tbuckley/cabot-search huggingface dataset:
Trevor Orchard: Fruitful Contributions to Diabetes Epidemiology
Authors: Amanda I. Adler
Journal: Diabetes Care (2015)

Respected on both sides of the Atlantic for questioning the tenets underlying the pathophysiology of diabetes and its complications, Trevor Orchard continues to influence the fields of epidemiology and medicine. With a self-effacing style that might be described as typically British, he remains provocative and prominent among the research community.

An Englishman educated in Wales and living in the U.S., Orchard is known for his work on influential large-scale publicly funded interventional studies (Diabetes Control and Complications Trial [DCCT], Diabetes Prevention Program [DPP], Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]), observational studies (Pittsburgh Epidemiology of Diabetes Complications Study [EDC]), and interventional-turned-observational studies (Diabetes Prevention Program Outcomes Study [DPPOS], Epidemiology of Diabetes Interventions and Complications [EDIC]). He is best known for the EDC, which he has led for nearly 30 years.

In EDC, a well-characterized long-term cohort of people with type 1 diabetes started in 1986, Orchard has followed nearly 800 participants identified within 1 year of diagnosis between 1950 and 1980 at Children’s Hospital of Pittsburgh (1). Orchard gives credit for inspiration and guidance to Professor Ronald Klein of the long-running Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR); Klein continues to this day to grade the retinal fundal photographs from EDC. EDC was also preceded by the Allegheny County Type 1 Diabetes Registry (2), which still contributes data on longevity (3). Unlike a registry, EDC offers regular follow-up, data on censoring, and the ability to characterize multiple exposures. EDC generates vital statistics to verify life expectancy (4), descriptive statistics to monitor incidence of complications (1), and relational statistics to test associations between patient characteristics and subsequent complications. Orchard and coworkers have identified associations, but have also identified when associations do not exist, for example, between BMI and the complications of diabetes (5). Orchard and colleagues (6) have …
Brief Communication: Shift of Organotropy of Azoxy Compounds-Replacement of Methyl With an Octyl Group2
Authors: Jerrold M. Ward, Elizabeth K. Weisburger, Timothy Benjamin, Robert A. Moss
Journal: JNCI Journal of the National Cancer Institute (1974)

To investigate structure-activity correlations, male NIH Swiss mice were inoculated with methylazoxyoctane (MAO), an analogueof the carcinogenazoxymethane (ADM). Those receiving 14 weekly injections developed bladder, pulmonary, renal, skin, and harderian gland tumors. One injection of MAO was also carcinogenic. The bladder neoplasms were accompanled by epithelial hyper. plasia, submucosal inflammation, and vascularization. Transitional tell tumors and hemangiosarcomas were induced and each occurred concurrently in 2 mice. Intestinal neoplasms were not observed. Since ADM induced colon tumors, and MAO induced bladder lesions in the same mouse strain, the replacement of a methyl group by an octyl group was responsible for the difference in organotropy of the carcinogen.
Exhaled MMP-9 in lung cancer
Authors: Giovanna Elisiana Carpagnano, Donato Lacedonia, Elio Costantino, Anna Rita Depalo, Cinzia Ruggeri, Grazia Pia Palladino, Maria Pia Foschino Barbaro
Journal: European Respiratory Journal (2012)

Background:  MMP-9 has been recognized in several types of tumour development and progression, including lung cancer, for its role in the degradation and remodelling of lung tissue. Furthermore, increased MMP-9 has been commonly described in the serum and airways of non small cell lung cancer (NSCLC) patients.   Objective  :  The aim of this study was to investigate, for the first time, MMP-9 in the exhaled breath condensate (EBC) of NSCLC patients.  Participants :  We enrolled 40 NSCLC patients and 40 controls affected by transudative pleural effusion.   Measurements:  MMP-9 concentrations were measured in the EBC, whole blood (WB) and pleural effusion (PE) of all the subjects under study using EIA kits.   Results:  MMP-9 levels were found to be significantly higher in EBC, WB and PE of NSCLC patients compared with controls. A positive correlation was observed between MMP-9 in EBC, cigarettes smoked and stage of cancer.   Conclusion:  Exhaled MMP-9 was elevated in NSCLC patients, especially during tumour progression, and could represent a suitable non-invasive marker in the diagnosis and monitoring of lung cancer.
Independent Radiological Evaluation of Objective Response, Early Tumor Shrinkage, and Depth of Response in Fire-3 (Aio Krk-0306) in the Final Ras Evaluable Population
Authors: S. Stintzing, D.P. Modest, L. Fischer von Weikersthal, T. Decker, A. Kiani, U. Vehling-Kaiser, S. Al-Batran, T. Heintges, C. Lerchenmueller, C. Kahl, G. Seipelt, F. Kullmann, W. Scheithauer, S. Held, C. Giessen, M. Moehler, A. Jagenburg, A. Jung, T. Kirchner, V. Heinemann
Journal: Annals of Oncology (2014)
Expression and functionality of Toll- and RIG-like receptors in HepaRG cells
Authors: Souphalone Luangsay, Malika Ait-Goughoulte, Maud Michelet, Océane Floriot, Marc Bonnin, Marion Gruffaz, Michel Rivoire, Simon Fletcher, Hassan Javanbakht, Julie Lucifora, Fabien Zoulim, David Durantel
Journal: Journal of Hepatology (2015)
Campylobacter coli cultured from the stools of a patient with immunoproliferative small intestinal disease
Authors: S. Coeuret, A. de La Blanchardière, V. Saguet-Rysanek, S. Chèze, M. Tavernier, D. Arsène, A. Criscuolo, S. Brisse, M. Vergnaud, R. Verdon, M. Lecuit
Journal: Clinical Microbiology and Infection (2014)
Mouse Mammary Tumor Virus Infections: Viral Expression and Tumor Risk&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bruce W. Altrock, Robert D. Cardiff
Journal: JNCI Journal of the National Cancer Institute (1979)

Concentrations of murine mammary tumor virus (MuMTV) antigen in the milk of individual naturally infected BALB/cfC3H and BALB/c mice given injections of MuMTV were related to their risk of developing a mammary tumor. Two distinct groups of MuMTV-infected mice were identified. One group exhibited high viral antigen levels in their milk (greater than or equal to 100 micrograms/ml), whereas the other group exhibited low viral antigen levels in their milk (less than or equal to 3 micrograms/ml). Mice that exhibited high levels developed tumors by 17 months of age, whereas those with low levels did not. Viral expression levels in mice having high risks of tumor development were also related to the length of the latency period preceding overt tumor development. The tumor risk potential of naturally infected mice was frequently that of their mothers. Various doses of MuMTV were injected into BALB/c mice, and the resulting infections differed in latency period, level of viral expression, and potential for neoplastic transformation.
Transient compulsive foraging behavior associated with crack cocaine use
Authors: R B Rosse, M Fay-McCarthy, J P Collins, D Risher-Flowers, T N Alim, S I Deutsch
Journal: American Journal of Psychiatry (1993)

Compulsive foraging behavior associated with use of crack cocaine involves compulsively searching the environment for possibly misplaced pieces of crack. Of 41 crack cocaine addicts evaluated, 33 (80.5%) reported at least some compulsive foraging associated with use of crack; 21 (51.2%) reported such behavior as always associated with crack use. The mean length of time spent in compulsive foraging was 90 minutes. Cocaine-induced foraging may represent a drug-induced model of a type of compulsive behavior.
Na,K-ATPase β1-subunit is a target of sonic hedgehog signaling and enhances medulloblastoma tumorigenicity
Authors: Seung Joon Lee, Alisa Litan, Zhiqin Li, Bruce Graves, Stephan Lindsey, Sonali P. Barwe, Sigrid A. Langhans
Journal: Molecular Cancer (2015)

The Sonic hedgehog (Shh) signaling pathway plays an important role in cerebellar development, and mutations leading to hyperactive Shh signaling have been associated with certain forms of medulloblastoma, a common form of pediatric brain cancer. While the fundamentals of this pathway are known, the molecular targets contributing to Shh-mediated proliferation and transformation are still poorly understood. Na,K-ATPase is a ubiquitous enzyme that maintains intracellular ion homeostasis and functions as a signaling scaffold and a cell adhesion molecule. Changes in Na,K-ATPase function and subunit expression have been reported in several cancers and loss of the β1-subunit has been associated with a poorly differentiated phenotype in carcinoma but its role in medulloblastoma progression is not known. Human medulloblastoma cell lines and primary cultures of cerebellar granule cell precursors (CGP) were used to determine whether Shh regulates Na,K-ATPase expression. Smo/Smo medulloblastoma were used to assess the Na,K-ATPase levels in vivo. Na,K-ATPase β1-subunit was knocked down in DAOY cells to test its role in medulloblastoma cell proliferation and tumorigenicity. Na,K-ATPase β1-subunit levels increased with differentiation in normal CGP cells. Activation of Shh signaling resulted in reduced β1-subunit mRNA and protein levels and was mimicked by overexpression of Gli1and Bmi1, both members of the Shh signaling cascade; overexpression of Bmi1 reduced β1-subunit promoter activity. In human medulloblastoma cells, low β1-subunit levels were associated with increased cell proliferation and in vivo tumorigenesis. Na,K-ATPase β1-subunit is a target of the Shh signaling pathway and loss of β1-subunit expression may contribute to tumor development and progression not only in carcinoma but also in medulloblastoma, a tumor of neuronal origin.
Diaphragm Muscle Fiber Dysfunction in Chronic Obstructive Pulmonary Disease
Authors: Coen A. C. Ottenheijm, Leo M. A. Heunks, P. N. Richard Dekhuijzen
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Inspiratory muscle weakness in patients with chronic obstructive pulmonary disease (COPD) is of major clinical relevance; maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered of pathologic nature. Although the fiber-type shift toward oxidative type I fibers in COPD diaphragm is regarded as beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single-fiber level is associated with loss of myosin content. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. The current Pulmonary Perspective postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force-generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients do not appear to be limited in their daily-life activities. Therefore, investigating in vivo diaphragm function in mild to moderate COPD should be the focus of future research. Treatment of diaphragm dysfunction in COPD is complex because its etiology is unclear, but recent findings show promise for the use of proteasome inhibitors in syndromes associated with muscle wasting, such as the diaphragm in COPD.
New GOLD recommendations in a seven years follow up - changes in symptoms and risk categories
Authors: Bjorn Stallberg, Christer Janson, Josefin Sundh, Scott Montgomery, Mary Kampe, Eva Osterlund Efraimsson, Anna Ericson, Karin Lisspers
Journal: European Respiratory Journal (2013)

New GOLD recommendations in a seven years follow up - changes in symptoms and risk categories
Voltage-Gated Sodium Channels and Hyperalgesia
Authors: Josephine Lai, Frank Porreca, John C. Hunter, Michael S. Gold
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.
Cognitive function in patients with COPD after virtual admission - a randomized clinical trial
Authors: Lone Schou, Birte Østergaard, Lars Rasmussen, Susan Rydahl-Hansen, Anna Svarre Jakobsen, Christina Emme, Klaus Phanareth
Journal: European Respiratory Journal (2012)

Background : Substantial healthcare resources are spent on Chronic Obstructive Pulmonary Disease (COPD). As a result, the involvement of patients in monitoring of their condition has been suggested. However, the level of cognitive functioning must be taken into consideration before self-care strategies can be adopted.   Aim : We hypothesized that cognitive performance would be better in COPD patients allocated to virtual admission - using a telemedicine solution - compared to patients admitted to conventional hospitalization after exacerbation.   Methods : This study was a Randomized Clinical Trial. The primary outcome was cognitive function evaluated at discharge and after six weeks using a neuropsychological test battery comprising 4 tests and 7 variables. Secondary outcomes included self-reported cognitive function (SCF), activities of daily living (IADL), and anxiety and depression (HADS).   Results : We included 44 patients consecutively. Baseline data were; Mean age 70 years (SD 10); forced expiratory volume in one second (FEV1) 1.0 L (SD 0.55); Oxygen saturation 94.5 (SD 2.0); and a Mini Mental State Examination score of 27.5 points (SD 1.6). The performance in all seven neuropsychological test variables tended to be better in the group allocated to virtual admission, but the difference was only statistically significant in the time for the Stroop Color Word test, (p=0.05). The pattern was the same at follow-up after six weeks but the differences were less pronounced. There were no significant differences in SCF, IADL, and HADS at discharge or after 6 weeks.   Conclusion:  Cognitive function may be better preserved in COPD patients treated for exacerbation during virtual admission at home.
AN APPROACH TO PSYCHOLOGICAL CONTROL STUDIES OF URINARY SEX HORMONES
Authors: GEORGE E. DANIELS
Journal: American Journal of Psychiatry (1943)

In this paper I have attempted to show that serial psychological observations promote a dynamic process in which the relationship to the investigator not only facilitates the collection of data, but also modifies it in the process. The utilization of the awareness of this phenomenon in the interpretation and evaluation of material I have termed the psychological control study. This was applied to the study of correlations of psychological factors in relation to urinary sex hormone output, but has a wider application to psychological research. Psychiatric interviews occurring at times of hormonal pressure brought increased spontaneous production of material, relief of tension and improved social adjustment. In one instance this appeared to be associated with a conversion symptom produced or accentuated by the tension. Repeated observations on these relationships may throw important light on relation of symptoms to hormonal pressure, and have implications or psychotherapy in general. In the present study no correlation could be made between psychological data and 17-ketosteroids because of the flatness of the androgen curve. Although correlations between the psychological picture and minor variations in gonadotropin and estrogen could not be regularly demonstrated, a reflection of the general trends seemed clear, with a definite correspondence at the periods when ovulation was suspected. If Benedek's conclusions are correct, the presence of progesterone, though not demonstrated chemically during the control period, was evidenced in the subject's behavior and productions during the latter half of each cycle. Generalizations on hormonal correlations, of course, cannot be made on the basis of this one observation; it is presented primarily as an illustration of the psychological approach. On the whole, however, it seems to bear out Benedek's contention that sex hormone changes are reflected in psychological productions. Further control studies on urinary hormones are in progress in both men and women, and will be reported in a subsequent communication. From our experience thus far, we believe this approach will prove valuable not only in the field of normal sexual biology, but also in the study of sex variants, neuroses and selected psychosomatic disease pictures.
Differentiation of Normal and Cultured Preneoplastic Tracheal Epithelial Cells in Rats: Importance of Epithelial Mesenchymal Interactions&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Margaret Terzaghi, A. J. P. Klein-Szanto
Journal: JNCI Journal of the National Cancer Institute (1980)

Changes in the dependence on mesenchymal tissues for survival and differentiation in inbred F344 female rats were investigated in tracheal epithelial cells exposed to 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol 13-acetate (TPA). Fresh suspensions of normal tracheal epithelium or cultured preneoplastic cells were inoculated into isolated organ segments (trachea, esophagus, bladder, or small intestine) or into Dacron containers that were then implanted subdermally into isogenic recipients. At various times after cell inoculation and implantation, tissues were removed for histologic evaluation. Normal cells inoculated into frozen-thawed trachea, esophagus, bladder, and intestine yielded a regular mucociliary epithelium. Normal cell inocula did not, however, survive in tracheae previously heated (100 degrees C), fixed in ethanol, or digested with collagenase; nor did normal cells survive in Dacron containers unless tracheal fibroblasts plus epithelial cells were inoculated together. DMBA- and TPA-exposed cell populations with increased growth capacity in vitro survived and differentiated on all of the above substrates. Our observations were consistent with those of other investigators in that normal cell survival and differentiation depend to some extent on interaction with extracellular material(s) present in various organs. The essential elements were not supplied by subdermal fibroblasts alone. For survival and differentiation in vivo, preneoplastic cells appeared to have less stringent substrate requirements than did normal cells. Application of the described techniques to the study of changes occurring early in the development of neoplastic disease is discussed.
Smoking and COPD exacerbations
Authors: Elena Badaran, Ezequiel Ortega, Carlos Bujalance, Lola Del Puerto, Mirian Torres, Juan Antonio Riesco
Journal: European Respiratory Journal (2012)

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality throughout the world. And evidence shows that COPD exacerbations are a frequent cause of hospital admission, as an indicator of a poor prognosis and elevated mortality.  Objective: To study smoking habits among patients hospitalised/admitted for COPD exacerbations in a conventional hospital ward.  Material and methods:We carried out a retrospective descriptive study by reviewing discharge reports of patients admitted to our centre during the period of September 2010 to September 2011. We analysed epidemiological, clinical and smoking history.  Results: We studied 196 patients, of whom 180 men (91.8%) and 16 women (8.2%) with a mean age of 77 years. 41% have a diagnosis of severe COPD. The most frequent co morbidity found is cardiovascular. 18% associated cancer. The prevalence of current smoking is 26.5%, 52 patients continue to smoke including 47 males (27%) and 5 women (31%). The ex-smoker population represents 68.9% (131) while non-smokers comprise 1.5% (3). 73% of male smokers have a moderate to severe COPD degree. Pneumonia is present in 26% of smokers, (14), while in ex-smokers it is present in 23% (33). A total of 37 patients (18.8%) were readmitted within a year, of which 62% are severe COPD (28); 9 of them were still smoking.  Conclusions: 1) Smoking is a major factor in COPD exacerbations. 2) There is a high prevalence of COPD exacerbations requiring admission to a hospital unit in those patients who continue to smoke. 3) Most smokers admitted for exacerbation of COPD were included in the severe COPD group. 4) There are 37 readmissions within a year, representing almost one fifth of all COPD exacerbations, 9 of whom continue smoking.
Dose-ranging study of oxycodone for chronic pain in advanced cancer.
Authors: P A Glare, T D Walsh
Journal: Journal of Clinical Oncology (1993)

PURPOSE AND METHODS We assessed the analgesic efficacy and safety of single-entity oxycodone solution at doses greater than 10 mg orally every 4 hours in 24 patients with chronic cancer pain not controlled by weaker analgesics. RESULTS Twenty of 24 patients completed the study. Pain relief was obtained with doses up to 60 mg every 4 hours. When oxycodone was taken for long periods, further dose increments could be made safely. The side effects of oxycodone are mild, and common to all opioids, with sedation and constipation most frequent. Nausea was more common in females in all age groups and in patients of either sex less than 50 years of age. Episodes of serious toxicity were rare, and responded to dose reduction. Patients older than 65 years required lower doses, suggesting pharmacokinetic similarities between oxycodone and morphine. Patients changed from oral oxycodone to morphine remained pain-free when relative milligram potency ratios of 1:1 to oral morphine and 3:1 to intravenous morphine were used. CONCLUSION Oxycodone has been shown for the first time to be as versatile and flexible as oral morphine in the management of chronic pain in patients with advanced cancer.