tbuckley/cabot-search huggingface dataset:
The National Health Service Act 1946
Authors: J. Lister
Journal: BMJ (2011)

The active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)<sub>2</sub>D], interacts with vitamin D receptor (VDR) and induces antiproliferative, anti-invasive, proapoptotic and pro-differentiation activities in prostate cancer cells. Three cytochrome P-450 (CYP) hydroxylases are responsible for vitamin D synthesis and degradation, including vitamin D-25-hydroxylase (25-OHase) in the liver, and 25(OH)D-1α-hydroxylase (1α-OHase) or CYP27B1, and 25(OH)D-24-hydroxylase (24-OHase) or CYP24A1 in the kidneys. However, it is now recognized that CYP27B1 and CYP24A1 are also expressed in many tissues and cells, including the prostate. Although at least six CYP enzymes have been identified with 25-OHase activity, the two major ones are CYP27A1 and CYP2R1, and both are expressed in the prostate, with CYP2R1 as the predominate type. This indicates that prostate tissue has the ability to activate and inactivate vitamin D in an autocrine/paracrine fashion. Recent evidence indicates that 25-hydroxyvitamin D [25(OH)D] and its analogs can bind to VDR as agonists, without converting them to 1α,25(OH)<sub>2</sub>D or the corresponding 1α-hydroxylated metabolites, to modulate gene expressions that will lead to cell growth arrest and other antitumor activities. This finding suggests that the circulating levels of 25(OH)D, and the autocrine synthesis of 25(OH)D may play an important role in regulating the growth of prostate cancer. Thus, in addition to 1α,25(OH)<sub>2</sub>D analogs, the presence of CYP2R1, CYP27B1 and CYP24A1 in the prostate suggests that the analogs of vitamin D and 25(OH)D, especially those that are resistant to CYP24A1 degradation, can be developed and used for the prevention and treatment of prostate cancer.
Abstract 2273: Validation of putative stem cell factor SOX2 as predictive marker in breast cancer – with overall poor prognosis
Authors: Leon Paul Pradel, Stefan Swierczynski, Richard Greil, Otto Dietze, Cornelia Hauser-Kronberger
Journal: Cancer Research (2011)

Abstract As member of the high-mobility-group (HMG)-domain containing proteins – SOX2 (Sex determining Region Y – box 2) transcriptional activator is known for its pivotal role in maintaining self-renewal, pluripotency and cellular identity in embryonic stem cells. While its status in adult tissue, e.g. in homeostasis – is still less understood and controversy – SOX2 has shown recently to be up regulated in a huge variety of human tumors like oesophagus, lung, brain and breast. Within this study whole sections – provided as formalin-fixed paraffin-embedded tumor samples, derived from 86 patients with advanced breast cancer disease were stained via immunohistochemistry (IHC) for SOX2 positivity. Further on – six breast cancer cell lines (MCF-7, MDA-MB231, MDA-MB453, SK-BR3, SUM-159, T47-D) as well as an individual based tissue micro array (TMA) containing 1080 fine needle biopsies were additionally analyzed using IHC and qRT-PCR. Initially – all samples have been evaluated for their particular molecular subtype (Luminal A, Luminal B, Normal-like, HER2 Overexpressing, Basal-like) and their histopathological parameters (histological subtype, grade, size, lymph node metastasis). For further proof of principle the applied SOX2 polyclonal antibody (SOX2 PAb AF2018, R&amp;D SystemsTM) was validated for its marker capacity via Surface Plasmon Resonance (SPR) Spectroscopy and Western Blot to determine the kinetic profile, limit of detection, epitope variety and specificity of this antibody. With the so called ‘fishing’ opportunity for analyte recovery in SPR, native putative antigen bound by the SOX2 PAb can be enriched and further characterized from whole cell lysates. In conclusion – SOX2 showed association to overall bad prognosis due to high grade (p&amp;lt;0.001), huge size (p=0.003), lymph node metastasis (p&amp;lt;0.001) as well as histological and molecular subtypes with poor overall-survival (p&amp;lt;0.001). Further on it is independent (p=0.6) of oestrogen receptor (ER) presence but correlated to EGFR expression (p=0.007). During antibody-based validation – SOX2 PAb revealed to possess high specificity, sensitivity and affinity to native and recombinant SOX2 full length protein finally. In this way SOX2 – as marker, can be applied to predict overall poor prognosis in breast cancer in an ER- and subtype-independent fashion. 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 2273. doi:10.1158/1538-7445.AM2011-2273
The Chemistry of the American Indian's Burden
Authors: Franz J. Ingelfinger
Journal: New England Journal of Medicine (1979)

Gallstones consisting principally of cholesterol are common in Western industrialized and "developed" nations. On the other hand, cholesterol stones have been uncommon to rare in many Asian and African peoples1 (who do, however, have calcium bilirubinate and parasite-related biliary-tract concretions). In Japan, since that nation has increasingly adopted Western ways and food, the prevalence of cholesterol gallstones is reported as on the increase.2 It is therefore not surprising that those who enthusiastically advocate high-fiber foods, and with equal fervor denounce the consumption of "refined sugar" products, list cholesterol gallstones among our diseases of civilization.3 How is it then that American . . .
Neuroscience Critical Care: Pathophysiology and Patient Management
Authors: J. Rankin
Journal: JAMA (1991)

<i>Neuroscience Critical Care</i>is a ground-breaking work for neuroscience nursing and provides the neuro—critical care nurse with what may be the first manual tailored specifically to the decision making required in the neurological intensive care unit (NICU). Any neuroscience nurse would find this book use ful, but the NICU nurse and the neuro nurse in advanced practice will find it a necessary adjunct to daily practice. And, since the standard intensive care unit still provides most neurological intensive care, the generalist intensive care unit nurse has at long last a competent guide and reference for the care of the neurologically impaired individual. Neuroscience nursing has undergone drastic changes in recent years, as research, new diagnostic techniques, and new treatment modalities have generated a veritable "information explosion" in the clinical neurosciences. The responsibilities of the neuro nurse are greater than ever and are unlikely to diminish over time. To the contrary,
Interaction of Cimetidine and Alcohol-Reply
Authors: Alastair J. J. Wood
Journal: JAMA (1983)

In Reply.—  The data in our article demonstrated a small increase in plasma alcohol levels when patients received cimetidine concurrently with alcohol. Although the mechanism responsible for these changes is unclear, the various possibilities, including increased absorption, were fully discussed in our article. It seems that Dr Tan and colleagues have data that show an increased peak plasma alcohol concentration after cimetidine administration, compatible with our findings, but no notable change in the rate of alcohol absorption. It is unclear, therefore, why they think that increased gastric motility is responsible for the increased alcohol concentrations with cimetidine seen in our study not only at peak levels but for eight hours after administration. The only published reference cited by Dr Tan and colleagues 1 in support of their claim is a letter published by themselves that measured skin oxygen tension on the face after alcohol consumption with and without H 1 and
Nerve As a Tissue
Authors: Monroe Cole
Journal: JAMA (1967)

Of the three stated goals of this symposium two have been amply realized. All those interested in basic research can become acquainted with the work of colleagues in other fields, and clinicians may gain a glimpse of what is new. But the book fails to attain the third goal, of providing information immediately pertinent to diagnosis and patient care. The book is organized into four parts: morphology, biochemistry, physiology and pharmacology, and pathophysiology. Each part concludes with a discussion consisting mainly of questions, generally of a sophisticated nature, from the audience. Except for a few chapters, eg, Lowry's essay on energy metabolism of the nerve cell, most of the subject matter concerns the<i>synapse</i>, which is, after all, the functional end of the nervous system. But a common failing of most symposia is repeated here: there is no final synthesis. Such a synthesis may in fact be impossible without the
A Nomogram for Staging of Exclusive Nonobturator Lymph Node Metastases in Men with Localized Prostate Cancer
Authors: Alberto Briganti, Felix K.-H. Chun, Andrea Salonia, Giuseppe Zanni, Andrea Gallina, Federico Dehò, Nazareno Suardi, Luigi Filippo Da Pozzo, Luc Valiquette, Patrizio Rigatti, Francesco Montorsi, Pierre I. Karakiewicz
Journal: European Urology (2006)
Immune Mechanisms in Non–Hodgkin Lymphoma: Joint Effects of the <i>TNF</i> G308A and <i>IL10</i> T3575A Polymorphisms with Non–Hodgkin Lymphoma Risk Factors
Authors: Sophia S. Wang, Wendy Cozen, James R. Cerhan, Joanne S. Colt, Lindsay M. Morton, Eric A. Engels, Scott Davis, Richard K. Severson, Nathaniel Rothman, Stephen J. Chanock, Patricia Hartge
Journal: Cancer Research (2007)

Abstract Two common single nucleotide polymorphisms in immunoregulatory genes (TNF G308A, rs1800629 and IL10 T3575A, rs1800890) have been recently reported as risk factors for non–Hodgkin lymphoma (NHL) in a large pooled analysis. We systematically investigated the effects of other established NHL risk factors in relation to the tumor necrosis factor (TNF) G308A or interleukin 10 (IL10) T3575A genotypes. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) from 1,172 cases and 982 population-based controls in a U.S. multicenter study. We investigated NHL overall and two common subtypes [diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma]. NHL risks were increased among those with both an autoimmune condition and the TNF G308A GA/AA (ORNHL, 2.1; 95% CI, 1.0–4.2) or the IL10 T3575A TA/AA genotype (ORNHL, 1.6; 95% CI, 0.9–2.6) compared with individuals without an autoimmune condition and with the common TNF G308A GG or IL10 T3575A TT genotype, respectively; results were similar for DLBCL and follicular lymphoma. We found that elevated DLBCL risk associated with last-born status was more pronounced among those with TNF G308A GA/AA (ORDLBCL, 2.7; 95% CI, 1.1–6.4) or IL10 T3575A TA/AA (ORDLBCL, 2.9; 95% CI, 1.6–5.2). Similarly, elevated DLBCL risk associated with obesity (body mass index, ≥35 versus &amp;lt;25 kg/m2) was observed only among those with TNF G308A GA/AA (ORDLBCL, 2.5; 95% CI, 1.1–5.7) or IL10 T3575A TA/AA genotypes (ORDLBCL, 2.0; 95% CI, 1.1–3.5). These exploratory results require replication but provide evidence that autoimmune conditions, late birth order, and obesity act partly through a common inflammatory pathway, posing a greater risk to individuals with variant TNF and IL10 genotypes than those with wild-type alleles. [Cancer Res 2007;67(10):5042–54]
Transmembrane potential in isolated human heart
Authors: G. E. FREUD
Journal: Cardiovascular Research (1972)

The TMP was measured in normal parts of the left ventricular wall of two artificially perfused human hearts at different heart rates, using microelectrodes and a field effect transistor. The membrane resting potentials were − 82 and − 87 mV. The duration of the upstroke coinciding with the intrinsic deflection of the unipolar complex, recorded just before entering the cell, was 1 msec. No overshoot was present in one heart, because of cancellation of a possible overshoot by the S-wave of the unipolar complex. The relation between frequency and duration of the TMP is identical with the QT-time-frequency relation, as found in extremity leads. The changes in duration of the TMP caused by changes in heart rate, result from changes in the duration of the plateauphase exclusively. The phase 3 of the TMP has a constant form, independent of rate and rhythm. The form of the T wave from driven hearts in clinically used ECG leads is not dependent on the stimulation rate. The advantages of the field effect transistor in intracellular recording are discussed.
Association of immunity and tolerance to host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain.
Authors: J Sprent, H V Boehmer, M Nabholz
Journal: The Journal of Experimental Medicine (1975)

Semiallogenetic radiation chimeras were prepared by injecting heavily irradiated F1 hybrid mice with bone marrow cells from one parental strain; the bone marrow cells were treated with anti-theta serum and complement to remove T cells and injected in large numbers (2 times 10-7 cells). The mice survived in excellent health until sacrifice 6 mo later. Thoracic duct cannulation at this stage showed that the mice possessed normal numbers of recirculating lymphocytes. Close to 100% of thoracic duct lymphocytes and lymph node cells were shown to be of donor strain origin. The capacity of lymphocytes from the chimeras to respond to host-type determinants was tested in mixed leukocyte culture and in an assay for cell-mediated lympholysis (CML). Mixed leukocyte reactions (MLR) were measured both in vitro and in vivo; tumor cells and phytohemmaglutinin-stimulated blast cells were used as target cells for measuring CML. While responding normally to third party determinants, cells from the chimeras gave a definite, though reduced MLR when exposed to host-type determinants. However, this proliferative response to host-type determinants, unlike that to third party determinants, was not associated with differentiation into cytotoxic lymphocytes. No evidence could be found that unresponsiveness in this situation was due to blocking serum factors or suppressor T cells. It is argued that the results support the concept that lymphocytes responsive in mixed leukocyte culture have a different specificity to those exerting cell-mediated lympholysis.
AN ANALYSIS OF 700 CASES OF LABOR
Authors: H. R. COSTON
Journal: JAMA (1913)

For a number of years I have kept a record of obstetric cases occurring in my practice. I have thought a careful study of these might be of general interest. It certainly has been of service to me. These results would seem to controvert the popular idea that most babies are born in very cold weather, as by far the larger number of my cases (383) occurred in the months from April 1 to September 30. Delivery occurred at the following times of day, in threc-hour periods:
Hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predicts survival after partial hepatectomy in mice
Authors: Ji Ling, Todd Chaba, Lin-Fu Zhu, René L. Jacobs, Dennis E. Vance
Journal: Hepatology (2011)

A major predictor of failed liver resection and transplantation is nonalcoholic fatty liver disease (NAFLD). NAFLD is linked to a wide spectrum of diseases including obesity and diabetes that are increasingly prevalent in Western populations. Thus, it is important to develop therapies aimed at improving posthepatectomy outcomes in patients with NAFLD, as well as to improve the evaluation of patients slated for hepatic surgery. Decreased hepatic phosphatidylcholine (PC) content and decreased ratio of hepatic PC to phosphatidylethanolamine (PE) have previously been linked to NAFLD. To determine if decreased hepatic PC/PE could predict survival after hepatectomy, we used mouse models lacking key enzymes in PC biosynthesis, namely, phosphatidylethanolamine N-methyltransferase and hepatic-specific CTP:phosphocholine cytidylyltransferase α. These mice were fed a high-fat diet to induce NAFLD. We then performed a 70% partial hepatectomy and monitored postoperative survival. We identified hepatic PC/PE to be inversely correlated with the development of steatosis and inflammation in the progression of NAFLD. Decreased hepatic PC/PE before surgery was also strongly associated with decreased rates of survival after partial hepatectomy. Choline supplementation to the diet increased hepatic PC/PE in Pemt(-/-) mice with NAFLD, decreased inflammation, and increased the survival rate after partial hepatectomy.Decreased hepatic PC/PE is a predictor of NAFLD and survival following partial hepatectomy. Choline supplementation may serve as a potential therapy to prevent the progression of NAFLD and to improve postoperative outcome after liver surgery.
(11) Dyskeratosis congenita with pancytopenia
Authors: H. BAKER, B. COLVIN, M.T. GLOVER
Journal: British Journal of Dermatology (1991)

Journal Article (11) Dyskeratosis congenita with pancytopenia Get access H. BAKER, H. BAKER The Royal London Hospital, London Search for other works by this author on: Oxford Academic Google Scholar B. COLVIN, B. COLVIN The Royal London Hospital, London Search for other works by this author on: Oxford Academic Google Scholar M.T. GLOVER M.T. GLOVER The Royal London Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue s38, 1 July 1991, Page 50, https://doi.org/10.1111/j.1365-2133.1991.tb05482.x Published: 01 July 1991
Effect of a xanthine analog on human hepatocellular carcinoma cells (Alexander) in culture and in xenografts in SCID mice
Authors: L Marucci, L Varticovski, I M Arias
Journal: Hepatology (1997)

Hepatocellular carcinoma (HCC) frequently overexpresses the MDR1 gene and is resistant to drugs transported by the multidrug-resistance efflux pump. A xanthine analog, 1-(11-dodecylamino-10-hydroxyundecyl)- 3,7-dimethylxanthine (CT-2584,CTI), is cytotoxic to many tumors in culture and was four times more effective than verapamil in inhibiting Rhodamine 123 secretion in MDR1-overexpressing Chinese hamster ovary cells. However, studies using PRF/PLC/5 (Alexander) cells revealed that CT-2584 is cytotoxic by another mechanism not involving inhibition of MDR1 function. Alexander cells have integrated the hepatitis B surface antigen (HBsAg) gene and quantitatively secrete HBsAg. The parent cell line, Alex 0, has low MDR1 expression and is drug-sensitive, whereas a derived line, Alex 0.5, is drug-resistant and overexpresses MDR1 100 times. Both cell lines were similarly killed within 24 or 48 hours by CT-2584. Freshly isolated rat and human hepatocytes were considerably more resistant to killing by CT-2584. In vivo , CT-2584 significantly reduced tumor growth in SCID mice bearing Alex 0 or 0.5 xenografts as determined by serial measurements of HBsAg. Hepatic parenchyma was normal, whereas apoptosis and cellular loss were observed in xenografts. The xenograft model is useful for testing pharmacological therapy of HCC.
The Role of Data Audits in Detecting Scientific Misconduct
Authors: Bernhard Heersink
Journal: JAMA (1990)

To  Editor.—  Regarding  article 1 about Food and Drug Administration audits, I was particularly disturbed by  authors' proposal to suspend investigators  prior to any hearing. Further, the burden of proof would be on  investigator to demonstrate that he or she should not be disqualified.  This proposal appears to turn a centuries-old principle of jurisprudence on its head. The accused used to be presumed innocent until proved guilty. Why should an individual be stripped of his or her livelihood and reputation by nothing more than  arbitrary judgment of a bureaucrat? Why should  burden of proof not rest with  accusers? Why should they not have to give sufficient objective evidence to demonstrate  incompetence or dishonesty of investigators?  The answer given by Shapiro and Charrow is that shifting  burden of proof to  investigator should reduce  cost to  FDA of a
Hyperthyroidism and Potassium
Authors: M. El Shahawy
Journal: JAMA (1971)

<h3>To the Editor.—</h3> The effect of hyperthyroidism on body mineral shifts and content remains incompletely characterized. Hypercalcemia, hyperphosphatemia,<sup>1</sup>and hypomagnesemia<sup>2</sup>are known consequences. We have recently completed a study measuring the acute effects of exogenously induced hyperthyroidism on the total body and serum potassium values in six mongrel dogs. These experimental animals received 2.0 mg of thyroxine subcutaneously daily for three weeks. They ate a carefully controlled diet<sup>3</sup>and were compared over the same period with two control dogs which did not receive thyroxine but ingested the same diet. At the end of the third and fourth weeks of thyroxine treatment, the total body potassium value of the hyperthyroid dogs was significantly increased over that of the controls (P&lt;0.05) while the serum potassium level remained unchanged. Body weight tended to decrease. The mean total body potassium level in the two controls was 55.06 mEq, and the mean
Early Post-Discharge Bleeding and Antiplatelet Therapy Discontinuation Among Acute Myocardial Infarction Patients Treated With Percutaneous Coronary Intervention
Authors: Tracy Y Wang, Lisa McCoy, Timothy D Henry, Mark B Effron, John C Messenger, David J Cohen, Daniel B Mark, Gregg W Stone, Marjorie Zettler, Mandeep Singh, Gregg C Fonarow, Eric D Peterson
Journal: Journal of the American College of Cardiology (2014)
High cost of cancer treatment doesn't reflect benefits, say specialists
Authors: N. Hawkes
Journal: BMJ (2011)

Care of patients with cancer has become “a culture of excess” in rich countries, says a team of specialists assembled by the Lancet . “We overdiagnose, overtreat, and overpromise. We are heading towards a crisis in medical-care delivery,” they say.

The report of the 37 strong commission, headed by Richard Sullivan from King’s Health Partners Integrated Cancer Centre in London, is uncompromising ( Lancet Oncology 2011;12:933-80, doi:10.1016/S1470-2045(11)70141-3). It says that expensive new drugs often contribute modest benefits while imposing huge cost burdens.

Surgery, the mainstay of cancer care, is going the same way, with the increasing use of robot assisted surgery that drives costs up with no …