tbuckley/cabot-search huggingface dataset:
Smokeless Tobacco and Cancer: The Epidemiologic Evidence
Authors: D. M. Winn
Journal: CA A Cancer Journal for Clinicians (1988)

In summary, evidence from human populations has shown that smokeless tobacco users have risks of cancer several times higher than that of nonsmokers. Smokeless tobacco is very strongly related to cancers of the cheek and gums, locations typically in direct contact with the tobacco. The association is evident in studies in the US and Scandinavia and also in Asia, where the chewing of quids containing tobacco and other ingredients is strongly related to the region's high rates of oral cancer. Reports on health effects date back to the 18th century and the evidence is consistent, with most investigators reporting positive findings. Dose-response relationships--increasing risk with increasing use--are also evident in several studies. Finally, preliminary work on cancers in other anatomic sites suggests that smokeless tobacco may also be related to other upper digestive tract cancers. With the exception of one group of medical scientists who described the relationship as only an "association," expert consensus conferences and committees in both the US and France have agreed that the evidence from clinical, epidemiologic, and carcinogenesis studies supports a causal relationship between the use of smokeless tobacco and oral cancer in humans. These expert groups include the International Agency for Research on Cancer (1984), the National Institutes of Health Consensus Conference on the Health Implications of Smokeless Tobacco Use (1986), and the Surgeon General's Advisory Committee on the Health Consequences of Using Smokeless Tobacco (1986).(ABSTRACT TRUNCATED AT 250 WORDS)
<i>In Vivo</i>Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB)
Authors: De-Gang Song, Qunrui Ye, Carmine Carpenito, Mathilde Poussin, Li-Ping Wang, Chunyan Ji, Mariangela Figini, Carl H. June, George Coukos, Daniel J. Powell
Journal: Cancer Research (2011)

Human T cells engineered to express a chimeric antigen receptor (CAR) specific for folate receptor-α (FRα) have shown robust antitumor activity against epithelial cancers in vitro but not in the clinic because of their inability to persist and home to tumor in vivo. In this study, CARs were constructed containing a FRα-specific scFv (MOv19) coupled to the T-cell receptor CD3ζ chain signaling module alone (MOv19-ζ) or in combination with the CD137 (4-1BB) costimulatory motif in tandem (MOv19-BBζ). Primary human T cells transduced to express conventional MOv19-ζ or costimulated MOv19-BBζ CARs secreted various proinflammatory cytokines, and exerted cytotoxic function when cocultured with FRα(+) tumor cells in vitro. However, only transfer of human T cells expressing the costimulated MOv19-BBζ CAR mediated tumor regression in immunodeficient mice bearing large, established FRα(+) human cancer. MOv19-BBζ CAR T-cell infusion mediated tumor regression in models of metastatic intraperitoneal, subcutaneous, and lung-involved human ovarian cancer. Importantly, tumor response was associated with the selective survival and tumor localization of human T cells in vivo and was only observed in mice receiving costimulated MOv19-BBζ CAR T cells. T-cell persistence and antitumor activity were primarily antigen-driven; however, antigen-independent CD137 signaling by CAR improved T-cell persistence but not antitumor activity in vivo. Our results show that anti-FRα CAR outfitted with CD137 costimulatory signaling in tandem overcome issues of T-cell persistence and tumor localization that limit the conventional FRα T-cell targeting strategy to provide potent antitumor activity in vivo.
Should atypical lymphocytes and plasma cells in well patients with psoriasis on cyclosporin cause concern?
Authors: B.D. Edwards, F.W. Ballardie, D.J. Morris, J.B. O'Driscoll, R.J.G. Chalmers
Journal: British Journal of Dermatology (1993)

Journal Article Should atypical lymphocytes and plasma cells in well patients with psoriasis on cyclosporin cause concern? Get access B.D. Edwards, B.D. Edwards Department of Renal Medicine Manchester Royal Infirmary Manchester M13 9WL, U.K. Search for other works by this author on: Oxford Academic Google Scholar F.W. Ballardie, F.W. Ballardie Department of Renal Medicine Manchester Royal Infirmary Manchester M13 9WL, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.J. Morris, D.J. Morris The Virology Unit, University of Manchester, Manchester M13 9PT, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.B. O'Driscoll, J.B. O'Driscoll Skin Hospital Salford M60 9EP, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.J.G. Chalmers R.J.G. Chalmers Skin Hospital Salford M60 9EP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 2, 1 August 1993, Page 222, https://doi.org/10.1111/j.1365-2133.1993.tb03534.x Published: 01 August 1993
Insulin and Risk of Cardiovascular Disease
Authors: J. B. Ruige, W. J. J. Assendelft, J. M. Dekker, P. J. Kostense, R. J. Heine, L. M. Bouter
Journal: Circulation (1998)

Our purposes were to estimate the strength of the longitudinal relationship between hyperinsulinemia and cardiovascular diseases (CVD) from the available literature and to identify study characteristics that modify this relationship.Articles were identified by means of a MEDLINE and Embase search and citation tracking. Eligible studies were prospective population-based cohort studies and nested case-control studies on the relationship between, on the one hand, fasting or nonfasting insulin levels and, on the other hand, myocardial infarction, death from coronary heart disease, and/or ECG abnormalities. Data were extracted pertaining to insulin measurements, type of outcome studied, adjustment for confounding, sex, mean age of the study population, follow-up period, insulin assay, and ethnic background (white or nonwhite). Associations of insulin and CVD were reexpressed in a uniform manner, an estimate of relative risk (RR) and 95% CI, to be used in meta-regression analyses. Twelve of 17 potentially eligible articles provided sufficient information. Overall, a weak positive association was found. The meta-analysis resulted in an estimated summary RR (95% CI) of 1.18 (1.08 to 1.29) for differences in insulin level, equivalent to the difference between the 75th and the 25th percentiles of the general population in The Netherlands. Ethnic background and type of insulin assay modified the relationship between insulin and CVD with borderline significance.Hyperinsulinemia is a weak risk indicator for the occurrence of CVD. The relationship between hyperinsulinemia and CVD was modified by ethnic background and by the type of insulin assay involved.
Hyponatraemia and catatonic stupor after taking "ecstasy".
Authors: D L Maxwell, M I Polkey, J A Henry
Journal: BMJ (1993)

placed to address the problem of retrospective cohorts of unvaccinated patients.This initiative in South Glamorgan has provoked similar action in other areas (D Periera Gray, personal communication).This study has implications for surgeons, who should ensure that all patients are vaccinated and that discharge letters are accurate, and for general practitioners, who should ensure adequate follow up and be alert to the possibility of pneumococcal sepsis.
Young age as a prognostic factor in cervical cancer: analysis of population based data from 10 022 cases
Authors: C. A Meanwell, K. A Kelly, S. Wilson, C. Roginski, C. Woodman, R. Griffiths, G. Blackledge
Journal: BMJ (1988)

The effect of young age on survival in cervical cancer is not fully known, although evidence has suggested that it is a poor prognostic factor and that young patients should therefore be treated differently from older patients. All 10 022 cases of invasive cervical cancer in the west Midlands during 1957-81, which comprised 10% of the cases in England and Wales, were analysed to determine the prognostic effect of age. Univariate analysis showed a median survival time of 54 months for all cases, with survival rates at five years of 69% for patients aged under 40 and 45% for those aged 40 or older (χ<sub>1</sub><sup>2</sup> (log rank)=331·4; p&lt;0·0001). This difference remained significant after stratification for stage (χ<sub>1</sub><sup>2</sup> (log rank)=7·1; p=0·008). Cox regression analysis with nine covariables, including age and year of registration, reaffirmed the importance of conventional prognostic factors such as stage of disease, size of tumour, state of lymph nodes, and differentiation of the tumour. After allowance was made for the effects of other prognostic factors young age was found to be a small but significant favourable factor that did not change during the period of the study. Estimated survival distributions obtained from the Cox model showed that for women presenting with the common characteristics associated with stage Ib disease who were treated with radical radiotherapy the survival rate at five years fell non-linearly from 71% in the group aged 25-29 to 65% in the group aged 65-69. Young age alone is not a reason to alter existing policies for treatment for patients with invasive cervical cancer.
Abstract P3-10-01: Quantitative Gene Expression Analysis in a Large Cohort of Estrogen-Receptor Positive Breast Cancers: Characterization of the Tumor Profiles in Younger Patients (≥40 yrs) and in Older Patients (≥70 yrs)
Authors: S Shak, FL Baehner, M Stein, I Chen, C Yoshizawa, D Watson, SM. Swain
Journal: Cancer Research (2010)

Abstract Background: Previous studies have identified differences in the presentation, biology, and behavior of breast cancer as a function of patient age. To directly study breast cancer tumor profiles as a function of patient age, we examined the Oncotype DX Recurrence Score (RS) and the expression of ER, PR, and proliferation-related genes in a large cohort of invasive breast cancers. Material and Methods: All tumor specimens successfully examined in the Genomic Health laboratory from June 2004 through March 2010 were included. Standard RS testing was performed. Quantitative expression for ER, PR, HER2, and the five proliferation genes, CCNB1, Ki-67, MYBL2, STK15, and Survivin, was measured by quantitative RT-PCR on a scale from 2 to 15 (relative to reference genes), where a one unit increment is associated with an approximate 2-fold increase in expression. The proliferation index (PI), a component of the RS, was calculated as the average of the expression of the five proliferation genes. ER negative tumors (ER&amp;lt;6.5) were excluded. Means and medians were calculated; with this very large sample size, all comparisons between groups were statistically significant (P&amp;lt;0.05). Results: Among the 145,236 breast cancers, 5,794 (4.0%) were ≥40 yrs, 117,740 (81.1%) were 41 — 69 yrs, and 21,702 (14.9%) were ≥70 yrs. A wide range of RS (0 to &amp;gt;80) was observed in all age groups. The mean RS, median RS, and proportion of patients in each of the standard RS groups are shown in the Table. The average RS is slightly higher in the younger age group and lower in the older age group. Similarly, the proportion of high RS tumors is higher in the younger age group and lower in the older age group. However, many young patients are in the low RS group and many older patients are in the high RS group. Small differences in the mean expression of quantitative ER, quantitative PR, and the Proliferation Index were observed. Younger patients had lower mean ER, higher mean PR and higher proliferation. Discussion: Among estrogen receptor positive breast cancers, the average RS is slightly higher in younger patients and is slightly lower in older patients. However, it is notable that a wide range of RS was observed in all age groups; many young patients are in the low RS group and many older patients are in the high RS group. These results demonstrate the importance of standardized quantitative measurement of gene expression on a continuous scale, and suggest that, for ER positive breast cancer, age per se does not predict individual tumor biology. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-01.
Direct Comparison of Different Stem Cell Types and Subpopulations Reveals Superior Paracrine Potency and Myocardial Repair Efficacy With Cardiosphere-Derived Cells
Authors: Tao-Sheng Li, Ke Cheng, Konstantinos Malliaras, Rachel Ruckdeschel Smith, Yiqiang Zhang, Baiming Sun, Noriko Matsushita, Agnieszka Blusztajn, John Terrovitis, Hideo Kusuoka, Linda Marbán, Eduardo Marbán
Journal: Journal of the American College of Cardiology (2012)
Noise in Medical Helicopters
Authors: Daniel C. Garner
Journal: JAMA (1991)

To The Editor.  —Hunt et al1have effectively demonstrated the inability of medical flight crews to assess breath sounds during helicopter medical evacuation operations. With over 1400 hours as an air force helicopter pilot and flight surgeon, I can verify that any medical activity requiring auditory acuity is nearly impossible in a helicopter in flight. This includes assessment of breath sounds, bowel sounds, blood pressure determinations by auscultation, and even verbal communications with patients whose ability to yell loudly is impaired.  The assumption that a helicopter is a flying critical care unit is false. Without detracting one iota from the professional skill of flight nurses and emergency medical technicians who perform most admirably under difficult conditions, air transport is still basically a scoop and run operation. All critically ill patients, especially those who are intubated, should have breath sounds assessed immediately before and after transport. Ground medical personnel in
Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia
Authors: Christie M. Ballantyne, John Houri, Alberto Notarbartolo, Lorenzo Melani, Leslie J. Lipka, Ramachandran Suresh, Steven Sun, Alexandre P. LeBeaut, Philip T. Sager, Enrico P. Veltri
Journal: Circulation (2003)

Despite the established efficacy of statins, many patients do not achieve recommended LDL cholesterol (LDL-C) goals. Contributing factors may be inadequate dosing, increased risk for adverse effects with high-dose monotherapy, and increased potential for intolerance and adverse effects with combinations of available agents.In a double-blind study, 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides < or =350 mg/dL were randomly assigned to receive 1 of the following for 12 weeks: ezetimibe (10 mg/d); atorvastatin (10, 20, 40, or 80 mg/d); ezetimibe (10 mg) plus atorvastatin (10, 20, 40, or 80 mg/d); or placebo. The primary efficacy end point was percentage reduction in LDL-C for pooled ezetimibe plus atorvastatin versus pooled atorvastatin treatment groups. Ezetimibe plus atorvastatin significantly improved LDL-C, HDL cholesterol (HDL-C), triglycerides, total cholesterol:HDL-C, and high-sensitivity C-reactive protein (hs-CRP) compared with atorvastatin alone (P<0.01). Coadministration of ezetimibe provided a significant additional 12% LDL-C reduction, 3% HDL-C increase, 8% triglyceride reduction, and 10% hs-CRP reduction versus atorvastatin alone. Ezetimibe plus atorvastatin provided LDL-C reductions of 50% to 60%, triglyceride reductions of 30% to 40%, and HDL-C increases of 5% to 9%, depending on atorvastatin dose. LDL-C reductions with ezetimibe plus 10 mg atorvastatin (50%) and 80 mg atorvastatin alone (51%) were similar.Ezetimibe plus atorvastatin was well tolerated, with a safety profile similar to atorvastatin alone and to placebo. When coadministered with atorvastatin, ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia.
The participation of proliferative keratinocytes in the preimmune response to sensitizing agents
Authors: None Little, None Metcalfe, None Haycock, None Healy, None Gawkrodger, None Mac Neil
Journal: British Journal of Dermatology (1998)

The aims of this study were to investigate whether keratinocytes are capable of playing a direct preimmune role in the pathophysiology of allergic contact dermatitis (ACD) and to examine to what extent the degree of differentiation might influence this. We measured the ability of sensitizing agents to up-regulate intercellular adhesion molecule 1 (ICAM-1) expression in cultured normal human keratinocytes (NHK) and in the transformed human keratinocyte HaCaT cell line. In proliferative HaCaT cells, following a 24 h exposure, nickel compounds, para-phenylenediamine (pPD) and 1-chloro-2,4-dinitrobenzene produced a concentration-dependent up-regulation of ICAM-1 expression without reducing cell viability, while K2Cr2O7 led to ICAM-1 up-regulation at cytotoxic concentrations, and CrCl3 was without effect. In NHK, NiSO4 and pPD induced ICAM-1 expression to a significantly greater extent in proliferative cells than in differentiated cells, where involucrin expression was measured to assess the differentiation state. NiSO4- or pPD-pretreatment of proliferative HaCaT cells enhanced T-cell binding, which was abolished by neutralizing antibodies to ICAM-1 or CD18. Our investigations concerning the involvement of oxidative stress in the induction of ICAM-1 expression in response to sensitizing agents were inconclusive. The oxidizing agents FeCl3 and H2O2 up-regulated ICAM-1 expression in HaCaT cells but there was no clear relationship between the ability of agents to induce ICAM-1 expression and their ability to alter the levels of reduced glutathione. Although pPD increased interleukin-1α release from NHK, this cytokine was not capable of inducing ICAM-1 expression in NHK. Tumour necrosis factor-α, which does induce ICAM-1 expression in NHK, was not detected in response to pPD, arguing against an autocrine pathway of ICAM-1 induction in response to pPD. In summary, we report the direct interaction of sensitizing agents with keratinocytes leading to the generation of immune signals, particularly by proliferative keratinocytes, suggesting an active role for the proliferative keratinocyte in the pathophysiology of ACD.
PD08-11: Targeting Porcupine, a Critical Node for Wnt Signalling in Cancer.
Authors: J Liu, S Pan, F Sun, S Kasibhatla, A Schuller, A Li, C Li, X Cui, T Wang, M Villarroel, M Mclaughlin, W Sellers, A Boral, J Harris
Journal: Cancer Research (2011)

Abstract Wnt ligands were first discovered based upon their transforming activity in the setting of mouse mammary tumor virus (MMTV) induced mammary carcinogenesis. Wnt signalling is required for normal development of the mammary gland and dysregulated Wnt signalling is implicated in cancers of the breast and colon among others. Furthermore, lobular breast cancer commonly shows reduced expression of E-cadherin that can lead to release of membrane-bound b-catenin into the cytoplasm and potentially increase Wnt signalling in the presence of Wnt ligand. To date, however, low-molecular weight therapeutic inhibitors of the Wnt pathway have not been developed. We set out to discover key points of intervention in the Wnt pathway and to develop low molecular weight inhibitors against such nodes. To this end, a cellular high-throughput screen for small molecule inhibitors of the Wnt pathway was performed. In this assay, cells secreting Wnt3a were co-cultured with cells harboring a luciferase reporter driven by the Wnt/beta-catenin responsive elements. Potent and specific Wnt pathway inhibitors were identified from this screen. To discern the mechanism of action of these compounds, a lead inhibitor was radiolabeled and used to probe protein targets in a radioligand binding assay. From these assays a candidate target of the inhibitor was identified as Porcupine. Porcupine is a membrane bound O-acyltransferase enzyme that is required for and dedicated to palmitoylating Wnt ligands, a necessary step in the process of Wnt ligand secretion. Inhibition of Porcupine blocks Wnt dependent activities, including LRP6 phosphorylation and the expression of Wnt target genes, such as Axin2, which in turn reduces the growth of cancer cells dependent on autocrine or paracrine Wnt signaling. A selective and orally bioavailable Porcupine inhibitor (NVP-LGK974) that inhibits the Wnt pathway in vitro and in vivo was developed through medicinal chemistry optimization. In preclinical evaluation, the compound robustly suppressed Wnt pathway signaling in vivo resulting in tumor regression in a murine breast cancer model driven by MMTV-Wnt1. In addition, this inhibitor attenuated tumor growth as a single agent and induced tumor regression in combination with Taxol in a human primary breast tumor model. Wnt signalling is also important for the maintenance and homeostasis of normal tissues including gastrointestinal tissue. However, preclinical rodent efficacy models of cancer demonstrate that intermittent pharmacological inhibition of Porcupine can be effective against the tumor and mostly spare the normal gastrointestinal tissue, with an acceptable therapeutic window. A Phase I dose escalation study of NVP-LGK974 in patients with melanoma and lobular breast cancer to evaluate the safety, tolerability, PK, and PD properties is expected to begin this year. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-11.
The Oil Treatment of Pellagra
Authors: J. W. Torbett
Journal: JAMA (1910)

<h3>To the Editor:—</h3> Much has been written about pellagra, its symptoms, etc., but very little has been written about its successful treatment; some physicians with large experience still believe that no pellagra patient in this country has recovered. Within the past 4 years I have had 16 cases, 7 being so far advanced that little or no treatment was given and the patients all soon died. The other 9 were all without a doubt true cases with all the classic symptoms of diarrhea, offensive stools, dermatitis, red tongue, insomnia, etc., and were treated by the oil method, which no one else so far as I know has used in such cases, with the following results: The first 3 patients were treated about 4 years ago by means of petroleum emulsion, sulphocarbolates for the diarrhea and Morton wave and static sparks for the insomnia and nervousness. One, a woman, gained 30
1002-84 Eplerenone normalizes diastolic relaxation and extracellular matrix accumulation in aged rats with myocardial infarction
Authors: Serge Masson, Lidia Staszewsky, Giorgio Annoni, Eleonora Carlo, Beatrice Arosio, Monica Salio, Carmen Calabresi, Fabio Fiordaliso, Elena Martinoli, Antonio Bai, Amy E Rudolph, Roberto Latini
Journal: Journal of the American College of Cardiology (2004)
Successful treatment of infertility due to polycystic ovary disease using a combination of luteinising hormone releasing hormone agonist and low dosage menotrophin.
Authors: M Armitage, T Wilkin, K Dewbury
Journal: BMJ (1987)

detection.This study showed that questioning patients about their drinking habits was not perceived by doctors as a priority.Many patients who drink to excess therefore remain unidentified and a major reducible cause of disease and death is ignored.We thank the staff of York District Hospital for their cooperation in this work.The study was
Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B
Authors: Grace Lai-Hung Wong, Henry Lik-Yuen Chan, Catherine Ka-Yan Wong, Calvin Leung, Candace Yim Chan, Patricia Po-Lai Ho, Vivian Chi-Yee Chung, Zhan Cham-Yan Chan, Yee-Kit Tse, Angel Mei-Ling Chim, Tina Kit-Ting Lau, Vincent Wai-Sun Wong
Journal: Journal of Hepatology (2013)