tbuckley/cabot-search huggingface dataset:
Localized depigmentation on genital melanosis: a clue for the understanding of vitiligo
Authors: Y. Harmelin, N. Cardot-Leccia, J.-P. Ortonne, P. Bahadoran, J.-P. Lacour, T. Passeron
Journal: British Journal of Dermatology (2012)

Journal Article Localized depigmentation on genital melanosis: a clue for the understanding of vitiligo Get access Y. Harmelin, Y. Harmelin Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar N. Cardot‐Leccia, N. Cardot‐Leccia Histopathology, University Hospital of Nice, 06200 Nice, France Search for other works by this author on: Oxford Academic Google Scholar J.‐P. Ortonne, J.‐P. Ortonne Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar P. Bahadoran, P. Bahadoran Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar J.‐P. Lacour, J.‐P. Lacour Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar T. Passeron T. Passeron Departments of Dermatology andC3M, INSERM U1065, Team 12, University of Nice, Nice, France Thierry Passeron. E‐mail: passeron@unice.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 3, 1 March 2013, Pages 663–664, https://doi.org/10.1111/bjd.12006 Published: 01 March 2013
Abstract 16306: Activation of the Wnt/Planar Cell Polarity Pathway is Required for Pericyte Recruitment During Pulmonary Angiogenesis
Authors: Ke Yuan, Mark Orcholski, Cristina Panaroni, Ngan Huang, Xinguo Jiang, Wen Tian, Eszter Vladar, Mark Nicolls, Joy Wu, Vinicio de Jesus Perez
Journal: Circulation (2014)

Rationale:  Pericytes are perivascular cells localized to capillaries that promote vessel maturation and their absence can contribute to vessel loss. Whether impaired pericyte interaction with endothelial cells contributes to small vessel loss in pulmonary arterial hypertension (PAH) is unclear.   Objective:  To measure the ability of PAH pericytes to associate with pulmonary microvascular endothelial cells (PMVECs) in vitro and in vivo.   Methods and Results:  Using 3G5 specific IgG-coated magnetic beads, we isolated pericytes from lungs of healthy and PAH patients followed by lineage validation. When seeded with healthy PMVECs, PAH pericytes failed to associate with endothelial tubes, resulting in smaller vascular networks compared to those seen with healthy pericytes. Following demonstration of abnormal polarization towards endothelium via live imaging and wound-healing studies, we screened PAH pericytes for abnormalities in the Wnt/planar cell polarity (PCP) pathway, which has been shown to regulate cell motility and polarity in the pulmonary vasculature. We found that PAH pericytes have reduced expression of frizzled 7 (Fzd7) and cdc42, two genes critical for Wnt/PCP activation. Simultaneous knockdown of Fzd7 and cdc42 in healthy pericytes resulted in reduced motility and polarization towards PMVECs both in vitro and in a murine model of angiogenesis, whereas restoration of both genes in PAH pericytes resulted in improved endothelial-pericyte association and larger vascular networks.   Conclusions:  These studies suggest that the motility and polarity of pericytes during pulmonary angiogenesis is regulated by Wnt/PCP activation. Therapies targeting Wnt/PCP in pericytes could help prevent vessel loss in PAH.
UPLC-ESI-MS/MS Quantitation of cisplatin 1,2 guanine-guanine intrastrand cross links
Authors: Irene Baskerville-Abraham, Gunnar Boysen, Esra Mutlu, Stephen G. Chaney, James A. Swenberg
Journal: Clinical Cancer Research (2006)

A6   Platinum chemotherapeutic agents have been successfully used in the treatment of various epithelial cell based cancers for over 30 years. However, much remains unknown about the mode of action of these agents. It is generally believed that about 1% of the total cellular platinum binds to DNA, causing the induction of intra- and interstrand cross links. These DNA cross links are repaired to some extent by nucleotide excision repair. However, if not repaired they may lead to the induction of apoptosis via the inhibition of DNA replication and transcription, or cause mutations leading to cancer. It remains to be seen if specific adducts are responsible for varied responses to treatment, as current methods measure total platinum. The most prevalent DNA modification is the formed between two adjacent guanines at the N7 position producing the intrastrand cross link between cisplatin and 29-deoxyguanylyl(39,59)-29-deoxyguanosine or CP-d(GpG). We report here a new sensitive and specific quantitation method employing electro spray ionization mass spectrometry (ESI-MS) to measure the formation of the intrastrand cross link. Analyte standards have been synthesized and characterized by UV, ESI-MS/MS and NMR. Platinum has a characteristic isotopic cluster which aids in MS identification, but complicates quantitation. The following mass to charge (m/z) ratios therefore list the most prevalent ion. ESI-MS and ESI-MS/MS analysis revealed ions at [M+H] +  and [M+H-phosphate -2 deoxyribose - 2 amine] +  (m/z 824 and 496, respectively) for CP-d(GpG). Synthesis and characterization of stable isotope internal standard CP-[ 13 C 5 ]d(GpG) are underway. Preliminary studies have shown that anion exchange columns are an effective way of separating this adduct from unmodified nucleosides. Ultra performance liquid chromatography (UPLC) was used in combination with ESI-MS/MS to gain further sensitivity. Currently, analysis of CP-d(GpG) spiked DNA after anion exchange clean-up with selected reaction monitoring (SRM; m/z 824 → 496) resulted in a preliminary limit of detection of 9 adducts per 10 8  nucleotides. The addition of an internal standard and further method optimization is anticipated to allow accurate quantitation at lower concentrations of CP-d(GpG). The goal of this project is to measure CP-d(GpG) in specimens from human patients undergoing chemotherapy as a marker for tissue specific uptake at therapeutic doses. This work is supported by in part by grants from the NIEHS (T32ES07126, R42ES011746, P30ES10126) and the NCI (RO1CA084480).
Abstract 18742: Exercise Echocardiography with Speckle-Tracking Derived Strain and Strain-Rate Analysis Allows Detection of Heart Transplant Recipients with Focal Coronary Stenoses
Authors: Shwan Hussein, Michael Dandel, Roland Hetzer
Journal: Circulation (2014)

Background:  Transplant vasculopathy (TVP) is a major cause of graft failure after heart transplantation (HTx). Coronary angiography (CA) is necessary for TVP diagnosis but TVP surveillance by frequent angiographies is risky, especially for patients with renal dysfunction. Timing of CA by non-invasive methods especially by stress echocardiography (stressecho) thus appears necessary. Unfortunately, visual echo assessment of cardiac wall motion is highly operator dependent and allows only limited evaluation of radial deformation and no assessment of longitudinal shortening. This study assessed the usefulness of strain imaging for detection of exercise-induced left ventricle (LV) myocardial contraction abnormalities.   Methods:  HTx patients with known and unknown TVP (n = 20) underwent exercise stress-echo before their routine follow-up CA. A cohort of 20 healthy persons underwent the same stress-echo investigation. In all patients, the two-dimensional (2D) echo-loops acquired at unloaded phase, low load, peak load and recovery phase were analyzed by speckle tracking derived strain imaging. In the 20 HTx patients, longitudinal, radial and circumferential strain and strain rate data were tested for relationship with CA findings.   Results:  Global strain and strain-rate values were lower in HTx patients (p 50% narrowing) showed significant reduction in longitudinal strain and strain-rate, although conventional 2D-echo revealed no visually detectable regional wall motion alterations. Longitudinal strain and strain-rate showed the highest predictive value for new appearance of coronary stenoses and/or aggravation of preexistent stenoses.   Conclusion:  Quantitative segmental myocardial deformation analysis of LV loops acquired during exercise echocardiography using speckle tracking derived 2D strain imaging is effective for detection of coronary stenoses in HTx patients even before regional wall motion disturbances become visible. This analysis provides potentially useful information for non-invasive timing of coronary angiography.
Abstract P305: Prospective Associations of Serum Ferritin Levels With Cardiovascular Disease Incidence Among African Americans: The Jackson Heart Study
Authors: Benjamin Renelus, Heather R Millard, Maihemuti Axiyan, Solomon K Musani, Ervin R Fox, Jiankang Liu, Herman A Taylor, Aurelian Bidulescu
Journal: Circulation (2015)

Introduction: The role of inflammation in vascular endothelial remodeling initiating and propagating atherosclerosis has been well documented. There has been conflicting results regarding the role of ferritin, a nonspecific marker for systemic inflammation, in identifying high risk patients for cardiovascular disease (CVD) incidence. We thus investigated the association of ferritin with CVD incidence and subclinical measures of atherosclerosis among African Americans (AA), with the hypothesis that there is a direct association between ferritin and incident CVD events, and a putative effect measure modification by cholesterol levels. Methods: We measured serum ferritin levels at baseline visit (2000 - 2004) in 4,679 AA participants enrolled in the Jackson Heart Study. Sex-specific, age-adjusted correlations, multivariable linear and proportional hazards regression models were used to assess the cross-sectional and longitudinal associations of ferritin with carotid intima-media thickness, coronary artery ca...
Flynn of the Inland.
Authors: Ion Llewellyn Idriess
Journal: JAMA (1933)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 17368: The Diagnosis of Heterozygous Familial Hypercholesterolemia: Genotype versus Phenotype
Authors: Frederick Raal, Evan A Stein, Bertrand Cariou, Daniel Gaudet, Jacques Genest, Ransi Somaratne, Ian Bridges, Scott M Wasserman, Rob Scott, G. Kees Hovingh
Journal: Circulation (2014)

Background: Heterozygous familial hypercholesterolemia (HeFH) is the most common dominantly-inherited disorder in man, affecting between 1:250 and 1:300 persons worldwide and estimates of more than 3 million with HeFH in the USA and Europe alone. Diagnosis is usually made by clinical criteria and confirmed with genetic testing. Despite next-generation gene sequencing, a causative mutation cannot be identified in up to 20% of patients even with a clinical diagnosis of definite HeFH. Given the prevalence, clinical diagnostic criteria are important tools for detection and early treatment of HeFH patients, particularly for clinicians outside of referral centers. Methods: The RUTHERFORD-1 and -2 studies enrolled patients with a clinical and/or genetic diagnosis of HeFH. All consenting patients in this analysis underwent FH genotyping. We compare the accuracy of clinical and genetic diagnosis of HeFH. Results: Of the 416 patients enrolled who consented to genetic testing, 342 (82%) were found to have genetically-confirmed HeFH. Of these patients, 288 (84%) met the Simon Broome criteria for definite and 54 (16%) for probable HeFH; 250 (75%) met the MEDPED clinical criteria for 100%, and 301 (90%) the 80% likelihood for a diagnosis of HeFH (Table). Conclusion: Although the optimal method to diagnose HeFH remains unclear, from these two trials there was close agreement between the two clinical classifications and genetic criteria. There were only a relatively small number of patients in whom genetic testing could not confirm the clinical diagnosis. Clinical criteria offer an inexpensive, low-technology ability for widespread screening in patients suspected of having HeFH. The advantage of genetic testing is that it allows for cascade testing of family members for the identified mutation who may not fulfill clinical criteria for the diagnosis of HeFH and application of family-oriented preventive strategies.
Clues to the Deadly 1918 Flu Revealed
Authors: Tracy Hampton
Journal: JAMA (2004)

FOR DECADES, THE CHARACTERISTICS of the virus that caused the largest recordedoutbreakofany infectious disease in history have remained mysterious. But now scientists have unveiled important structural properties of a key viral protein that may help explain why the 1918 “Spanish” influenza pandemic was so devastating, killing 20 to 40 million individuals worldwide. Several researchers have retrieved viral DNA fragments from Alaskan flu victims buried in permafrost, as well as from archived autopsy materials. Historical records show that influenza spread through one village in Alaska in 5 days, killing about 85% of the adult population; the dead were buried in a mass grave in permafrost. The researchers used the DNA fragments to recreate the genetic code of H1 hemagglutinin, a protein necessary for influenza virus to bind and fuse with a host cell. With the synthesized gene in hand, they were then able to produce the protein and obtain its crystal structure. Two new reports suggest the unique structure of the 1918 virus’s hemagglutinin protein may be the reason for the rapid and deadly spread of the disease (Science. 2004. Feb 5; Epub ahead of print).One study looked at the structural elements involved with binding to receptors on host cells; the other probed the fusion of viral hemagglutinin with host cells. The results, researchers hope, could aid in the identification of other potentially dangerous influenza viruses and in vaccine development.
The A9 Antigen Associated with Aggressive Human Squamous Carcinoma Is Structurally and Functionally Similar to the Newly Defined Integrin α6β4
Authors: C. Van Waes, K. F. Kozarsky, A. B. Warren, L. Kidd, D. Paugh, M. Liebert, T. E. Carey
Journal: Cancer Research (1991)

We previously reported that altered expression of the A9 antigen (defined by monoclonal antibody UM-A9) is a predictive marker of early recurrence and progression of squamous cell carcinoma (SCC). In normal squamous cells A9 expression is limited to the site of contact with the basement membrane in vivo and the culture surface in vitro , whereas aggressive SCCs exhibit loss of polarity and increased intensity of A9 expression. The potential relationship of the A9 antigen to structures known to be involved in cell adhesion was analyzed by immunobiochemical and cell adhesion assay. UM-A9 precipitates a complex of protein chains reminiscent of the α and β heterodimer glycoproteins that characterize the integrin family of extracellular matrix receptors. Proteins were isolated from A9-positive cells using UM-A9 and well-defined antibodies specific for integrin α and β chains. UM-A9, anti-α6, and anti-β4 monoclonal antibodies (mAbs) all precipitated proteins with comparable electrophoretic mobilities. Furthermore, UM-A9 mAb precleared the SCC α6β4 integrin complex isolated with anti-α6 or anti-β4 mAbs but not that isolated by anti-β1 mAb. The isoelectric points of the A9 complex chains were consistent with those reported for α6 and β4. Three of the polypeptide chains (140, 175, and 205 kDa) precipitated by UM-A9 showed peptide homology to one another and to the β4 chain precipitated by mAb 439-9B. The A9/α6 subunit is composed of 125- and 30-kDa chains and was distinguished from β4 and β1 chains by its peptide map and isoelectric point. UM-A9 binds to an epitope common to the β4 subunits since in pulse-chase analysis the β4 species are precipitated at an early time point, whereas detection of α-subunit synthesis is detected during assembly of the mature complex. Immunoprecipitation and preclearing experiments demonstrated that in SCC the α6 subunit is associated primarily with the β4 species and not with the 130-kDa β1 subunit. In cell adhesion assays on extracellular matrix proteins, the α6-specific GoH3 mAb inhibited binding of SCC to laminin, suggesting that α6β4 may function as a laminin receptor in SCC. These data and our prior observations showing an association between altered A9 expression and early recurrence in SCC provide the first evidence that altered expression of α6β4 integrin is associated with the clinical behavior of human squamous cell carcinomas.
423. Isolation of an Adeno-Associated Virus (AAV)-Specific Camelid-Derived Single Chain Antibody Fragment: A Novel Tool for Purification of AAV Vectors of Different Serotypes
Authors: Xiaofei Wang, Sooah Sohr, Floro Cataniag, Fraser Wright, Guang Qu
Journal: Molecular Therapy (2004)

The manufacture of recombinant AAV2 to support clinical studies has been carried out using transient transfection of HEK293 cells grown in roller bottles. While this method gives high productivity (50,000 vg/cell) relative to other methods of vector production, we have recently completed a series of studies aimed at further increasing the productivity and consistency of the transfection process. An experimental design approach was taken to initially screen for parameters that significantly affect vector yield. Sets of 7 parameters relating to the cell growth, transfection and post-transfection conditions were tested in a fractional factorial design. Results of this screening revealed that transfection efficiency is the key parameter that plays a critical role in determining AAV vector yield. Levels of certain media components such as glutamine also significantly influence vector productivity. The transfection procedure was then further optimized by examining the effects of pH, plasmid concentration, method of mixing of transfection reagents, and timing and method of addition of the transfection reagent to the cells. We observed that reduced agitation during CaPO4 buffer mixing led to an approximate 3-fold increase in average productivity to approximately 1.5 E13 vg/roller bottle (150,000 vg/cell). We further found that stabilization of the CaPO4 / plasmid precipitate following addition to cells provided a further 2-fold increase in productivity. With these optimized procedures, we are capable of producing recombinant AAV2 vectors at a level of 2-3E13 vg/roller bottle (200,000–300,000 vg/cell), making the transient transfection method more efficient and economically viable for large-scale manufacturing.
Challenges in ductal carcinoma in situ risk communication and decision‐making
Authors: Ann H. Partridge, Joann G. Elmore, Debbie Saslow, Worta McCaskill‐Stevens, Stuart J. Schnitt
Journal: CA A Cancer Journal for Clinicians (2012)

Abstract In September 2010, the American Cancer Society and National Cancer Institute convened a conference to review current issues in ductal carcinoma in situ (DCIS) risk communication and decision‐making and to identify directions for future research. Specific topics included patient and health care provider knowledge and attitudes about DCIS and its treatment, how to explain DCIS to patients given the heterogeneity of the disease, consideration of nomenclature changes, and the usefulness of decision tools/aids. This report describes the proceedings of the workshop in the context of the current literature and discusses future directions. Evidence suggests that there is a lack of clarity about the implications and risks of a diagnosis of DCIS among patients, providers, and researchers. Research is needed to understand better the biology and mechanisms of the progression of DCIS to invasive breast cancer and the factors that predict those subtypes of DCIS that do not progress, as well as efforts to improve the communication and informed decision‐making surrounding DCIS. CA Cancer J Clin 2012. © 2012 American Cancer Society.
Time- and Rate-Dependent Alterations of the QT Interval Precede the Onset of Torsade de Pointes in Patients With Acquired QT Prolongation
Authors: Robert F. Gilmour, Mark L. Riccio, Emanuela H. Locati, Pierre Maison-Blanche, Philippe Coumel, Peter J. Schwartz
Journal: Journal of the American College of Cardiology (1997)

Objectives. The purpose of this study was to determine whether the QT interval dynamics that precede torsade de pointes are consistent with the initiation of this arrhythmia by early afterdepolarization-induced triggered activity. Background. Early afterdepolarization-induced triggered activity has been suggested as an electrophysiologic mechanism for torsade de pointes. Consequently, the initiation of torsade de pointes should involve time- and rate-dependent alterations of ventricular repolarization similar to those known to modulate the development of early afterdepolarizations. Methods. RR and QT intervals were measured in digitized 24-h ambulatory electrocardiographic recordings obtained from seven patients with acquired prolongation of ventricular repolarization. Each patient had one or more episodes of torsade de pointes. The relation between RR and QT intervals was determined before, during and after multiple episodes of torsade de pointes. Results. In patients with multiple episodes of ventricular arrhythmias, the onset of the arrhythmias was associated with a critical prolongation of the QT interval. In some episodes, prolongation of the QT interval was associated with sudden prolongation of the sinus cycle length, whereas in other episodes, the QT interval prolonged progressively at a constant cycle length. Conclusions. The association between a critically prolonged QT interval and the onset of ventricular arrhythmias suggests that the initial complex of torsade de pointes is an early afterdepolarization-induced triggered response. However, prolongation of the QT interval itself was not sufficient to account for the initiation of torsade de pointes, suggesting that other, as yet unidentified factors are required. (J Am Coll Cardiol 1997;30:209–17)
Heterologous Growth and Passages of Mouse Sarcomas in Hamsters (Mesocricetus auratus)
Authors: Joseph Patti, John J. Biesele
Journal: Cancer Research (1951)

Summary  Serial passages of Crocker mouse sarcoma 180 and a methylcholanthrene-induced mouse sarcoma were made in adult hamsters by means of intraperitoneal inoculation. Sarcoma 180 was transplanted from the mouse to the peritoneal cavity of the hamster with greater success when the hamsters were 1 or a few days old than when older. Subcutaneous inoculations in adult hamsters failed to grow and in suckling hamsters regressed after about 2 weeks of growth. No regressions were noted with either mouse sarcoma implanted intraperitoneally in the hamster.