tbuckley/cabot-search huggingface dataset:
Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. II. Effects on Microbial Proliferation and Host Survival in Vivo
Authors: Pietro Mastroeni, Andrés Vazquez-Torres, Ferric C. Fang, Yisheng Xu, Shahid Khan, Carlos E. Hormaeche, Gordon Dougan
Journal: The Journal of Experimental Medicine (2000)

The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS) in host resistance to virulent Salmonella typhimurium were investigated in gp91phox−/−, iNOS−/−, and congenic wild-type mice. Although both gp91phox−/− and iNOS−/− mice demonstrated increased susceptibility to infection with S. typhimurium compared with wild-type mice, the kinetics of bacterial replication were dramatically different in the gp91phox−/− and iNOS−/− mouse strains. Greater bacterial numbers were present in the spleens and livers of gp91phox−/− mice compared with C57BL/6 controls as early as day 1 of infection, and all of the gp91phox−/− mice succumbed to infection within 5 d. In contrast, an increased bacterial burden was detected within reticuloendothelial organs of iNOS−/− mice only beyond the first week of infection. Influx of inflammatory CD11b+ cells, granuloma formation, and serum interferon γ levels were unimpaired in iNOS−/− mice, but the iNOS-deficient granulomas were unable to limit bacterial replication. The NADPH phagocye oxidase and iNOS are both required for host resistance to wild-type Salmonella, but appear to operate principally at different stages of infection.
Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial
Authors: Matthew T Seymour, Timothy S Maughan, Jonathan A Ledermann, Clare Topham, Roger James, Stephen J Gwyther, David B Smith, Stephen Shepherd, Anthony Maraveyas, David R Ferry, Angela M Meade, Lindsay Thompson, Gareth O Griffiths, Mahesh KB Parmar, Richard J Stephens
Journal: The Lancet (2007)
BIOMETRICAL STUDIES IN PSYCHIATRY
Authors: Walter Freeman
Journal: American Journal of Psychiatry (1928)

Based upon the study of about 1100 psychotic patients coming to necropsy in the past ten years, figures are presented to show graphically what has always been recognized, that individuals in their susceptibility to disease vary according to their psychologic responses. The preponderance of tuberculosis in the schizoid individual is contrasted with the susceptibility to carcinoma, chronic streptococcus infections and circulatory disasters in the extroverted individuals, particularly the paranoid. Methods of prevention of morbidity and mortality are suggested. It would seem possible to apply these preventive measures intensively to the groups to which they are best adapted.
Molecular assays for the detection of prostate tumor derived nucleic acids in peripheral blood
Authors: Matthias Jost, John R Day, Ryan Slaughter, Theodore D Koreckij, Deanna Gonzales, Martin Kinnunen, Jack Groskopf, Harry G Rittenhouse, Robert L Vessella, Mark A Reynolds
Journal: Molecular Cancer (2010)

Abstract Background Prostate cancer is the second leading cause of cancer mortality in American men. Although serum PSA testing is widely used for early detection, more specific prognostic tests are needed to guide treatment decisions. Recently, the enumeration of circulating prostate epithelial cells has been shown to correlate with disease recurrence and metastasis following definitive treatment. The purpose of our study was to investigate an immunomagnetic fractionation procedure to enrich circulating prostate tumor cells (CTCs) from peripheral blood specimens, and to apply amplified molecular assays for the detection of prostate-specific markers (PSA, PCA3 and TMPRSS2:ERG gene fusion mRNAs). Results As few as five prostate cancer cells were detected per 5 mL of whole blood in model system experiments using anti-EpCAM magnetic particles alone or in combination with anti-PSMA magnetic particles. In our experiments, anti-EpCAM magnetic particles alone exhibited equivalent or better analytical performance with patient samples compared to a combination of anti-EpCAM + anti-PSMA magnetic particles. Up to 39% of men with advanced prostate cancer tested positive with one or more of the molecular assays tested, whereas control samples from men with benign prostate hyperplasia gave consistently negative results as expected. Interestingly, for the vast majority of men who tested positive for PSA mRNA following CTC enrichment, their matched plasma samples also tested positive, although CTC enrichment gave higher overall mRNA copy numbers. Conclusion CTCs were successfully enriched and detected in men with advanced prostate cancer using an immunomagnetic enrichment procedure coupled with amplified molecular assays for PSA, PCA3, and TMPRSS2:ERG gene fusion mRNAs. Our results indicate that men who test positive following CTC enrichment also exhibit higher detectable levels of non-cellular, circulating prostate-specific mRNAs.
Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study
Authors: Michael Pfreundschuh, Anthony D Ho, Eva Cavallin-Stahl, Max Wolf, Ruth Pettengell, Ingrid Vasova, Andrew Belch, Jan Walewski, Pier-Luigi Zinzani, Walter Mingrone, Stein Kvaloy, Ofer Shpilberg, Ulrich Jaeger, Mads Hansen, Claudia Corrado, Adriana Scheliga, Markus Loeffler, Evelyn Kuhnt
Journal: The Lancet Oncology (2008)
A Novel Model of Dormancy for Bone Metastatic Breast Cancer Cells
Authors: Rebecca Marlow, Gabriella Honeth, Sara Lombardi, Massimiliano Cariati, Sonya Hessey, Aikaterini Pipili, Veronica Mariotti, Bharath Buchupalli, Katie Foster, Dominique Bonnet, Agamemnon Grigoriadis, Pranela Rameshwar, Anand Purushotham, Andrew Tutt, Gabriela Dontu
Journal: Cancer Research (2013)

Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy.
Features in hospitalized patients with symptom-detected or radiologically-detected pulmonary tuberculosis
Authors: B Herer, C Kuaban, F Papillon, P Durieux, J Chretien, G Huchon
Journal: European Respiratory Journal (1989)

To compare features of tuberculosis detected either clinically or radiologically, we studied 498 patients hospitalized for tuberculosis. Tuberculosis was less frequently radiologically-detected in patients over 65 yrs old (p less than 0.01) and in directorial staff and inactive subjects (p less than 0.0001). Pleural effusion and radiological cavities were more frequent in the symptom-detected group, but half of the radiologically-detected patients had clinical symptoms which could have led to the diagnosis of tuberculosis, especially in alcoholics and office workers. Finally, 26% of the radiologically-detected patients had positive direct tuberculosis smears and should be considered contagious.
Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease
Authors: Burton E. Sobel, Robert Frye, Katherine M. Detre
Journal: Circulation (2003)

A paradoxical increase in mortality attributable to diabetes has occurred, particularly during the last decade, despite the overall decrease in mortality attributable to coronary artery disease in patients without diabetes. Insulin resistance with or without frank type 2 diabetes has emerged as a major determinant of accelerated coronary artery disease and its sequelae. The advent of insulin sensitizers enables clinicians to target treatment of insulin resistance, as well as hyperglycemia and dyslipidemia. The prevalence of diabetes in the United States is enormous and is increasing rapidly. Patients with diabetes respond less favorably to percutaneous coronary interventions and surgery compared with nondiabetic patients. These considerations led to the initiation of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. It is designed to determine whether treatment targeted to attenuate insulin resistance can arrest or retard progression of coronary artery disease compared with treatment targeted to the same level of glycemic control with an insulin-providing approach. It is designed also to determine whether early revascularization reduces mortality and morbidity in patients with type 2 diabetes whose cardiac symptoms are mild and stable. Despite challenges in study design and enrollment, intensive follow-up, and the long duration of follow-up planned, the questions being addressed are compelling and seem to merit the effort.
Translating Molecular Insights in Autoimmunity into Effective Therapy
Authors: Marc Feldmann
Journal: Annual Review of Immunology (2008)

Autoimmunity and the pathogenesis of autoimmune diseases were a major focus of the Walter and Eliza Hall Institute, where I started my research career. After my initial studies on immune cell culture and immune regulation, I returned to an analysis of the pathogenesis of human autoimmunity in London. Linking upregulated antigen presentation to autoimmunity led to an investigation of the role of cytokines in rheumatoid arthritis (RA), in collaboration with Ravinder Maini. These experiments defined the concept of a TNF-dependent cytokine cascade driving the manifestations of RA, which led to successful clinical trials of anti-TNF monoclonal antibody in RA patients, heralding a major change in medical practice. This success was made possible by enthusiastic support from many laboratory and clinical colleagues and taught us that cytokines are important rate-limiting steps and hence good therapeutic targets. My current scientific challenge is exploring the hypothesis of whether all major medical needs can be approached via cytokine blockade.
Foucher's sign of the Baker's cyst.
Authors: J J Canoso, M R Goldsmith, S G Gerzof, J R Wohlgethan
Journal: Annals of the Rheumatic Diseases (1987)

We investigated the mechanism of Foucher's sign, the change in pressure in the Baker's cyst with extension and flexion of the knee, by echography, arthrography, and computed tomography. With extension the gastrocnemius and the semimembranosus muscles approximate each other and the joint capsule compressing the cyst against the deep fascia. Opposite effects in flexion allow the cyst to relax.
Effect of Addition of Adjuvant Paclitaxel on Radiotherapy Delivery and Locoregional Control of Node-Positive Breast Cancer: Cancer and Leukemia Group B 9344
Authors: Carolyn I. Sartor, Bercedis L. Peterson, Susan Woolf, Thomas J. FitzGerald, Frances Laurie, Andrew J. Turrisi, Jeff Bogart, I. Craig Henderson, Larry Norton
Journal: Journal of Clinical Oncology (2004)

We compared radiotherapy (RT) delivery and locoregional control in patients with node-positive breast cancer randomly assigned on Cancer and Leukemia Group B 9344 to receive adjuvant doxorubicin/cyclophosphamide (AC) with patients assigned to receive AC followed by paclitaxel (AC+T).Eligible patients were randomly assigned to receive adjuvant AC versus AC+T chemotherapy. RT was required if breast-conserving surgery was performed but was elective after mastectomy. Information about RT delivery was retrospectively collected. Cumulative incidence of locoregional recurrence (LRR), use of elective RT, and RT delivery were compared between treatment arms.For patients treated with breast-conserving surgery and RT, the 5-year cumulative incidence of isolated LRR was 9.7% in the AC arm and 3.7% in the AC+T arm (P = .04) and of LRR as any component of failure was 12.9% versus 6.1%, respectively (P = .04). Although LRR rates in patients who did not receive postmastectomy RT were lower in the AC+T arm, the difference was not statistically significant. Despite the lack of protocol guidelines, RT use did not differ between arms, nor did RT dose, treatment interruption, or completion.Despite the delay to RT during additional chemotherapy, adjuvant AC+T afforded better local control than AC alone in patients treated with breast-conserving therapy. Addition of paclitaxel did not adversely affect delivery or ability to tolerate RT, as indicated by similar rates of completion of timely, full-dose RT between arms.
Interventricular Mechanical Asynchrony in Pulmonary Arterial Hypertension
Authors: J. Tim Marcus, C. Tji-Joong Gan, Jaco J.M. Zwanenburg, Anco Boonstra, Cor P. Allaart, Marco J.W. Götte, Anton Vonk-Noordegraaf
Journal: Journal of the American College of Cardiology (2008)
Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling.
Authors: R T Ingram, Y K Park, B L Clarke, L A Fitzpatrick
Journal: Journal of Clinical Investigation (1994)

With increasing age, bone undergoes changes in remodeling that ultimately compromise the structural integrity of the skeleton. The presence of osteocalcin in bone matrix may alter bone remodeling by promoting osteoclast activity. Whether age- and/or gender-related differences exist in the distribution of osteocalcin within individual bone remodeling units is not known. In this study, we determined the immunohistochemical distribution of osteocalcin in the extracellular matrix of iliac crest bone biopsies obtained from normal male and female volunteers, 20-80 yr old. Four different distribution patterns of osteocalcin within individual osteons were arbitrarily defined as types I, II, III, or IV. The frequency of appearance of each osteon type was determined as a percent of the total osteons per histologic section. The proportion of osteons that stained homogeneously throughout the concentric lamellae (type I) decreased in females and males with increasing age. The proportion of osteons that lack osteocalcin in the matrix immediately adjacent to Haversian canals (type III) increased in females and males with age. Osteons staining intensely in the matrix adjacent to Haversian canals (type II) increased in females and was unchanged in aging males. Osteons that contained osteocalcin-positive resting lines (type IV) increased in bone obtained from males with increasing age but were unchanged in females. Sections of bone immunostained for osteopontin (SPP-I), osteonectin, and decorin did not reveal multiple patterns or alterations in staining with gender or increasing age. We suggest that the morphology of individual bone remodeling units is heterogeneous and the particular morphologic pattern of osteocalcin distribution changes with age and gender. These results suggest that differences in the distribution of osteocalcin in bone matrix may be responsible, in part, for the altered remodeling of bone associated with gender and aging.
Characteristics of Reactive Hyperemia in the Canine Intestine
Authors: EWALD E. SELKURT, CARL F. ROTHE, DANIEL RICHARDSON
Journal: Circulation Research (1964)

The isolated ileum of the dog shows a characteristic hyperemia following brief periods of arterial occlusion. The magnitude of this reactive hyperemia depends more upon prolongation of flow related to duration of ischemia, than upon increases of maximal or peak blood flow. Repayment of flow deficit, by the added flow of reactive hyperemia, averaged only 35% in the intestine, far below that found by others in skeletal muscle and in the coronary circulation. Nevertheless, estimates of oxygen debt indicated that this debt was overpaid, even after five minutes of ischemia. A small but consistent increase in weight of the isolated segment was observed during the postocclusion phase. It was found that this weight increase was due largely to increase of the volume of blood in the ileum. The peak of the volume increment appeared slightly later than the peak of flow increase, and for this reason was ascribed to increase in volume of the capacity vessels. In an attempt to assess the respective roles of myogenic vs. metabolic mechanisms in causation of reactive hyperemia, arterial pressure was restored during occlusion by injecting dextran solution into the arterial segment. Pressures in excess of control values did not abolish the hyperemic response. It was concluded that the reactive hyperemia observed in the ileum was chiefly metabolic in origin.
Immunoglobulin G inhibitor of thyroid-stimulating antibody is a cause of delay in the onset of neonatal Graves' disease.
Authors: M Zakarija, J M McKenzie, D S Munro
Journal: Journal of Clinical Investigation (1983)

Studies were carried out with the serum IgG from a mother and her two children who developed neonatal Graves' disease several weeks after birth. The maternal IgG: (a) stimulated the human thyroid in vitro, but maximal stimulation was found only with dilution of the IgG; (b) was very potent in the long-acting thyroid stimulator (LATS)-protector assay, but only when an inhibitor of the system was diluted out; (c) inhibited a standard preparation of LATS in the mouse bioassay; (d) was biphasic in the thyrotropin-binding inhibition (TBI) assay, i.e., enhanced binding at low concentrations of IgG and inhibited binding at high levels. Enhancement in the TBI assay was found only with particulate preparations of human thyroid membranes as receptor and not when that material was solubilized, nor with guinea pig fat cell membranes as receptor. Serial blood samples from the second child were obtained at birth and until 3 mo of age. In the thyroid slice (cyclic AMP) assay system there was a negative dose-response relationship in testing IgG until age 45 d when it became positive, coinciding with the clinical recognition that hyperthyroidism had developed. The data are compatible with a concept that this mother's IgG contained thyroid-stimulating antibody (TSAb) and another moiety that inhibited TSAb through an action on the thyroid cell membrane, thus delaying the onset of hyperthyroidism in the neonate until the inhibiting IgG was metabolically cleared to an ineffective concentration.
Withdrawal of Personal Genome Service
Authors: Leo G. M. van Rossum
Journal: JAMA (2014)

Reading the Viewpoint by Mr Downing and Dr Ross1 about the US Food and Drug Adminstration’s mandated withdrawal of 23andMe’s Personal Genome Service (PGS), I was confident the authors were working toward a conclusion stating the need to establish analytical as well as clinical validity. However, the authors concluded “When it becomes clear that the sequencing process used by the PGS is accurate, the use of this product could be allowed under the supervision of a physician.” This conclusion indicates analytical validity only.
Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib
Authors: Michael W. N. Deininger, Brian J. Druker
Journal: Pharmacological Reviews (2003)

Chronic myeloid leukemia (CML) is characterized by the Philadelphia translocation that fuses BCR sequences from chromosome 22 upstream of the ABL gene on chromosome 9. The chimerical Bcr-Abl protein expressed by CML cells has constitutive tyrosine kinase activity, which is essential for the pathogenesis of the disease. Imatinib, an ATP-competitive selective inhibitor of Bcr-Abl, has unprecedented efficacy for the treatment of CML. Most patients with early stage disease achieve durable complete hematological and complete cytogenetic remissions, with minimal toxicity. In contrast, responses are less stable in patients with advanced CML. This review highlights the pathogenesis of CML, its clinical features, and the development of imatinib as a specific molecularly targeted therapy. Aspects of disease monitoring and side effects are covered as well as resistance to imatinib and strategies to overcome resistance, such as alternative signal transduction inhibitors and drug combinations. Perspectives for further development are also discussed.
Addiction science as a hedgehog and as a fox
Authors: Warren K. Bickel, Richard Yi
Journal: Behavioral and Brain Sciences (2008)

Abstract Redish et al. provide a significant advance in our understanding of addiction by showing that the various addictive processes are in fact all decision-making processes and each may undergird addiction. We propose means for identifying more central addiction processes. This recognition of the complexity of addiction followed by identification of more central processes would help guide the development of prevention and treatment.
Studies of the metabolism and distribution of fibrinogen in healthy men with autologous 125-I-labeled fibrinogen.
Authors: Y Takeda
Journal: Journal of Clinical Investigation (1966)

A few studies of the metabolism and distribu- tion of fibrinogen in healthy men have been re- ported (1-3), but because of the lability of fibrino- gen and the methods employed the earlier of these do not appear to have been entirely successful.Recent advances in the preparation of fibrinogen- 131I (4, 5) and in the mathematics of its kinetic behavior (6) have made possible more reliable and extensive studies.Observations have therefore been made on 12 healthy male volunteers with autologous fibrinogen labeled with 125J. MethodsThe subjects, mainly graduate students or janitors, were healthy male volunteers, ranging from 16 to 54 years in age.They took 10 drops of saturated K(I solution three times a day for the 3 days preceding the ex- periment and 10 drops once daily during the 7 to 9 days of the experiment.The preparation of fibrinogen for labeling was carried out by a minor modification of the method of Atencio, Burdick, and Reeve (4) as follows: About 20 ml plasma, separated from the subject's heparinized blood, was diluted with an equal volume of 0.09 M sodium citrate and recentrifuged for 10 minutes to re- move any remaining platelets and red cells.The diluted plasma was mixed with 4 M (NH4)2SO4 (saturated) in a volume ratio of 3 to 1, left at room temperature for 5 minutes, and spun for 5 minutes at 2,000 rpm, and the supernatant was discarded.The precipitate, after wash- ing three times with a total of 120 ml of 1 M (NH4) 2SO4, was dissolved in 15 ml of 0.005 M sodium citrate, reprecipitated with 5 ml of 4 M (NH4)2SO4, and washed once *