tbuckley/cabot-search huggingface dataset:
Abstract P1-02-04: The Influence of Matriptase-2 on Angiogenesis and Tumour Growth <i>In Vivo.</i>
Authors: SL Webb, AJ Sanders, MD Mason, WG. Jiang
Journal: Cancer Research (2010)

Abstract Background: Metastasis is a key part of cancer progression and angiogenesis plays a large role in the ability of cancer cells to spread around the body and in the progressive growth of the primary tumour. Matriptase-2 is a cell surface serine protease believed to have implications in cancer metastasis. The current study aims to assess the importance of matriptase-2 in angiogenesis and tumour growth, using in vitro and in vivo models. Methods: Matriptase-2 was over-expressed in the HECV endothelial cell line, previously displaying minimal matriptase-2 expression, through the transfection of a mammalian expression construct containing the full coding sequence for matriptase-2. Following verification of forced expression, the cellular effects of matriptase-2 were examined using a number of in vitro cell models. The effect of matriptase-2 over-expression was also examined in in vivo mouse models by co-delivery of endothelial cells and tumour cells. Results: Matriptase-2 significantly reduced the motility (46.47±16.18 vs 10.93±2.80 p=&amp;lt;0.01) of the HECV cells and their ability to form tubule structures (23841.60±744.75 vs 9817.80±933.85 p=0.01) in an in vitro angiogenesis Matrigel tubule formation model. Matriptase-2 was found to have no significant effect on the growth (691.52±100.17 vs 763.50±91.43 p=0.110) and cell-matrix adhesion of the HECV cells (64.20±8.70 vs 57.42±4.50 p=0.530). However, the in vivo studies showed a reduction in tumour growth and development following co-injection of cancer cells with endothelial cells over-expressing matriptase-2 compared to co-injection with control endothelial cells. The sizes of tumours in two tumour models were: 70.99±19.52mm3 for tumour cells with control endothelial cells vs 0.17±0.10 mm3 for tumours with Matriptase-2 over-expression endothelial cells, p=&amp;lt;0.01; and 80.41±18.31 mm3 vs 43.12±20.33 mm3 p=0.08, in the other tumour model. Conclusion: Matriptase-2 appears to negatively influence angiogenesis through its inhibitory effect on endothelial cell motility and tubule formation. This is corroborated by the reduction of tumour growth, in vivo. Together this data suggests that matriptase-2 has an important role in the control of angiogenesis and tumour development. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-04.
Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in the rat ileum: Effects of bile acids and lovastatin
Authors: Lien B. Nguyen, Sarah Shefer, Gerald Salen, Gene C. Ness, Ashok Batta, Indu R. Chowdhary, Eva Paroulek, Susan Hauser
Journal: Metabolism (1994)
Factors affecting the response to clomiphene therapy.
Authors: D Ferriman, A W Purdie, M Corns
Journal: BMJ (1967)

of evolutionary-or, if you like, teleological-thinking so necessary to the study of biology.For in biology, because of Darwinian selection, we are entitled to ask not only " What ?" and " How ?" as in physical science, but also " Why ?" and "What for ?" Because in clinical science we pride ourselves that we are building up medical knowledge we should not complacently assume that we are always doing it the right way, or making the best use of resources which in any society are bound to be limited.We should remember with John Aubrey that " Pride has been one of the greatest stoppers of the Advancement of Learning."The defects may be only part of a temporary chapter in the history of medicine, and a symptom of a more widespread ailment.For man has put most of his efforts into improving the material state of society (and perfecting the engines of war), and has given scant attention to the ills of the mind of man and woman, and the study of their behaviour in health and disease and in society.I know that I have spoken some heresies.If they are rather disturbing ones, my personal researches lead me to believe that the defences of the clinical scientists will be equal to them.Perhaps for another few years.Nevertheless, with Harvey, " I fear lest I have mankind at large " (or at any rate some of my colleagues) " for my enemies, so much doth wont and custom become a second nature.Doctrine once sown strikes deep its root . . . .Still the die is cast and my trust is in the love of truth and the candour of cultivated minds."
A Glimpse Backstage
Authors: David Shih Wu
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The human p53 gene mutated at position 249per se is not sufficient to immortalize human liver cells
Authors: Claudia Schleger, Roger Becker, Franz Oesch, Pablo Steinberg
Journal: Hepatology (1999)

A particular point mutation of the tumor suppressor gene p53, namely a G→T transversion at the third base of codon 249, is frequently detected in primary hepatocellular carcinomas from patients living in areas where the levels of dietary exposure to aflatoxin B 1 and the rates of infection with the hepatitis B virus are very high. Very recently, a nontumorigenic liver epithelial cell line (HACL–1) with a finite life–span and expressing a number of hepatocyte–specific markers was established from a human hepatocellular adenoma in our laboratory. To analyze the role of mutated p53 in the immortalization of human liver cells, we transfected HACL–1 cells with an expression vector containing a human p53 complementary DNA mutated at the third base of codon 249 and analyzed the consequences of this gene transfer on the growth properties of this cell line. HACL–1 cells transfected with mutant p53 showed no increase in their life–span (when compared with HACL–1 cells transfected with the antibiotic resistance gene alone) and did not grow in soft agar, whereas transfection of wild–type p53 into HACL–1 cells led to a proliferation stop. Thus, these results strongly support the view that the mutation at codon 249 of the p53 gene may serve as a fingerprint for aflatoxin B 1 –induced hepatocellular carcinomas, but is not, by itself, sufficient to immortalize human liver cells.
Mecillinam in enteric fever.
Authors: B K Mandal, A G Ironside, J Brennand
Journal: BMJ (1979)

Twelve consecutive patients with enteric fever entered a trial of 14 days9 treatment with mecillinam. Only three patients became afebrile within three days; four continued unimproved with fever and toxaemia for seven to nine days, when treatment was changed to chloramphenicol with good results. In one case the fever did not settle until the 13th day, and five days later the patient had a clinical relapse. Although all organisms recovered were fully sensitive to mecillinam, this drug is not an effective or consistent treatment for enteric fever.
Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis
Authors: Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine S. Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia M. Lachel, Karen Deffenbacher, Timothy C. Greiner, Julie M. Vose, Sharathkumar Bhagavathi, Louis M. Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita M. Braziel, James R. Cook, Raymond R. Tubbs, Randy D. Gascoyne, James O. Armitage, Dennis D. Weisenburger, Timothy W. McKeithan, Wing C. Chan
Journal: Blood (2012)
Doctor-anarchists in class war
Authors: Theodore Dalrymple
Journal: BMJ (2007)

There is no more distinguished a writer in Britain today than J G Ballard, who was briefly a medical student but gave up to become a writer. He was born in Shanghai in 1930, but was interned in a Japanese camp there in 1943. Having previously lived the comfortable life of the rich and privileged expatriate in a poor country, he became sensitive as no one else in contemporary letters to the fragility of our well ordered existence.

Many of his books record the barbarism that lies just below the surface of our apparently civilised conduct, and that our highly technological society favours because of its tendency to isolate us emotionally from one another. Ballard is the prophet of social …
School-leavers and Factory Doctors
Authors: E. Saphier
Journal: BMJ (1966)

here-which incidentally is shared by the *B.B.C.-that intelligent people stop up until midnight every night of the week.Surely 11 p.m. would be an average time for retirement, and many would agree that to be called just afterwards was as bad as being woken later on in the night.Incidentally, why is no notice taken of the times a doctor is called out of bed into his surgery in the early hours ?Above all, if sufficiently paid over- all, do we require anything more to induce us to get up at night, or anything to induce the patients to wait until after midnight to call us ?Our representatives certainly should not have agreed to debarring us from payment for ancillary help by our wives.There are numerous instances where wives are doing work of amount and quality that a secretary could not possibly tackle, even where one could be found to attempt it.Obviously there should be an onus upon the doctor to establish the amount of ancillary help he actually gets in N.H.S. work from anyone on his payroll; but it's simply not anybody's business what his relationship with the girl is out of hours.Surely if he is married to her, so much the better.No recognition of the work of some doctors' wives in a payment that was made equally to all doctors could possibly be reasonable or just.-Iam, etc.,
Does electricity give you cancer?
Authors: G. Draper
Journal: BMJ (1996)

Ionising radiation causes cancer; in particular, radiation produced as a result of the radioactive decay of radon gas causes lung cancer, though it is not generally accepted that it causes other cancers. It is not clear that the non-ionising radiation associated with power frequency electromagnetic fields (that produced by the production and transmission of electricity) causes cancer. Professor Denis Henshaw and his colleagues have just published a paper in the International Journal of Radiation Biology saying that the reported associations between such electromagnetic fields and cancer might be explained by their finding that the radioactive disintegration products of radon are concentrated in the vicinity of such fields.

Using Henshaw's paper as a starting point, Dispatches dealt not only with this new suggestion but also with some of the more general issues concerning the possible risks of exposure to this type of electromagnetic field. The paper commands respect; the same cannot be …
Cellular Uptake of Imatinib into Leukemic Cells Is Independent of Human Organic Cation Transporter 1 (OCT1)
Authors: Anne T. Nies, Elke Schaeffeler, Heiko van der Kuip, Ingolf Cascorbi, Oliver Bruhn, Michael Kneba, Christiane Pott, Ute Hofmann, Christopher Volk, Shuiying Hu, Sharyn D. Baker, Alex Sparreboom, Peter Ruth, Hermann Koepsell, Matthias Schwab
Journal: Clinical Cancer Research (2013)

In addition to mutated BCR-ABL1 kinase, the organic cation transporter 1 (OCT1, encoded by SLC22A1) has been considered to contribute to imatinib resistance in patients with chronic myeloid leukemia (CML). As data are conflicting as to whether OCT1 transports imatinib and may serve as a clinical biomarker, we used a combination of different approaches including animal experiments to elucidate comprehensively the impact of OCT1 on cellular imatinib uptake.Transport of imatinib was studied using OCT1-expressing Xenopus oocytes, mammalian cell lines (HEK293, MDCK, V79) stably expressing OCT1, human leukemic cells, and Oct1-knockout mice. OCT1 mRNA and protein expression were analyzed in leukemic cells from patients with imatinib-naïve CML as well as in cell lines.Transport and inhibition studies showed that overexpression of functional OCT1 protein in Xenopus oocytes or mammalian cell lines did not lead to an increased cellular accumulation of imatinib. The CML cell lines (K562, Meg-01, LAMA84) and leukemic cells from patients expressed neither OCT1 mRNA nor protein as demonstrated by immunoblotting and immunofluorescence microscopy, yet they showed a considerable imatinib uptake. Oct1 deficiency in mice had no influence on plasma and hepatic imatinib concentrations.These data clearly demonstrate that cellular uptake of imatinib is independent of OCT1, and therefore OCT1 is apparently not a valid biomarker for imatinib resistance.
Transcutaneous Temporary Pacing in the Operating Room
Authors: David Berliner
Journal: JAMA (1985)

The safety and efficacy of transcutaneous temporary pacing were assessed in 21 patients undergoing elective surgical procedures under general anesthesia. Complete capture was achieved in all patients. The pacing threshold was 50 mamp in two patients, 100 mamp in nine, and 200 mamp in ten. The threshold was influenced by electrode position and also, possibly, by age, heart size, and chest size. No adverse effects of pacing were encountered. Transcutaneous pacing is a rapid, safe, and effective means of temporary pacing in the operating room.
Effect of Molecular Disease Subsets on Disease-Free Survival in Randomized Adjuvant Chemotherapy Trials for Estrogen Receptor–Positive Breast Cancer
Authors: Lajos Pusztai, Kristine Broglio, Fabrice Andre, W. Fraser Symmans, Kenneth R. Hess, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2008)

The majority of estrogen receptor (ER)-positive cancers are sensitive to endocrine therapy and may not derive much further benefit from chemotherapy, but a subset are potentially chemotherapy sensitive. Molecular diagnostic tests allow the identification of these various subsets with some accuracy. The goal of the current analysis was to examine how the proportion of cases in the various risk (recurrence score [RS]) categories of a commercially available multigene assay influences the power of randomized trials to show benefit from adjuvant chemotherapy.We modeled 10-year disease-free survival (DFS) for hypothetical, two-arm clinical trials that randomly assigned patients with ER-positive breast cancer to endocrine therapy alone or endocrine therapy plus chemotherapy. We varied the proportion of patients in low, intermediate, and high RS categories and used DFS estimates for each risk group based on results from the Southwest Oncology Group 8814 study.The probability of observing significant improvement in DFS as a result of chemotherapy decreases as the proportion of patients in the low RS category increases. For example, if a trial is designed with 80% power and the actual proportion of low RS patients accrued to the study increases from 40% to 60%, the power drops to 63%.Variable accrual of low RS patients into different randomized adjuvant chemotherapy trials may partly explain contradictory results in the literature. Studies can be underpowered to detect improvement with chemotherapy as a result of inclusion of too many patients with low RS. Future adjuvant studies for ER-positive breast cancer will need to consider stratifying patients by molecular subtype.
Regulation of Renal Blood Flow by Plasma Chloride
Authors: Christopher S. Wilcox
Journal: Journal of Clinical Investigation (1983)

Micropuncture studies have shown that glomerular filtration rate (GFR) falls in response to a rise in Na+ or Cl- concentrations in the loop of Henle, whereas studies in isolated kidneys have shown that GFR falls in response to osmotic diuresis. To define the separate effects of an acute increase in plasma sodium (PNa), chloride (PCl) or osmolality (Posmol), changes in renal blood flow (RBF) and GFR were measured during intrarenal infusions of hypertonic NaCl, NaHCO3, Na acetate, dextrose, NH4Cl or NH4acetate to denervated kidneys. The infusions raised Posmol at the experimental kidney by 30-45 mosmol. RBF increased abruptly by 10-30% with all hypertonic infusions indicating that an acute increase in plasma tonicity causes renal vasodilatation. Renal vasodilatation persisted or increased further during infusion of dextrose, NaHCO3 and Na acetate, but GFR was unchanged. In contrast, during infusion of the two Cl-containing solutions, vasodilatation was reversed after 1-5 min and RBF and GFR decreased (P < 0.01) below preinfusion levels. Prior salt depletion doubled the vasoconstriction seen with hypertonic NaCl infusions. Overall, changes in RBF were unrelated to changes in PNa or fractional Na or fluid reabsorption but correlated with changes in PCl (r = -0.91) and fractional Cl- reabsorption (r = 0.94). The intrafemoral arterial infusion of the two Cl-containing solutions did not increase femoral vascular resistance. In conclusion, hyperchloremia produces a progressive renal vasoconstriction and fall in GFR that is independent of the renal nerves, is potentiated by prior salt depletion and is related to tubular Cl- reabsorption. Chloride-induced vasoconstriction appears specific for the renal vessels.
Plasma Absorption of Vitamin B12 in Food
Authors: A. DOSCHERHOLMEN
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The plasma absorption of vitamin B<sub>12</sub>in man following oral administration of physiologic doses of crystalline radioactive cobalt-labeled cyanocobalamin has been known for many years.<sup>1-3</sup>The absorption curve shows a delay in appearance of radioactivity for 3 to 4 hours, followed by a rapid rise to a maximum 8 to 12 hours after ingestion of the test dose. The subsequent falloff is gradual over a period of days. Since vitamin B<sub>12</sub>in nature is present in coenzyme forms<sup>4,5</sup>and bound to proteins,<sup>6</sup>the question was raised whether vitamin B<sub>12</sub>in food is absorbed into the blood in a manner similar to that of crystalline radioactive cobalt-labeled cyanocobalamin. We have tried to answer this question by studying the plasma absorption of radioactive isotope-labeled cyanocobalamin incorporated into food in vivo. An egg-laying hen was injected with cyanocobalamin Co 57, and the radioactive eggs
Appraisal of Surgical Atrial Septectomy for Transposition of the Great Arteries
Authors: S. BERT LITWIN, WILLIAM H. PLAUTH, JIMMY E. JONES, WILLIAM F. BERNHARD
Journal: Circulation (1971)

The results of surgical atrial septectomy alone, septectomy with pulmonary artery banding, and septectomy with shunting procedures in 105 patients are reported. There were 82 survivors with eight deaths directly related to surgery, seven related to specific preoperative complications, and eight resulting from associated cardiac malformations. Excellent improvement in arterial oxygen saturation was achieved and maintained over an extended period of time in the majority of survivors. Although balloon septostomy has proved to be a helpful palliative maneuver in patients with TGA, 34 children who had this procedure later required surgical septectomy. A late fall in arterial oxygen saturation was often indicative of diminishing pulmonary blood flow on the basis of increasing pulmonary stenosis or pulmonary vascular obstructive disease.
Abstract P4-13-09: The effect of weight change on breast adipose and dense tissue
Authors: HJ Graffy, MN Harvie, RM Warren, CR Boggis, SM Astley, GD Evans, JE Adams, A Howell
Journal: Cancer Research (2012)

Abstract Background Observational studies indicate that weight gain or loss alters breast cancer risk. Hormonal prevention with tamoxifen or ovarian suppression reduces mammographic breast density, but has no impact on breast adipose tissue.1 The aim of this study was to assess whether change in weight is associated with change in breast density, breast fat or both. Methods 74 premenopausal women aged between 35 and 45 years, with a family history of breast cancer, were recruited from our Family History Clinic. 36 were allocated to a 25% calorie-restricted Mediterranean diet and exercise intervention; a further 38 women were separately recruited into a control group and given written diet and exercise advice only. At baseline and 12 months breast dense and non-dense (largely adipose) components of the breast were measured: area using Cumulus2 and volume using the Manchester ‘stepwedge’ method.3 Visual assessment of percentage density was reported to the nearest 5%.4 We used correlations to relate percentage change in absolute dense and non-dense (area and volume) to percentage change in: weight, total body fat (DXA), intra-abdominal and subcutaneous abdominal fat (MRI), as well as serum total IGF-I. Results At 12 months, 40 (54%) women lost &amp;gt;1.5% body weight, 14 (19%) gained &amp;gt;1.5% and 21 (28%) remained weight stable, &amp;lt;+/−1.5% weight change. There was a range of percentage weight change from −16.3% to +9.8%. There were no significant changes in dense area (r = −0.14 p = 0.29) or volume (r = −0.01 p = 0.97) with weight change. However, both the area and volume of non-dense breast tissue changed significantly in relation to change in body weight (r = 0.52 p &amp;lt; 0.0001 &amp; r = 0.78 p &amp;lt; 0.0001 respectively), total body fat (r = 0.49 p &amp;lt; 0.001 &amp; r = 0.75 p = &amp;lt;0.0001 respectively), intra-abdominal fat (r = 0.45 p &amp;lt; 0.0001 &amp; r = 0.36 p = 0.03 respectively) and subcutaneous abdominal fat (r = 0.55 p &amp;lt; 0.0001 &amp; r = 0.52 p = 0.002 respectively). Visually assessed percentage mammographic density was significantly inversely related to weight (r = −0.27 p = 0.038). Serum total IGF-I was not significantly correlated with breast dense area. (r = −0.21 and p = 0.09). Conclusions These data indicate that dense area and volume remain stable irrespective of change in weight. Non-dense area changes significantly in response to weight change in parallel with total and abdominal fat stores. These observations were performed on relatively small numbers of women and require confirmation in larger series. 1. Cuzick et al J Natl Cancer Inst. 103(9): 744–52, 2011. 2. Boyd NF et al J Natl Cancer Inst. 87(9) 670–675 1995. 3. Diffy et al IWIDM 2006, LNCS 4046 p1-9. In Astley et al (Eds) Springer-Verlag Berlin Heidelberg 2006 4. Brisson J et al. Cancer Epidemiol Biomarkers Prev 2003;12:7288–32. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-09.
Philosophical medical ethics. Rights.
Authors: R Gillon
Journal: BMJ (1985)

In one of a series of articles on philosophical medical ethics, Gillon examines problems associated with the term "rights." He focuses on the distinction between legal and institutional rights on the one hand and moral rights on the other, and then on the distinction between universal moral rights possessed by all human beings and those moral rights that arise as a result of prior actions or special social relationships. Finally, he discusses the distinction between rights that impose moral obligations on others to act and rights that require others to refrain from acting.