tbuckley/cabot-search huggingface dataset:
Role of apoptosis and melanocytorrhagy: a comparative study of melanocyte adhesion in stable and unstable vitiligo
Authors: R. Kumar, D. Parsad, A.J. Kanwar
Journal: British Journal of Dermatology (2010)

Journal Article Role of apoptosis and melanocytorrhagy: a comparative study of melanocyte adhesion in stable and unstable vitiligo R. Kumar, R. Kumar Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India Search for other works by this author on: Oxford Academic Google Scholar D. Parsad, D. Parsad Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India Correspondence: Davinder Parsad. E‐mail: parsad@mac.com Search for other works by this author on: Oxford Academic Google Scholar A.J. Kanwar A.J. Kanwar Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 1, 1 January 2011, Pages 187–191, https://doi.org/10.1111/j.1365-2133.2010.10039.x Published: 01 January 2011
Long-Term Therapy for Postmenopausal Osteoporosis: Stronger Bones but Weaker Arteries?
Authors: Mark R. Goldstein
Journal: Circulation (1999)

To the Editor:The intriguing article by Jono et al 1 suggests that long-term supplementation with vitamin D for postmenopausal osteoporosis may increase vascular calcification.This is not a new concept 2 and raises important and practical issues.Alendronate, an inhibitor of osteoclast-mediated bone resorption, is widely promoted for the treatment and prevention of osteoporosis in postmenopausal women. 3 This group of women
Frequent and subtype-related genetic mutational signature suggesting the involvement of specific signaling pathway.
Authors: S. Boyault, Y. Drouet, C. Lasset, C. Navarro, A. Puisieux, T. D. Bachelot, Q. Wang
Journal: Journal of Clinical Oncology (2010)

e21015 Background: Studies with expression microarray profiling have enabled the classification of beast cancers into four types: luminal A, luminal B, ERBB2 + and basal-like. Little is known about whether there exist an “mutational profile” characteristic of each tumour and whether there is any correlation with the classification of luminal A, B, ERBB2+ and basal-like, and the correlation with clinical outcome. Methods: In an attempt to have an insight into the involvement of frequently mutated genes in different subtype of breast cancer, we analysed 125 invasive breast tumours which were classed on the basis of immunostaining (IHC) and FISH as Luminal (ER+ and HER2-), ERBB2 + and triple-negative (as a surrogate for basal like). Search for mutations in 5 genes frequently mutated in human cancers: TP53, PIK3CA, CDH1, PTEN and KRAS using direct sequencing was conducted. Results: Mutations were detected in a total of 80 samples (64%), among which 71 (57%) carried single-gene mutation. Nine tumors harbored more than 2 mutations involving different genes. We found that mutations were not randomly distributed in different subtypes. High frequent mutations of p53 were detected in ERBB2+ and triple-negative tumors (65% and 73%, respectively). On the other hand PIK3CA mutations were prevalent in the luminal subtype. It is also interesting to note that, contrary to previously reported in the literature, the p53 mutations found in ERBB2+ and triple-negative tumors were predominantly framshift and nonsense mutation leading to the disruption of protein synthesis. Conclusions: Our data clearly demonstrated that genetic alterations play an important role in breast cancer genesis. The fact that the majority of the tumors carried mutations in one single gene suggested the involvement of specific signaling pathways in each tumor; which could be of importance as to the choice for targeted therapy. The study is still ongoing, especially on the correlation of mutation data to clinical outcome. No significant financial relationships to disclose.
Abstract 159: Immediate Transnasal Evaporative Cooling During Resuscitation from Cardiac Arrest: The Cool Before Airway Study
Authors: Marie-Sophie Grave, Raphael van Tulder, Alexander Nürnberger, Stergios Fykatas, Dieter Sebald, Fritz Sterz
Journal: Circulation (2014)

BACKGROUND: Therapeutic hypothermia is an integral part of the standard resuscitation care. One method to induce therapeutic hypothermia is transnasal evaporative cooling. PURPOSE/AIMS: We wanted to demonstrate that transnasal evaporative cooling initiated prior to achieving a protected airway during CPR in an out-of-hospital setting is safe and feasible. METHODS: Transnasal evaporative cooling via the RhinoChill® (RC) System (BeneChill Inc. San Diego, CA, USA) was initiated prior to a protected airway after initiating cardiac resuscitation, and was continued until either the subject was declared dead, standard institutional systemic cooling methods were implemented or cooling equipment (oxygen and perfluorcarbone) was empty. The subject was monitored throughout the hypothermia period, and followed until either death or hospital discharge. Clinical assessments and clinically relevant adverse events were documented over this period of time. RESULTS: In total 21 patients were included in this trial. Four of them had to be excluded subsequently. One patient had been excluded due to a pre-existing secured airway, the others due to user errors. Finally, 17 patients (f=6; mean age 65.5 years, CI95%: 57.7-73.4) met all the eligibility criteria and were included for further investigation. Device-related adverse events occurred in only two patients, which were mild and had no consequence on the patient’s outcome. One was reversible nose-whitening and the other epistaxis. According to the filed reports of the EMS personnel, no severe technical problems occurred by using the RC device that led to a delay or the impairment of quality of the CPR. The most common observed interruption in the application was a short blockage of the device (n=12). In four cases the bag-valve-mask-ventilation wasn’t possible due to blockage or a sealing lack and in two cases a moderate orificial fluid spraying was observed during chest compressions. CONCLUSIONS/RECOMMENDATIONS: Early application of the RC device, during cardiac arrest in the out-of-hospital setting of Vienna, is feasible, safe and easy to handle and does not delay or hinder CPR, or establishment of a secure intubation. For efficacy and further safety data additional studies will be needed.
Abstract 2014: SHP2 stabilizes EGFR and beta-catenin to promote the transformation and tumorigenic potential of basal-like and triple-negative breast cancer cells
Authors: Hua Zhao, Yehenew M. Agazie
Journal: Cancer Research (2014)

Abstract Basal-like and triple-negative breast cancer (BTBC) causes disproportionately high mortalities in women. One of the major reasons is lack of targeted therapy, and the other is the highly aggressive and metastatic nature of the disease. The primary complication in finding viable drug targets has been the dysregulation of multiple signaling pathways, making one pathway inhibition an unlikely strategy to lead to effective treatment for BTBC. Therefore, targeting multiple pathways or finding proteins that control multiple signaling pathways and targeting them remain to be the only hope. In line with this, we have discovered that the Src homology phosphotyrosyl phosphatase 2 (SHP2) controls EGFR and Wnt/β-catenin signaling, major pathways known to be dysregulated in BTBC. We show that SHP2 overexpression in BTBC tumors is associated with elevated EGFR expression and cytoplasmic and nuclear accumulation of β-catenin. Silencing SHP2 expression in BTBC cells destabilizes EGFR and β-catenin and inhibits respective downstream signaling, confirming that SHP2 overexpression is essential for dysregulation of EGFR and β-catenin in this subtype of breast cancer. Furthermore, we demonstrate that inhibition of SHP2 in BTBC cells induces luminal epithelial morphology, suppresses cell proliferation, reverses transformation, blocks invasiveness in 3D matrigel, and abolishes tumorigenesis and metastasis. These findings suggest that SHP2 controls the EGFR and the Wnt/β-catenin signaling pathways to promote BTBC. Citation Format: Hua Zhao, Yehenew M. Agazie. SHP2 stabilizes EGFR and beta-catenin to promote the transformation and tumorigenic potential of basal-like and triple-negative breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2014. doi:10.1158/1538-7445.AM2014-2014
Abstract #5555: 14-3-3\#963;, a marker for poor prognosis of pancreatic cancers, contributes to gemcitabine and radiation resistance
Authors: Zhaomin Li, Zizheng Dong, David Myer, Michelle Yip-Schneider, C Max Schmidt, Jian-Ting Zhang
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Pancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which can now be curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, 14-3-3\#963; has been shown to cause drug resistance when over-expressed in cancer cells and its mRNA level has been found to increase in pancreatic cancers. These observations raise a possibility that 14-3-3\#963; expression is up-regulated in pancreatic cancers which in turn contributes to the failure in treatment of pancreatic cancers. In this study, we tested this hypothesis using fresh-frozen human pancreatic cancer tissues in combination with western blot analysis. We found that the 14-3-3\#963; protein level is increased in about 71% (17 of 24) of human pancreatic cancer tissues examined and that the 14-3-3\#963; expression level in the cancers examined correlates with lymph node metastasis, which is consistent with poor prognosis. Furthermore, we demonstrated that over-expression of ectopic 14-3-3\#963; in a pancreatic cancer cell line caused significant resistance to anticancer drugs gemcitabine, mitoxantrone and Adriamycin as well as to \#947;-irradiation by causing resistance to the treatment-induced apoptosis.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5555.
Ferredoxin reductase affects p53-dependent, 5-fluorouracil–induced apoptosis in colorectal cancer cells
Authors: Paul M. Hwang, Fred Bunz, Jian Yu, Carlo Rago, Timothy A. Chan, Michael P. Murphy, Geoffry F. Kelso, Robin A. J. Smith, Kenneth W. Kinzler, Bert Vogelstein
Journal: Nature Medicine (2001)
Abstract 2157: Racial Differences in Hospitalizations for Atrial Fibrillation in the United States
Authors: Paul B Tabereaux, Todd M Brown, Jose Osorio, G. N Kay, Dawn M Bravada
Journal: Circulation (2008)

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the United States; however a paucity of population-based data about nonwhite individuals exist. The objectives of this study were to compare hospitalizations among Whites and African Americans (AA) and to determine whether race is an independent predictor of hospitalization for AF in the United States. Methods: Data was obtained from the National Hospital Discharge Survey (years 1996 –2005) and included hospitalizations with a principal diagnosis of AF for patients aged ≥18 yrs and race designated as either White or AA. Codes from the International Classification of Diseases -9th revision were used to define AF (427.31), hypertension (401– 405), ischemic heart disease (410 – 414), diabetes mellitus (250), heart failure (425,428) and valvular heart disease (424). Multivariable analysis with logistic regression was used to identify factors that were independently associated with AF hospitalizations Results: Among 297,962,043 hospitalizations between 1996 –2005, 3,676,787 (1.2%) had a principal diagnosis of AF. Among the hospitalizations for AF, white race was more common than AA race (2,393,659/186,904,962 of whites (1.3% of white’s hospitalized) and 209,788/33,972,665 of African Americans (0.6% of AA’s hospitalized), p&lt;0.0001). After adjusting for the most common risk factors for AF (age, sex, hypertension, ischemic heart disease, diabetes mellitus, heart failure and valvular heart disease) AA race was independently associated with a decreased odds of hospitalizations for AF (Table 1 : adjusted OR=0.49, 95%CI 0.46 – 0.51). Conclusions: After adjusting for the most common risk factors for AF, the odds of hospitalization for AF in AA’s remained half that of whites. Race may be a novel and unaccounted risk factor for atrial fibrillation.
Association of Anti–Acidic Ribosomal Protein P0 and Anti–Galectin 3 Antibodies With the Development of Skin Lesions in Systemic Lupus Erythematosus
Authors: Zhen‐rui Shi, Guo‐zhen Tan, Zhen Meng, Min Yu, Kai‐wen Li, Jing Yin, Kai‐hua Wei, Yi‐jin Luo, Shu‐qing Jia, Shu‐juan Zhang, Jian Wu, Xiang‐bin Mi, Liangchun Wang
Journal: Arthritis & Rheumatology (2014)

The specific autoantibodies and antigens that mediate systemic lupus erythematosus (SLE)-related organ injuries remain largely unknown. This study was undertaken to investigate the antibody-mediated immune response that leads to SLE skin lesions. The study included 85 SLE patients with lupus-specific skin lesions and 31 without skin lesions. The reactivity of serum antibody with skin antigens was determined by immunoblotting using human foreskin as the substrate. Skin antigens were identified using mass spectrometry. Serum antibody was isolated by affinity purification and was injected intracutaneously into mouse skin to determine pathogenicity. Serum antibody levels were monitored by enzyme-linked immunosorbent assay. We determined that 78% of the patients with skin lesions had serum antibodies reactive with 35-kd and/or 25-kd skin antigens, which was significantly higher than the percentage of patients without skin lesions (P < 0.0001), suggesting a correlation between immune response and skin lesions. Acidic ribosomal protein P0 (RPLP0) and galectin 3 were 2 target antigens identified from 35-kd and 25-kd proteins, respectively. Purified serum anti-RPLP0 and anti-galectin 3 antibodies induced lupus-like histologic changes after intracutaneous injection. Anti-RPLP0 and anti-galectin 3 antibody levels were significantly higher in SLE patients than in healthy controls and decreased with skin recovery. Anti-galectin 3 antibody levels were not significantly higher in SLE patients than in patients with dermatomyositis or scleroderma, but strongly related to lupus cutaneous vasculitis. Additionally, levels of the 2 antibodies were positively correlated with leukopenia and C3 deficiency, and the anti-RPLP0 antibody level was also positively correlated with arthritis and SLE disease activity. Our findings indicate that the immune response mediated by serum anti-RPLP0 and anti-galectin 3 antibodies plays a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders.
The foremost cancer--revisited
Authors: J. A. Petrek, A. I. Holleb
Journal: CA A Cancer Journal for Clinicians (1995)

In 1969, the late Roald M. Grant, MD, then Editor in Chief of CA, wrote an editorial on breast cancer titled "The Foremost Cancer." In this issue, Jeanne A. Petrek, MD, an Associate Attending Surgeon in the Department of Surgery at the Memorial Sloan-Kettering Cancer Center, and Arthur I. Holleb, MD, CA's Editor Emeritus, update Dr. Grant's essay on breast cancer and comment on the articles that appear in this issue.
Abstract 12816: Cellular Iron Transport Protein, Transferrin Receptor 1 Plays a Role in the Pathophysiology of Pulmonary Arterial Hypertension
Authors: Manani Hosokawa, Yoshiro Naito, Hisashi Sawada, Makiko Oboshi, Toshihiro Iwasaku, Yoshitaka Okuhara, Daisuke Morisawa, Akiyo Eguchi, Shinichi Hirotani, Toshiaki Mano, Takeshi Tsujino, Tohru Masuyama
Journal: Circulation (2014)

Introduction: Cellular iron transport protein, transferrin receptor 1 (TfR1) is required for the uptake of transferrin-bound iron into the cells. Some reports have shown that iron deficiency is reported to be prevalent in patients with pulmonary arterial hypertension (PAH); however, the role of TfR1 in the pathophysiology of PAH remains unknown. Hypothesis: We hypothesiged that TfR1 plays a role in the pathophysiology of PAH. Here, we investigate TfR1 in the experimental models of PAH. Methods: Male Sprague-Dawley rats were subcutaneously injected with monocrotaline (60 mg/kg). Saline-injected rats were served as controls. In addition, we knocked down TfR1 expression in human pulmonary arterial smooth muscle cells (hPASMCs) and primary cardiomyocytes prepared from neonatal rats using its siRNA. Results: Monocrotaline-injected rats showed pulmonary vascular remodeling, increased right ventricular pressure, and right ventricular hypertrophy. Of interest, TfR1 expression was increased in the pulmonary remodeled artery and the hypertrophied right ventricle of monocrotaline-injected rats, as compared with the controls. Meanwhile, iron content did not differ in the pulmonary artery and right ventricle between the control and monocrotaline-injected rats. Transfection of hPASMCs and cardiomyocytes with TfR1 siRNA significantly reduced TfR1 gene expression. Importantly, TfR1 silencing suppressed platelet-derived growth factor (PDGF)-induced proliferation of hPASMCs. Moreever, TfR1 silencing attenuated phenylephrine-induced increase in cell size of cardiomyocytes. Conclusions: These results indicate that TfR1 plays a role in the pathophysiology of pulmonary artery remodeling and right ventricular hypertrophy in PAH.
Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice
Authors: Hisashi Tagaya, Takahiro Kunisada, Hidetoshi Yamazaki, Toshiyuki Yamane, Takeshi Tokuhisa, Erwin F. Wagner, Tetsuo Sudo, Leonard D. Shultz, Shin-Ichi Hayashi
Journal: Blood (2000)
Abstract 1511: Gap Junction Internalization and Autophagic Degradation in the Failing Heart
Authors: Geoffrey G Hesketh, Manish H Shah, David A Kass, Jennifer E Van Eyk, Gordon F Tomaselli
Journal: Circulation (2008)

INTRODUCTION Gap junctions (GJs) mediate electrical coupling between cardiomyocytes, and are required for coordinated electrical activation and contraction of the heart. GJs are remodeled in diseased myocardium, resulting in impaired intercellular coupling and a predisposition to life threatening arrhythmias. To understand the mechanisms of GJ remodeling in heart failure (HF), we examined the ultrastructure of GJs in failing canine myocardium. METHODS and RESULTS Using transmission electron microscopy, we observed the formation of GJs between lateral membranes of ventricular myocytes in rapid pacing induced heart failure (HF) in dogs. Lateral GJs exhibited complex membrane bending and extensive internalization. Lateral GJs were frequently adjacent to mitochondria and internalized GJs often formed concentric ring structures surrounding cellular debris. Internalized GJ membranes were associated with multi-lamellar membrane structures, with features characteristic of autophagosomes. Connexin43 (Cx43) and the autophagosome marker GFP-LC3 were extensively co-localized when expressed in HeLa cells. A hyperphosphorylated form of Cx43 previously associated with GJ degradation co-fractionated with LC3-II (autophagosome targeted form) in a Triton-insoluble and buoyant fraction of ventricular tissue. The hyperphosphorylated/buoyant population of Cx43 as well as LC3-II were both significantly increased (n=5 each, p=0.011 and p=0.016 respectively), and whole tissue levels of Cx43 were significantly decreased (n=5, p=0.01), in pacing-induced HF. CONCLUSION We show that structurally heterogeneous GJs are present at the lateral membranes of cardiomyocytes in HF, suggesting aberrant targeting of GJs. Internalized GJs are degraded via autophagy, which involves a hyperphosphorylated form of Cx43, and is enhanced in HF. These findings reveal a novel pathway of GJ targeting and degradation in HF, and suggest potential therapeutic targets for HF-related conduction slowing and arrhythmias.
Anatomic and Visual Outcomes of Scleral Buckling versus Primary Vitrectomy in Pseudophakic and Aphakic Retinal Detachment
Authors: Hamid Ahmadieh, Siamak Moradian, Hooshang Faghihi, Mohammad M. Parvaresh, Heshmatollah Ghanbari, Morsal Mehryar, Ebadollah Heidari, Hasan Behboudi, Touka Banaee, Banafsheh Golestan
Journal: Ophthalmology (2005)
Lenf Nodu Diseksiyonu ile Birlikte Yapılan ve Yapılmayan Radikal Nefrektomi: Avrupa Kanser Araştırma ve Tedavi Organizasyonu (EORTC) 3 881 Randomize Faz 3 Çalışmasının Nihai Sonuçları
Authors: Jan H.M. Blom a, Hein van Poppel, Jean M. Maréchal, Didier Jacqmin, Fritz H. Schröder, Linda de Prijck, Richard Sylvesterf
Journal: European Urology (2009)
Correlation of severity of psychiatric patients' delusions with right hemispatial inattention (left-turning behavior)
Authors: H S Bracha, R L Livingston, J Clothier, B B Linington, C N Karson
Journal: American Journal of Psychiatry (1993)

Studies associate psychotic disorders with various forms of subtle inattention to the right hemispace (left-turning behavior). The authors examined the correlation between this dopamine-related sign and severity of delusions (presumably dopaminergic symptoms) in 20 psychotic patients. Delusions were significantly correlated with severity of left-turning bias, and this neurological sign accounted for 33% of the variance in severity of delusions.
1041. Treatment of Hyperbilirubinemia in the Gunn Rat by Intravascular Gene Transfer into Muscle with Naked Plasmid DNA (pDNA)
Authors: Istvan Danko, Zhen Jia
Journal: Molecular Therapy (2004)

Background: Use of pDNA vectors to express hepatic enzymes in muscle would enable gene therapy for inborn errors of metabolism without the risks inherent in viral gene transfer into the liver. We tested the feasibility of this approach in the bilirubin uridine glucuronosyl transferase (UGT1A1) deficient Gunn rat, animal model of Crigler-Najjar syndrome type I. UGT1A1 deficiency results from mutations of the UGT gene and is characterized by hyperbiliriubinemia due to inefficient biliary excretion of bilirubin. Goal of treatment is prevention of the major complication, encephalopathy, by decreasing serum bilirubin levels.
A Single miRNA-mRNA Interaction Affects the Immune Response in a Context- and Cell-Type-Specific Manner
Authors: Li-Fan Lu, Georg Gasteiger, I-Shing Yu, Ashutosh Chaudhry, Jing-Ping Hsin, Yuheng Lu, Paula D. Bos, Ling-Li Lin, Carolyn L. Zawislak, Sunglim Cho, Joseph C. Sun, Christina S. Leslie, Shu-Wha Lin, Alexander Y. Rudensky
Journal: Immunity (2015)
Hepatitis C Infection Is Associated with Hepatic Toxicity but Does Not Compromise the Survival of Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab-Based Chemotherapy
Authors: Li-Yuan Bai, Tzu-Ting Chen, Chang-Fang Chiu, Tse-Yen Yang, Su-Peng Yeh, Yu-Min Liao
Journal: Blood (2014)