tbuckley/cabot-search huggingface dataset:
Phase I/II Study of Galiximab, an Anti-CD80 Antibody, for Relapsed or Refractory Follicular Lymphoma
Authors: Myron S. Czuczman, Aron Thall, Thomas E. Witzig, Julie M. Vose, Anas Younes, Christos Emmanouilides, Thomas P. Miller, Joseph O. Moore, John P. Leonard, Leo I. Gordon, John Sweetenham, Baha Alkuzweny, Deborah M. Finucane, Bryan R. Leigh
Journal: Journal of Clinical Oncology (2005)

This multicenter, dose-escalation study evaluates the safety, pharmacokinetics, and efficacy of galiximab (anti-CD80 monoclonal antibody) in patients with relapsed or refractory follicular lymphoma.Patients had follicular lymphoma that had relapsed or failed to respond to primary therapy; the majority (90%) presented with stage III or IV disease. Four weekly intravenous infusions of galiximab were administered at doses of 125, 250, 375, or 500 mg/m2.Thirty-seven patients received galiximab treatment and were evaluated for safety; 35 were assessable for response. Antibody infusions were safe and well tolerated with no dose-limiting toxicities. A total of 22 (60%) of 37 patients experienced adverse events related to galiximab. All but one of the events were grade 1 or 2; the most common were fatigue, nausea, and headache. Cytopenias were rare; only one patient experienced anemia and febrile neutropenia, which were unrelated to galiximab and resolved after treatment. No patient developed antigaliximab antibody formation. The mean serum half-life ranged from 13 to 24 days. The overall response rate was 11% (two complete responses and two partial responses). Time to best response was delayed (months 3, 6, 9, and 12). Twelve patients (34%) maintained stable disease. Nearly half of all patients (49%) had a decrease in indicator lesions. Two responders remain on study without progression (22 and 24.4 months).The favorable safety profile of galiximab and evidence of single-agent biologic activity and dose-dependent pharmacokinetics support further evaluation of galiximab as a treatment for follicular lymphoma, possibly in combination with other lymphoma therapies.
Rescuing Human Embryonic Stem Cell Research: The Blastocyst Transfer Method
Authors: S. Matthew Liao
Journal: The American Journal of Bioethics (2005)

Despite the therapeutic potential of human embryonic stem (HES) cells, many people believe that HES cell research should be banned. The reason is that the present method of extracting HES cells involves the destruction of the embryo, which for many is the beginning of a person. This paper examines a number of compromise solutions such as parthenogenesis, the use of defective embryos, genetically creating a "pseudo embryo" that can never form a placenta, and determining embryo death, and argues that none of these proposals are likely to satisfy embryoists, that is, those who regard the embryo as a person. This paper then proposes a method of extracting HES cells, what might be called the Blastocyst Transfer Method, that meets the ethical requirements of embryoists, and it considers some possible concerns regarding this method. It concludes by encouraging future HES cell research to investigate this method.
Drug Resistance Patterns, Genetic Subtypes, Clinical Features, and Risk Factors in Military Personnel with HIV-1 Seroconversion
Authors: Stephanie K. Brodine, Richard A. Shaffer, Monica J. Starkey, Sybil A. Tasker, Joyce L. Gilcrest, Mark K. Louder, Anthony Barile, Thomas C. VanCott, Maryanne T. Vahey, Francine E. McCutchan, Deborah L. Birx, Douglas D. Richman, John R. Mascola
Journal: Annals of Internal Medicine (1999)

Background: Regular testing of military personnel identifies early HIV infection; this identification provides a sentinel cohort in which to describe the evolving molecular epidemiology of HIV-1 transmission. Objective: To describe the prevalence and epidemiologic correlates associated with the acquisition of non-subtype B and drug-resistant HIV infections. Design: Cross-sectional study. Setting: Military referral hospital. Patients: 95 military personnel with HIV-1 seroconversion. Measurements: Self-reported questionnaire, CD4 cell counts, plasma HIV-1 RNA levels, and nucleic acid sequence analysis for drug-resistant mutations and HIV-1 genetic subtype. Results: 95 patients were enrolled between February 1997 and February 1998. The likely geographic location of HIV-1 acquisition was overseas in 8% of patients, the United States in 68%, and either overseas or the United States in 24%. Seven patients (7.4%) had subtype E infection; the remainder had subtype B infection. Eight of 31 (26%) treatment-naive patients had mutations in the reverse transcriptase or protease gene associated with drug resistance. Conclusions: The percentage of HIV-1 non-subtype B infection and antiretroviral drug-resistant mutations was relatively high in U.S. military personnel with recently acquired HIV-1 infection.
The role of the LRRK2 gene in Parkinsonism
Authors: Jie-Qiong Li, Lan Tan, Jin-Tai Yu
Journal: Molecular Neurodegeneration (2014)

Parkinson's disease (PD), like many common age-related conditions, has been recognized to have a substantial genetic component. Multiple lines of evidence suggest that Leucine-rich repeat kinase 2 (LRRK2) is a crucial factor to understanding the etiology of PD. LRRK2 is a large, widely expressed, multi-domain and multifunctional protein. LRRK2 mutations are the major cause to inherited and sporadic PD. In this review, we discuss the pathology and clinical features which show diversity and variability of LRRK2-associated PD. In addition, we do a thorough literature review and provide theoretical data for gene counseling. Further, we present the evidence linking LRRK2 to various possible pathogenic mechanism of PD such as α-synuclein, tau, inflammatory response, oxidative stress, mitochondrial dysfunction, synaptic dysfunction as well as autophagy-lysosomal system. Based on the above work, we investigate activities both within GTPase and outside enzymatic regions in order to obtain a potential therapeutic approach to solve the LRRK2 problem.
The Expression and Function of Organic Anion Transporting Polypeptides in Normal Tissues and in Cancer
Authors: Amanda Obaidat, Megan Roth, Bruno Hagenbuch
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Organic anion transporting polypeptides (OATPs) are members of the SLCO gene superfamily of proteins. The 11 human OATPs are classified into 6 families and subfamilies on the basis of their amino acid sequence similarities. OATPs are expressed in several epithelial tissues throughout the body and transport mainly amphipathic molecules with molecular weights of more than 300 kDa. Members of the OATP1 and OATP2 families are functionally the best-characterized OATPs. Among these are the multispecific OATP1A2, OATP1B1, OATP1B3, and OATP2B1. They transport various endo- and xenobiotics, including hormones and their conjugates as well as numerous drugs such as several anticancer agents. Recent reports demonstrate that some OATPs are up- or downregulated in several cancers and that OATP expression might affect cancer development. On the basis of the findings summarized in this review, we propose that OATPs could be valuable targets for anticancer therapy.
Chronic pulmonary paracoccidioidomycosis masquerading as lymphangitis carcinomatosa.
Authors: S Bowler, A Woodcock, P Da Costa, M Turner-Warwick
Journal: Thorax (1986)

Many pulmonary disorders may produce a non-specific granulomatous reaction.We describe a case of unsuspected chronic pulmonary paracoccidioidomycosis that emphasises the importance of performing fungal stains on lung biopsy specimens in all cases where an interstitial granulomatous reaction is present without an obvious cause. Case reportA 57 year old caucasian female clerk was admitted for in- vestigation of possible lymphangitis carcinomatosa.She complained of cough and of breathlessness and wheeze on exertion, which had developed gradually over a period of three years.Four years earlier she had had a left mastectomy ' Fig I Chest radiograph showing reticular shadowing in mid and lower zones and left mastectomy site.
A Citywide Protocol for Primary PCI in ST-Segment Elevation Myocardial Infarction
Authors: Michel R. Le May, Derek Y. So, Richard Dionne, Chris A. Glover, Michael P.V. Froeschl, George A. Wells, Richard F. Davies, Heather L. Sherrard, Justin Maloney, Jean-François Marquis, Edward R. O'Brien, John Trickett, Pierre Poirier, Sheila C. Ryan, Andrew Ha, Phil G. Joseph, Marino Labinaz
Journal: New England Journal of Medicine (2008)

If primary percutaneous coronary intervention (PCI) is performed promptly, the procedure is superior to fibrinolysis in restoring flow to the infarct-related artery in patients with ST-segment elevation myocardial infarction. The benchmark for a timely PCI intervention has become a door-to-balloon time of less than 90 minutes. Whether regional strategies can be developed to achieve this goal is uncertain.
Involvement of Avidity for Major Histocompatibility Complex in Homeostasis of Naive and Memory T Cells
Authors: George Kassiotis, Rose Zamoyska, Brigitta Stockinger
Journal: The Journal of Experimental Medicine (2003)

The requirements for survival and self-renewal of peripheral T cells and the nature of mechanisms controlling the size of the naive and memory pool are not completely understood. Here, we examine the involvement of the major histocompatibility complex (MHC) in survival and homeostatic expansion of naive and memory T cells. We show that the homeostatic behavior of naive T cell receptor (TCR)-transgenic T cells can be deduced by the expression levels of TCR and CD5, a negative regulator of TCR signaling. Both these factors determine the strength of TCR stimulation by MHC-derived signals. We further show that, similarly to naive T cells, MHC-derived signals influence the homeostatic expansion capacity of memory T cells under lymphopenic conditions. In contrast to naive T cells, however, memory T cells can reach a homeostatic equilibrium, in which survival/self-renewal of each clone is dissociated from their avidity for MHC-derived signals.
Patterns of Linkage Disequilibrium and Long Range Hitchhiking in Evolving Experimental<i>Drosophila melanogaster</i>Populations
Authors: Susanne U. Franssen, Viola Nolte, Ray Tobler, Christian Schlötterer
Journal: Molecular Biology and Evolution (2014)

Whole-genome resequencing of experimental populations evolving under a specific selection regime has become a popular approach to determine genotype–phenotype maps and understand adaptation to new environments. Despite its conceptual appeal and success in identifying some causative genes, it has become apparent that many studies suffer from an excess of candidate loci. Several explanations have been proposed for this phenomenon, but it is clear that information about the linkage structure during such experiments is needed. Until now only Pool-Seq (whole-genome sequencing of pools of individuals) data were available, which do not provide sufficient information about the correlation between linked sites. We address this problem in two complementary analyses of three replicate Drosophila melanogaster populations evolving to a new hot temperature environment for almost 70 generations. In the first analysis, we sequenced 58 haploid genomes from the founder population and evolved flies at generation 67. We show that during the experiment linkage disequilibrium (LD) increased almost uniformly over much greater distances than typically seen in Drosophila. In the second analysis, Pool-Seq time series data of the three replicates were combined with haplotype information from the founder population to follow blocks of initial haplotypes over time. We identified 17 selected haplotype-blocks that started at low frequencies in the base population and increased in frequency during the experiment. The size of these haplotype-blocks ranged from 0.082 to 4.01 Mb. Moreover, between 42% and 46% of the top candidate single nucleotide polymorphisms from the comparison of founder and evolved populations fell into the genomic region covered by the haplotype-blocks. We conclude that LD in such rising haplotype-blocks results in long range hitchhiking over multiple kilobase-sized regions. LD in such haplotype-blocks is therefore a major factor contributing to an excess of candidate loci. Although modifications of the experimental design may help to reduce the hitchhiking effect and allow for more precise mapping of causative variants, we also note that such haplotype-blocks might be well suited to study the dynamics of selected genomic regions during experimental evolution studies.
Optimised sample preparation of synovial fluid for detection of Chlamydia trachomatis DNA by polymerase chain reaction
Authors: J. G Kuipers, L. Nietfeld, U. Dreses-Werringloer, L. Koehler, J. Wollenhaupt, H. Zeidler, M. Hammer
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To optimise sample preparation of synovial fluid for <i>Chlamydia trachomatis</i> (CT) specific polymerase chain reaction (PCR). <h3>METHODS</h3> Serial dilutions of purified CT elementary bodies in synovial fluid were prepared. The synovial fluid pellet was processed by eight different methods of sample preparation. Then samples were analysed by CT specific PCR. The sensitivity of PCR was the basis of ranking of the eight different methods. <h3>RESULTS</h3> Highest sensitivity was achieved by methods including an additional step of DNA isolation. Additional extraction of protein and polysaccharides by cetyltrimethylammonium bromide (CTAB) increased sensitivity. Addition of hyaluronidase did not increase sensitivity of QIAEX-DNA extraction but was necessary, however, before phenol-chloroform-DNA extraction. <h3>CONCLUSIONS</h3> The method of synovial fluid sample preparation significantly influences the sensitivity of subsequent PCR. Additional DNA isolation and extraction of PCR inhibitors by CTAB led to higher sensitivity.
Evidence of impaired sense of smell in hereditary angioedema
Authors: C. Perricone, N. Agmon-Levin, N. Shoenfeld, C. De Carolis, M. D. Guarino, G. Gigliucci, I. Milana, L. Novelli, G. Valesini, R. Perricone, Y. Shoenfeld
Journal: Allergy (2010)

Hereditary angioedema (HAE) is an autosomal-dominant disorder resulting from C1-inhibitor (C1INH) deficiency. Smell impairments were found in patients affected with systemic lupus erythematosus, that, similarly to HAE, is characterized by the activation of the classical complement pathway with C4 consumption. In this study, we aimed at evaluating the sense of smell in patients with HAE.Thirty patients with HAE and 30 healthy age- and sex-matched controls were evaluated for olfactory functions using the 3-stages Sniffin'-Sticks kit (threshold, discrimination, and identification [TDI]). TDI scores were analyzed according to complement levels (C1INH, C3, C4 and CH50), Beck depression inventory (BDI-II) and danazol treatment.A significant decrease in olfactory function was observed in patients affected with HAE compared with controls in total TDI score (P < 0.001), and in the discrimination (P < 0.001) and identification scores (P = 0.012). Anosmia was present only in patients with HAE (3.3%) who also exhibited more frequently hyposmia (53.3%vs 3.3%, P < 0.0001). Complement levels were reduced in patients with HAE. C4 serum levels showed positive correlation with total TDI score (P < 0.001), and with discrimination (P = 0.002) and identification (P = 0.011) scores. CH50 complement levels showed positive correlation with total TDI score (P < 0.001), and with threshold (P = 0.002) and discrimination (P = 0.011) scores. Sex, age, danazol treatment, BDI-II scores were not different between the patients and controls and did not influence TDI scores significantly.Evidence for an impaired sense of smell was found in patients with HAE. The reduction in olfactory function in these cases seems to correlate with complement C4 and CH50 levels. Immune and genetic mechanisms might play a role in this defect.
Intensive Salvage Therapy With High-Dose Chemotherapy for Patients With Advanced Hodgkin's Disease in Relapse or Failure After Initial Chemotherapy: Results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial
Authors: C. Ferme
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin’s disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P = .0001), 71% for the 101 patients given HDCT, and 32% ...
Update on the Application of Interleukin-2 in the Treatment of Renal Cell Carcinoma
Authors: David F. McDermott
Journal: Clinical Cancer Research (2007)

Abstract High-dose bolus interleukin 2 (IL-2) was granted Food and Drug Administration approval based on its ability to produce durable complete responses in a small number of patients with metastatic renal cell carcinoma. Results from randomized phase 3 trials suggest that regimens involving lower doses of IL-2, either alone or in combination with IFN, produce fewer tumor regressions of less overall quality. Given the toxicity, expense, and limited efficacy of this treatment, recent studies have focused on identifying predictors of response (or resistance) to IL-2 therapy. This year, investigators launched a clinical trial designed to prospectively determine if patients who are more likely to respond to high-dose IL-2 can be identified before starting therapy. As the list of effective therapies for metastatic renal cell carcinoma grows, improvements in patient selection will be necessary to ensure that patients who might attain a durable remission with IL-2 will not miss this opportunity.
Exercise-Induced Pulmonary Edema in Heart Failure
Authors: Piergiuseppe Agostoni, Gaia Cattadori, Michele Bianchi, Karlman Wasserman
Journal: Circulation (2003)

In heart failure (HF) patients, exercise may increase pulmonary capillary hydrostatic pressure and thereby generate pulmonary edema. If pulmonary edema developed, alveolar-capillary membrane conductance (Dm), measured immediately after exercise, would decrease. To test this hypothesis, we measured Dm before and at 2 and 60 minutes after exercise.We studied 10 HF patients with exercise-induced periodic breathing, 10 with peak o2 < or =15 mL x min(-1) x kg(-1) (severe HF), 10 with o2=15 to 20 mL x min(-1) x kg(-1) (moderate HF), and 10 normal subjects (control). Using the Roughton-Forster technique, we measured carbon monoxide diffusion capacity (DLco) and its components, capillary blood volume (Vc) and Dm, at rest and 2 and 60 minutes after exercise. At rest, DLco and Dm were lowest in periodic breathing and highest in control subjects. Dm decreased in periodic breathing, severe HF, and moderate HF (-7.83+/-3.98, -5.57+/-2.03, and -3.85+/-3.53 mL x min(-1) x mm Hg(-1), respectively; P<0.01) at 2 minutes after exercise but not in control subjects. Vc increased in all groups at 2 minutes and remained elevated at 60 minutes only in periodic breathing. Dm/Vc was decreased in periodic breathing, severe HF, and moderate HF at 2 minutes but not in control subjects. Dm and Dm/Vc remained low at 60 minutes only in periodic breathing.Dm decreases after exercise in HF patients but not in control subjects, which suggests a decrease in conductance across the alveolar-capillary barrier, as with pulmonary edema. The reductions were most marked in HF patients with periodic breathing and less reduced in less severe HF.
Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer
Authors: Gouji Toyokawa, Ken Masuda, Yataro Daigo, Hyun-Soo Cho, Masanori Yoshimatsu, Masashi Takawa, Shinya Hayami, Kazuhiro Maejima, Makoto Chino, Helen I Field, David E Neal, Eiju Tsuchiya, Bruce AJ Ponder, Yoshihiko Maehara, Yusuke Nakamura, Ryuji Hamamoto
Journal: Molecular Cancer (2011)

Abstract Background The research emphasis in anti-cancer drug discovery has always been to search for a drug with the greatest antitumor potential but fewest side effects. This can only be achieved if the drug used is against a specific target located in the tumor cells. In this study, we evaluated Minichromosome Maintenance Protein 7 (MCM7) as a novel therapeutic target in cancer. Results Immunohistochemical analysis showed that MCM7 was positively stained in 196 of 331 non-small cell lung cancer (NSCLC), 21 of 29 bladder tumor and 25 of 70 liver tumor cases whereas no significant staining was observed in various normal tissues. We also found an elevated expression of MCM7 to be associated with poor prognosis for patients with NSCLC ( P = 0.0055). qRT-PCR revealed a higher expression of MCM7 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues ( P &lt; 0.0001), and we confirmed that a wide range of cancers also overexpressed MCM7 by cDNA microarray analysis. Suppression of MCM7 using specific siRNAs inhibited incorporation of BrdU in lung and bladder cancer cells overexpressing MCM7, and suppressed the growth of those cells more efficiently than that of normal cell strains expressing lower levels of MCM7. Conclusions Since MCM7 expression was generally low in a number of normal tissues we examined, MCM7 has the characteristics of an ideal candidate for molecular targeted cancer therapy in various tumors and also as a good prognostic biomarker for NSCLC patients.