tbuckley/cabot-search huggingface dataset:
Abstract 886: Developing a new concept for specific targeting of cancer cells
Authors: Ken M. Kosak
Journal: Cancer Research (2012)

Abstract The purpose of this work is to demonstrate the feasibility for 100% specific killing of cancer cells and virtually zero killing of normal cells. This is an obvious goal that seems to have been lost in most of the current targeting strategies for treating cancer. For instance, one well-known strategy employs drugs that kill or inhibit cancer cells through their generally higher metabolic rate and uptake of nutrients. A second strategy uses drug conjugates and/or carrier systems that target cell surface receptors or antigens. Another strategy now gaining rapid acceptance is using cancer genomics and/or proteomics to more “specifically” inhibit various up-regulated metabolic targets in cancer cells. The use of inhibitors and/or the current limitations of toxic drugs result in incomplete killing of the cancer, which frequently results in resistance. Another purpose of this work is to redirect some of the massive resources of industry and academia back to the harder task of specifically killing cancer instead of just inhibiting it. If all cancer cells are killed during treatment, there is no opportunity for resistant cells to grow back. Therefore, the ideal goal is to produce a drug and/or drug delivery system that is virtually 100% specific for killing cancer. This 100% specificity must be based on properties that only cancer cells possess. This eliminates normal cell surface receptors or metabolic pathways that are simply up-regulated or down-regulated compared to normal cells. Cancer is caused by one or more mutations in DNA. Therefore, all cancers have at least one or more mutations that are not found in normal cells. These unique mutations are the truly specific targets that should be used for killing cancer cells. The methods in this work identify mutations inside live cancer cells through specific binding to mutated DNA, (or the resulting mutated proteins). By employing a unique delivery system, a highly toxic compound is released into the cancer cell only when specific binding occurs. This feasibility study will show that nearly 100% of cancer cells can be killed through cancer-specific, intracellular targets while normal cells are not. 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 886. doi:1538-7445.AM2012-886
Depression in Acute Schizophrenic Psychosis
Authors: MALCOLM B. BOWERS, BORIS M. ASTRACHAN
Journal: American Journal of Psychiatry (1967)

In this study of 36 schizophrenic patients, conventional antidepressant therapies did not result in a clinically observable lifting of depression among those patients who were seriously depressed in the hospital after acute psychotic symptoms had been controlled by phenothiazines. The authors point out that depression in the convalescent schizophrenic remains a problem since it seems relatively unresponsive to conventional antidepressant therapies.
IMPACT OF TOTAL CORONARY CALCIUM SCORE ON PROCEDURAL AND LONG-TERM OUTCOMES IN PATIENTS WHO UNDERWENT PERCUTANEOUS CORONARY INTERVENTION WITH DRUG ELUTING STENTS: 3 YEARS FOLLOW-UP
Authors: Youngkeun Ahn, Hae Chang Jeong, Jum Suk Ko, Min Goo Lee, Keun Ho Park, Hyun Ju Yoon, Nam Sik Yoon, Hyung Wook Park, Kye Hun Kim, Young Joon Hong, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang
Journal: Journal of the American College of Cardiology (2010)
P B S Fowler
Authors: R. Savage
Journal: BMJ (2011)

P B S (“Bruce”) Fowler was a medical polymath. One of the last truly general physicians of English medicine, he balanced original research with teaching while the individual patient remained paramount in his work.

Born to an American mother and a successful English businessman, he returned to England at the age of 3 and was looked after by his father’s chauffeur, who fed him raw suet and taught him to smoke Wills’s Woodbines. He was sent to boarding preparatory school at the age of 6. A bad stammer suggested that he was stupid as, when asked to buy a stamp from the local post office, he would return with one of the wrong value because he was unable to speak properly. He then boarded at Harrow School, where they noticed that when talking about his hobby of bee keeping his stammer disappeared. He attended a stammering school, where he fell in love with a woman who also stammered, and learnt to say “I love you.” It was unlikely that his life would conform to a stereotype.

Bruce excelled at all sports, especially swimming, rugby, and cricket; his parents led him to believe that sport was more important than academic achievement. He formed strong relationships, including with his housemaster, who wrote in his last school report before going up to Balliol College Oxford: “He has a great reserve of faith, of kindliness, of grit, and of good fellowship, Oxford’s gain will definitely be Harrow’s loss.”

He decided to he wanted to become a doctor at the age of 8, when his mother was taken seriously ill and the doctor was called. He arrived at the house, went upstairs, examined his mother and then came down saying, “She will be fine now,” to great rejoicing.

Bruce completed his clinical training at St …
Expression of the early growth response 1 and 2 zinc finger genes during induction of monocytic differentiation.
Authors: S Kharbanda, T Nakamura, R Stone, R Hass, S Bernstein, R Datta, V P Sukhatme, D Kufe
Journal: Journal of Clinical Investigation (1991)

Members of the early growth response (EGR) gene family are rapidly induced after mitogenic stimulation of diverse cell types. The present work has examined EGR gene expression during differentiation of myeloid leukemia cells along the monocytic lineage and in activated monocytes. Low levels of EGR-1 transcripts were detectable in untreated U-937 and HL-60 leukemia cells. In contrast, treatment of these cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) was associated with increases (within 1 h) in EGR-1 mRNA levels. The induction of monocytic differentiation by TPA and other agents was further associated with increases in EGR-2, but not EGR-3 or EGR-4, mRNA levels in these cells. Treatment of resting peripheral blood monocytes with the macrophage colony-stimulating factor (M-CSF) was also associated with rapid (within 15 min) increases in expression of the EGR-1 and EGR-2 genes. The results of nuclear run-on assays demonstrate that EGR-1 mRNA levels are increased in part by transcriptional activation of this gene in M-CSF-stimulated monocytes. The results also demonstrate that both EGR-1 and EGR-2 mRNA levels are regulated at the posttranscriptional level by a labile protein that destabilizes these transcripts. Finally, we demonstrate that dexamethasone, an inhibitor of monocytic differentiation, blocks the associated increases in EGR-1 and EGR-2 expression. Taken together, the results indicate that the EGR-1 and EGR-2 early response genes are involved in the induction of myeloid leukemia cell differentiation along the monocytic lineage and in the activation of human monocytes.
Cost‐effectiveness analysis of new drugs for chronic hepatitis C: The importance of updating utility values
Authors: Paolo A. Cortesi, Luciana Scalone, Lorenzo G. Mantovani
Journal: Hepatology (2014)

View this article online at wileyonlinelibrary.com. Potential conflict of interest: Dr. Mantovani consults and is on the speakers' bureau for Bayer. He received grants from MSD and Janssen. To the Editor: We read with interest the article of Petta et al.1 We would like to highlight two sources of bias in the analysis. One bias is generated by the use of incorrect utility indices to calculate quality‐adjusted life‐years (QALYs). In Table 1, the authors report the utility indexes for each health state included in the model by referring to their reference number 29, which corresponds to the article by Liu et al.2 Actually, Liu et al. drew utility index data from different sources in the literature, but none of these corresponds to any of the ones used by Petta et al. Furthermore, because the cost effectiveness analysis specifically refers to Italy, actually, to our best knowledge, updated Italian‐specific empirical estimates of utility indexes for chronic hepatic diseases are available from the COME study since November 2012,3 obtained from a sample of 1,088 patients classified according to their chronic hepatic condition, using state‐of‐the‐art quality of life instruments and methods. Hence, from the COME study, it is possible to use the Italy‐specific mean utility index data, particularly for hepatocellular carcinoma (HCC; 0.757) and liver transplantation (LT; 0.767), which are significantly higher than those used by Petta et al. (0.250 and 0.500, respectively) and much more similar to those reported by the quoted article by Liu et al. (i.e., 0.720 for HCC and 0.825 for LT. The use of lower utility estimates for hepatitis C virus sequelae would result, ceteris paribus, in biasing cost‐effectiveness estimates toward more‐favorable ratios. A second bias is related with the willingness‐to‐pay threshold used to ascertain the cost‐effectiveness ratio. The authors used a cutoff of €25,000 per life years gained (LYGs), quoting the article by Shoroiwa et al.,4 who instead have proposed a new classification of cost‐effectiveness plane and methodology based on QALYs, and not on LYGs. Actually, from the article by Messori et al., it is possible to use a cutoff specifically proposed for Italy of €1,000‐€5,000 per month of life gained.5
Vascular Endothelium Viability and Function after Total Cardiopulmonary Bypass in Neonatal Piglets
Authors: ALAIN SERRAF, HASSAN SELLAK, PHILIPPE HERVÉ, NICOLAS BONNET, MONICA ROBOTIN, HÉLÈNE DETRUIT, BRUNEAU BAUDET, GUY MICHEL MAZMANIAN, CLAUDE PLANCHE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Endothelium dysfunction with severe pulmonary hypertension may occur after total cardiopulmonary bypass (CPB) in infants as a result of a widespread inflammatory response. The aim of this study was to separate out the effects of lung ischemia–reperfusion from membrane oxygenator–induced activation of leukocytes on the function and viability of the pulmonary and systemic endothelia in neonatal piglets submitted to 90-min total CPB followed by 60-min reperfusion or in sham animals. Hemodynamics, gas exchange, endothelial-dependent relaxation in pulmonary and femoral arteries, and lung and skeletal muscle myeloperoxidase activity were assessed before, during, and after CPB, i.e., after reperfusion. Pulmonary and aortic endothelial cells and circulating leukocytes were harvested to assess reperfusion-induced changes in endothelial cells' viability and proliferation, and leukocyte–endothelial cell adhesion and cytotoxicity. Gas exchange worsened after reperfusion with pulmonary hypertension, increase in lung but not skeletal myeloperoxidase, and reduction of endothelial-dependent relaxation in pulmonary but not femoral arteries. After reperfusion, viabilities of pulmonary and aortic endothelial cells were reduced to 50%, endothelial cell growths were faster in pulmonary arteries than aorta, and leukocyte–pulmonary endothelial cell adhesion and cytotoxicity increased. These results suggest that in total CPB lung ischemia–reperfusion aggravates the inflammatory response and predisposes the lung endothelium to leukocyte-mediated injury.
Management of Traumatic Hyphema
Authors: Marc A. Horowitz
Journal: JAMA (1983)

To the Editor.—  The reply discussing the circumstances under which patients with traumatic hyphema should be hospitalized 1 does not adequately address the complexities or controversies that hyphema management has generated in the ophthalmic literature. For example, it is imperative that all black patients with hyphemas have immediate examination for the presence of sickle cell disease. It has been clearly shown that patients with sickle cell disease or trait do not tolerate elevated intraocular pressure and that the use of acetazolamide is probably contraindicated because the hemoconcentration and acidosis that result exacerbate the sickling process. 2 Early surgical intervention may be the best treatment for this type of hyphemainduced glaucoma in patients with sickle cell disease.  Other modalities of treatment mentioned in the response are also open to question. The value of systemic steroids in the treatment of hyphema is to date unproved. The only controlled double-blind, prospective study has
Dietary Factors and Risk of Breast Cancer: Combined Analysis of 12 Case--Control Studies
Authors: G. R. Howe, T. Hirohata, T. G. Hislop, J. M. Iscovich, J.-M. Yuan, K. Katsouyanni, F. Lubin, E. Marubini, B. Modan, T. Rohan, P. Toniolo, Y. Shunzhang
Journal: JNCI Journal of the National Cancer Institute (1990)

We conducted a combined analysis of the original data to evaluate the consistency of 12 case-control studies of diet and breast cancer. Our analysis shows a consistent, statistically significant, positive association between breast cancer risk and saturated fat intake in postmenopausal women (relative risk for highest vs. lowest quintile, 1.46; P <.0001). A consistent protective effect for a number of markers of fruit and vegetable intake was demonstrated; vitamin C intake had the most consistent and statistically significant inverse association with breast cancer risk (relative risk for highest vs. lowest quintile, 0.69; P <.0001). If these dietary associations represent causality, the attributable risk (i.e., the percentage of breast cancers that might be prevented by dietary modification) in the North American population is estimated to be 24% for postmenopausal women and 16% for premeno-pausal women. [J Natl Cancer Inst 82: 561–569, 1990]
Joan Sugden (née Parsons)
Authors: Len Tuckwell
Journal: BMJ (2006)

​FormerFormer consultant psychiatrist Lincoln (b 1948; q University College Hospital, London, 1971; MRCPsych), d 5 November 2005.



Figure 1



After registrar posts in psychiatry in Swindon and Cwmbran, Joan held registrar and visiting specialist posts in Brisbane, Australia (1974-7), followed by two years at RAF Akroti in Cyprus. She then spent two years in the climatic hostility of St Anthony, Newfoundland, nurturing a mental health service covering 150 000 square miles. In 1987 she was appointed consultant in acute adult psychiatry at Lincoln, followed by various locum consultant posts, until she retired in 1998. Her wide interests included horse riding, karate (black belt), and the piano. She leaves a husband, Keith, and two children.
Enhancement of bioavailability by lowering of fat content in topical formulations
Authors: K. Wirén, H. Frithiof, C. Sjöqvist, M. Lodén
Journal: British Journal of Dermatology (2008)

Background The cosmetic properties of topical formulations are important parameters for the adherence to treatment, where modern oil-in-water emulsions are considered more acceptable compared with ointments. After application of an emulsion to the skin, the concentration of active ingredients in the formulation residue on the skin will increase, due to evaporation of volatile ingredients. Objectives The aim of the present study was to investigate the effect of changes in vehicle fatty content on the skin penetration of two active ingredients: benzyl nicotinate (BN) and betamethasone valerate (BV). Methods Formulations containing 0·5% BN and 0·3% BV in vehicles with different lipid content (10–80%) were applied in a randomized and double-blind manner to the forearm of healthy volunteers. The changes in skin colour (erythema and blanching) were then monitored visually and with a new noninvasive instrument. Results The BN formulation containing 10% fat induced erythema more rapidly and with higher intensity than the formulations with higher fat content. Increased efficacy was also observed from the low-fat content formulation of BV, which gave more blanching than the formulations with high fat content. Conclusions The rate of penetration of the active ingredients was inversely related to the lipid content, i.e. simple changes of the cosmetic properties by modifications of the lipid content may affect the efficacy of a formulation.
Inhibition of Metastatic Spread by I.C.R.F. 159: Selective Deletion of a Malignant Characteristic
Authors: A. J. Salsbury, K. Burrage, K. Hellmann
Journal: BMJ (1970)

Treatment with I.C.R.F. 159 completely inhibited metastasis formation in mice implanted with Lewis lung carcinoma at doses having little influence on the rate of growth of the primary implant. This inhibition was due to the effect of I.C.R.F. 159 on the development of blood vessels of the invading margins of the primary tumour. So far as is known, this is the first time a drug has induced a specific loss of the malignant characteristic of blood-borne tumour cell dissemination.
Tarsorrhaphy From Accidental Instillation of Cyanoacrylate Adhesive in the Eye
Authors: Curtis E. Margo
Journal: JAMA (1982)

Three patients mistakenly instilled cyanoacrylate adhesives into their eyes, resulting in firm upper-to-lower lid adhesion and transient keratoconjunctivitis. In one case, the "tarsorrhaphy" had to be undone with scissors. Adequate prevention of these accidents can be achieved only by changing the packaging of glues so that it will not resemble the containers used for ophthalmic medications. (<i>JAMA</i>1982;247:660-661)
Rich countries must not exploit poorer nations for research purposes
Authors: Z. Kmietowicz
Journal: BMJ (2002)

Companies or organisations in wealthy countries that plan to carry out research in developing countries should ensure that certain ethical standards are in place before they go ahead with studies that may hold little value to participants, warns the Nuffield Council on Bioethics.

In a report published this week the council advises developed nations to pay special attention to how they plan to gain consent from the people they wish to participate in trials. …
Spontaneous Myxoedema Developing after Thyrotoxicosis
Authors: R. Fraser, B. E. C. Nordin
Journal: BMJ (1955)

GTANT-CELL POLYPHLEBITIS,. 255features.The condition in many respects resembled polyarteritis nodosa, but differed from it in that the vascular lesions were limited to the veins and in the presence of giant cells.A full account of the clinical and laboratory findings is given and the differential diagnosis discussed.The patient is alive and is being followed up.We are most grateful to Professor Dible for his valuable opinion on the tissue slides.Our thanks are also due to Dr.
Folic Acid and Neural-Tube Defects — Time for Action?
Authors: Irwin H. Rosenberg
Journal: New England Journal of Medicine (1992)

IN this issue of the Journal, Czeizel and Dudás1 report from Hungary that vitamin supplements can prevent the occurrence of neural-tube defects (spina bifida and anencephaly). This report is a landmark in the definition of the requirements for vitamins and in the evolution of the role of scientific evidence in public health policy. It has long been suspected that dietary factors have a role in neural-tube closure; the possibility that folic acid might be involved was first proposed in the mid-1960s.2 During the past decade our understanding of the relation between folic acid and birth defects has unfolded with . . .
A useful diagnostic and prognostic tool for acute appendicitis and acute pancreatitis
Authors: R. K. Choudhary, M. Choudhary
Journal: BMJ (2012)

Watson and colleagues did not cover the diagnostic and prognostic value of raised inflammatory markers in common surgical conditions, such as acute appendicitis and acute pancreatitis.1

Interest in C reactive protein (CRP) and white cell count as diagnostic markers for acute appendicitis has grown …
Intestinal apoproteins during fat absorption.
Authors: G Schonfeld, E Bell, D H Alpers
Journal: Journal of Clinical Investigation (1978)

To compare the roles of apolipoprotein (Apo) A-I, B, and E (or arginine-rich apoprotein, ARP) in the intracellular production of intestinal chylomicrons (and/or VLDL), these apoproteins were localized in rat intestinal mucosa by the light microscope method of indirect immunofluorescence. In addition, tissue levels of ApoA-I and ApoB were measured during fat absorption by radioimmunoassay. Antisera were produced using ApoA-I isolated from rat plasma high density lipoprotein, and ApoB and ARP from plasma VLDL by column chromatography. The apoproteins yielded single bands on polyacrylamide disc gel electrophoresis in urea and in sodium dodecyl sulfate. Anti-apoprotein antisera were produced in rabbits. These antisera appeared to be monospecific on double-antibody immunoprecipitation of 125I-labeled apoproteins. In fasted animals granular staining of ApoA-I was noted in the supranuclear (Golgi) regions of epithelial cells in the top third of the villus. At 30 min, when fat droplets were seen in the supranuclear cytoplasm of the cells along the top two-thirds of the villus, intense ApoA-I staining surrounded droplets in the cytoplasm. At later times when epithelial cells and lamina propria both contained fat droplets, bright ApoA-I stain surrounded many droplets in the supranuclear cytoplasm of cells and in the lamina propria. Over the same period of time, tissue levels of ApoA-I rose 10-fold. The distribution and time-course of ApoB staining was nearly identical with that of ApoA-I. Concomitantly, tissue ApoB levels doubled. By contrast, in fasting rat intestine, staining of ARP was sparse, punctate, and confined to the lower quarter of the villus. After fat feeding, stained droplets were seen only in the lamina propria near the base of the villus even though abundant ARP was found in cells along most of this length of the villus. Stain was never seen to surround any droplets inside cells. Thus, ApoA-I and ApoB appeared to participate in the intracellular assemply of lipoproteins in gut, whereas ARP did not, although ARP was found within mucosal cells. Liver and intestine differed in their stainable contents of ApoA-I and ARP. Whereas intestine stained heavily for ApoA-I and lightly for ARP, liver stained heavily for ARP and lightly for ApoA-I. Both organs stained for ApoB. These findings suggest that there may be some quantitative "specialization" of the two organs which secrete lipoproteins.
Australian surgeons protest at health reforms
Authors: C. Zinn
Journal: BMJ (1996)

Australia's new federal health minister has confirmed that the health service faces cuts, despite an election pledge by the incoming coalition government to leave the Medicare health system untouched. The move comes as a surgeons' revolt has caused the new government to review controversial reforms to private health insurance introduced only a year ago.

The health minister, Dr Michael Wooldridge, said that the health budget, worth about £10bn, could not be exempt from the …
Customized Probability Models for Severe Sepsis: Correction and Clarification
Authors: Gordon D. Rubenfeld
Journal: JAMA (1995)

<h3>To the Editor.</h3> —In a recent issue of<i>JAMA</i>, Dr Le Gall and colleagues<sup>1</sup>contributed two intensive care risk-adjustment models, newly calibrated for severe sepsis, to the growing list of tools available for critical care outcome prediction. The fact that the original MPM and SAPS II models required recalibration to fit patients with severe sepsis raises a question about their use in generating risk-adjusted outcomes figures for critical care audit. This need for recalibration indicates that the original models inadequately account for the severity of illness of patients with severe sepsis. Can ICUs with high adjusted mortality rates based on the original versions of MPM and SAPS II defend their standard of care by pointing to their case mix of severely septic patients? On page 649, the authors ask, "[H]ow are the probability models useful for a therapeutic trial?" Presumably, the authors would have investigators report treatment efficacy from