tbuckley/cabot-search huggingface dataset:
Abstract 1225: α-Catulin promotes tumor growth by preventing cellular senescence
Authors: Yuh-Ling Chen, Li-Ching Fan, Chen-Hsien Liang, Yao-Tsung Tsai, Keng-Fu Hsu, Tse-Ming Hong
Journal: Cancer Research (2011)

Abstract Cellular senescence is a proven tumor-suppressive strategy that forces transformed cancer cells to re-enter irreversible cell-cycle arrest. Triggering the senescence of tumor cells may contribute to successful cancer therapy. α-Catulin, an α-catenin-related protein, is reported to have tumorigenic potential because it regulates the NF-κB pathway, but little is known about its clinical relevance and the mechanism through which it regulates cancer progression. Here, we provide evidence that the expression of α-catulin is upregulated in most human cancer cells and clinical oral cancer tissues and positively correlated with tumor size (P = 0.001) and cancer stage (P = 0.004) of OSCC. α-Catulin knockdown in the OC2 and A549 cancer cell lines dramatically decreased cell proliferation and contributed to cellular senescence, and inhibited OC2 xenograft growth. Mechanistic dissection showed that α-catulin depletion strongly induced the DNA damage response (DDR) via a p53/p21-dependent pathway in A549 cells, but a p53/p21-independent pathway in OC2 cells carrying mutant p53. Global gene expression analysis revealed that α-catulin knockdown altered several crucial genes related to mitotic chromosome condensation, DDR, and DNA repair systems, which suggests that its depletion-induced cellular senescence might be caused by chromosome condensation failures, severe DNA damage, and impaired DNA repair ability. Our study provides evidence that α-catulin promotes tumor growth by preventing cellular senescence and suggests that downregulating α-catulin may be a promising therapeutic approach for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1225. doi:10.1158/1538-7445.AM2011-1225
Medicare Coverage for Technological Innovations — Time for New Criteria?
Authors: Muriel R. Gillick
Journal: New England Journal of Medicine (2004)

In 2003, Medicare approved coverage for three new procedures: lung-volume–reduction surgery, implantation of cardioverter–defibrillators, and implantation of left ventricular assist devices. The annual cost to Medicare for these treatments could be as high as $11 billion, which is more than 20 percent of the expected annual cost of the Medicare drug benefit. Medicare's current policy is to pay for services that are "reasonable and necessary." The author argues that explicit criteria should be developed to guide Medicare's decisions about which procedures it will cover.
Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation
Authors: N Schaap, A Schattenberg, E Mensink, F Preijers, M Hillegers, R Knops, A Pennings, J Boezeman, AGeurts van Kessel, B de Pauw, T de Witte
Journal: Leukemia (2002)
Thyroid Storm Treatment With Blood Exchange and Plasmapheresis
Authors: Fuad S. Ashkar
Journal: JAMA (1970)

Conventional therapy for hyperthyroidism is designed to reduce the rate of thyroid hormone release from the gland and also to ameliorate the effects on the tissues and consists of iodine, antithyroid drugs, adrenergic blocking drugs, and corticosteroids. Because of the long half-life of thyroxine in the serum these measures cannot produce a sharp decrease in the very high level of circulating thyroid hormone. Plasmapheresis was effective in removing a substantial quantity of hormone from a dog in a hyperthyroid-like state and reduced serum thyroxine levels to 40% of the initial value. A striking improvement was observed in three patients after the use of blood exchange or plasmapheresis procedures when death appeared imminent despite conventional therapy for thyrotoxic crisis.
Abstract 4155: Simultaneous quantitation of multiple signaling molecules in individual circulating tumor cells (CTCs) by multi-color laser scanning cytometry
Authors: Weiguo Wu, Yujian Zhang, Chris Neil, Geoffrey M. Copper, Larry Kahn, Vladislava Melnikova, Jacky Woo, Darren Davis
Journal: Cancer Research (2011)

Abstract Introduction: Recent advances in circulating tumor cell (CTC) technology provide a new alternative approach to examine proteomic and molecular characteristic of tumor cells from cancer patients. The current trend in anti-cancer drug development focuses on new compounds that modulate multiple signaling pathways. With CTC detection used as a potential liquid biopsy, the simultaneous examination of signaling molecules for multiple pathways on the same CTC could provide insight into the drug activity in tumor cells. We used proprietary laser scanner cytometry (LSC) technology and developed a multi-color immunofluorescence (IF) procedure to detect 7 biomarkers within the same CTC. We validated this new staining technology using the (1) receptor tyrosine kinase pathways based molecules included total and phospho-IGF-1R, in combination with total and phospho-EGFR, or with total and phospho-ERK1/2, or with total and phospho-AKT (S473) in HT-29 colorectal tumor cells, and (2) same marker expression in CTCs enriched from cancer patients. Purpose: To validate the new multiple marker IF staining procedure and laser scanning cytometry (LSC) platform using ligand treated or untreated tumor cells, and in CTCs enriched from cancer patients. Method: A target biomarker staining panel was combined with standard CTC staining (DAPI, CK+ and CD45-) to create a 7-color IF staining panel to examine marker expression in tumor cell lines and in CTCs from cancer patients. Cultured tumor cells and CTCs enriched from Cellsearch Profile were cytospun onto slides, stained, scanned (by LSC) and analyzed. Results: Using a simultaneous co-staining procedure and LSC-based analysis, we demonstrated that treatment of HT29 cells with IGF1 for 15-30 minutes induced significant increases in both p-IGF1R expression and p-ERK1/2 and p-AKT expression on HT29 cells. In addition, anti-IGF1R and/or anti-EGFR, or with multi-kinase inhibitor treatment leads to differential reduction of p-ERK1/2 and p-AKT. Using CTCs enriched from cancer patient, simultaneous detection of multiple signaling molecules was also observed. Summary A multi-color, LSC-based methodology was developed to quantify expression of up to 4 biomarkers in CTCs. Application of this technology in clinical studies to examine the activation status of CTCs from patients could provide important information on pathway-specific drug activity and guide dosing selection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4155. doi:10.1158/1538-7445.AM2011-4155
Cross-species malaria immunity induced by chemically attenuated parasites
Authors: Michael F. Good, Jennifer M. Reiman, I. Bibiana Rodriguez, Koichi Ito, Stephanie K. Yanow, Ibrahim M. El-Deeb, Michael R. Batzloff, Danielle I. Stanisic, Christian Engwerda, Terry Spithill, Stephen L. Hoffman, Moses Lee, Virginia McPhun
Journal: Journal of Clinical Investigation (2013)

Vaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with seco-cyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite DNA, blocking their ability to replicate. After administration in mice, DNA from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by CD4+ T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species.
An open democracy
Authors: Shawn Mathur, Christian Schmidt
Journal: Molecular Cancer (2007)

Sovereign power is retained and shared by the citizens of a country. Using electoral tools, governing structures are formed to ensure protection of national interests. As with any institution, proper control of the government guarantees its adherence to the tasks delegated to it by its citizens. In turn, citizens have to be provided with, and are encouraged to access and evaluate, information generated by the government. On the other hand, governments generate sensitive information (e.g., intelligence, internal reports, etc) that are required for self-evaluation and defense against threats to the nation. Governments are granted a privilege to collect, store and use such information to perform necessary tasks. How far does governmental privilege go relative tothe intrinsic right of citizens to access and evaluate information?
Fentanyl-Laced Heroin
Authors: Daniel Fernando
Journal: JAMA (1991)

<h3>To the Editor.—</h3> The article<sup>1</sup>on drug overdose deaths associated with fentanyl in Pennsylvania was timely and revealing. Readers in the tristate area (New York, New Jersey, and Connecticut) were made aware of the presence of fentanyl in the illegal heroin market through radio, television, and newspapers during early February. As the ethnographer for the Paterson (NJ) Health Behavior Project, I interviewed 28 drug users during the "epidemic," 24 of whom were searching for "Tango and Cash," the brand of heroin contaminated with fentanyl. Earlier ethnographic research<sup>2</sup>has noted that heroin overdoses create a demand for that "bag of dope." The effects of the media campaign must be interpreted in the context of drug users. In Paterson, there were two drug overdose deaths and 10 overdoses. Flirting with possible overdose only confirmed this subculture's belief in the purity of heroin. Victims were said to have become greedy when
On Disease of the Suprarenal Capsules
Authors: S. J. Jeaffreson
Journal: BMJ (1857)

tion of the first; and probably before the rheumatic attack came on, andwlhen he was in good health, it was quite as indistinct as the systolic mitral murmur.The amount of valvular lesion was so very sliglht, that it would have beeni no wonder if the natural sounds hial been heard throughout.With respect to peri- cardial friction sound, none was discovered.There was probably extensive pericarditis during his former attack of rheu- inatic fever, but only a very limited affection of the membrane this time; aind that not until a few hours before death.
Caring for the young disabled
Authors: T G Williams
Journal: BMJ (1983)

<b>1378</b> <h3><b>Background:</b></h3> Flurpiridaz F18 is a promising <sup>18</sup>F-labeled myocardial perfusion radiotracer utilising all intrinsic advantages of PET technology. We aimed to elucidate the stability of myocardial Flurpiridaz F18 distribution in a pig model of transient coronary occlusion. <h3><b>Methods:</b></h3> Myocardial Flurpiridaz F18 distribution was analyzed by 120 min dynamic cardiac PET imaging in controls (n = 4 healthy pigs), pigs with 2 min transient mid left descending artery occlusion at the time of tracer injection followed by reperfusion (n = 4) and a pig model of myocardial infarction with permanent mid left descending artery occlusion one month prior to the imaging study (n = 3). <h3><b>Results:</b></h3> Normal control hearts demonstrated rapid, intense and almost homogenous radiotracer uptake throughout the left ventricle over the imaging session of 2 hours, while both coronary occlusion models demonstrated a clear tracer uptake defect in the distal anteroseptal wall. Using a 50% threshold, the investigated tracer uptake defect remained almost similar in a model of myocardial infarction (% defect areas normalized at 8 min: 13 min, 104 ± 4%; 23 min, 107 ± 1%; 45 min, 110 ± 1%; 75 min, 114 ± 3%; 105 min, 116 ± 3% LV, averaged slope 0.12 ± 0.10%/min). On the other hand, in a transient coronary occlusion model at the time of tracer injection, the defect size showed continuous and significant decrease throughout the 2 hour imaging session (% defect areas normalized at 8 min: 13 min, 96 ± 8%; 23 min, 82 ± 11%; 45 min, 68 ± 16%; 75 min, 56 ± 21%; 105 min, 37 ± 32% LV, averaged slope -0.62± 0.19%/min[asterisk], [asterisk]p&lt;0.05 vs infarction model). <b>Conclusions: </b>Clear myocardial distribution defect in both coronary occlusion models indicates promising properties of this new class of <sup>18</sup>F perfusion PET tracer. The observed change of perfusion defect size after coronary reperfusion emphasizes the relevance of early imaging protocols after tracer injection for accurate assessment of perfusion abnormalities. Moreover, assessment of viability with an additional delayed imaging session using a single tracer injection protocol is feasible. This work was supported by the Competence Network of Heart Failure funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF) and German Research Council (DFG grant HI 1789/3-3). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701983.
Inhibition of fibrinolysis and abruptio placentae
Authors: B Astedt, I M Nilsson
Journal: BMJ (1978)

The patient referred to seems to have been unusual.It is thought that activation of fibrinolysis during pregnancy is uncommon.Indeed this is the very reason why the classic disseminated intravascular coagulation syn- dromes were first recognised in human pregnancy.Could it be that this patient lacked one of the normal fibrinolytic inhibitors that are known to act either locally5 or in the general circulation ?If this is the case then the extrapolation is unjustifiable.I feel that we need clarification of this case or more work by an expert unit before this suggestion is put into widespread practice.
The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression
Authors: Jun Chul Kim, Jose L Badano, Sonja Sibold, Muneer A Esmail, Josephine Hill, Bethan E Hoskins, Carmen C Leitch, Kerrie Venner, Stephen J Ansley, Alison J Ross, Michel R Leroux, Nicholas Katsanis, Philip L Beales
Journal: Nature Genetics (2004)
Erythropoietin acts as a trophic factor in neonatal rat intestine
Authors: S E Juul, D J Ledbetter, A E Joyce, C Dame, R D Christensen, Y Zhao, V DeMarco
Journal: Gut (2001)

BACKGROUND Erythropoietin (Epo) receptors are present on enterocytes of fetal and neonatal small bowel but the role of Epo in the bowel is not known. AIMS We tested the following hypotheses: (1) enterally dosed Epo is absorbed from the intestines of neonatal rats, (2) Epo acts as a trophic factor in developing small bowel, and (3) the trophic effects of Epo are dependant on the route of administration. METHODS The dose dependant effects of enterally dosed recombinant human erythropoietin (rEpo 0–1000 U/kg/day) were studied in artificially raised rat pups and compared with dam raised controls and dam raised pups given rEpo in rat milk. After one week, reticulocyte counts, haematocrits, and plasma Epo concentrations were measured, and calibrated morphometric measurements of villi were performed. The effects of route of rEpo administration (enteral v parenteral) on erythropoiesis, bowel growth, and disaccharidase activity were studied in nursing pups treated for one and two weeks. RESULTS Serum Epo concentrations ranged from undetectable (&lt;0.6 mU/ml) to 8.4 mU/ml in control and enterally dosed pups (median 1.8 mU/ml), and from 4.9 to 82.3 mU/ml (median 20.4 mU/ml) in parenterally dosed animals. No increase in haematocrit or reticulocyte count was noted in enterally treated pups compared with controls after up to two weeks of treatment. Small bowel length was greater in rEpo treated pups, and a dose dependent increase in villus surface area which was independent of the route of dosing and associated with increased BrdU uptake was found. CONCLUSIONS rEpo is not enterally absorbed in an intact and functional form from the intestines of neonatal rat pups. Thus enterally dosed rEpo has no erythropoietic effects. However, rEpo acts as a trophic factor in developing rat small bowel whether given enterally or parenterally.
THE ROLE OF LIBERAL ARTS IN PREPARATION FOR MEDICINE
Authors: John C. Baker
Journal: JAMA (1960)

All too little attention is paid to the importance of liberal arts in preparing students for the medical profession. Few of the students with whom I have talked about being medical doctors ever ask what they should study as students in other fields of learning do—they seem to know the answer—German, a smattering of Latin, mathematics, and science. And they frequently comment, "These courses will help me get into medical school"! Unfortunately this ready, almost naive, answer is all too often an indication of lack of knowledge rather than wisdom. It overlooks the complicated world today in which medical doctors serve and the beings who inhabit it. The significance of this question, what should prospective doctors study in college, is all too often recognized only by those doctors who have lived long enough and hard enough to realize the characteristics of our world and what they mean in the way
Factors influencing rubella immunity in women.
Authors: M S Vaile
Journal: BMJ (1981)

coccoid rods used by Mayberry.There are indications from our results that Eubacterium and Bifidobacterium are antigenically related.We have also noted a close correlation between IgG antibodies to Bifidobacterium bifidum and the duration of Crohn's disease (p =0 0006).It would therefore be of interest to know if the patients in the study by Dr Mayberry and colleagues giving poor correlations with agglutinations were recently diagnosed cases of Crohn's disease.In our study ulcerative colitis patients gave a slightly raised level of antibodies to Bifidobacterium bifidum but this was not significantly different from that in normal subjects.Finally, we should state that Wensinckt found no difference between the numbers of Bifidobacterium in the faecal flora of Crohn's patients and of normal subjects.
Mandatory Continuing Medical Education?
Authors: Rutledge W. Howard
Journal: JAMA (1976)

The American Medical Association supports the principle of continuing medical education strongly, but it recommends that such education be on a voluntary basis (Resolution 6, adopted, House of Delegates, 124th Annual Convention, June 1975). Nevertheless, medical practice acts in 15 states give the state board of medical examiners in each of them authority to require physicians to produce evidence of continuing medical education as a condition for reregistration of the license to practice medicine. Is the public (or its representatives) being deluded by such legislation?  The purpose of such mandatory continuing medical education, and the motivation behind such legislation is not always clear. Perhaps it is felt that more continuing medical education, or at least the documentation of physician participation in such activities, will result in competence when physicians provide health care.  The question of whether continuing medical education should be voluntary or mandatory is difficult to answer. Certainly, consensus
Abstract 509: The CTGF antibody FG-3019 blocks CTGF-stimulated migration in ovarian cancer cells
Authors: Goli Samimi, Carol Wong, Suzanne M. Spong, Michael J. Birrer
Journal: Cancer Research (2011)

Abstract Ovarian tumors generally arise from the surface epithelium of the ovary, and require interactions with host stroma to promote tumor cell proliferation and expansion. The signaling mechanisms between tumor-associated stroma and adjacent ovarian epithelial tumor cells remain unclear. We have previously analyzed gene expression profiles of laser-capture microdissected stromal cells from normal ovary and ovarian tumors and have demonstrated that normal ovarian stroma undergoes significant gene expression changes in response to the epithelial tumor microenvironment. Connective Tissue Growth Factor (CTGF), a TGF-β-regulated gene, was identified as specifically up-regulated in tumor-associated versus normal stroma. CTGF is a component of the tumor microenvironment with a demonstrated role in tumor progression and metastasis. FG-3019, a fully human monoclonal antibody against CTGF, is currently under clinical investigation in pancreatic cancer. The aim of this current study was to further elucidate the role of CTGF in ovarian cancer and examine its potential as a therapeutic target. We demonstrate that normal ovarian fibroblasts and ovarian cancer-associated fibroblasts treated with TGF-β secreted high levels of CTGF, whereas ovarian cancer epithelial cells secreted significantly lower levels. We next assessed the paracrine effect of CTGF on three different ovarian cancer cell lines, A224, OVCAR3, and SKOV3. Expression of endogenous CTGF is low in these cells which is consistent with the level found in primary ovarian tumor cells. Addition of recombinant CTGF for 6-hr stimulated migration of A224 (443 ± 20.5 vs. 85 ± 24.4 cells), OVCAR3 (104 ± 11.7 vs. 68 ± 30.1 cells) and SKOV3 (334 ± 45.6 vs. 82 ± 16.6 cells) in a transwell migration assay. Addition of the CTGF-blocking antibody FG-3019 significantly inhibited transwell migration in the presence of recombinant CTGF in all three cell lines (from 443 ± 20.5 to 197 ± 65.4 cells in A224, 334 ± 45.6 to 119 ± 29.0 cells in SKOV3 and 104 ± 11.7 to 36 ± 2.5 cells in OVCAR3). However, recombinant CTGF did not promote proliferation of these cell lines. We demonstrate that CTGF may contribute to ovarian tumor biology and that its function can be blocked by FG-3019, thus determining CTGF as a potential therapeutic target in ovarian tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 509. doi:10.1158/1538-7445.AM2011-509
Points: Drug treatment in Parkinson's disease
Authors: M Hildick-Smith
Journal: BMJ (1984)

despite the evidence that in countries where health education of the public receives much higher priority than here, mortality from coronary heart disease has fallen below our own.The fall in mortality among doctors (and other professions) is almost certainly the result of the reduction of cigarette smoking and improved eating and exercise habits.This is what a population policy is likely to effect and is the responsibility of community physicians, health educators, and other health workers.The high risk strategy of detecting and advising those at greater risk whether from theirgenes or from their habits makes good sense and is already being carried out in several general practices.If Professor Oliver believes that this should be extended to the screening of the whole adult population to identify the 5%/, at highest risk he should spell out how this is to be done.Meanwhile it should be accepted that both strategies are necessary.