tbuckley/cabot-search huggingface dataset:
Plasminogen and Plasminogen Activators Protect against Renal Injury in Crescentic Glomerulonephritis
Authors: A. Richard Kitching, Stephen R. Holdsworth, Victoria A. Ploplis, Edward F. Plow, Désiré Collen, Peter Carmeliet, Peter G. Tipping
Journal: The Journal of Experimental Medicine (1997)

The plasminogen/plasmin system has the potential to affect the outcome of inflammatory diseases by regulating accumulation of fibrin and other matrix proteins. In human and experimental crescentic glomerulonephritis (GN), fibrin is an important mediator of glomerular injury and renal impairment. Glomerular deposition of matrix proteins is a feature of progressive disease. To study the role of plasminogen and plasminogen activators in the development of inflammatory glomerular injury, GN was induced in mice in which the genes for these proteins had been disrupted by homologous recombination. Deficiency of plasminogen or combined deficiency of tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA) was associated with severe functional and histological exacerbation of glomerular injury. Deficiency of tPA, the predominant plasminogen activator expressed in glomeruli, also exacerbated disease. uPA deficiency reduced glomerular macrophage infiltration and did not significantly exacerbate disease. uPA receptor deficiency did not effect the expression of GN. These studies demonstrate that plasminogen plays an important role in protecting the glomerulus from acute inflammatory injury and that tPA is the major protective plasminogen activator.
The role of mitochondria in aging
Authors: Ana Bratic, Nils-Göran Larsson
Journal: Journal of Clinical Investigation (2013)

Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysfunction and major phenotypes associated with aging. Somatic mitochondrial DNA (mtDNA) mutations and respiratory chain dysfunction accompany normal aging, but the first direct experimental evidence that increased mtDNA mutation levels contribute to progeroid phenotypes came from the mtDNA mutator mouse. Recent evidence suggests that increases in aging-associated mtDNA mutations are not caused by damage accumulation, but rather are due to clonal expansion of mtDNA replication errors that occur during development. Here we discuss the caveats of the traditional mitochondrial free radical theory of aging and highlight other possible mechanisms, including insulin/IGF-1 signaling (IIS) and the target of rapamycin pathways, that underlie the central role of mitochondria in the aging process.
Effect of peroxisome proliferator activated receptor ligands on growth and gene expression profiles of gastric cancer cells
Authors: W K Leung
Journal: Gut (2004)

<b>Background and aims:</b> Although peroxisome proliferator activated receptor γ (PPARγ) agonists have been implicated in differentiation and growth inhibition of cancer cells, the potential therapeutic and chemopreventive effects on gastric cancer are poorly defined. We examined the in vitro and in vivo effects of PPARγ ligands on growth of gastric cancer, and the effect of PPARγ activation on expression of cyclooxygenase 2 (COX-2) and cancer related genes. <b>Methods:</b> Gastric cell lines (MKN28 and MKN45) were treated with two specific PPARγ ligands: ciglitazone and 15-deoxy-Δ<sup>12,</sup><sup>14</sup>-prostaglandin J<sub>2</sub>. Cell growth was determined by bromodeoxyuridine incorporation assay and apoptosis was measured by DNA fragmentation. Expression of COX-2 was determined by western blot and real time quantitative polymerase chain reaction (PCR). Expression profiles of cancer related genes were screened with cDNA array. In vivo growth of implanted MKN45 cells in nude mice was monitored after oral treatment with rosiglitazone. <b>Results:</b> PPARγ ligands suppressed the in vitro growth of MKN45 cells in a dose dependent manner whereas prostacyclin, a PPARδ agonist, had no growth inhibitory effect. Growth inhibition was more pronounced in MKN45 cells, which was accompanied by DNA fragmentation and downregulation of COX-2. Screening by cDNA microarray showed that PPARγ ligand treatment was associated with upregulation of <i>bad</i> and <i>p53</i>, and downregulation of <i>bcl-2</i>, <i>bcl-xl</i>, and <i>cyclin E1</i> in MKN45 cells, which was confirmed by quantitative real time PCR. In contrast, MKN28 cells with lower PPARγ and COX-2 expression levels had lower growth inhibitory responses to PPARγ ligands. Microarray experiments only showed induction of the <i>bad</i> gene in MKN28 cells. In vivo growth of MKN45 cells in nude mice was retarded by rosiglitazone. Mean tumour volume in rosiglitazone treated mice was significantly lower than controls at six weeks (p = 0.019) and seven weeks (p = 0.001) after treatment. <b>Conclusions:</b> PPARγ ligands suppress both in vitro and in vivo growth of gastric cancer and may play a major role in cancer therapy and prevention.
Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients
Authors: Per Ljungman, Giorgio Lambertenghi Deliliers, Uwe Platzbecker, Susanne Matthes-Martin, Andrea Bacigalupo, Hermann Einsele, Johanna Ullmann, Maurizio Musso, Rudolf Trenschel, Patricia Ribaud, Martin Bornhäuser, Simone Cesaro, Bruce Crooks, Adrian Dekker, Nicole Gratecos, Thomas Klingebiel, Elena Tagliaferri, Andrew J. Ullmann, Pierre Wacker, Catherine Cordonnier
Journal: Blood (2001)
O123 POST SORAFENIB SURVIVAL IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA: THE ROLE OF TUMOR PROGRESSION AND LIVER IMPAIRMENT
Authors: M. Iavarone, G. Cabibbo, M. Biolato, C. Della Corte, M. Maida, M. Basso, S. Vavassori, C. Cammà, A. Grieco, A. Craxì, M. Colombo
Journal: Journal of Hepatology (2014)
BCG provides protection for a lifetime
Authors: A E Boyd
Journal: Thorax (2004)

▴ Aronson NE, Santosham M, Comstock GW, et al . Long-term efficacy of BCG vaccine in American Indians and Alaska natives: a 60-year follow-up study. JAMA2004;291:2086–91 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This paper analyses the efficacy of BCG vaccination in 2792 American Indians and Alaska natives enrolled in a placebo controlled trial of BCG between 1935 and 1938. They were recruited aged 1 month to 20 years following a normal chest radiograph and absence of reaction to a strong dose of purified … [1]: {openurl}?query=rft.jtitle%253DJAMA%26rft.stitle%253DJAMA%26rft.issn%253D0002-9955%26rft.aulast%253DAronson%26rft.auinit1%253DN.%2BE.%26rft.volume%253D291%26rft.issue%253D17%26rft.spage%253D2086%26rft.epage%253D2091%26rft.atitle%253DLong-term%2BEfficacy%2Bof%2BBCG%2BVaccine%2Bin%2BAmerican%2BIndians%2Band%2BAlaska%2BNatives%253A%2BA%2B60-Year%2BFollow-up%2BStudy%26rft_id%253Dinfo%253Adoi%252F10.1001%252Fjama.291.17.2086%26rft_id%253Dinfo%253Apmid%252F15126436%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/jama.291.17.2086&link_type=DOI [3]: /lookup/external-ref?access_num=15126436&link_type=MED&atom=%2Fthoraxjnl%2F59%2F8%2F724.atom [4]: /lookup/external-ref?access_num=000221174300025&link_type=ISI
Immune reactions to Pityrosporum ovale in adult patients with atopic and seborrheic dermatitis
Authors: Marianne Kieffer, Inge-Marie Bergbrant, Jan Faergemann, Gregor B.E. Jemec, Vibeke Ottevanger, Per Stahl Skov, Else Svejgaard
Journal: Journal of the American Academy of Dermatology (1990)
A Fatal Poisoning From the Oregon Rough-Skinned Newt (Taricha granulosa)
Authors: Susan G. Bradley
Journal: JAMA (1981)

CERTAIN newts possess a neurotoxin that can be fatal if ingested. Toxic varities include the<i>Taricha</i>species that are found in Oregon, California, and southern Alaska (Figure). In addition, certain species found on the east coast such as the<i>Notophthalmus</i>species of the Carolinas are toxic, but the toxin is only 1/100th as potent as that found in Taricha.<sup>1</sup> <h3>Report of Cases</h3><h3>Case 1.—</h3> A 29-year-old man drank approximately 150 mL of whiskey at about 11 AM July 9, 1979. At 6 PM he swallowed a 20-cm newt on a dare. Within ten minutes he complained of tingling of the lips. During the next two hours he began complaining of numbness and weakness and stated that he thought he was going to die. He refused to be transported to a hospital and was left alone for 15 minutes and then experienced cardiopulmonary arrest. Resuscitation measures were initiated, but two
Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis
Authors: Amir Abdollahi, Minglun Li, Gong Ping, Christian Plathow, Sophie Domhan, Fabian Kiessling, Leslie B. Lee, Gerald McMahon, Hermann-Josef Gröne, Kenneth E. Lipson, Peter E. Huber
Journal: The Journal of Experimental Medicine (2005)

Pulmonary fibrosis is the consequence of a variety of diseases with no satisfying treatment option. Therapy-induced fibrosis also limits the efficacy of chemotherapy and radiotherapy in numerous cancers. Here, we studied the potential of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors (RTKIs) to attenuate radiation-induced pulmonary fibrosis. Thoraces of C57BL/6 mice were irradiated (20 Gy), and mice were treated with three distinct PDGF RTKIs (SU9518, SU11657, or Imatinib). Irradiation was found to induce severe lung fibrosis resulting in dramatically reduced mouse survival. Treatment with PDGF RTKIs markedly attenuated the development of pulmonary fibrosis in excellent correlation with clinical, histological, and computed tomography results. Importantly, RTKIs also prolonged the life span of irradiated mice. We found that radiation up-regulated expression of PDGF (A–D) isoforms leading to phosphorylation of PDGF receptor, which was strongly inhibited by RTKIs. Our findings suggest a pivotal role of PDGF signaling in the pathogenesis of pulmonary fibrosis and indicate that inhibition of fibrogenesis, rather than inflammation, is critical to antifibrotic treatment. This study points the way to a potential new approach for treating idiopathic or therapy-related forms of lung fibrosis.
Inhibition of the Sodium/Potassium ATPase Impairs <i>N</i>-Glycan Expression and Function
Authors: Reza Beheshti Zavareh, Ken S. Lau, Rose Hurren, Alessandro Datti, David J. Ashline, Marcela Gronda, Pam Cheung, Craig D. Simpson, Wei Liu, Amanda R. Wasylishen, Paul C. Boutros, Hui Shi, Amudha Vengopal, Igor Jurisica, Linda Z. Penn, Vern N. Reinhold, Shereen Ezzat, Jeff Wrana, David R. Rose, Harry Schachter, James W. Dennis, Aaron D. Schimmer
Journal: Cancer Research (2008)

Abstract Aberrant N-linked glycans promote the malignant potential of cells by enhancing the epithelial-to-mesenchymal transition and the invasive phenotype. To identify small molecule inhibitors of N-glycan biosynthesis, we developed a chemical screen based on the ability of the tetravalent plant lectin L-phytohemagglutinin (L-PHA) to bind and crosslink surface glycoproteins with β1,6GlcNAc-branched complex type N-glycans and thereby induce agglutination and cell death. In this screen, Jurkat cells were treated with a library of off-patent chemicals (n = 1,280) to identify molecules that blocked L-PHA–induced death. The most potent hit from this screen was the cardiac glycoside (CG) dihydroouabain. In secondary assays, a panel of CGs was tested for their effects on L-PHA–induced agglutination and cell death. All of the CGs tested inhibited L-PHA–induced death in Jurkat cells, and the most potent CG tested was digoxin with an EC50 of 60 ± 20 nmol/L. Digoxin also increased the fraction of some concanavalin A–binding N-glycans. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, digoxin specifically increased GlcNAc1Man3GlcNAc2Fuc1 and GlcNAc2Man3GlcNAc2Fuc1 oligosaccharides demonstrating an impairment of the N-glycan pathway. Consistent with this effect on the N-glycan pathway, digoxin inhibited N-glycosylation–mediated processes of tumor cell migration and invasion. Furthermore, digoxin prevented distant tumor formation in two mouse models of metastatic prostate cancer. Thus, taken together, our high throughput screen identified CGs as modifiers of the N-glycan pathway. These molecules can be used as tools to better understand the role of N-glycans in normal and malignant cells. Moreover, these results may partly explain the anticancer effect of CGs in cardiovascular patients. [Cancer Res 2008;68(16):6688–96]
Absolute Prostate-Specific Antigen Value After Androgen Deprivation Is a Strong Independent Predictor of Survival in New Metastatic Prostate Cancer: Data From Southwest Oncology Group Trial 9346 (INT-0162)
Authors: Maha Hussain, Catherine M. Tangen, Celestia Higano, Paul F. Schelhammer, James Faulkner, E. David Crawford, George Wilding, Atif Akdas, Eric J. Small, Bryan Donnelly, Gary MacVicar, Derek Raghavan
Journal: Journal of Clinical Oncology (2006)

To establish whether absolute prostate-specific antigen (PSA) value after androgen deprivation (AD) is prognostic in metastatic (D2) prostate cancer (PCa).D2 PCa patients with baseline PSA of at least 5 ng/mL received 7 months induction AD. Patients achieving PSA of 4.0 ng/mL or less on months 6 and 7 are randomly assigned to continuous versus intermittent AD on month 8. Eligibility for this analysis required a prestudy PSA with at least two subsequent PSAs and that patients be registered at least 1 year before analysis date. Survival was defined as time to death after 7 months of AD. Associations were evaluated by proportional hazards regression models.One thousand one hundred thirty four of 1,345 eligible patients achieved a PSA of 4 ng/mL or less. At end of induction, 965 patients maintained PSA of 4 or less and 604 had a PSA of 0.2 ng/mL or less. After controlling for prognostic factors, patients with a PSA of 4 or less to more than 0.2 ng/mL had less than one third the risk of death (ROD) as those with a PSA of more than 4 ng/mL (P < .001). Patients with PSA of 0.2 ng/mL or less had less than one fifth the ROD as patients with a PSA of more than 4 ng/mL (P < .001) and had significantly better survival than those with PSA of more than 0.2 to 4 ng/mL or less (P < .001). Median survival was 13 months for patients with a PSA of more than 4 ng/mL, 44 months for patients with PSA of more than 0.2 to 4 ng/mL or less, and 75 months for patients with PSA of 0.2 ng/mL or less.A PSA of 4 ng/mL or less after 7 months of AD is a strong predictor of survival. This data should be used to tailor future trial design for D2 prostate cancer.
Intratumoral Estrogens and Estrogen Receptors in Human Non–Small Cell Lung Carcinoma
Authors: Hiromichi Niikawa, Takashi Suzuki, Yasuhiro Miki, Satoshi Suzuki, Shuji Nagasaki, Junichi Akahira, Seijiro Honma, Dean B. Evans, Shin-ichi Hayashi, Takashi Kondo, Hironobu Sasano
Journal: Clinical Cancer Research (2008)

The possible involvement of gender-dependent factors has been suggested in human non-small cell lung carcinomas (NSCLC), but their precise roles remain largely unclear. Therefore, we examined intratumoral estradiol concentrations in NSCLC to examine local actions of estrogens in NSCLC.Fifty-nine frozen specimens of NSCLC were available for liquid chromatography/electrospray tandem mass spectrometry to study intratumoral estradiol concentrations. In addition, A549 NSCLC cells stably expressing estrogen receptor (ER) alpha (A549 + ERalpha) or ERbeta (A549 + ERbeta) were used in vitro studies.Forty-three (73%) of 59 NSCLC showed higher concentration of estradiol in carcinoma tissues than the corresponding nonneoplastic lung tissues from the same patient, and intratumoral estradiol concentrations were significantly (P = 0.0002 and 2.2-fold) higher than the corresponding nonneoplastic lungs. The intratumoral concentration of estradiol was positively correlated with aromatase expression, tumor size, and Ki-67 status in ERalpha- or ERbeta-positive cases. In in vitro studies, estradiol significantly increased cell proliferation of A549 + ERalpha or A549 + ERbeta, which was significantly suppressed by selective ER modulators, tamoxifen or raloxifene. Both A549 + ERalpha and A549 + ERbeta cells expressed aromatase. The cell proliferation level in these cells was significantly increased under treatment with testosterone, and it was inhibited by addition of the aromatase inhibitor letrozole.These results suggest that estradiol is locally produced in NSCLC mainly by aromatase and plays an important role in the growth of ERalpha- or ERbeta-positive NSCLC. Therefore, use of selective ER modulators and/or aromatase inhibitors may be clinically effective in NSCLC that are positive for both ER and aromatase.
Protective effect of BCG vaccination in a nursery outbreak in 2009: time to reconsider the vaccination threshold?
Authors: J. Eriksen, J. Y. Chow, V. Mellis, B. Whipp, S. Walters, E. Abrahamson, I. Abubakar
Journal: Thorax (2010)

<h3>Background</h3> In July 2008 a case of smear-positive pulmonary tuberculosis (TB) in a white UK-born nursery teacher was notified in London. The case had been symptomatic for 9 months while working in the nursery. The outbreak is described and the protective effect of BCG vaccination against latent <i>Mycobacterium tuberculosis</i> infection as measured by an interferon gamma release assay (IGRA) is assessed. <h3>Methods</h3> Screening by chest X-ray and IGRA of nursery children, staff and their contacts was conducted using a 'stone-in-the pond' approach. Information was collected on various factors including BCG vaccination status, and data were analysed using multivariable logistic regression. <h3>Results</h3> Overall, 168 children, 31 staff members and 57 other adults associated with the nursery were screened for TB. There were 12 cases of active TB and 43 cases of latent TB (72% children). 37.5% (95% CI 18% to 56%) and 40% (95% CI 30% to 50%) had a positive IGRA among teachers and children, respectively. 42% of children and 60% of adults were BCG vaccinated. In the adjusted analysis, BCG vaccination showed a significant protective effect against <i>M tuberculosis</i> infection in children (OR 0.25, 95% CI 0.09 to 0.69) and being taught by the index case was associated with acquiring TB infection (OR 18.91, 95% CI 4.43 to 80.79). A vaccine effectiveness of 66% was calculated, implying that 21 of the 32 infections could have been avoided if all children had been vaccinated with BCG. <h3>Conclusions</h3> This outbreak shows extensive transmission of TB among very young children. BCG seems to have a protective effect against TB infection as assessed by positive IGRA in this cohort.
Nanoscale liposomal formulation of a SYK P-site inhibitor against B-precursor leukemia
Authors: Fatih M. Uckun, Sanjive Qazi, Ingrid Cely, Kazim Sahin, Anoush Shahidzadeh, Ibrahim Ozercan, Qian Yin, Paul Gaynon, Amanda Termuhlen, Jianjun Cheng, Seang Yiv
Journal: Blood (2013)
Genetic ancestry and its association with asthma exacerbations among African American subjects with asthma
Authors: Jennifer A. Rumpel, Brian K. Ahmedani, Edward L. Peterson, Karen E. Wells, Mao Yang, Albert M. Levin, James J. Yang, Rajesh Kumar, Esteban González Burchard, L. Keoki Williams
Journal: Journal of Allergy and Clinical Immunology (2012)
Merkel Cell Carcinoma: A Virus-Induced Human Cancer
Authors: Yuan Chang, Patrick S. Moore
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Merkel cell polyomavirus (MCV) is the first polyomavirus directly linked to human cancer, and its recent discovery helps to explain many of the enigmatic features of Merkel cell carcinoma (MCC). MCV is clonally integrated into MCC tumor cells, which then require continued MCV oncoprotein expression to survive. The integrated viral genomes have a tumor-specific pattern of tumor antigen gene mutation that incapacitates viral DNA replication. This human cancer virus provides a new model in which a common, mostly harmless member of the human viral flora can initiate cancer if it acquires a precise set of mutations in a host with specific susceptibility factors, such as age and immune suppression. Identification of this tumor virus has led to new opportunities for early diagnosis and targeted treatment of MCC.
FACTORS INFLUENCING THE RESPONSE OF THE SEBACEOUS GLANDS OF THE RAT TO ANDROGEN
Authors: F. J. EBLING
Journal: British Journal of Dermatology (1970)

Journal Article FACTORS INFLUENCING THE RESPONSE OF THE SEBACEOUS GLANDS OF THE RAT TO ANDROGEN Get access F. J. EBLING F. J. EBLING Department of Zoology, The University, Sheffield S10 2TN Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue s6, 1 June 1970, Page 9, https://doi.org/10.1111/j.1365-2133.1970.tb07999.x Published: 01 June 1970
GASTRIC SPIRAL BACTERIA
Authors: J. Meyrick Thomas, D. Poynter, C. Gooding, D.F. Woodings, Simone Selway, A.R. Cook, M.J. Hill, J.J. Misiewicz, A.D. Phillips, K.R. Hine, G.K.T. Holmes, D.F. Woodings, S. Shousha, T.B. Bull, R.A. Parkins
Journal: The Lancet (1984)
Selective activation of tumor growth-promoting Ca2+ channel MS4A12 in colon cancer by caudal type homeobox transcription factor CDX2
Authors: Michael Koslowski, Özlem Türeci, Christoph Huber, Ugur Sahin
Journal: Molecular Cancer (2009)

Abstract Colon cancer-associated MS4A12 is a novel colon-specific component of store-operated Ca 2+ (SOC) entry sensitizing cells for epidermal growth factor (EGF)-mediated effects on proliferation and chemotaxis. In the present study, we investigated regulation of the MS4A12 promoter to understand the mechanisms responsible for strict transcriptional restriction of this gene to the colonic epithelial cell lineage. DNA-binding assays and luciferase reporter assays showed that MS4A12 promoter activity is governed by a single CDX homeobox transcription factor binding element. RNA interference (RNAi)-mediated silencing of intestine-specific transcription factors CDX1 and CDX2 and chromatin immunoprecipitation (ChIP) in LoVo and SW48 colon cancer cells revealed that MS4A12 transcript and protein expression is essentially dependent on the presence of endogenous CDX2. In summary, our findings provide a rationale for colon-specific expression of MS4A12 . Moreover, this is the first report establishing CDX2 as transactivator of tumor growth-promoting gene expression in colon cancer, adding to untangle the complex and conflicting biological functions of CDX2 in colon cancer and supporting MS4A12 as important factor for normal colonic development as well as for the biology and treatment of colon cancer.
DISQUISITIONS ON ORIGINAL ANTIGENIC SIN
Authors: S. Fazekas de St.Groth, R. G. Webster
Journal: The Journal of Experimental Medicine (1966)

Experiments in rabbits were designed to test the two unproven assumptions of the hypothesis proposed in the companion paper (1): that Original Antigenic Sin is fundamentally a restricted anamnestic response, and that there exists a trapping mechanism capable of deflecting antigen from one kind of cell and guiding it to another. It is shown that whole-body X-irradiation, sufficient to abolish primary but not secondary production of antibodies, leaves all manifestations of the Original Antigenic Sin untouched. This proves the first assumption. Primary immune animals challenged with very large doses of a related antigen produce an immediate response of cross-reactive antibodies, followed by a standard primary response to the challenging antigen. When boosted with an appropriate mixture of both antigens, the response is of standard secondary type to the homologous antigen, followed by a standard primary response to the crossreacting antigen. When animals are primarily vaccinated with a mixture of two related antigens, small booster doses of either will stimulate a standard secondary response only. When such animals are given very large booster doses of either antigen, the response is a compound of a homologous secondary and of an Original Antigenic Sin-type against the related antigen. Each of these findings demonstrates a corollary of the second assumption. The results are discussed in terms of the limitations they impose on theories concerned with the production of antibodies.