tbuckley/cabot-search huggingface dataset:
A Human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo
Authors: Philip Meuleman, Maria Teresa Catanese, Lieven Verhoye, Isabelle Desombere, Ali Farhoudi, Christopher T. Jones, Timothy Sheahan, Katarzyna Grzyb, Riccardo Cortese, Charles M. Rice, Geert Leroux-Roels, Alfredo Nicosia
Journal: Hepatology (2011)

Abstract Endstage liver disease caused by chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the Western world. However, immediate reinfection of the grafted donor liver by circulating virus is inevitable and liver disease progresses much faster than the original disease. Standard antiviral therapy is not well tolerated and usually ineffective in liver transplant patients, whereas anti-HCV immunotherapy is hampered by the extreme genetic diversity of the virus and its ability to spread by way of cell-cell contacts. We generated a human monoclonal antibody against scavenger receptor class B type I (SR-BI), monoclonal antibody (mAb)16-71, which can efficiently prevent infection of Huh-7.5 hepatoma cells and primary hepatocytes by cell-culture-derived HCV (HCVcc). Using an Huh7.5 coculture system we demonstrated that mAb16-71 interferes with direct cell-to-cell transmission of HCV. Finally we evaluated the in vivo efficacy of mAb16-71 in “human liver urokinase-type plasminogen activator, severe combined immune deficiency (uPA-SCID) mice” (chimeric mice). A 2-week anti-SR-BI therapy that was initiated 1 day before viral inoculation completely protected all chimeric mice from infection with serum-derived HCV of different genotypes. Moreover, a 9-day postexposure therapy that was initiated 3 days after viral inoculation (when viremia was already observed in the animals) suppressed the rapid viral spread observed in untreated control animals. After cessation of anti-SR-BI-specific antibody therapy, a rise of the viral load was observed. Conclusion : Using in vitro cell culture and human liver-chimeric mouse models, we show that a human mAb targeting the HCV coreceptor SR-BI completely prevents infection and intrahepatic spread of multiple HCV genotypes. This strategy may be an efficacious way to prevent infection of allografts following liver transplantation in chronic HCV patients, and may even hold promise for the prevention of virus rebound during or following antiviral therapy. (Hepatology 2012)
Abstract 3062: A comparative analysis of phosphothioated DNA and peptide nucleic acid molecular beacons targeting specific K-ras mutation
Authors: Yossi Kam, Abraham Rubinstein, Aviram Nissan, David Halle, Eylon Yavin
Journal: Cancer Research (2011)

Abstract Introduction: Early detection of gastrointestinal malignancies may improve disease-related outcome. In vivo, real time imaging using hybridization of fluorescently-labeled complementary transcripts to intracellular RNA sequences may facilitate early detection of malignant and pre-malignant lesions Methods: Using K-ras oncogene as a model target, and adapting the molecular beacon technology, we performed an hybridization kinetics and hybridization specificity comparison of two types of molecular beacons (MBs) based on either phosphothioated DNA (PS-DNA-MB) or peptide nucleic acid (PNA-TO-MB, where thiazole orange [TO] was used as the fluorescent molecule) both in vitro and in a variety of cell lines. In order to determine the sequence-specificity of MB's at a single base resolution, a codon 12 K-ras oncogene mutation (GGT→GAT) was used as target in different cell lines. Both PS-DNA and PNA-TO MB's were designed to target this specific K-ras point mutation. We studied the hybridization of the two MBs to wild-type K-ras (HT-29 colon cancer cell line) and two cell lines, one harboring this K-ras point mutation (PANC-1) and SW-480 harboring a different (GGT→GTT) mutation. Results: Hybridization kinetics of PNA-TO-MB to target DNA or RNA was faster compared to PS-DNA-MB highlighting the advantage of such probes to be developed into diagnostic kits for the early detection of cancer. However, in solution, using synthetic DNA oligomers as targets, PS-DNA-MB demonstrated higher specificity to its complementary target (3-to 4.6-fold increase in fluorescence in comparison to DNA with a single mismatch) compared to the PNA-TO-MB (only 1.3- to 2.2-fold increase). Yet, incubation of PNA-TO-MB with total RNA (isolated from these cell lines) and with fixed cells, resulted in a significantly higher fluorescent signal (p &amp;lt; 0.001) detected for target (fully complement, PANC-1) compared to single mismatch mRNA transcript in HT29 and SW-480. In contrast, the PS-DNA-MB showed poor discrimination in total RNA and no fluorescent signal with all cell lines after 5 minutes incubation. Conclusions: Based on the fast hybridization kinetics and based on the single mismatch discrimination found for PNA-TO-MB in fixed cells and with total RNA, it is speculated that such PNA-TO-MB's are promising candidates for the early detection of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3062. doi:10.1158/1538-7445.AM2011-3062
Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol
Authors: Ian D. Pavord, Peter K. Jeffery, Yusheng Qiu, Jie Zhu, Debbie Parker, Åsa Carlsheimer, Ian Naya, Neil C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2009)
The potential role of viruses in the pathogenesis of atherosclerosis.
Authors: M J Cunningham, R C Pasternak
Journal: Circulation (1988)

DESPITE the fact that atherosclerotic vascular disease is the major cause of morbidity and mortality in devel- oped countries, there are wide gaps in the understand- ing of its cause.Extensive epidemiologic studies have revealed the importance of diabetes, hyperlipidemia, hypertension, and cigarette smoking in the atheroscle- rotic process and provide clinically important variables through which this disease process can potentially be favorably modified.'Also, effective medical therapies as well as improved mechanical techniques such as angioplasty and bypass surgery have improved our ability to control the clinical manifestations ofvascular disease.Despite these advances, the primary inciting events in the atherosclerotic process remain poorly defined.
CARDIOVASCULAR EFFECTS OF CARFILZOMIB, A NEW PROTEASOME INHIBITOR, ON CORONARY RESISTENCIES, VASCULAR TONE AND VASCULAR REACTIVITY
Authors: Tiziano M. Scarabelli, Carol Chen-Scarabelli, Mara Gavazzoni, Gagan Sahni, Louis Saravolatz, Riccardo Raddino, Jagat Narula
Journal: Journal of the American College of Cardiology (2015)
The Effect of Inspiration of Cold Air on the Electrocardiogram of Normal Dogs, Normal Humans, and Humans with Angina Pectoris.
Authors: M. J. Murray
Journal: Annals of Internal Medicine (1963)

s1 April 1963The Effect of Inspiration of Cold Air on the Electrocardiogram of Normal Dogs, Normal Humans, and Humans with Angina Pectoris.M. J. Murray, M.D., F.R.A.C.P.M. J. Murray, M.D., F.R.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-712_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAngina pectoris may be precipitated by exposure of subjects to cold air. This study was designed to decide whether angina resulted from inhalation of cold air rather than from external contact with it. Normal anesthetized dogs were allowed to inhale air with a mouth delivery temperature of -10 F from a positive pressure breathing apparatus. Electrocardiograms were recorded continuously. Despite a 5-F fall in temperature of left atrial blood recorded by a thermistor, there were no significant electrocardiographic changes. Twelve young healthy males, with normal resting electrocardiograms, inhaled air with a delivery temperature of -10 F from a similar machine.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: M. J. Murray, M.D., F.R.A.C.P. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 712-712KeywordsAnginaBloodBreathingElectrocardiographyElectrode recordingFallsInhalationMouthTemperature ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...
Abstract 3801: Prostate cancer cells are selectively targeted by zinc-sequestration chemotherapy
Authors: Shweta K. Dambal, Brittany Mihelich, Paul Hergenrother, Larisa Nonn
Journal: Cancer Research (2012)

Abstract Introduction: Zinc accumulates at levels 10-fold higher in the prostate than other soft tissues and this metal is implicated in prostate cancer (PCa) pathogenesis. Prostatic lesions have 6-fold lower concentrations of zinc than normal adjacent prostate tissue. Zinc levels are even lower in normal and malignant prostate tissue from African American (AA) men, who are 1.5 times more likely to develop prostate cancer than their Caucasian (Cauc) counterparts, thus highlighting the associative that that zinc could have in prostate cancer carcinogenesis. PAC-1 is a chemotherapeutic agent that induces cell death via zinc sequestration by activation of pro-caspase 3, which is a major player in cell death. We hypothesized that the low zinc levels in prostate cancer cells will cause the cells to be uniquely sensitive to cell death by PAC-1. Secondarily we hypothesized that AA patients, who have lower zinc in the prostate, may have enhanced response to PAC-1. Methods: PAC-1 cytotoxicity was investigated in LNCaP, PC-3, 957e/hTERT (immortalized normal primary cell line) and patient-derived normal and cancer primary epithelial cells (PrE) by treatment with 100, 50, 25,10,1, 0 micromolar concentrations of PAC-1 and PAC-1 analogs. Cell death was analyzed via the MTS colorimetric assay. Results and conclusion: Normal and cancer prostate cells are sensitive to PAC-1 and even more sensitive to PAC-1 analogs. PAC-1 was growth inhibitory and induced cell death at higher concentrations. Ongoing studies will examine zinc-dependency of PAC-1-induced death. PAC-1 and its analogs-induced cell death and caspase-3 activation will be measured in zinc-depleted, zinc sufficient and zinc-excess media. Studies will also determine PAC-1 cytotoxicity in normal and cancer prostatic epithelial cells. PAC-1 cytotoxicity levels in patient-matched prostate cancer cells (PrCa) from AA and Cauc men will also be studied to interrogate the disparate role of zinc in regards to sensitivity to PAC-1. These results may be translated to the clinic since a derivative of PAC-1 (S-PAC-1) has been shown to have positive effects in a Phase I clinical trial in pet dogs with lymphoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3801. doi:1538-7445.AM2012-3801
Supplementary oxygen in healthy subjects and those with COPD increases oxidative stress and airway inflammation
Authors: G E Carpagnano
Journal: Thorax (2004)

<b>Background:</b> Hyperoxia increases oxidative stress through the generation of reactive oxygen species and may therefore enhance inflammation in the lungs. The aim of this study was to investigate whether short term supplementary oxygen (28%) increases oxidative stress and inflammation in the airways by measuring 8-isoprostane and interleukin 6 (IL-6) concentrations in exhaled breath condensate. <b>Methods:</b> Twenty three healthy subjects (12 men, mean (SD) age 48 (7) years) and 23 patients with chronic obstructive pulmonary disease (COPD; 15 men, mean (SD) age 56 (5) years) were studied. 8-isoprostane and IL-6 concentrations were measured by immunoassay. <b>Results:</b> Increased concentrations of 8-isoprostane and IL-6 were found in all subjects after breathing 28% oxygen for 1 hour. In healthy subjects the concentrations of 8-isoprostane and IL-6 were 10.9 (2.9) pg/ml and 4.9 (0.8) pg/ml, respectively, compared with baseline concentrations of 6.1 (1.3) pg/ml and 2.9 (0.6) pg/ml, and in patients with COPD the concentrations were 27.9 (3.1) pg/ml and 8.3 (1.2) pg/ml), respectively, compared with baseline concentrations of 18.9 (3.6) pg/ml and 6.3 (0.6) pg/ml. By contrast, breathing air through the same face mask for 1 hour had no significant effects on 8-isoprostane or IL-6 concentrations in normal subjects or those with COPD. <b>Conclusions:</b> These findings suggest that short term supplementary oxygen may enhance oxidative stress and inflammation in the airways. Whether this happens with long term oxygen therapy needs to be determined.
EG-16 * ABERRANT Myst4/Brpf1 SIGNALING MISDIRECTS REGIONAL NEUROGENESIS PROGRAMS, SUSTAINING EXPRESSION OF SELF-RENEWAL GENES IN PEDIATRIC BRAIN CANCERS
Authors: T. E. Van Meter, A. Khan, K. Fitzmartin, M. D. Taylor, S. Mack, J. Cote
Journal: Neuro-Oncology (2014)

The Myst family of acetyltransferase proteins has been shown to play important role in development and self-renewal, primarily through lysine acetylation on Histones H3 and H4. In neural development, Myst4 (Morf/KAT6B) has been found to be critical for self-renewal and for neuron generation in the developing nervous system and during adult neurogenesis. This chromatin modifier exists in a complex with Myst3 (Moz/KAT6A), the bromodomain factor Brpf1, which acts as a protein scaffold, targeting histone acetyltransferases to chromatin, as well as Inhibitor of Growth 5 (ING5) and Esa1-associated factor 6 (EAF6). Our laboratories have found alteration of these elements in pediatric brain cancers, suggesting a pathological role in abnormal neural progenitor growth. Exon-specific microarrays, DNA methylation studies and functional perturbation were performed to study the impact on tumor behavior. RNA interference in tumors and neural progenitors led to loss of H3K4acetylation in target genes and altered expression, including Spondin-1. Conversely, exogenous over-expression of targeting factors, such as Brpf1, enhanced expression of target genes, assessed by quantitative PCR analysis. Furthermore, expression of Myst3/4 and Brpf1 positively correlated with tumor malignancy markers in large patient cohorts, including Ki67, PCNA, and MELK, and with decreased overall survival. Assessment of direct functional relationships with tumor markers using ChIP-Seq approaches is currently being pursued to investigate direct Myst3/4/Brpf1-mediated promoter activity at known and novel target genes. These studies aim to elucidate the role of an important epigenetic mechanism in neurogenesis, the alteration of which may underlie global chromatin changes that contribute to tumor growth or initiation. Sustained progenitor growth may be suppressed by targeted therapies that disrupt these factors.
Metabolic acidosis due to D-lactate.
Authors: P D Mason
Journal: BMJ (1986)

Une observation rare: acidose metabolique provoquee par l'acide D-(-)lactique sans chirurgie sur l'intestin mais apres transplantation renale chez un malade atteint au debut de pancreatite puis de diabete. Des episodes de rejet sont traites avec succes mais le malade finit par mourir d'acidose
Estrogen Supports Urothelial Defense Mechanisms
Authors: Petra Lüthje, Hanna Brauner, Nubia L. Ramos, Amanda Övregaard, Regine Gläser, Angelica Lindén Hirschberg, Pontus Aspenström, Annelie Brauner
Journal: Science Translational Medicine (2013)

Estrogen supports urothelial defense against infection by increasing the expression of antimicrobial peptides and by protecting epithelial integrity.
Chemotherapy-Induced Peripheral Neurotoxicity and Ototoxicity: New Paradigms for Translational Genomics
Authors: L. B. Travis, S. D. Fossa, H. D. Sesso, R. D. Frisina, D. N. Herrmann, C. J. Beard, D. R. Feldman, L. C. Pagliaro, R. C. Miller, D. J. Vaughn, L. H. Einhorn, N. J. Cox, M. E. Dolan
Journal: JNCI Journal of the National Cancer Institute (2014)

In view of advances in early detection and treatment, the 5-year relative survival rate for all cancer patients combined is now approximately 66%. As a result, there are more than 13.7 million cancer survivors in the United States, with this number increasing by 2% annually. For many patients, improvements in survival have been countered by therapy-associated adverse effects that may seriously impair long-term functional status, workplace productivity, and quality of life. Approximately 20% to 40% of cancer patients given neurotoxic chemotherapy develop chemotherapy-induced peripheral neurotoxicity (CIPN), which represents one of the most common and potentially permanent nonhematologic side effects of chemotherapy. Permanent bilateral hearing loss and/or tinnitus can result from several ototoxic therapies, including cisplatin- or carboplatin-based chemotherapy. CIPN and ototoxicity represent important challenges because of the lack of means for effective prevention, mitigation, or a priori identification of high-risk patients, and few studies have applied modern genomic approaches to understand underlying mechanisms/pathways. Translational genomics, including cell-based models, now offer opportunities to make inroads for the first time to develop preventive and interventional strategies for CIPN, ototoxicity, and other treatment-related complications. This commentary provides current perspective on a successful research strategy, with a focus on cisplatin, developed by an experienced, transdisciplinary group of researchers and clinicians, representing pharmacogenomics, statistical genetics, neurology, hearing science, medical oncology, epidemiology, and cancer survivorship. Principles outlined herein are applicable to the construction of research programs in translational genomics with strong clinical relevance and highlight unprecedented opportunities to understand, prevent, and treat long-term treatment-related morbidities.
The Measurement of Glomerular Filtration Rate and Effective Renal Plasma Flow in Man by Iothalamate <sup>125</sup> I and Iodopyracet <sup>131</sup> I
Authors: CHARLES M. ELWOOD, EUGENE M. SIGMAN
Journal: Circulation (1967)

In 21 patients, 90 simultaneous renal clearances of inulin and sodium iothalamate 125 I, and para-amino-hippuric acid (PAH) and iodopyracet 131 I were determined by a constant infusion technique. The activities of iothalamate 125 I and iodopyracet 131 I were determined simultaneously in a dual-channel scintillation counter. The concentrations of inulin and PAH were determined by standard chemical techniques. The ratio of iothalamate 125 I to inulin clearance ranged from 0.93 to 1.09 with a mean of 1.00. The ratio of iodopyracet 131 I to PAH clearance varied from 0.86 to 1.04 with a mean of 0.96. The chemical determination of PAH and inulin required approximately 8 hours of technician time as compared with 30 minutes by the radioactive technique. The determination of the renal clearances of iothalamate 125 I and iodopyracet 131 I is an accurate and time-saving technique for the measurement of glomerular filtration rate and effective renal plasma flow.
Results of a Program to Reduce Admissions for Adult Asthma
Authors: Paul H. Mayo
Journal: Annals of Internal Medicine (1990)

Study Objective: To determine the effect of an outpatient program designed to reduce readmissions for asthma exacerbations among adults with asthma. Design: Randomized patient selection with crossover. Setting: Bellevue Hospital, New York City, New York. Patients: We identified 104 adult asthmatics who had previously required multiple hospitalizations for asthma attacks. Forty-seven patients were randomly assigned to an intensive outpatient treatment clinic and 57 patients continued to receive their previous outpatient care. Nineteen patients from this latter group were then crossed to the intensive outpatient therapy clinic. Interventions: Attenders of the intensive outpatient treatment program were treated with a vigorous medical regimen and educational program. Emphasis was placed on teaching patients aggressive self-management strategies in case of marked asthma exacerbation. Measurements and Main Results: The main measurement used to determine efficacy of the study program was readmission rate and hospital days used. Prospective comparison of treated compared with untreated patients indicated that program enrollment resulted in a threefold reduction in readmission rate and a twofold reduction in hospital day use rate (P < 0.004 and P < 0.02, respectively). Using retrospective data with patients serving as their own controls, we found a threefold reduction in readmission rate and in hospital day use (P < 0.003) during a 32-month follow-up period. A similar magnitude of reduction in hospital utilization was found when patients were crossed over to the intensive treatment group (P < 0.004). Conclusions: By using a vigorous medical regimen and intensive educational program, we were able to decrease hospital use among a group of adult asthmatics who had previously required repeated readmissions for acute asthma exacerbations.
Prolonged QT-Interval Syndromes
Authors: Arthur J. Moss
Journal: JAMA (1986)

PROLONGATION of the QT interval, either on a congenital or an acquired basis, is associated with an increased likelihood of malignant ventricular arrhythmias.<sup>1-3</sup>Patients with QT prolongation frequently develop recurrent attacks of syncope or may present with sudden death. The malignant ventricular arrhythmias are characterized by rapid, irregular tachycardias that usually have a polymorphous configuration or a torsades de pointes pattern. The latter is a French term that describes the tachycardia as a "twisting of the points," so called because the QRS axis shifts back and forth around the baseline. Although polymorphous ventricular tachycardia and torsade frequently occur in the setting of QT prolongation, these malignant arrhythmias may also occur in the absence of a repolarization abnormality. Effective cardiac output and blood pressure are markedly impaired during torsades de pointes, with resultant syncope. Most tachyarrhythmic episodes terminate spontaneously with return of consciousness, but some may degenerate into ventricular fibrillation,
Narrow band imaging for detecting superficial squamous cell carcinoma of the head and neck in patients with esophageal squamous cell carcinoma
Authors: C. Katada, S. Tanabe, W. Koizumi, K. Higuchi, T. Sasaki, M. Azuma, N. Katada, T. Masaki, M. Nakayama, M. Okamoto, M. Muto
Journal: Endoscopy (2010)

See also: Commentaire de travail de T. Matysiak-Budnik et al., pp. 191Endoscopy 2010; 42(03): 241-241DOI: 10.1055/s-0031-1291838
The structure of major birch pollen allergens ‐ epitopes, reactivity and cross‐reactivity
Authors: Michael D. Spangfort, Osman Mirza, Jens Holm, Jørgen N Laisen, Henrik Ipsen Henning Løwenstein
Journal: Allergy (1999)

To cite this article: Spangfort Michael D., Mirza Osman., Holm Jens., Laisen Jørgen N., Ipsen Henrik., Løwenstein Henning . The structure of major birch pollen allergens ‐ epitopes, reactivity and cross‐reactivity. Allergy 1999, 54, 23–26. Copyright © Munksgaard 1999 ISSN 0108–1675