tbuckley/cabot-search huggingface dataset:
Effect of Disrupting Seven-in-Absentia Homolog 2 Function on Lung Cancer Cell Growth
Authors: Atique U. Ahmed, Rebecca L. Schmidt, Cheol Hong Park, Nanette R. Reed, Shayla E. Hesse, Charles F. Thomas, Julian R. Molina, Claude Deschamps, Ping Yang, Marie C. Aubry, Amy H. Tang
Journal: JNCI Journal of the National Cancer Institute (2008)

Background Hyperactivated epidermal growth factor receptor (EGFR) and/or RAS signaling drives cellular transformation and tumorigenesis in human lung cancers, but agents that block activated EGFR and RAS signaling have not yet been demonstrated to substantially extend patients’ lives. The human homolog of Drosophila seven-in-absentia—SIAH-1 and SIAH-2—are ubiquitin E3 ligases and conserved downstream components of the RAS pathway that are required for mammalian RAS signal transduction. We examined whether inhibiting SIAH-2 function blocks lung cancer growth.
Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study
Authors: Marcel A Müller, Benjamin Meyer, Victor M Corman, Malak Al-Masri, Abdulhafeez Turkestani, Daniel Ritz, Andrea Sieberg, Souhaib Aldabbagh, Berend-J Bosch, Erik Lattwein, Raafat F Alhakeem, Abdullah M Assiri, Ali M Albarrak, Ali M Al-Shangiti, Jaffar A Al-Tawfiq, Paul Wikramaratna, Abdullah A Alrabeeah, Christian Drosten, Ziad A Memish
Journal: The Lancet Infectious Diseases (2015)
Determinants of Agreement between the Confocal Scanning Laser Tomograph and Standardized Assessment of Glaucomatous Progression
Authors: Gianmarco Vizzeri, Christopher Bowd, Robert N. Weinreb, Madhusudhanan Balasubramanian, Felipe A. Medeiros, Pamela A. Sample, Linda M. Zangwill
Journal: Ophthalmology (2010)
The CCN family member Wisp3, mutant in progressive pseudorheumatoid dysplasia, modulates BMP and Wnt signaling
Authors: Yukio Nakamura, Gilbert Weidinger, Jennifer O. Liang, Allisan Aquilina-Beck, Keiko Tamai, Randall T. Moon, Matthew L. Warman
Journal: Journal of Clinical Investigation (2007)

In humans, loss-of-function mutations in the gene encoding Wnt1 inducible signaling pathway protein 3 (WISP3) cause the autosomal-recessive skeletal disorder progressive pseudorheumatoid dysplasia (PPD). However, in mice there is no apparent phenotype caused by Wisp3 deficiency or overexpression. Consequently, the in vivo activities of Wisp3 have remained elusive. We cloned the zebrafish ortholog of Wisp3 and investigated its biologic activity in vivo using gain-of-function and loss-of-function approaches. Overexpression of zebrafish Wisp3 protein inhibited bone morphogenetic protein (BMP) and Wnt signaling in developing zebrafish. Conditioned medium-containing zebrafish and human Wisp3 also inhibited BMP and Wnt signaling in mammalian cells by binding to BMP ligand and to the Wnt coreceptors low-density lipoprotein receptor-related protein 6 (LRP6) and Frizzled, respectively. Wisp3 proteins containing disease-causing amino acid substitutions found in patients with PPD had reduced activity in these assays. Morpholino-mediated inhibition of zebrafish Wisp3 protein expression in developing zebrafish affected pharyngeal cartilage size and shape. These data provide a biologic assay for Wisp3, reveal a role for Wisp3 during zebrafish cartilage development, and suggest that dysregulation of BMP and/or Wnt signaling contributes to cartilage failure in humans with PPD.
Infection-Related Hospitalization Rates in Pediatric versus Adult Patients with End-Stage Renal Disease in the United States
Authors: Blanche M. Chavers, Craig A. Solid, David T. Gilbertson, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2007)

Infection is a common cause of morbidity and mortality in patients with ESRD. Infection-related hospitalization (IH) incidence among US Medicare incident pediatric and adult dialysis and transplant patients within 3 yr of presentation was compared from 1996 to 2001: Hemodialysis (HD) patients (pediatric n = 1469; adult n = 305,323); peritoneal dialysis (PD) patients (pediatric n=982; adult n=27,119), and kidney transplant (KTx) patients (pediatric n=1108; adult n=31,663). IH were identified from principal diagnosis codes; IH cumulative incidence and rates were calculated from claims data. Cumulative incidence of IH at 36 mo for incident pediatric patients with ESRD during 1996 to 2001 was 39.9% in HD, 51.2% in PD, and 47.4% in KTx patients (HD or PD versus KTx, P<0.0001). Cumulative incidence for adults was 52.6% in HD, 51.8% in PD, and 39.8% in KTx patients (HD or PD versus KTx, P<0.0001). IH rates per 1000 patient-months were highest for pediatric KTx patients (adjusted rate ratio 1.53 versus HD and 1.90 versus PD, P<0.001 for each) and adult HD patients (adjusted rate ratio 1.20 versus KTx and 1.11 versus PD, P < 0.001 for each). Within the first 36 mo of incidence, IH rates are highest for incident pediatric KTx patients compared with HD and PD patients, in contrast to findings for adult patients with ESRD. Pediatric KTx patients require infection surveillance after transplantation.
DNA Polymerases as Potential Therapeutic Targets for Cancers Deficient in the DNA Mismatch Repair Proteins MSH2 or MLH1
Authors: Sarah A. Martin, Nuala McCabe, Michelle Mullarkey, Robert Cummins, Darren J. Burgess, Yusaku Nakabeppu, Sugako Oka, Elaine Kay, Christopher J. Lord, Alan Ashworth
Journal: Cancer Cell (2010)

Synthetic sickness/lethality (SSL) can be exploited to develop therapeutic strategies for cancer. Deficiencies in the tumor suppressor proteins MLH1 and MSH2 have been implicated in cancer. Here we demonstrate that deficiency in MSH2 is SSL with inhibition of the DNA polymerase POLB, whereas deficiency in MLH1 is SSL with DNA polymerase POLG inhibition. Both SSLs led to the accumulation of 8-oxoG oxidative DNA lesions. MSH2/POLB SSL caused nuclear 8-oxoG accumulation, whereas MLH1/POLG SSL led to a rise in mitochondrial 8-oxoG levels. Both SSLs were rescued by silencing the adenine glycosylase MUTYH, suggesting that lethality could be caused by the formation of lethal DNA breaks upon 8-oxoG accumulation. These data suggest targeted, mechanism-based therapeutic approaches.
Uptake and Distribution of &lt;sup&gt;3&lt;/sup&gt;H-Methotrexate by the Murine Ependymoblastoma
Authors: Victor A. Levin, Thomas P. Clancy, James I. Ausman, David P. Rall
Journal: JNCI Journal of the National Cancer Institute (1972)

Steady-state 14C-inulin and 3H-methotrexate (MTX) plasma levels were maintained in nephrectomized C57BL/6 mice with an intracerebral (ic) glioma (or varying periods up to 3 hours for MTX and 6 hours for inulin. 3H-MTX tumor uptake was studied under 3 experimental conditions: 1) varying doses of MTX of 0.12 mM/kg, 1.4 mM/kg, and 42.8 mM/kg mouse; 2) low-dose MTX with citrovorum factor at a concentration 100-fold greater; and 3) a single quantitated injection of MTX. It was found that a) MTX distributed in a space almost identical to the inulin space in ic tumor; b) there was no difference in uptake or distribution of MTX in ic tumor, brain adjacent to tumor, or normal distant brain at the 3 dose levels of 3H-MTX used; c) the distant brain was relatively impermeable to MTX; d) the brain adjacent to tumor had a space between tumor and normal brain; e) citrovorum factor had no effect on the distribution space or equilibrium t½ for MTX in ic tumor; and f) 24 hours after a single injection of MTX and inulin, nearly 5 times (P = 0.001) more MTX than inulin was present in tumor.
Health Care Disparities — Science, Politics, and Race
Authors: M Gregg Bloche
Journal: New England Journal of Medicine (2004)

Do members of disadvantaged minority groups receive poorer health care than whites? Overwhelming evidence shows that they do.1 Among national policymakers, there is bipartisan acknowledgment of this bitter truth. Department of Health and Human Services (DHHS) Secretary Tommy Thompson has said that health disparities are a national priority, and congressional Democrats and Republicans are advocating competing remedies.2,3 So why did the DHHS issue a report last year, just days before Christmas, dismissing the “implication” that racial differences in care “result in adverse health outcomes” or “imply moral error . . . in any way”?4 And why did top officials . . .
Predicting Drug Responsiveness in Human Cancers Using Genetically Engineered Mice
Authors: Jerry Usary, Wei Zhao, David Darr, Patrick J. Roberts, Mei Liu, Lorraine Balletta, Olga Karginova, Jamie Jordan, Austin Combest, Arlene Bridges, Aleix Prat, Maggie C. U. Cheang, Jason I. Herschkowitz, Jeffrey M. Rosen, William Zamboni, Norman E. Sharpless, Charles M. Perou
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To use genetically engineered mouse models (GEMM) and orthotopic syngeneic murine transplants (OST) to develop gene expression-based predictors of response to anticancer drugs in human tumors. These mouse models offer advantages including precise genetics and an intact microenvironment/immune system. Experimental Design: We examined the efficacy of 4 chemotherapeutic or targeted anticancer drugs, alone and in combination, using mouse models representing 3 distinct breast cancer subtypes: Basal-like (C3(1)-T-antigen GEMM), Luminal B (MMTV-Neu GEMM), and Claudin-low (T11/TP53−/− OST). We expression-profiled tumors to develop signatures that corresponded to treatment and response, and then tested their predictive potential using human patient data. Results: Although a single agent exhibited exceptional efficacy (i.e., lapatinib in the Neu-driven model), generally single-agent activity was modest, whereas some combination therapies were more active and life prolonging. Through analysis of RNA expression in this large set of chemotherapy-treated murine tumors, we identified a pair of gene expression signatures that predicted pathologic complete response to neoadjuvant anthracycline/taxane therapy in human patients with breast cancer. Conclusions: These results show that murine-derived gene signatures can predict response even after accounting for common clinical variables and other predictive genomic signatures, suggesting that mice can be used to identify new biomarkers for human patients with cancer. Clin Cancer Res; 19(17); 4889–99. ©2013 AACR.
Angiotensin II modulates cardiac Na+ channels in neonatal rat.
Authors: J R Moorman, G E Kirsch, A E Lacerda, A M Brown
Journal: Circulation Research (1989)

Since chronic congestive heart failure syndromes are associated with both elevated circulating levels of angiotensin II and potentially lethal ventricular tachyarrhythmias, we investigated the effect of angiotensin II on voltage-dependent cardiac Na+ currents. Single-channel Na+ currents in neonatal rat ventricular myocytes were studied using the patch clamp method in the cell-attached mode. Angiotensin II applied outside the patch increased the frequency of opening and rates of activation and inactivation of single-channel Na+ currents within the patch. These effects were mimicked by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and were prevented by prior incubation with TPA. Therefore, we propose that angiotensin II modulates cardiac Na+ currents by a cytoplasmic second messenger, perhaps protein kinase C, and this may predispose toward arrhythmia.
Protective Efficacy of Pneumococcal Polysaccharide Vaccines
Authors: Pieter Smit
Journal: JAMA (1977)

Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci.
THE ATARACTIC DRUGS: THE PRESENT POSITION OF CHLORPROMAZINE, FRENQUEL, PACATAL, AND RESERPINE IN THE PSYCHIATRIC HOSPITAL
Authors: H. ANGUS BOWES
Journal: American Journal of Psychiatry (1956)

The ataractic drugs are so called from their ability to produce ataraxy: freedom from confusion and anxiety. In a veterans psychiatric unit of 550 beds with a high rate of admissions and discharges, chlorpromazine and reserpine have been intensively studied during the past 2 years and since June 1955, Frenquel has been given to 130 patients, and Pacatal to over 250, in an effort to clarify the indications for these ataraxics in the treatment of acute and chronic psychoses. Our experiences with Frenquel are described in some detail as the originally hopeful and eventually disillusioning results obtained may explain many ambiguous findings in this complex field of research. Frenquel appears to have antihallucinatory and physically tonic effects in a small minority of regressed schizophrenics but to be of no value in the treatment of acute psychoses. Reserpine has also failed to fulfill earlier expectations. It is now reserved for the tranquillization of arteriosclerotics and as an adjuvant in the psychotherapy of some withdrawn schizophrenics. Pacatal, a phenothiazine derivitive recently developed in Europe, and chlorpromazine are virtually interchangeable and synergistic. Pacatal is almost twice as strong a tranquillizer but a weaker hypnotic. It is mildly euphoriant and strongly parasympatholytic unlike chlorpromazine, a sympatholytic and depressant. Both are indicated in the symptomatic relief of psychomotor excitation, aggression, destructiveness, restlessness, and tension in acute and chronic psychoses. A combination of both, in which their mutually antagonistic autonomic effects reduce the incidence of complications and abolish the Parkinsonian syndrome, is yielding promising results. In this study these drugs have significantly reduced the need for ECT and lobotomy without replacing these valuable methods of treatment. The seclusion of disturbed patients has been reduced to one-tenth. Since July 1955, insulin coma therapy has been replaced by group psychotherapy using ataraxics as adjuvants. Over twice the number of patients can be treated, so far with better results. Our discharges during 1955 outnumbered our admissions; the hospital atmosphere is calmer, and there is increased confidence and optimism. These latter factors cannot be ignored. Alone, ataraxics merely modify symptoms but in conjunction with psychotherapy they open up wide vistas of therapeutic promise.
Response to Pomozi et al’s Research Commentary
Authors: Lisa J. Martin, Edward Lau, Harpreet Singh, Laurent Vergnes, Elizabeth J. Tarling, Margarete Mehrabian, Imran Mungrue, Sheila Xiao, Diana Shih, Lawrence Castellani, Peipei Ping, Karen Reue, Enrico Stefani, Thomas A. Drake, Kristina Bostrom, Aldons J. Lusis
Journal: Circulation Research (2013)
Interleukin 13 inhibits human immunodeficiency virus type 1 production in primary blood-derived human macrophages in vitro.
Authors: L J Montaner, A G Doyle, M Collin, G Herbein, P Illei, W James, A Minty, D Caput, P Ferrara, S Gordon
Journal: The Journal of Experimental Medicine (1993)

The mechanisms by which cellular immunity maintains the asymptomatic state after human immunodeficiency virus type 1 (HIV-1) infection are poorly understood. CD4+ T lymphocytes play a complex role in regulating anti-HIV effector pathways, including activation of macrophages, which are themselves implicated in clinical latency and pathogenesis of symptomatic acquired immune deficiency syndrome. We have found that a newly identified T helper type 2 lymphokine, interleukin 13 (IL-13), inhibits HIV-1ADA and Ba-L replication in primary tissue culture-derived macrophages but not in peripheral blood lymphocytes. Viral production in cells was measured by viral protein (p24) and reverse transcriptase levels, while entry was assessed by proviral DNA analysis at timed intervals after infection. Inhibition by IL-13 was dose and time dependent and not mediated through altered viral entry, reverse transcription, or viral release. IL-13 is therefore a candidate cytokine for the suppression of HIV infection within monocytes and macrophages in vivo.
A CASE OF PSEUDOXANTHOMATOUS MASTOCYTOSIS
Authors: K.-M. Niemi, J. Karvonen
Journal: British Journal of Dermatology (1976)

Journal Article A CASE OF PSEUDOXANTHOMATOUS MASTOCYTOSIS Get access K.‐M. Niemi, K.‐M. Niemi Department of Dermatology, University Central Hospital, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar J. Karvonen J. Karvonen Department of Dermatology, University Central Hospital, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue 3, 1 March 1976, Pages 343–344, https://doi.org/10.1111/j.1365-2133.1976.tb04396.x Published: 01 March 1976
Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A
Authors: B Sun, T Curstedt, G Lindgren, B Franzén, A A Alaiya, A Calkovská, B Robertson
Journal: European Respiratory Journal (1997)

Surfactant protein A (SP-A), a major protein component of natural pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice. We investigated the physical and physiological properties of one of these modified natural surfactants (Curosurf) after enrichment with 5% SP-A (SP-A-Curosurf). A pulsating bubble system was used for in vitro assessments and ventilated newborn rabbits for evaluation of in vivo effects. In the presence of various potential inhibitors (meconium 5 mg.mL-1, fibrinogen 5 mg.mL-1, albumin 25 mg.mL-1, or whole serum proteins 25 mg.mL-1), Curosurf at a concentration of 5 mg.mL-1 was inactivated while SP-A-Curosurf and natural porcine surfactant at the same concentration had normal maximum and minimum surface tension. This protective effect of SP-A was calcium dependent. In immature newborn rabbits, the improvement of lung-thorax compliance observed after treatment with 100 mg.kg-1 of SP-A-Curosurf was equivalent to that obtained with 200 mg.kg-1 of Curosurf. Similarly, in near-term newborn rabbits with respiratory failure induced by instillation of fibrinogen via the airways, the increase in compliance after administration of 100 mg.kg-1 of SP-A-Curosurf corresponded to that seen after treatment with 200 mg.kg-1 of Curosurf, whereas Curosurf at a dose of 100 mg.kg-1 had no substantial effect. Our data thus indicate that surfactant protein A increases the resistance of Curosurf to inactivation under in vivo conditions.
A Dimorphic Fungus Causing Disseminated Infection in South Africa
Authors: Chris Kenyon, Kim Bonorchis, Craig Corcoran, Graeme Meintjes, Michael Locketz, Rannakoe Lehloenya, Hester F. Vismer, Preneshni Naicker, Hans Prozesky, Marelize van Wyk, Colleen Bamford, Moira du Plooy, Gail Imrie, Sipho Dlamini, Andrew M. Borman, Robert Colebunders, Cedric P. Yansouni, Marc Mendelson, Nelesh P. Govender
Journal: New England Journal of Medicine (2013)

The genus emmonsia contains three species that are associated with human disease. Emmonsia crescens and Emmonsia parva are the agents that cause adiaspiromycosis, and one human case of Emmonsia pasteuriana infection has been described. We report a fungal pathogen within the genus emmonsia that is most closely related to E. pasteuriana in human immunodeficiency virus (HIV)-infected adults in South Africa.Between July 2008 and July 2011, we conducted enhanced surveillance to identify the cause of systemic, dimorphic fungal infections in patients presenting to Groote Schuur Hospital and other hospitals affiliated with the University of Cape Town, Cape Town, South Africa. DNA sequencing was used to identify pathogenic fungi.A total of 24 cases of dimorphic fungal infection were diagnosed, 13 of which were caused by an emmonsia species. All 13 patients were HIV-infected, with a median CD4+ T-cell count of 16 cells per cubic millimeter (interquartile range, 10 to 44), and all had evidence of disseminated fungal disease. Three patients died soon after presentation, but the others had a good response to a variety of antifungal agents and antiretroviral therapy. Phylogenetic analysis of five genes (LSU, ITS1-2, and the genes encoding actin, β-tubulin, and intein PRP8) revealed that this fungus belongs in the genus emmonsia and is most closely related to E. pasteuriana.The findings suggest that these isolates of an emmonsia species represent a new species of dimorphic fungus that is pathogenic to humans. The species appears to be an important cause of infections in Cape Town.
Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer
Authors: Wun-Jae Kim, Eun-Jung Kim, Seon-Kyu Kim, Yong-June Kim, Yun-Sok Ha, Pildu Jeong, Min-Ju Kim, Seok-Joong Yun, Keon Lee, Sung-Kwon Moon, Sang-Cheol Lee, Eun-Jong Cha, Suk-Chul Bae
Journal: Molecular Cancer (2010)

While several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer. We used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression. We identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.