tbuckley/cabot-search huggingface dataset:
General Anesthesia and Altered States of Arousal: A Systems Neuroscience Analysis
Authors: Emery N. Brown, Patrick L. Purdon, Christa J. Van Dort
Journal: Annual Review of Neuroscience (2011)

Placing a patient in a state of general anesthesia is crucial for safely and humanely performing most surgical and many nonsurgical procedures. How anesthetic drugs create the state of general anesthesia is considered a major mystery of modern medicine. Unconsciousness, induced by altered arousal and/or cognition, is perhaps the most fascinating behavioral state of general anesthesia. We perform a systems neuroscience analysis of the altered arousal states induced by five classes of intravenous anesthetics by relating their behavioral and physiological features to the molecular targets and neural circuits at which these drugs are purported to act. The altered states of arousal are sedation-unconsciousness, sedation-analgesia, dissociative anesthesia, pharmacologic non-REM sleep, and neuroleptic anesthesia. Each altered arousal state results from the anesthetic drugs acting at multiple targets in the central nervous system. Our analysis shows that general anesthesia is less mysterious than currently believed.
Mouse mammary tumor virus in hybrids from strains C57BL and GR: breeding test of backcross segregants.
Authors: W E Heston, B Smith, W P Parks
Journal: The Journal of Experimental Medicine (1976)

F1 and F2 and first backcross hybrids and second backcross families of the high mammary tumor incidence strain GR and the low incidence strain C57BL were examined for the segregation of mouse mammary tumor viral (MMTV) expression. Although GR has been reported to transmit MMTV as a single dominant gene, several lines of evidence suggest there are multiple genetic factors that influence MMTV expression, MMTV expression as measured by double antibody radioimmunoassay for MMTV p14 segregated in 106 first backcross progeny at a 60:40 ratio, intermediate between what would be expected for either a single or two gene hypothesis. In female second backcross progeny of either male or female first backcross, a heterogeneous pattern of expression was noted that does not fit any simple Mendalian pattern. From an analysis of serial lactations of first backcross and second backcross families, it appears that all hybrid females contain MMTV proviral information that may be expressed either at late lactations or in a variable proportion of progeny mice. These combined results are most consistent with a vertically transmitted genome regulated by multiple factors in these crosses.
Nested case-control studies: advantages and disadvantages
Authors: P. Sedgwick
Journal: BMJ (2014)

Researchers investigated whether antipsychotic drugs were associated with venous thromboembolism. A population based nested case-control study design was used. Data were taken from the UK QResearch primary care database consisting of 7 267 673 patients. Cases were adult patients with a first ever record of venous thromboembolism between 1 January 1996 and 1 July 2007. For each case, up to four controls were identified, matched by age, calendar time, sex, and practice. Exposure to antipsychotic drugs was assessed on the basis of prescriptions on, or during the 24 months before, the index date.1

There were 25 532 eligible cases (15 975 with deep vein thrombosis and 9557 with pulmonary embolism) and 89 491 matched controls. The primary outcome was the odds ratios for venous thromboembolism associated with antipsychotic drugs adjusted for comorbidity and concomitant drug exposure. When adjusted using logistic regression to control for potential confounding, prescription of antipsychotic drugs in the previous 24 months was significantly associated with an increased occurrence of venous thromboembolism compared with non-use (odds ratio 1.32, 95% confidence interval 1.23 to 1.42). The researchers concluded that prescription of antipsychotic drugs was associated with venous thromboembolism in a large primary care population.

Which of the following statements, if any, are true?

Statements a , b , and c are true, …
Prognostic Significance of Activated Akt Expression in Melanoma: A Clinicopathologic Study of 292 Cases
Authors: Derek L. Dai, Magdalena Martinka, Gang Li
Journal: Journal of Clinical Oncology (2005)

Akt is a serine/threonine kinase that leads to stimulation of cell cycle progression, cell proliferation, and inhibition of apoptosis. To investigate the role of Akt in melanoma pathogenesis, we examined the expression of phospho-Akt (p-Akt; Ser-473) in melanocytic lesions at different stages and analyzed the correlations between the p-Akt expression level and clinicopathologic factors and patient survival.We evaluated the p-Akt expression in 12 cases of normal nevi, 58 cases of dysplastic nevi, 170 cases of primary melanomas, and 52 cases of melanoma metastases using tissue microarray and immunohistochemistry.Strong p-Akt expression was observed in 17%, 43%, 49%, and 77% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for p-Akt staining pattern were observed between normal nevi and primary melanomas (P < .05), and between primary melanomas and melanoma metastases (P < .001). Furthermore, our Kaplan-Meier survival curves showed that strong p-Akt expression is inversely correlated with both overall and disease-specific 5-year survival of patients with primary melanoma (P < .05 for both). Strikingly, our multivariate Cox regression analysis revealed that p-Akt is an independent prognostic factor in low-risk melanomas (thickness < or = 1.5 mm; relative risk, 6.44; 95% CI, 1.28 to 32.55; P = .018).The expression of p-Akt increases dramatically with melanoma invasion and progression and is inversely correlated with patient survival. In addition, p-Akt may serve as an independent prognostic marker and help to identify those patients with low-risk melanomas who are at increased risk of death.
MicroRNA-34a Plays a Key Role in Cardiac Repair and Regeneration Following Myocardial Infarction
Authors: Yanfei Yang, Hui-Wen Cheng, Yiling Qiu, David Dupee, Madyson Noonan, Yi-Dong Lin, Sudeshna Fisch, Kazumasa Unno, Konstantina-Ioanna Sereti, Ronglih Liao
Journal: Circulation Research (2015)

In response to injury, the rodent heart is capable of virtually full regeneration via cardiomyocyte proliferation early in life. This regenerative capacity, however, is diminished as early as 1 week postnatal and remains lost in adulthood. The mechanisms that dictate postinjury cardiomyocyte proliferation early in life remain unclear.To delineate the role of miR-34a, a regulator of age-associated physiology, in regulating cardiac regeneration secondary to myocardial infarction (MI) in neonatal and adult mouse hearts.Cardiac injury was induced in neonatal and adult hearts through experimental MI via coronary ligation. Adult hearts demonstrated overt cardiac structural and functional remodeling, whereas neonatal hearts maintained full regenerative capacity and cardiomyocyte proliferation and recovered to normal levels within 1-week time. As early as 1 week postnatal, miR-34a expression was found to have increased and was maintained at high levels throughout the lifespan. Intriguingly, 7 days after MI, miR-34a levels further increased in the adult but not neonatal hearts. Delivery of a miR-34a mimic to neonatal hearts prohibited both cardiomyocyte proliferation and subsequent cardiac recovery post MI. Conversely, locked nucleic acid-based anti-miR-34a treatment diminished post-MI miR-34a upregulation in adult hearts and significantly improved post-MI remodeling. In isolated cardiomyocytes, we found that miR-34a directly regulated cell cycle activity and death via modulation of its targets, including Bcl2, Cyclin D1, and Sirt1.miR-34a is a critical regulator of cardiac repair and regeneration post MI in neonatal hearts. Modulation of miR-34a may be harnessed for cardiac repair in adult myocardium.
The mark of T reg cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Brain-tethered T cellsOn page 1805, Kawakami et al. show that antigen-specific CD4 ϩ T cells that attack the brain become stationary within brain tissue, whereas nonspecific T cells cruise through without stopping.These intravital images-the first to capture T cells launching an autoimmune attack on the brain-suggest that antigenspecific T cells behave similarly in dense brain tissue as they do in lymph nodes.Activated CD4 ϩ T cells specific for the endogenous brain protein myelin basic protein (MBP) trigger fatal encephalomyelitis in a rat model of multiple sclerosis.These cells migrate into the central nervous system (CNS) where they become reactivated.Previous studies by this group showed that both antigen-specific and nonspecific T cells gain access to the CNS, but only specific cells become reactivated once there.Kawakami et al. now show that a subset of MBP-specific T cells-likely those that have encountered antigen-stopped moving inside the brain, appearing tethered to a fixed point.T cells specific for a control antigen kept moving, suggesting that the presence of antigen was required for T cells to stop moving and to trigger disease.The authors were surprised to find that T cells move as rapidly through the dense brain tissue as in the more aqueous environment of the lymph nodes.How they do this is not known but the authors suggest that the T cells may produce proteases that help clear a path through the compact tissue.
Access to phenomenality: A necessary condition of phenomenality?
Authors: Katalin Balog
Journal: Behavioral and Brain Sciences (2007)

Abstract Block argues that relevant data in psychology and neuroscience show that access consciousness is not constitutively necessary for phenomenality. However, a phenomenal state can be access conscious in two radically different ways. Its content can be access conscious, or its phenomenality can be access conscious. I argue that while Block's thesis is right when it is formulated in terms of the first notion of access consciousness, there is an alternative hypothesis about the relationship between phenomenality and access in terms of the second notion that is not touched by Block's argument.
Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin's lymphomas: Treatment results and prognostic factor analysis in a multi-centre trial
Authors: H. Köppler, K.-H. Pflüger, I. Eschenbach, R. Pfab, J. Birkmann, W. Zeller, R. Holle, U.E. Steinhauer, C. Gropp, S. Oehl, K. Lennert, M.R. Parwaresch, H. Kuhn, P. Drings, H.H. Gossmann, M. Khoury, R. Schubotz, K. Havemann
Journal: Annals of Oncology (1994)
Previous Cytomegalovirus Infection and Restenosis After Coronary Stent Placement
Authors: Franz-Josef Neumann, Adnan Kastrati, Thomas Miethke, Julinda Mehilli, Gisela Pogatsa-Murray, Werner Koch, Melchior Seyfarth, Albert Schömig
Journal: Circulation (2001)

Reactivated cytomegalovirus may promote neointima formation after percutaneous coronary interventions by facilitating cell cycle progression through inhibition of the eukariotic tumor suppressor protein p53. This prospective study sought to investigate the effect of previous cytomegalovirus infection on restenosis after coronary stenting.In 551 consecutive patients with successful stent placement, we determined cytomegalovirus IgG titers. Primary and secondary end points were the rate of angiographic restenosis at 6 months and the rate of target vessel reintervention at 1 year, respectively. Three hundred forty patients (62%) had a positive cytomegalovirus IgG titer. We obtained angiographic follow-up in 82% of all patients. Angiographic restenosis rate was 28.7% in patients with positive cytomegalovirus titers and 34.6% in patients with negative titers (P=0.18). Between the groups with and without positive cytomegalovirus titers, there were no significant differences in late lumen loss (1.16+/-0.90 mm and 1.23+/-0.86 mm, respectively, P=0.44). Target vessel reintervention was performed in 16.8% of the patients with positive cytomegalovirus titers and in 17.5% of those without (P=0.82). Even after correction for potential confounding variables by multivariate analysis, positive cytomegalovirus titers did not manifest as a predictor of angiographic restenosis (adjusted odds ratio [95% confidence interval], 0.78 [0.52 to 1.19]).Previous cytomegalovirus infection does not carry an increased risk of restenosis after stenting.
NORMAL STRUCTURE AND DEGENERATIVE CHANGES OF THE CYTOPLASM OF LIVER CELLS AND OF TUMOR CELLS DERIVED FROM THEM
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1947)

Discrete bodies which may be designated cytochondria occupy the greater part of the cytoplasm of liver cells. A part, but not all, of these bodies have the characteristics of mitochondria. They consist of a rim which stains deeply and a central part which stains faintly or remains unstained. In liver cells about portal spaces, in foci of regeneration, and in tumor cells the rims of the cytochondria stain with basic dyes and contain ribonucleic acid or related substances. With increasing accumulation of basophile substances about cytochondria as the central veins are approached, these bodies aggregate to form clumps or orient themselves with palisade-like arrangment in two rows just within the margins of the liver cell columns. With aggregation of the cytochondria that are surrounded by basophile material, other cytochondria in the same cells are devoid of this material and wholly acidophile. With chromatolysis (disappearance of basophile substance) caused by dimethylaminoazobeiizene (butter yellow) cytochondria lose their peripheral basophilia and stain only with acid dyes. When ribonucleic acid is removed from fixed liver tissue by ribonuclease, cytochondria lose their affinity for basic stains and become acidophile. Of the cytochondria that are surrounded by ribonucleic acid or related substances part have the characteristics of mitochondria. Under the influence of butter yellow cytochondria may become greatly swollen and intensely acidophile in the center though they retain their basophile rim. These swollen bodies in part at least have the reactions of mitochondria. In tumor cells of hepatomas mitochondria are smaller and less abundant than in parenchymatous cells of the liver, and accompanying them are bodies of similar size which do not react as mitochondria. The cytochondria of hepatomas produced by butter yellow undergo acidophile degeneration similar to that of liver cells and form swollen spherical bodies with basophile rims. With partial or complete loss of basophile substance, these altered cytochondria may form conspicuous cell inclusions.
Novel Serpinopathy in Rat Kidney and Pancreas Induced by Overexpression of Megsin
Authors: Reiko Inagi, Masaomi Nangaku, Nobuteru Usuda, Akira Shimizu, Hiroshi Onogi, Yuko Izuhara, Kiyokazu Nakazato, Yasuhiko Ueda, Hisashi Oishi, Satoru Takahashi, Masayuki Yamamoto, Daisuke Suzuki, Kiyoshi Kurokawa, Charles van Ypersele de Strihou, Toshio Miyata
Journal: Journal of the American Society of Nephrology (2005)

The intracellular polymerization of abnormal serine protease inhibitors (serpins) results in liver or neuronal cell abnormalities recently identified as “serpinopathies.” It was demonstrated in transgenic rats that overexpression of megsin, a recently discovered serpin located in the kidney, produces renal and pancreatic lesions characteristic of serpinopathies. Megsin expression is elevated in a variety of organs, including kidney and pancreas. Periodic acid-Schiff–positive, diastase-resistant intracellular inclusions develop only in the kidney and the pancreas. They correspond to electron-dense deposits, shown to contain megsin by immunohistochemistry and immunoelectron microscopy. In the kidney, inclusions are located mainly in the endoplasmic reticulum of glomerular epithelial, distal, and collecting duct cells, and are associated with massive proteinuria and an impaired renal function. In the pancreas, similar inclusions are found in the exocrine and Langerhans islet cells, where islet β cells are reduced as a result of apoptosis. They are associated with diabetes with low insulin levels. The animals have an impaired growth and die within 10 wk. Rats that overexpress a mutant megsin, characterized by a deficient conformational transition activity, do not develop the serpinopathy, suggesting that some conformational flexibility of the serpin is required for the development of serpinopathy. This model of serpinopathy is the first to involve the kidney and the pancreas.
Non-invasive mechanical ventilation: when to start for what benefit?
Authors: B Fauroux
Journal: Thorax (2005)

When is the optimal time to perform polysomnography in patients with neuromuscular disease?

Non-invasive ventilation (NIV) is recognised as an efficient therapeutic option in patients with chronic respiratory insufficiency due to neuromuscular disorders. However, the long standing clinical experience with NIV contrasts with the absence of validated criteria for initiating this treatment and the paucity of data on its long term physiological and psychometric effects.

Several consensus conferences agree on the value of daytime hypercapnia and an acute exacerbation as criteria for starting NIV because they are characteristic signs of established ventilatory failure.1–3 However, these two classical criteria are preceded by a variable period of nocturnal hypoventilation during which treatable symptoms—such as frequent arousals, severe orthopnoea, daytime fatigue, and alterations in cognitive function—may cause deterioration in the quality of the patient’s daily life.

The first problem is to decide when to perform polysomnography in a patient with only a few symptoms.4 Polysomnography should be undertaken without delay when the patient develops symptoms related to sleep disordered breathing, but patients with neuromuscular disorders tend to underestimate symptoms such as fatigue before using mechanical ventilation. Sleep disordered breathing is difficult to establish in children because of reliance on parents and other caregivers who have a different perception of the child’s disease. Lung function parameters are poor indicators of nocturnal hypoventilation and data are only available for patients with neuromuscular disorders. Indeed, forced expiratory volume in 1 second (FEV1) has been shown to be inversely correlated with daytime arterial carbon dioxide tension (Paco2) and base excess in patients with Duchenne muscular dystrophy.5 But the recommendation to perform …
Identification of a Novel Developmental Stage Marking Lineage Commitment of Progenitor Thymocytes
Authors: James R. Carlyle, Alison M. Michie, Caren Furlonger, Toru Nakano, Michael J. Lenardo, Christopher J. Paige, Juan Carlos Zúñiga-Pflücker
Journal: The Journal of Experimental Medicine (1997)

Bipotent progenitors for T and natural killer (NK) lymphocytes are thought to exist among early precursor thymocytes. The identification and functional properties of such a progenitor population remain undefined. We report the identification of a novel developmental stage during fetal thymic ontogeny that delineates a population of T/NK-committed progenitors (NK1.1+/CD117+/CD44+/CD25−). Thymocytes at this stage in development are phenotypically and functionally distinguishable from the pool of multipotent lymphoid-restricted (B, T, and NK) precursor thymocytes. Exposure of multipotent precursor thymocytes or fetal liver– derived hematopoietic progenitors to thymic stroma induces differentiation to the bipotent developmental stage. Continued exposure to a thymic microenvironment results in predominant commitment to the T cell lineage, whereas coculture with a bone marrow–derived stromal cell line results in the generation of mature NK cells. Thus, the restriction point to T and NK lymphocyte destinies from a multipotent progenitor stage is marked by a thymus-induced differentiation step.
Macrophage Expression of Hypoxia-Inducible Factor-1α Suppresses T-Cell Function and Promotes Tumor Progression
Authors: Andrew L. Doedens, Christian Stockmann, Mark P. Rubinstein, Debbie Liao, Na Zhang, David G. DeNardo, Lisa M. Coussens, Michael Karin, Ananda W. Goldrath, Randall S. Johnson
Journal: Cancer Research (2010)

T cells can inhibit tumor growth, but their function in the tumor microenvironment is often suppressed. Many solid tumors exhibit abundant macrophage infiltration and low oxygen tension, yet how hypoxic conditions may affect innate immune cells and their role in tumor progression is poorly understood. Targeted deletion of the hypoxia-responsive transcription factor hypoxia-inducible factor-1α (HIF-1α) in macrophages in a progressive murine model of breast cancer resulted in reduced tumor growth, although vascular endothelial growth factor-A levels and vascularization were unchanged. Tumor-associated macrophages can suppress tumor-infiltrating T cells by several mechanisms, and we found that hypoxia powerfully augmented macrophage-mediated T-cell suppression in vitro in a manner dependent on macrophage expression of HIF-1α. Our findings link the innate immune hypoxic response to tumor progression through induction of T-cell suppression in the tumor microenvironment.
Engraftment in Nonobese Diabetic Severe Combined Immunodeficient Mice of Human CD34+ Cord Blood Cells After Ex Vivo Expansion: Evidence for the Amplification and Self-Renewal of Repopulating Stem Cells
Authors: Wanda Piacibello, Fiorella Sanavio, Antonella Severino, Alessandra Danè, Loretta Gammaitoni, Franca Fagioli, Eliana Perissinotto, Giuliana Cavalloni, Orit Kollet, Tsvee Lapidot, Massimo Aglietta
Journal: Blood (1999)
Update on Typical and Atypical Antipsychotic Drugs
Authors: Herbert Y. Meltzer
Journal: Annual Review of Medicine (2012)

Antipsychotic drugs (APDs) are best classified as typical or atypical. The distinction is based solely on their ability to cause extrapyramidal side effects (EPS), including tardive dyskinesia (TD). The two classes differ in mechanism of action, with atypical APDs providing important modulation of serotonergic neurotransmission. TD increases the death rate and can be minimized by limiting use of typical APDs. Clozapine is unique among the atypical APDs in its efficacy for ameliorating psychosis in patients with treatment-resistant schizophrenia (TRS), for reduction of suicide, and for improving longevity. The typical and atypical APDs do not differ in improving psychopathology in non-TRS. The atypicals vary in metabolic side effects: some have little burden. Cognitive benefits of the atypical APDs may be superior for some domains of cognition and require less use of anticholinergic drugs, which impair memory, for treatment of EPS. Overall, choosing among the atypical APDs as first-line treatment represents the best course for schizophrenia and most likely other disorders for which APDs are used.