tbuckley/cabot-search huggingface dataset:
Oral ezatiostat HCl (Telintra®, TLK199) and Idiopathic Chronic Neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor
Authors: Roger M Lyons, Sharon T Wilks, Shelby Young, Gail L Brown
Journal: Journal of Hematology & Oncology (2011)

Abstract Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent fevers, chronic mucosal inflammation, and severe systemic infections. The severity and risk of complications, including serious infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 × 10 9 /L. This case report describes a 64-year-old female with longstanding rheumatoid arthritis who subsequently developed ICN with frequent episodes of sepsis requiring hospitalization and prolonged courses of antibiotics over a 4-year period. She was treated with granulocyte colony stimulating factors (G-CSF) but had a delayed, highly variable, and volatile response. She was enrolled in a clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat, a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. She responded by the end of the first month of treatment with stabilization of her ANC (despite tapering and then stopping G-CSF), clearing of fever, and healing of areas of infection. This ANC response to ezatiostat treatment has now been sustained for over 8 months and continues. These results suggest potential roles for ezatiostat in the treatment of patients with ICN who are not responsive to G-CSF, as an oral therapy alternative, or as an adjunct to G-CSF, and further studies are warranted.
Electroanatomic Left Ventricular Mapping in the Porcine Model of Healed Anterior Myocardial Infarction
Authors: David J. Callans, Jian-Fang Ren, John Michele, Francis E. Marchlinski, Stephen M. Dillon
Journal: Circulation (1999)

Background —Catheter ablation for ventricular tachycardia in healed infarction is limited to patients with inducible, tolerated arrhythmias. Strategies that would allow mapping during sinus rhythm might obviate this limitation. Methods and Results —Two sets of experiments were performed in adult pigs to refine a new technique for left ventricular mapping. First, detailed endocardial maps were done in 5 normal pigs and 7 pigs 6 to 10 weeks after left anterior descending coronary artery infarction to characterize electrograms in normal and infarcted tissue by electroanatomic mapping (CARTO, Biosense). Electrogram recording sites were verified by intracardiac echo (ICE, 9 MHz) and grouped by location: infarct (area of akinesis by ICE), border (0.5-cm perimeter of akinetic area), and remote. Compared with remote sites, electrograms from infarct sites had smaller amplitudes (1.2±0.5 versus 5.1±2.1 mV, P &lt;0.001), longer durations (74.2±26.3 versus 36.3±6.4 ms, P &lt;0.001), and more frequent notched or late components. Border zone electrograms were intermediate in amplitude and duration. Second, infarct characterization by electroanatomic mapping was compared with pathological (exclusion of triphenyltetrazolium chloride staining) and ICE measurements. Infarct size by pathology correlated with the area defined by contiguous electrograms with amplitude ≤1 mV ( r =0.98, P =0.0001). Infarct size by ICE imaging correlated with the area defined by contiguous electrograms with amplitude ≤2 mV ( r =0.95, P =0.0016). Conclusions —Electroanatomic mapping during sinus rhythm allows accurate 3D characterization of infarct architecture and defines the relationship of electrophysiological and anatomic abnormalities. This technique may prove useful in devising anatomically based strategies for ablation of ventricular tachycardia.
Antigen-Specific Immune Responses and Clinical Outcome After Vaccination With Glioma-Associated Antigen Peptides and Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose in Children With Newly Diagnosed Malignant Brainstem and Nonbrainstem Gliomas
Authors: Ian F. Pollack, Regina I. Jakacki, Lisa H. Butterfield, Ronald L. Hamilton, Ashok Panigrahy, Douglas M. Potter, Angela K. Connelly, Sharon A. Dibridge, Theresa L. Whiteside, Hideho Okada
Journal: Journal of Clinical Oncology (2014)

Diffuse brainstem gliomas (BSGs) and other high-grade gliomas (HGGs) of childhood carry a dismal prognosis despite current treatments, and new therapies are needed. Having identified a series of glioma-associated antigens (GAAs) commonly overexpressed in pediatric gliomas, we initiated a pilot study of subcutaneous vaccinations with GAA epitope peptides in HLA-A2-positive children with newly diagnosed BSG and HGG.GAAs were EphA2, interleukin-13 receptor alpha 2 (IL-13Rα2), and survivin, and their peptide epitopes were emulsified in Montanide-ISA-51 and given every 3 weeks with intramuscular polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose for eight courses, followed by booster vaccinations every 6 weeks. Primary end points were safety and T-cell responses against vaccine-targeted GAA epitopes. Treatment response was evaluated clinically and by magnetic resonance imaging.Twenty-six children were enrolled, 14 with newly diagnosed BSG treated with irradiation and 12 with newly diagnosed BSG or HGG treated with irradiation and concurrent chemotherapy. No dose-limiting non-CNS toxicity was encountered. Five children had symptomatic pseudoprogression, which responded to dexamethasone and was associated with prolonged survival. Only two patients had progressive disease during the first two vaccine courses; 19 had stable disease, two had partial responses, one had a minor response, and two had prolonged disease-free status after surgery. Enzyme-linked immunosorbent spot analysis in 21 children showed positive anti-GAA immune responses in 13: to IL-13Rα2 in 10, EphA2 in 11, and survivin in three.GAA peptide vaccination in children with gliomas is generally well tolerated and has preliminary evidence of immunologic and clinical responses. Careful monitoring and management of pseudoprogression is essential.
Application of the comprehensive set of heterozygous yeast deletion mutants to elucidate the molecular basis of cellular chromium toxicity
Authors: Sara Holland, Emma Lodwig, Theodora Sideri, Tom Reader, Ian Clarke, Konstantinos Gkargkas, David C Hoyle, Daniela Delneri, Stephen G Oliver, Simon V Avery
Journal: Genome biology (2007)

The serious biological consequences of metal toxicity are well documented, but the key modes of action of most metals are unknown. To help unravel molecular mechanisms underlying the action of chromium, a metal of major toxicological importance, we grew over 6,000 heterozygous yeast mutants in competition in the presence of chromium. Microarray-based screens of these heterozygotes are truly genome-wide as they include both essential and non-essential genes.The screening data indicated that proteasomal (protein degradation) activity is crucial for cellular chromium (Cr) resistance. Further investigations showed that Cr causes the accumulation of insoluble and toxic protein aggregates, which predominantly arise from proteins synthesised during Cr exposure. A protein-synthesis defect provoked by Cr was identified as mRNA mistranslation, which was oxygen-dependent. Moreover, Cr exhibited synergistic toxicity with a ribosome-targeting drug (paromomycin) that is known to act via mistranslation, while manipulation of translational accuracy modulated Cr toxicity.The datasets from the heterozygote screen represent an important public resource that may be exploited to discover the toxic mechanisms of chromium. That potential was validated here with the demonstration that mRNA mistranslation is a primary cause of cellular Cr toxicity.
STREPTOCOCCAL SKIN INFECTION AND ACUTE GLOMERULONEPHRITTS*
Authors: M. T. PARKER
Journal: British Journal of Dermatology (1969)

Journal Article STREPTOCOCCAL SKIN INFECTION AND ACUTE GLOMERULONEPHRITTS Get access M. T. PARKER M. T. PARKER Central Public Health Laboratory, Colindale, London, N. W.9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue s1, 1 January 1969, Pages 37–46, https://doi.org/10.1111/j.1365-2133.1969.tb12832.x Published: 01 January 1969
Zinc-finger protein 545 is a novel tumour suppressor that acts by inhibiting ribosomal RNA transcription in gastric cancer
Authors: Shiyan Wang, Yingduan Cheng, Wan Du, Leina Lu, Liang Zhou, Huating Wang, Wei Kang, Xiaoxing Li, Qian Tao, Joseph J Y Sung, Jun Yu
Journal: Gut (2012)

<h3>Objective</h3> Zinc-finger protein 545 (ZNF545) is a member of the family of Krüppel-associated box-containing zinc-finger proteins. The aim of this study was to clarify its biological function as a tumour suppressor in gastric cancer. <h3>Design</h3> The biological function of ZNF545 was determined by cell growth and apoptosis assays. The ZNF545 target signal pathway was identified by promoter luciferase assay, northern blot, run-on transcription assay, chromatin immunoprecipitation and coimmunoprecipitation assays. The clinical application of ZNF545 was assessed in primary gastric cancers. <h3>Results</h3> ZNF545 was silenced or reduced in 16 out of 18 gastric cancer cell lines by promoter hypermethylation. Restoration of ZNF545 expression in gastric cancer cell lines suppressed cell proliferation and induced apoptosis. These effects of ZNF545 were attributed to inhibition of ribosomal RNA (rRNA) transcription. Inhibition of rRNA transcription by ZNF545 was further revealed to be associated with direct ribosomal DNA (rDNA) promoter binding, recruitment of the corepressor, heterochromatin protein 1β, and reduction of trimethylated histone H3 at the Lys4 residue at the rDNA locus. ZNF545 methylation was detected in 51.9% (41/79) of gastric cancer tissues, 27.0% (20/74) of adjacent non-tumour gastric tissues (p=0.001), but none of 20 normal controls. Multivariate analysis revealed that patients with ZNF545 methylation had a significant decrease in overall survival. Kaplan–Meier survival curves showed that ZNF545 methylation was significantly associated with shortened survival in patients with stage I–II gastric cancer. <h3>Conclusions</h3> ZNF545 acts as a functional tumour suppressor in gastric cancer by inhibiting rRNA transcription. Its methylation at early stages of gastric carcinogenesis is an independent prognostic factor.
Leukocyte common antigen (CD45) is required for immunoglobulin E-mediated degranulation of mast cells.
Authors: S A Berger, T W Mak, C J Paige
Journal: The Journal of Experimental Medicine (1994)

We demonstrate using primary mast cell cultures derived from wild-type and CD45-deficient mice that mast cell triggering through the high-affinity immunoglobulin E (IgE) receptor requires the cell surface tyrosine phosphatase CD45. Unlike wild-type cells, cross-linking of surface-bound IgE in mast cells deficient in CD45 does not induce degranulation. Degranulation in these mutant cells does occur after treatment with the calcium ionophore A23187 indicating that the degranulation machinery is intact in these cells. We also demonstrate that the tyrosine phosphatase inhibitors orthoVanadate and perVanadate inhibit degranulation in wild-type mast cells, as does cross-linking of CD45 by anti-CD45 antibodies. Finally, we show that CD45-deficient mice are resistant to IgE-dependent systemic anaphylaxis. These results show that, like the T cell receptor and the antigen receptor on B cells, there is an absolute requirement for CD45 in signaling via the high affinity IgE receptor, expanding the number of receptors for which CD45 is an essential component.
Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma
Authors: Ning-Fang Ma, Liang Hu, Jackie M. Fung, Dan Xie, Bo-Jian Zheng, Leilei Chen, Dong-Jiang Tang, Li Fu, Zhenguo Wu, Muhan Chen, Yan Fang, Xin-Yuan Guan
Journal: Hepatology (2007)

Amplification of 1q21 is the most frequent genetic alteration in human hepatocellular carcinoma (HCC), being detected in 58%-78% of primary HCC cases by comparative genomic hybridization. Recently, we isolated a candidate oncogene, Amplified in Liver Cancer 1 (ALC1), from 1q21 by hybrid selection. Here we demonstrate that ALC1 was frequently amplified and overexpressed in HCC. ALC1-transfected cells possessed a strong oncogenic ability, increasing the colony formation in soft agar and increasing the tumorigenicity in nude mice, which could be effectively suppressed by small interfering RNA against ALC1. Functional studies showed that overexpression of ALC1 could promote G1/S phase transition and inhibit apoptosis. Molecular studies revealed that the oncogenic function of ALC1 might be associated with its roles in promoting cell proliferation by down-regulating p53 expression.These results suggest that ALC1 is the target oncogene within the 1q21 amplicon and plays a pivotal role in HCC pathogenesis.
Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy
Authors: Peng Huang, Cheng Xu, Jing Lin, Can Wang, Xiansong Wang, Chunlei Zhang, Xuejiao Zhou, Shouwu Guo, Daxiang Cui
Journal: Theranostics (2011)

Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation.The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine.In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity.The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking.The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation.These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT.
Downregulation of microRNA-29 by antisense inhibitors and a PPAR-γ agonist protects against myocardial ischaemia–reperfusion injury
Authors: Yumei Ye, Zhaoyong Hu, Yu Lin, Congfang Zhang, Jose R. Perez-Polo
Journal: Cardiovascular Research (2010)

AimsMicroRNAs (miRNAs) regulate various cardiac processes including cell proliferation and apoptosis. Pioglitazone (PIO), a peroxisome proliferator-activated receptor (PPAR)-γ agonist, protects against myocardial ischaemia–reperfusion (IR) injury. We assessed the effects of PPAR-γ activation on myocardial miRNA levels and the role of miRNAs in IR injury.
Knowledge and perceptions of asthma in Zambia: A preliminary report
Authors: Emilia Jumbe Marsden, Somwe Wa Somwe, Chishala Chabala, Jordi Casafont, Joan Soriano, Cesar Picado, Julio Ancochea
Journal: European Respiratory Journal (2012)

Adults and adolescents visiting four clinics, representing different socioeconomic areas in urban Lusaka were surveyed from July to December 2011 with a standardised questionnaire. The research protocol was approved by the National Research Ethics Committee, and all participants gave written informed consent.

Up to January 2012, data from 946 participants were collected. Mean age was 26 yr. old, 64.2% were female, 69.7% were living in high, 21.6% medium, and 8.5% in low-density areas respectively. The educational attainment of participants was 19.5% up to primary, 54.5% up to secondary, and 24.0% higher than secondary. Self-reported asthma symptoms in the last year were: 48.0% cough, 25.7% night-awakening, 19.7% shortness of breath, 15.8% wheezing and 7.7% asthma attack, while 6.3% reported using asthma medication currently. Medications used to alleviate asthma symptoms were mostly oral (antibiotics 40.0%, antihistamines 26.0%, SABA 24.0%, cough mixtures 16.0%, theophyllines 9.5%, and steroids 6.5%), while inhaled medications were seldom used (SABA 13.0%, steroids 7.5%, and LABA none). Many misconceptions on asthma were identified, with 45% reporting that asthma cannot be symptom-free and 59.9% that asthmatics cannot exercise or engage in strenuous exercises, among others. Finally, on asthma perceptions only 47.1% reported that hospitalizations for asthma are preventable, although 68.9% thought asthma symptoms can be prevented with medications. Overall, 64.2% of participants agreed that asthma is a serious health problem in Zambia.

We conclude that knowledge on asthma and its management is poor. Awareness and medical education programmes would improve asthma patients quality of life.
Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor
Authors: Yasuo Mori, Hiromi Iwasaki, Kentaro Kohno, Goichi Yoshimoto, Yoshikane Kikushige, Aki Okeda, Naokuni Uike, Hiroaki Niiro, Katsuto Takenaka, Koji Nagafuji, Toshihiro Miyamoto, Mine Harada, Kiyoshi Takatsu, Koichi Akashi
Journal: The Journal of Experimental Medicine (2008)

To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872–11877) was composed of the interleukin 5 receptor α chain+ (IL-5Rα+) and IL-5Rα− fractions, and the former was the hEoP. The IL-5Rα+CD34+CD38+IL-3Rα+CD45RA− hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5Rα− hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an “IL-5Rα–negative” criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders.
Socioeconomic Position, Race/Ethnicity, and Inflammation in the Multi-Ethnic Study of Atherosclerosis
Authors: Nalini Ranjit, Ana V. Diez-Roux, Steven Shea, Mary Cushman, Hanyu Ni, Teresa Seeman
Journal: Circulation (2007)

Background— Low socioeconomic position is known to be associated with cardiovascular events and atherosclerosis. Reasons for these associations remain a topic of research. Inflammation could be an important mediating mechanism linking socioeconomic position to cardiovascular risk. Methods and Results— This cross-sectional study used data from the baseline examination of the Multi-Ethnic Study of Atherosclerosis (MESA), a study of 6814 men and women 45 to 84 years of age. Race- and ethnicity-stratified regression analyses were used to estimate associations of household income and education with C-reactive protein and interleukin-6 before and after adjustment for infection and medication use, psychosocial factors, behaviors, adiposity, and diabetes mellitus. Low income was associated with higher concentrations of interleukin-6 in all race/ethnic groups. Percent differences associated with 1-SD–lower income were 9% (95% confidence interval [CI], 7 to 11), 6% (95% CI, 1 to 10), 8% (95% CI, 4 to 11), and 8% (95% CI, 3 to 13) for whites, Chinese, blacks, and Hispanics. Low levels of education were associated with higher levels of interleukin-6 only among whites and blacks (percent difference in interleukin-6 associated with 1-SD–lower education: 9% [95% CI, 6 to 12] among Whites, and 7% [95% CI, 3 to 10] among blacks). Similar patterns were observed for C-reactive protein. Adiposity was the single most important factor explaining socioeconomic position associations, especially among blacks and whites. A smaller effect was seen for psychosocial factors and behaviors in all race groups. Conclusions— Both household income and education are associated with inflammation, but associations vary across race/ethnic groups. Associations likely result from socioeconomic position patterning of adiposity and other factors.
Entering the Era of Targeted Therapy for Chronic Lymphocytic Leukemia: Impact on the Practicing Clinician
Authors: John C. Byrd, Jeffrey J. Jones, Jennifer A. Woyach, Amy J. Johnson, Joseph M. Flynn
Journal: Journal of Clinical Oncology (2014)

Chemoimmunotherapy has been the standard of care for chronic lymphocytic leukemia (CLL). However, the introduction of B-cell receptor (BCR) kinase inhibitors such as ibrutinib has the potential to eliminate the role of chemotherapy in the treatment of CLL. How to best incorporate old and new therapies for CLL in this landscape is increasingly complex.This article reviews current data available to clinicians and integrates these data to provide a strategy that can be used to approach the treatment of CLL in the era of BCR signaling inhibitors.Current strategies separate patients based on age or functional status as well as genetics [presence or absence of del(17)(p13.1)]. In the era of targeted therapy, this will likely continue based on current available data. Phase III studies support chemoimmunotherapy as the initial standard therapy for patients without del(17)(p13.1). Choice of chemotherapy (fludarabine plus cyclophosphamide, bendamustine, or chlorambucil) and anti-CD20 antibody (rituximab, ofatumumab, or obinutuzumab) varies based on regimen and patient status. For patients with del(17)(p13.1), no standard initial therapy exists, although several options supported by phase II clinical trials (methylprednisolone plus alemtuzumab or ibrutinib) seem better than chemoimmunotherapy. Treatment of relapsed CLL seems to be best supported by ibrutinib-based therapy. Completion of trials with ibrutinib and other new agents in the near future will offer opportunity for chemotherapy-free treatment across all groups of CLL.Therapy for CLL has evolved significantly over the past decade with introduction of targeted therapy for CLL. This has the potential to completely transform how CLL is treated in the future.
CPAP treatment of sleep apnoea in the early phase of stroke: growing evidence of effectiveness
Authors: P. Lévy, J-L. Pépin
Journal: European Respiratory Journal (2011)

Sleep apnoea has been shown to be a cardiovascular risk factor 1, 2, presumably with a major role attributable to intermittent hypoxia 3, 4. Early reports have suggested a relationship between sleep-disordered breathing and stroke 5–8. The association between sleep apnoea and both prevalent and incident stroke has been further established in general population cohorts 9, 10. Specifically, the Wisconsin Sleep Cohort provided prospective evidence that sleep-disordered breathing precedes stroke and may contribute to the development of stroke 9. The prospective analysis of the Sleep Heart and Health Study also showed, in males  50% of the stroke patients. Also, central events were limited to 7% of the total number of abnormal respiratory events during sleep. Consequently, as this association between sleep apnoea and stroke has been demonstrated, treating sleep-disordered breathing could be expected to be beneficial 13, 14 …