tbuckley/cabot-search huggingface dataset:
Loss of a unique tumor antigen by cytotoxic T lymphocyte immunoselection from a 3-methylcholanthrene-induced mouse sarcoma reveals secondary unique and shared antigens.
Authors: M E Dudley, D C Roopenian
Journal: The Journal of Experimental Medicine (1996)

Most chemically induced tumors of mice express unique antigens that can be recognized by cytotoxic T lymphocytes (CTL) and thereby mediate tumor rejection. The number of different antigens expressed by a single tumor and their interplay during immunization and rejection are largely unexplored. We used CTL clones specific to individual tumor antigens to examine the number and distribution of CTL antigens expressed by cell lines derived from 3-methylcholanthrene-induced sarcomas of (C57BL/6J X SPRET/Ei)F1 mice. Each tumor cell line expressed one or more antigens that were unique, that is, not detected on cell lines from independent sarcomas. Immunoselection against an immunodominant antigen produced both major histocompatibility complex class I antigen and unique tumor antigen loss variants. Immunization of mice with antigen-negative immunoselected variants resulted in CTL that recognized additional antigens that were also expressed by the progenitor tumor. Some CTL recognized additional unique tumor antigen(s); other CTL recognized a shared antigen expressed not only by the immunizing cell line, but also by independent sarcoma cell lines and untransformed myoblastoid cell lines. CTL that recognized the shared antigen were also recovered from mice immunized in vivo with an untransformed myoblastoid cell line. These findings support a model of immunodominance among chemically induced tumor antigens in which shared antigens are masked by unique immunodominant antigens.
Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage.
Authors: Ning Li, Constantinos Sioutas, Arthur Cho, Debra Schmitz, Chandan Misra, Joan Sempf, Meiying Wang, Terry Oberley, John Froines, Andre Nel
Journal: Environmental Health Perspectives (2003)

The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria.
Medical Care, Medical Costs: The Search for a Health Insurance Policy
Authors: Roger W. Evans
Journal: JAMA (1987)

This book is a historical account of national health insurance in the United States, and yet it is more. Unlike his economist colleagues, many of whom have narrow views, few concrete suggestions, and unclear motivations, Fein is extremely successful in melding economics, politics, history, and sociology. He exhibits a social conscience that seems to evade a growing number of people who consider themselves "health economists." Fein offers us both a sensitive account of the development of health insurance and the basic elements of a plan of action for the future. For people unfamiliar with the origins of public and private insurance, this book proves particularly valuable. For example, Fein refers to the precedent-setting experience of the Baylor University Hospital in Dallas in 1929. At that time, much like today, there was concern over the growing number of unpaid patient-care bills. To reduce these, Dallas schoolteachers were the first to be
Low-Molecular-Weight Heparins
Authors: B Cosmi, J Hirsh
Journal: New England Journal of Medicine (1997)

Low molecular weight heparins are derived from unfractionated heparin by chemical or enzymatic depolymerization; as a result, the mean molecular weight of unfractionated heparin is reduced by about one third and its biochemical and pharmacologic properties are improved. Demonstrated advantages of low molecular weight heparins over unfractionated heparin are the greater bioavailability at low doses, the longer half-life, and the more predictable dose response, which allows for fixed doses to be administered without laboratory monitoring; a potential advantage is the reduced hemorrhagic-to-thrombotic ratio observed in experimental animals. Clinical studies in the prevention of venous thromboembolism have shown that whereas the advantages offered by low molecular weight heparin over unfractionated heparin are modest in general surgery, they are substantial when compared with these and other agents in orthopedic surgery. In addition, low molecular weight heparins are at at least as safe and effective as unfractionated heparin in the treatment of established deep vein thrombosis, but have the advantage that they can be administered once or twice daily without laboratory monitoring and can be used to treat uncomplicated deep venous thrombosis on outpatient basis.
Patients admitted as emergencies should see consultant in 12 hours, NCEPOD recommends
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

Nearly four in 10 patients who are admitted to hospital as emergencies receive suboptimal care that in many cases is detrimental to their outcome, a UK study has found.

The latest report from the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) says that such patients should be seen by a senior doctor within 12 hours and that standardised forms should be introduced across the NHS to make it clear that this has happened.

NCEPOD, an independent charity that aims to improve the delivery of health services, reviewed …
Electrical Propagation in Synthetic Ventricular Myocyte Strands From Germline Connexin43 Knockout Mice
Authors: Philippe Beauchamp, Cécile Choby, Thomas Desplantez, Karin de Peyer, Karen Green, Kathryn A. Yamada, Robert Weingart, Jeffrey E. Saffitz, André G. Kléber
Journal: Circulation Research (2004)

To characterize the role of connexin43 (Cx43) as a determinant of cardiac propagation, we synthesized strands and pairs of ventricular myocytes from germline Cx43 −/− mice. The amount of Cx43, Cx45, and Cx40 in gap junctions was analyzed by immunohistochemistry and confocal microscopy. Intercellular electrical conductance, g j , was measured by the dual-voltage clamp technique (DVC), and electrical propagation was assessed by multisite optical mapping of transmembrane potential using a voltage-sensitive dye. Compared with wild-type (Cx43 +/+ ) strands, immunoreactive signal for Cx43 was reduced by 46% in Cx43 +/− strands and was absent in Cx43 −/− strands. Cx45 signal was reduced by 46% in Cx43 +/− strands and to the limit of detection in Cx43 −/− strands, but total Cx45 protein levels measured in immunoblots of whole cell homogenates were equivalent in all genotypes. Cx40 was detected in ≈ 2% of myocytes. Intercellular conductance, g j , was reduced by 32% in Cx43 +/− cell pairs and by 96% in Cx43 −/− cell pairs. The symmetrical dependence of g j on transjunctional voltage and properties of single-channel recordings indicated that Cx45 was the only remaining connexin in Cx43 −/− cells. Propagation in Cx43 −/− strands was very slow (2.1 cm/s versus 52 cm/s in Cx43 +/+ ) and highly discontinuous, with simultaneous excitation within and long conduction delays (2 to 3 ms) between individual cells. Propagation was abolished by 1 mmol/L heptanol, indicating residual junctional coupling. In summary, knockout of Cx43 in ventricular myocytes leads to very slow conduction dependent on the presence of Cx45. Electrical field effect transmission does not contribute to propagation in synthetic strands.
Reversal of Tamoxifen Resistance of Human Breast Carcinomas In Vivo by Neutralizing Antibodies to Transforming Growth Factor- 
Authors: C. L. Arteaga, K. M. Koli, T. C. Dugger, R. Clarke
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Overexpression of transforming growth factor (TGF)-β has been reported in human breast carcinomas resistant to antiestrogen tamoxifen, but the role of TGF-β in this resistant phenotype is unclear. We investigated whether inhibition of TGF-β2, which is overexpressed in LCC2 tamoxifen-resistant human breast cancer cells, could modify antiestrogen resistance. METHODS: TGF-β2 expression was evaluated in LCC2 cells and tamoxifen-sensitive LCC1 cells by northern blot analysis. Secreted TGF-β activity was quantified by use of an 125 I-TGF-β competitive radioreceptor assay. Sensitivity to tamoxifen was measured in a soft agarose colony-forming assay and in a xenograft model in nude and beige/nude mice. Natural killer (NK) cell cytotoxicity was measured by 51 Cr release from LCC1 and LCC2 cell targets coincubated with human peripheral blood mononuclear cells. Decrease in TGF-β2 expression in LCC2 cells was achieved by treatment with antisense oligodeoxynucleotides and confirmed by TGF-β2 immunoblot analysis. RESULTS AND CONCLUSIONS: The proliferative response of LCC2 cells to tamoxifen in vitro was not altered by TGF-β neutralizing antibodies. However, established LCC2 tumors in nude mice treated with tamoxifen plus TGF-β antibodies failed to grow, whereas tumors treated with tamoxifen plus a control antibody continued to proliferate. This reversal of tamoxifen resistance by TGF-β antibodies did not occur in beige/nude mice, which lack NK-cell function, suggesting that immune mechanisms may be involved in the antitumor effects of tamoxifen. Antisense TGF-β2 oligodeoxynucleotides enhanced the NK sensitivity of LCC2 cells in the presence of tamoxifen. Finally, LCC1 tumors were markedly more sensitive to tamoxifen in NK-active than in NK-deficient mice. IMPLICATIONS: These data suggest that host NK function mediates, in part, the antitumor effect of tamoxifen and that TGF-β2 may abrogate this mechanism, thus contributing to tamoxifen resistance.
TWO CASES OF OCULAR DISEASE ASSOCIATED WITH PYORRHOEA ALVEOLARIS
Authors: S. G. Tibbles
Journal: BMJ (1914)

4= I9=IMC1A .Ut 5 5. Doubt rewnains as to tlhe,exact, route of infection: if infection was established in the accepted way-by means of aii infective stalk passing through the tympanic roof, tlhrough the dura, and tlleni along the course of tlle vessels of the pia mater to their free bifurcation beyond the deep surface of the grey miatter-the facts at least show how small may be the clhanges in these intermediate tissues for the establislhment of a large abscess in the temporo- spllenoidal lobe.I ani indebted to Dr. Percy Jakins for his kindness in allowinig ime to write an account of this case, and also to Dr.
International Comparison of Prevalence of Resistance to Antibiotics
Authors: Thomas F. O'Brien
Journal: JAMA (1978)

Prevalence of bacterial resistance to antibiotics was found to be substantially different in two separate regions of the world. The average percent resistant to individual antibiotics was nearly three times greater, and the percent of isolates resistant to six or more antibiotics 14 times greater among isolates at the Hôpital St Joseph in Paris than among those at the Peter Bent Brigham Hospital in Boston or at any of six US hospitals. Differences were not due to culture sampling or susceptibility testing methods used in the hospitals. Differences were nearly as great between isolates from patients recently admitted to the two hospitals, suggesting differences in the bacterial flora of their communities. Similar systematic comparisons of resistance prevalence in different parts of the world might help to define optimal antibiotic usage practices.
HPV Vaccination — More Answers, More Questions
Authors: George F. Sawaya, Karen Smith-McCune
Journal: New England Journal of Medicine (2007)

The availability of a “cancer vaccine” has elicited enormous enthusiasm from the medical community and the public, culminating in advocacy for mandatory vaccination against human papillomavirus (HPV) and a recommendation from the Centers for Disease Control and Prevention (CDC) that 30 million girls and women between the ages of 11 and 26 years in the United States be vaccinated.1 Previous reports2,3 showed a remarkable 100% efficacy of a quadrivalent vaccine targeting HPV types 6, 11, 16, and 18 on outcomes related to vaccine HPV types in women with no evidence of previous exposure to those types. Since HPV types . . .
Myelotoxicity in Cancer Patients Treated with Chemotherapy: Negative or Positive Prognostic Factor?
Authors: Angelos K. Koutras, Haralabos P. Kalofonos
Journal: Clinical Cancer Research (2008)

To the Editor : We read with great interest the article by Dubsky et al. ([1][1]) reporting on the prognostic role of anemia in premenopausal breast cancer patients receiving adjuvant cyclophosphamide/methotrexate/5-fluorouracil chemotherapy. In this study, the investigators showed that patients who
The novel tribody [(CD20)2xCD16] efficiently triggers effector cell-mediated lysis of malignant B cells
Authors: P Glorius, A Baerenwaldt, C Kellner, M Staudinger, M Dechant, M Stauch, F J Beurskens, P W H I Parren, J G J van de Winkel, T Valerius, A Humpe, R Repp, M Gramatzki, F Nimmerjahn, M Peipp
Journal: Leukemia (2012)
Abstract 2931: Zerumbone, a phytochemical from asian ginger inhibits JAK/STAT pathway, growth, apoptosis and increase taxol sensitivity of hormone refractory prostate cancer cells
Authors: Arup Chakraborty, Jessica Jorvig
Journal: Cancer Research (2011)

Abstract Objectives: Prostate cancer (PCa) is the most common cancer incidence and the second cancer death in U.S. men. In 2010, an estimated 217,730 new cases of PCa will be diagnosed, and 32,050 people will die from the disease in USA alone. IL-6 is strongly associated with malignant phenotype of PCa. IL-6 potently activates signal transducers and activators of transcription 3 (STAT3), a member of the family of latent cytoplasmic transcription factors that transmit signals from the cell membrane to the nucleus. STAT3 activation is known to promote tumor cell proliferation, survival, angiogenesis, and metastasis in vivo. In PCa, IL-6 strongly promotes mitogenic and angiogenic signaling through phosphorylation of Jak2 and then STAT3. Zerumbone, a relatively new anticancer component isolated from Zingiber zerumbet Smith has not been previously evaluated for prostate cancer. AIM: 1. Determine the activity and mechanism of zerumbone on hormone refractory prostate cancer cells. 2. Evaluate the combined effect of taxol (paclitaxel) with zerumbone in killing hormone-refractory prostate cancer cells. Methods and Results: The apoptosis and cytotoxic effect of zerumbone were determined by PARP cleavage (western blot) and MTS assay in DU145 cells. Zerumbone induced cytotoxicity with IC50 = 24 µM and significant PARP cleavage. Zerumbone (25 μM) potently inhibited constitutively activated Jak2/STAT3 phosphorylation and IL-6-stimulated STAT3 phosphorylation in DU145 cells as determined by western blots. Zerumbone (25 μM) also blocked expression of STAT3 dependent antiapoptotic proteins Bcl-xL. Interestingly, zerumbone even at a higher dose like 50uM has no effect on p65 subunit phosphorylation of NFkB and MAP kinase phosphorylation indicating a relative specificity. Next, we determined the combined effect of zerumbone and taxol in DU145 cells. Zerumbone as low as 10µM (4% cytotoxicity) synergistically increased cytotoxicity of taxol (5 nM, 7% cytotoxicity) to 25% cytotoxicity when combined. Zerumbone (10µM) also decreased IC50 of taxol from 12 nM to 7 nM. Conclusion: We showed that zerumbone is a potential therapeutic agent in prostate cancer by effectively blocking Jak2/STAT3-mediated signaling pathways and in addition, zerumbone combining with taxol based cytotoxic therapies may offer encouraging strategies for combating hormone-refractory prostate cancers. 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 2931. doi:10.1158/1538-7445.AM2011-2931
Respiratory recording from the oesophagus.
Authors: J S Robinson
Journal: BMJ (1974)

mathod of naintaining air cleanliness at a level of two to three colony-producing particles/100 ft3 (2-8 m3) air in the presence of four persons working as an active operting team in a relatively small enclosure.To equal this without complicating the installation it is necessary for surgeons to suffer what may at first seem oertain incoveniences, but it they appreciate the rationale behind the design they will very soon beome adapted to it.-Iam, etc.,
O8.09 * THE LEEDS LOW GRADE GLIOMA SERVICE 2010-13
Authors: R. Mathew, S. Spink, D. O'Hara, C. Loughrey, E. Wright, A. Chakrabarty, T. Patankar, J. MacMullen-Price, J. Goodden, P. Chumas
Journal: Neuro-Oncology (2014)

INTRODUCTION: Low grade gliomas have historically been overlooked, perhaps because of the challenges their often eloquent locations pose, and their perceived “good” prognosis relative to GBM. Although there are no randomised trials to date, the work of Duffau and Berger has shown that radical surgery can alter prognosis. We present our experience of managing presumed low grade gliomas through a multidisciplinary team. METHODS: Retrospective database review of patients undergoing surgery for presumed low grade glioma between January 2010-December 2013. Demographics, procedure type, histological diagnosis, morbidity, tumour location, progression-free (PFS) and overall survival (OS) were analysed. Results were statistically analysed by Kaplan-Meier and Log Rank (Cox Proportional Regression Hazard) Testing (p < 0.05). RESULTS: Patients (n = 100, 70% male, 30% female) underwent 115 procedures - 26 biopsies, 40 asleep and 49 awake craniotomies. Mean age 41 years (range 16-70 years). Tumour locations were predominantly frontal, peri-Rolandic and insular. The majority of patients had WHO Grade II astrocytomas. Morbidity, PFS and OS will be discussed. CONCLUSION: Sub-specialising in low grade glioma management is important. We have demonstrated, through ever-increasing experience and familiarity, that awake surgery is well tolerated, minimises morbidity and imbues confidence for better resection. Most importantly, our patients have benefited and appreciated the multidisciplinary approach, throughout their journey.
A talk that changed my practice: My latterday Demosthenes
Authors: C. Waddell
Journal: BMJ (1997)

Bernard Dixon's article—“Sorry, you won't be able to see this…” ( BMJ 1996;313:1407) had a familiar ring. My Road to Damascus came at a meeting such as his. We had dozed through the mutterings of serial grim speakers when a young lady took the platform. Her talk was understandable and to the point, her slides simple, her delivery polished yet relaxed. The effect was electric, instantly piercing our postprandial stupor.

Her influence on me was even more profound. Here was someone who was either a “natural speaker,” unlikely I thought, or one who had taken the trouble to acquire effective platform technique. The next week I found myself signing …
Non-insulin dependent diabetes and ischaemic heart disease.
Authors: J. T. Salonen
Journal: BMJ (1989)

the consensus view has indicated that the risk is slightly increased.Nevertheless, this view relates to the higher dose oral contraceptives and not to those currently used.There is no evidence that women who develop cardiovascular disease while using oral contraceptives are those whose metabolic responses are excessive.Nor is there any evidence suggesting a difference among different oral contraceptives in the inci- dence of cardiovascular disease.Some consider that oral contraceptives are not typical atherogenic risk factors at all4; occlusive coronary thrombosis may occur without appreciable atherogenic changes on angiography or histology of coronary vessels.Metabolic changes occur in all women using oral contra- ceptives but few of them develop cardiovascular disease.Nevertheless, it is sensible to follow general therapeutic principles by using formulations containing the lowest doses consistent with efficacy and acceptability.