tbuckley/cabot-search huggingface dataset:
Testosterone-aggression relationship: An exemplar of interactionism
Authors: Linda Mealey
Journal: Behavioral and Brain Sciences (1998)

Mazur &amp; Booth provide life scientists with an example of the multilevel biopsychosocial approach. Research paradigms have to become more flexible and multidisciplinary if we are to free ourselves from the nature–nurture dichotomy that we have long agreed was simplistic and shortsighted. I point out a variety of kinds of interactions that may be the next frontier for behavioral scientists.
Renal mRNA Levels as Prognostic Tools in Kidney Diseases
Authors: Michael Eikmans, Hans J. Baelde, E. Chris Hagen, Leendert C. Paul, Paul H. C. Eilers, Emile de Heer, Jan A. Bruijn
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Molecular biologic techniques are currently considered as new diagnostic and prognostic parameters with a sensitivity and specificity exceeding those of histologic and functional data currently used in clinical practice. The results in various clinical settings have been of limited value up to now. This study is an investigation of the use of tissue levels of RNA determined in routine clinical kidney biopsies as prognostic tools. The focus was on RNA encoding for molecules known to be involved in the pathogenesis of renal disorders. Fresh kidney biopsy tissue was obtained from 52 patients with various renal diseases. The GFR was followed for 12 mo. The extent of glomerulosclerosis and interstitial fibrosis in the biopsies was determined with quantitative digital image analysis. Glomerular and tubulointerstitial compartments from each biopsy specimen were separated, and mRNA levels of TGF-β, collagen I, collagen IV, and fibronectin were quantitated by real-time PCR. Correlations, along with 95% confidence intervals (CI), between all variables tested at time biopsy were determined. To assess their prognostic value, these variables were correlated with the slope of GFR within several time intervals after biopsy. In addition, to evaluate the predictive value of the variables for outcome in individual patients, differences for each variable were tested between patients showing progressive decline in renal function (slope GFR < 0) and patients showing stable or improving renal function over time (slope GFR ≥ 0). In chronic renal diseases, the extent of histologic damage correlated with the GFR at the time of biopsy (r = −0.44; CI −0.68 to −0.11), but it did not correlate with the slope expressing a change in GFR after the biopsy. Tubulointerstitial TGF-β mRNA levels correlated with the rate of change in GFR between time of biopsy and 1 mo later (r = 0.41; CI, 0.07 to 0.67). The GFR at the time of biopsy correlated with the slope of change in GFR between time of biopsy and 12 mo later (r = −0.50; CI, −0.73 to −0.18). In chronic renal diseases, glomerular fibronectin mRNA levels, in comparison with the GFR at time of biopsy, correlated relatively strongly with the slope of change in GFR between 3 and 12 mo (r = 0.50; CI, 0.16 to 0.74). Patients with favorable renal outcome after 12 mo showed significantly higher TGF-β mRNA levels and lower proteinuria levels at time of biopsy (P < 0.05) than patients with a progressive decline in renal function. This study shows that mRNA levels measured in kidney biopsies can function as prognostic tools in human renal diseases. In particular, relatively high levels of tubulointerstitial TGF-β mRNA and glomerular fibronectin mRNA are associated with less deterioration in renal function. E-mail: [email protected]
Atrioventricular Ring Reentry in Embryonic Mouse Hearts
Authors: Miguel Valderrábano, Fuhua Chen, Amish S. Dave, Scott T. Lamp, Thomas S. Klitzner, James N. Weiss
Journal: Circulation (2006)

During development, AV conduction switches from base-to-apex to apex-to-base conduction after emergence of the conduction system. We hypothesize that after this transition, the bulk of the AV ring, although no longer required for AV conduction, remains transiently able to conduct, providing a potential arrhythmia substrate. We studied AV conduction during this transition and its sensitivity to autonomic modulation.Simultaneous voltage and Ca2+ mapping with RH-237 and Rhod-2 was performed with 2 CCD cameras in embryonic mouse hearts (n = 43). Additionally, isolated calcium mapping was performed in 309 hearts with fluo-3AM. Propagation patterns in voltage and Ca2+ mapping coincided. Arrhythmias were uncommon under basal conditions, with AV block in 14 (4%) and junctional rhythms in 4 (1%). Arrhythmias increased after stimulation with isoproterenol-junctional rhythm in 9 (3%) and ventricular rhythms in 22 (6%)-although AV block decreased (3 hearts, 1%). Adding carbachol after isoproterenol caused dissociated antegrade and retrograde AV ring conduction in 30 (8.6%) of E10.5 and E11.5 hearts, occurring preferentially in the right and left sides of the ring, respectively. In 2 cases, reentry occurred circumferentially around the AV ring, perpendicular to normal propagation. Reentry persisted for multiple beats, lasting from 3 to 22 minutes. No episodes of AV ring reentry occurred in E9.5 hearts.AV ring reentry can occur by spatial dissociation of antegrade and retrograde conduction during combined adrenergic and muscarinic receptor stimulation. Critical maturation (> E9.5) seems to be required to sustain reentry.
Long-Term Impact of Smoking on Lung Epithelial Proliferation in Current and Former Smokers
Authors: J. J. Lee, D. Liu, J. S. Lee, J. M. Kurie, F. R. Khuri, H. Ibarguen, R. C. Morice, G. Walsh, J. Y. Ro, A. Broxson, W. K. Hong, W. N. Hittelman
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Lung cancer risk remains elevated for many years after quitting smoking. To assess using proliferation indices in bronchial tissues as an intermediate endpoint biomarker in lung cancer chemoprevention trials, we determined the relationship between the extent, intensity, and cessation of tobacco smoking and proliferative changes in bronchial epithelial biopsy specimens. Methods: Bronchial biopsy specimens were obtained from up to six epithelial sites in 120 current smokers (median pack-years, 42) and 207 former smokers (median pack-years, 40; median quit-years, 8.1). Sections from the paraffin-embedded specimens were stained with hematoxylin–eosin to determine the metaplasia index and with an antibody to Ki-67 to determine the proliferative (labeling) index for the basal and parabasal (Ki-67 PLI) layers. All statistical tests were two-sided. Results: Biopsy sites with metaplasia had statistically significantly higher Ki-67-labeling indices than those without metaplasia (P<.001) in both current and former smokers. Increased proliferation was observed in multiple biopsy sites, with the average Ki-67 PLI of the subject strongly correlating with the metaplasia index (r = .72 for current smokers; P<.001), even in sites without metaplasia (r = .23 for current smokers; P<.001). In current smokers, the Ki-67 PLI was associated with the number of packs smoked/day (P = .02) but not with smoking years or pack-years. In subjects who had quit smoking, the Ki-67 PLI dropped statistically significantly within 1 year (P = .008) but remained detectable for more than 20 years, even in the absence of squamous metaplasia. Conclusion: Smoking appears to elicit a dose-related proliferative response in the bronchial epithelia of active smokers. Although the proliferative response decreased gradually in former smokers, a subset of individuals had detectable proliferation for many years and may benefit from targeted chemoprevention. Bronchial epithelial proliferation, measured by Ki-67, may provide a useful biomarker in the assessment of lung cancer risk and in the response to chemopreventive interventions.
Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension
Authors: Jan A Staessen, Robert Fagard, Lutgarde Thijs, Hilde Celis, Guramy G Arabidze, Willem H Birkenhäger, Christopher J Bulpitt, Peter W de Leeuw, Colin T Dollery, Astrid E Fletcher, Françoise Forette, Gastone Leonetti, Choudomir Nachev, Eoin T O' Brien, Joseph Rosenfeld, José L Rodicio, Jaakko Tuomilehto, Alberto Zanchetti
Journal: The Lancet (1997)
Imaging of Cardiac Sarcoid Lesions Using Fasting Cardiac <sup>18</sup> F-Fluorodeoxyglucose Positron Emission Tomography: An Autopsy Case
Authors: Hiroaki Koiwa, Ichizo Tsujino, Hiroshi Ohira, Keiichiro Yoshinaga, Noriyuki Otsuka, Masaharu Nishimura
Journal: Circulation (2010)
Inactivation of <i>gadd45a</i> Sensitizes Epithelial Cancer Cells to Ionizing Radiation <i>In vivo</i> Resulting in Prolonged Survival
Authors: Xiangdong Lu, Chunyu Yang, Reginald Hill, Chaoyin Yin, M. Christine Hollander, Albert J. Fornace, Terry Van Dyke
Journal: Cancer Research (2008)

Abstract Ionizing radiation (IR) therapy is one of the most commonly used treatments for cancer patients. The responses of tumor cells to IR are often tissue specific and depend on pathway aberrations present in the tumor. Identifying molecules and mechanisms that sensitize tumor cells to IR provides new potential therapeutic strategies for cancer treatment. In this study, we used two genetically engineered mouse carcinoma models, brain choroid plexus carcinoma (CPC) and prostate, to test the effect of inactivating gadd45a, a DNA damage response p53 target gene, on tumor responses to IR. We show that gadd45a deficiency significantly increases tumor cell death after radiation. Effect on survival was assessed in the CPC model and was extended in IR-treated mice with gadd45a deficiency compared with those expressing wild-type gadd45a. These studies show a significant effect of gadd45a inactivation in sensitizing tumor cells to IR, implicating gadd45a as a potential drug target in radiotherapy management. [Cancer Res 2008;68(10):3579–83]
Reanalyses of Randomized Clinical Trial Data
Authors: Shanil Ebrahim, Zahra N. Sohani, Luis Montoya, Arnav Agarwal, Kristian Thorlund, Edward J. Mills, John P. A. Ioannidis
Journal: JAMA (2014)

Reanalyses of randomized clinical trial (RCT) data may help the scientific community assess the validity of reported trial results.To identify published reanalyses of RCT data, to characterize methodological and other differences between the original trial and reanalysis, to evaluate the independence of authors performing the reanalyses, and to assess whether the reanalysis changed interpretations from the original article about the types or numbers of patients who should be treated.We completed an electronic search of MEDLINE from inception to March 9, 2014, to identify all published studies that completed a reanalysis of individual patient data from previously published RCTs addressing the same hypothesis as the original RCT. Four data extractors independently screened articles and extracted data.Changes in direction and magnitude of treatment effect, statistical significance, and interpretation about the types or numbers of patients who should be treated.We identified 37 eligible reanalyses in 36 published articles, 5 of which were performed by entirely independent authors (2 based on publicly available data and 2 on data that were provided on request; data availability was unclear for 1). Reanalyses differed most commonly in statistical or analytical approaches (n = 18) and in definitions or measurements of the outcome of interest (n = 12). Four reanalyses changed the direction and 2 changed the magnitude of treatment effect, whereas 4 led to changes in statistical significance of findings. Thirteen reanalyses (35%) led to interpretations different from that of the original article, 3 (8%) showing that different patients should be treated; 1 (3%), that fewer patients should be treated; and 9 (24%), that more patients should be treated.A small number of reanalyses of RCTs have been published to date. Only a few were conducted by entirely independent authors. Thirty-five percent of published reanalyses led to changes in findings that implied conclusions different from those of the original article about the types and number of patients who should be treated.
Capecitabine and irinotecan as first-line chemotherapy in patients with metastatic colorectal cancer: results of an extended phase I study†
Authors: M. Tewes, N. Schleucher, W. Achterrath, H.J. Wilke, S. Frings, S. Seeber, A. Harstrick, Y.M. Rustum, U. Vanhoefer
Journal: Annals of Oncology (2003)
Cell Death via DR5, but not DR4, Is Regulated by p53 in Myeloma Cells
Authors: Sylvanie Surget, David Chiron, Patricia Gomez-Bougie, Géraldine Descamps, Emmanuelle Ménoret, Régis Bataille, Philippe Moreau, Steven Le Gouill, Martine Amiot, Catherine Pellat-Deceunynck
Journal: Cancer Research (2012)

Myeloma cells are sensitive to TRAIL through the two death receptors DR4 and DR5. Because p53 directly modulates expression of death receptors, we investigated here whether p53 can modulate myeloma sensitivity to TRAIL. We found that p53 affects the sensitivity of myeloma cells to the DR5 agonistic human antibody lexatumumab but not the DR4 antibody mapatumumab. TP53 wild-type myeloma cells overexpressed DR5 in correlation with sensitivity to lexatumumab. Both nongenotoxic (nutlin-3a) and genotoxic (melphalan) p53-inducing stresses increased DR5 expression only in TP53 wild-type cells and synergistically increased lexatumumab efficiency yet did not increase DR4 expression, nor sensitivity to mapatumumab. Silencing of p53 strongly decreased DR5 expression and induced resistance to nutlin-3a and lexatumumab but did not modulate DR4 expression or sensitivity to mapatumumab. Increase of lexatumumab efficiency induced by nutlin-3a was related to a p53-dependent increase of DR5 expression. In primary myeloma cells, nutlin-3a increased DR5 expression and lexatumumab efficiency but did not increase mapatumumab efficiency. Taken together, our findings indicate that p53 controls the sensitivity of myeloma through DR5 but not DR4 and suggest that a subset of patients with multiple myeloma may benefit from DR5 therapy.
Independent and Exclusive Modulation of Cardiac Delayed Rectifying K <sup>+</sup> Current by Protein Kinase C and Protein Kinase A
Authors: C. Frederick Lo, Randal Numann
Journal: Circulation Research (1998)

Expression of minK in Xenopus oocytes results in a current similar to the cardiac slow delayed rectifying K+ (IKs) current. Modulation of the IKs current in cardiac myocytes has been studied extensively because of its role in shaping the cardiac action potential. The human and cat minK cDNA have been cloned, but their regulation by protein kinases has not been characterized. We report here on the complex modulation of human and cat IKs currents by protein kinase C (PKC) and protein kinase A (PKA). Activation of PKC by phorbol ester (100 nmol/L phorbol 12,13-didecanoate [PDD]) produces an increase in IKs current that peaks after 20 minutes and then subsequently decreases to approximately 50% of the control level after 1 hour. PKA activation only produces a sustained increase in IKs current. Interestingly, premodulation by PKC prevents IKs current modulation by PKA, and PKC has no effect on IKs current after potentiation by PKA. This shows that the IKs current is modulated by PKC and PKA in a mutually exclusive manner and suggests that multiple interacting phosphorylation sites are involved. Activation of PKC by diacylglycerol analogues only produces a slow decrease in IKs current. The biphasic effects of PKC on IKs current activated by PDD can also be separated by dose and duration. Low doses of PDD (5 nmol/L) or brief applications (5 minutes) of 100 nmol/L PDD only produces IKs current activation. These data suggest that there are at least 2 independent PKC phosphorylation sites in the minK-KvLQT1 channel. Additionally, long-term activation of PKC strongly attenuates the IKs current expression even when the corresponding changes in capacitance are taken into account.
Implementing NICE guidance
Authors: Jayne Chidgey, Gillian Leng, Terence Lacey
Journal: Journal of the Royal Society of Medicine (2007)

The National Institute for Health and Clinical Excellence (NICE) was established as a Special Health Authority in April 1999 to promote clinical excellence and the effective use of resources within the NHS. NICE is the independent organization responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health (Box 1). This article highlights the robust methodology used to develop NICE guidance and NICE's approach to economic analysis, the mechanisms by which the clinical community is involved in guidance development, the practical support available to aid implementation of guidance, and the advantages to doctors (and other clinicians) of using NICE guidance.
Fluconazole in the management of patients with chronic mucocutaneous candidosis
Authors: R.J. Hay, Y.M. Clayton
Journal: British Journal of Dermatology (1988)

Journal Article Fluconazole in the management of patients with chronic mucocutaneous candidosis Get access R.J. Hay, R.J. Hay Department of Medical Mycology, St. John's Hospital for Diseases of the Skin, Lisle St, London WC2, U.K. Search for other works by this author on: Oxford Academic Google Scholar Y.M. Clayton Y.M. Clayton Department of Medical Mycology, St. John's Hospital for Diseases of the Skin, Lisle St, London WC2, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue 5, 1 November 1988, Pages 683–684, https://doi.org/10.1111/j.1365-2133.1988.tb03483.x Published: 01 November 1988
Feather Development Genes and Associated Regulatory Innovation Predate the Origin of Dinosauria
Authors: Craig B. Lowe, Julia A. Clarke, Allan J. Baker, David Haussler, Scott V. Edwards
Journal: Molecular Biology and Evolution (2014)

The evolution of avian feathers has recently been illuminated by fossils and the identification of genes involved in feather patterning and morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics and more than 600,000 conserved regulatory elements, we show that patterns of genome evolution in the vicinity of feather genes are consistent with a major role for regulatory innovation in the evolution of feathers. Rates of innovation at feather regulatory elements exhibit an extended period of innovation with peaks in the ancestors of amniotes and archosaurs. We estimate that 86% of such regulatory elements and 100% of the nonkeratin feather gene set were present prior to the origin of Dinosauria. On the branch leading to modern birds, we detect a strong signal of regulatory innovation near insulin-like growth factor binding protein (IGFBP) 2 and IGFBP5, which have roles in body size reduction, and may represent a genomic signature for the miniaturization of dinosaurian body size preceding the origin of flight.
ACUTE DISSEMINATED ENCEPHALOMYELITIS FOLLOWING IMMUNIZATION WITH HOMOLOGOUS BRAIN EXTRACTS
Authors: Lewis Thomas, Philip Y. Paterson, Betty Smithwick
Journal: The Journal of Experimental Medicine (1950)

1. A severe demyelinating condition characterized by ataxia and paralysis, in some instances leading to death, was produced in thirty-five of a total of fifty-five dogs following immunization with homologous brain tissue combined with Freund's adjuvants. In more than 30 per cent of instances paralysis did not occur until immunization was continued for 6 or more months. Only eight dogs became paralyzed after a single injection of antigen. The condition appeared between 6 and 15 days after the last injection in all animals, irrespective of the total number of injections or the duration of immunization. 2. An antibody which reacted in complement fixation tests with aqueous and alcoholic extracts of homologous brain tissue was demonstrable in the majority of immunized dogs, whether or not the animals became paralyzed. It appeared during or after the 3rd week of immunization, and its occurrence or titer could not be correlated with the incidence of the encephalomyelitis. In general, there were fewer dogs with demonstrable antibody in the paralyzed group than in the non-paralyzed group. 3. A flocculation reaction with alcohol extracts of homologous brain was demonstrated in the serum of immunized dogs. The antigen and antibody involved were apparently identical with those responsible for the complement fixation reactions. 4. The brain tissue component which reacted as antigen in the complement fixation test was present in adult brain from several mammalian species, and peripheral nerve. It was not present in the brain of newborn dogs nor in other unrelated organs. It was demonstrable in brain tissue which had been allowed to autolyze, or treated with 10 per cent formalin. It was not impaired by boiling, or by acid hydrolysis, and was contained in the unsaponifiable fraction of brain lipids. It was separable from cholesterol by digitonin precipitation of the latter. 5. Immunization of dogs with the unsaponifiable fraction of homologous brain, in adjuvants, caused the appearance of antibrain antibody similar to that in animals injected with whole brain. Encephalomyelitis was not observed during a 2 month period of immunization with this fraction. 6. In guinea pigs, an injection of the unsaponifiable fraction of brain, in adjuvants, was followed by fatal meningoencephalitis, but the identity of the state with that caused by whole brain antigens was not established.
EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs
Authors: G K Bertsias, J P A Ioannidis, M Aringer, E Bollen, S Bombardieri, I N Bruce, R Cervera, M Dalakas, A Doria, J G Hanly, T W J Huizinga, D Isenberg, C Kallenberg, J C Piette, M Schneider, N Scolding, J Smolen, A Stara, I Tassiulas, M Tektonidou, A Tincani, M A van Buchem, R van Vollenhoven, M Ward, C Gordon, D T Boumpas
Journal: Annals of the Rheumatic Diseases (2010)

Objectives To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations. Methods The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design. Results Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence &gt;5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD. Conclusions Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.