tbuckley/cabot-search huggingface dataset:
Hypoxia Regulates Choline Kinase Expression through Hypoxia-Inducible Factor-1α Signaling in a Human Prostate Cancer Model
Authors: Kristine Glunde, Tariq Shah, Paul T. Winnard, Venu Raman, Tomoyo Takagi, Farhad Vesuna, Dmitri Artemov, Zaver M. Bhujwalla
Journal: Cancer Research (2008)

Abstract The intensity of the total choline (tCho) signal in spectroscopic images of tumors is spatially heterogeneous. The likewise heterogeneous physiologic tumor microenvironment may contribute to this heterogeneity. We therefore investigated the relationship between hypoxia, choline metabolites, and choline kinase (Chk) in a human prostate cancer model. Human PC-3 prostate cancer cells were engineered to express enhanced green fluorescent protein (EGFP) under hypoxic conditions. These PC-3-5HRE-EGFP cells were characterized in culture and as tumors transplanted in mice using 1H magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI) combined with EGFP fluorescence microscopy and imaging. Hypoxic EGFP-fluorescing tumor regions colocalized with regions of high tCho in combined MRSI and optical imaging studies. Cellular phosphocholine (PC) and tCho concentrations as well as Chk expression levels significantly increased following exposure of PC-3 cells to hypoxia. A putative promoter region located 5′ of the translation start site of the human chk-α gene was cloned and luciferase (Luc)-based reporter vector constructs were generated. Luc reporter assays provided evidence that some of the putative hypoxia response elements (HRE) within this putative chk-α promoter region functioned in vitro. Chromatin immunoprecipitation assays using an antibody against hypoxia-inducible factor (HIF)-1α showed that HIF-1 can directly bind this region of the endogenous chk-α promoter in hypoxic PC-3-5HRE-EGFP cells. These data suggest that HIF-1 activation of HREs within the putative chk-α promoter region can increase Chk-α expression within hypoxic environments, consequently increasing cellular PC and tCho levels within these environments. [Cancer Res 2008;68(1):172–80]
The Emerging Limbs and Twigs of the East Asian mtDNA Tree
Authors: Toomas Kivisild, Helle-Viivi Tolk, Jüri Parik, Yiming Wang, Surinder S. Papiha, Hans-Jürgen Bandelt, Richard Villems
Journal: Molecular Biology and Evolution (2002)

We determine the phylogenetic backbone of the East Asian mtDNA tree by using published complete mtDNA sequences and assessing both coding and control region variation in 69 Han individuals from southern China. This approach assists in the interpretation of published mtDNA data on East Asians based on either control region sequencing or restriction fragment length polymorphism (RFLP) typing. Our results confirm that the East Asian mtDNA pool is locally region-specific and completely covered by the two superhaplogroups M and N. The phylogenetic partitioning based on complete mtDNA sequences corroborates existing RFLP-based classification of Asian mtDNA types and supports the distinction between northern and southern populations. We describe new haplogroups M7, M8, M9, N9, and R9 and demonstrate by way of example that hierarchically subdividing the major branches of the mtDNA tree aids in recognizing the settlement processes of any particular region in appropriate time scale. This is illustrated by the characteristically southern distribution of haplogroup M7 in East Asia, whereas its daughter-groups, M7a and M7b2, specific for Japanese and Korean populations, testify to a presumably (pre-)Jomon contribution to the modern mtDNA pool of Japan.
Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample
Authors: Emma Colvert, Beata Tick, Fiona McEwen, Catherine Stewart, Sarah R. Curran, Emma Woodhouse, Nicola Gillan, Victoria Hallett, Stephanie Lietz, Tracy Garnett, Angelica Ronald, Robert Plomin, Frühling Rijsdijk, Francesca Happé, Patrick Bolton
Journal: JAMA Psychiatry (2015)

Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population.To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD.We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview-Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs).Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis.On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]).The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD.
Sorafenib in combination with erlotinib or with gemcitabine in elderly patients with advanced non-small-cell lung cancer: a randomized phase II study
Authors: C. Gridelli, F. Morgillo, A. Favaretto, F. de Marinis, A. Chella, G. Cerea, R. Mattioli, G. Tortora, A. Rossi, M. Fasano, G. Pasello, S. Ricciardi, P. Maione, M. Di Maio, F. Ciardiello
Journal: Annals of Oncology (2011)
Catheter tip cultures on open-heart surgery patients: associations with site of catheter and age of patients.
Authors: R Freeman, N Hjersing, A Burridge
Journal: Thorax (1981)

The results of culture of 668 catheter tips from 422 patients are analysed with relation to the site of the catheter and the age of the patient. Coagulase-negative staphylococci were the most common bacterial isolate, but Gram-negative bacilli were found in the venous lines, femoral artery lines, and peripheral lines. Isolations of Gram-negative bacilli were associated with age, being found mainly in those under 1 year and those over 40 years of age. Typing of coagulase-negative staphylococci revealed that Staphylococcus epidermidis is the only variety found in peripheral lines and in lines inserted after operation for complications (central venous, sub-clavian, and long lines), whereas other types occur (along with Staphylococcus epidermidis) in the other lines (left atrial, arterial, and venous). Use of extra lines for the management of postoperative complications thereby increases the risk of Staphylococcus epidermidis gaining access to the circulation. A subgroup of venous lines used to administer inotropic agents was found to be sterile on culture, and this was the result of the anti-oxidant (sodium metabisulphite) in the inotrope solution acting as an antiseptic.
URINARY EXCRETION OF NUCLEIC ACID DERIVATIVES IN PERSONS WITH MYELOID LEUKEMIA 1
Authors: Daniel L. Horrigan
Journal: Journal of Clinical Investigation (1954)

Considerable evidence has been presented to link growth and maturation of granulocytic leukocytes with cellular nucleic acid metabolism. The mechanisms of this relationship, however, remain unclear. Thus, Thorell (1), by microspectrophotometric techniques, has correlated the concentration of ribonucleic acid (RNA) present in the cytoplasm and nucleolus with growth potentialities of the blood cell. He showed that during maturation, cellular RNA concentration decreased progressively, paralleling the declining growth activity of the cell. Furthermore, he demonstrated the failure of rapidly proliferating cells in acute leukemia to show the rapid decline in RNA metabolism which is seen in normally proliferating cells following their active growth phase. These differences in RNA content between immature and mature blood cells have been confirmed by Davidson, Leslie, and White (2). In this study, peripheral blood cells showed a significantly lower content of RNA phosphorus than bone marrow cells both in normal and in leukemic persons. However, decrease in the content of desoxyribonucleic (DNA) phosphorus in peripheral blood cells as compared with marrow cells was of borderline significance.
Critical Role Of T Follicular-helper Cells In B Cell Autoimmunity During Lymphopenia
Authors: M. Imamura, T. Kanzaki, K. Kawahata, L. Akahira, K. Michishita, T. Eri, M. Dohi, T. Tokuhisa, K. Yamamoto
Journal: Journal of Allergy and Clinical Immunology (2012)
Randomized Trial of Postoperative Reirradiation Combined With Chemotherapy After Salvage Surgery Compared With Salvage Surgery Alone in Head and Neck Carcinoma
Authors: François Janot, Dominique de Raucourt, Ellen Benhamou, Christophe Ferron, Gilles Dolivet, René-Jean Bensadoun, Marc Hamoir, Bernard Géry, Morbize Julieron, Marine Castaing, Etienne Bardet, Vincent Grégoire, Jean Bourhis
Journal: Journal of Clinical Oncology (2008)

Purpose Full-dose reirradiation combined with chemotherapy has been shown to be feasible after salvage surgery with acceptable toxicity. The Groupe d’Etude des Tumeurs de la Tête et du Cou and Groupe d’Oncologie Radiothérapie Tête Et Cou groups performed a randomized study to assess its efficacy. Patients and Methods Between 1999 and 2005, 130 patients with head and neck cancer were treated with salvage surgery and randomly assigned to full-dose reirradiation combined with chemotherapy (RT arm) or to observation (a “wait and see” approach; WS arm). Eligibility criteria were recurrence or a second primary tumor in a previously irradiated area, no major sequelae resulting from the first radiotherapy, good general condition, no distant metastasis, and salvage surgery with macroscopic complete resection. Patients in the RT arm received 60 Gy over 11 weeks combined with concomitant fluorouracil and hydroxyurea. Results Sixty-five patients were randomly assigned to each arm. There was no imbalance in the distribution of the main tumor and patients characteristics. The most serious acute toxicity in the RT arm was mucositis, attaining grade 3 or 4 in 28% of patients. At 2 years, 39% of patients in the RT arm and 10% in the WS arm experienced grade 3 or 4 late toxicity according to Radiation Therapy Oncology Group criteria (P = .06). Disease-free survival (DFS) was significantly improved in the RT arm, with a hazard ratio of 1.68 (95% CI, 1.13 to 2.50; P = .01), but overall survival (OS) was not statistically different. Conclusion Full-dose reirradiation combined with chemotherapy after salvage surgery significantly improved DFS, but had no significant impact on OS. An increase in both acute and late toxicity was observed.
Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes
Authors: S Wei
Journal: Cardiovascular Research (2002)

Objective: Cardiac Na/Ca exchanger (NCX) protein is up-regulated and intracellular free magnesium ([Mg2+]i) is significantly reduced in experimental heart failure. We asked whether changes in [Mg2+]i in a physiologically relevant range could alter the INCX. Methods: The nickel-sensitive current was measured in voltage-clamped myocytes (Yorkshire pig; left ventricular) exposed to ramp pulses at 37°C in Tyrode's solution containing ouabain, nifedipine and ±Ni2+ (5 mmol/l). The intracellular free [Ca2+] and [Mg2+] concentrations were set at 50 nmol/l and 1.25 mmol/l (HiMg) or 0.13 mmol/l (LoMg), respectively, through pipette dialysis. Results: Reducing [Mg2+]i resulted in a significant increase in both outward and inward Ni-sensitive current without a shift in the reversal potential. This effect was not due to the inadvertent reduction of intracellular free [ATP] secondary to binding of ATP to Mg2+; reducing intracellular [ATP] in LoMg cells from 1.35 mmol/l to 0.18 mmol/l did not affect INCX. The intracellular free [Ca2+] was raised from 50 to 200 nmol/l, resulting in augmented inward and outward current due to calcium activation. HiMg attenuated both inward and outward currents significantly compared to LoMg, suggesting that [Mg2+]i competes with [Ca2+]i at the allosteric regulatory site. Conclusion: Cytosolic free magnesium modulates the INCX over a physiologic range independent of [ATP]i. Reduced [Mg2+]i in heart failure could contribute to altered calcium regulation of the NCX, contributing to the altered heart failure phenotype through enhanced NCX activity.
Tiotropium Respimat Inhaler and the Risk of Death in COPD
Authors: Robert A. Wise, Antonio Anzueto, Daniel Cotton, Ronald Dahl, Theresa Devins, Bernd Disse, Daniel Dusser, Elizabeth Joseph, Sabine Kattenbeck, Michael Koenen-Bergmann, Gordon Pledger, Peter Calverley
Journal: New England Journal of Medicine (2013)

Tiotropium delivered at a dose of 5 μg with the Respimat inhaler showed efficacy similar to that of 18 μg of tiotropium delivered with the HandiHaler inhalation device in placebo-controlled trials involving patients with chronic obstructive pulmonary disease (COPD). Although tiotropium HandiHaler was associated with reduced mortality, as compared with placebo, more deaths were reported with tiotropium Respimat than with placebo.In this randomized, double-blind, parallel-group trial involving 17,135 patients with COPD, we evaluated the safety and efficacy of tiotropium Respimat at a once-daily dose of 2.5 μg or 5 μg, as compared with tiotropium HandiHaler at a once-daily dose of 18 μg. Primary end points were the risk of death (noninferiority study, Respimat at a dose of 5 μg or 2.5 μg vs. HandiHaler) and the risk of the first COPD exacerbation (superiority study, Respimat at a dose of 5 μg vs. HandiHaler). We also assessed cardiovascular safety, including safety in patients with stable cardiac disease.During a mean follow-up of 2.3 years, Respimat was noninferior to HandiHaler with respect to the risk of death (Respimat at a dose of 5 μg vs. HandiHaler: hazard ratio, 0.96; 95% confidence interval [CI], 0.84 to 1.09; Respimat at a dose of 2.5 μg vs. HandiHaler: hazard ratio, 1.00; 95% CI, 0.87 to 1.14) and not superior to HandiHaler with respect to the risk of the first exacerbation (Respimat at a dose of 5 μg vs. HandiHaler: hazard ratio, 0.98; 95% CI, 0.93 to 1.03). Causes of death and incidences of major cardiovascular adverse events were similar in the three groups.Tiotropium Respimat at a dose of 5 μg or 2.5 μg had a safety profile and exacerbation efficacy similar to those of tiotropium HandiHaler at a dose of 18 μg in patients with COPD. (Funded by Boehringer Ingelheim; TIOSPIR ClinicalTrials.gov number, NCT01126437.).
Crohn's disease in Blackpool--incidence and prevalence 1968-80.
Authors: F I Lee, F T Costello
Journal: Gut (1985)

The occurrence of Crohn9s disease has been studied in a population of approximately 300,000 in Blackpool, a seaside town in the north of England, and the surrounding area. Between 1968 and 1980, 156 patients resident in the area were diagnosed as having Crohn9s disease - an annual incidence of 4 per 10(5). For the years 1971-75, the incidence was 3.3 per 10(5) and for 1976-80 it was 6.1 per 10(5). The trend is upwards but there was an apparent fall in incidence in 1974-75. In 1979 there was a peak incidence of 8 per 10(5). Over the period of study, there was an increase in all three anatomical types, small intestinal, large intestinal, and mixed disease but this increase was most marked for purely large intestinal disease. Of the 156 cases, 35% had small intestinal disease at presentation, 35% had large intestinal disease and 30% had mixed disease. The overall sex ratio was female to male 1.89:1 but highest for large bowel disease -2.6:1. Analysis of age at presentation at different sites shows a unimodal distribution for small intestinal and mixed disease with a peak in the third and fourth decades. Large bowel Crohn9s disease shows a bimodal distribution with peaks in the third and eighth decades. During the period of study we identified 185 cases of Crohn9s disease in the study population. On 31 December 1980, 141 patients with the condition were living, a prevalence of 47 per 10(5).
Elevated Peroxiredoxin 1, but not NF-E2–Related Factor 2, Is an Independent Prognostic Factor for Disease Recurrence and Reduced Survival in Stage I Non–Small Cell Lung Cancer
Authors: Joo-Heon Kim, Paul N. Bogner, Nithya Ramnath, Yoorim Park, Jihnhee Yu, Young-Mee Park
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Lung cancer is the leading cause of cancer death with chance of survival restricted to a subset of non–small cell lung cancer (NSCLC) patients able to undergo surgical resection. However, the recurrence rate of NSCLC after surgery remains high with few prognostic indicators of clinical outcome. Peroxiredoxin1 (Prx1) is shown to be elevated in various cancers and confers an aggressive survival phenotype. We recently cloned the prx1 promoter and found that NF-E2–related factor 2 (Nrf2) is a key transcription factor for prx1 up-regulation. Previous studies suggest that Nrf2 may be constitutively activated in NSCLC. Based on the above information, we investigated whether Prx1 and/or Nrf2 levels have prognostic significance in stage I NSCLC. Methods and Results: Immunohistochemical expression of Prx1 and Nrf2 was evaluated in paraffin-embedded tissues from 90 patients who underwent a curative surgical resection. Increased expression of cytosolic Prx1 (66.7%) and nuclear Nrf2 (61.8%) was observed in this series. Prx1 elevation, but not Nrf2, correlated with reduced recurrence-free survival and overall survival on univariate (P = 0.01 and P = 0.03) and multivariate (P = 0.003 and P = 0.005) analyses. Conclusion: This is the first study to test the prognostic significance of Prx1 and Nrf2 in human cancers. Our results show that Prx1 expression status predicts for recurrence and shorter survival in stage I NSCLC after surgery. Considering the possible role of Prx1 and Nrf2 in radioresistance/chemoresistance, it warrants future investigation to evaluate whether elevated Prx1 and/or Nrf2 levels are predictive of treatment response in advanced lung cancer and other malignancies.
Pathology, Symptoms, and Treatment of Cellulitis of the Neck
Authors: G. H. Younge
Journal: BMJ (1884)

August 3rd.-The patient was dressed, anid sitting uip.The lhead couild be placed quite straight without pain.Auguist 4th (third day after operation).-Theboy recommiienced the iie(lical gymnliastic treatment.The two sterno-mastoids were of exactly the saine length.Tlle patient couldl hold the head perfectly straiglht on payilng atteiltioIn.August 7tli.-Theleft muscle contractedl a little while the boy was lying on hi.s back, on attempting to raise the hlead from off the couch (flexion of the neck).August 9th.-Thedivided muiscle had healedl sufficienitly to contract rigorously, although only the ninth day after the operlatio.August 30th.-Thepatient ceased treatment.The spine wvas quite straight.The two sterino-mastoids remained of equal length.A year aftelrwards, there had not been any relapse, and the head remainedl qjuite straighlt.i
New variant Creutzfeldt-Jakob disease: psychiatric features
Authors: M Zeidler, EC Johnstone, RW K Bamber, CM Dickens, CJ Fisher, AF Francis, R Goldbeck, R Higgo, EC Johnson-Sabine, GJ Lodge, P McGarry, S Mitchell, L Tarlo, M Turner, P Ryley, RG Will
Journal: The Lancet (1997)
Pharmacological manipulation of Bcl-2 family members to control cell death
Authors: A. Letai
Journal: Journal of Clinical Investigation (2005)

The commitment to programmed cell death involves complex interactions among pro- and antiapoptotic members of the Bcl-2 family of proteins. The physiological result of a decision by these proteins to undergo cell death is permeabilization of the mitochondrial outer membrane. Pharmacologic manipulation of proteins in this family appears both feasible and efficacious, whether the goal is decreased cell death, as in ischemia of the myocardium or brain, or increased cell death, as in cancer.
Aggressive Chronic Lymphocytic Leukemia with Elevated Genomic Complexity Is Associated with Multiple Gene Defects in the Response to DNA Double-Strand Breaks
Authors: Peter Ouillette, Samuel Fossum, Brian Parkin, Li Ding, Paula Bockenstedt, Ammar Al-Zoubi, Kerby Shedden, Sami N. Malek
Journal: Clinical Cancer Research (2010)

Genomic complexity is present in approximately 15% to 30% of all chronic lymphocytic leukemia (CLL) and has emerged as a strong independent predictor of rapid disease progression and short remission duration in CLL. We conducted this study to advance our understanding of the causes of genomic complexity in CLL.We have obtained quantitative measurements of radiation-induced apoptosis and radiation-induced ATM autophosphorylation in purified CLL cells from 158 and 140 patients, respectively, and have used multivariate analysis to identify independent contributions of various biological variables on genomic complexity in CLL.Here, we identify a strong independent effect of radiation resistance on elevated genomic complexity in CLL and describe radiation resistance as a predictor for shortened CLL survival. Furthermore, using multivariate analysis, we identify del17p/p53 aberrations, del11q, del13q14 type II (invariably resulting in Rb loss), and CD38 expression as independent predictors of genomic complexity in CLL, with aberrant p53 as a predictor of approximately 50% of genomic complexity in CLL. Focusing on del11q, we determined that normalized ATM activity was a modest predictor of genomic complexity but was not independent of del11q. Through single nucleotide polymorphism array-based fine mapping of del11q, we identified frequent monoallelic loss of Mre11 and H2AFX in addition to ATM, indicative of compound del11q-resident gene defects in the DNA double-strand break response.Our quantitative analysis links multiple molecular defects, including for the first time del11q and large 13q14 deletions (type II), to elevated genomic complexity in CLL, thereby suggesting mechanisms for the observed clinical aggressiveness of CLL in patients with unstable genomes.