tbuckley/cabot-search huggingface dataset:
Metabolic Dysregulation in Melanoma: Cause or Consequence?
Authors: Rizwan Haq
Journal: Cancer Discovery (2014)

Abstract Summary: Parmenter and colleagues identify molecular pathways by which BRAF–MAPK signaling regulates glycolysis in melanoma, suggesting novel approaches to target these metabolic dependencies. Cancer Discov; 4(4); 390–1. ©2014 AACR. See related article by Parmenter et al., p. 423
First-aid supplies for backpacking.
Authors: S L Puretz
Journal: British Journal of Sports Medicine (1992)

A portable first-aid kit should be carried in the backpack of campers, hikers, and anyone who expects to spend time in a remote and unoccupied area. That is the recommendation found in lay texts dealing with medical care, in backpacking books, as well as in articles appearing in popular magazines. It goes without saying that it is far better to practise safety and prevention than to have to use first aid. However, many times medical problems occur which no amount of safety and forethought could have prevented. Information in this paper indicates that hikers are generally well prepared for the health-related problems they encounter. Hikers carry diverse supplies to meet health problems but there are some basic supplies with which hikers start their long-distance sojourn. Those supplies and their usage rates are discussed, as are attitudes toward using the supplies.
High-Throughput Characterization of 10 New Minor Histocompatibility Antigens by Whole Genome Association Scanning
Authors: Cornelis A.M. Van Bergen, Caroline E. Rutten, Edith D. Van Der Meijden, Simone A.P. Van Luxemburg-Heijs, Ellie G.A. Lurvink, Jeanine J. Houwing-Duistermaat, Michel G.D. Kester, Arend Mulder, Roel Willemze, J.H. Frederik Falkenburg, Marieke Griffioen
Journal: Cancer Research (2010)

Patients with malignant diseases can be effectively treated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Polymorphic peptides presented in HLA molecules, the so-called minor histocompatibility antigens (MiHA), play a crucial role in antitumor immunity as targets for alloreactive donor T cells. Identification of multiple MiHAs is essential to understand and manipulate the development of clinical responses after allo-SCT. In this study, CD8+ T-cell clones were isolated from leukemia patients who entered complete remission after allo-SCT, and MiHA-specific T-cell clones were efficiently selected for analysis of recognition of a panel of EBV-transformed B cells positive for the HLA restriction elements of the selected T-cell clones. One million single nucleotide polymorphisms (SNP) were determined in the panel cell lines and investigated for matching with the T-cell recognition data by whole genome association scanning (WGAs). Significant association with 12 genomic regions was found, and detailed analysis of genes located within these genomic regions revealed SNP disparities encoding polymorphic peptides in 10 cases. Differential recognition of patient-type, but not donor-type, peptides validated the identification of these MiHAs. Using tetramers, distinct populations of MiHA-specific CD8+ T cells were detected, demonstrating that our WGAs strategy allows high-throughput discovery of relevant targets in antitumor immunity after allo-SCT.
Role of truncating mutations in MME gene in fetomaternal alloimmunisation and antenatal glomerulopathies
Authors: Hanna Debiec, Jeroen Nauta, Florence Coulet, Mirjam van der Burg, Vincent Guigonisy, Thierry Schurmans, Emile de Heer, Florent Soubrier, Francoise Janssen, Pierre Ronco
Journal: The Lancet (2004)
Specialist investigation of obscure gastrointestinal bleeding.
Authors: J N Thompson, R R Salem, A P Hemingway, H C Rees, H J Hodgson, C B Wood, D J Allison, J Spencer
Journal: Gut (1987)

The investigation and treatment of 131 patients with 'obscure' gastrointestinal bleeding has been reviewed. One hundred and six patients were assessed electively for recurrent haemorrhage, 25 presented as emergencies. The major presenting feature was melaena (55 patients), anaemia (35), rectal bleeding (34), haematemesis (six) and ileostomy bleeding (one). The lesions responsible for haemorrhage were colonic angiodysplasia (52 patients), small bowel vascular anomalies (16), Meckel's diverticula (nine), small bowel smooth muscle tumours (seven), gastric vascular anomalies (four), chronic pancreatitis (three), colonic diverticular disease (three) and 16 other miscellaneous lesions. No lesion was found in 21 cases. Lesions were first shown by visceral angiography (69 patients), at laparotomy (23), on endoscopy (11), on gastrointestinal contrast radiological studies (four), and at ERCP (three). Lesions which were undetectable at operation increased markedly with age (p less than 0.0001). Expert visceral angiography is strongly recommended before surgery in patients over 45 years of age and after laparotomy when no cause has been found. Exploratory laparotomy is recommended at an early stage for younger patients, and for older patients after non-diagnostic angiography.
Heterozygosity for p53 (<i>Trp53</i> <i>+/−</i>) Accelerates Epithelial Tumor Formation in Fanconi Anemia Complementation Group D2 (<i>Fancd2</i>) Knockout Mice
Authors: Scott Houghtaling, Laura Granville, Yassmine Akkari, Yumi Torimaru, Susan Olson, Milton Finegold, Markus Grompe
Journal: Cancer Research (2005)

Abstract Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure and an increased susceptibility to cancer. FA is genetically heterogeneous, consisting of at least 11 complementation groups, FA-A through L, including FA-D1 (BRCA2) and D2. We have previously reported an increased incidence of epithelial tumors in Fancd2 knockout mice. To further investigate the role of the FA pathway in tumor prevention, Fancd2 mutant mice were crossed to mice with a null mutation in the tumor suppressor gene, Trp53. The tumor spectrum in Fancd2−/−/Trp53+/− mice included sarcomas expected in Trp53 heterozygotes, as well as mammary and lung adenocarcinomas that occur rarely in Trp53 heterozygotes. These tumors occurred earlier than in Fancd2−/− control mice. Therefore, the Fancd2−/−/Trp53+/− mice represent an improved model for the study of adenocarcinoma in FA. In addition, it was found that Fancd2−/− mouse embryonic fibroblasts but not Fancd2−/−/Trp53−/− mouse embryonic fibroblasts arrest following DNA damage. Therefore, Trp53 is required for the S phase checkpoint activation observed in Fancd2 mutant cells. Fancd2−/−/Trp53−/− cells showed an increase in aneuploidy and had multiple gross chromosomal rearrangements.
Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis
Authors: M. Martinez-Losa, J. Cortijo, G. Juan, M. Ramon, M. J. Sanz, E. J. Morcillo
Journal: European Respiratory Journal (2007)

Eosinophils are oxidant-sensitive cells considered relevant in allergic inflammation. The present study aimed to examine the effects of the antioxidant N-acetyl-L-cysteine (NAC) on constitutive and cytokine-delayed apoptosis in human isolated eosinophils. Human eosinophils were purified from the blood of healthy donors by a magnetic separation system. Apoptosis and cellular glutathione were assessed by cytofluorometric analysis and nuclear factor (NF)-kappaB binding activity assessed by electrophoresis mobility shift assay. The rate of spontaneous apoptosis of human eosinophils after 24 h culture, as assessed by annexin-V-positive staining, was mean+/-sem 48.2+/-1.4%, n = 5. Granulocyte-macrophage colony-stimulating factor (GM-CSF; 10 ng.mL(-1)) decreased apoptosis to 19.4+/-1.8%, n = 5. NAC (5 mM) inhibited spontaneous apoptosis (33.6+/-2.7%, n = 5) but augmented apoptosis in the presence of GM-CSF (30.9+/-1.5%, n = 5). NAC (5 mM) also increased the rate of apoptosis in the presence of tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) and interleukin-5 (5 ng.mL(-1)). NAC (5 mM) increased eosinophil glutathione content. The increase in eosinophil NF-kappaB binding activity induced by GM-CSF and TNF-alpha was suppressed by NAC. In conclusion, N-acetylcysteine modulates eosinophil apoptosis by inhibiting constitutive apoptosis but reversing the survival effect produced by inflammatory cytokines in human eosinophils.
Pancreatic Adenocarcinoma, Version 2.2014
Authors: Margaret A. Tempero, Mokenge P. Malafa, Stephen W. Behrman, Al B. Benson, Ephraim S. Casper, E. Gabriela Chiorean, Vincent Chung, Steven J. Cohen, Brian Czito, Anitra Engebretson, Mary Feng, William G. Hawkins, Joseph Herman, John P. Hoffman, Andrew Ko, Srinadh Komanduri, Albert Koong, Andrew M. Lowy, Wen Wee Ma, Nipun B. Merchant, Sean J. Mulvihill, Peter Muscarella, Eric K. Nakakura, Jorge Obando, Martha B. Pitman, Sushanth Reddy, Aaron R. Sasson, Sarah P. Thayer, Colin D. Weekes, Robert A. Wolff, Brian M. Wolpin, Jennifer L. Burns, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2014)

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.
Plasticity: Implications for opioid and other pharmacological interventions in specific pain states
Authors: Anthony H. Dickenson
Journal: Behavioral and Brain Sciences (1997)

The spinal mechanisms of action of opioids under normal conditions are reasonably well understood. The spinal effects of opioids can be enhanced or reduced depending on pathology and activity in other segmental and nonsegmental pathways. This plasticity will be considered in relation to the control of different pain states using opioids. The complex and contradictory findings on the supraspinal actions of opioids are explicable in terms of heterogeneous descending pathways to different spinal targets using multiple transmitters and receptors – therefore opioids can both increase and decrease activity in descending pathways. These pathways could exhibit considerable plasticity. There is increasing evidence that delta opioid receptor agonists have the potential to replace morphine as major analgesics with reduced side-effect profiles. The concept of preemptive analgesia, based on preventing the induction of some of the negative plastic influences on opioid controls and the detrimental effects of pain, is sound, but experimental verification in the clinical setting is difficult. For example, a delayed compensatory upregulation of inhibitory systems, particularly in inflammation, may counter persistent painful inputs. Combination therapy with opioids may be beneficial in many pain states where either negative influences are blocked or inhibitory controls are enhanced. Finally, developmental aspects of these systems are discussed in connection with the treatment of pain in young children, where inhibitory systems in the spinal cord are immature.
The effect of lifestyle on wheeze, atopy, and bronchial hyperreactivity in Asian and white children.
Authors: O J Carey, J B Cookson, J Britton, A E Tattersfield
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

There is increasing evidence linking Western culture to increasing prevalence of asthma. We have measured the prevalence of symptoms of asthma, bronchial hyperreactivity, and atopy in a sample of white and Asian inner city schoolchildren aged 8-11 yr in the U.K. and assessed the influence of certain aspects of western culture on these variables. Bronchial reactivity was measured by methacholine challenge, atopy by allergen skin prick tests, and symptoms of asthma and aspects of lifestyle by questionnaire. Degree of Westernization was assessed from dietary habit categorized as exclusively Asian, mostly Asian, mixed, or exclusively English. The questionnaire was completed by 92% of children. The 308 white and 539 Asian children were of similar age (mean 9.3 yr versus 9.4 yr) with slightly more girls in the Asian group (52.6% versus 47.4%). The white children reported more wheeze within the past year (14.2% versus 8.8%, p = 0.01) but less were atopic (29.5% versus 38.4%, p = 0.01) with no significant difference in the prevalence of hyperreactivity (31.5% versus 29.6%, p = 0.57). Most Asians (97%) included Asian food in their diet; 35% ate a mostly Asian diet, 45% ate a mixed English and Asian diet, and 17% ate an exclusively Asian diet. After controlling for confounding factors whites were at higher risk of hyperreactivity and lower risk of atopy, and the risk of hyperreactivity and to a lesser extent atopy among Asian children was related to diet in a dose response fashion. The relative odds for hyperreactivity with an exclusively Asian, mostly Asian, or a mixed diet relative to an English diet were 0.31 (95% CI 0.15 to 0.62), 0.88 (0.56 to 1.37), and 0.99 (0.65 to 1.49), and for atopy were 1.22 (0.72 to 2.06), 1.47 (0.99 to 2.19), and 1.78 (1.23 to 2.58). These results suggest that diet or other closely related factors associated with Westernization are involved in the etiology of atopy and hyperreactivity.
Standardized testing with chlorhexidine in perioperative allergy – a large single‐centre evaluation
Authors: M. S. Opstrup, H.‐J. Malling, M. Krøigaard, H. Mosbech, P. S. Skov, L. K. Poulsen, L. H. Garvey
Journal: Allergy (2014)

Perioperative allergic reactions to chlorhexidine are often severe and easily overlooked. Although rare, the prevalence remains unknown. Correct diagnosis is crucial, but no validated provocation model exists, and other diagnostic tests have never been evaluated. The aims were to estimate (i) the prevalence of chlorhexidine allergy in perioperative allergy and (ii) the specificity and sensitivity for diagnostic tests for chlorhexidine allergy.We included all patients investigated for suspected perioperative allergic reactions in the Danish Anaesthesia Allergy Centre during 2004-2012. The following tests were performed: specific IgE (Immunocap® ; Phadia AB, Sweden), histamine release test (HR) (RefLab ApS, Denmark), skin prick test (SPT) and intradermal test (IDT). Positivity criteria were as follows: specific IgE >0.35 kUA/l; HR class 1-12; SPT mean wheal diameter ≥3 mm; IDT mean wheal diameter ≥ twice the diameter of negative control. Chlorhexidine allergy was post hoc defined as a relevant clinical reaction to chlorhexidine combined with two or more positive tests. Based on this definition, sensitivity and specificity were estimated for each test.In total, 22 of 228 patients (9.6%) met the definition of allergy to chlorhexidine. Estimated sensitivity and specificity were as follows: specific IgE (sensitivity 100% and specificity 97%), HR (sensitivity 55% and specificity 99%), SPT (sensitivity 95% and specificity 97%) and IDT (sensitivity 68% and specificity 100%).In patients investigated for suspected perioperative allergic reactions, 9.6% were diagnosed with allergy to chlorhexidine. Using our definition of chlorhexidine allergy, the highest combined estimated sensitivity and specificity was found for specific IgE and SPT.
Prediction of Psychiatric Morbidity in Severely Injured Accident Victims at One-year Follow-up
Authors: ULRICH SCHNYDER, HANSPETER MOERGELI, OTMAR TRENTZ, RICHARD KLAGHOFER, CLAUS BUDDEBERG
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The objective of this study was to assess the prevalence of posttraumatic stress disorder (PTSD) and symptoms of depression and anxiety in severely injured accident victims 1 yr posttrauma and to predict psychiatric morbidity by means of variables assessed shortly after the accident. The sample consisted of 106 consecutive patients with accidental injuries (mean Injury Severity Score = 21.9, mean Glasgow Coma Scale score = 14.4) admitted to the intensive care unit of a University Hospital. Patients with severe head injuries, suicide attempters, and victims of physical assault were excluded. At 1-yr follow-up, two patients (1.9%) had PTSD, and 13 (12.3%) had subsyndromal PTSD. Eighteen patients (17%) had clinically relevant symptoms of anxiety, and nine (8.5%) were depressed. Overall, 27 patients (25.5%) showed some form of psychiatric morbidity (full or subsyndromal PTSD and/or anxiety and/or depression). Logistic regression analysis, using 1-yr psychiatric morbidity status as the dependent variable, allowed correct classification of 83.8% of patients 12 mo postaccident (specificity 91.8%, sensitivity 61.5%). Biographical risk factors and a sense of death threat contributed significantly to the predictive model. We conclude that a substantial proportion of severely injured accident victims develop some form of psychiatric morbidity that can be predicted to some degree by mainly psychosocial variables.Keywords: accidents; psychology; post-traumatic stress disorder; depression; anxiety
Phase I Trial of Temozolomide Plus <i>O</i><sup>6</sup>-Benzylguanine for Patients With Recurrent or Progressive Malignant Glioma
Authors: Jennifer A. Quinn, Annick Desjardins, Jon Weingart, Henry Brem, M. Eileen Dolan, Shannon M. Delaney, James Vredenburgh, Jeremy Rich, Allan H. Friedman, David A. Reardon, John H. Sampson, Anthony E. Pegg, Robert C. Moschel, Robert Birch, Roger E. McLendon, James M. Provenzale, Sridharan Gururangan, Janet E. Dancey, Jill Maxwell, Sandra Tourt-Uhlig, James E. Herndon, Darell D. Bigner, Henry S. Friedman
Journal: Journal of Clinical Oncology (2005)

We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG.For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined.The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression.This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.
Clozapine in the Treatment of Refractory Psychotic Mania
Authors: Alan I. Green, Maricio Tohen, Jayendra K. Patel, Michael Banov, Curtiss DuRand, Ileana Berman, Howard Chang, Carlos Zarate, Joel Posener, Hang Lee, Ree Dawson, Carol Richards, Jonathan O. Cole, Alan F. Schatzberg
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The efficacy of clozapine was examined in a group of patients with treatment-refractory bipolar disorder, manic type with psychotic features.METHOD: Twenty-two subjects with treatment-refractory bipolar disorder with active manic and psychotic symptoms participated in a 12-week open-label trial of clozapine. After a 2–10-day drug washout period, patients began treatment with clozapine at 25 mg/day; the dose was increased 25 mg/day (as tolerated) to a maximum level of 550 mg/day. Patients were evaluated longitudinally over the course of the study with the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale, and the Clinical Global Impressions (CGI) scale.RESULTS: Fourteen of the 22 subjects in the study continued taking clozapine for at least 10 of the 12 weeks. Among the entire group, mean improvements of 56.7%, 56.6%, and 39.1% were seen on the BPRS, Young Mania Rating Scale, and CGI, respectively. Seventeen of the 22 subjects (77.3%) experienced at least a 20% improvement in scores on all three scales.CONCLUSIONS: The findings from this open-label study, which are consistent with previous retrospective studies, case reports, and one other open-label prospective study, suggest that clozapine is an effective agent for patients with treatment-refractory psychotic mania.
Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence
Authors: Devasmitha Venkataraman, Nelís Soto-Ramírez, Ramesh J. Kurukulaaratchy, John W. Holloway, Wilfried Karmaus, Susan L. Ewart, S. Hasan Arshad, Mich Erlewyn-Lajeunesse
Journal: Journal of Allergy and Clinical Immunology (2014)
Favorable outcome of haploidentical hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter study in Southwest China
Authors: Li Gao, Cheng Zhang, Lei Gao, Yao Liu, Yi Su, Sanbin Wang, Bin Li, Tonghua Yang, Zhong Yuan, Xi Zhang
Journal: Journal of Hematology & Oncology (2015)

Since the introduction of tyrosine kinase inhibitors (TKIs) into combination chemotherapy regimens, the majority of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved complete remission (CR). However, without allogeneic hematopoietic stem cell transplantation (HSCT), long-term outcomes in adults remain unsatisfactory. Indeed, haploidentical HSCT has become a common treatment for adult patients who lack an HLA-matched donor, though limited data are available on the efficacy of haploidentical HSCT in Ph+ ALL patients. We analyzed the clinical outcomes of 82 Ph+ ALL patients who underwent haploidentical HSCT (n = 47) or HLA-matched HSCT (n = 35). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess BCR-ABL expression. All of the patients were treated with an imatinib-based regimen before undergoing HSCT. Imatinib treatment was resumed in the patients' posttransplantation following detection of BCR-ABL transcripts. All of the patients achieved neutrophil and platelet engraftment, with the exception of five patients who died prior to engraftment. Haploidentical HSCT was associated with higher incidences of acute graft-versus-host disease (GVHD) (51.1 vs. 25.7 %, p < 0.05) and chronic GVHD (48.9 vs. 25.7 %, p < 0.05) compared with HLA-matched HSCT, but there was no difference in the incidence of either grades III–IV acute GVHD or extensive chronic GVHD. The incidence of cytomegalovirus (CMV) infection was significantly higher in the patients treated with haploidentical HSCT than in those treated with HLA-matched HSCT (38.3 vs. 14.3 %, p < 0.05). Haploidentical HSCT was associated with a significantly lower relapse rate compared with HLA-matched HSCT (44.8 vs. 19.1 %, p < 0.05). There were no differences in non-relapse mortality (NRM), leukemia-free survival (LFS), or overall survival (OS) between the patients who received HLA-matched HSCT and those who underwent haploidentical HSCT. Our data indicate that the incidence of NRM after HSCT is similar between the patients who receive HLA-matched donor cells and those who receive haploidentical donor cells and that haploidentical HSCT reduces the relapse rate. Haploidentical HSCT represents an encouraging treatment option for Ph+ ALL patients who lack a suitable HLA-matched donor.