tbuckley/cabot-search huggingface dataset:
Abstract 1799: Can trastuzumab enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, Stage II/III or Stage IV gastric cancer
Authors: Takashi Oshima, Chikara Kunisaki, Shoichi Fujii, Roppei Yamada, Yasushi Rino, Munetaka Masuda, Toshio Imada
Journal: Cancer Research (2011)

Abstract Objectives: Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), in combination with chemotherapy has been reported to significantly prolong survival in patients with HER2-positive, unresectable, advanced gastric cancer. However, the therapeutic usefulness of this regimen for surgically resected gastric cancer remains unclear. Adjuvant chemotherapy with S-1 has been shown to be beneficial in patients with stage II or III gastric cancer. Whether trastuzumab should be given to patients with resected, HER2-positive gastric cancer is a very interesting problem. We therefore examined whether trastuzumab can be expected to enhance the effectiveness of chemotherapy in patients with resected, HER2-positive, stage II/III or IV gastric cancer. Methods: The study group comprised 183 patients: 116 had stage II or III gastric cancer and received adjuvant chemotherapy with S-1 after surgery from May 2003 through March 2008; the other 67 had stage IV gastric cancer and sequentially received new anticancer agents after surgery from July 1999 through September 2005. HER2 was evaluated by inmmunohistochemistry and FISH according to the protocol of a Study of Trastuzumab in Combination with Chemotherapy Compared with Chemotherapy Alone in Patients with HER2-Positive Advanced Gastric Cancer (ToGA study). Positive expression of HER2 was defined as a score of 3+ on immunohistochemical staining or as a score of 2+ on immunohistochemical staining plus relative HER2 DNA expression of &amp;gt;2.2 on FISH. Cumulative survival rates were compared between HER2-positive patients and HER2-negative patients. Results: Among patients with stage II or III gastric cancer who received adjuvant chemotherapy with S-1, 20% had HER2-positive tumors; however, cumulative survival rates did not differ significantly between HER2-positive patients and HER2-negative patients. Among patients with stage IV gastric cancer who underwent surgery, 22% had HER2 positive tumors; however, cumulative survival rates did not differ significantly between HER2-positive and HER2-negative patients. Conclusions: The survival benefit of adding trastuzumab to standard chemotherapy was considered minimal in patients with resected, HER2-positive stage II/III or stage IV gastric cancer. 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 1799. doi:10.1158/1538-7445.AM2011-1799
Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro.
Authors: R W Whitcomb, W M Linehan, R A Knazek
Journal: Journal of Clinical Investigation (1988)

Adrenoleukodystrophy (ALD) and adrenomyeloneuropathy are inherited disorders in which long-chain, saturated fatty acids (LCFA) accumulate in various tissues. A mechanism by which LCFA cause the endocrine and neurological dysfunction characteristic of these diseases is proposed based on in vitro response of human adrenocortical cells to ACTH in the presence of various fatty acids. Human adrenocortical cells cultured in the presence of 5 microM hexacosanoic (C26:0) or lignoceric (C24:0) acids showed decreased basal and ACTH-stimulated cortisol release compared with cells cultured without exogenous fatty acids or in the presence of linoleic acid (C18:2). Measurement of fluorescence polarization demonstrates a significant increase in the membrane microviscosity of cells cultured in the presence of LCFA. It is hypothesized that cells exposed to LCFA have increased membrane microviscosity with a consequent decrease in their ability to respond to ACTH. This decrease in trophic support may contribute to the adrenal insufficiency and atrophy in patients with ALD.
Continuous Intravenous Deferoxamine Infusion
Authors: Karl G. Blume
Journal: JAMA (1978)

Adult patients with chronic iron overload were given oral ascorbic acid and continuous intravenous infusions of deferoxamine mesylate. The dosage of deferoxamine mesylate was altered every 48 hours from 1 g/sq m/24 hr to 2 or 4 g/sq m/24 hr. The average iron mobilization was 55.6 mg per day at the 1 g/sq m/24 hr dosage level, 78.6 mg every 24 hours at the 2 g/sq m/24 hr dosage level, and 90.1 mg every 24 hours at the 4 g/sq m/24 hr dosage level. Iron mobilization was undiminished when successive 14-day courses of deferoxamine separated by six-week intervals were administered. (<i>JAMA</i>239:2149-2151, 1978)
E1AF/PEA3 Activates the Rho/Rho-Associated Kinase Pathway to Increase the Malignancy Potential of Non–Small-Cell Lung Cancer Cells
Authors: Nobuyuki Hakuma, Ichiro Kinoshita, Yasushi Shimizu, Koichi Yamazaki, Koichi Yoshida, Masaharu Nishimura, Hirotoshi Dosaka-Akita
Journal: Cancer Research (2005)

Abstract E1AF/PEA3, an Ets family transcription factor, is frequently overexpressed in non–small-cell lung cancers (NSCLCs). Overexpression of E1AF increases motility and invasion of VMRC-LCD and NCI-H226 NSCLC cells, which lack endogenous E1AF expression, and the effect is synergistically increased by hepatocyte growth factor (HGF). The small GTPase Rho/Rho-associated kinase (ROCK) pathway is also involved in motility and invasion. To determine the role of the Rho/ROCK pathway in malignant phenotypes induced by E1AF, we analyzed VMRC-LCD cells transfected with an E1AF expression vector (LCD-E1AF cells) or with empty vector (LCD-vector cells). LCD-E1AF cells had more GTP-bound (active) Rho than LCD-vector cells and Rho activation was synergistically increased by HGF. The Rho activation by E1AF and HGF was also shown in NCI-H226 cells. Phosphorylation of myosin light chain (MLC), a downstream effector of ROCK signaling, was higher in LCD-E1AF cells than in LCD-vector cells, especially under HGF treatment. A specific ROCK inhibitor, Y27632, strongly suppressed MLC phosphorylation, cell motility, and invasion. In nude mice implanted s.c. and intrapulmonarily, LCD-E1AF cells made more local tumors than LCD-vector cells (six of six versus one of seven mice and four of seven versus one of seven mice, respectively). Three of the four mice with lung tumors from LCD-E1AF cells had lymph node metastases whereas the mouse with LCD-vector tumors did not. LCD-E1AF tumors showed higher MLC phosphorylation than LCD-vector tumors. These results suggest that E1AF activates the Rho/ROCK pathway in an HGF-enhanced manner and its activation is important in E1AF-induced motility and invasion as well as tumorigenesis and metastasis in NSCLC cells.
Impact of Low Flow on the Outcome of High-Risk Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Florent Le Ven, Mélanie Freeman, John Webb, Marie-Annick Clavel, Miriam Wheeler, Éric Dumont, Chris Thompson, Robert De Larochellière, Robert Moss, Daniel Doyle, Henrique B. Ribeiro, Marina Urena, Luis Nombela-Franco, Josep Rodés-Cabau, Philippe Pibarot
Journal: Journal of the American College of Cardiology (2013)
A5.12 Disappearance and Reappearance of IgG, IgA and IgM Autoantibody Isotypes and Immune Complexes in Rituximab-Treated SLE Patients
Authors: Barbro Persson, Fionnuala McAree, Malin Müller, Tina Trollmo, Ioannis Parodis, Thorunn Jonsdottir, Vivianne Malmström, Iva Gunnarsson, Johan Rönnelid
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> We have earlier investigated the content of specific IgG autoantibodies in SLE immune complexes (IC; Åhlin <i>et al</i>, Lupus 2012; 21:586). For that purpose we have developed a line blot technique for the quantification also of non-classical (IgA and IgM) SLE autoantibody isotypes. In SLE patients, IgG autoantibody levels drop after institution of Rituximab therapy. The objective was to investigate parallel changes IgG, IgA and IgM autoantibody isotypes in parallel to IC levels. <h3>Materials and Methods</h3> Nine SLE patients initially treated with two infusions of Rituximab were followed with repeated samplings at baseline and after 1, 3, 6 and 12 months. Thawed samples were investigated simultaneously concerning rheumatoid factor (RF) isotypes and C1q-binding IC with enzyme immunoassays. All samples from patients with ANA-associated autoantibodies (6/9) were investigated concerning IgG/A/M autoantibodies with line blot quantitated with densitometry and concerning IgG autoantibodies with ALBIA/Luminex technique. Significant changes were defined either as ≥33% drop or as ≥50% increase, compared to the lowest levels experienced during the follow-up period. <h3>Results</h3> ALBIA measurements showed significant initial drop in anti-dsDNA in 4/6 patients but also significant drop in levels of anti-histone, anti-SSA/Ro60, anti-Sm and anti-Sm/RNP in individual patients. Late increases in IC and antibodies against dsDNA, SSA/Ro52, SSA/Ro60, SSB, Sm, Sm/RNP ribosomal P protein and histones were associated with clinical relapse. Late increase in IgA/IgM anti-DNA, anti-histones and anti-nucleosomes was also found in one patient with persistent kidney disease treated with mycophenolate mofetil at 10 months. Non-classical autoantibody isotypes showed late increases that often were not paralleled by the corresponding IgG autoantibodies. Two patients showed late increase in RF isotypes in parallel to clinical relapse. Different autoantibodies/isotypes showed different kinetics of appearance/disappearance. All ANA autoantibody positive patients initially had increased IC levels, which dropped significantly after therapy in 4/6 patients. The autoantibody negative patients never had increased IC levels and showed no significant changes in RF. <h3>Conclusions</h3> Measurement of non-classical isotypes of RF and ANA-associated autoantibodies might yield clinically useful information when monitoring SLE patients treated with B cell depleting therapy.
Introduction to Anesthesia: The Principles of Safe Practice
Authors: J. S. Gravenstein
Journal: JAMA (1968)

When new residents arrive or when medical students come on our anesthesia service, I recommend this book to them. It is, as far as I know, the best<i>Introduction to Anesthesia</i>in the world. I must augment encomium with further praise: Rather than let a professional draftsman sketch the many line drawings, the publishers added warmth and personality by employing for this a gifted painter, who happens to be one of the authors (Dr. Vandam). The book contains two peculiar features that deserve comment even though neither is related to the medical aspects of anesthesia. Under the title "Surgeon-Anesthetist Relationships" the authors discuss disputes between surgeons and anesthetists. Perhaps significantly, they sandwich this chapter between one on explosions and another on asepsis. While they give good advice against explosions and for asepsis, they offer little more than paternal admonitions to bring surgeons and anesthetists closer together. The other feature that
Dose-Response Relationship of Insulin Glulisine in Subjects With Type 1 Diabetes
Authors: Reinhard H.A. Becker, Annke D. Frick, Leszek Nosek, Lutz Heinemann, Klaus Rave
Journal: Diabetes Care (2007)

Rapidly absorbed and acting insulin analogs are increasingly being used to improve postprandial metabolic control (1), which may help in reducing cardiovascular-related and all-cause mortality in patients who already have good metabolic control (A1C <8%) (2). Insulin glulisine is a new insulin analog (3) and, unlike other insulin analog products, is formulated without added zinc to achieve sufficient physical shelf life (4). This unique formulation allows for the immediate availability of monomeric and dimeric insulin glulisine molecules after injection, which is key for rapid absorption into the blood stream from subcutaneous tissue (5). Pharmacokinetic, pharmacodynamic, and safety studies of insulin glulisine in healthy volunteers and patients with diabetes have shown that subcutaneous injection of insulin glulisine more closely mimics physiologic postprandial insulin action than regular human insulin (RHI) (6). Indeed, superior metabolic control was achieved with insulin glulisine compared with RHI in subjects with type 1 diabetes on effectively titrated basal insulin regimens (7). However, despite the increasing use of rapid-acting insulin analogs, surprisingly little is known about dose escalation on systemic insulin concentrations and metabolic activity in subjects with diabetes. This study was conducted to investigate the dose-exposure and dose-response relationships of insulin glulisine compared with RHI in subjects with type 1 diabetes.

In a single-center, randomized, euglycemic, glucose clamp trial, 18 male patients with type 1 diabetes were included in the study (aged 35.0 ± 9.2 years, BMI 24.5 ± 2.7 kg/m2, A1C 7.7 ± 0.9%). The study included a screening visit, three glucose clamp visits …
NICE recommends long term campaign to encourage young people to exercise
Authors: S. Mayor
Journal: BMJ (2009)

Children and teenagers should do a minimum of 60 minutes of at least moderate intensity physical activity each day, recommends new public health guidance from the National Institute for Health and Clinical Excellence (NICE). Young people who are currently not exercising at this level should be involved with local service providers in planning opportunities for physical activity that are more appealing, it says.

The guidance on promoting physical activity among young people up to the age of 18 warns that just under half (45%) of 15 year old girls and two thirds (68%) of boys of the same age are reaching the recommended level of at least one hour of moderate to …
Chemoproteomics-based kinome profiling and target deconvolution of clinical multi-kinase inhibitors in primary chronic lymphocytic leukemia cells
Authors: U Kruse, C P Pallasch, M Bantscheff, D Eberhard, L Frenzel, S Ghidelli, S K Maier, T Werner, C M Wendtner, G Drewes
Journal: Leukemia (2010)
THE POLICY OF THE UNIVERSITY OF LONDON IN RELATION TO LONDON MEDICAL EDUCATION AND MEDICAL SCIENCE
Authors: W. Hunter
Journal: BMJ (1907)

Since the policies pursued in the three great University ?entres of  Edinburgh, and Cambridge present ?distinctive features, the policy of the University of London in relation to medical education was in my last article inferentially contrasted with that of the two great ^Universities of Edinburgh and of Cambridge, by whose prosperity that of London has undoubtedly been most affected. The comparison with Cambridge in particular was specially invited by the original basis of the  Univer sity of London, namely, that it was :  A Board of examiners to perform all the functions of the examiners in the Senate of Cambridge, this body to -be termed the * University of London '  (1835). . It was further invited by the additional important statute passed in 1854 : To extend the rights enjoyed by the graduates of Oxford and Cambridge in respect to the practice of physic to the graduates of the University of London ?an act by which the degree of M.B. in the University of London ^became recognized as a licence to practise?and the University was placed on the same terms as other ^universities. The comparison was further invited by the last Charter -of the University of London (1898), by which the various medical schools in London were affiliated to the University of London and recognized as  constituent colleges w of the University, in much the same way, it is alleged, as the various colleges of Cambridge, while financially inde pendent, are related to the University of Cambridge?but -erroneously, so alleged, since in Cambridge the University .provides all the laboratories and expenses required for medical education, while in London the University leaves -everything to its medical schools.
Abstract 4207: CCN5/WISP-2 upregulates p27Kip1 in breast cancer cell lines through AKT/FOXO3a signaling
Authors: Inamul Haque, Snigdha Banerjee, Archana De, Saheli Sinha Jha, Sushanta K. Banerjee
Journal: Cancer Research (2012)

Abstract CCN5 is a member of the CCN (cysteine rich 61-connective tissue growth factor-nephroblastoma-overexpressed) family of growth factors. Our studies have shown that CCN5 is mainly expressed in less aggressive human breast cancer cells (i.e., MCF-7 and ZR-75-1) and noninvasive lesion (i.e., atypical ductal hyperplasia and ductal carcinoma in situ), whereas its expression is minimally detected in moderately aggressive breast cancer cell lines (i.e., SKBR-3), and it is undetected in triple negative highly aggressive breast cancer cell line (i.e., MDA-MB-231) and invasive lesion. Ectopic expression of CCN5 has been shown to inhibit tumorigenicity in MDA-MB-231-xenograft models therefore suggesting that CCN5 is an anti-invasive molecule. The objective of the present study was to determine how CCN5 overexpression affects cell-cycle progression of breast cancer cells. We found knocking down of CCN5 in non-invasive breast cancer cells significantly downregulated the expression of p27Kip1, a tumor suppressor molecule. In contrast, enforced/ectopic expression of CCN5 overexpression in MDA-MB-231 breast cancer cells caused cell cycle arrest at G1 phase and dramatically reduced proliferation of these cells. CCN5 overexpression results in increased the stability as well as the expression of p27Kip1 protein. The regulation of p27Kip1 by CCN5 is mediated through AKT/FOXO3a signaling. Collectively, the studies suggest that CCN5 exerts its anti-invasive action through the regulation of p27Kip1. 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 4207. doi:1538-7445.AM2012-4207
Abstract 4456: Molecular events required for the induction of lethal iron deprivation in malignant hematopoietic cells via an antibody-avidin fusion protein specific for human transferrin receptor 1
Authors: José A. Rodríguez, Héctor E. López-Valdes, Gustavo F. Helguera, Sokuntheavy So, Rosendo Luria-Pérez, Tracy R. Daniels, Andrew C. Charles, Manuel L. Penichet
Journal: Cancer Research (2010)

Abstract Iron is an essential nutrient for cell growth and division. The transferrin receptor 1 (TfR1 or CD71) is a major gateway for iron import, and as such is expressed on a variety of cells; it is over-expressed in a number of tumors including hematopoietic malignancies. We have previously shown that an antibody-avidin fusion protein (ch128.1Av) specific for TfR1 is toxic to cancer cells, capable of inducing lethal iron deprivation in some malignant B-cells such as IM-9, but not in others such as U266. Importantly, ch128.1Av induces iron deprivation without directly preventing the binding of transferrin (Tf) to TfR1. In an attempt to identify the molecular events behind the iron deprivation induced by ch128.1Av, we have found that like Tf, internalization of ch128.1Av bound to TfR1 is clathrin, dynamin, and temperature dependent. Additionally, recycling of TfR1-bound ch128.1Av at short timescales (30min) is also similar to that of Tf and does not significantly alter the rate of Tf uptake. Long-term incubation (&amp;gt;6h) of IM-9 cells with ch128.1Av precludes their uptake of Tf and induces degradation of TfR1. This is not the case with U266 cells, in which Tf uptake remains unaffected and degradation of TfR1 is negligible in the presence of ch128.1Av. Clustering of cell surface TfR1 by ch128.1Av, given its multivalent nature, was previously thought to cause degradation of the receptor in sensitive cells such as IM-9. We now show that clustering of TfR1 occurs both in cells that are sensitive and resistant to treatment with the antibody (IM-9 and U266), indicating that clustering of TfR1 induced by ch128.1Av is not sufficient to induce receptor degradation and subsequent iron deprivation. Instead, resistance to treatment with ch128.1Av may be attributed to elements downstream of receptor binding/clustering; possibly related to those involved with TfR1 recycling and degradation. Further studies are needed to identify these resistance factors and potentially enhance the efficacy of ch128.1Av as well as other antibodies and/or small molecules that similarly target TfR1 for the treatment of hematologic malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4456.
Management of Hyperkinetic And Handicapped Children
Authors: J. Gordon Millichap
Journal: JAMA (1969)

<h3>To the Editor:—</h3> In the article, "Drugs in the Management of Hyperkinetic and Perceptually Handicapped Children" (<b>206</b>:1527, 1968), I have reviewed the literature concerning the evaluation of drugs in treatment of "... children of normal intelligence in whom control of motor hyperactivity should be accompanied by improvement in attention, memory, perception, and coordination." Reports of drugs employed primarily in mentally retarded children and notations of reputed efficacy unsupported by data were omitted from the discussion. Thioridazine hydrochloride did not qualify for inclusion in this communication because the majority of trials reported in the literature had been conducted in patients who were mentally deficient or epileptic. The reference cited by Drs. Livingston and Pauli is unacceptable because details of the numbers of patients treated and methods of evaluation are not provided. In a study of thioridazine in the management of "organic behavior disorders" in 33 children with epilepsy or mental retardation
FAMILIAL MAMMARY TUMORS IN THE RABBIT
Authors: Harry S. N. Greene
Journal: The Journal of Experimental Medicine (1939)

The clinical and pathological course of 25 mammary tumors in rabbits has been described. The antecedent breast history and morphology of the growths allowed a natural classification into two distinct types, one of which was distinguished by a preexisting cystic mastitis and a papillary structure, while the other originated in clinically normal mammary tissue and was characterized by an adenomatous structure. The two types of neoplasia occurred almost exclusively in two family groups and heredity played a fundamental rôle both in the occurrence of the tumors and in the determination of tumor type. Endocrine changes, comparable with those found in animals after long continued administration of estrogenic substances, occurred in tumor-bearing rabbits and it was inferred that the spontaneous growths represented a natural counterpart of the experimental induction of neoplasia with estrone.
Macrophage migration inhibitory factor in the nucleus of solitary tract decreases blood pressure in SHRs
Authors: André Henrique Freiria-Oliveira, Graziela Torres Blanch, Hongwei Li, Eduardo Colombari, Débora Simões Almeida Colombari, Colin Sumners
Journal: Cardiovascular Research (2012)

AimsThe macrophage migration inhibitory factor (MIF) is an intracellular inhibitor of the central nervous system actions of angiotensin II on blood pressure. Considering that angiotensin II actions at the nucleus of the solitary tract are important for the maintenance of hypertension in spontaneously hypertensive rats (SHRs), we tested if increased MIF expression in the nucleus of the solitary tract of SHR alters the baseline high blood pressure in these rats.