tbuckley/cabot-search huggingface dataset:
Root of the Eukaryota Tree as Inferred from Combined Maximum Likelihood Analyses of Multiple Molecular Sequence Data
Authors: Nobuko Arisue, Masami Hasegawa, Tetsuo Hashimoto
Journal: Molecular Biology and Evolution (2004)

Extensive studies aiming to establish the structure and root of the Eukaryota tree by phylogenetic analyses of molecular sequences have thus far not resulted in a generally accepted tree. To re-examine the eukaryotic phylogeny using alternative genes, and to obtain a more robust inference for the root of the tree as well as the relationship among major eukaryotic groups, we sequenced the genes encoding isoleucyl-tRNA and valyl-tRNA synthetases, cytosolic-type heat shock protein 90, and the largest subunit of RNA polymerase II from several protists. Combined maximum likelihood analyses of 22 protein-coding genes including the above four genes clearly demonstrated that Diplomonadida and Parabasala shared a common ancestor in the rooted tree of Eukaryota, but only when the fast-evolving sites were excluded from the original data sets. The combined analyses, together with recent findings on the distribution of a fused dihydrofolate reductase–thymidylate synthetase gene, narrowed the possible position of the root of the Eukaryota tree on the branch leading to Opisthokonta or to the common ancestor of Diplomonadida/Parabasala. However, the analyses did not agree with the position of the root located on the common ancestor of Opisthokonta and Amoebozoa, which was argued by Stechmann and Cavalier-Smith [Curr. Biol. 13:R665–666, 2003] based on the presence or absence of a three-gene fusion of the pyrimidine biosynthetic pathway: carbamoyl-phosphate synthetase II, dihydroorotase, and aspartate carbamoyltransferase. The presence of the three-gene fusion recently found in the Cyanidioschyzon merolae (Rhodophyta) genome sequence data supported our analyses against the Stechmann and Cavalier-Smith-rooting in 2003.
Multicenter Phase III Study of Uracil/Tegafur and Oral Leucovorin Versus Fluorouracil and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer
Authors: Jean-Yves Douillard, Paulo M. Hoff, Jamey R. Skillings, Peter Eisenberg, Neville Davidson, Peter Harper, Mark D. Vincent, Barry C. Lembersky, Seth Thompson, Antonella Maniero, Steven E. Benner
Journal: Journal of Clinical Oncology (2002)

PURPOSE: This phase III study was designed to demonstrate equivalence in survival of oral uracil/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma. Safety was also compared. PATIENTS AND METHODS: Eight hundred sixteen patients were randomized to receive either UFT (300 mg/m 2 /d) and LV (75 or 90 mg/d) for 28 days every 35 days or IV bolus 5-FU (425 mg/m 2 /d) and LV (20 mg/m 2 /d) for 5 days every 28 days. RESULTS: UFT/LV produced survival comparable to the IV 5-FU/LV regimen. Median survival was 12.4 months (95% confidence interval [CI], 11.2 to 13.6 months) with UFT/LV and 13.4 months (95% CI, 11.6 to 15.4 months) with 5-FU/LV (P = .630). The hazard ratio for survival was 0.964 (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response rate did not differ between treatment arms (UFT/LV, 11.7%; 5-FU/LV, 14.5%; P = .232). Median time to progression favored 5-FU/LV (UFT/LV, 3.5 months; 5-FU/LV, 3.8 months; P = .011), but tumor assessment schedules differed between arms. UFT/LV significantly improved safety compared with 5-FU/LV. Diarrhea, nausea and vomiting, and stomatitis and mucositis were significantly less frequent with UFT/LV, as was myelosuppression. Patients treated with UFT/LV had fewer episodes of febrile neutropenia (P &lt; .001) and documented infections (P &lt; .05). Increased bilirubin, without other liver function abnormalities, was observed more often with UFT/LV (P &lt; .001). Concomitant medications were more frequent with 5-FU/LV, including use of antibiotics, growth factors, and antiemetics. CONCLUSION: UFT/LV provided a safer, more convenient oral alternative to a standard bolus IV 5-FU/LV regimen for metastatic colorectal cancer while producing equivalent survival.
Phosphatidylinositol 3-Kinase Is Required for Insulin-Like Growth Factor-I–Induced Vascular Smooth Muscle Cell Proliferation and Migration
Authors: Cunming Duan, Jeanette R. Bauchat, Tzefu Hsieh
Journal: Circulation Research (2000)

Abstract —Insulin-like growth factor–I (IGF-I) plays an important role in regulating vascular smooth muscle cell (VSMC) proliferation and directed migration. The mitogenic and chemotactic actions of IGF-I are mediated through the IGF-I receptor, but how the activation of the IGF-I receptor leads to these biological responses is poorly understood. In this study, we examined the role of phosphatidylinositol 3-kinase (PI3 kinase) in mediating the mitogenic and chemotactic signals of IGF-I. IGF-I treatment resulted in a significant increase in phosphotyrosine-associated PI3 kinase activity in cultured primary VSMCs. To determine whether insulin receptor substrate (IRS)–1, -2, or both are involved in IGF-I signaling in VSMCs, cell lysates were immunoprecipitated with either an anti-IRS-1 or an anti-IRS-2 antibody, and the associated PI3 kinase activity was determined. IGF-I stimulation resulted in a significant increase in IRS-1– but not IRS-2–associated PI3 kinase activity, suggesting that IGF-I primarily utilizes IRS-1 to transmit its signal in VSMCs. The IGF-I–induced increase in IRS-I–associated PI3 kinase activity was concentration dependent. At the maximum concentration (50 ng/mL), IGF-I induced a 60-fold increase. This activation occurred within 5 minutes and was sustained at high levels for at least 6 hours. IGF-I also caused a concentration-dependent and long-lasting activation of protein kinase B (PKB/Akt). Inhibition of PI3 kinase activation by LY294002 or wortmannin abolished IGF-I–stimulated VSMC proliferation and reduced IGF-I–directed VSMC migration by ≈60%. These results indicate that activation of PI3 kinase is required for both IGF-I–induced VSMC proliferation and migration.
Campylobacter jejuni O:19 serotype-associated Guillain–Barré syndrome in a child: the first case reported from Greece
Authors: S. Chatzipanagiotou, K. Kilidireas, G. Trimis, C. Nicolaou, M. Anagnostouli, C. Athanassaki, A. Giannoulia, N. Legakis, S. Youroukos
Journal: Clinical Microbiology and Infection (2003)
Prophylactic contraceptives for HIV/AIDS
Authors: F M Uckun, O J D'Cruz
Journal: Human Reproduction Update (1999)

The current pandemic of sexually transmitted human immunodeficiency virus (HIV) infection--the causative agent of acquired immunodeficiency syndrome (AIDS), has created an urgent need for a new type of contraceptive: one that is both a spermicide and a microbicide. Because most women at risk for HIV infection are of reproductive age (15-44 years), effective use of dual-function contraceptives is important to prevent HIV transmission and unintended pregnancies. In the absence of an effective prophylactic anti-HIV therapy or vaccine, new emphasis has been placed on the development of intravaginal microbicidal agents capable of reducing the transmission of HIV. Topical microbicidal spermicides would ideally provide a female-controlled method of self-protection against HIV as well as preventing pregnancy. However, several microbicides that are undergoing preclinical and human clinical trials contain detergent-type ingredients. The detergent-type spermicide, nonoxynol-9, the only recommended microbicide for protection against sexual transmission of HIV has been shown to cause lesions in vaginal and cervical epithelia leaving women more vulnerable to HIV infection. Therefore, a major challenge in microbicide research has been to design mechanism-based microbicides that are highly effective against pregnancy and HIV transmission while lacking detergent-type effects on epithelial cells and normal vaginal flora. We present an overview of current microbicide research and report on the identification and preclinical development of novel non-detergent spermicidal nucleoside and non-nucleoside inhibitors aimed at decreasing pregnancy and preventing sexual transmission of HIV.
Coagulation factor V gene mutation associated with activated protein C resistance leading to recurrent thrombosis, leg ulcers, and lymphedema: successful treatment with intermittent compression
Authors: Dominik Peus, Sherko v Schmiedeberg, Andreas Pier, Rüdiger E Scharf, Artur Wehmeier, Thomas Ruzicka, Jean Krutmann
Journal: Journal of the American Academy of Dermatology (1996)
NHS Scotland reduces the postcode lottery for hip arthroplasty: an ecological study of the impact of waiting time initiatives
Authors: Graham Kirkwood, Allyson M Pollock, Colin Howie, Sarah Wild
Journal: Journal of the Royal Society of Medicine (2014)

Following the election of the Labour government in 1997, policies were developed in England to reduce waiting times for NHS treatment with commitments to reduce health inequalities. Similar policies were adopted in Scotland but with less emphasis on the use of the private sector to deliver NHS treatments than in England. This study uses routinely collected NHS Scotland data to analyse geographical and socioeconomic inequalities in elective hip arthroplasty treatment before and after the introduction of the waiting time initiatives in Scotland in 2003.Ecological study design.Scotland.NHS-funded patients receiving elective hip arthroplasty delivered by the NHS and private hospitals between 1 April 1998 and 31 March 2008.Directly standardised treatment rates and incidence rate ratios calculated using Poisson regression.There was a 42% increase in NHS-funded hip arthroplasties carried out in Scotland from 4095 in 2002-2003 (1 April 2002-31 March 2003) to 5829 in 2007-2008. There is evidence of a statistically significant reduction in geographical inequality (likelihood ratio test p < 0.001) but no evidence of any statistically significant change in socioeconomic inequality (p = 0.108), comparing the 5 years after 1 April 2003 with the 5 years before 1 April 2003. The number of NHS-funded hip arthroplasties undertaken privately rose from 1.1% in 2002-2003 to 2.9% in 2007-2008, whereas the NHS Golden Jubilee National Hospital increased its share from 3.3% to 10.6% over the same period.The reduction in geographical inequality, or 'postcode lottery', in hip arthroplasty treatment in Scotland may be due to increased NHS capacity, in particular the development of the NHS Golden Jubilee National Hospital in Clydebank, Greater Glasgow as a dedicated centre to reduce surgery waiting times.
Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma
Authors: J C Reubi, B Waser, H Friess, M Buchler, J Laissue
Journal: Gut (1998)

New imaging possibilities for early diagnosis of the devastating exocrine pancreatic adenocarcinomas would be highly welcome. Recently, pancreatic neuroendocrine tumours have been successfully visualised in vivo on the basis of their high density of receptors for the regulatory peptide somatostatin. Unfortunately, exocrine pancreatic tumours do not express sufficient amounts of somatostatin receptors. Therefore over-expression of other regulatory peptide receptors in these tumours needs to be found.Receptors for the regulatory peptide neurotensin were evaluated in vitro by receptor autoradiography in 24 ductal pancreatic adenocarcinomas, 20 endocrine pancreatic cancers, 18 cases of chronic pancreatitis, and 10 normal pancreatic glands.Some 75% of all ductal pancreatic adenocarcinomas, most of them differentiated, were neurotensin receptor positive, whereas endocrine pancreatic cancers did not express neurotensin receptors. No neurotensin receptors were found in chronic pancreatitis or normal pancreatic tissues, including pancreatic acini, ducts, and islets.The selective and high expression of neurotensin receptors in ductal pancreatic adenocarcinomas could form the molecular basis for potential clinical applications, such as in vivo neurotensin receptor scintigraphy for early tumour diagnosis, radiotherapy with radiolabelled neurotensin analogues, and chemotherapy with neurotensin receptor antagonists.
Surface Sialic Acids Taken from the Host Allow Trypanosome Survival in Tsetse Fly Vectors
Authors: Kisaburo Nagamune, Alvaro Acosta-Serrano, Haruki Uemura, Reto Brun, Christina Kunz-Renggli, Yusuke Maeda, Michael A.J. Ferguson, Taroh Kinoshita
Journal: The Journal of Experimental Medicine (2004)

The African trypanosome Trypanosoma brucei, which causes sleeping sickness in humans and Nagana disease in livestock, is spread via blood-sucking Tsetse flies. In the fly's intestine, the trypanosomes survive digestive and trypanocidal environments, proliferate, and translocate into the salivary gland, where they become infectious to the next mammalian host. Here, we show that for successful survival in Tsetse flies, the trypanosomes use trans-sialidase to transfer sialic acids that they cannot synthesize from host's glycoconjugates to the glycosylphosphatidylinositols (GPIs), which are abundantly expressed on their surface. Trypanosomes lacking sialic acids due to a defective generation of GPI-anchored trans-sialidase could not survive in the intestine, but regained the ability to survive when sialylated by means of soluble trans-sialidase. Thus, surface sialic acids appear to protect the parasites from the digestive and trypanocidal environments in the midgut of Tsetse flies.
Stress, Dysregulation of Drug Reward Pathways, and the Transition to Drug Dependence
Authors: George Koob, Mary Jeanne Kreek
Journal: American Journal of Psychiatry (2007)

This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from limited access to drugs to long-term compulsive use of drugs. A dramatic escalation in drug intake with extended access to drug self-administration is characterized by a dysregulation of brain reward pathways. Hormonal studies using an experimenter-administered cocaine binge model and an escalation self-administration model have revealed large increases in ACTH and corticosterone in rats during an acute binge with attenuation during the chronic binge stage and a reactivation of the hypothalamic-pituitary-adrenal axis during acute withdrawal. The activation of the hypothalamic-pituitary-adrenal axis with cocaine appears to depend on feed-forward activation of the mesolimbic dopamine system. At the same time, escalation in drug intake with either extended access or dependence-induction produces an activation of the brain stress system's corticotropin-releasing factor outside of the hypothalamus in the extended amygdala, which is particularly evident during acute withdrawal. A model of the role of different levels of hormonal/brain stress activation in addiction is presented that has heuristic value for understanding individual vulnerability to drug dependence and novel treatments for the disorder.
Critical Shortage of African American Medical Oncologists in the United States
Authors: Lauren M. Hamel, Robert Chapman, Mary Malloy, Susan Eggly, Louis A. Penner, Anthony F. Shields, Michael S. Simon, Justin F. Klamerus, Charles Schiffer, Terrence L. Albrecht
Journal: Journal of Clinical Oncology (2015)

Lauren M. Hamel, Karmanos Cancer Institute/Wayne State University, Detroit, MI Robert Chapman, Josephine Ford Cancer Institute/Henry Ford Health System, Detroit, MI Mary Malloy, Michigan Society of Hematology and Oncology, Detroit, MI Susan Eggly, Louis A. Penner, Anthony F. Shields, Michael S. Simon, Justin F. Klamerus, Charles Schiffer, and Terrence L. Albrecht, Karmanos Cancer Institute/Wayne State University, Detroit, MI
True Immunogenicity of Oncofetal Antigen/Immature Laminin Receptor Protein
Authors: Joseph H. Coggin, James W. Rohrer, Adel L. Barsoum
Journal: Cancer Research (2004)

Su et al . [(1)][1] described the detection of RNA present in renal cell carcinoma (RCC) that achieved expression of oncofetal antigen (OFA) in RCC patient’s monocytes and gave rise to OFA-expressing dendritic cells ex vivo . When these OFA-expressing dendritic cells were infused back into
EPSTEIN-BARR-VIRUS-INDUCED LYMPHOPROLIFERATIVE DISORDER CONVERTING TO FATAL BURKITT-LIKE LYMPHOMA IN A BOY WITH INTERFERON- INDUCIBLE CHROMOSOMAL DEFECT
Authors: Kristian Thestrup-Pedersen, Viggo Esmann, JørgenR Jensen, Jørgen Hastrup, Karen Thorling, AriK Saemundsen, Susanne Bisballe, Gorm Pallesen, Melvin Madsen, Maria Grazia-Masucci, Ingemar Ernberg
Journal: The Lancet (1980)
Blogging During Terminal Care: Communication, Color Schemes, and Creating a Community
Authors: Leon A. Bach
Journal: Journal of Clinical Oncology (2008)

Ilana, my wife, was diagnosed with breast cancer in late 2000 at the age of 39 years. Despite a lumpectomy with axillary node clearance, chemotherapy, and radiotherapy followed by tamoxifen treatment, she developed a vertebral metastasis in 2003. Over the next 3 years, she developed further bony metastases despite treatment with several hormonal modalities and then taxane-based chemotherapy. In early 2007, ocular metastases requiring radiotherapy were detected, and liver metastases were found soon after. Over the next 3 months, her disease progressed, her functional status deteriorated, and further active treatment was considered to be inappropriate. She fervently wished to remain at home, and this was made possible with the help of supportive doctors and an excellent community palliative care nursing team. She died at home in June 2007. Ilana had a wide circle of caring friends and a devoted family who wished to support her by all possible means. When first diagnosed with breast cancer, she did not wish to participate in support groups or talk about her diagnosis. When the cancer recurred, her attitude began to change, and she became a public advocate for women with advanced disease. Nevertheless, she often could not respond to the numerous phone calls and messages she received whenever a recurrence was diagnosed, and we found it difficult to cope with this wholly understandable requirement for information. I would despair of arriving home to an answering machine blatantly announcing eight new messages, as well as each of our cell phones declaring multiple missed calls and messages. Everyone wanted and needed to know what was happening and everyone wanted us to know that they cared, but where was the time, and where was the emotional energy? And if I did answer all of these calls, how would I find time to tend to Ilana’s needs, my needs, and those of our two daughters? Over the years, we would ask a couple of friends to create a chain call to other friends or send group e-mails to keep people informed. However, these approaches have several limitations. First, some friends missed out on the chain call because they were not part of the network. Additionally, many felt the need to call us immediately, thereby negating the intention to give us time and space. Finally, e-mail can be an impersonal medium, and it is difficult to convey sensitive, emotionally charged information without seeming blunt. In the last few weeks before Ilana died, her ability to socialize became increasingly limited as her physical state declined, which intensified the concern of friends and family but simultaneously curtailed their ability to communicate with her. Approximately a week before Ilana died, a close friend, after a discussion with her daughters, suggested using the Internet to disseminate information about Ilana. After speaking to my own daughters, I decided to set up a blog.
Complex evolution of a salmonid microsatellite locus and its consequences in inferring allelic divergence from size information
Authors: B Angers, L Bernatchez
Journal: Molecular Biology and Evolution (1997)

Sequence analysis of 78 alleles of a microsatellite locus was resolved at various taxonomic levels among salmonid fishes to test for congruence between size and sequence information. Allelic variability of this locus involved changes in number of dinucleotide repeats as expected for microsatellite loci. However, additional mutational events involving large indels and base substitutions also occurred frequently among and within species. These caused the evolution of different imperfect microsatellite variants, from an ancestral perfect one, which was undetectable from allelic size information only. Alleles of the same length resulting from different mutational events were also observed among and within species. Altogether, these results revealed the incongruence between size and number of mutation events, implying that it may be imprecise to interpret mutational rates and relationships on the basis of size information alone in interspecific comparisons and, to a lesser extent, within species.
Oozing and Bruising Due to Abnormal Platelet Function (Thrombocytopathia)
Authors: STANLEY ZUCKER
Journal: Annals of Internal Medicine (1972)

This report describes 6 unrelated patients with mild bleeding disorders caused by abnormalities of platelet function. This syndrome has its onset in childhood and has one or more of these characteristics: easy bruising, spontaneous bleeding from mucosal membranes, excessive bleeding after minor or major surgery, and menorrhagia. Coagulation tests in these patients showed a prolonged bleeding time and a delayed and diminished platelet aggregation response to epinephrine and collagen. The platelet count, platelet adhesiveness, platelet factor-3 release, and factor VIII activity were usually normal. Pedigree studies suggested an autosomal-dominant mode of inheritance. An experimental trial of prednisone therapy in five patients resulted in significant improvement in the bleeding time, yet platelet aggregation test results were unaltered.
Locoregional Failure Rate After Preoperative Chemoradiation of Esophageal Adenocarcinoma and the Outcomes of Salvage Strategies
Authors: Kazuki Sudo, Takashi Taketa, Arlene M. Correa, Maria-Claudia Campagna, Roopma Wadhwa, Mariela A. Blum, Ritsuko Komaki, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Heath D. Skinner, Dipen M. Maru, David C. Rice, Stephen G. Swisher, Wayne L. Hofstetter, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2013)

Purpose The primary purpose of surveillance of patients with esophageal adenocarcinoma (EAC) and/or esophagogastric junction adenocarcinoma after local therapy (eg, chemoradiotherapy followed by surgery or trimodality therapy [TMT]) is to implement a potentially beneficial salvage therapy to overcome possible morbidity/mortality caused by locoregional failure (LRF). However, the benefits of surveillance are not well understood. We report on LRFs and salvage strategies in a large cohort. Patients and Methods Between 2000 and 2010, 518 patients with EAC who completed TMT were analyzed for the frequency of LRF over time and salvage therapy outcomes. Standard statistical techniques were used. Results For 518 patients, the median follow-up time was 29.3 months (range, 1 to 149 months). Distant metastases (with or without LRF) occurred in 188 patients (36%), and LRF only occurred in 27 patients (5%). Eleven of 27 patients had lumen-only LRF. Most LRFs (89%) occurred within 36 months of surgery. Twelve patients had salvage chemoradiotherapy, but only five survived more than 2 years. Four patients needed salvage surgery, and three who survived more than 2 years developed distant metastases. The median overall survival of 27 patients with LRF was 17 months, and 10 patients (37%) survived more than 2 years. Thus, only 2% of all 518 patients benefited from surveillance/salvage strategies. Conclusion Our surveillance strategy, which is representative of many others currently being used, raises doubts about its effectiveness and benefits (along with concerns regarding types and times of studies and costs implications) to patients with EAC who have LRF only after TMT. Fortunately, LRFs are rare after TMT, but the salvage strategies are not highly beneficial. Our data can help develop an evidence-based surveillance strategy.