tbuckley/cabot-search huggingface dataset:
COUP-TFII regulates satellite cell function and muscular dystrophy
Authors: Xin Xie, Sophia Y. Tsai, Ming-Jer Tsai
Journal: Journal of Clinical Investigation (2016)

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle-wasting disease caused by mutations in the dystrophin gene. Although dystrophin deficiency in myofiber triggers the disease's pathological changes, the degree of satellite cell (SC) dysfunction defines disease progression. Here, we have identified chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) hyperactivity as a contributing factor underlying muscular dystrophy in a dystrophin-deficient murine model of DMD. Ectopic expression of COUP-TFII in murine SCs led to Duchenne-like dystrophy in the muscles of control animals and exacerbated degenerative myopathies in dystrophin-deficient mice. COUP-TFII-overexpressing mice exhibited regenerative failure that was attributed to deficient SC proliferation and myoblast fusion. Mechanistically, we determined that COUP-TFII coordinated a regenerative program through combined regulation of multiple promyogenic factors. Furthermore, inhibition of COUP-TFII preserved SC function and counteracted the muscle weakness associated with Duchenne-like dystrophy in the murine model, suggesting that targeting COUP-TFII is a potential treatment for DMD. Together, our findings reveal a regulatory role of COUP-TFII in the development of muscular dystrophy and open up a potential therapeutic opportunity for managing disease progression in patients with DMD.
Chronic Myeloid Leukemia (CML) Patients with “Suboptimal” Response to Imatinib (IM) According to European LeukemiaNet Criteria Have a Poorer Outcome with Respect to “Optimal” Responders: A GIMEMA CML WORKING PARTY Analysis.
Authors: Fausto Castagnetti, Gabriele Gugliotta, Francesca Palandri, Massimo Breccia, Marilina Amabile, Ilaria Iacobucci, Nicoletta Testoni, Giulia Marzocchi, Simona Luatti, Giorgina Specchia, Tamara Intermesoli, Elisabetta Abruzzese, Adele Capucci, Luciano Levato, Franca Radaelli, Bruno Martino, Patrizia Pregno, Enrico Montefusco, Livio Trentin, Giuliana Alimena, Giovanni Martinelli, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Gianantonio Rosti
Journal: Blood (2009)
Adolescent Pregnancy Prevention: Primary, Secondary, and Tertiary
Authors: Judith A. Ganser
Journal: JAMA (1990)

<h3>To the Editor.—</h3> It was appropriate that two thoughtful and helpful articles about adolescent pregnancy should appear in<i>JAMA</i>.<sup>1,2</sup>However, I would like to suggest a broader model for the prevention of adolescent pregnancy. In the original description of the levels of application of preventive medicine, Leavell and Clark<sup>3</sup>defined primary prevention procedures as "measures designed to promote general optimum health by the specific protection of man against disease agents or the establishment of barriers against agents in the environment." They state that secondary prevention may be accomplished by early diagnosis and prompt treatment to prevent sequelae and limit disability. They consider tertiary prevention to be accomplished by rehabilitation. When considering adolescent pregnancy as a public health problem, it seems more appropriate to define primary prevention as all the approaches Drs McAnarney and Hendee included as well as the specific protection of providing birth control for sexually
A Large-Pore IEF Gel Electrophoresis Separates the Complex in Both of ADAMTS13 Bound to VWF and to the IgG Autoantibodies From the Unbound in Plasma Milieu
Authors: Masanori Matsumoto, Ayami Isonishi, Yuji Hori, Masaki Hayakawa, Kenji Soejima, Yoshihiro Fujimura
Journal: Blood (2011)
Mutations in main candidate genes (egfr, kras, braf) among patients with non-small-cell lung cancer from sardinia
Authors: M. Colombino, P. Paliogiannis, E. Defraia, G. Porcu, A. Pazzola, L. Cordero, G. Palomba, M.C. Sini, A. Manca, A. Carta, E.M. Saba, T. Scotto, M.G. Sarobba, F. Capelli, S. Ortu, G. Baldino, T. Sedda, P. Pirina, M. Budroni, A. Cossu, G. Palmieri
Journal: Annals of Oncology (2015)
Current approach and recommendations for standardized dosing of anticancer drugs in infants.
Authors: Frank M. Balis, Richard B. Womer, Stacey L. Berg, Peter C. Adamson, Elizabeth Fox
Journal: Journal of Clinical Oncology (2016)

10546 Background: In children, most anticancer drugs are dosed based on body surface area (BSA), but BSA dosing is often too toxic for infants. This led to empirical dose modifications in infants, usually by converting to a body weight-based dose, which results in up to a 50% dose reduction compared to BSA dosing. Methods: Doses and schedules of anticancer drugs used in 29 ongoing and recently conducted COG clinical trials were tabulated. The variability and complexity of dose modifications for infants led to the development of a single table-based method for dosing these agents based on the rationale that modifications for infants were implemented to reduce toxicity, which is not cancer-specific. Results: We identified 11 sets of criteria to define the infant population and eight dose modification methods in the 29 protocols across 10 cancer types. Six sets of criteria used different age-based conversion milestones ranging from 7 d to 36 mo (12 mo most common). Other criteria used weight, BSA or some combination of age, weight and BSA. The 30-Rule ([BSA dose/30] weight in kg) is the most common dose modification for infants. These methods can result in up to a 2-fold increase in the dose when conversion milestones are reached. The new dosing method, which was devised using weights and BSAs from > 1,000 infants and young children previously treated on COG trials, uses BSA-based dose banding in dosing tables for infants and children with a BSA < 0.6 m2and gradually transitions from the dose calculated using the 30-Rule to BSA dosing in a stepwise fashion (Table). No dose calculations are required and the 2 most widely used EMR systems support table-based dosing. Conclusions: This uniform, table-based method of dosing anticancer drugs in infants will eliminate the variability and complexity of current methods and should enhance the safety of anticancer drugs in infants. In the future, adaptive dosing methods that account for the effect of ontogeny on drug metabolism and elimination should be developed based on pharmacokinetic studies in infants. Vincristine 1.5 mg/m2 BSA [m2] Dose [mg] 0.2 to 0.24 0.14 0.25 to 0.3 0.26 0.31 to 0.34 0.36 0.35 to 0.4 0.46 0.41 to 0.44 0.55 0.45 to 0.5 0.65 0.51 to 0.54 0.74 0.55 to 0.59 0.85 ≥ 0.6 1.5 mg/m2
Docosahexaenoic acid causes rapid pulmonary arterial relaxation <i>via</i> KCa channel-mediated hyperpolarisation in pulmonary hypertension
Authors: Chandran Nagaraj, Bi Tang, Bence M. Nagy, Rita Papp, Pritesh P. Jain, Leigh M. Marsh, Andrea L. Meredith, Bahil Ghanim, Walter Klepetko, Grazyna Kwapiszewska, E. Kenneth Weir, Horst Olschewski, Andrea Olschewski
Journal: European Respiratory Journal (2016)

Cardioprotective benefits of ω-3 fatty acids such as docosahexaenoic acid (DHA) are well established, but the regulatory effect of DHA on vascular tone and pressure in pulmonary hypertension is largely unknown. As DHA is a potent regulator of K + channels, we hypothesised that DHA modulates the membrane potential of pulmonary artery smooth muscle cells (PASMCs) through K + channels and thus exerts its effects on pulmonary vascular tone and pressure. We show that DHA caused dose-dependent activation of the calcium-activated K + (KCa) current in primary human PASMCs and endothelium-dependent relaxation of pulmonary arteries. This vasodilation was significantly diminished in KCa –/– (Kcnma1 –/– ) mice. In vivo , acute DHA returned the right ventricular systolic pressure in the chronic hypoxia-induced pulmonary hypertension animal model to the level of normoxic animals. Interestingly, in idiopathic pulmonary arterial hypertension the KCa channels and their subunits were upregulated. DHA activated KCa channels in these human PASMCs and hyperpolarised the membrane potential of the idiopathic pulmonary arterial hypertension PASMCs to that of the PASMCs from healthy donors. Our findings indicate that DHA activates PASMC KCa channels leading to vasorelaxation in pulmonary hypertension. This effect might provide a molecular explanation for the previously undescribed role of DHA as an acute vasodilator in pulmonary hypertension.
TBCRC030: A randomized, phase II study of preoperative cisplatin versus paclitaxel in patients (pts) with <i>BRCA1/2-</i>proficient triple-negative breast cancer (TNBC)—Evaluating the homologous recombination deficiency (HRD) biomarker.
Authors: Erica L. Mayer, Ines Vaz-Luis, Andrea L. Richardson, Charles M. Perou, Nadine M. Tung, Vandana Gupta Abramson, Carey K. Anders, Andres Forero-Torres, P. Kelly Marcom, Kathy Miller, Shannon Puhalla, Mothaffar F. Rimawi, Vered Stearns, Tiffany A. Traina, William Thomas Barry, Joshua Timothy Jones, Kirsten Timms, Anne-Renee Hartman, Antonio C. Wolff, Eric P. Winer
Journal: Journal of Clinical Oncology (2014)

TPS1145 Background: Both platinum and taxane chemotherapy have activity in TNBC, however biomarkers predictive for activity of either agent are lacking. The HRD assay detects impaired double strand DNA break repair, and may identify BRCA1/2-proficient tumors with a 'BRCA-like' phenotype suitable for treatment with DNA repair targeted therapies. A significant correlation between HRD score and response to platinum was reported in a preoperative study of gemcitabine, carboplatin and iniparib for TNBC. The current trial will prospectively determine the association between HRD score and response to platinum or taxane preoperative chemotherapy in TNBC, as well as explore other potential novel biomarkers of response. Methods: This is a phase II multicenter study randomizing pts with BRCA1/2-proficient, stage I (T1 > 1.5 cm)-III TNBC to preoperative cisplatin 75 mg/m2 q3 wks x 4 or paclitaxel 80 mg/m2 weekly x 12 wks, followed by surgery. Mandatory tissue collection will occur at baseline and surgery. Pts with significant residual disease after 12 weeks will have a tumor biopsy, be classified as a non-responder (RCB>1), and can cross-over to alternative treatment. The primary objective is to determine the association of HRD score with pathologic response, defined as RCB 0-1, to neoadjuvant platinum or taxane in TNBC. Secondary objectives include overall clinical and pathologic responses and the positive predictive value of HRD for platinum therapy. Correlative analyses include evaluation of markers: NtAI, LST, HRD combined score, Hereditary Cancer Profile, PMS2 and CHEK2 HCP, RAD17/RAD50 expression values, PAM50, Vanderbilt TNBC subgroups, tumor infiltrating lymphocyte predictor, and signatures of taxane response; whole exome and RNA sequencing will be used to identify novel markers of response. Target accrual is 160 pts randomized 1:1. Assuming response rates of 40% to cisplatin and 30% to taxane and a drop-out rate of 12%, there will be 91% and 87% power, respectively, to detect a difference of 0.75 standard deviations in HRD score by RCB score. Clinical trial information: NCT01982448.
Relieving dyspnoea by non-invasive ventilation decreases pain thresholds in amyotrophic lateral sclerosis
Authors: Laurence Dangers, Louis Laviolette, Marjolaine Georges, Jésus Gonzalez-Bermejo, Isabelle Rivals, Thomas Similowski, Capucine Morelot-Panzini
Journal: Thorax (2016)

<h3>Background</h3> Dyspnoea is a threatening sensation of respiratory discomfort that presents many similarities with pain. Experimental dyspnoea in healthy subjects induces analgesia. This ‘dyspnoea-pain counter-irritation’ could, in reverse, imply that relieving dyspnoea in patients with chronic respiratory diseases would lower their pain thresholds. <h3>Methods</h3> We first determined pressure pain thresholds in 25 healthy volunteers (22–31 years; 13 men; handheld algometer), during unloaded breathing (BASELINE) and during inspiratory threshold loading (ITL). Two levels of loading were used, adjusted to induce dyspnoea self-rated at 60% or 80% of a 10 cm visual analogue scale (ITL6 and ITL8). 18 patients with chronic respiratory failure due to amyotrophic lateral sclerosis (ALS) were then studied during unassisted breathing and after 30 and 60 min of non-invasive ventilation—NIV30 and NIV60—(same dyspnoea evaluation). <h3>Results</h3> In healthy volunteers, pressure pain thresholds increased significantly in the deltoid during ITL6 (p&lt;0.05) and ITL8 (p&lt;0.05) and in the trapezius during ITL8 (p&lt;0.05), validating the use of pressure pain thresholds to study dyspnoea-pain counter-irritation. In patients with ALS, the pressure pain thresholds measured in the deltoid during unassisted breathing decreased by a median of 24.5%–33.0% of baseline during NIV30 and NIV60 (p&lt;0.05). <h3>Conclusion</h3> Relieving dyspnoea by NIV in patients with ALS having respiratory failure is associated with decreased pressure pain thresholds. Clinical implications have yet to be determined, but this observation suggests that patients with ALS could become more susceptible to pain after the institution of NIV, hence the need for reinforced attention towards potentially painful diagnostic and therapeutic interventions.
Detection of Occult Invasion in Melanoma In Situ
Authors: Michael J. Bax, Timothy M. Johnson, Paul W. Harms, Jennifer L. Schwartz, Lili Zhao, Douglas R. Fullen, May P. Chan
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> It is unclear why some patients with in situ melanoma develop metastases. Few reports demonstrate occult invasion with immunohistochemistry staining, which were discordant with reports interpreting such staining as false-positive. <h3>Objective</h3> To investigate the occurrence of occult invasive disease within in situ melanoma by using methods to circumvent potential limitations in prior study designs. <h3>Design, Setting, and Participants</h3> Unequivocal in situ melanoma without associated nevi or regression was identified using a consecutive sample of 33 cases plus 1 index case in an academic medical center. After cutting deeper into the most representative tissue block, 3 sequential slides were stained with hematoxylin-eosin (H-E), melanoma antigen (melan-A), and again with H-E. Melan-A–stained slides showing definitive invasion were double-stained with Sry-related HMg-Box gene 10 (SOX10) to confirm the melanocytic nature of the cells of interest. The study evaluated the possibilities of occult invasion detected by immunohistochemistry, sectioning deeper into the tissue block, or both. Slides were independently scored by 3 dermatopathologists with interrater reliability assessed. The study was conducted from January 1, 2012, to July 31, 2014. <h3>Main Outcomes and Measures</h3> Assessment of the occurrence of occult invasion, diagnosis of invasion by immunohistochemistry alone vs cutting deeper into the tissue block, and occurrence of false-positive results using immunohistochemistry alone. <h3>Results</h3> Occult invasive melanoma was detected in 11 of 33 consecutive cases (33%) of previously diagnosed unequivocal in situ melanoma. Six of 11 melanomas (55%) were diagnosable only by immunohistochemistry. The remaining 5 tumors (45%) were diagnosable by both melan-A and H-E staining, likely as a result of simply cutting deeper into the tissue block. Four cases (12%) showed a few melan-A–positive cells in the dermis, which was insufficient for a diagnosis of invasive melanoma and most consistent on a cytomorphologic basis with occult nevi. <h3>Conclusions and Relevance</h3> Although rare, in situ melanoma may metastasize. Occult microinvasion was demonstrated in up to one-third of the specimens in the present study, which provides a plausible explanation for this adverse event. Thus, history and physical examination including regional lymph nodes, education, and surveillance recommendations should be based on a very low, but not zero, risk of metastasis.
Lobe-Specific Lymph Node Dissection as a Standard Procedure in Surgery for Non–Small Cell Lung Cancer: A Propensity Score Matching Study
Authors: Hiroyuki Adachi, Kentaro Sakamaki, Teppei Nishii, Taketsugu Yamamoto, Takuya Nagashima, Yoshihiro Ishikawa, Kohei Ando, Kazuki Yamanaka, Katsuya Watanabe, Yutaka Kumakiri, Masahiro Tsuboi, Takamitsu Maehara, Haruhiko Nakayama, Munetaka Masuda
Journal: Journal of Thoracic Oncology (2016)
Benefits and Risks Associated With Thrombolysis for Pulmonary Embolism
Authors: Carlo Bova
Journal: JAMA (2014)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Experimental studies on Excitation Process in Septal Myocardium
Authors: Ikuo Ohashi
Journal: Circulation (1967)

The excitation process within the septal myocardium has been described by many investigators. However, some of details of the process have been left as problems to be discussed. It is also the purpose of this study to investigate the details of the process. Method : Hearts of 11 adult mongrel dogs were used in situ. Flexible multipolar electrodes were inserted across the ventricular septum through the right ventricular free wall. A 3-channel oscillograph was used for recording. In normal sinus excitation, in RBBB, and in extrasystole, the arrival time of excitation was measured on direct lead ECGS which were led from many points in the septal myocardium. Reference electrode was set in the apical free wall. To produce BBB, right or left bundle branch was cut. To provoke extrasystole, electrical stimulation was put on the right or left ventricular free wall with a set delay after previous QRS complex. Results : A) In normal sinus excitation 1. On the septal surface, the excitation spread from apex to base. The mean conduction velocity of excitation was 620 cm/sec on left endocardial surface and 180 cm/sec on right endocardial surface. 2. Through the septum, the excitation spread from both (left and right) surface to medial layer of the septum in 15 of 21 electrodes. In other 6 electrodes, one-way (from left to right) excitation was observed. The mean conduction velocity was 31 cm/sec (right to left) and 33 cm/sec (left to right). 3. In 18 of 21 electrodes, excitation appeard on the left endocardium before on the right endocardium. B) In BBB, the septum excited from the non blocked side to the blocked side. The mean conduction velocity was 29 cm/sec (LBBB) and 26 cm/sec (RBBB). C) In extrasystole, the septal excitation spread from the stimulated side to the other side. The mean conduction velocity was 38 cm/sec (L-stimulation) and 51 cm/sec (R-stimulation).
Abstract P3-01-02: Correlation of Mammographic breast density and tumor characteristics in Korean breast cancer patients
Authors: JY Cho, SH Ahn, JW Lee, JH Yu, BS Koh, HJ Kim, JW Lee, BH Son, G-y Gong, HH Kim
Journal: Cancer Research (2012)

Abstract Introduction: Western studies have demonstrated high breast density as a strong risk factor for breast cancer, it is poorly understood whether breast density affects the diverse phenotypes of breast cancer. We examined the association between various tumor characteristics and mammographic breast density in women with breast cancer. Methods: We conducted a cross-sectional analysis in 910 Korean women diagnosed with breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphovascular invasion, histologic grade, estrogen receptor, progesterone receptor, HER2. Breast density was classified as fatty (percent density less than 50% by a computer-assisted thresholding program, named “Cumulus™”; n = 470) or dense (percent density 50% or more; n = 440) for the cancer-free breast at the time of operation. Logistic regression was used to examine whether the relationships were modified by adjustment for body mass index, age at diagnosis, age at first birth, menopausal status, history of breast-feeding, and breast cancer staging. Results: Total 910 patients were involved, the mean age and median age at the operation was 48 years old (range 20–82), and the mean percent density was 48.09 (SD = 9.62 %: normally distributed, Kolmogorov-Smirnov test p = 0.32). Crude analysis shows that tumor size over than 0.5cm were more likely to have dense breasts compared with women with a tumor size &amp;lt;=0.5 cm (OR = 3.21, 95% CI = 1.59–6.45, p = 0.001 for tumor sizes 0.6–1.0cm; OR = 2.02, 95% CI = 1.09–3.74, p = 0.03 for tumor sizes 1.1–1.5cm; OR = 1.8, 95% CI = 0.97–3.33, p = 0.06 for tumor sizes 1.6–2.0cm; and OR = 1.64, 95% CI = 0.92–2.94, p = 0.1 for tumor sizes 2.1cm or more). PD and histologic grade shows reverse association between histologic grade 1 and grade 2,3. Progesteron receptor positive patients tend to have more dense(OR = 1.27, 95% CI=0.97–1.66, p = 0.07) breast than receptor negative patients, although after adjustment of age the statistical significant disappeared. Percent density was not significantly associated with, ER (p = 0.74), HER2 (p = 0.72). Conclusion: These results suggest that breast density is associated with tumor size and histologic grade and progesterone receptor positivity. Additional studies are needed to address whether these associations are due to just density masking the detection of some tumors, biological causation, or both. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-02.
A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with Temozolomide in Acute Leukemias
Authors: Ivana Gojo, Jan H. Beumer, Keith Pratz, Jiuping Ji, Lihua Wang, Michelle A. Rudek, Michael A. McDevitt, Maria R. Baer, Amanda Blackford, B. Douglas Smith, Steven D. Gore, Hetty E. Carraway, Margaret M. Showel, Mark J. Levis, Amy E. DeZern, Douglas Gladstone, Tania Jain, Jackie Greer, Marie Pouquet, Ali-walbi Ismail, James Herman, Weijie Poh, Larry Karnitz, Scott H. Kaufmann, Alice Chen, Judith E Karp
Journal: Blood (2015)