tbuckley/cabot-search huggingface dataset:
Hyperinsulinism Due to Islet-cell Adenoma
Authors: W. G. D. Murray
Journal: BMJ (1949)

A whole-body positron-emission transaxial tomograph (PETT III) was to image the cross-sectional distribution of <sup>13</sup>NH<sub>3</sub> and <sup>11</sup>CO-hemoglobin in the human brain and heart. Carotid and intravenous bolus injections of <sup>13</sup>NH<sub>3</sub> in the rhesus monkey had shown that <sup>13</sup>NH<sub>3</sub> is efficiently extracted by the brain and clears from it slowly (half-time, 40–50 min for carotid injections and 60–70 min for intravenous injections). The intravenous tomographic images in humans showed an excellent relationship between <sup>13</sup>NH<sub>3</sub> uptakes in the cortex, subcortical white matter, cerebellum, and brain stem and normal blood perfusion or flow in these structures. Cerebral lesions with high (metastasis) and low (stroke) blood flows showed correspondingly high and low uptakes of <sup>13</sup>NH<sub>3</sub>. Large- and small-vascular structures of the brain were also clearly seen in <sup>11</sup>CO-hemoglobin tomographic images. Normal myocardium and the ventricular chambers were well defined, and a transmural anterior myocardial infarct was clearly shown. The effective combination of positron transaxial tomography and compounds labeled with positron-emitters provides a safe new method for quantitatively imaging hemodynamic and physiologic functions of selected organs with tomographic image quality.
Computer Quantitation of the ST-Segment Response during Maximal Treadmill Exercise
Authors: PAUL L. MCHENRY, DARWELL E. STOWE, MALCOLM C. LANCASTER
Journal: Circulation (1968)

The ST-segment response during maximal treadmill exercise was quantitated by digital computer after excessive noise in the electrocardiographic data was reduced by computer averaging. Both the slope and the depression were quantitated. Two groups of subjects were studied. Group A consisted of 35 subjects between 33 and 57 years of age with confirmed or suspected coronary artery disease. Group N consisted of 73 clinically normal subjects between 24 and 52 years of age. The responses of the group A subjects and the 26 subjects over age 35 in group N were compared by graphically plotting their ST slope and depression values from the last minute of exercise. A linear discriminant analysis computed from these values resulted in a line of separation between the majority of subjects in each of these two groups. This separation was accomplished even though the majority of subjects in group A did not demonstrate segmental ST depression.
Fat Intake and Breast Cancer Revisited
Authors: S. A. Smith-Warner, M. J. Stampfer
Journal: JNCI Journal of the National Cancer Institute (2007)

fat intake, the uncorrected HR was 1.15 (95% CI = 1.05 to 1.26) and the corrected HR was 1.32 (95% CI = 1.11 to 1.58). Thus, even with correction for measurement error, this study provides further evidence that the association between total fat intake and the risk of breast cancer among postmenopausal women is likely to be modest. Analyses of specifi c subtypes of fat yielded increased risks that ranged from 10% to 13% for a doubling of percent energy from fat, an unrealistic scenario except, perhaps, for the small minority of women with the lowest intakes . When all types of fat were considered simultaneously, only the association for saturated fat re mained statistically signifi cant. Thiebaut et al. found a stronger association between saturated and monounsaturated fat intakes and breast cancer risk among current users of menopausal hormone therapy than among never or former users, which suggests that dietary fat intake may have more infl uence on breast cancer risk when it occurs in the context of an estrogen-rich environment (i.e., menopausal hormone therapy users or premenopausal women). Indeed, the pooled analysis of prospective studies ( 4 ) reported positive associations for polyunsaturated fat and vegetable fat among current users of menopausal hormones but not among never or former users. Furthermore, in the Women’s Health Initiative Dietary Modifi cation Trial ( 6 ), women who were randomly assigned to the low-fat group and who were either using postmenopausal hormones at baseline or who were also randomly assigned to the estrogen plus progestin arm of the trial had a 17% (95% CI = 1% to 31%) reduction in breast cancer incidence compared with the control group; by contrast, there was no difference in breast cancer incidence between the low-fat dietary pattern group and the control group among women not using postmenopausal hormones ( P for interaction = .06). Similarly, in the predominantly premenopausal Nurses’ Health
Retraction: Hussain HM, Hotopf M, Oyebode F. Atypical Antipsychotic Drugs and Alzheimer's Disease. N Engl J Med 2007;356:416.
Authors: Hadi Meeran Hussain
Journal: New England Journal of Medicine (2007)

To the Editor: A letter that I submitted to the Journal was published in the January 25 issue.1 Because there has been concern about the provenance and authorship of that letter, I request that it be retracted.
Opposing effects of nasal epithelial NAD(P)H dehydrogenase quinine 1 and heme oxygenase 1 expression on upper and lower airway symptoms in adolescents with asthma
Authors: Sanjeev Noel, Joy Saams, Mary Jane C. Ong, Patrick Breysse, Gregory Diette, Shyam Biswal, Elizabeth C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2011)
Research Participants' High Expectations of Benefit in Early-Phase Oncology Trials: Are We Asking the Right Question?
Authors: Kevin P. Weinfurt, Damon M. Seils, Li Lin, Daniel P. Sulmasy, Alan B. Astrow, Herbert I. Hurwitz, Roger B. Cohen, Neal J. Meropol
Journal: Journal of Clinical Oncology (2012)

To determine whether patients' expectations of benefit in early-phase oncology trials depend on how patients are queried and to explore whether expectations are associated with patient characteristics.Participants were 171 patients in phase I or II oncology trials in the United States. After providing informed consent for a trial but before receiving the investigational therapy, participants answered questions about expectations of benefit. We randomly assigned participants to one of three groups corresponding to three queries about expectations: frequency type, belief type, or both. Main outcomes were differences in expectations by question type and the extent to which expectations were associated with demographic characteristics, numeracy, dispositional optimism, religiousness/spirituality, understanding of research, and other measures.The belief-type group had a higher mean expectation of benefit (64.4 of 100) than the combination group (51.6; P = .01) and the frequency-type group (43.1; P < .001). Mean expectations in the combination and frequency groups were not significantly different (P = .06). Belief-type expectations were associated with a preference for nonquantitative information (r = -0.19; 95% CI, -0.19 to -0.36), knowledge about research (r = -0.21; 95% CI, -0.38 to -0.03), dispositional optimism (r = 0.20; 95% CI, 0.01 to 0.37), and spirituality (r = 0.22; 95% CI, 0.03 to 0.38). Frequency-type expectations were associated with knowledge about clinical research (r = -0.27; 95% CI, -0.27 to -0.51).In early-phase oncology trials, patients' reported expectations of benefit differed according to how patients were queried and were associated with patient characteristics. These findings have implications for how informed consent is obtained and assessed.
Progress and prospects in rat genetics: a community view
Authors: Timothy J Aitman, John K Critser, Edwin Cuppen, Anna Dominiczak, Xose M Fernandez-Suarez, Jonathan Flint, Dominique Gauguier, Aron M Geurts, Michael Gould, Peter C Harris, Rikard Holmdahl, Norbert Hubner, Zsuzsanna Izsvák, Howard J Jacob, Takashi Kuramoto, Anne E Kwitek, Anna Marrone, Tomoji Mashimo, Carol Moreno, John Mullins, Linda Mullins, Tomas Olsson, Michal Pravenec, Lela Riley, Kathrin Saar, Tadao Serikawa, James D Shull, Claude Szpirer, Simon N Twigger, Birger Voigt, Kim Worley
Journal: Nature Genetics (2008)
Androgen-Independent Molecular Imaging Vectors to Detect Castration-Resistant and Metastatic Prostate Cancer
Authors: Ziyue Karen Jiang, Makoto Sato, Liu H. Wei, Chinghai Kao, Lily Wu
Journal: Cancer Research (2011)

Abstract Prostate-specific promoters are frequently employed in gene-mediated molecular imaging and therapeutic vectors to diagnose and treat castration-resistant prostate cancer (CRPC) that emerges from hormone ablation therapy. Many of the conventional prostate-specific promoters rely on the androgen axis to drive gene expression. However, considering the cancer heterogeneity and varying androgen receptor status, we herein evaluated the utility of prostate-specific enhancing sequence (PSES), an androgen-independent promoter in CRPC. The PSES is a fused enhancer derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen gene regulatory region. We augmented the activity of PSES by the two-step transcriptional amplification (TSTA) system to drive the expression of imaging reporter genes for either bioluminescent or positron emission tomography (PET) imaging. The engineered PSES–TSTA system exhibits greatly elevated transcriptional activity, androgen independency, and strong prostate specificity, verified in cell culture and preclinical animal experimentations. These advantageous features of PSES–TSTA elicit superior gene expression capability for CRPC in comparison with the androgen-dependent PSA promoter–driven system. In preclinical settings, we showed robust PET imaging capacity of PSES–TSTA in a castrated prostate xenograft model. Moreover, intravenous administrated PSES–TSTA bioluminescent vector correctly identified tibial bone marrow metastases in 9 of 9 animals, whereas NaF- and FDG-PET was unable to detect the lesions. Taken together, this study showed the promising utility of a potent, androgen-independent, and prostate cancer–specific expression system in directing gene-based molecular imaging in CRPC, even in the context of androgen deprivation therapy. Cancer Res; 71(19); 6250–60. ©2011 AACR.
The Human WRN and BLM RecQ Helicases Differentially Regulate Cell Proliferation and Survival after Chemotherapeutic DNA Damage
Authors: Frances J. Mao, Julia M. Sidorova, Julia M. Lauper, Mary J. Emond, Raymond J. Monnat
Journal: Cancer Research (2010)

Loss-of-function mutations in the human RecQ helicase genes WRN and BLM respectively cause the genetic instability/cancer predisposition syndromes Werner syndrome and Bloom syndrome. To identify common and unique functions of WRN and BLM, we systematically analyzed cell proliferation, cell survival, and genomic damage in isogenic cell lines depleted of WRN, BLM, or both proteins. Cell proliferation and survival were assessed before and after treatment with camptothecin, cis-diamminedichloroplatinum(II), hydroxyurea, or 5-fluorouracil. Genomic damage was assessed, before and after replication arrest, by gamma-H2AX staining, which was quantified at the single-cell level by flow cytometry. Cell proliferation was affected strongly by the extent of WRN and/or BLM depletion, and more strongly by BLM than by WRN depletion (P = 0.005). The proliferation of WRN/BLM-codepleted cells, in contrast, did not differ from BLM-depleted cells (P = 0.34). BLM-depleted and WRN/BLM-codepleted cells had comparably impaired survival after DNA damage, whereas WRN-depleted cells displayed a distinct pattern of sensitivity to DNA damage. BLM-depleted and WRN/BLM-codepleted cells had similar, significantly higher gamma-H2AX induction levels than did WRN-depleted cells. Our results provide new information on the role of WRN and BLM in determining cell proliferation, cell survival, and genomic damage after chemotherapeutic DNA damage or replication arrest. We also provide new information on functional redundancy between WRN and BLM. These results provide a strong rationale for further developing WRN and BLM as biomarkers of tumor chemotherapeutic responsiveness.
Abstract 14381: Balloon Aortic Valvuloplasty and Percutaneous Coronary Intervention in Patients with Severe Aortic Stenosis
Authors: Itsik Ben-Dor, Augusto D. Pichard, Lowell F. Satler, Gabriel Maluenda, Michael A. Gaglia, Asmir Syed, Manuel A. Gonzalez, Mali Mahmoudi, Kohei Wakabayashi, Loic Belle, Rebecca Torguson, Okubagzi Petros, Zhenyi Xue, William O. Suddath, Kenneth M. Kent, Joseph Lindsay, Ron Waksman
Journal: Circulation (2010)

Background: Coronary artery disease is often present with severe aortic stenosis. The feasibility and safety of combined balloon aortic valvuloplasty (BAV) and percoutaneous intervention are unknow...
Citrulline/malate promotes aerobic energy production in human exercising muscle
Authors: D Bendahan, J P Mattei, B Ghattas, S Confort-Gouny, M E Le Guern, P J Cozzone
Journal: British Journal of Sports Medicine (2002)

Background: Previous studies have shown an antiasthenic effect of citrulline/malate (CM) but the mechanism of action at the muscular level remains unknown. Objective: To investigate the effects of CM supplementation on muscle energetics. Methods: Eighteen men complaining of fatigue but with no documented disease were included in the study. A rest-exercise (finger flexions)-recovery protocol was performed twice before (D−7 and D0), three times during (D3, D8, D15), and once after (D22) 15 days of oral supplementation with 6 g/day CM. Metabolism of the flexor digitorum superficialis was analysed by 31 P magnetic resonance spectroscopy at 4.7 T. Results: Metabolic variables measured twice before CM ingestion showed no differences, indicating good reproducibility of measurements and no learning effect from repeating the exercise protocol. CM ingestion resulted in a significant reduction in the sensation of fatigue, a 34% increase in the rate of oxidative ATP production during exercise, and a 20% increase in the rate of phosphocreatine recovery after exercise, indicating a larger contribution of oxidative ATP synthesis to energy production. Considering subjects individually and variables characterising aerobic function, extrema were measured after either eight or 15 days of treatment, indicating chronological heterogeneity of treatment induced changes. One way analysis of variance confirmed improved aerobic function, which may be the result of an enhanced malate supply activating ATP production from the tricarboxylic acid cycle through anaplerotic reactions. Conclusion: The changes in muscle metabolism produced by CM treatment indicate that CM may promote aerobic energy production.
Comparative Longevity in a College Cohort of Christian Scientists
Authors: William Franklin Simpson
Journal: JAMA (1989)

The cumulative death rate of Christian Scientists who received an undergraduate college education at Principia College in Elsah, III, a liberal arts college for Christian Scientists, was compared with that of a control population that received an undergraduate college education in the College of Liberal Arts and Sciences at the University of Kansas in Lawrence. In this study, the cumulative death rate is expressed as the percentage of the graduating class known to have died as of June 1987. The study included the graduating classes from 1934 to 1983. The graduates from Principia College had a significantly higher death rate than the control population.
Evidence of association of human papillomavirus with prognosis worsening in glioblastoma multiforme
Authors: Michele Vidone, Federica Alessandrini, Gianluca Marucci, Anna Farnedi, Dario de Biase, Fulvio Ricceri, Claudia Calabrese, Ivana Kurelac, Anna Maria Porcelli, Monica Cricca, Giuseppe Gasparre
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults, but its etiology still remains unknown. Recently, a role of viruses such as cytomegalovirus and JC virus in gliomagenesis has been suggested. Since human papillomavirus (HPV) is considered the most common oncogenic virus in humans, we evaluated its occurrence in GBM samples. Fifty-two formalin-fixed paraffin-embedded primary glioblastoma specimens were retrospectively analyzed. The presence of HPV genome on tumor DNA was assessed by MY/GP nested PCR. Confirmation of HPV detection was obtained by chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) with an antibody directed against the L1 capsidic protein. Finally, univariate and multivariate proportional-hazards models were used to compare the risk of death among HPV-positive and HPV-negative patients. Strikingly, viral DNA was detected after PCR in 12 cases (23%). HPV16 genome was present in 25% infected samples, whereas the remaining samples tested positive for HPV6. CISH confirmed positivity in all infected samples for which enough material was available. Moreover, IHC positivity suggested that production of viral proteins from HPV genome is an ongoing process in GBM cancer cells. Finally an association between HPV infection and a worse prognosis was found in patients upon age stratification with a univariate analysis (HR, 2.10; 95% CI, 1.00–4.44; log-rank P = .045). HPV infection status may be considered an independent prognostic factor in GBM patients and suggests that prevention may be considered, should HPV be recognized as a causative agent in gliomagenesis.
Doctors' leaders ask GMC to rethink its plans for reform
Authors: Linda Beecham
Journal: BMJ (2001)

The BMA and the UK Academy of Medical Royal Colleges have urged the General Medical Council to rethink the plans for its reform.

They have set out their proposals in a plan, which they say will make the council more “effective, efficient, and accountable to patients.” They want the current 104 strong council reduced to about 50, with a small executive of 10 to 15 members. The council, however, had suggested a small executive backed by a …
Estrogen receptor β mediates the inhibitory effect of estradiol on vascular smooth muscle cell proliferation
Authors: T Watanabe
Journal: Cardiovascular Research (2003)

Objectives: It has been demonstrated that 17β-estradiol (E2) has an inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs) through an estrogen receptor (ER)-dependent pathway. Both ER subtypes, classical ER (ERα) and the newly identified ER subtype (ERβ), are expressed in VSMCs. However, it remains unknown which receptor plays the critical role in the inhibitory effect on VSMC proliferation. Methods and results: We constructed replication-deficient adenoviruses bearing the coding region of human ERα, ERβ, and the dominant-negative form of ERβ (designated AxCAERα, AxCAERβ, and AxCADNERβ, respectively). Prior to infection with the adenoviruses, 100 nmol/l E2 attenuated DNA synthesis by up to 14% and transactivated the estrogen-induced expression of the desired mRNA in rat VSMCs. This was accompanied by increased transcriptional activity of estrogen responsive element in response to E2, and the increase was comparable between AxCAERα and AxCAERβ. When VSMCs were infected with AxCAERβ at a multiplicity of infection of 5 or higher, DNA synthesis as well as cell number decreased by 50% in response to E2, and the effect was abolished by co-infection with AxCADNERβ. In contrast, when VSMCs were infected with AxCAERα, the reduction in DNA synthesis was minimal. Conclusions: Our results indicate that ERβ is more potent than ERα in the inhibitory effect on VSMC proliferation.
850 EARLY PREDICTION OF RENAL DYSFUNCTION IN CIRRHOSIS – A COMPARATIVE STUDY EVALUATING THE ROLE OF CREATININE CLEARANCE, SERUM CYSTATIN C AND RENAL RESISTIVE INDEX
Authors: P. Mohan, R. Murali, E. Prabhu, B. Suhasini, R. Vijayakumar, V. Jayanthi
Journal: Journal of Hepatology (2010)
Nano-sized drug-loaded micelles deliver payload to lymph node immune cells and prolong allograft survival
Authors: Karen Y. Dane, Chiara Nembrini, Alice A. Tomei, Jackson K. Eby, Conlin P. O'Neil, Diana Velluto, Melody A. Swartz, Luca Inverardi, Jeffrey A. Hubbell
Journal: Journal of Controlled Release (2011)
A conundrum of modern times that's still unresolved
Authors: E. von Mutius
Journal: European Respiratory Journal (2003)

In recent decades, there has been an abundance of publications about wheezing illnesses and asthma, although none have had the capability to sufficiently define this object of curiosity and concern. Confidence has been lost in traditional approaches, such as locking up key people until one ultimate and final decision has been reached, indicated by white fumes emanating from grave chimneys. Moreover, trust in accepting and following such truths has also been lost. Yet, many will argue that these semantic discussions are purely intellectual and aimed at satisfying the scientific flock, but that a clinician, thanks to his or her intuitive skills, will easily recognise the condition. After all, humanity has successfully dealt with other comparable problems: myriads of poets, literates, psychologists and neurobiologists failed to identify love, yet everybody knows what love is 1. However, love is probably as faceted and complex as living systems are and its presence is not always recognised. The full­embracing approach towards this mysterious phenomenon is through the arts, bundling all sensual, intuitive and intellectual forces at everyone's disposition.

Clinical work is an art too, even in these modern days of computer algorithms, globalised treatment guidelines and ever­increasing scientific knowledge. As with every artist, some talent is needed, but more importantly, constant practice and improvements in digesting and incorporating novel aspects identified in clinical, basic and epidemiological research are required. The paper by Yeatts et al. …
Shear flow increases S-nitrosylation of proteins in endothelial cells
Authors: Bin Huang, Shih Chung Chen, Danny Ling Wang
Journal: Cardiovascular Research (2009)

Endothelial cells (ECs) constantly exposed to shear flow increase nitric oxide production via the activation of endothelial nitric oxide synthase. Nitric oxide-mediated S-nitrosylation has recently been identified as an important post-translational modification that may alter signalling and/or protein function. S-nitrosylation of endothelial proteins after shear flow treatment has not been fully explored. In this study, the CyDye switch method was utilized to examine S-nitrosylated proteins in ECs after exposure to shear flow. Human umbilical vein ECs were subjected to shear flow for 30 min, and S-nitrosylated proteins were detected by the CyDye switch method. In principle, free thiols in proteins become blocked by alkylation, the S-nitrosylated bond is reduced by ascorbate, and then CyDye labels proteins. Proteins that separately labelled with Cy3 or Cy5 were mixed and subjected to two-dimensional gel electrophoresis for further analysis. More than 100 S-nitrosoproteins were detected in static and shear-treated ECs. Among these, 12 major proteins of heterogeneous function showed a significant increase in S-nitrosylation following shear flow. The S-nitrosylated residues in tropomyosin and vimentin, which were localized in the hydrophobic motif of each protein, were identified as Cys170 and Cys328, respectively. Post-translational S-nitrosylation of proteins in ECs can be detected by a reliable CyDye switch method. This flow-induced S-nitrosylation of endothelial proteins may be essential for the adaptation and remodelling of ECs under flow conditions.