tbuckley/cabot-search huggingface dataset:
Antitumor Effect of a Novel Proapoptotic Peptide that Impairs the Phosphorylation by the Protein Kinase 2 (Casein Kinase 2)
Authors: Silvio E. Perea, Osvaldo Reyes, Yaquelin Puchades, Osmani Mendoza, Nelson S. Vispo, Isis Torrens, Alicia Santos, Ricardo Silva, Boris Acevedo, Ernesto López, Viviana Falcón, Daniel F. Alonso
Journal: Cancer Research (2004)

Abstract Protein Kinase (casein kinase 2, CK2) is a serine-threonine kinase that is frequently dysregulated in many human tumors. Therefore we hypothesized that peptides capable of binding to the CK2 acidic domain may exhibit potential anticancer properties. By screening a random cyclic peptide phage display library, we have identified a novel peptide, P15, that abrogated CK2 phosphorylation by blocking the substrate in vitro. To verify its potential antineoplastic effect, P15 was fused to the cell-penetrating peptide derived from the HIV-Tat protein. Interestingly, P15-Tat induced apoptosis as evidenced by rapid caspase activation and cellular cytotoxicity in a variety of tumor cell lines. Furthermore, direct injection of P15-Tat into C57BL6 mice bearing day 7-established solid tumors, resulted in substantial regression of the tumor mass. Our findings describe a new proapoptotic cyclic peptide that blocks the CK2 phosphorylation and exhibits antitumor effect in vivo, indicating that the P15 peptide may potentially be used clinically to treat solid tumors or as an adjuvant for cancer therapy.
Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis
Authors: Jeffrey D Greenberg, Joel M Kremer, Jeffrey R Curtis, Marc C Hochberg, George Reed, Peter Tsao, Michael E Farkouh, Adeel Nasir, Soko Setoguchi, Daniel H Solomon
Journal: Annals of the Rheumatic Diseases (2010)

Objective To examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA). Methods The study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death. Results There were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74). Conclusion TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA.
Management of enterocutaneous fistulae in Crohn's disease.
Authors: P C Hawker, J C Givel, M R Keighley, J Alexander-Williams, R N Allan
Journal: Gut (1983)

The outcome among 39 patients with enterocutaneous fistulae complicating Crohn's disease has been reviewed. The patients were considered in two groups: (1) no disease - all were early postoperative fistulae (n = 9); (2) active disease (i) without abscess formation (n = 16), (ii) with abscess formation (n = 14). Postoperative fistulae with no evidence of active Crohn's disease healed spontaneously. Fistulae in the presence of active disease did not heal even with prolonged medical management. The only effective treatment was excision of the diseased segment from which the fistulae arose and any distal obstruction. None of the fistulae closed surgically has recurred.
A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma
Authors: S Kelly
Journal: Gut (2001)

BACKGROUND Endoscopic ultrasound (EUS) may be used for preoperative staging of gastro-oesophageal carcinoma but performance values given in the literature differ. AIMS To identify and synthesise findings from all articles on the performance of EUS in tumour, node, metastasis (TNM) staging of gastro-oesophageal carcinoma. SOURCE Published and unpublished English language literature, 1981–1996. METHODS Data on the staging performance of EUS were retrieved and evaluated. Summary receiver operator characteristic methodology was used for synthesis, and a summary estimate of performance, Q*, obtained. Multiple regression analysis was used to assess study validity and investigate reasons for differences in performance. RESULTS Twenty seven primary articles were assessed in detail. Thirteen supplied results for staging oesophageal cancer, 13 for gastric cancer, and four for cancers at the gastro-oesophageal junction. For gastric T staging, Q*=0.93 (95% confidence interval (CI) 0.91–0.95) and for oesophageal T staging, Q*=0.89 (95% CI 0.88–0.92). For gastro-oesophageal T staging, including cancers at the gastro-oesophageal junction, Q*=0.91 (95% CI 0.89–0.93). Inclusion of cases with non-traversable stenosis was found to slightly reduce staging performance. For N staging, Q*=0.79 (95% CI 0.75–0.83). In articles that compared EUS directly with incremental computed tomography, EUS performed better. None of the variables assessed in the regression analysis was significant using a Bonferroni correction. Three variables (anatomical location, traversability, and blinding) showed strong relationships for future research and validation. CONCLUSIONS EUS is highly effective for discrimination of stages T1 and T2 from stages T3 and T4 for primary gastro-oesophageal carcinomas. The failure rate of EUS from non-traversability of a stenotic cancer may be a limitation in some patient groups. * CT : computed tomography EUS : endoscopic ultrasound FPR : false positive rate SROC : summary receiver operating characteristic TNM : tumour, node, metastasis TPR : true positive rate
Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans
Authors: Jérôme Reboul, Philippe Vaglio, Nia Tzellas, Nicolas Thierry-Mieg, Troy Moore, Cindy Jackson, Tadasu Shin-i, Yuji Kohara, Danielle Thierry-Mieg, Jean Thierry-Mieg, Hongmei Lee, Joseph Hitti, Lynn Doucette-Stamm, James L. Hartley, Gary F. Temple, Michael A. Brasch, Jean Vandenhaute, Philippe E. Lamesch, David E. Hill, Marc Vidal
Journal: Nature Genetics (2001)
CD2 regulates responsiveness of activated T cells to interleukin 12.
Authors: J A Gollob, J Li, E L Reinherz, J Ritz
Journal: The Journal of Experimental Medicine (1995)

Interleukin (IL) 12 is a 70-kD heterodimeric cytokine produced by antigen-presenting cells (APCs) such as macrophages in response to infectious pathogens and interferon (IFN) gamma. The varied immunomodulatory effects of IL-12 include the stimulation of proliferation and IFN-gamma production by T cells, and it also has a central role in the development of the T helper cell type 1 immune phenotype. We undertook the production of antibodies capable of modulating the response of T cells to IL-12, and in the process we discovered two antibodies that inhibited the ability of IL-12 to stimulate T cell proliferation. In this report, we demonstrate that these anti-bodies recognize CD2, and we show how antibodies directed toward either the adhesion domain of CD2 or its ligand, CD58, specifically inhibit IL-12 induced proliferation and IFN-gamma production by phytohemagglutinin-activated T cells, leaving the response to IL-12 unaffected. A three-to fourfold reduction in proliferation and IFN-gamma production was observed at IL-12 concentrations as high as 1 nM, with complete inhibition occurring at &amp;lt; or = 1 pM. This novel effect is not directly mediated at the level of the IL-12 receptor, as shown by the inability of these antibodies to block IL-12 binding to activated T cells. Furthermore, by using activating pairs of CD2 antibodies, we show that CD2 stimulation strongly synergizes with IL-12, even at 0.1 pM, in inducing both T cell proliferation and IFN-gamma production. Cytolytic T lymphocyte-associated antigen 4-immunoglobulin-mediated inhibition of the B7/CD28 interaction did not affect the T cell response to either IL-12 or IL-2, but the removal of APCs selectively diminished the proliferative response to IL-12. Based on this data, we hypothesize that CD2 has a central role in an IL-12/IFN-gamma positive feedback loop between T cell and APC, providing the key functional link via a CD2/CD58 interaction that controls T cell responsiveness to IL-12. This model provides a basis for future investigations aimed at defining the signaling mechanisms that mediate this cytokine-specific regulatory effect of CD2, and it offers insight into how a cytokine receptor and distinct adhesion molecule can interact to modulate responsiveness to that cytokine. In addition, it underscores the possibility that the clinical potential of an immunomodulatory drug like IL-12 may be governed by the presence or absence of specific costimulation.
Osteoprotegerin upregulates endothelial cell adhesion molecule response to tumor necrosis factor-α associated with induction of angiopoietin-2☆
Authors: S MANGAN, A CAMPENHOUT, C RUSH, J GOLLEDGE
Journal: Cardiovascular Research (2007)

Objective Osteoprotegerin (OPG) and osteopontin (OPN) have been identified within unstable atherosclerosis and circulating concentrates have been linked to cardiovascular events. We studied the influence of OPG and OPN on endothelial adhesion molecule expression and monocyte binding.
Prospective study of mycobacterial infections in patients with cystic fibrosis.
Authors: L Hjelte, B Petrini, G Kallenius, B Strandvik
Journal: Thorax (1990)

Fifty four patients with cystic fibrosis, aged 3-67 years, were studied prospectively for pulmonary mycobacterial infection. Sputum smears and cultures were carried out and intradermal skin tests performed. Mycobacteria were cultured from six patients in association with clinical deterioration; four patients had positive direct smears. Mycobacterium tuberculosis, M aviumintracellulare, M kansasii, and M gordonae were isolated. There were no deaths and all improved with chemotherapy. A third of the other 48 patients had positive skin test responses (greater than 6 mm) to purified protein derivative (PPD) tuberculin and 21 to one or more antigens prepared from non-tuberculous mycobacteria. Sensitisation increased with age; before the age of 11 only one patient had a positive response to PPD tuberculin and none to any other antigen. This was less than in healthy control subjects of similar age. After age 11 the reactions in sensitised patients were stronger than in positive healthy control subjects. Our study indicates that it is important to consider mycobacterial infection in patients with cystic fibrosis who deteriorate without obvious cause.
Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial
Authors: Annemiek Broyl, Sophie L Corthals, Joost LM Jongen, Bronno van der Holt, Rowan Kuiper, Yvonne de Knegt, Mark van Duin, Laila el Jarari, Uta Bertsch, Henk M Lokhorst, Brian G Durie, Hartmut Goldschmidt, Pieter Sonneveld
Journal: The Lancet Oncology (2010)
Sildenafil enhances systolic adaptation, but does not prevent diastolic dysfunction, in the pressure‐loaded right ventricle
Authors: Marinus A.J. Borgdorff, Beatrijs Bartelds, Michael G. Dickinson, Bibiche Boersma, Michel Weij, Andre Zandvoort, Herman H.W. Silljé, Paul Steendijk, Maartje de Vroomen, Rolf M.F. Berger
Journal: European Journal of Heart Failure (2012)
AIDS-Antiviral Sulfolipids From Cyanobacteria (Blue-Green Algae)
Authors: K. R. Gustafson, J. H. Cardellina, R. W. Fuller, O. S. Weislow, R. F. Kiser, K. M. Snader, G. M. L. Patterson, M. R. Boyd
Journal: JNCI Journal of the National Cancer Institute (1989)

A recently developed tetrazolium-based microculture assay was used to screen extracts of cultured cyanobacteria (blue-green algae) for inhibition of the cytopathic effects of the human immunodeficiency virus (HIV-1), which is implicated as a causative agent of AIDS. A number of extracts were found to be remarkably active against the AIDS virus. A new class of HIV-1-inhibitory compounds, the sulfonic acid-containing glycolipids, was discovered through the use of the microculture assay to guide the fractionation and purification process. The pure compounds were active against HIV-1 in cultured human lymphoblastoid CEM, MT-2, LDV-7, and C3-44 cell lines in the tetrazolium assay as well as in p24 viral protein and syncytium formation assays.
Intramural Foci During Long Duration Fibrillation in the Pig Ventricle
Authors: Li Li, Qi Jin, Jian Huang, Kang-An Cheng, Raymond E. Ideker
Journal: Circulation Research (2008)

For more than 50 years, it has been assumed that ventricular fibrillation (VF) is maintained solely by reentry in the working myocardium. This hypothesis has never been tested by recording VF with electrodes spaced sufficiently close to map activation sequences in 3D. We recorded the first 10 minutes of electrically induced VF from the anterior left ventricular (LV) free wall near the insertion of the anterior papillary muscle in 6 pigs. A 3D transmural unipolar electrode array consisting of a 9×9 array of needles with 2-mm spacing and 6 electrodes 2 mm apart on each needle was used for recordings. Automatic analyses were performed to recognize 3D reentry and foci. Our results showed that intramural reentry is present early but not late during VF in the mapped region. The incidence of reentry in working myocardium decreases almost to 0 after 3 minutes of VF. In contrast, intramural foci are present during early VF and, as VF continues, increase in incidence, so that by 10 minutes of VF, 27% of wavefronts arise from intramural foci. These results suggest that, particularly after the first 3 minutes of VF, mechanisms other than local reentry in the working myocardium maintain VF in the anterior LV free wall near the root of the anterior papillary muscle. Intramural foci may play an important role in later VF maintenance. It remains to be determined if these foci arise from Purkinje fibers attributable to abnormal automaticity, afterdepolarizations, or reentry.
Management of the effects of exposure to tear gas
Authors: P.-N. Carron, B. Yersin
Journal: BMJ (2009)

#### Summary points 

Despite the frequent use of riot control agents by European law enforcement agencies, limited information exists on this subject in the medical literature. The effects of these agents are typically limited to minor and transient cutaneous inflammation, but serious complications and even deaths have been reported. During the 1999 World Trade Organisation meeting and at the 2001 Summit of the Americas in Quebec, exposure to tear gas was the most common reason for medical consultations.1 2 Primary and emergency care physicians play a role in the first line management of patients as well as in the identification of those at risk of complications from exposure to riot control agents. In 1997 the National Poisons Information Service in England received 597 inquiries from doctors seeking advice about problems related to crowd control.3 Our article reviews the different riot control agents, including the most common tear gases and pepper sprays, and provides an up to date overview of related medical sequelae.

We searched the following resources for relevant information on the medical toxicity and management of acute exposure to tear gas and pepper spray: Medline, PreMedline, Embase, CINAHL, SCIRUS, the Cochrane Library, ISI Web of Knowledge, Toxnet, Google Scholar, and personal archives. We used the subject headings “riot control agents”, “pepper spray”, “lacrimator”, “tear gas”, “irritants”, “incapacitating agents”, as well as the toxicological terms “chlorobenzylidene-malononitrile”, “chloroacetophenone”, “dibenzoxazepine”, “chlorodiphenylarsine” …
Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus
Authors: M Odendahl
Journal: Annals of the Rheumatic Diseases (2003)

To investigate the distribution of peripheral B cell subpopulations of children with active and inactive systemic lupus erythematosus (SLE) compared with healthy controls.Peripheral B cell subpopulations of 11 children with SLE (6 with active and 5 with inactive disease) and 14 age matched normal healthy children were analysed. Active disease was diagnosed in children with a flare of SLE, who received treatment by i.v. cyclophosphamide or i.v. methylprednisolone pulse to control the disease. Additionally, the peripheral B cells of the children with SLE were compared with those of 13 consecutive patients with adult onset SLE.No major difference was found in the frequency and total number of CD27(-)/CD19(+) naïve B cells and CD27(+)/CD19(+) memory B cells between patients with active and inactive lupus and healthy controls, but there was a significant increase in CD27(high) expressing plasma blasts in patients with active SLE. These cells coexpress CD38(+), HLA-DR(dim), surface Ig(low) and lack the expression of CD20 but are clearly positive for intracellular Ig, indicative of early plasma cells. Most CD138(+) cells coexpress CD27(high)/CD19(+). The enhanced frequency of peripheral plasma blasts in children with active SLE is consistent with previous findings in adult patients with SLE, whereas a relative predominance of CD27(+) memory B cells was only identified in the adult patients.Profound abnormalities in the distribution of B cell compartments are more pronounced in older patients with SLE, but an enhanced frequency and cell number of peripheral plasma blasts is characteristic of both diseases during active stages. Thus detection of CD27(high) plasma blasts significantly correlates with active lupus in both children and adults.
THE TREATMENT OF ASTHMA: AND AN IMPROVEMENT OF THE PEPTONED AGAR SERUM
Authors: A. G. Auld
Journal: BMJ (1928)

<h3>Abstract</h3> A translationally silent single nucleotide mutation, in exon 44 of the von Willebrand factor (VWF) gene, is associated with inefficient removal of intron 44 in a von Willebrand disease (VWD) patient. This intron retention (IR) event was previously attributed to altered secondary structure that sequesters the normal splice donor site. We propose an alternative mechanism: that the mutation introduces a cryptic splice donor site that interferes with function of the annotated site to favor IR. We evaluated both models using minigene splicing reporters engineered to vary in secondary structure and/or cryptic splice site content. Analysis of reporter splicing efficiency in transfected K562 cells suggested that the mutation-generated internal splice site was sufficient to induce substantial IR. Mutations predicted to vary secondary structure at the annotated site had modest effects on IR, and also shifted the balance of residual splicing between the cryptic site and annotated site, supporting competition between the sites. Further studies demonstrated that introduction of cryptic splice donor motifs at other positions in E44 did not promote IR, indicating that interference with the annotated site is context-dependent. We conclude that mutant deep exon splice sites can interfere with proper splicing by inducing IR.
CELLULAR IMMUNITY TO PENICILLIN IN NEWBORNS
Authors: MARTINE HERVE, J. H. SAURAT, J. PAUPE
Journal: Allergy (1977)

A leukocyte migration micromethod has been used to study the cellular immunity to penicillin (CIP) in newborns. No detectable CIP has been found in newborns who had not been treated with penicillin. Fifteen per cent of the newborns treated with pencillin were found to have a CIP as early as the 12th day of life.
Transmission of tuberculosis in the metropolitan area of Zurich: a 3 year survey based on DNA fingerprinting
Authors: GE Pfyffer, A Strassle, N Rose, R Wirth, O Brandli, H Shang
Journal: European Respiratory Journal (1998)

Between 1991 and 1993, 444 inhabitants of the metropolitan area of Zurich were reported as confirmed or suspected cases of tuberculosis (TB). Overall, isolates of Mycobacterium tuberculosis of 361 patients (90% of the bacteriologically confirmed cases) were available to study the frequency of transmission of the strains on a molecular level. Restriction fragment length polymorphism (RFLP) analysis was performed by using IS6110 and the polymorphic GC-rich sequence (PGRS) as genetic markers. Ninety nine isolates shared by 77 patients (21.3%) were associated with 28 IS6110-defined clusters. However, secondary typing of low copy number isolates decreased the number of clusters to 25, encompassing 81 isolates from 63 (17.5%) patients. By deoxyribonucleic acid (DNA) fingerprinting plus conventional contact tracing, definite transmission of TB was proven in only five patients (1.4%) and assumed in 20 patients (5.6%). In all other cluster-associated isolates, no epidemiological connections between the patients could be found using the clinical and sociodemographic data available. The present study demonstrates that in the time period studied only minor transmission occurred.
Circulating and tumor-based biomarkers predict clinical activity in cancer patients treated with the engineered anti-PD-L1 antibody MPDL3280A
Authors: Marcin Kowanetz, Christina Rabe, Yuanyuan Xiao, Qun J Wu, Hartmut Koeppen, Cecilia Leddy, Rajesh D Patel, John Powderly, Holbrook Kohrt, Scott Gettinger, Jean-Charles Soria, Roy S Herbst, Rupal Desai, Mitchell Denker, Jane Ruppel, Marigold Boe, Rin Nakamura, Ling Fu, Teiko Sumiyoshi, Ahmad Mokatrin, Xiaodong Shen, Gregg Fine, Daniel S Chen, Priti S Hegde
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts PD-L1 expressed in the tumor microenvironment regulates Th1 immune responses and mediates cancer immune evasion through interactions with PD-1 or B7.1 receptors on activated T cells. MPDL3280A, an engineered human monoclonal antibody, targets PD-L1 and inhibits its function. To
Resazurin microtitre assay (REMA) plate - A simple, rapid and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis
Authors: Siddharth Kunte, Alaka Karmarkar, Sujata Dharmashale, Swarupa Hatolkar
Journal: European Respiratory Journal (2012)

OBJECTIVES: Comparison of REMA Plate method with the Standard Proportion Method using L-J medium as approved by Revised National Tuberculosis Control Programme (RNTCP) for Drug Sensitivity Testing(DST).  METHODS: 26 isolated strains of M. tuberculosis obtained from suspected patients were subjected to DST by 2 methods viz. REMA Plate and Proportion Method for the first line antitubercular drugs INH, RIF, STR and ETM. REMA plate method was performed in 7H9-S medium containing Middlebrook broth and supplements in 96 well microtiter plates. The results of REMA were obtained on days 7, 10 and 14 using resazurin. Any strain having an MIC equal or above the tentative breakpoint concentration was considered resistant.  RESULTS: The sensitivity of REMA for the respective drugs was found to be 94.4%, 93.75%, 93.3% and 66.6%. The specificity of REMA for the respective drugs was found to be 100%, 100%, 45.5% and 35.3%. The cost of REMA Plate method came out to be half of that required for Proportion Method.  CONCLUSIONS: REMA can be considered as one of the most rapid and inexpensive method to find out drug resistance to INH and RIF and hence aid in the diagnosis of MDR-TB. ETM and STR, two drugs known to be difficult to test showed a low specificity.