tbuckley/cabot-search huggingface dataset:
Sialyl Lewisx (sLex) and an sLexMimetic, CGP69669A, Disrupt E-Selectin–Dependent Leukocyte Rolling In Vivo
Authors: Keith E. Norman, Gary P. Anderson, Hartmut C. Kolb, Klaus Ley, Beat Ernst
Journal: Blood (1998)

Abstract Leukocyte rolling is the earliest observable event in their recruitment from the circulation to inflamed tissue. This rolling is mediated largely by interaction between the selectin family of adhesion molecules and their glycosylated ligands. Although the nature of these ligands and their interaction with the selectins is not fully understood, it is accepted that expression of fucosylated sialylated glycans such as sialyl Lewisx (sLex) is required for function. Despite findings that sLex inhibits binding of leukocytes to E-selectin in vitro, and has beneficial effects in inflammatory disease models, inhibition of E-selectin–dependent leukocyte rolling in vivo has not been described. Functional overlap between the selectins has been noted and reduction of rolling by E-selectin antibodies only occurs if P-selectin is absent or blocked. We demonstrate that leukocyte rolling velocity in tumor necrosis factor alpha (TNFα)-stimulated mouse cremaster is increased following treatment with either sLex or the sLex-mimetic CGP69669A and that rolling is dramatically reduced if CGP69669A is applied in the presence of anti–P-selectin antibody. These effects are characteristic of E-selectin antagonism. In contrast, surgically stimulated (L- or P-selectin–dependent) rolling is unaffected by either sLex or CGP69669A. Our data demonstrate that CGP69669A is an effective and selective antagonist of E-selectin in vivo.
Abstract 4524: Characterization of 28 patient derived colorectal cancer xenografts and analysis for response markers to an antiangiogenic treatment
Authors: Maria Rivera, Michael Becker, Peter M. Schlag, Alexandra Schwan, Johannes Merk, Andre Rosenthal, Bernd Hinzmann, Jens Hoffmann, Iduna Fichtner
Journal: Cancer Research (2012)

Abstract We have recently described an extended panel of new primary human CRC xenografts and their preclinical chemo-sensitivity to anti-cancer drugs (Poster 1584/3 AACR Annual Meeting 2010). These models consider more thoroughly the heterogeneity and genetic instability of tumors in a way ultimately enabling treatment decisions on an individualized basis. The approach is based on large scale screening for activity in new in vivo models combined with extensive characterization of these models (gene expression and mutations). Bioinformatic methods are used to further evaluate the mechanism of action of new drugs in colorectal cancer, to investigate possible resistance mechanisms and provide a rationale for combination therapies. Here we describe the evaluation of an antiangiogenic treatment in this panel of primary patient derived colorectal cancer models. Primary colon carcinoma tissue samples were collected using a standardized procedure. Tumor pieces were transplanted into immunodeficient mice immediately after surgery. A panel of 28 stably passagable colon cancer xenografts could be established as permanent tumor models. The results obtained so far, show that these patient-derived colon cancer models feature a high coincidence with the original tumor regarding histology and gene expression profiling. Response analysis in a subset of 19 xenografts evaluating the treated-to-control (T/C) ratios of tumor volumes revealed that the human specific VEGF antibody bevacizumab induces a meaningful biological effect (T/C below 50%) in 13 of 19 models. A first comparative genome-wide gene expression analyses of this subset revealed reasonable genes and pathways possibly involved in bevacizumab sensitivity. We will extend this investigation to all 28 tumor models in order to enhance the statistical robustness of the preliminary data. Our approach demonstrates that analysis of drug sensitivity together with bioinformatics correlations can provide candidate markers for further studies. An early implementation of such an approach in the drug development process could be helpful for the identification of predictive markers helping to select tumors likely to benefit from the drug as well as provide a rationale for combinations to be tested in clinical trials. These new strategies may help to better integrate research results in clinical development and may increase the success of new anti-cancer drugs in clinical studies. 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 4524. doi:1538-7445.AM2012-4524
Hepatocyte Growth Factor Promotes Cell Survival From Fas-Mediated Cell Death in Hepatocellular Carcinoma Cells via Akt Activation and Fas-Death–Inducing Signaling Complex Suppression
Authors: Atsushi Suzuki, Midori Hayashida, Hirokazu Kawano, Kazushi Sugimoto, Takeshi Nakano, Katsuya Shiraki
Journal: Hepatology (2000)

The Akt/PI-3 kinase pathway is a system essential for cell survival. In the current study, we showed that hepatocyte growth factor (HGF) activates the Akt/PI-3 kinase pathway to suppress Fas-mediated cell death in human hepatocellular carcinoma (HCC; 3 lines; SK-Hep1, HLE, and Chang Liver cell lines), hepatoblastoma (1 line; HepG2), and embryonic hepatocyte (1 line; WRL). Five tested cell lines showed the resistance to Fas-mediated cell death by the pretreatment of HGF. This HGF-induced cell survival was suppressed by wortmannin (Akt/PI-3 kinase pathway inhibitor), suggesting an involvement of Akt. When cells were pretreated with HGF, Fas-mediated cell death was suppressed, followed by Akt phosphorylation at Ser473. Fas-death-inducing signaling complex (DISC) formation, especially FADD and caspase 8 interaction, was suppressed by HGF and the suppression of the Akt/PI-3 kinase pathway by transient expression of PTEN, resulting in acquisition of Fas-DISC formation and Fas-mediated cell death in HGF-treated cells. We suggest that HGF promotes cell survival in hepatocyte-derived cell lines (HCC, hepatoblastoma, and embryonic hepatocyte) from Fas-mediated cell death via Fas-DISC suppression as a result of Akt activation.
Carcinogenicity of trichloroethylene, tetrachloroethylene, some other chlorinated solvents, and their metabolites
Authors: Neela Guha, Dana Loomis, Yann Grosse, Béatrice Lauby-Secretan, Fatiha El Ghissassi, Véronique Bouvard, Lamia Benbrahim-Tallaa, Robert Baan, Heidi Mattock, Kurt Straif
Journal: The Lancet Oncology (2012)
ON THE RÔLE OF CARBOHYDRATE HAPTENS IN BACTERIAL ANAPHYLAXIS
Authors: Joseph Tomcsik, T. J. Kurotchkin
Journal: The Journal of Experimental Medicine (1928)

1. In passively sensitized animals bacterial anaphylaxis has been produced, in vivo and in vitro, with haptens from B. lactis aerogenes, the pneumobacillus, and a yeast. 2. The smallest amount of hapten causing fatal anaphylaxis is less than the minimal amount of protein which will cause death in properly sensitized animals. 3. The haptens used were largely carbohydrates, and gave none of the protein reactions, but since they did contain a small amount of nitrogen we cannot yet assert positively that carbohydrate alone will produce shock. 4. Since haptens will not sensitize animals we must conclude that the anaphylactogenic and shock-producing parts of the antigen are not identical. 5. These experiments provide further evidence of the close relationship of precipitins to anaphylaxis.
END SYSTOLIC VOLUME AND SCAR BURDEN PREDICT GENDER DIFFERENCES IN SURVIVAL IN PATIENTS WITH SEVERE ISCHEMIC CARDIOMYOPATHY UNDERGOING REVASCULARIZATION
Authors: Deborah Kwon, Rory Hachamovitch, Lisa Asamoto, Zoran Popovic, Randall Starling, Milind Desai, Scott Flamm, Thomas Marwick
Journal: Journal of the American College of Cardiology (2012)
Prognostic Factors Associated to Persistent IgE-mediated Cow's Milk Allergy (CMA)
Authors: C.M.A. Jacob, A.C. Pastorino, Â.B.F. Fomin, L.A. Watanabe, V.Z. Fucci, A.K.F. Gushken, A. Brandão, U. Doria, C.A. Silva, A.B.M. Castro
Journal: Journal of Allergy and Clinical Immunology (2009)
Bone Marrow Transplantation for Severe Combined Immune Deficiency
Authors: Eyal Grunebaum
Journal: JAMA (2006)

Context Bone marrow transplantation (BMT) using stem cells obtained from a familyrelated, HLA-identical donor (RID) is the optimal treatment for patients with severe combined immune deficiency (SCID).In the absence of an RID, HLA-mismatched related donors (MMRDs) are often used.However, compared with RIDs, use of MMRDs for BMT is associated with reduced survival and inferior long-term immune reconstitution.Use of HLA-matched unrelated donors (MUDs) represents another potential alternative for BMT.Objective To compare outcomes and immune reconstitution in a large cohort of patients with SCID who received RID, MUD, or MMRD BMT. Design, Setting, and PatientsRetrospective study of medical records from 94 infants diagnosed as having SCID who received BMT between 1990 and 2004 at 1 Canadian and 1 Italian pediatric referral center.Thirteen, 41, and 40 patients received RID, MUD, and MMRD BMT, respectively. Main Outcome MeasuresSurvival and graft failure, along with incidence of graftvs-host disease, infections, and other complications; immune reconstitution was assessed in children who survived for more than 2 years after BMT. ResultsSurvival after RID BMT was highest.Twelve (92.3%) of 13 patients who received RID BMT, 33 (80.5%) of 41 who received MUD BMT, and 21 (52.5%) of 40 patients who received MMRD BMT survived.Compared with MMRD BMT, survival was significantly higher with RID (P = .008)or with MUD (P = .03).Graft failures and need for repeat BMT were more common in patients receiving MMRD BMT than in those who underwent MUD BMT.Long-term reconstitution of a full T-cell repertoire was achieved more frequently following MUD BMT (94.7%) than after MMRD BMT (61.1%) (P=.02).Acute graft-vs-host disease was documented in 73.1% of patients following MUD BMT but in only 45% after MMRD BMT (P=.009).Conversely, interstitial pneumonitis was observed more frequently after MMRD BMT (14 [35.0%] of 40) than after MUD BMT (3 [7.3%] of 41; P=.002). ConclusionOur study suggests that in the absence of a relative with identical HLA, MUD BMT may provide better engraftment, immune reconstitution, and survival for patients with SCID than MMRD BMT.
SOME MEDICO-LEGAL ASPECTS OF SENILE DEMENTIA.
Authors: WILLIAM B. FLETCHER
Journal: JAMA (1898)

Perhaps the most marked feature in the relations of Law and Medicine which has become prominent within the last twenty-five years, is the tendency to "break wills," or contest them upon the ground of mental unsoundness; said mental unsoundness being usually attributed to the advanced age of the testator which the medical expert—being compelled to give a name—denominates "Senile Dementia." It is not likely there are more old persons making wills, or that senile dementia is on the increase, and our query is: Why has litigation on this ground become more frequent than it was a half century ago? As our laws pertaining to wills have not changed, and as the disease—so-called senile dementia—has not changed, why is that about nine in ten wills made by wealthy persons are subject to litigation, and the wealth earned by the testator, which was as much his own as his watch or his
Hospital- and Patient-Level Characteristics and the Risk of Appendiceal Rupture and Negative Appendectomy in Children
Authors: Todd A. Ponsky
Journal: JAMA (2004)

The rates of appendiceal rupture and negative appendectomy in children remain high despite efforts to reduce them. Both outcomes are used as measures of hospital quality. Little is known about the factors that influence these rates.To investigate the association between hospital- and patient-level characteristics and the rates of appendiceal rupture and negative appendectomy in children.Retrospective review using the Pediatric Health Information System database containing information on 24,411 appendectomies performed on children aged 5 to 17 years at 36 pediatric hospitals in the United States between 1997 and 2002.Rates of negative appendectomy and appendiceal rupture; the odds ratio (OR) of negative appendectomy and appendiceal rupture by hospital, patient age, race, and health insurance status, and hospital fiscal year and appendectomy volume. Negative appendectomy rate was defined as the number of patients with appendectomy but without appendicitis divided by the total number of appendectomies.The median negative appendectomy rate was 3.06% (range, 1%-12%) and the median appendiceal rupture rate was 35.08% (range, 22%-62%). The adjusted OR for appendiceal rupture was higher in Asian children (1.66; 95% confidence interval [CI], 1.24-2.23) and black children (1.13; 95% CI, 1.01-1.30) compared with white children. Children without health insurance and children with public insurance had increased odds of appendiceal rupture compared with children who had private health insurance (adjusted OR, 1.36; 95% CI, 1.22-1.53 for self-insured; adjusted OR, 1.48; 95% CI, 1.34-1.64 for public insurance). No correlation existed between negative appendectomy rate and race, health insurance status, or hospital appendiceal rupture rate. The negative appendectomy rate improved as the hospital appendectomy volume increased.The rate of appendiceal rupture in school-aged children was associated with race and health insurance status and not with negative appendectomy rate and therefore is more likely to be associated with prehospitalization factors such as access to care, quality of care, and patient or physician education.
Updates from the British Association of Dermatologists 87th Annual Meeting, 10–13 July 2007, Birmingham, U.K.
Authors: A. Birnie, S. Langan, J.S.C. English
Journal: British Journal of Dermatology (2008)

This is a synopsis of the main research and clinical findings presented at the British Association of Dermatologists meeting held during 10-13 July 2007 in Birmingham, U.K. The conference highlighted the recent biological, epidemiological and therapeutic advances that have been made recently in the field of dermatology. The authors focus on the more important advances or summaries of findings, but this is not meant as a substitute for reading the conference proceedings and related references quoted in this article.
The Karen Ann Quinlan Case
Authors: Richard A. McCormick
Journal: JAMA (1975)

The medical profession should be terrified at the possibilities hidden in the happenings in Morristown, NJ. The Karen Ann Quinlan case does not, as such, raise problems unfamiliar to the physician. For some years, physicians— though perhaps not all, or even as many as some would like—have been refusing to inflict artificial life-supports on irretrievably dying patients. Two principles are crucial to the ethos of the medical profession and are imprinted deep in the hearts of individual physicians. First, their task is to heal and cure, whenever possible. Second, when a cure is no longer possible, they are to care for and comfort the dying. Members of the medical profession, understandably and laudably, resist—and sometimes even resent their inability always to cure; they, like all of us, recoil when they see that death is to be the victor. Like all of us, the physician has much to learn about companying
Linking Automated Databases for Research in Managed Care Settings
Authors: Joe V. Selby
Journal: Annals of Internal Medicine (1997)

Spurred by demands for data from employer-purchasers and accreditation agencies and the adoption of strategies for disease management and outcome-based quality assurance, managed care organizations have recognized the need for rapid, convenient access to clinical information. Large investments in administrative and clinical data systems have also produced unprecedented opportunities for research on health care and epidemiology in large, defined populations. There is a long history of contributions to research by investigators who are based in the older nonprofit group and staff models of health maintenance organizations (HMOs). Many of these organizations maintain research units that are primarily funded by outside sources. Research includes descriptive and etiologic studies of epidemiology, randomized and observational studies of the effectiveness of treatment regimens, studies of disease costs and estimation of cost-effectiveness, investigations of risk predictions in populations, of risk and changes in organizational behavior, and evaluations of interventions to alter physician and patient behavior. The work is often conducted in collaboration with academic researchers. The HMO Research Network has recently been established to foster a scientific exchange among HMO-based researchers. As managed care organizations come to provide health care coverage to most U.S. citizens, research conducted by these organizations increasingly overlaps with public health research. Collaboration between HMO-based research centers and researchers from academia and government will undoubtedly continue to increase.
Setting Research Priorities for Preconception Care in Low- and Middle-Income Countries: Aiming to Reduce Maternal and Child Mortality and Morbidity
Authors: Sohni Dean, Igor Rudan, Fernando Althabe, Aimee Webb Girard, Christopher Howson, Ana Langer, Joy Lawn, Mary-Elizabeth Reeve, Katherine C. Teela, Mireille Toledano, Chandra-Mouli Venkatraman, José M. Belizan, Josip Car, Kit Yee Chan, Subidita Chatterjee, Stanley Chitekwe, Tanya Doherty, France Donnay, Majid Ezzati, Khadija Humayun, Brian Jack, Zohra S. Lassi, Reynaldo Martorell, Ysbrand Poortman, Zulfiqar A. Bhutta
Journal: PLoS Medicine (2013)

Sohni Dean and colleagues report their CHNRI exercise that developed health research priorities for effective pre-conception care in low- and middle-income countries. Please see later in the article for the Editors' Summary
Physiology, Biochemistry, and Molecular Biology of the Skin
Authors: Walter B. Shelley
Journal: JAMA (1992)

To open this book is to enter a vast cathedral of knowledge about the skin around us. As you walk in, you will see no stained glass, but rather the subdued light from scores of interesting black-and-white illustration windows. Just inside the vestibule is the baptismal font for newborn skin, with insight into the developing structure and ultrastructure of the epidermis and dermis. Behold these wonders of the epidermis: the keratinocyte, which lives to die for your protection; the melanocyte, your shield from the sun; the Langerhans cell, your outermost immune guard; and the Merkel cell, your touch button. You also see the dermis, with collagen and elastic fibers embedded in a glycosaminoproteoglycan gel, and a mesh of blood vessels, lymphatic channels, and nerves. If you peer down into the holes in the epidermis, you will see the wonders of hair, sweat, and oil formation. As the great doors swing
Thalassemia intermedia caused by heterozygosity for both β-thalassemia and hemoglobin saki [β14 (a11) leu→pro]
Authors: Paul F. Milnera, Charles C. Corley, William L. Pomeroy, Jerry B. Wilson, Marsha Gravely, Titus H. J. Huisman
Journal: American Journal of Hematology (1976)

Abstract The syndrome thalassemia intermedia can be the clinical expression of heterozygosity for different types of thalassemia, β‐thalassemia and hereditary persistence of fetal hemoglobin, β‐thalassemia and Hb‐Lepore, and in blacks it may even represent a true β‐thalassemia homozygote. This report describes thalassemia intermedia in a white male due to β‐thalassemia and an unstable hemoglobin. Chain‐synthesis studies showed an excess of β‐chain production over β‐chain production in the propositus and his mother but balanced chain synthesis in the clinically normal father, who is heterozygous for the unstable hemoglobin. The unstable hemoglobin was found to be β 14 (A11) Leu→Pro, which has previously been described in a clinically normal African woman, and named Hb‐Saki. This hemoglobin is not distinguishable from Hb‐A on routine electrophoresis at alkaline or acid pH and tests for unstable hemoglobins are necessary for its detection. The increasing list of such hemoglobin variants and previous cases of heterozygosity for β‐thalassemia and unstable hemoglobins are reviewed.
The secret life of the NHS
Authors: J. Jones
Journal: BMJ (2000)

See also pp 1460, 1480, 1483

Despite the fact that the Labour party promised greater openness when in opposition, now that it is in government it seems as anxious as its Conservative predecessor to ensure that bad news about the health service is suppressed. In this article and the next, Judy Jones looks at ways in which the government controls what we hear about the NHS and at how it took the health department 10 months to reply to the BMJ 's critique of its policy on the private finance initiative.

When the last Conservative government was in power the BMJ published articles about the suppression of free speech and information and the politicisation of the NHS and health care.1 2 These cited numerous examples, ranging from “gagging” clauses in contracts and suppression of independent reports to people being told, in essence, to keep quiet about service cuts or other matters that were potentially embarrassing to politicians.

The Labour party's promises of free speech, openness, impartiality, and more democracy and accountability in and around the NHS and elsewhere helped secure the party a landslide victory in the last general election. In the interests of free speech and pursuance of political impartiality, the BMJ has repeated these earlier exercises. We have collected some fresh examples of attempts to prevent disclosure of “public interest” information and of political chicanery since the change of government in May 1997. Against the backcloth of recent rebellion in Labour's ranks over the government's freedom of information bill, we feel it timely to report, once again, on what the government of the day would rather you didn't know.

#### Summary points

The Labour party's promises of openness and more democracy and accountability in the NHS helped secure the party a landslide victory in the last general election, but the …
Variation in pulmonary retention of 131I-macroaggregated albumin
Authors: R. P. Spencer
Journal: Thorax (1972)

Counting over the right lung after the intravenous injection of <sup>131</sup>I-macroaggregated albumin revealed a wide spread in retention half-times of the radiolabel (7 hours to 31 hours) even among patients having identical preparations. This needs further exploration as to its mechanism and its effect on the calculated radiation exposure of the lungs.
Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C: Evidence for a role of HCV genotype 3 in steatosis
Authors: L. Castera, C. Hezode, F. Roudot-Thoraval, I. Lonjon, E.S. Zafrani, J.M. Pawlotsky, D. Dhumeaux
Journal: Journal of Hepatology (2003)
GLP-1 Inhibits and Adrenaline Stimulates Glucagon Release by Differential Modulation of N- and L-Type Ca2+ Channel-Dependent Exocytosis
Authors: Yang Z. De Marinis, Albert Salehi, Caroline E. Ward, Quan Zhang, Fernando Abdulkader, Martin Bengtsson, Orit Braha, Matthias Braun, Reshma Ramracheya, Stefan Amisten, Abdella M. Habib, Yusuke Moritoh, Enming Zhang, Frank Reimann, Anders H. Rosengren, Tadao Shibasaki, Fiona Gribble, Erik Renström, Susumu Seino, Lena Eliasson, Patrik Rorsman
Journal: Cell Metabolism (2010)
Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma
Authors: Virginia Norris, Lee Choong, Duyen Tran, Zoe Corden, Malcolm Boyce, Hasan Arshad, Stephen Holgate, Brian O'Connor, Sylvaine Millet, Barry Miller, Shashank Rohatagi, Stephane Kirkesseli
Journal: Journal of Allergy and Clinical Immunology (2005)