tbuckley/cabot-search huggingface dataset:
Abstract 5419: Targeting colon cancer stem cells using sulforaphane
Authors: Parthasarathy Rangarajan, Dharmaligam Subramaniam, Shrikant Anant, Animesh Dhar
Journal: Cancer Research (2012)

Abstract Colon cancer is a leading cause of cancer death in the United States, accounting for approximately 51,000 deaths each year. For patients with advanced colon cancer, the 5-year survival rate is less than 10%. Recent evidence suggests the existence of a small population of tumorigenic stem cells responsible for tumor initiation, metastasis and resistance to chemotherapy and radiation. Identification of the regulatory mechanisms and signalling pathways involved in cancer stem cells will help in designing novel agents to target this refractory cell population in colon cancers. We are currently investigating the mechanism by which sulforaphane, an isothiocyanate present in cruciferous vegetables such as broccoli, Brussels sprouts and cabbage inhibits growth of colon cancer cells. Our studies demonstrate that the compound had significant cytotoxicity against HCT116 colon cancer cells in both a dose- and time-dependent manner. Colon CSCs can be allowed to divide and grow in ultra-low binding tissue culture dishes to form multicellular spheroids called colospheres. Treatment with sulforaphane decreased the number and size of the primary and secondary colospheres in a dose dependent manner, suggesting that sulforaphane targets CSCs. To understand the mechanism of inhibition of colospheres, the signaling pathways affected by sulforaphane were dissected. Aberrant activation of Sonic Hedgehog signaling pathway has been associated with renewal of cancer stem cells, and in the development of several solid cancers. Sonic hedgehog (Shh) upon binding to its cognate receptor patched, allows smoothened to accumulate and activate Gli transcription factor. Treatment with sulforaphane inhibited the expression of both Shh and smoothened in the colon CSCs. Furthermore, it inhibited the expression of patched-1 and Gli-1, downstream targets of the hedgehog signalling pathway. Taken together, these data suggest that sulforaphane effectively inhibits colon cancer stem cells by down regulating the sonic hedgehog pathway, thereby inhibiting tumorigenesis (supported in-part by the US PHS grants CA 109269 and CA 135569 to SA and CA 151727 to AD). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5419. doi:1538-7445.AM2012-5419
The Thucydides Syndrome
Authors: A D Langmuir, T D Worthen, J Solomon, C G Ray, E Petersen
Journal: New England Journal of Medicine (1985)

The absence of romance in my history will, I fear, detract somewhat from its interest. Thucydides, 460–400 B.c.The plague of Athens, 430 to 427 B.c., was perhaps the most disastrous and fateful epidemic of recorded ancient history. It fell upon a city that had in just two generations created or nurtured such basic pursuits of Western culture as philosophy, history, tragedy, comedy, and of course, democracy. Her empire spanned the Aegean Sea and generated enough taxes to finance the magnificent Parthenon. But within three decades Athens had been defeated in the Peloponnesian War against Sparta and would never again . . .
The Advent of Medicare
Authors: Saul S. Radovsky
Journal: New England Journal of Medicine (1968)

ON July 30, 1965, President Johnson signed into effect the new Medicare law, providing medical care under Social Security for people 65 years old and older. He signed it at the Truman Memorial Library in Independence, Missouri, and afterward he said, "We marvel not simply at the passage of this bill, but.. that it took so many years to pass it."With his signature, the United States joined the company of virtually all industrial societies, starting with Germany in the late nineteenth century, providing some form of compulsory health insurance for their citizens. The law was the culmination of a . . .
An Investigation of the Manifest Dream Content Associated with Migraine Headaches: A Study of the Dreams That Precede Nocturnal Migraines
Authors: Gail Q. Heather-Greener, Dana Comstock, Roby Joyce
Journal: Psychotherapy and Psychosomatics (1996)

Background: Clinical observations of a relationship between unpleasant dreams and migraine headaches have been reported previously. Methods: Due to the anecdotal quality of these case reports, this study empirically investigated the significance of this relationship. Dream content categories were selected corresponding to emotional factors associated with stress that trigger migraine headaches. A total of 37 migraineurs recorded 10 dreams each, 5 that preceded migraines and 5 that did not. Results: Univariate F tests revealed that 4 of the 5 variables contributed significantly to the overall effect, specifically anger, misfortune, apprehension, and aggressive interactions. Conclusions: Recommendations include discussing the predictive value of dreams with regard to nocturnal migraine attacks, and therapeutic implications are suggested.
Transcriptional Enhancers Induce Insertional Gene Deregulation Independently From the Vector Type and Design
Authors: Giulietta Maruggi, Simona Porcellini, Giulia Facchini, Serena K Perna, Claudia Cattoglio, Daniela Sartori, Alessandro Ambrosi, Axel Schambach, Christopher Baum, Chiara Bonini, Chiara Bovolenta, Fulvio Mavilio, Alessandra Recchia
Journal: Molecular Therapy (2009)

The integration characteristics of retroviral (RV) vectors increase the probability of interfering with the regulation of cellular genes, and account for a tangible risk of insertional mutagenesis in treated patients. To assess the potential genotoxic risk of conventional or self-inactivating (SIN) γ-RV and lentiviral (LV) vectors independently from the biological consequences of the insertion event, we developed a quantitative assay based on real-time reverse transcriptase—PCR on low-density arrays to evaluate alterations of gene expression in individual primary T-cell clones. We show that the Moloney leukemia virus long terminal repeat (LTR) enhancer has the strongest activity in both a γ-RV and a LV vector context, while an internal cellular promoter induces deregulation of gene expression less frequently, at a shorter range and to a lower extent in both vector types. Downregulation of gene expression was observed only in the context of LV vectors. This study indicates that insertional gene activation is determined by the characteristics of the transcriptional regulatory elements carried by the vector, and is largely independent from the vector type or design. The integration characteristics of retroviral (RV) vectors increase the probability of interfering with the regulation of cellular genes, and account for a tangible risk of insertional mutagenesis in treated patients. To assess the potential genotoxic risk of conventional or self-inactivating (SIN) γ-RV and lentiviral (LV) vectors independently from the biological consequences of the insertion event, we developed a quantitative assay based on real-time reverse transcriptase—PCR on low-density arrays to evaluate alterations of gene expression in individual primary T-cell clones. We show that the Moloney leukemia virus long terminal repeat (LTR) enhancer has the strongest activity in both a γ-RV and a LV vector context, while an internal cellular promoter induces deregulation of gene expression less frequently, at a shorter range and to a lower extent in both vector types. Downregulation of gene expression was observed only in the context of LV vectors. This study indicates that insertional gene activation is determined by the characteristics of the transcriptional regulatory elements carried by the vector, and is largely independent from the vector type or design.
Effect of a Monetary Sanction on Immunization Rates of Recipients of Aid to Families With Dependent Children
Authors: Larry C. Kerpelman
Journal: JAMA (2000)

Immunization rates among low-income families have lagged behind those for the general community, with several possible barriers cited in the literature.To evaluate the effect of an initiative aimed at improving immunization rates among low-income preschool children by imposing a sanction on families who failed to provide proof of up-to-date immunization status.Randomized, controlled before-after trial conducted from January 1, 1993, through December 31, 1996, in Muscogee County, Georgia.A total of 2500 families with children aged 6 years or younger who received Aid to Families with Dependent Children assistance.Families in the intervention group (n=1500) were informed that receipt of the welfare benefit for any preschool-aged children was contingent on provision of proof of up-to-date immunization status at the beginning of welfare eligibility and, subsequently, semiannually or annually. Case families in the control group (n=1000) were encouraged to immunize their preschool children but were not informed of any aid sanctions nor did such sanctions apply to them.Age-appropriate rates of 5 immunizations (measles-mumps-rubella; poliovirus; diphtheria and tetanus toxoids and pertussis; Haemophilus influenzae type b; and hepatitis B), based on examination (with family's written consent) of medical provider records, compared among intervention-group vs control-group families.There were no significant differences at baseline between intervention and control families in immunization rates of preschool children. Families in the intervention group were significantly more likely than families in the control group to have up-to-date immunization status in all 4 years of the study for all 5 immunizations (with 3 exceptions). At age 2 years, 72.4% of children in the intervention group vs 60.6% of those in the control group achieved vaccine series completion, which included 4 diphtheria and tetanus toxoids and pertussis, 3 poliovirus, and 1 measles-mumps-rubella (P<.001). Sanctions were implemented only 11 times. There was relatively little increased burden on the part of families to comply with requirements.In our study, a monetary sanction in a population receiving welfare benefits stimulated a significant increase in childhood immunization rates, suggesting that when welfare recipients are given an incentive to keep their children's immunizations up-to-date, most are able to do so. JAMA. 2000;284:53-59
Cyclopropane fatty acid synthase mutants of probiotic human-derived<i>Lactobacillus reuteri</i>are defective in TNF inhibition
Authors: Sara E. Jones, Kristi Whitehead, Delphine Saulnier, Carissa M. Thomas, James Versalovic, Robert A. Britton
Journal: Gut Microbes (2011)

Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts. Many probiotic strains are now marketed to consumers and include organisms such as lactobacilli, streptococci, bifidobacteria, Escherichia coli Nissle 1917, and the yeast Saccharomyces cerevisiae strain, "Saccharomyces boulardii". In general, probiotics are considered safe for human consumption based on previous clinical trials, epidemiological studies, and historical usage in fermented foods. A subset of these probiotics have been derived from commensal bacteria indigenous to Homo sapiens. One such indigenous Lactobacillus species, Lactobacillus reuteri, includes a variety of strains derived from human breast milk and the gastrointestinal tract. The mechanisms by which commensal-derived probiotics promote health and combat diseases are poorly understood. Possible mechanisms include improving nutrient absorption, pathogen exclusion, strengthening intestinal barrier function and regulation of the immune system. A better understanding of how probiotics influence health is critical to fully optimize the integrative physiology of commensal microbial communities and mammalian hosts.
A Clinical Lecture ON THE TREATMENT OF PERNICIOUS ANAEMIA: Delivered at the Royal Infirmary, Edinburgh
Authors: B. Bramwell
Journal: BMJ (1913)

I BEGAN the study of pernicious anaemia now almost years ago, wllen I was plhysician -to the Newcastle-on- Tyne Infirmary.In theyear 1874 two cases anaemia were admitted to the New-castle Infirmary my care; both.died,-as these.cases so often do..Theli disease was then very little known in -this country, thouglh ithad been described by the celebrated.Dr. Addison.metvith a'.numbei of cases of fatal and apparently cause- less anaemia-; he termed it"idiopathic anaemia," wasv while hunting about in tlle bodie-s of patients deatlh to try and find the cause of this peculiar anaeimia that he discovered the remarkable suprarenal capsules which is the pathological substratumD- of the disease, wllich we now, of course, Addison's disease.The terms pernicious anaemia and "progressive pernicious anaemia" were subsequently .the idiopatllic anaemia described by Addison, found-as, indeed, lhe lhad found-that sufferinig froin tllis form of anaemia always, always,died, whatever the form of treatment employed.Addison failed to discover any cause for this fatal anaemia, and we are still ignorant of its exact cause.Now, profound anaemia arising without of blood or other apparent cause may, theoretically least, be due to one or other of two great causes-namely, either a defective production or an excessive destruction thc red blood corpuscles.Either of these two conditions may, when acting in a marked degree, produce profodnd fcrm of anaemia.About the time that I commenced the nicious anaemia a celebratee American physician, Pepper, Professor of Medicine, and afterwards Principal or Provost of the University of Pennsylvania, the lesion in the marrow of the bones found of patients who have died of pernicious anaemia.termed the disease " myelogenous anaemia," hle thought it was due to defective production cells in the bone marrow.The bone marrow need not say, the most.important red-blood-producing Pepper thought that this lesion in the bone the fundamental lesion of 'the disease.Some years later, when I was assistant physician infirmary, I had as one of my assistants Hunter,wo o has identified hiimself with pernicious anaemia.While he was my assistant out-patient department he made a series of observations with regard to the post-mortem pernicious anaemia and with regard-to the duuction of aneaemia in animals.He came to sion that pernicious anaemia is not due formation of red blood corpuscles in bone Pepper had supposed, but to excessive destruction red blood cells in the portal circulation.
Biodiversity, cultural pathways, and human health: a framework
Authors: Natalie E. Clark, Rebecca Lovell, Benedict W. Wheeler, Sahran L. Higgins, Michael H. Depledge, Ken Norris
Journal: Trends in Ecology & Evolution (2014)

Direct contact with biodiversity is culturally important in a range of contexts. Many people even join conservation organisations to protect biodiversity that they will never encounter first-hand. Despite this, we have little idea how biodiversity affects people's well-being and health through these cultural pathways. Human health is sensitive to apparently trivial psychological stimuli, negatively affected by the risk of environmental degradation, and positively affected by contact with natural spaces. This suggests that well-being and health should be affected by biodiversity change, but few studies have begun to explore these relationships. Here, we develop a framework for linking biodiversity change with human cultural values, well-being, and health. We argue that better understanding these relations might be profoundly important for biodiversity conservation and public health.
Mutation in the Gene Responsible for Cystic Fibrosis and Predisposition to Chronic Rhinosinusitis in the General Population
Authors: XinJing Wang
Journal: JAMA (2000)

ContextChronic rhinosinusitis (CRS) is a common condition in the US general population, yet little is known about its underlying molecular cause. Chronic rhinosinusitis is a consistent feature of the autosomal recessive disorder cystic fibrosis (CF).ObjectiveTo determine whether mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, which is responsible for CF, predispose to CRS.DesignCase-control study conducted from 1996 to 1999 in which the DNA of CRS patients and controls was typed for 16 mutations that account for 85% of CF alleles in the general population. Chronic rhinosinusitis patients with 1 CF mutation were evaluated for a CF diagnosis by sweat chloride testing, nasal potential difference measurement, and DNA analysis for additional mutations.SettingOtolaryngology–head and neck clinic of a US teaching hospital.ParticipantsOne hundred forty-seven consecutive adult white patients who met stringent diagnostic criteria for CRS and 123 CRS-free white control volunteers of similar age range, geographic region, and socioeconomic status.Main Outcome MeasuresPresence of CF mutations by DNA analysis among CRS patients vs controls.ResultsEleven CRS patients were found to have a CF mutation (ΔF508, n = 9; G542X, n = 1; and N1303K, n = 1). Diagnostic testing excluded CF in 10 of these patients and led to CF diagnosis in 1. Excluding this patient from the analyses, the proportion of CRS patients who were found to have a CF mutation (7%) was significantly higher than in the control group (n = 2 [2%]; P = .04, both having ΔF508 mutations). Furthermore, 9 of the 10 CF carriers had the polymorphism M470V, and M470V homozygotes were overrepresented in the remaining 136 CRS patients (P = .03).ConclusionThese data indicate that mutations in the gene responsible for CF may be associated with the development of CRS in the general population.
Multiple Sclerosis: Pathology, Diagnosis and Management
Authors: Charles M. Poser
Journal: JAMA (1984)

The literature of multiple sclerosis is distinguished by several features: it is enormous; it is multidisciplinary, venturing into the fields of virology, immunology, clinical neurophysiology, neuropathology, experimental pathology, and psychology, to name just a few; it is controversial; and it has, unfortunately, led to little new in our understanding of its pathogenesis or etiology. Because of these problems, it is necessary from time to time, to attempt to collate, codify, and, if possible, clarify this vast amount of published and unpublished material.  The authors of this latest attempt are eminently qualified to do just what is necessary and have assembled a group of experts from many centers to try to bring order to the chaos. The amount of information contained in this book is truly stupendous and it can unquestionably be called a state-of-the-art compendium. Many points of view are represented, many theories are discussed with candor and erudition, but
Acetylsalicylic acid-induced hemolysis and its mechanism
Authors: N. T. Shahidi, D. W. Westring
Journal: Journal of Clinical Investigation (1970)

Acetylsalicylic acid (ASA) is known to cause severe hemolytic anemia in some glucose-6-phosphate-dehydrogenase-deficient (G-6-PD-deficient) individuals. To study its mechanism, erythrocytes from an ASA-sensitive patient were transfused into a normal compatible recipient. The administration of 2,5-dihydroxybenzoic (gentisic) acid, a known ASA metabolite with redox properties, to the recipient resulted in a marked decrease in the survival of the patient's erythrocytes. Similar studies with red cells from individuals with A- and Mediterranean variants of G-6-PD revealed no alteration in the erythrocytes' survival. Further studies disclosed that both salicylate and gentisate competitively inhibited the G-6-PD from the ASA-sensitive patient resulting in a marked change in the K(m) for NADP. These drugs also inhibited the A- and Mediterranean variants of G-6-PD. The magnitude of inhibition, however, was comparatively small and not different from that observed with a normal enzyme. The above studies suggested that enzyme inhibition by salicylate and gentisate may play an important role in ASA-induced hemolysis. Such an inhibition would further curtail NADPH regeneration, rendering the cells more vulnerable to oxidants. In this connection, gentisate seems to play a major role in ASA-induced hemolysis for it is both a G-6-PD inhibitor and an "oxidant."
Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis
Authors: Zandra A Jenkins, Margriet van Kogelenberg, Tim Morgan, Aaron Jeffs, Ryuji Fukuzawa, Esther Pearl, Christina Thaller, Anne V Hing, Mary E Porteous, Sixto Garcia-Miñaur, Axel Bohring, Didier Lacombe, Fiona Stewart, Torunn Fiskerstrand, Laurence Bindoff, Siren Berland, Lesley C Adès, Michel Tchan, Albert David, Louise C Wilson, Raoul C M Hennekam, Dian Donnai, Sahar Mansour, Valérie Cormier-Daire, Stephen P Robertson
Journal: Nature Genetics (2008)
Atrial Reciprocal Rhythm and Reciprocating Tachycardia in Wolff-Parkinson-White Syndrome
Authors: J. ROELANDT, LUC G. VAN DER HAUWAERT
Journal: Circulation (1968)

In an infant with type A Wolff-Parkinson-White syndrome, atrial reciprocal beats and attacks of reciprocating tachycardia were repeatedly recorded. Their dependence on a prolongation of the P-R interval could be well demonstrated during Wenckebach periods. Because of the normal aspect of the QRS complex during arrhythmia, the short ventriculo-atrial conduction time (0.08 sec), and the vectorial orientation of the secondary P wave, it was concluded that retrograde reactivation of the atria probably took place via the anomalous bundle. The versatility of the conduction through the accessory bundle is shown by the fact that its direction may change from antegrade in one beat to retrograde in the next. The importance of a circus movement in the genesis of some types of tachycardia in the WPW syndrome is discussed.
Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion
Authors: Claudio Tripodo, Sabina Sangaletti, Carla Guarnotta, Pier P. Piccaluga, Matilde Cacciatore, Michela Giuliano, Giovanni Franco, Claudia Chiodoni, Marika Sciandra, Silvia Miotti, Giuseppe Calvaruso, Alessandra Carè, Ada M. Florena, Katia Scotlandi, Attilio Orazi, Stefano A. Pileri, Mario P. Colombo
Journal: Blood (2012)
Duodenal calcium outputs in health and pancreatic disease.
Authors: P T Regan, J R Malagelada, E P DiMagno
Journal: Gut (1980)

To investigate the relationship between the duodenal outputs of calcium and diseases of the pancreas, we measured calcium secretion into the duodenum (during saline perfusion and after stimulation with an intravenous infusion of cholecystokinin (CCK) or secretin) in healthy controls, patients with chronic alcoholic or idiopathic pancreatitis, and patients with pancreatic cancer. The effects of acute and chronic hypercalcaemia and previous cholecystectomy were also studied. Our results indicate a characteristic increase in duodenal calcium outputs in response to CCK in chronic pancreatitis which is unaffected by the level of serum calcium, aetiology of the pancreatitis, previous cholecystectomy, and the presence or absence of radiological pancreatic calcifications. Although unproven, indirect observations support a pancreatic source for the increased calcium secretion. As we measured the outputs of calcium into the duodenum, previously described increases in calcium concentration are not merely a reflection of reduced volume secretion in chronic pancreatitis. Duodenal calcium outputs were significantly reduced in patients with cancer of the pancreas.