with asthma, and that it is more that simply a mucolytic drug.
Screening for Neurocognitive Impairment in Pediatric Cancer Long-Term Survivors
Authors: Kevin R. Krull, M. Fatih Okcu, Brian Potter, Neelam Jain, ZoAnn Dreyer, Kala Kamdar, Pim Brouwers
Journal: Journal of Clinical Oncology (2008)

Recent studies suggest that up to 40% of childhood cancer survivors may experience neurocognitive problems, a finding that has led the Children's Oncology Group to recommend regular evaluation. However, for a variety of reasons, including costs, time restraints, health insurance, and access to professional resources, these guidelines are often difficult to implement. We report reliability and validity data on a brief neurocognitive screening method that could be used to routinely screen patients in need of comprehensive follow-up.Two hundred forty consecutive patients were screened during their annual visits to a long-term survivor clinic using standard neurocognitive measures and brief parent rating. From this total, 48 patients had a second screening, and 52 patients had a comprehensive follow-up evaluation. Test-retest reliability and predictive and discriminative validity were examined.Good test-retest reliability was demonstrated, with an overall r = 0.72 and all individual subtest correlations greater than r = 0.40. Although means tended to improve from first to second testing, no significant changes were detected (all P > .10). The screen accurately predicted global intellect (F(6,45) = 11.81, P < .0001), reading skills (F(6,45) = 4.74, P < .001), and mathematics (F(6,45) = 3.35, P < .008). Parent rating was a marginal indicator of global intellect only.The brief neurocognitive screening was a better predictor of child functioning than specific parent rating. This brief measure, which can be completed in 30 minutes, is a practical and reliable method to identify cancer survivors in need of further neurocognitive follow-up.
Endoplasmic Reticulum Stress and Inflammation in Obesity and Diabetes
Authors: Sarah Hummasti, Gökhan S. Hotamisligil
Journal: Circulation Research (2010)

Abstract: Obesity is a major problem worldwide that increases risk for a wide range of diseases, including diabetes and heart disease. As such, it is increasingly important to understand how excess adiposity can perturb normal metabolic functions. It is now clear that this disruption involves not only pathways controlling lipid and glucose homeostasis but also integration of metabolic and immune response pathways. Under conditions of nutritional excess, this integration can result in a metabolically driven, low-grade, chronic inflammatory state, referred to as “metaflammation,” that targets metabolically critical organs and tissues to adversely affect systemic homeostasis. Endoplasmic reticulum dysfunction is another important feature of chronic metabolic disease that is also linked to both metabolic and immune regulation. A thorough understanding of how these pathways intersect to maintain metabolic homeostasis, as well as how this integration is altered under conditions of nutrient excess, is important to fully understand, and subsequently treat, chronic metabolic diseases.
Tension hydrothorax--an unrecognized danger.
Authors: K Rabinov, M Stein, H Frank
Journal: Thorax (1966)

Shortness of breath and slight mediastinal shift are not uncommon in the presence of a large pleural effusion.It is not generally recognized, however, that in certain circumstances pleural fluid may accumulate under such greatly increased pressure that it results in gross mediastinal shift and irreversible respiratory and circulatory changes.The following is a report of such a case of fatal 'tension hydrothorax'. CASE REPORTC.A., a 43-year-old woman, suffered increasingly severe dyspnoea, weakness, and right chest pain for two months.
Elevated Pulmonary Pressure in Survivors of Pediatric Cancer: A Physiologic Finding, Not a Specific Disease
Authors: Peter J. Leary, Stephanie J. Harris Nolley, David D. Ralph, Sarah E.S. Leary
Journal: Journal of Clinical Oncology (2013)

1 entitled, "Culture Matters As Well."We share their enthusiasm for the promotion of "nondiscriminatory referring clinician practices," as well as greater exploration of the impact of anthropology and ethnography on patients' decisions regarding cancer care and clinical trial involvement.However, we have no evidence in the early-phase setting that these factors are more important than, for example, objective measures of fitness and comorbidities.Improving cancer clinical trial access for all patients requires greater understanding of the social, cultural, physical, and emotional barriers that patients face.We are reminded by Unger et al 2 not to overlook the importance of aspects of trial design and possible toxicity in patients' decisions to participate.They demonstrated that choosing not to participate in a clinical trial was more likely to be motivated by such clinical considerations than by cost or convenience.Now that we have demonstrated a disparity in referrals for earlyphase trials between the least and most affluent patients in our catchment area, we are motivated to explore causality.At present, we can only speculate on the relative importance of factors such as culture, comorbidity, and referrer bias.
Risk factors for local and regional recurrence in patients with resected N0–N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy
Authors: J.L. Lopez Guerra, D.R. Gomez, S.H. Lin, L.B. Levy, Y. Zhuang, R. Komaki, J. Jaen, A.A. Vaporciyan, S.G. Swisher, J.D. Cox, Z. Liao, D.C. Rice
Journal: Annals of Oncology (2012)
Adenoviral Gene Transfer of FGF-5 to Hibernating Myocardium Improves Function and Stimulates Myocytes to Hypertrophy and Reenter the Cell Cycle
Authors: Gen Suzuki, Te-Chung Lee, James A. Fallavollita, John M. Canty
Journal: Circulation Research (2005)

Fibroblast growth factors (FGFs) have diverse actions on the myocardium but the importance of stimulating angiogenesis versus direct effects of FGFs on cardiac myocytes is unclear. We used intracoronary injection of a replication-deficient adenoviral construct overexpressing FGF-5 (AdvFGF-5) to improve flow and function in swine with hibernating myocardium. Two-weeks after AdvFGF-5 (n=8), wall-thickening increased from 2.4±0.04 to 4.7±0.7 mm in hibernating LAD regions ( P &lt;0.05) whereas remote wall-thickening was unchanged (6.7±0.4 to 5.8±0.5 mm). This was associated with small increases in resting flow to dysfunctional myocardium, but flow during adenosine was unchanged (LAD 1.45±0.27 versus 1.46±0.23 mL/min per g and remote 4.84±0.23 versus 4.71±0.47 mL/min per g, P =NS). Unexpectedly, animals receiving AdvFGF-5 demonstrated a 29% increase in LV mass over the 2-week period ( P &lt;0.05 versus untreated animals with hibernating myocardium and normal shams). Histological analysis confirmed profound myocyte cellular hypertrophy in AdvFGF-5 treated myocardium (19.9±0.32 versus 15.2±0.92 μm in untreated, P &lt;0.001). Myocytes in the proliferative phase of the cell cycle (Ki-67 staining) increased 7-fold after AdvFGF-5 (2,904±405 versus 409±233 per 10 6 myocyte nuclei in untreated, P &lt;0.05). Myocyte nuclei in the mitotic phase (phosphorylated histone H3 staining) also increased after AdvFGF-5 (127±24 versus 35±13 per 10 6 myocyte nuclei in untreated, P &lt;0.05). Thus, rather than angiogenesis, stimulation of hypertrophy and reentry of a small number of myocytes into the mitotic phase of the cell cycle are responsible for the effects of AdvFGF-5 on function. Although additional mechanisms may contribute to the improvement in wall-thickening, overexpression of AdvFGF-5 may afford a way to restore function in hibernating myocardium and ameliorate heart failure in chronic ischemic cardiomyopathy.
Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo
Authors: Heather B. Adkins, Caterina Bianco, Susan G. Schiffer, Paul Rayhorn, Mohammad Zafari, Anne E. Cheung, Olivia Orozco, Dian Olson, Antonella De Luca, Ling Ling Chen, Konrad Miatkowski, Chris Benjamin, Nicola Normanno, Kevin P. Williams, Matthew Jarpe, Doreen LePage, David Salomon, Michele Sanicola
Journal: Journal of Clinical Investigation (2003)

Cripto, a cell surface–associated protein belonging to the EGF-CFC family of growth factor–like molecules, is overexpressed in many human solid tumors, including 70–80% of breast and colon tumors, yet how it promotes cell transformation is unclear. During embryogenesis, Cripto complexes with Alk4 via its unique cysteine-rich CFC domain to facilitate signaling by the TGF-β ligand Nodal. We report, for the first time to our knowledge, that Cripto can directly bind to another TGF-β ligand, Activin B, and that Cripto overexpression blocks Activin B growth inhibition of breast cancer cells. This result suggests a novel mechanism for antagonizing Activin signaling that could promote tumorigenesis by deregulating growth homeostasis. We show that an anti–CFC domain antibody, A8.G3.5, both disrupts Cripto-Nodal signaling and reverses Cripto blockade of Activin B–induced growth suppression by blocking Cripto’s association with either Alk4 or Activin B. In two xenograft models, testicular and colon cancer, A8.G3.5 inhibited tumor cell growth by up to 70%. Both Nodal and Activin B expression was found in the xenograft tumor, suggesting that either ligand could be promoting tumorigenesis. These data validate that functional blockade of Cripto inhibits tumor growth and highlight antibodies that block Cripto signaling mediated through its CFC domain as an important class of antibodies for further therapeutic development.
The Kidney as a Sensor of Cardiovascular Risk in Essential Hypertension
Authors: Luis M. Ruilope
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Renal damage as a consequence of uncontrolled arterial hypertension is well recognized. Antihypertensive therapy has come to very significantly decrease the vascular damage in the kidneys of hypertensive patients. However, prevalence of mild renal insufficiency remains present in a significant proportion of the hypertensive population. This is accompanied by a marked increase in cardiovascular risk, as a consequence of the clustering of other cardiovascular risk factors and of insufficiently controlled BP. Prevention and protection of renal and cardiovascular damage in these patients will be one of the most relevent tasks in the future. E-mail: Luis_M_Ruilope@teleline.es
Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex.
Authors: K Onoé, R Yasumizu, T Oh-Ishi, M Kakinuma, R A Good, K Morikawa
Journal: The Journal of Experimental Medicine (1981)

Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient.
Androgen- and Estrogen-Receptor Content in Spontaneous and Experimentally Induced Canine Prostatic Hyperplasia
Authors: John Trachtenberg, L. Louise Hicks, Patrick C. Walsh
Journal: Journal of Clinical Investigation (1980)

To gain insight into the mechanism by which steroidal hormones influence the development of canine prostatic hyperplasia, nuclear and cytosolic androgen- and estrogen-receptor content, as measured under exchange conditions by the binding of [3H]R1881 (methyltrienolone) and [3H]estradiol, respectively, were quantitated in the prostates of purebred beagles of known age. In young dogs with spontaneously arising and experimentally induced (androstanediol plus estradiol treatment) prostatic hyperplasia, nuclear, but not cytosolic, prostatic androgen-receptor content was significantly greater than that determined in the normal prostates of age-matched dogs (3,452±222 and 4,035±274 fmol/mg DNA vs. 2,096±364 fmol/mg DNA, respectively). No differences were observed between the androgen-receptor content of the normal prostates of young dogs and the hyperplastic prostates of old dogs. The cytosolic and nuclear estrogen-receptor content of spontaneously arising prostatic hyperplasia in both young and old animals was similar to that found in normal prostates. The administration of estradiol plus androstanediol to castrate dogs significantly increased the prostatic nuclear androgen-receptor content over that found in dogs treated only with androstanediol. This estradiol-associated increase in nuclear androgen-receptor content was accompanied by the development of benign prostatic hyperplasia.