tbuckley/cabot-search huggingface dataset:
Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo
Authors: M Ohashi, F Kanai, H Ueno, T Tanaka, K Tateishi, T Kawakami, Y Koike, T Ikenoue, Y Shiratori, H Hamada, M Omata
Journal: Gut (1999)

BACKGROUND/AIMS Gastric cancer is one of the most prevalent forms of cancer in East Asia. Point mutation of the p53 gene has been reported in more than 60% of cases of gastric cancer and can lead to genetic instability and uncontrolled cell proliferation. The purpose of this investigation was to evaluate the potential of p53 gene therapy for gastric cancer. METHODS The responses of human gastric cancer cell lines, MKN1, MKN7, MKN28, MKN45, and TMK-1, to recombinant adenoviruses encoding wild type p53 (AdCAp53) were analysed in vitro. The efficacy of the AdCAp53 treatment for MKN1 and MKN45 subcutaneous tumours in nude mice was assessed in vivo. RESULTS p53-specific growth inhibition was observed in vitro in two of four gastric cancer cell lines with mutated p53, but not in the wild type p53 cell line. The mechanism of the killing of gastric cancer cells by AdCAp53 was found, by flow cytometric analysis and detection of DNA fragmentation, to be apoptosis. In vivo studies showed that the growth of subcutaneous tumours of p53 mutant MKN1 cells was significantly inhibited by direct injection of AdCAp53, but no significant growth inhibition was detected in the growth of p53 wild type MKN45 tumours. CONCLUSIONS Adenovirus mediated reintroduction of wild type p53 is a potential clinical utility in gene therapy for gastric cancers.
Blood Levels of Parathyroid Hormone in Disorders of Calcium Metabolism
Authors: E Reiss, J M Canterbury
Journal: Annual Review of Medicine (1973)

During the past three years, new information concerning clinical parathyroid physiology has been generated rapidly. In much of the recent research, radio­ immunoassay of parathyroid hormone (PTH) has been the critical method. Mter the initial description of the assay in 1963, several years elapsed during which many attempts to develop reliable assays failed (1). Even in retrospect, these early difficulties are not readily explained. Problems that appeared formidable at first did not prove troublesome in the long run, but unsuspected problems emerged as experience was gained. Three major problems engendered delay: 1. Production of high affinity anti­ sera to bovine PTH was difficult. It is now known that many different immuniza­ tion schedules can be successfully employed for antibody production. The species of animal used for immunization is not critical since several species have yielded useful antisera. The early difficulties in antibody production can be at­ tributed, at least in part, to limited supplies of antigen. 2. Antisera possessing high affinity to bovine PTH cross-reacted poorly with PTH in human plasma or serum.2 Bovine hormone is most commonly used as the immunizing antigen since it is readily produced in quantity and can now be obtained commercially. The problem of low affinity of antibovine PTH sera to human PTH persists, but many antisera with sufficient binding of human PTH have been prepared so that sensitive assays in man can be performed. 3. Unavailability of a human PTH reference standard for expressing assay results posed a problem that only re­ cently has been recognized as illusory. Investigations from several laboratories have shown that even if human PTH were available in sufficient quantity for immunization, labeling, and stan­ dardization of assay results, the primary difficulty in PTH assays and their in­ terpretation-the heterogeneity of circulating PTH peptides-would not be resolved.
Diagnosis and management of superior labrum anterior posterior lesions in overhead athletes
Authors: Geoffrey D Abrams, Marc R Safran
Journal: British Journal of Sports Medicine (2010)

Shoulder pain is a common complaint in overhead athletes, and superior labrum anterior posterior (SLAP) lesions are a common cause of this pain. The pathological cascade which results in the SLAP lesion consists of a combination of posterior inferior capsular tightness and scapular dyskinesis, resulting in a ‘peel back’ phenomenon at the biceps anchor and leading to the SLAP tear. Physical exam tests vary in their sensitivity and specificity in detecting SLAP lesions, so MRI is helpful in demonstrating the anatomical alteration. Treatment can be conservative, with posterior inferior capsular stretching and scapular open and closed chain exercises. Many SLAP lesions in overhead athletes require surgical treatment that involves repair of the labrum back to the glenoid. Treatment of concomitant injuries such as rotator cuff tears and Bankart lesions in conjunction with the SLAP repair may be necessary.
Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure
Authors: Mihai Gheorghiade, Michael Böhm, Stephen J Greene, Gregg C Fonarow, Eldrin F Lewis, Faiez Zannad, Scott D Solomon, Fabio Baschiera, Jaco Botha, Tsushung A Hua, Claudio R Gimpelewicz, Xavier Jaumont, Anastasia Lesogor, Aldo P Maggioni
Journal: JAMA (2013)

Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality.To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular (CV) death or HF rehospitalization among HHF patients.International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction (LVEF) 40% or less, elevated natriuretic peptides (brain natriuretic peptide [BNP] ≥ 400 pg/mL or N -terminal pro-BNP [NT-proBNP] ≥ 1600 pg/mL), and signs and symptoms of fluid overload. Patients were recruited from 316 sites across North and South America, Europe, and Asia between May 2009 and December 2011. The follow-up period ended in July 2012.All patients received 150 mg (increased to 300 mg as tolerated) of aliskiren or placebo daily, in addition to standard therapy. The study drug was continued after discharge for a median 11.3 months. MAIN OUTCOME MEASURES Cardiovascular death or HF rehospitalization at 6 months and 12 months.In total, 1639 patients were randomized, with 1615 patients included in the final efficacy analysis cohort (808 aliskiren, 807 placebo). Mean age was 65 years; mean LVEF, 28%; 41% of patients had diabetes mellitus, mean estimated glomerular filtration rate, 67 mL/min/1.73 m2. At admission and randomization, median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL, respectively. At randomization, patients were receiving diuretics (95.9%), β-blockers (82.5%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (84.2%), and mineralocorticoid receptor antagonists (57.0%). In total, 24.9% of patients receiving aliskiren (77 CV deaths, 153 HF rehospitalizations) and 26.5% of patients receiving placebo (85 CV deaths, 166 HF rehospitalizations) experienced the primary end point at 6 months (hazard ratio [HR], 0.92; 95% CI, 0.76-1.12; P = .41). At 12 months, the event rates were 35.0% for the aliskiren group (126 CV deaths, 212 HF rehospitalizations) and 37.3% for the placebo group (137 CV deaths, 224 HF rehospitalizations; HR, 0.93; 95% CI, 0.79-1.09; P = .36). The rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo.Among patients hospitalized for HF with reduced LVEF, initiation of aliskiren in addition to standard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge.clinicaltrials.gov Identifier: NCT00894387.
Independent validation of genes and polymorphisms reported to be associated with radiation toxicity: a prospective analysis study
Authors: Gillian C Barnett, Charlotte E Coles, Rebecca M Elliott, Caroline Baynes, Craig Luccarini, Don Conroy, Jennifer S Wilkinson, Jonathan Tyrer, Vivek Misra, Radka Platte, Sarah L Gulliford, Matthew R Sydes, Emma Hall, Søren M Bentzen, David P Dearnaley, Neil G Burnet, Paul DP Pharoah, Alison M Dunning, Catharine ML West
Journal: The Lancet Oncology (2011)

Several studies have reported associations between radiation toxicity and single nucleotide polymorphisms (SNPs) in candidate genes. Few associations have been tested in independent validation studies. This prospective study aimed to validate reported associations between genotype and radiation toxicity in a large independent dataset.92 (of 98 attempted) SNPs in 46 genes were successfully genotyped in 1613 patients: 976 received adjuvant breast radiotherapy in the Cambridge breast IMRT trial (ISRCTN21474421, n=942) or in a prospective study of breast toxicity at the Christie Hospital, Manchester, UK (n=34). A further 637 received radical prostate radiotherapy in the MRC RT01 multicentre trial (ISRCTN47772397, n=224) or in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer (CHHiP) trial (ISRCTN97182923, n=413). Late toxicity was assessed 2 years after radiotherapy with a validated photographic technique (patients with breast cancer only), clinical assessment, and patient questionnaires. Association tests of genotype with overall radiation toxicity score and individual endpoints were undertaken in univariate and multivariable analyses. At a type I error rate adjusted for multiple testing, this study had 99% power to detect a SNP, with minor allele frequency of 0·35, associated with a per allele odds ratio of 2·2.None of the previously reported associations were confirmed by this study, after adjustment for multiple comparisons. The p value distribution of the SNPs tested against overall toxicity score was not different from that expected by chance.We did not replicate previously reported late toxicity associations, suggesting that we can essentially exclude the hypothesis that published SNPs individually exert a clinically relevant effect. Continued recruitment of patients into studies within the Radiogenomics Consortium is essential so that sufficiently powered studies can be done and methodological challenges addressed.Cancer Research UK, The Royal College of Radiologists, Addenbrooke's Charitable Trust, Breast Cancer Campaign, Cambridge National Institute of Health Research (NIHR) Biomedical Research Centre, Experimental Cancer Medicine Centre, East Midlands Innovation, the National Cancer Institute, Joseph Mitchell Trust, Royal Marsden NHS Foundation Trust, Institute of Cancer Research NIHR Biomedical Research Centre for Cancer.
Evolution of British Attitudes Toward Homosexuality
Authors: JOHN WOLFENDEN
Journal: American Journal of Psychiatry (1968)

The author, who chaired the British departmental committee to examine the law and practice relating to homosexual offenses and prostitution, explains the thinking behind the recommendations of the committee's report. The function of the criminal law is to preserve public order and decency and to protect the weak from exploitation rather than to impose a particular pattern of moral behavior. It follows, then, that there are areas of life which are no concern of the criminal law even though they may be of significant moral concern to individuals and to society.
Long-Term Outcome of Adults With Systemic Anaplastic Large-Cell Lymphoma Treated Within the Groupe d'Étude des Lymphomes de l'Adulte Trials
Authors: David Sibon, Marion Fournier, Josette Brière, Laurence Lamant, Corinne Haioun, Bertrand Coiffier, Serge Bologna, Pierre Morel, Jean Gabarre, Olivier Hermine, Anne Sonet, Christian Gisselbrecht, Georges Delsol, Philippe Gaulard, Hervé Tilly
Journal: Journal of Clinical Oncology (2012)

Systemic anaplastic large-cell lymphoma (ALCL) is a T-cell lymphoma, whose anaplastic lymphoma kinase (ALK) expression varies according to age. Long-term outcomes of chemotherapy-treated adults are not definitively established and should be evaluated.Patients treated in three Groupe d'Étude des Lymphomes de l'Adulte prospective clinical trials with confirmed systemic ALCL after immunohistopathologic review and defined ALK expression status were analyzed.Among the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β(2)-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β(2)-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. CONCLUSION Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment.
TRACER IODINE STUDIES ON THYROID ACTIVITY AND THYROID RESPONSIVENESS IN SCHIZOPHRENIA
Authors: EDWARD H. CRANSWICK
Journal: American Journal of Psychiatry (1955)

1. Thyroid activity has been studied by measurement of 24 hours' fractional uptake of tracer dose of I131 in 31 schizophrenics and 35 normal subjects. 2. Following T.S.H. (10 mg.) intramuscular injection, there has been shown to exist a highly significant difference in the normal subjects and the patients in the incremental response of thyroid uptake. 3. Bowman's findings of increased thyroid activity (as measured by I131 uptake) and of lowered B. M. R. in schizophrenics are confirmed here. 4. The possible role of environment is discussed and future studies are outlined.
Natural killer cell behavior in lymph nodes revealed by static and real-time imaging
Authors: Marc Bajénoff, Béatrice Breart, Alex Y.C. Huang, Hai Qi, Julie Cazareth, Veronique M. Braud, Ronald N. Germain, Nicolas Glaichenhaus
Journal: The Journal of Experimental Medicine (2006)

Natural killer (NK) cells promote dendritic cell (DC) maturation and influence T cell differentiation in vitro. To better understand the nature of the putative interactions among these cells in vivo during the early phases of an adaptive immune response, we have used immunohistochemical analysis and dynamic intravital imaging to study NK cell localization and behavior in lymph nodes (LNs) in the steady state and shortly after infection with Leishmania major. In the LNs of naive mice, NK cells reside in the medulla and the paracortex, where they closely associate with DCs. In contrast to T cells, intravital microscopy revealed that NK cells in the superficial regions of LNs were slowly motile and maintained their interactions with DCs over extended times in the presence or absence of immune-activating signals. L. major induced NK cells to secrete interferon-γ and to be recruited to the paracortex, where concomitant CD4 T cell activation occurred. Therefore, NK cells form a reactive but low mobile network in a strategic area of the LN where they can receive inflammatory signals, interact with DCs, and regulate colocalized T cell responses.
Effect of fiberoptic bronchoscopy on respiratory performance in patients with chronic airways obstruction.
Authors: B G Salisbury, L F Metzger, M D Altose, N N Stanley, N S Cherniack
Journal: Thorax (1975)

Lung volumes, airway resistance, expiratory flow rates, distribution of ventilation, and arterial blood gases were measured before and after fiberoptic bronchoscopy in 13 patients with moderately severe chronic airways obstruction and in 10 healthy non-smoking controls. Arterial blood gases were also monitored serially during the procedure. Arterial oxygen tension (Pao2) fell during fiberoptic bronchoscopy in both patients and controls whereas arterial carbon dioxide tension and pH remained unchanged. Control subjects had no change in lung mechanics after fiberoptic bronchoscopy. However, the patients consistently developed increased airway obstruction after fiberoptic bronchoscopy. Within 24 hours after bronchoscopy lung function in the patients returned to baseline values, except for the residual volume which remained abnormally high. The topical application of lignocaine (Lidocaine) for local anesthesia before fiberoptic bronchoscopy produced no effect on lung mechanics in nine patients and 10 controls, but Pao2 decreased in both the patient and control groups. These results indicate that fiberoptic bronchoscopy consistently inpairs lung mechanics and gas exchange in patients with chronic airways obstruction but that the impairment is mild and reversible. Lignocaine administration as well as the intubation procedure contribute to the fall in Pao2 which occurs both in the patients and in subjects without pre-existing lung disease.
Of mice and men, rats and atherosclerosis
Authors: J Russell
Journal: Cardiovascular Research (2003)

See article by Lyngdorf et al. [10] (pages 854–862) in this issue. 

In less than 100 years, biology and medicine have been transformed by the effects of research that has eclipsed that of the 19th century in chemistry and that of the early half of the 20th century in physics. Whereas clinical research on human subjects has been important at the level of the application of knowledge at the bedside, the fundamental discoveries have been the result of basic science. Since the days of Harvey [1], real advances in the biomedical sciences have depended critically on the use of animals as models of human physiology, pathophysiology, and metabolism. Current animal models constitute technology that has been derived from scientific advances that, in turn, foster new scientific understanding and developments.

The widespread use of rodent models dates from seminal work at the Wistar Institute where, starting in 1906, Donaldson [2] established the rat as a defined animal model for the study of many aspects of physiology. As he pointed out, the rat has many similarities to humans and its rapid development makes the study of life cycle processes practical. It is also both small enough to be inexpensive to breed and house and large enough to allow many studies of physiology and metabolism that are difficult or impossible in smaller species. The development of the mouse came somewhat later, led by work at the Jackson Laboratory, and benefited greatly from new techniques in genetics.

The unraveling of the genetic code … 

*Tel.: +1-780-492-6359; fax: +1-780-492-1308.
Central serotonergic agents raise the repetitive extrasystole threshold of the vulnerable period of the canine ventricular myocardium.
Authors: C M Blatt, S H Rabinowitz, B Lown
Journal: Circulation Research (1979)

Systemic administration of three central serotonergic agents, melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), produced significant increases in the threshold of the vulnerable period for repetitive electrical activity in the canine cardiac ventricle. MK-212 was effective despite bilateral vagotomy. The specific serotonin antagonist, metergoline, blocked the effect of MK-212 on the threshold. An increase in central serotonergic activity may inhibit the flow of arrhythmogenic sympathetic nerve traffic from the brain to the heart.
Effectiveness of headgear in football
Authors: C Withnall, N Shewchenko, M Wonnacott, J Dvorak
Journal: British Journal of Sports Medicine (2005)

Commercial headgear is currently being used by football players of all ages and skill levels to provide protection from heading and direct impact. The clinical and biomechanical effectiveness of the headgear in attenuating these types of impact is not well defined or understood. This study was conducted to determine whether football headgear has an effect on head impact responses.Controlled laboratory tests were conducted with a human volunteer and surrogate head/neck system. The impact attenuation of three commercial headgears during ball impact speeds of 6-30 m/s and in head to head contact with a closing speed of 2-5 m/s was quantified. The human subject, instrumented to measure linear and angular head accelerations, was exposed to low severity impacts during heading in the unprotected and protected states. High severity heading contact and head to head impacts were studied with a biofidelic surrogate headform instrumented to measure linear and angular head responses. Subject and surrogate responses were compared with published injury assessment functions associated with mild traumatic brain injury (MTBI).For ball impacts, none of the headgear provided attenuation over the full range of impact speeds. Head responses with or without headgear were not significantly different (p>0.05) and remained well below levels associated with MTBI. In head to head impact tests the headgear provided an overall 33% reduction in impact response.The football headgear models tested did not provide benefit during ball impact. This is probably because of the large amount of ball deformation relative to headband thickness. However, the headgear provided measurable benefit during head to head impacts.
Endothelial dysfunction of coronary resistance vessels in apoE−/− mice involves NO but not prostacyclin-dependent mechanisms
Authors: A Gödecke
Journal: Cardiovascular Research (2002)

Objective: We have analyzed the extent of endothelial dysfunction in cardiac resistance vessels of hyperlipidaemic apoE−/− mice and explored whether NO and/or prostacyclin dependent pathways are involved. Methods: Coronary resistance was measured in isolated perfused hearts from WT and apoE−/− mice. To discriminate between NO and PGI2-dependent flow responses, we made use of the finding that acetylcholine (ACh) predominantly activates the prostaglandin pathway whereas bradykinin (Bk) mainly acts via NO in murine cardiac resistance vessels. Results: Basal coronary flow as well as the ACh induced vasodilation (0.1–1 μM) were not different between WT and apoE−/− hearts (flow increase+100%). Similarly, vasodilation in response to the prostacyclin mimetic iloprost reached the same levels. In contrast, the Bk-stimulated [3.3 μM Bk] coronary flow was reduced from 31.6±4.2 in WT to 19.2±2.7 ml min−1 g−1 in apoE−/− hearts. NOS inhibition by ethylisothiourea (ETU, 10 μM) reduced basal as well as Bk-stimulated coronary flow in WT and apoE−/− hearts to the same extent. RT–PCR and Western analysis demonstrated that neither eNOS expression nor protein levels were reduced. Similarly, the flow response to the NO donor SNAP (0.3–33 μM) was not altered suggesting that soluble guanylyl cyclase was not affected. Intracoronary application of superoxide dismutase augmented the Bk-induced vasodilation of apoE−/− hearts almost back to WT levels (26.6±3.3 ml min−1 g−1). In line with this finding the NADPH induced O2− formation was enhanced in cardiac extracts from apoE−/− hearts. Conclusion: apoE−/− hearts develop a hemodynamically relevant endothelial dysfunction at the level of coronary resistance vessels most likely via inactivation of bioavailable NO by superoxide anions. The function of the prostacyclin system is not altered.
2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group
Authors: P. Debourdeau, D. Kassab Chahmi, G. Le Gal, I. Kriegel, E. Desruennes, M.-C. Douard, I. Elalamy, G. Meyer, P. Mismetti, M. Pavic, M.-L. Scrobohaci, H. Lévesque, J.M. Renaudin, D. Farge
Journal: Annals of Oncology (2009)