tbuckley/cabot-search huggingface dataset:
Abstract 143: Non-canonical role of TAM receptors in breast cancer
Authors: Shelly Hsieh, Khanh Q. Nguyen, Stanley Kimani, Raymond B. Birge
Journal: Cancer Research (2014)

Abstract TAM receptors (Tyro-3, Axl, Mer) are a family of three homologous receptor tyrosine kinases that play a role in the phagocytosis of apoptotic cells (a process termed efferocytosis in recent years). TAM receptors on the surface of epithelial cells bind to soluble ligands Gas6 and Protein S, which in turn, bind to phosphatidylserine-expressing apoptotic cells. After epithelial cells phagocytose apoptotic cells, they release anti-inflammatory cytokines (e.g. IL-10, TGFβ) to attenuate the immune response. This non-canonical role of TAM receptors as efferocytosis receptors is in addition to their well-studied canonical role as tyrosine kinase receptors that activate cell proliferation signaling pathways (e.g. PI3K, Ras, ERK). Therefore, overexpression of TAM receptors on cancer cells has a dual effect on tumor progression. To date, TAM receptors have been implicated in numerous cancers, including breast cancer; and various family members have been shown to be overexpressed in mouse and human mammary tumor cells. We propose that efferocytosis is a unique and novel oncogenic event by virtue of its role in the production of immunosuppressing factors into the tumor microenvironment. To study this, we set up a unique 3D acini model, where luminal apoptotic cells are engulfed by the basal cells of the acini. Using this system along with 2D cultures, we demonstrated that overexpression of Mer increased the rate of efferocytosis, but does not act as a classical oncogene by filling in the luminal space. Additional studies such as time-lapse studies of acini stained with caspases showed that Mer increased the rate of clearance. This adapted method offers a unique system to study cancer cell efferocytosis, and the role of TAM receptors in cancer progression and immune evasion. Citation Format: Shelly Hsieh, Khanh Q. Nguyen, Stanley Kimani, Raymond B. Birge. Non-canonical role of TAM receptors in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 143. doi:10.1158/1538-7445.AM2014-143
Validation of a cholangiographic prognostic model in primary sclerosing cholangitis
Authors: C. Ponsioen, J. Reitsma, K. Boberg, L. Aabakken, E. Rauws, E. Schrumpf
Journal: Endoscopy (2010)

Background and study aims: We previously developed a prognostic model for primary sclerosing cholangitis (PSC), which was primarily based on a cholangiographic classification of the intra- and extrahepatic biliary tree lesions. The aim of the present study was to validate the performance of this model in an external cohort.
Variety of Organizations Scrutinize Tobacco
Authors: Phil Gunby
Journal: JAMA (1987)

THE STRUGGLE against adverse health effects of tobacco continues.  The American Cancer Society has announced that it will conduct its 11th Great American Smokeout—urging smokers to forgo tobacco for 24 hours and perhaps break the habit entirely— Nov 19. It estimates that 23.8 million US smokers participated last year and about 7 million of them made it through the day without smoking.  American Association for Cancer Research members present at this year's business meeting in Atlanta adopted a resolution urging the federal government to end the unconscionable practice of providing governmental subsidies to the tobacco industry, and to instead help tobacco farmers to begin growing other crops.  United Nations World Health Organization experts from seven nations have prepared a report calling for a ban on smokeless tobacco, wherever possible, to prevent a new public health epidemic.  And, until late summer adjournment, Congress continued to debate whether some or all tobacco
Permanent Diabetes Without Serological Evidence of Autoimmunity After Transient Neonatal Diabetes
Authors: Michael E Gottschalk, Desmond A Schatz, Michael Clare-Salzler, Daniel L Kaufman, Grace S P Ting, Mitchell E Geffner
Journal: Diabetes Care (1992)

OBJECTIVE To describe a probable association between TNDM and subsequent permanent IDDM. RESEARCH DESIGN AND METHODS A longitudinal follow-up of a single case from birth to 12 yr of age was conducted analyzing sequential OGTTs, ICAs, AIAs, anti-GAD antibodies, and other organ-specific and nonspecific antibodies. RESULTS A small-for-gestational-age infant developed hyperglycemia at 20 h of age and required insulin therapy for the 1st 14 wk of life (TNDM). Transient hyperglycemia and ketonuria were noted again at age 2 yr 10 mo during an intercurrent illness, but OGTT was normal; and ICA, AIA, anti-GAD65 and anti-GAD67 antibodies, antithyroid microsomal, anti-gastric parietal cell, antiadrenal, antisteroidal, and antinuclear antibodies were negative 3 wk later. At age 9 yr, hyperglycemia returned and persisted in the setting of hypoinsulinemia; ICA, AIA, anti-GAD65 and anti-GAD67 antibodies, and other organ-specific and nonspecific antibodies were again negative. Insulin therapy was initiated and has been maintained over 3 yr of follow-up. CONCLUSIONS Our case is the fifth reported with permanent diabetes occurring after resolution of TNDM. The etiology of permanent diabetes in this setting is unknown but, unlike classical IDDM, appears unrelated to autoimmunity in our patient. The true frequency of this association remains unknown.
Ice Hockey Injuries
Authors: Hugh H. Hussey
Journal: JAMA (1976)

Ice hockey is a graceful, vicious game, especially as it is played by North American professional teams. If anyone doubts the sport's brutality, he failed to see or read about the contest earlier this year between an all-star Russian team and the Philadelphia Flyers. As might be expected with sticks slashing, a puck flying at tremendous speed, fast skating, and rampant body-checking, injuries (many of them serious) are frequent. Like any other body-contact sport, hockey produces its share of fractures, bruises, and damages to vulnerable joints. In addition, there are traumas almost peculiar to hockey, including lacerations of the head and face, punched-out incisor and canine teeth, and ocular injuries. Of the last, Vinger<sup>1</sup>reported ocular injuries suffered by 38 hockey players over a three-year period. From the nature of his report and from his tabulation of age ranges of the injured, it seems evident that he was writing
Low Incidence of End-Stage Renal Disease and Chronic Renal Failure in Type 2 Diabetes
Authors: Graziella Bruno, Annibale Biggeri, Franco Merletti, Giuseppe Bargero, Stefania Ferrero, Gianfranco Pagano, Paolo Cavallo Perin
Journal: Diabetes Care (2003)

OBJECTIVE—Data on the incidence of end-stage renal disease (ESRD) and chronic renal failure from population-based studies in Caucasian type 2 diabetic patients are lacking. To provide such data, a population-based cohort of type 2 diabetic patients was identified in Casale Monferrato, Italy, and prospectively examined from 1991 to 2001. RESEARCH DESIGN AND METHODS—During the follow-up period, patients were regularly examined with centralized measurements of plasma creatinine and HbA1c. Independent predictors of progression to renal events were identified with multivariate Cox proportional hazards modeling, with sex, age, and individual follow-up time as confounders. RESULTS—We followed 1,408 of 1,540 (91.4%) patients (average follow-up time 6.7 years, range 0.011–11.1); 10 new cases of ESRD and 72 of chronic renal failure (plasma values of creatinine ≥2.0 mg/dl) were identified, giving incidence rates/1,000 person-years of 1.04 (95% CI 0.56–1.94) and 7.63 (6.06–9.61), respectively. Cumulative risks for chronic renal failure adjusted for competing mortality were 6.1 and 9.3% after 20 and 30 years from diagnosis of diabetes, respectively. Incidence rates and cumulative risks of chronic renal failure defined by plasma creatinine values &amp;gt;1.5 mg/dl increased to 13.1/1,000 person-years, 8.6 and 14.8%, respectively. In Cox regression analysis, predictors of progression (after adjustment for confounders) were hypertension (P = 0.078), diastolic blood pressure (P = 0.034), BMI (P = 0.03), and albumin excretion rate (AER) (P &amp;lt; 0.0001). CONCLUSIONS—We provide evidence that the individual risk of ESRD and chronic renal failure is low. AER and diastolic blood pressure are independent predictors of progression. These findings underline the relevance of primary prevention to reduce the number of diabetic patients with ESRD.
Chlorpyrifos Affects Phenotypic Outcomes in a Model of Mammalian Neurodevelopment: Critical Stages Targeting Differentiation in PC12 Cells
Authors: Ruth R. Jameson, Frederic J. Seidler, Dan Qiao, Theodore A. Slotkin
Journal: Environmental Health Perspectives (2005)

The organophosphate insecticide chlorpyrifos (CPF) adversely affects mammalian brain development through multiple mechanisms. To determine if CPF directly affects neuronal cell replication and phenotypic fate, and to identify the vulnerable stages of differentiation, we exposed PC12 cells, a model for mammalian neurodevelopment, to CPF concentrations spanning the threshold for cholinesterase inhibition (5-50 microM) and conducted evaluations during mitosis and in early and mid-differentiation. In undifferentiated cells, exposure to 5 microM CPF for 1-3 days reduced DNA synthesis significantly without eliciting cytotoxicity. At the same time, CPF increased the expression of tyrosine hydroxylase (TH), the enzymatic marker for the catecholamine phenotype, without affecting choline acetyltransferase (ChAT), the corresponding marker for the cholinergic phenotype. Upon exposure to nerve growth factor (NGF), PC12 cells developed neuritic projections in association with vastly increased TH and ChAT expression accompanying differentiation into the two phenotypes. CPF exposure begun at the start of differentiation significantly reduced ChAT but not TH activity. In contrast, when CPF was added in mid-differentiation (4 days of NGF pretreatment), ChAT was unaffected and TH was increased slightly. Thus, CPF exerts stage-specific effects, reducing DNA synthesis in the undifferentiated state, impairing development of the cholinergic phenotype at the start of differentiation, and promoting expression of the catecholaminergic phenotype both in undifferentiated and differentiated cells. CPF administration in vivo produces deficits in the number of neurons and cholinergic function, and because we were able to reproduce these effects in vitro, our results suggest that CPF directly influences the phenotypic fate of neuronal precursors.
Stimulation of bone marrow erythropoiesis by T lymphocytes of anaemic patients with rheumatoid arthritis.
Authors: P J Prouse, B Bonner, J M Gumpel, C D Reid
Journal: Annals of the Rheumatic Diseases (1985)

An inappropriate response of the bone marrow is implicated in the aetiology of the anaemia of chronic disease complicating rheumatoid arthritis. T lymphocyte subsets have been shown to inhibit early erythroid development in vitro in association with some cases of bone marrow failure, and an expanded peripheral blood pool of these cells is reported in rheumatoid arthritis. We have studied the role of peripheral blood T lymphocytes in erythroid bone marrow culture from seven normal volunteers and nine anaemic patients with rheumatoid arthritis and found comparable stimulation of growth in both groups.
Conditional survival and cause-specific mortality after autologous hematopoietic cell transplantation for hematological malignancies
Authors: A M VanderWalde, C-L Sun, L Laddaran, L Francisco, S Armenian, J Berano-Teh, F L Wong, L Popplewell, G Somlo, A S Stein, A Nademanee, A Krishnan, N Kogut, S J Forman, S Bhatia
Journal: Leukemia (2012)
Holland decriminalises voluntary euthanasia
Authors: T. Sheldon
Journal: BMJ (2001)

The Netherlands has become the first country in the world to pass a law decriminalising voluntary euthanasia. Dutch doctors carrying out the practice under strict conditions will no longer be judged automatically as criminals when the law comes into force this autumn.

The legislation will give statutory force to the conditions that apply to voluntary euthanasia, ending decades of uncertainty for the medical profession.

It will empower the regional committees of doctors, lawyers, and ethicists, to whom doctors must report euthanasia cases, to decide whether a doctor has acted with due care and if so to close the case. Currently that power rests with the public prosecution service: the …
Direct-to-Consumer Genomics Companies Should Provide Guidance to Their Customers on (Not) Sharing Personal Genomic Information
Authors: Nanibaa’ A. Garrison, Amy L. Non
Journal: The American Journal of Bioethics (2014)

their perspective fails to fully contrast the U.S. broader GD context and to integrate a number of national and international privacy implications concerning online data sharing. First, while stakeholders will have to work in concert nationally and internationally, they will need to adhere to a broader perspective of the type of health information that needs to be protected online beyond just genetic data. Second, DTC and social networking companies should be motivated and equipped to play a more significant role in educating their users; employers should refrain from requesting access to candidate or employees’ online accounts; and Internet users should be aware that third parties may come across the information they share online. We content that it is a combination of legal, policy, and privacy approaches beyond GINA and at both the national and international levels that will serve to prevent GD based on information shared online (and the fear thereof). Such an approach may in turn contribute to foster a broader dialogue about a more equitable access to health care and the expected benefits that personalized medicine may offer. &
Difenacoum (Neosorexa) poisoning.
Authors: A M Barlow, A L Gay, B K Park
Journal: BMJ (1982)

Difenacoum (Neosorexa) poisoningDifenacoum is a coumarin anticoagulant developed as a rodenticidel that is freely available from supermarkets, chemists, and hardware stores.Accidental or criminal poisoning or self-poisoning is a hazard, and the effect on the anticoagulant mechanism is considerably more prolonged than that of warfarin.The following case history and details of animal experiments indicate the danger associated with this and related compounds.
A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults
Authors: Daniel Gotthardt, Heiko Runz, Verena Keitel, Christine Fischer, Christa Flechtenmacher, Michael Wirtenberger, Karl Heinz Weiss, Sandra Imparato, Annika Braun, Kari Hemminki, Wolfgang Stremmel, Franz Rüschendorf, Adolf Stiehl, Ralf Kubitz, Barbara Burwinkel, Peter Schirmacher, A. S. Knisely, Johannes Zschocke, Peter Sauer
Journal: Hepatology (2008)

Cholestatic liver disease (CLD) is a major cause of progressive liver damage and liver failure. Several forms of biliary cirrhosis are caused by mutations in specific genes. We sought to identify a genetic defect in a family with CLD impossible to assign to a distinct pathogenic entity. Clinical and histopathological characterization of the family members, microarray-based single-nucleotide polymorphism genotyping, and analysis of candidate genes were performed. Among six of 11 siblings severely affected by idiopathic CLD in a family from a population isolate in Transylvania, three died of cirrhosis (aged 5, 7, and 43 years) and three had adult-onset disease with small duct cholangiopathy, including ductopenia. Others were mildly affected and experienced intrahepatic cholestasis of pregnancy, miscarriages, or stillbirth. Pedigree studies revealed distant parental consanguinity. Genome-wide linkage analysis and autozygosity mapping yielded a single maximal lod-score of 3.88 on chromosome 7q21.1-7q22, excluding other genomic loci. Sequencing of ABCB4 at this locus revealed a novel missense mutation c.2362C>T (p.Arg788Trp) which cosegregated with severity of disease. Bile from a mutation homozygote showed a reduced phosphatidylcholine/bile acid ratio, consistent with reduced ABCB4 phosphatidylcholine transport activity. Conclusion: We show that a missense mutation in ABCB4 is a cause for ductopenic CLD in adulthood. Allelic status correlated with severity of liver disease ranging from intrahepatic cholestasis of pregnancy through fibrosis to cirrhosis and death in childhood and adulthood. Mutational analysis of ABCB4 should be generally considered in all patients with cholestatic liver disease of unknown etiology regardless of age and onset of disease. (HEPATOLOGY 2008.)
How important are role models in making good doctors?
Authors: E. Paice
Journal: BMJ (2002)

The use of teaching staff as role models for professional behaviour has long been an informal part of medical training. The authors consider whether role models can still be an effective means of imparting professional values, attitudes, and behaviours in a health service that is increasingly sensitive to society's expectations 

Role models—people we can identify with, who have qualities we would like to have, and are in positions we would like to reach—have been shown as a way to inculcate professional values, attitudes, and behaviours in students and young doctors. 1 2 Because good role models are seen as important in the making of a good doctor, we need to know more about them. What are the attributes young people look for in role models? Are these the attributes they really emulate? How do they react when they find that seniors lack these attributes? We consider these questions and whether we should rely on role models as a mechanism for developing doctors who are more patient centred and ethically sensitive.

#### Summary points

The attributes of medical role models have been the subject of several interesting studies. Wright and colleagues looked at physicians who had been identified as excellent role models by students and residents.3– …
Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance.
Authors: P J Ballem, G M Segal, J R Stratton, T Gernsheimer, J W Adamson, S J Slichter
Journal: Journal of Clinical Investigation (1987)

Mechanisms of thrombocytopenia were studied in 38 patients with mild to moderately severe chronic autoimmune thrombocytopenia (AITP). 51Cr and 111In-labeled autologous platelet turnover studies and in vitro analysis of committed megakaryocyte progenitors (CFU-Meg) were used as independent measures of platelet production. Autologous 111In-labeled platelet localization studies were performed to assess platelet clearance. Although there was no increase in the frequency of marrow CFU-Meg, a specific increase in the CFU-Meg [3H]TdR suicide rate was seen which was inversely correlated with the platelet count (P less than 0.001). Platelet turnover studies showed significant numbers of patients had inappropriate thrombopoietic responses to their reduced platelet counts. Platelet-associated antibody levels correlated inversely with platelet turnover suggesting that antiplatelet antibody impairs platelet production. The circulating platelet count was best predicted by an index relating platelet production (i.e., turnover) to the spleen-liver platelet clearance that correlated directly with platelet survival (P less than 0.001). In summary, both depressed platelet production and increased platelet clearance by the liver and spleen contribute to the thrombocytopenia of AITP.
RADIOACTIVE IRON ABSORPTION BY GASTRO-INTESTINAL TRACT
Authors: P. F. Hahn, W. F. Bale, J. F. Ross, W. M. Balfour, G. H. Whipple
Journal: The Journal of Experimental Medicine (1943)

Iron absorption is a function of the gastro-intestinal mucosal epithelium. The normal non-anemic dog absorbs little iron but chronic anemia due to blood loss brings about considerable absorption-perhaps 5 to 15 times normal. In general the same differences are observed in man (1). Sudden change from normal to severe anemia within 24 hours does not significantly increase iron absorption. As the days pass new hemoglobin is formed. The body iron stores are depleted and within 7 days iron absorption is active, even when the red cell hematocrit is rising. Anoxemia of 50 per cent normal oxygen concentration for 48 hours does not significantly enhance iron absorption. In this respect it resembles acute anemia. Ordinary doses of iron given 1 to 6 hours before radio-iron will cause some "mucosa block"-that is an intake of radio-iron less than anticipated. Many variables which modify peristalsis come into this reaction. Iron given by vein some days before the dose of radio-iron does not appear to inhibit iron absorption. Plasma radio-iron absorption curves vary greatly. The curves may show sharp peaks in 1 to 2 hours when the iron is given in an empty stomach but after 6 hours when the radio-iron is given with food. Duration time of curves also varies widely, the plasma iron returning to normal in 6 to 12 hours. Gastric, duodenal, or jejunal pouches all show very active absorption of iron. The plasma concentration peak may reach a maximum before the solution of iron is removed from the gastric pouch-another example of "mucosa block." Absorption and distribution of radio-iron in the body of growing pups give very suggestive experimental data. The spleen, heart, upper gastro-intestinal tract, marrow, and pancreas show more radio-iron than was expected. The term "physiological saturation" with iron may be applied to the gastro-intestinal mucosal epithelium and explain one phase of acceptance or refusal of ingested iron. Desaturation is a matter of days not hours, whereas saturation may take place within 1 to 2 hours. We believe this change is a part of the complex protein metabolism of the cell.
Benefit-Risk Considerations in Preventive Treatment for Tuberculosis in Elderly Persons
Authors: WILLIAM W. STEAD
Journal: Annals of Internal Medicine (1987)

Of 2135 elderly residents of nursing homes in Arkansas (mean age, 79.4 years) who have been treated with isoniazid for prevention of tuberculosis, data from 1935 were suitable for analysis. About 12 months of therapy was successfully completed in 1600 persons. Therapy could not be completed in 84 persons (4.4%) because of incipient hepatic toxicity and in 116 (6.0%) because of other types of drug intolerance. Although 135 persons (7.0%) died during the course of therapy, no evidence was found that isoniazid contributed to any death. The ratio of benefit (reduction of risk for tuberculosis) to risk (for nonfatal isoniazid-related hepatitis) was clearly favorable in persons who had definite conversions (1.6 for women, 3.4 for men) but less so for persons who had tuberculin reactions of unknown duration and for persons with minor increases in size of tuberculin reaction (less than 12 mm increase from an initially negative reaction).