tbuckley/cabot-search huggingface dataset:
Abstract 334: Mcl-1 protects prostate cancer cells from chemotherapy-induced DNA damage
Authors: Carlos Perez-Stable, Teresita Reiner, Alicia de las Pozas, Ricardo Parrondo
Journal: Cancer Research (2014)

Abstract Mcl-1 (myeloid cell leukemia sequence 1 [Bcl2-related]) is predominantly localized in the cytoplasm and protects cells from apoptosis by blocking mitochondrial outer membrane permeabilization. There is evidence that nuclear localization of Mcl-1 has pleiotropic effects independent of apoptosis, including functional roles in DNA damage response. Mcl-1 is highly expressed in castration-resistant prostate cancer (CRPC), resulting in resistance to apoptosis and association with poor prognosis. The role of nuclear Mcl-1 in mediating sensitivity to chemotherapy-induced DNA damage and apoptotic cell death in prostate cancer (PCa) is not known. The novel antimitotic agent ENMD-1198 is a more stable and potent derivative of 2-methoxyestradiol (2ME2). We confirmed that 1198 was a more potent inhibitor of androgen-dependent LNCaP and castration-resistant DU145 and PC3 PCa cell viability compared to 2ME2 and induced apoptotic cell death in docetaxel-resistant PC3 cells that overexpress the multi-drug resistance protein (MDR). The ability of 1198 to increase the proteasomal-mediated degradation of Mcl-1 correlated with enhanced apoptotic cell death and shRNA knockdown of Mcl-1 further sensitized LNCaP and PC3 cells to 1198-mediated cell death. We then showed that the combination of 1198 with betulinic acid (BA, a plant-derived small molecule that can increase apoptosis specifically in cancer but not in normal cells) reduced nuclear Mcl-1, increased a pro-death Mcl-1 isoform, increased gamma histone 2AX (marker of DNA damage), and enhanced apoptotic cell death in human PC3 CRPC cells. In the TRAMP mouse model of PCa, the 1198 (75 mg/kg) + BA (10 mg/kg) combination significantly reduced PCa weights compared to 1198, BA alone, and vehicle controls. However, the reduced PCa weights between the 1198 + BA combination and BA alone was more associated with decreased Mcl-1 and increased gamma-H2AX (DNA damage) immunostaining compared to cleaved caspase-3 (apoptosis), CD31(angiogenesis), or Ki67 (proliferation). Furthermore, our results showed that blocking the DNA damage response signaling pathway with an ATM kinase (KU55933) or DNA-PK (NU7441) inhibitor lowered apoptotic cell death induced by the 1198 + BA combination in PC3 cells. Overall, our results demonstrate that nuclear Mcl-1 has an important role in protecting PCa cells from DNA damage and that agents such as 1198 and BA that reduce total/nuclear Mcl-1 and increase pro-death Mcl-1 isoforms will sensitize PCa cells to antimitotic DNA damaging agents. Citation Format: Carlos Perez-Stable, Teresita Reiner, Alicia de las Pozas, Ricardo Parrondo. Mcl-1 protects prostate cancer cells from chemotherapy-induced DNA damage. [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 334. doi:10.1158/1538-7445.AM2014-334
Dendritic cells from patients with rheumatoid arthritis lack the interleukin 13 mediated increase of Fc RII expression, which has clear functional consequences
Authors: T R D J Radstake
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Dendritic cell (DC) function is largely tailored by Fc gamma receptors (FcγR) and is critical for every immune response. <b>Objective:</b> To compare interleukin (IL) 13 mediated regulation of FcγRII and its related DC function between healthy controls and patients with rheumatoid arthritis (RA). <b>Methods:</b> DC were derived from peripheral blood mononuclear cells according to standardised protocols. FcγRI, II, and III expression and DC phenotype were assessed by FACS analysis. The level of cytokine production and chemokine expression was measured by Luminex and real time quantitative polymerase chain reaction techniques. Antigen uptake capacity was studied by DC fluorescent heat aggregated immunoglobulins and FACS analysis. <b>Results:</b> Replacement of IL4 by IL13 clearly increased the expression of FcγRII on DC from healthy controls (CDC), but had no effect on DC from patients with RA (RADC). The lower production of inflammatory mediators by IL13 CDC upon FcγR mediated triggering suggests that IL13 induces up regulation of specifically FcγRII. RADC co-cultured with IL4 already displayed an inhibitory DC phenotype, but this inhibitory phenotype was not augmented by the addition of IL13. The defective FcγRII regulation was further substantiated by the finding that IL13 CDC increased antigen uptake capacity, whereas IL13 RADC did not. <b>Conclusion:</b> IL13 regulates the expression of inhibitory FcγRII in normal subjects but not in RA, potentially resulting in a chronic proinflammatory immune reaction in RA. Unravelling the underlying mechanisms of FcγRII regulation might lead to new therapeutic targets in RA.
Population and Sampling
Authors: Sidney Shindell
Journal: JAMA (1963)

A STATISTIC IS simply a number which describes, characterizes, or summarizes an occurrence. As an example, one might note that the preceding sentence contains 13 words consisting of 76 letters, eight of which are<i>a</i>'s and eight,<i>s</i>'s. These are statistics obtained by simple enumeration. It's true they tell us little about the substance of the sentence, but they do tend to describe some of its components. If we were particularly interested in dissecting sentences, we could take these data and state that there is an average of 5.85 letters per word, 21.05% of the letters are either<i>a</i>'s or<i>s</i>'s, 69.23% of the words contain either an<i>a</i>or an<i>s</i>, and the ratio of letters to spaces is 6.33 to 1. The mere fact that these are statistics does not make them either useful or valid. If one were a manufacturer of printing materials,
Effect of farming environment on atopic diseases in mongolia
Authors: A. Viinanen, S. Munhbayarlah, T. Zevgee, T. Tseregmaa, L. Narantsetseg, T. Naidansuren, T. Lkhagwasuren, M. Koskenvuo, H. Helenius, E.O. Terho
Journal: Journal of Allergy and Clinical Immunology (2003)
Aerosols and Aerosol Propellants in Asthma
Authors: Alex Silverglade
Journal: JAMA (1971)

<h3>To the Editor.—</h3> A recent issue ofThe Journal(<b>214:</b>81, 1970) carried both a report of a study by Taylor and Harris and an editorial entitled "Cardiac Toxicity of Aerosol Propellants." The authors attempt the conclusion that the fluorinated hydrocarbon propellants used in bronchodilator aerosols are related to a claimed increase in sudden, unexpected deaths from asthma during the last decade. As a service to those many physicians and their patients who find pressurized bronchodilating aerosols helpful, we feel it our responsibility to question the conclusions stated by Taylor and Harris and the data used in their support. The conclusions appear unwarranted and have no application to the use of pressurized aerosols under the supervision of a physician. The positive correlation between an increased number of deaths from asthma and an increase in the number of pressurized aerosols distributed to patients appears to apply principally in England and Wales.
Undernotification of whooping cough
Authors: M. R Evans
Journal: BMJ (1995)

EDITOR,—Dougls Jenkinson is to be commended for his painstaking documentation of whooping cough in general practice.1 He points out that the incidence observed in his practice between 1977 and 1992 was six times the rate of notifications in England and Wales over the same period and highlights an appreciable number of cases among adults. This prompted me to examine notification data on whooping cough in Cardiff.

During 1984-92 there were 1034 notifications of whooping cough …
NHS needs another 65bn by 2030-31, think tank says
Authors: N. Hawkes
Journal: BMJ (2015)

The NHS in England will need to find another £65bn (€85bn; $98bn) by 2030-31 to balance the books, even if it maintains its current, higher than usual productivity gains, a new analysis from the think tank the Health Foundation shows.1

The gap could be closed if productivity gains rose to 2-3% a year and governments undertook to increase funding by 1.5% a year in real terms from 2014-15 onwards. But that would demand productivity improvements at a rate two to three times the long run average and funding to increase at more than twice the rate achieved in the current parliament.

NHS England said in its Five Year Forward View published in October that a total of £8bn of additional money was needed to sustain the existing pattern of services up to 2020-21, and the chancellor of the …
Blood transfusions may increase the risk of death in critically ill patients
Authors: Deborah Josefson
Journal: BMJ (2002)

Doctors who give critically ill patients blood transfusions to correct their anaemia may be doing those patients a disservice, a new study has found.

In a two part, multicentre international study involving 3543 patients drawn from 146 intensive care units across western Europe, patients who received packed red blood cell transfusions had a higher death rate than their similarly ill counterparts who did not receive transfusions ( JAMA 2002;288:1499-507).

Patients who were given a transfusion had significantly higher mortality in intensive care and overall mortality than patients who weren't, with 18.5% of patients in the transfusion group dying within 28 days, compared to 10.1% in the non-transfusion group (χ2=50.1; P< 0.001).

When patients were matched for disease severity this disparity still held, with a 28 day mortality of 23% in the transfusion group and 17.1% in the non-transfusion group (χ2=5.1; P=0.02).

In seriously ill patients anaemia …
Loss of ARF Sensitizes Transgenic BRAFV600E Mice to UV-Induced Melanoma via Suppression of XPC
Authors: Chi Luo, Jinghao Sheng, Miaofen G. Hu, Frank G. Haluska, Rutao Cui, Zhengping Xu, Philip N. Tsichlis, Guo-Fu Hu, Philip W. Hinds
Journal: Cancer Research (2013)

Abstract Both genetic mutations and UV irradiation (UVR) can predispose individuals to melanoma. Although BRAFV600E is the most prevalent oncogene in melanoma, the BRAFV600E mutant is not sufficient to induce tumors in vivo. Mutation at the CDKN2A locus is another melanoma-predisposing event that can disrupt the function of both p16INK4a and ARF. Numerous studies have focused on the role of p16INK4a in melanoma, but the involvement of ARF, a well-known p53 activator, is still controversial. Using a transgenic BRAFV600E mouse model previously generated in our laboratory, we report that loss of ARF is able to enhance spontaneous melanoma formation and cause profound sensitivity to neonatal UVB exposure. Mechanistically, BRAFV600E and ARF deletion synergize to inhibit nucleotide excision repair by epigenetically repressing XPC and inhibiting the E2F4/DP1 complex. We suggest that the deletion of ARF promotes melanomagenesis not by abrogating p53 activation but by acting in concert with BRAFV600E to increase the load of DNA damage caused by UVR. Cancer Res; 73(14); 4337–48. ©2013 AACR.
A prospective study of oesophageal function in patients with normal coronary angiograms and controls with angina
Authors: R A Cooke, A Anggiansah, J B Chambers, W J Owen
Journal: Gut (1998)

Aims —To compare the incidence of oesophageal abnormalities and their correlation with chest pain in patients with normal coronary angiograms, and in controls with angina. Patients —Sixty one patients with normal coronary angiograms (NCA group) referred to a single cardiac centre between March 1990 and April 1991; 25 matched controls with confirmed coronary artery disease (CAD group). Setting —Cardiac referral centre and oesophageal function testing laboratory. Main outcome measures —Oesophageal manometry, provocation tests, and 24 hour ambulatory pH monitoring. Results —Simultaneous contractions were more common (6.7% versus 0.8%, p&lt;0.01), and the duration of peristaltic contractions was longer (2.9 versus 2.4 seconds, p&lt;0.01) in the NCA group than in the CAD group. There were no group differences in the amplitude of peristaltic contractions, and none had nutcracker oesophagus. Ten (16%) patients with NCA and no patients with CAD had diffuse spasm (p=0.03). Twenty one (34%) patients with NCA, and five (20%) patients with CAD had abnormal gastro-oesophageal reflux (p&gt;0.05). There was no significant difference between the groups in the number of patients whose pain was temporally related to pH events. Particular chest pain characteristics, or the presence of additional oesophageal symptoms, were not predictive of an oesophageal abnormality. Conclusion —Oesophageal function tests commonly implicate the oesophagus as a source of pain in patients with normal coronary angiograms. With the exception of simultaneous contractions during manometry however, the incidence of abnormalities and in particular the correlation of pH events with chest pain are as common in patients with normal coronary angiograms as in controls with angina. The oesophagus may often be an unrecognised source of pain in both groups of patients.
The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices
Authors: Alice Zwerling, Marcel A. Behr, Aman Verma, Timothy F. Brewer, Dick Menzies, Madhukar Pai
Journal: PLoS Medicine (2011)

Madhu Pai and colleagues introduce the BCG World Atlas, an open access, user friendly Web site for TB clinicians to discern global BCG vaccination policies and practices and improve the care of their patients.
Corrigendum to “Factor VII activating protease (FSAP) exerts anti-inflammatory and anti-fibrotic effects in liver fibrosis in mice and men” [J Hepatol 2013;58:104–111]
Authors: Erawan Borkham-Kamphorst, Henning W. Zimmermann, Nikolaus Gassler, Ute Bissels, Andreas Bosio, Frank Tacke, Ralf Weiskirchen, Sandip M. Kanse
Journal: Journal of Hepatology (2014)
Cuts in aid are linked to Ebola crisis, say MPs
Authors: A. Gulland
Journal: BMJ (2014)

The United Kingdom must reverse its cuts to funding of health sector support in Sierra Leone and Liberia, two of the countries devastated by the current Ebola outbreak, a group of MPs have said.

A report by the International Development Committee about UK aid to Sierra Leone and Liberia has shown that the UK will cut its total financial support to the two countries by nearly a fifth, from £85.9m (€110m; $139m) in 2013-14 to £71.4m in 2015-16.1

Malcolm Bruce, chair of the committee, said, “The scale of the Ebola crisis now unfolding in Sierra Leone and Liberia …
Vascular Disorders of the Upper Extremity
Authors: John J. Bergan
Journal: JAMA (1990)

When the first edition of this volume appeared in 1983,I was disappointed by its somewhat thin coverage of a very important topic. Fortunately, the editor did not let the concept die of inanition, but instead added eight contributors and six chapters, thus producing a volume that borders on being a textbook. Adding a chapter on complications of vascular access allowed Eric Wilson to expand upon some ideas expressed in his textbook on this subject of vascular access. John Porter's chapter, the best in the first edition, has been totally rewritten by the author and his colleagues at the Clinical Research Center of the University of Oregon's School of Medicine, Portland. Here, the diagnosis and treatment of vasospastic disease are upgraded and updated and the reference list has been more than doubled. Even the editor has reassigned his topics so that the initial chapter on arterial and venous occlusive disorders now
Aberrantly glycosylated IgA1 induces mesangial cells to produce platelet-activating factor that mediates nephrin loss in cultured podocytes
Authors: Rosanna Coppo, Valentina Fonsato, Sabrina Balegno, Emanuela Ricotti, Elisa Loiacono, Roberta Camilla, Licia Peruzzi, Alessandro Amore, Benedetta Bussolati, Giovanni Camussi
Journal: Kidney International (2009)
Cellular FLIP is expressed in cardiomyocytes and down-regulated in TUNEL-positive grafted cardiac tissues
Authors: Toshio Imanishi, Charles E. Murry, Hans Reinecke, Takuzo Hano, Ichiro Nishio, W.Conrad Liles, Leonard Hofsta, Koanhoi Kim, Kevin D. O'Brien, Stephen M. Schwartz, David K.M. Han
Journal: Cardiovascular Research (2000)

c-FLIP is a natural homologue of caspase 8, and may antagonize activation of death pathways mediated by FADD. c-FLIP is highly expressed in the heart, and a recent report suggests that c-FLIP may protect against certain types of myocyte death. The present study was designed to define the expression patterns of c-FLIP in the heart.The expression pattern of c-FLIP in end-stage human hearts, and rat cardiomyocyte grafting models was analyzed by in situ hybridization, immunohistochemistry and TUNEL assay. In addition, to determine whether Fas-dependent pathway is active in cardiomyocytes in vitro, we examined whether activated monocytes can kill neonatal cardiomyocytes in a co-culture system.c-FLIP mRNA and protein were abundantly expressed in normal cardiomyocytes from failing human heart. In animal models, c-FLIP protein was absent in TUNEL-positive grafted cardiomyocytes. Double staining demonstrated that c-FLIP-positive cells rarely had fragmented DNA, while TUNEL-positive cells rarely contained c-FLIP. Finally, activated monocytes induced death of neonatal rat cardiomyocytes via the Fas/FasL system.Loss of c-FLIP expression correlates with cardiomyocyte cell death. We hypothesize that diminished c-FLIP expression may predispose cardiomyocytes to apoptotic death.
XDR-TB in South Africa: Back to TB Sanatoria Perhaps?
Authors: Ramalitse Sakoane
Journal: PLoS Medicine (2007)

It is only about 25 years since the abolition or abandonment of TB sanatoria in South Africa.It is likely that there are people in South Africa who are familiar with the idea of isolation of TB patients from the general public emanating from the era of TB sanatoria, and it is conceivable that they are likely to be understanding of the reasons that were used to keep patients there during their treatment.These people could help to make the idea of isolation in sanatoria acceptable again to the general public.Anyway, the TB sanatoria of this era were rightfully regarded as hospitals, as indeed they were, and I cannot see why modern day sanatoria should be viewed any differently.Granted, with the likelihood that the patients detained in these envisaged isolation areas may be more likely to die than be discharged, it will be a mammoth task to convince the "detainees" to stay there or their families to allow them to be kept there, especially if they are minors or the elderly infi rm.It is a tough call but it is worth a try.
The Dilemma of Competency for Trial and Mental Illness
Authors: Paul D. Lipsitt
Journal: New England Journal of Medicine (1970)

UNDER statutory provisions in all states a court may request an opinion from a state mental hospital about whether a person accused of a crime possesses the required mental capacity to be tried. The common-law standard for such capacity includes an understanding of the nature and object of the proceedings against him, an ability to comprehend his own circumstances in reference to these proceedings, and an ability to communicate with his attorneys so that they can aid him in the development of his defense.A recent decision of the Supreme Judicial Court of Massachusetts could lead to radical changes in . . .
Uptake of In-111 Leukocytes in Soft Tissue Metastases from Adenocarcinoma of Lung
Authors: MARIE LOUISE HAYMON, HAROLD R. NEELY
Journal: Clinical Nuclear Medicine (1992)

In-111 oxine-labeled leukocytes have been demonstrated to have relatively high sensitivity and specificity for acute infection. False positives have been reported secondary to noninfectious inflammatory disease, hematoma, infarct, cerebral vascular accident, fracture, and a variety of tumors. A case of In-111 leukocyte uptake by gluteal metastases from an adenocarcinoma of the lung is reported.
Software for screening to assess risk of Down's syndrome.
Authors: T M Reynolds
Journal: BMJ (1991)

Software for screening to assess risk of Down's syndrome SIR,-The brief reference to screening for Down's syndrome in the ABC of antenatal care' is perhaps indicative of the few centres currently offering screening to assess the risk of Down's syndrome despite the considerable benefits that the screen offers.The delays in introducing the screen are possibly due to uncertainty about the analytes required to perform an effective screen.a Feto- protein and human chorionic gonadotrophin are well established, but there is still dispute over whether unconjugated oestriol should be included.2'Furthermore, other potential screen- ing variables have been suggested, including preg- nancy specific f1 glycoprotein (SP-1),4 ratio of biparietal diameter to length of femur,s and maternal urea resistant neutrophil alkaline phosphatase activity.6A further cause of delay in introducing the screen is the poor availability of commercial software to calculate the risk.In Gwent and South Glamorgan screening using a fetoprotein and human chorionic gonadotrophin has been offered with considerable success for the past 16 months.
Cancer of the Breast
Authors: Michael B. Shimkin
Journal: JAMA (1963)

Cancer of the breast is the most common sex-specific neoplastic entity in the United States. It is estimated that about 50,000 new cases are diagnosed annually, and approximately 25,000 deaths are attributed to breast cancer among the 91 million females of the US population. The lifetime risk of breast cancer for a woman is 5.5 percent. This means that in one of every 18 women breast cancer will develop during her anticipated 72 yr of life. <h3>Statistical Data</h3> One of the striking characteristics of breast cancer in the United States has been the very uniform<i>mortality</i>rate recorded during the past 30 or more years.<sup>1,2</sup>In terms of absolute numbers and gross mortality rates, there has been a steady increase. Thus, in 1930, there were 11,000 deaths and a crude annual death rate of 18 per 100,000 females, whereas, by 1958, there were 22,500 deaths and a
Advance Directives and Withdrawal of Dialysis in the United States, Germany, and Japan
Authors: Ashwini R. Sehgal, Christian Weisheit, Yasuhiko Miura, Martin Butzlaff, Rita Kielstein, Yoshio Taguchi
Journal: JAMA (1996)

To determine the role of advance directives in decisions to withdraw chronic dialysis in the United States, Germany, and Japan.Survey by questionnaire.Seventy-two American, 87 German, and 73 Japanese nephrologists.Each nephrologist's total number of (1) dialysis patients, (2) cases of withdrawal of dialysis, (3) patients with advance directives, and (4) uses of such directives. Nephrologists also stated whether they would continue or stop dialysis in 8 hypothetical cases.American, German, and Japanese nephrologists reported withdrawing dialysis for 5.1%, 1.6%, and 0.7% of their patients in the last year, respectively. Thirty percent of American patients had advance directives, and such directives were used in decision making for 3.2% of all patients. Only 0.3% of German and Japanese patients had advance directives, and such directives were used in decision making for 0.09% of patients. When asked about a hypothetical mentally incompetent patient whose family requests withdrawal of dialysis, American nephrologists were much more likely to stop dialysis in the absence of an advance directive than German or Japanese nephrologists. However, almost all nephrologists from the 3 countries would stop dialysis when a family request to withdraw was supported by a patient advance directive.There is a high prevalence of advance directives among American dialysis patients, and such directives frequently play a role in decision making. German and Japanese nephrologists appear willing to follow advance directives, but the low prevalence of such directives limits the frequency of their use.