tbuckley/cabot-search huggingface dataset:
Abstract 72: Targeting PI-3K/Akt signaling pathway by a PI-3K inhibitor BKM120 for radiosensitization in murine hepatocellular carcinoma.
Authors: Wei-Lin Liu, Melissa Gao, Ann-Lii Cheng, Jason Chia-Hsien Cheng
Journal: Cancer Research (2013)

Abstract Purpose: Tumor control of hepatocellular carcinoma (HCC) by radiotherapy remains unsatisfactory and the sub-lethal effect associates with secondary spread. Phosphatidylinositol 3-kinase (PI-3K)/Akt pathway plays a critical role in promoting cancer cell proliferation and inhibiting cell death. Elevated PI-3K/Akt activity is associated with increased cellular resistance to irradiation. Our aim was to assess if the inhibition of PI-3K/Akt activity by a PI-3K inhibitor, BKM120, contributes to the increasing sensitivity of murine liver cancer cells to irradiation. Methods and Materials: Murine HCC cell line (BNL) was used to evaluate the in vitro synergism of combining BKM120 with irradiation. Flow cytometry analyzed the cell cycle changes, whereas Western blot investigated the protein expressions after the combined treatment. Balb/c mice bearing ectopic BNL xenografts were treated with BKM120 and/or radiotherapy for the in vivo response. Results: Clonogenic cell survival decreased dose-dependently either with irradiation or BKM120 treatment. Synergisms were achieved in cells treated together with greater or equal than 0.5μM BKM120 and 2 Gy radiation. BKM120 pretreatment significantly inhibited radiation-induced Akt phosphorylation. Western blots of active caspase-3 and cleaved PARP revealed that the combined BKM120 and radiation treatment strongly increased the expression of these apoptotic markers in response to irradiation compared with radiation alone. In ectopic xenografts, pretreatment with BKM120 significantly enhanced the tumor-suppressive effect by radiotherapy. Conclusion: The apparent synergism between BKM120 and irradiation or effect of pre-treatment with BKM120 suggests an option to mitigate the activation of Akt by radiation, leading to increased cell apoptosis in murine liver cancer. These data suggest that the BKM120/radiation combination be a strategy worthy of further clinical trials. Citation Format: Wei-Lin Liu, Melissa Gao, Ann-Lii Cheng, Jason Chia-Hsien Cheng. Targeting PI-3K/Akt signaling pathway by a PI-3K inhibitor BKM120 for radiosensitization in murine hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 72. doi:10.1158/1538-7445.AM2013-72
Stroke: A Practical Guide to Management, by
Authors: M. M Brown
Journal: BMJ (1997)

C P Warlow, M S Dennis, J van Gijn, G J Hankey, P A G Sandercock, J M Bamford, J Wardlaw: Blackwell Science, £99.50, pp 664 ISBN 0 865 42874 3

The value of this book was obvious before I had even opened a single page. Clinicians and research fellows kept borrowing the book from my desk, and now every member of the department has acquired a copy.

This book's publication is timely. For many years, patients with stroke have suffered from lack of interest and poorly organised services. At worst, they have been relegated to a corner of a ward and neglected. The 664 pages of this book provide ample testimony to the active nature of modern stroke management. Many more doctors interested in stroke are required, and this book should whet …
Tuberculous Meningitis
Authors: S. J. Shane, Clifford Riley
Journal: New England Journal of Medicine (1953)

THREE factors contribute to the unsatisfactory results that have been obtained in the treatmerit of tuberculous meningitis during the streptomycin era: mechanical obstruction of the circulatory channels of the cerebrospinal fluid by tuberculous exudate; the inability of antimicrobial agents to penetrate avascular tissue and reach tubercle bacilli buried therein; and the necessity of prolonged intrathecal therapy that may, of itself, produce local obstructions in the subarachnoid space by repeated irritation and trauma of the meninges. It is generally conceded that all the newer measures devised to counteract these effects — namely, anticoagulants,1 intrathecal injection of tuberculin,2 , 3 fibrinolytic enzymes 4 , 5 and neurosurgical . . .
BMA opens discussion on NHS financing Junior doctors should claim for intensive rotas BMA issues guidance on treating prisoners Cooperation welcomed between NHS and universities Timetable announced for cancer services framework
Authors: L. Beecham
Journal: BMJ (1996)

# BMA opens discussion on NHS financing {#article-title-2}

The BMA's health policy and economic research unit has published a new discussion document which looks at future demand for health care and the availability and use of resources. Financing the NHS does not necessarily represent BMA policy but is designed to provoke a debate.

The report says that the NHS would benefit from more funding and it remains the BMA's policy that the service is underfunded. But as there is no “right” level of funding for the NHS it is difficult to quantify the amount of additional funding; how much to spend is a political decision.

One option is to find extra funding from sources other than general taxation but the introduction of patient charges would affect the comprehensiveness of the NHS and some patients might opt to meet charges through private insurance. If patients increasingly chose to opt out of the system altogether public support for the NHS might decline.

The unit says that it is not the case that the demand for health care will necessarily outstrip available resources. Work is needed on methods of forecasting future demand and need for health care and how that might be met before a conclusion could be reached that the NHS could not meet the demands made on it. Savings could be made through greater efficiency and more effective use of resources in several areas. For example, the financial burden of prescription charges could be shared more equally and the system of charging reviewed. Revenue lost by changing the system of patient charges for …
The Final Maturation of at Least Some Single-Positive Cd4hiThymocytes Does Not Require T Cell Receptor–Major Histocompatibility Complex Contact
Authors: Ruben Dyall, Janko Nikolić-Z̆ugić
Journal: The Journal of Experimental Medicine (1999)

The majority ( approximately 70%) of postselection CD4(+) single-positive (SP) thymocytes are CD8(lo)CD4(hi). These cells express very low levels of CD8, undetectable by flow cytofluorimetric (FCM) analysis, but sufficiently high to allow purification by panning. Unlike the fully mature CD8(-)CD4(hi) thymocytes, which account for the remaining approximately 30% of the SP CD4(+) thymocytes, CD8(lo)CD4(hi) cells are functionally immature and short-lived unless they receive an unidentified maturation signal from the thymus. In this study, we tested the hypothesis that this signal is provided by a T cell receptor (TCR)-major histocompatibility complex (MHC) class II interaction. Using intrathymic transfer, we show that the immature CD8(lo)CD4(hi) cells could complete their intrathymic maturation and populate the peripheral lymphoid organs in the absence of MHC class II (and class I) molecules. Furthermore, in mice devoid of class II (and class I) molecules, the progeny of CD8(lo)CD4(hi) cells was long-lived and functionally reactive to allogeneic class II molecules, although their numbers in the spleen and the mesenteric lymph node were approximately 40-50% lower than those in class II(+) mice 5 mo after transfer. Control experiments demonstrated that the surviving cells did not originate from the contaminating mature thymocytes. These results demonstrate that the final maturation, proliferation, and peripheral survival (up to 5 mo) of at least some postselection CD4(+) SP cells do not require the TCR-MHC class II interaction. They also indicate that the TCR-MHC class II interaction(s) required for the intrathymic development of long-lived CD4(+) SP cells occurs before the CD4(hi) SP stage of development.
Coexistence of Three Variants Involving Two Different Fusion Partners of ROS1 Including a Novel Variant of ROS1 Fusions in Lung Adenocarcinoma: A Case Report
Authors: Weijing Cai, Wei Li, Shengxiang Ren, Limou Zheng, Xuefei Li, Caicun Zhou
Journal: Journal of Thoracic Oncology (2014)
Social Workers and General Practice
Authors: J. W. Evans, T. W. I Lovel, K. K. Eaton
Journal: BMJ (1969)

Weekly case conferences have been found valuable in the management of problem families in a general practice in a new town. These are attended by health visitors, mental welfare and child care officers, welfare officers, and psychiatric social workers, as well as by the family doctors. The conferences are a quick and easy way of exchanging important information and leading to rapid decisions.
THE METABOLISM OF ANBHOGENS BY SEBACEOUS GLANDS*
Authors: J. A. MILNE
Journal: British Journal of Dermatology (1969)

Journal Article THE METABOLISM OF ANBHOGENS BY SEBACEOUS GLANDS Get access J. A. MILNE J. A. MILNE Department of Dermatology, University of Glasgow Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue s2, 1 March 1969, Pages 23–28, https://doi.org/10.1111/j.1365-2133.1969.tb12842.x Published: 01 March 1969
216 OXALIPLATIN-ASSOCIATED VASCULAR LIVER INJURY IN METASTATIC COLORECTAL CANCER: PATHOLOGIC EXAMINATION LIMITED TO SINUSOIDAL DILATION MISSES THE MAJORITY OF PARENCHYMAL INJURIES
Authors: M. Guindi, P. Ryan, S. Nanji, A. Pollett, M. Moore, C.-A. Moulton, S. Gallinger
Journal: Journal of Hepatology (2010)
Swimming goggles causing severe eye injuries.
Authors: F Jonasson
Journal: BMJ (1977)

Swimming goggles causing severe eye injuriesIn 1976 in this hospital, which serves a population of about 1 5 million, we have seen three cases of severe eye injuries caused by a popular type of swimming goggle.The children affected were pulling the goggles forward in order to clear them of steam, when they slipped out of their wet fingers. Case reportsCase 1-A 1 3-year-old girl was hit in the right eye by a swimming goggle.On examination half an hour later the visual acuity of the injured eye was bare perception of light, but she was seeing 6 5 with the other eye.There was a penetrating corneosclcral injury, with some vitreous loss, iridodialysis, ruptured sphincter pupillae, flat anterior chamber, and dislocated lens.There was no view of the fundus because of hyphaema.The wound was sutured under general anasthesia the same day.The eye was treated with a pad, and topical cycloplegics and antibiotics, and later steroids, but remained irritable for several weeks.Some 13 weeks after the injury the eye had settled well and the wound had healed (see figure).The visual acuity at this stage was counting fingers at one foot, owing to dense cataract.Future treatment may improve this result, but some visual loss wrill be permanent.k-.Case 1.The injured eye 13 weeks after the accident.Case 2-A 13-year-old boy was hit in the right eye by a swimming goggle.On examination an hour later the visual acuity of this eye was 1/36 and in
Phase 1 Study of TLK286 (Telcyta) Administered Weekly in Advanced Malignancies
Authors: Lee S. Rosen, Bernadette Laxa, Leny Boulos, Laura Wiggins, James G. Keck, Anneliese J. Jameson, Richard Parra, Kiran Patel, Gail L. Brown
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To determine the dose-limiting toxicities, maximum tolerated dose, and pharmacokinetics of TLK286, a novel cancer prodrug, administered weekly. Patients and Methods: Patients with advanced malignancies were treated with TLK286 administered weekly by i.v. infusion over 30 min in escalating doses 60–960 mg/m2. A treatment cycle was defined as 3 weekly treatments. Patients underwent tumor assessments on day 43, and those patients receiving clinical benefit continued on treatment until disease progression or unacceptable toxicity. Safety was assessed by the WHO criteria. Results: Thirty-seven patients received 111 cycles of TLK286 at eight dose levels (median, 3 cycles; range, 1–16 cycles). In this study, TLK286 given weekly at 960 mg/m2 was well tolerated without dose-limiting toxicities. TLK286-related toxicities included grade 1–2 nausea and vomiting, fatigue and anemia. Nine of 31 evaluable patients continued therapy beyond day 43 and received a median of 5 cycles (range of 3–16 cycles) and experienced durable stable disease or minor tumor regression. Pharmacokinetic characteristics of TLK286 are described by an optimized two-compartment model. Mild to moderate renal or hepatic organ dysfunction did not impact the elimination of TLK286. Conclusions: TLK286 administered weekly at doses up to 960 mg/m2 were well tolerated. The safety and antitumor activity observed in a broad range of cancer types supports Phase 2 disease-specific investigations of TLK286 given weekly at 960 mg/m2.
Laparoscopy and hysterosalpingography as tests of tubal patency.
Authors: S Khunda
Journal: BMJ (1977)

bosis did not improve as formerly and residual pain, though not troublesome, still remained in the following June.The above case seems to be the first in which ancrod has been given in repeated courses.Antibody formation, investigated by radioimmunoassay after the fifth course, was negligible.Hydrocortisone may have played some part in this because it is known that corticosteroids can suppress antibody forma- tion under some conditions.'iIn this patient the most useful benefit appears to be in reducing the incidence of, thromboembolism after the ancrod therapy.Our evidence for this is based on the number of thromboembolic incidents pre-and post-ancrod administration.Though this point has not been established with certainty, it could, if confirmed, prove a valuable addition to our anticoagulant therapy.
Unusual reaction to trimethoprim in combined therapy.
Authors: G M Halpern
Journal: BMJ (1972)

increased serum F.D.P. levels in women with clinically significant menorrhagia, as compared with those in women without abnormal menstrual symptoms.Further studies being undertaken indicate that raised serum F.D.P. levels found in women with menorrhagia are often associated with in- creased levels of fibrin monomer complexes in the blood.Thus raised serum F.D.P. levels in women complaining of menorrhagia may be a manifestation of exaggerated intravascular microcoagulation associated with secondary fibrinolytic activity.-Iam, etc.,
Oncogenic osteomalacia presenting as a crippling illness in a young man
Authors: Melvin Khee-Shing Leow, Laniyati Hamijoyo, Huiling Liew, Umapathi Thirugnanam, Mathew Hern Wang Cheng, Kelvin S H Loke, Michael Song Kim Teo, Khoon Leong Chuah, Hiok Hee Chng
Journal: The Lancet (2014)
Abstract 239: A novel multimeric protein scaffold stimulates apoptotic signaling through TRAILR2
Authors: Hong Chen, Jeffery Swers, Ivan Inigo, Rosa A. Carrasco, Luba Grinberg, Lin Wang, Ching-Ching Leow, Zhan Xiao, Herren Wu, Bob Hollingsworth, Manuel Baca, David A. Tice
Journal: Cancer Research (2012)

Abstract TRAILR2 (DR5, TNFRSF10B) is a member of the TNF-receptor superfamily that mediates programmed cell death following stimulation with its ligand. Binding of homotrimeric ligand TRAIL to TRAILR2 induces oligomerization of the receptors and triggers the apoptotic pathway through induction of caspases. Although TRAILR2 is found to be expressed in a number of normal cell types it is routinely found at high levels in many cancer types. Since TRAIL has been shown to preferentially induce apoptosis in cancer cells versus normal cells, several TRAIL receptor agonists including monoclonal antibodies as well as the ligand itself, are currently in clinical development. Here, we describe a novel protein scaffold (Tn3) based on a fibronectin type-III domain from the protein Tenascin that was engineered to specifically agonize TRAILR2. Connecting TRAILR2-binding Tn3 domains together significantly improved the in vitro potency of the molecule in several cancer cell models. For example, a hexameric TRAILR2-binding Tn3 construct has an EC50 of 0.5 pM in a 72 hour cell viability assay with Colo-205 cells. This is approximately 2 logs better than TRAIL. Furthermore, a subset of TRAIL-resistant cancer cell lines derived from multiple tissues of origin is sensitive to the multimeric Tn3. The improved potency over TRAIL was demonstrated in colorectal cancer xenograft models. In addition, tumor regression was also observed at doses as low as 0.3 mg/kg. These results suggest that a multimeric Tn3 protein scaffold targeting TRAILR2 has more potent anti-tumor activity in vitro and in vivo compared than the natural ligand. 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 239. doi:1538-7445.AM2012-239
Successful pregnancy in severe chronic renal failure not requiring dialysis.
Authors: R A Coward, N P Mallick, D W Warrell, D Grimes, H Kirkpatrick
Journal: BMJ (1980)

for a patient with renal failure.Lowered blood viscosity, which usually accompanies the anaemia of chronic renal failure, may prevent sluggish mesenteric blood flow in other patients undergoing dialysis who are subjected to similar haemodynamic stresses.Digitalis should be considered as a possible cause when evaluating obscure abdominal pain in patients undergoing haemodialysis, who may benefit-and be rendered free of pain-when digitalis is withheld.
A common single-nucleotide variant in T is strongly associated with chordoma
Authors: Nischalan Pillay, Vincent Plagnol, Patrick S Tarpey, Samira B Lobo, Nadège Presneau, Karoly Szuhai, Dina Halai, Fitim Berisha, Stephen R Cannon, Simon Mead, Dalia Kasperaviciute, Jutta Palmen, Philippa J Talmud, Lars-Gunnar Kindblom, M Fernanda Amary, Roberto Tirabosco, Adrienne M Flanagan
Journal: Nature Genetics (2012)
Down-regulation of the forkhead transcription factor Foxp1 is required for monocyte differentiation and macrophage function
Authors: Can Shi, Masashi Sakuma, Toshifumi Mooroka, Alison Liscoe, Huiyun Gao, Kevin J. Croce, Arjun Sharma, David Kaplan, David R. Greaves, Yunmei Wang, Daniel I. Simon
Journal: Blood (2008)
Amniotic membrane transplantation for partial and total limbal stem cell deficiency secondary to chemical burn
Authors: José Alvaro Pereira Gomes, Myrna Serapião dos Santos, Marcelo Carvalho Cunha, Vera L.úcia Degaspare Mascaro, Jeison de Nadai Barros, Luciene Barbosa de Sousa
Journal: Ophthalmology (2003)
Hypothermia in a Patient with Carcinoid Syndrome during Treatment with Parachlorophenylalanine
Authors: Ashok B. Vaidya, Robert J. Levine
Journal: New England Journal of Medicine (1971)

PARA-CHLOROPHENYLALANINE (Fenclonine, PCP) is a drug that reduces levels of serotonin (5-hydroxytryptamine) in the tissues of animals and of man by inhibition of the rate-limiting enzyme in its biosynthesis, tryptophan hydroxylase. Recently, it has been used experimentally in the therapy of patients with carcinoid syndrome.1 , 2 The clinical manifestation of carcinoid syndrome most likely to be relieved by PCP therapy is the one that is thought to be mediated by serotonin — that is, diarrhea. Other humoral manifestations of carcinoid syndrome have been either shown or assumed to be mediated by other factors.3 The biochemical effect of PCP administration in man . . .
The Epidemiology and Clinical Aspects of the Hemolytic Uremic Syndrome in Minnesota
Authors: Dawn L. Martin, Kristine L. MacDonald, Karen E. White, John T. Soler, Michael T. Osterholm
Journal: New England Journal of Medicine (1990)

The frequency of the hemolytic uremic syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, is increasing. Although Escherichia coli serotype 0157:H7 has been implicated as a causative agent, more information is needed about the basic epidemiology and clinical aspects of this syndrome.
Amateur boxing and risk of chronic traumatic brain injury: systematic review of observational studies
Authors: Mike Loosemore, Charles H Knowles, Greg P Whyte
Journal: BMJ (2007)

To evaluate the risk of chronic traumatic brain injury from amateur boxing.Secondary research performed by combination of sport physicians and clinical academics. DESIGN, DATA SOURCES, AND METHODS: Systematic review of observational studies in which chronic traumatic brain injury was defined as any abnormality on clinical neurological examination, psychometric testing, neuroimaging studies, and electroencephalography. Studies were identified through database (1950 to date) and bibliographic searches without language restrictions. Two reviewers extracted study characteristics, quality, and data, with adherence to a protocol developed from a widely recommended method for systematic review of observational studies (MOOSE).36 papers had relevant extractable data (from a detailed evaluation of 93 studies of 943 identified from the initial search). Quality of evidence was generally poor. The best quality studies were those with a cohort design and those that used psychometric tests. These yielded the most negative results: only four of 17 (24%) better quality studies found any indication of chronic traumatic brain injury in a minority of boxers studied.There is no strong evidence to associate chronic traumatic brain injury with amateur boxing.
Pressure to keep up macho image might be behind rise in suicides among men
Authors: T. Pitts-Tucker
Journal: BMJ (2012)

Men struggling to maintain a “gold standard” of masculinity and prizing power and control may be behind the rise in suicides among those in their 30s, 40s, and 50s, says a new report from the Samaritans.1

Relationship breakdown, loneliness, alcohol misuse, and emotional illiteracy all contribute to a rise in suicide rates among middle aged men, especially among those from disadvantaged backgrounds, it says. The charity is calling on governments across Europe (but particularly in the UK and Ireland), health services, and voluntary services to recognise suicide as a health and social inequality. 

Figures from the Office for National Statistics show that suicides in …
Interaction of Tomato Lycopene and Ketosamine against Rat Prostate Tumorigenesis
Authors: Valeri V. Mossine, Pankaj Chopra, Thomas P. Mawhinney
Journal: Cancer Research (2008)

Prior investigations on the beneficial effect of dietary processed tomato products and lycopene on prostate cancer risk suggested that lycopene may require the presence of other constituents to exert its chemopreventive potential. We investigated whether ketosamines, a group of carbohydrate derivatives present in dehydrated tomato products, may interact with lycopene against prostate tumorigenesis. One ketosamine, FruHis, strongly synergized with lycopene against proliferation of the highly metastatic rat prostate adenocarcinoma MAT-LyLu cell line in vitro. The FruHis/lycopene combination significantly inhibited in vivo tumor formation by MAT-LyLu cells in syngeneic Copenhagen rats. Energy-balanced diets, supplemented with tomato paste, tomato powder, or tomato paste plus FruHis, were fed to Wistar-Unilever rats (n = 20 per group) treated with N-nitroso-N-methylurea and testosterone to induce prostate carcinogenesis. Survival from carcinogenesis was lowest in the control group (median survival time, 40 weeks) and highest in the group fed the tomato paste/FruHis diet (51 weeks; P = 0.004, versus control). The proportions of dying rats with macroscopic prostate tumors in the control, tomato paste, tomato powder, and tomato paste/FruHis groups were 63% (12 of 19), 39% (5 of 13), 43% (6 of 14), and 18% (2 of 11), respectively. FruHis completely blocked DNA oxidative degradation at >250 micromol/L in vitro, whereas neither ascorbate nor phenolic antioxidants from tomato were effective protectors in this assay. FruHis, therefore, may exert tumor-preventive effect through its antioxidant activity and interaction with lycopene.