tbuckley/cabot-search huggingface dataset:
Macrophage-Mediated Renal Injury Is Dependent on Signaling via the JNK Pathway
Authors: Yohei Ikezumi, Lyn Hurst, Robert C. Atkins, David J. Nikolic-Paterson
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Macrophage accumulation is a prominent feature in most forms of human glomerulonephritis and correlates with renal dysfunction. Macrophages can directly mediate acute renal injury in animal models, but the mechanisms of macrophage activation required for mediating renal injury are unknown. This study examined whether activation of the Jun amino terminal kinase (JNK) signaling pathway is necessary for macrophage-mediated renal injury. An adoptive transfer model was used in which rats were immunized with sheep IgG (day −5), made leukopenic by administration of cyclophosphamide (CyPh) (day −2), and then injected with sheep anti-glomerular basement membrane (GBM) serum (day 0). Animals were then given an intravenous injection of bone marrow-derived macrophages (BMM) (day 1) and killed 24 h later (day 2). The induction of proteinuria and glomerular cell proliferation (PCNA+ cells) in CyPh-treated anti-GBM disease was dependent on transfer of BMM. Exposure of BMM to the specific JNK inhibitor, SP600125, for 3 h before adoptive transfer had no effect on glomerular accumulation of BMM in CyPh-treated anti-GBM disease. However, SP600125 treatment of BMM caused a 75% reduction in proteinuria and a 70% reduction in glomerular cell proliferation (P < 0.01 versus vehicle or untreated BMM). In conclusion, this study has defined a critical role for the JNK signaling pathway in macrophage-mediated renal injury.
Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer
Authors: Zhe Jin, Alexandru Olaru, Jian Yang, Fumiaki Sato, Yulan Cheng, Takatsugu Kan, Yuriko Mori, Carmit Mantzur, Bogdan Paun, James P. Hamilton, Tetsuo Ito, Suna Wang, Stefan David, Rachana Agarwal, David G. Beer, John M. Abraham, Stephen J. Meltzer
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Our aim was to investigate whether and at what stage hypermethylation of the tachykinin-1 (TAC1) gene is associated with human esophageal neoplastic transformation. Experimental Design: TAC1 promoter hypermethylation was examined by real-time methylation-specific PCR in 258 human esophageal specimens and 126 plasma samples from patients or tissues at various stages of neoplastic evolution. Results: TAC1 hypermethylation in tissue samples showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (P &amp;lt; 0.0001). Both frequencies and normalized methylation values of TAC1 tissue methylation were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's esophagus, EAC, and ESCC than in normal esophagus (P &amp;lt; 0.01). The frequency of TAC1 hypermethylation increased dramatically and early during neoplastic progression, from 7.5% in normal esophagus to 55.6% in BE from patients with Barrett's metaplasia alone, 57.5% in dysplastic Barrett's esophagus, and 61.2% in EAC. There was a significant relationship between TAC1 hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Twelve (50%) of 24 ESCC exhibited TAC1 hypermethylation. Overall patient survival correlated significantly with TAC1 methylation status in ESCC patients (mean survival, 22 versus 110 months; P = 0.0102, log-rank test), but not in EAC patients. Both mean normalized methylation values and frequency of TAC1 hypermethylation in plasma samples were significantly higher in EAC patients than in control subjects. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2′-deoxycytidine reduced TAC1 methylation and increased TAC1 mRNA expression. Conclusions: TAC1 promoter hypermethylation is a common event in both major histologic types of human esophageal carcinoma, occurs early, correlates with other progression risk factors in esophageal adenocarcinogenesis, and is a tissue biomarker of a poor prognosis in ESCC. Circulating methylated TAC1 promoter DNA also offers potential as a biomarker for the diagnosis of EAC.
Corrosive Gastritis Resembling Carcinoma, Due to Ingestion of Acid
Authors: R. Thomas Holzbach
Journal: JAMA (1968)

To the Editor:—  Oral ingestion of corrosive substances has become an infrequent event. Most physicians remain familiar with the effects of lye ingestion resulting in esophageal stricture. Chronic effects resulting from other corrosives are encountered. In an experience in which the nature of the ingested corrosive was not clearly established at first (mistakenly assumed to have been lye) the history of ingestion was dismissed as clinically irrelevant.  Report of a Case:—  A 69-year-old man was admitted to St. Luke's Hospital on Feb 9, 1968, because of epigastric pain. The patient was apparently well until Jan 8, when because of depression, he swallowed about one third to one half cupful of cleaning material assumed to be lye. Immediately afterward the patient felt severe burning pain in the substernal and upper abdominal areas. During three weeks in a hospital the patient continued to have epigastric pain, more pronounced after eating. Vomitus on
Baseline Predictors for One-Year Visual Outcomes with Ranibizumab or Bevacizumab for Neovascular Age-related Macular Degeneration
Authors: Gui-shuang Ying, Jiayan Huang, Maureen G. Maguire, Glenn J. Jaffe, Juan E. Grunwald, Cynthia Toth, Ebenezer Daniel, Michael Klein, Dante Pieramici, John Wells, Daniel F. Martin
Journal: Ophthalmology (2012)
RESIDUAL VACCINES: A New Technique for Their Preparation, with a Description of Some Properties of the Bacterial Residue
Authors: C. E. Jenkins
Journal: BMJ (1921)

THE detoxication of vaccines has recently attracted con- siderable attention.Thomson's method1 depends upon the fact that alkaline solutions dissolve organisms and their toxins whilst mineral acids precipitate the organisms but retain the toxins in solution.The chief merit of this method is that the final concentration ready for administration can be adjusted to any desired strength.Professor 11.R. Dean2 has shown that a suspension of virulent organisms can be detoxicated by the action of eusol or hydrogen peroxide in weak solution.The author has
A comprehensive evaluation of assembly scaffolding tools
Authors: Martin Hunt, Chris Newbold, Matthew Berriman, Thomas D Otto
Journal: Genome biology (2014)

Genome assembly is typically a two-stage process: contig assembly followed by the use of paired sequencing reads to join contigs into scaffolds. Scaffolds are usually the focus of reported assembly statistics; longer scaffolds greatly facilitate the use of genome sequences in downstream analyses, and it is appealing to present larger numbers as metrics of assembly performance. However, scaffolds are highly prone to errors, especially when generated using short reads, which can directly result in inflated assembly statistics.Here we provide the first independent evaluation of scaffolding tools for second-generation sequencing data. We find large variations in the quality of results depending on the tool and dataset used. Even extremely simple test cases of perfect input, constructed to elucidate the behaviour of each algorithm, produced some surprising results. We further dissect the performance of the scaffolders using real and simulated sequencing data derived from the genomes of Staphylococcus aureus, Rhodobacter sphaeroides, Plasmodium falciparum and Homo sapiens. The results from simulated data are of high quality, with several of the tools producing perfect output. However, at least 10% of joins remains unidentified when using real data.The scaffolders vary in their usability, speed and number of correct and missed joins made between contigs. Results from real data highlight opportunities for further improvements of the tools. Overall, SGA, SOPRA and SSPACE generally outperform the other tools on our datasets. However, the quality of the results is highly dependent on the read mapper and genome complexity.
Morphological subtyping of acute myeloid leukemia with maturation (AML-M2): homogeneous pink-colored cytoplasm of mature neutrophils is most characteristic of AML-M2 with t(8;21)
Authors: H Nakamura, K Kuriyama, N Sadamori, M Mine, T Itoyama, I Sasagawa, K Matsumoto, Y Tsuji, N Asou, S-I Kageyama, H Sakamaki, N Emi, R Ohno, M Tomonaga
Journal: Leukemia (1997)
Nonpharmacological treatment and relief of symptoms in COPD
Authors: E M Clini, N Ambrosino
Journal: European Respiratory Journal (2008)

Evidence-based guidelines for chronic obstructive pulmonary disease (COPD) have recently been developed. Nonpharmacological treatments have evolved rapidly as an essential part of COPD therapy. They are especially important as complementary interventions in severe or very severe disease, when there is loss in function, a reduction in quality of life and when psychological impairments further complicate the disease. The present article discusses the most used nonpharmacological treatments for severe COPD patients (rehabilitation, long-term oxygen therapy, surgery, noninvasive positive pressure ventilation and supportive nutrition) and their evidence-based usefulness in promoting strategies that relieve symptoms. All of these interventions are used during end-stage disease, to promote self-efficacy, relieve symptoms and prevent further deterioration. These therapeutic options support physicians and allied professionals in improving symptom management for their patients.
Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma
Authors: Ye Song, Qisheng Luo, Hao Long, Zheng Hu, Tianshi Que, Xi’an Zhang, Zhiyong Li, Gang Wang, Liu Yi, Zhen Liu, WeiYi Fang, Songtao Qi
Journal: Molecular Cancer (2014)

Abstract Background The success of using glycolytic inhibitors for cancer treatment relies on better understanding the roles of each frequently deregulated glycolytic genes in cancer. This report analyzed the involvement of a key glycolytic enzyme, alpha-enolase (ENO1), in tumor progression and prognosis of human glioma. Methods ENO1 expression levels were examined in glioma tissues and normal brain (NB) tissues. The molecular mechanisms of ENO1 expression and its effects on cell growth, migration and invasion were also explored by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Transwell chamber assay, Boyden chamber assay, Western blot and in vivo tumorigenesis in nude mice. Results ENO1 mRNA and protein levels were upregulated in glioma tissues compared to NB. In addition, increased ENO1 was associated disease progression in glioma samples. Knocking down ENO1 expression not only significantly decreased cell proliferation, but also markedly inhibited cell migration and invasion as well as in vivo tumorigenesis. Mechanistic analyses revealed that Cyclin D1, Cyclin E1, pRb, and NF-κB were downregulated after stable ENO1 knockdown in glioma U251 and U87 cells. Conversely, knockdown of ENO1 resulted in restoration of E-cadherin expression and suppression of mesenchymal cell markers, such as Vimentin, Snail, N-Cadherin, β-Catenin and Slug. Furthermore, ENO1 suppression inactivated PI3K/Akt pathway regulating the cell growth and epithelial-mesenchymal transition (EMT) progression. Conclusion Overexpression of ENO1 is associated with glioma progression. Knockdown of ENO1 expression led to suppressed cell growth, migration and invasion progression by inactivating the PI3K/Akt pathway in glioma cells.
Clinical Risk Factors, DNA Variants, and the Development of Type 2 Diabetes
Authors: Valeriya Lyssenko, Anna Jonsson, Peter Almgren, Nicoló Pulizzi, Bo Isomaa, Tiinamaija Tuomi, Göran Berglund, David Altshuler, Peter Nilsson, Leif Groop
Journal: New England Journal of Medicine (2008)

Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts.We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time.Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased.As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up.
Calcineurin Signaling as a Negative Determinant of Keratinocyte Cancer Stem Cell Potential and Carcinogenesis
Authors: G. Paolo Dotto
Journal: Cancer Research (2011)

Abstract Calcineurin is the only known serine-threonine phosphatase under calcium–calmodulin control and key regulator of the immune system. Treatment of patients with calcineurin-inhibitory drugs like cyclosporin A and FK506 to prevent graft rejection dramatically increases the risk of cutaneous squamous cell carcinoma, which is a major cause of death after organ transplants. Recent evidence indicates that suppression of calcineurin signaling, together with its impact on the immune system, exerts direct tumor-promoting effects in keratinocytes, enhancing cancer stem cell potential. The underlying mechanism involves interruption of a double negative regulatory axis, whereby calcineurin and nuclear factors of activated T-cell signaling inhibits expression of ATF3, a negative regulator of p53. The resulting suppression of keratinocyte cancer cell senescence is of likely clinical significance for the many patients under treatment with calcineurin inhibitors and may be of relevance for other cancer types in which altered calcium–calcineurin signaling plays a role. Cancer Res; 71(6); 2029–33. ©2011 AACR.
Evidence for a bone-kidney axis regulating phosphate homeostasis
Authors: L. Darryl Quarles
Journal: Journal of Clinical Investigation (2003)

A novel circulation phosphaturic hormone is postulated to regulate systemic phosphate homeostasis. Two new studies reveal that the phosphaturic factor FGF-23 is increased in hypophosphatemic subjects with McCune-Albright syndrome and that secreted frizzled-related protein-4 (sFRP-4), a factor produced by tumors derived from subjects with tumor-induced osteomalacia, also has phosphaturic activity. It remains to be established whether FGF-23 and sFRP-4 represent two distinct phosphatonins or are somehow integrated in a novel phosphate-regulating bone-kidney axis.
The Pharmacology of Aldose Reductase Inhibitors
Authors: P F Kador, W G Robison, J H Kinoshita
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Mutualism is only a part of human morality
Authors: Herbert Gintis
Journal: Behavioral and Brain Sciences (2013)

Abstract Baumard et al. mischaracterize our model of individual and social choice behavior. We model individuals who maximize preferences given their beliefs, and subject to their informational and material constraints (Fehr &amp; Gintis 2007). Individuals thus must make trade-offs among self-regarding, other-regarding, and character virtue goals. Two genetic predispositions are particularly crucial. The first is strong reciprocity . The second is the capacity to internalize norms through the socialization process. Our model includes the authors' model as a subset.
Should All Patients with Non–Muscle-Invasive Bladder Cancer Receive Early Intravesical Chemotherapy after Transurethral Resection? The Results of a Prospective Randomised Multicentre Study
Authors: Sigurdur Gudjónsson, Lars Adell, Fekadu Merdasa, Ronnie Olsson, Bruno Larsson, Thomas Davidsson, Jonas Richthoff, Gunnar Hagberg, Magnus Grabe, Pär Ola Bendahl, Wiking Månsson, Fredrik Liedberg
Journal: European Urology (2009)
Recipe for a sexually dimorphic brain: Ingredients include ovarian and testicular hormones
Authors: Diane F. Halpern
Journal: Behavioral and Brain Sciences (1998)

New knowledge about the sexual differentiation of the brain profoundly changes our understanding of basic topics in brain development such as the false dichotomy between long-lasting and transient effects of hormones on neural activity, the importance of ovarian hormones in brain development, the plasticity of neural structures throughout the life span, and the way measurement issues affect research conclusions.
Effects of adipose tissue-derived stromal/stem cells transplantation on elastase-induced pulmonary emphysema in rats
Authors: Naoki Furuya, Mitsuko Takenaga, Teruomi Miyazawa
Journal: European Respiratory Journal (2011)

Many studies demonstrating lung repair by means of stem/progenitor cells or growth factors have been reported in animal emphysema models. We focused on adipose tissue-derived stromal/stem cells (ASCs) for regenerative medicine, since it has a high potential to secrete multiple angiogenic factors and differentiate various kinds of cells. To demonstrate the therapeutic impact of ASCs transplantation and to elucidate mechanisms of the effects in rat emphysema models. ASCs were isolated from Wistar rat inguinal subcutaneous adipose tissue. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE). One week after induction of PPE, cell transplantation was performed intravenously. At 1 and 2 weeks after transplantation, we assessed arterial blood analysis and histopathological changes and measurement of chemokine levels. After PPE induction, arterial oxygen pressure (PaO 2 ) was reduced. After ASCs transplantation, PaO 2  significantly improved. In addition, transplantation significantly prevented the enlargement of alveolar airspace elicited by PPE. PPE gradually reduced the levels of endogenous hepatocyte growth factor (HGF) in lung tissue. ASCs augmented HGF level was significantly higher than PPE alone. ASCs from GFP transgenic rats were localized at damaged alveolar spaces. Immunohistochemical analysis revealed some grafted ASCs were expressed CD31 or SP-C at 1w after transplantation. The results showed that transplantation of ASCs for emphysema rats improved gas exchange and inhibit enlargement of the airspaces. Transplantation of ASCs may be new therapeutic strategy to improve pulmonary function and inhibit alveolar destruction in COPD.
Biogeography of the ecosystems of the healthy human body
Authors: Yanjiao Zhou, Hongyu Gao, Kathie A Mihindukulasuriya, Patricio S La Rosa, Kristine M Wylie, Tatiana Vishnivetskaya, Mircea Podar, Barb Warner, Phillip I Tarr, David E Nelson, J Dennis Fortenberry, Martin J Holland, Sarah E Burr, William D Shannon, Erica Sodergren, George M Weinstock
Journal: Genome biology (2013)

Characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. Previous studies mainly focused on a single body habitat from a limited set of subjects. Here, we analyzed one of the largest microbiome datasets to date and generated a biogeographical map that annotates the biodiversity, spatial relationships, and temporal stability of 22 habitats from 279 healthy humans.We identified 929 genera from more than 24 million 16S rRNA gene sequences of 22 habitats, and we provide a baseline of inter-subject variation for healthy adults. The oral habitat has the most stable microbiota with the highest alpha diversity, while the skin and vaginal microbiota are less stable and show lower alpha diversity. The level of biodiversity in one habitat is independent of the biodiversity of other habitats in the same individual. The abundances of a given genus at a body site in which it dominates do not correlate with the abundances at body sites where it is not dominant. Additionally, we observed the human microbiota exhibit both cosmopolitan and endemic features. Finally, comparing datasets of different projects revealed a project-based clustering pattern, emphasizing the significance of standardization of metagenomic studies.The data presented here extend the definition of the human microbiome by providing a more complete and accurate picture of human microbiome biogeography, addressing questions best answered by a large dataset of subjects and body sites that are deeply sampled by sequencing.
Superior Antitumor Activity of SAR3419 to Rituximab in Xenograft Models for Non-Hodgkin's Lymphoma
Authors: Ayad M. Al-Katib, Amro Aboukameel, Ramzi Mohammad, Marie-Christine Bissery, Claudia Zuany-Amorim
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To investigate the activity of SAR3419, a novel humanized anti-CD19 antibody (huB4), conjugated to a cytotoxic maytansine derivative N2'-deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl) maytansine, in preclinical xenograft models for non–Hodgkin's lymphoma. Experimental Design: Antitumor activity of SAR3419 was assessed as a single agent and in comparison with conventional therapies using a subcutaneous model for diffuse large B-cell lymphoma (WSU-DLCL2) and a systemic model for follicular small cleaved cell lymphoma (WSU-FSCCL) in mice with severe combined immune deficiency. Results: Our results showed that in these chemotherapy-resistant models, SAR3419 was more effective than CHOP (cyclophosphamide-Adriamycin-vincristine-prednisone) regimen or rituximab. Only treatment with SAR3419 led to survival of the whole group of animals to the end of the experiment (150-155 days) in both models. Higher doses of SAR3419 (15 and 30 mg/kg) were more effective than lower dose of 7.5 mg/kg. The immunoconjugation was necessary because neither huB4 nor DM4 alone had significant activity. Treatment with rituximab resulted in antitumor activity in both models comparable with the low dose of SAR3419. Cyclophosphamide-Adriamycin-vincristine-prednisone alone showed modest activity in both models. Necropsy and tissue staining in the WSU-FSCCL systemic model revealed that all deaths featured leptomeningeal lymphoma in the control and treated groups. Interestingly, some of the animals that survived to the end of the experiment and seemed healthy at time of euthanasia did show microscopic evidence of lymphoma. Conclusions: Overall, SAR3419 is a very active immunotoxin in preclinical models for human B-cell lymphoma and holds promise as a novel and well-tolerated therapy in B-cell non–Hodgkin's lymphoma.