tbuckley/cabot-search huggingface dataset:
Cortical Activations During Auditory Verbal Hallucinations in Schizophrenia: A Coordinate-Based Meta-Analysis
Authors: Renaud Jardri, Alexandre Pouchet, Delphine Pins, Pierre Thomas
Journal: American Journal of Psychiatry (2010)

Objective: Auditory verbal hallucinations (AVHs) constitute severe, incapacitating symptoms of schizophrenia. Despite increasing interest in the functional exploration of AVHs, the available findings remain difficult to integrate because of their considerable variability. The authors' aim was to perform a robust quantitative review of existing functional data in order to elucidate consistent patterns observed during the emergence of AVHs and to orient new pathophysiological models of hallucinations. Method: Ten positron emission tomography or functional magnetic resonance imaging studies were selected for the meta-analysis after systematic review. A total of 68 patients with schizophrenia spectrum disorders experiencing AVHs during scanning were included. According to a random-effects activation likelihood estimation algorithm, stereotaxic coordinates of 129 foci, reported as significant in the source studies, were extracted and computed to estimate the brain locations most consistently associated with AVHs across studies (cluster-extent threshold: 200 mm3). Results: Patients experiencing AVHs demonstrated significantly increased activation likelihoods in a bilateral neural network, including the Broca's area (activation likelihood estimation=1.84×10−3), anterior insula (1.78×10−3), precentral gyrus (1.46×10−3), frontal operculum (1.29×10−3), middle and superior temporal gyri (1.59×10−3), inferior parietal lobule (1.33×10−3), and hippocampus/parahippocampal region (1.90×10−3). Conclusions: This meta-analysis demonstrated that experiencing AVHs is associated with increased activity in fronto-temporal areas involved in speech generation and speech perception, but also within the medial temporal lobe, a structure notably involved in verbal memory. Such findings support a model for AVHs in which aberrant cortical activations emerge within a distributed network involved at different levels of complexity in the brain architecture. Critical future directions are considered.
Cleavage and inactivation of alpha 1-antitrypsin by metalloproteinases released from neutrophils.
Authors: M C Vissers, P M George, I C Bathurst, S O Brennan, C C Winterbourn
Journal: Journal of Clinical Investigation (1988)

Human neutrophils, when stimulated with phorbol myristate acetate or fMet-Leu-Phe in the presence or absence of cytochalasin B, released metalloproteinases that catalytically inactivated the plasma serine proteinase inhibitor, alpha 1-antitrypsin. Inactivation, measured as loss of elastase inhibitory capacity, was accompanied by cleavage of a Mr 4,000 peptide from the COOH-terminus. Cleavage of alpha 1-antitrypsin by cell supernatants was inhibited by EDTA, o-phenanthroline, and DTT, but not by inhibitors of serine or thiol proteinases. Gelatinase and collagenase were separated from the medium of stimulated neutrophils. Both preparations cleaved and inactivated alpha 1-antitrypsin, with cleavage occurring close to the reactive center, at the Phe-Leu bond between positions P7 and P6. Cleavage by purified gelatinase was very slow and could account for only a minor fraction of the activity of neutrophil supernatants. The collagenase preparation was more active. However, the unusual cleavage site, and the ability of fMet-Leu-Phe-stimulated neutrophils to cleave alpha 1-antitrypsin without releasing collagenase, suggests that collagenase is not responsible for cleavage by the cells, which, by implication, is due to an as yet uncharacterized metalloenzyme. Our results demonstrate that by releasing metalloproteinases, neutrophils could proteolytically inactivate alpha 1-antitrypsin at sites of inflammation. This provides an alternative to the previously documented mechanism of inactivation by neutrophil-derived oxidants.
A Method of Performing Abdomino-Perineal Excision for Carcinoma of the Rectum and of the Terminal Portion of the Pelvic Colon (1908)
Authors: W. E. Miles
Journal: CA A Cancer Journal for Clinicians (1971)

CA: A Cancer Journal for Clinicians publishes information about the prevention, early detection, and treatment of cancer, as well as nutrition, palliative care, survivorship, and additional topics of interest related to cancer care.
THE PRODUCTION AND TITRATION OF POTENT HORSE ANTIPNEUMOTOXIN
Authors: Julia T. Parker, Mary Van S. McCoy
Journal: The Journal of Experimental Medicine (1929)

1. The serum of horses immunized with increasing doses of certain anaerobically produced autolysates of pneumococci contain potent neutralizing antibodies for the pneumotoxin. 2. The method for the in vitro titration of these horse antipneumotoxic serums is given.
Activation of NF-κB Signaling by Inhibitor of NF-κB Kinase β Increases Aggressiveness of Ovarian Cancer
Authors: Lídia Hernandez, Sarah C. Hsu, Ben Davidson, Michael J. Birrer, Elise C. Kohn, Christina M. Annunziata
Journal: Cancer Research (2010)

Abstract The NF-κB family of transcription factors has been implicated in the propagation of ovarian cancer, but the significance of constitutive NF-κB signaling in ovarian cancer is unknown. We hypothesized that constitutive NF-κB signaling defines a subset of ovarian cancer susceptible to therapeutic targeting of this pathway. We investigated the biological relevance of NF-κB in ovarian cancer using a small-molecule inhibitor of inhibitor of NF-κB kinase β (IKKβ) and confirmed with RNA interference toward IKKβ. We developed a gene expression signature of IKKβ signaling in ovarian cancer using both pharmacologic and genetic manipulation of IKKβ. The expression of IKKβ protein itself and the nine-gene ovarian cancer–specific IKKβ signature were related to poor outcome in independently collected sets of primary ovarian cancers (P = 0.02). IKKβ signaling in ovarian cancer regulated the transcription of genes involved in a wide range of cellular effects known to increase the aggressive nature of the cells. We functionally validated the effect of IKKβ signaling on proliferation, invasion, and adhesion. Downregulating IKKβ activity, either by a small-molecule kinase inhibitor or by short hairpin RNA depletion of IKKβ, blocked all of these cellular functions, reflecting the negative regulation of the target genes identified. The diversity of functions controlled by IKKβ in ovarian cancer suggests that therapeutic blockade of this pathway could be efficacious if specific IKKβ inhibitor therapy is focused to patients whose tumors express a molecular profile suggestive of dependence on IKKβ activity. Cancer Res; 70(10); 4005–14. ©2010 AACR.
THE POSSIBILITIES OF BISMUTH THERAPY IN THE TREATMENT OF CUTANEOUS DISEASES
Authors: R. M. B. MacKENNA
Journal: British Journal of Dermatology (1931)

Journal Article THE POSSIBILITIES OF BISMUTH THERAPY IN THE TREATMENT OF CUTANEOUS DISEASES Get access R. M. B. MacKENNA, M.A., M.D.Camb., M.R.C.P.Lond. R. M. B. MacKENNA, M.A., M.D.Camb., M.R.C.P.Lond. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 43, Issue 11, 1 November 1931, Pages 565–587, https://doi.org/10.1111/j.1365-2133.1931.tb09453.x Published: 01 November 1931
Inhibition of the p53 E3 Ligase HDM-2 Induces Apoptosis and DNA Damage–Independent p53 Phosphorylation in Mantle Cell Lymphoma
Authors: Richard J. Jones, Qing Chen, Peter M. Voorhees, Ken H. Young, Nathalie Bruey-Sedano, Dajun Yang, Robert Z. Orlowski
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The ubiquitin-proteasome pathway has been validated as a target in non–Hodgkin's lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib. Experimental Design: Another potentially attractive target is the human homologue of the murine double minute-2 protein, HDM-2, which serves as the major p53 E3 ubiquitin ligase; we therefore evaluated the activity of a novel agent, MI-63, which disrupts the HDM-2/p53 interaction. Results: Treatment of wild-type p53 mantle cell lymphoma (MCL) cell lines with MI-63 resulted in a dose- and time-dependent inhibition of proliferation, with an IC50 in the 0.5 to 5.0 μmol/L range. MI-63 induced p53 and HDM-2 accumulation, as well as other downstream p53 targets such as p53 up-regulated modulator of apoptosis and p21Cip1. This was associated with cell cycle arrest at G1-S; activation of caspase-3, caspase-8, and caspase-9; cleavage of poly-(ADP-ribose) polymerase; and loss of E2F1. HDM-2 inhibition caused phosphorylation of p53 at multiple serine residues, including 15, 37, and 392, which coincided with low levels of DNA strand breaks. DNA damage occurred in a small percentage of cells and did not induce phosphorylation of the DNA damage marker H2A.XSer139. Combinations of MI-63 with the molecularly targeted agents bortezomib and rapamycin showed synergistic, sequence-dependent antiproliferative effects. Treatment of primary MCL patient samples resulted in apoptosis and induction of p53 and p21, which was not seen in normal controls. Conclusions: These findings support the hypothesis that inhibition of the HDM-2/p53 interaction may be a promising approach both by itself and in combination with currently used chemotherapeutics against lymphoid malignancies.
Decline in Lung Function in the Busselton Health Study
Authors: Alan L. James, Lyle J. Palmer, Elizabeth Kicic, Peta S. Maxwell, Sharon E. Lagan, Gerard F. Ryan, A. William Musk
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Asthma in adults may be associated with chronic airflow obstruction, possibly resulting from airway disease in early life and/or a greater rate of decline in lung function in adult life compared with those with asthma. Treatment and cigarette smoking may also influence the rate of decline of lung function. The aim of this analysis was to examine the level and rate of decline in lung function in relationship to asthma and cigarette smoking in adults. Subjects (n = 9,317) had participated as adults (> 18 years) in one or more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the level and rate of decline in FEV1 were examined in a linear mixed effects model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers. Males, taller subjects, smokers, and subjects with asthma had greater declines in FEV1 with age. Smoking and asthma had additive but not multiplicative effects on decline. Thus, asthma is associated with reduced lung function at the beginning of adult life as well as an increased rate of decline during adult life.
Association Among Visual Hallucinations, Visual Acuity, and Specific Eye Pathologies in Alzheimer’s Disease: Treatment Implications
Authors: Fiona M. Chapman, Jane Dickinson, Ian McKeith, Clive Ballard
Journal: American Journal of Psychiatry (1999)

Studies suggest a link between visual acuity and visual hallucinations in dementia, but links with specific eye pathologies have not been evaluated.Fifty patients (20 with visual hallucinations, 30 without) with probable Alzheimer's disease had an evaluation of psychotic symptoms. Visual acuity was measured before and after refractions, and ophthalmological examinations included standardized assessments for cataracts and macular degeneration.Impaired visual acuity and the severity of cognitive impairments were significantly associated with visual hallucinations. No patients with normal acuity (6/5 or 6/6 on the Snellen chart) experienced these symptoms. Impaired acuity improved with refraction in 60% (N = 12) of the patients with visual hallucinations. Of specific eye pathologies, only cataracts were significantly associated with visual hallucinations. Descriptive follow-up information suggests that an optician's assessment for glasses improves outcome.Glasses and cataract surgery need evaluation as prophylactic or adjunctive treatments for visual hallucinations in patients with probable Alzheimer's disease.
Metformin and Pancreatic Cancer: A Clue Requiring Investigation
Authors: Michael Pollak
Journal: Clinical Cancer Research (2012)

Laboratory models show antineoplastic activity of metformin under certain conditions, and pharmacoepidemiologic studies have reported reduced cancer burden among diabetics taking metformin. Therefore, the hypothesis that metformin has antineoplastic activity is receiving increasing attention. However, gaps in knowledge must be addressed before metformin can be "repurposed" for oncologic indications.
Expression of E6AP and PML predicts for prostate cancer progression and cancer-specific death
Authors: S.E. Birch, J.G. Kench, E. Takano, P. Chan, A.-L. Chan, K. Chiam, A.-S. Veillard, P. Stricker, S. Haupt, Y. Haupt, L. Horvath, S.B. Fox
Journal: Annals of Oncology (2014)
Nature and Health
Authors: Terry Hartig, Richard Mitchell, Sjerp de Vries, Howard Frumkin
Journal: Annual Review of Public Health (2014)

Urbanization, resource exploitation, and lifestyle changes have diminished possibilities for human contact with nature in many societies. Concern about the loss has helped motivate research on the health benefits of contact with nature. Reviewing that research here, we focus on nature as represented by aspects of the physical environment relevant to planning, design, and policy measures that serve broad segments of urbanized societies. We discuss difficulties in defining “nature” and reasons for the current expansion of the research field, and we assess available reviews. We then consider research on pathways between nature and health involving air quality, physical activity, social cohesion, and stress reduction. Finally, we discuss methodological issues and priorities for future research. The extant research does describe an array of benefits of contact with nature, and evidence regarding some benefits is strong; however, some findings indicate caution is needed in applying beliefs about those benefits, and substantial gaps in knowledge remain. [ Erratum ]
Paul Ehrlich's Magic Bullets
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2004)

March 14, 2004, marks the 150th anniversary of the birth of Paul Ehrlich, one of the generation of pioneers who, during the 50 years that led up to World War I, laid the foundation of modern medicine. Pasteur, Röntgen, Curie, Koch, Freud, and Lister were his contemporaries in this company of trailblazers.Ehrlich's prodigious talents in the laboratory — he was called a virtuoso of test tubes — were matched by a combination of intuition and deduction that marked him as a genius. He was the father of hematology, a revolutionary immunologist, and the creator of the field of chemotherapy. . . .
Treatment Selection and Survival Outcomes in Early-Stage Diffuse Large B-Cell Lymphoma: Do We Still Need Consolidative Radiotherapy?
Authors: John A. Vargo, Beant S. Gill, Goundappa K. Balasubramani, Sushil Beriwal
Journal: Journal of Clinical Oncology (2015)

The choice between chemotherapy alone and chemotherapy plus consolidative radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) remains controversial. We aimed to define factors affecting treatment selection and the resulting survival outcomes.Using the National Cancer Data Base, we identified 59,255 patients with stages I and II DLBCL treated with multiagent chemotherapy alone or chemotherapy plus consolidative RT between 1998 and 2012. Univariable and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of overall survival (OS) and treatment use. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias.Of the 59,255 patients with DLBCL enrolled onto the study, 46% had stage II disease, 42% had extranodal disease, and 58% were more than 60 years of age. Only 39% received combined-modality therapy, and this proportion significantly declined from 47% in 2000 to 32% in 2012 (P < .001). Treatment selection was significantly influenced by race, comorbidity, insurance type, education quartile, facility type, age, stage, B symptoms, distance from treatment facility, and year of diagnosis. The median follow-up time was 60 months (interquartile range, 33 to 93). Estimated 5-year and 10-year OS rates were, respectively, 79% and 59% for all patients, 75% and 55% for patients receiving chemotherapy alone, and 82% and 64% for patients receiving combined-modality therapy (P < .001). Even after adjusting for immortal times and indication bias, combined-modality therapy was associated with better OS (HR, 0.66; 95% CI, 0.61 to 0.71; P < .001) than was chemotherapy alone.Use of consolidative RT after multiagent chemotherapy in DLBCL is decreasing in the modern era. Selection of treatment strategy is affected by both classical prognostic features and socioeconomic factors. Abandonment of combined-modality therapy in favor of chemotherapy alone negatively affects patient survival.
Cured of breast cancer?
Authors: H Joensuu, S Toikkanen
Journal: Journal of Clinical Oncology (1995)

PURPOSE That patients can be ultimately cured of breast cancer has been questioned, because late deaths from the disease have been observed even several decades after the diagnosis. The purpose of this study was to investigate late mortality caused by breast cancer. PATIENTS AND METHODS Using the files of local hospitals and the Finnish Cancer Registry, we identified all patients with histologically diagnosed invasive breast cancer in a defined urban area (city of Turku, Finland) from 1945 to 1969 (n = 601). In 563 cases (94%), clinical data and histologic and autopsy slides could be reviewed, and these women had been monitored for a median of 29 years (range, 22 to 44; n = 66) or until death (n = 497). RESULTS Mortality from breast cancer was observed even during the fourth follow-up decade, but if women who were diagnosed with contralateral breast cancer were excluded (n = 30), no deaths from breast cancer were identified after the 27th year of follow-up evaluation. The 30-year survival rates were 62% (95% confidence interval [CI], 54% to 70%), 19% (95% CI, 13% to 25%), and 0% for women with pN0 (node-negative) and pN1 or pN2 (node-positive) disease, respectively. High 30-year survival rates were found in small (pT1N0M0) unilateral cancers (80% alive; 95% CI, 66 to 94%), and in the lobular (45% alive; 95% CI, 31% to 59%) and the special histologic types (81% alive; 95% CI, 67% to 95%). These survival rates were obtained when correcting either for known intercurrent deaths or for mortality in the age- and sex-matched general population. CONCLUSION Breast cancer, node-negative and node-positive, may be permanently cured even if treated with locoregional therapy only. The survival figures listed here may be considered as minimum values, because women with breast cancer diagnosed in the same area from 1970 to 1984 showed significantly improved short-term (&lt; 20 years) survival rates over those diagnosed from 1945 to 1969.
Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference
Authors: Brent A. Neuschwander-Tetri, Stephen H. Caldwell
Journal: Hepatology (2003)

Fatty liver disease that develops in the absence of alcohol abuse is recognized increasingly as a major health burden. This report summarizes the presentations and discussions at a Single Topic Conference held September 20–22, 2002, and sponsored by the American Association for the Study of Liver Diseases. The conference focused on fatty liver disorders. Estimates based on imaging and autopsy studies suggest that about 20% to 30% of adults in the United States and other Western countries have excess fat accumulation in the liver. About 10% of these individuals, or fully 2% to 3% of adults, are estimated to meet current diagnostic criteria for nonalcoholic steatohepatitis (NASH). Sustained liver injury leads to progressive fibrosis and cirrhosis in a fraction, possibly up to one third, of those with NASH, and NASH may be a cause of cryptogenic cirrhosis. NASH is now a significant health issue for obese children as well, leading to cirrhosis in some. The diagnostic criteria for NASH continue to evolve and rely on the histologic findings of steatosis, hepatocellular injury (ballooning, Mallory bodies), and the pattern of fibrosis. Generally recognized indications for biopsy include establishing the diagnosis and staging of the injury, but strict guidelines do not exist. Liver enzymes are insensitive and cannot be used reliably to confirm the diagnosis or stage the extent of fibrosis. Older age, obesity, and diabetes are predictive of fibrosis. The pathogenesis of NASH is multifactorial. Insulin resistance may be an important factor in the accumulation of hepatocellular fat, whereas excess intracellular fatty acids, oxidant stress, adenosine triphosphate (ATP) depletion, and mitochondrial dysfunction may be important causes of hepatocellular injury in the steatotic liver. Efforts are underway to refine the role of insulin resistance in NASH and determine whether improving insulin sensitivity pharmacologically is an effective treatment. An altered lifestyle may be a more effective means of improving insulin sensitivity. The research agenda for the future includes establishing the role of insulin resistance and abnormal lipoprotein metabolism in NASH, determining the pathogenesis of cellular injury, defining predisposing genetic abnormalities, identifying better noninvasive predictors of disease, and defining effective therapy.
Beneficial effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis
Authors: Angelo Luca, Juan C. García-Pagán, Jaume Bosch, Faust Feu, Wladimiro Jiménez, Angels Ginés, Mercedes Fernández, Angels Escorsell, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1995)

The study investigated the hemodynamic and neurohumoral effects of albumin infusion after total paracentesis in 18 patients with cirrhosis and tense ascites. Measurements of systemic and splanchnic hemodynamics, and vasoactive neurohumoral systems were performed before and immediately after total paracentesis. The patients were then randomized to receive albumin or not, and hemodynamic and humoral measurements were repeated at 24 hours. Hemodynamic and humoral changes just after paracentesis were similar in patients later randomized to receive albumin infusion or not. Twenty-four hours after total paracentesis, patients nor receiving albumin had total significant reductions in cardiac index (-13%; P = .005), femoral blood flow (-17%; P = .004), and pulmonary capillary pressure (-16%; P = .02), which were accompanied by significant increases in plasma renin activity (PRA) and plasma aldosterone (PA) and by significant decreases in atrial natriuretic factor (ANF) and plasma sodium. By contrast, there was no significant changes in patients receiving albumin, except for an increase in ANF and a further decrease in PA. In both groups, hepatic venous pressure gradient (HVPG) and azygos blood flow decreased just after paracentesis returning to baseline at 24 hours. This study shows that albumin infusion prevents the impairment in systemic hemodynamics, vasoactive neurohumoral systems, and plasma sodium after a large-volume paracentesis, without detrimental effects on portal pressure and portocollateral blood flow.