tbuckley/cabot-search huggingface dataset:
Abstract P3-10-05: Triple Negative Breast Cancer: Clinical Characteristics in the Different Histological Subtypes
Authors: G Dreyer, T Vandorpe, K Forceville, P Neven, A Smeets, H Janssen, B Brouwers, K Deraedt, R Paridaens, H. Wildiers
Journal: Cancer Research (2010)

Abstract Purpose: To study clinical characteristics of different histological subtypes of triple negative breast cancer (TNC). TNC are often considered as one group, but consist of many different histological subtypes with different biology and behavior. We decided to analyze a large cohort of TNC in a single centre and focus on clinical behavior including age distribution, occurrence of lymph node invasion, and outcome in different histological subtypes. Patients and methods: We used data from the breast cancer database from UH Leuven, containing 479 newly diagnosed TNC from January 1999 till November 2009, of which 396 received upfront surgery, 64 neoadjuvant chemotherapy, and 18 with metastases at diagnosis. Univariate and multivariate relations were studied between age, lymph node status, histological subtype, treatment and outcome. Results: Apocrine and invasive lobular TNC occur more often in older patients compared to IDC-NOS (resp. P = 0.0004, P = 0.0496), the latter being by far the most common subtype (80,2%). Although TNC are considered as an aggressive subtype of breast cancer with a bad prognosis, only 35.1% have lymph nodal involvement. There were no significant differences in nodal invasion between subtypes, but most subtypes contained few patients. In contrast to previous reports, 7/14 (50%) of apocrine TNC had lymph node involvement. DFS was different in different histological subtypes, but most of the histological subgroups contained insufficient numbers to be able to draw firm conclusions. Within the histologically ‘homogeneous’ IDC-NOS group with primary surgery and outcome data (n=308), DFS with 3.5 year median FUP decreased with increasing age, but chemotherapy and also radiotherapy were much less frequently given with increasing age (in age &amp;lt;50, 50-69, 70+ no chemo in 2/135, 25/126, 39/44; no radiotherapy in 14/135, 22/126, 12/44 respectively). In multivariate analysis, increasing age (HR for 10 yr increase: 0.68 (0.52-0.89)), presence of lymph node involvement (HR 2.17 (1.24-3.77)), administration of chemotherapy (HR 0.28 (0.12 — 0.67)), and radiotherapy (HR 0.39 (0.20-0.73)) were significant predictors of relapse. Conclusion: TNC is not a uniform disease. Different histological subtypes have different age distribution and outcome. The prognosis of the most common group of TNC, IDA-NOS is unexpectedly better in older patients, but this is counterbalanced by the significantly decreased use of chemotherapy and radiotherapy in this population. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-05.
The role of serotonin in ischemic cellular damage and the infarct size-reducing effect of sarpogrelate, a 5-hydroxytryptamine-2 receptor blocker, in rabbit hearts
Authors: Yasuko Shimizu, Shinya Minatoguchi, Kazuaki Hashimoto, Yoshihiro Uno, Masazumi Arai, Ningyuan Wang, Xuehai Chen, Chuanjian Lu, Genzou Takemura, Masaaki Shimomura, Takako Fujiwara, Hisayoshi Fujiwara
Journal: Journal of the American College of Cardiology (2002)
Towards Global and Long-Term Neurological Gene Therapy: Unexpected Transgene Dependent, High-Level, and Widespread Distribution of HSV-1 Thymidine Kinase throughout the CNS
Authors: Adam J. Zermansky, Federico Bolognani, Daniel Stone, Christine M. Cowsill, Graham Morrissey, Maria G. Castro, Pedro R. Löwenstein
Journal: Molecular Therapy (2001)

One of the challenges of neurological gene therapy for the treatment of chronic neurodegener-ative disorders, such as Parkinson's and Alzheimer's diseases, is achieving high levels, widespread distribution, and long-lived transgene expression in the brain. Here, following the intracerebral injection of a recombinant adenovirus (RAd) encoding herpes simplex virus type 1 thymidine kinase (HSV1-TK), we detect very high levels of HSV1-TK immunoreactivity throughout the brain both ipsilaterally and contralaterally to the injection site, for up to 12 months following vector administration. This study concludes that long-term, high-level, and anatomically distributed HSV1-TK immunoreactivity can be obtained, and that this is most likely due to transgene-specific properties, because neither the distribution nor the longevity were observed for the transgene β-galactosidase encoded by a co-injected vector. Thus, we demonstrate that transgene expression can be achieved over widespread areas of the rodent brain, even 12 months after a single injection of first-generation adenovirus vector.
Abstract 4960: COX-2 inhibition with celecoxib delays the progression of invasive mammary carcinoma in a murine model of collagen dense stroma.
Authors: Karla Esbona, David R. Inman, Kevin W. Eliceiri, Lee G. Wilke, Patricia J. Keely
Journal: Cancer Research (2013)

Abstract Breast cancer is the most common invasive cancer in women causing over 40,000 deaths yearly in the United States. Increased mammographic density correlates with over four-fold greater risk for breast cancer, making it one of the most important risk factors known for this disease. High breast density is correlated to increased collagen in the breast tissue, and we have found that increased collagen in the Col1a1tm1jae mouse model promotes mammary tumor formation and progression. Elevated collagen density in vitro increases expression of PTGS2 (prostaglandin-endoperoxide synthase 2), the gene for COX-2, by over four fold. COX-2 over-expression is observed in 40% of invasive breast carcinoma cases and correlates with poor prognosis. Based on these findings, we hypothesized that inhibition of COX-2 may be an effective therapy in the context of mammary tumors arising in dense tissue. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID) that specifically inhibits COX-2. To understand the mechanism by which COX-2 affects cell signaling and response to collagen matrix density, we utilized our previously characterized model of MMTV-PyVT tumors on a wild type (wt) or Col1a1tm1jae background. Col1a1tm1jae heterozygote and wt littermates were randomly assigned at 11 weeks of age to treatment with placebo or celecoxib at 400mg per kilogram body weight. Oral treatment was given daily for 21 days. We found that MMTV-PyVT tumors responded to celecoxib in a manner that is regulated by matrix density (p-value &amp;lt;.0001). Tumors that arose on the dense Col1a1tm1jae background were larger and more invasive (p-value &amp;lt;.0001). Endpoint tumor size was diminished in mice treated with a daily dose of celecoxib, which delayed the development of tumors and changed the structure of the dense matrix. The effect of celecoxib was not as prominent for masses which developed on the low density wt background. Immunohistochemistry of relevant markers in these tissues is ongoing and will further our understanding of the effects of COX-2 inhibition in dense matrices. These findings suggest that COX-2 has a direct role in modulating the configuration of dense matrices which promote a more invasive cancer effect. Moreover, these findings suggest that COX-2 may be an effective therapeutic target for women with dense breast tissue. Citation Format: Karla Esbona, David R. Inman, Kevin W. Eliceiri, Lee G. Wilke, Patricia J. Keely. COX-2 inhibition with celecoxib delays the progression of invasive mammary carcinoma in a murine model of collagen dense stroma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4960. doi:10.1158/1538-7445.AM2013-4960
Chronotherapeutic drug delivery for early morning surge in blood pressure: A programmable delivery system
Authors: Usha Yogendra Nayak, Gopal Venktesh Shavi, Yogendra Nayak, Ranjith Kumar Averinen, Srinivas Mutalik, Sreenivasa Meka Reddy, Purshottam Das Gupta, Nayanabhirama Udupa
Journal: Journal of Controlled Release (2009)
Widespread Pulmonary Lesions in a Cyanotic Woman
Authors: Robert A. Boedecker
Journal: JAMA (1980)

<h3>History</h3> A 16-year-old girl presented with digital clubbing and peripheral cyanosis. She was first seen at 12 years of age for evaluation of shortness of breath with exertion. Circumoral and peripheral cyanosis had appeared during the previous several years. No family history of cardiac or vascular lesions or other medical problems was elicited. The patient's medical history was unremarkable. Her physical examination was normal with the exception of the circumoral and digital cyanosis with clubbing. Cardiac and chest examinations were normal without murmur or bruit. The ECG was normal. Laboratory tests showed an RBC count of 5.5 million/cu mm; hemoglobin level, 17 g/dL; and hematocrit reading, 50%. Arterial blood gas values on room air were as follows: oxygen saturation, 83%; Po2, 41 mm Hg; and Pco2, 34 mm Hg. The patient had a chest roentgenogram (Fig 1), showing multiple pulmonary nodules. Dye dilution and catheterization were done. <h3>Diagnosis</h3> Pulmonary micro-arteriovenous
Inflammation and hepatic encephalopathy: Ibuprofen restores learning ability in rats with portacaval shunts
Authors: Omar Cauli, Regina Rodrigo, Blanca Piedrafita, Jordi Boix, Vicente Felipo
Journal: Hepatology (2007)

One of the neurological alterations in patients with minimal or overt hepatic encephalopathy is cognitive impairment. This impairment is reproduced in rats with chronic liver failure due to portacaval shunt (PCS). These rats show decreased ability to learn a conditional discrimination task in a Y-maze, likely due to reduced function of the glutamate-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in brain. It has been proposed that inflammation exacerbates the neuropsychological alterations induced by hyperammonemia, suggesting that inflammation-associated alterations may contribute to cognitive impairment in hepatic encephalopathy. This study assessed whether treatment with an anti-inflammatory drug, ibuprofen, is able to restore the function of the glutamate-NO-cGMP pathway in cerebral cortex in brain in vivo and/or learning ability in PCS rats. We show that PCS rats have increased levels of interleukin-6 and increased activities of cyclooxygenase and of inducible NO synthase in cerebral cortex, indicating the presence of inflammation. Chronic treatment with ibuprofen normalizes cyclooxygenase and inducible NO synthase activities but not interleukin-6 levels. Moreover, ibuprofen normalizes the function of the glutamate-NO-cGMP pathway in cerebral cortex in vivo and completely restores the ability of rats with chronic liver failure to learn the Y-maze task. This supports that inflammation contributes to the cognitive impairment in hepatic encephalopathy.the results reported point to the possible therapeutic utility of decreasing inflammation in the treatment of the cognitive deficits in patients with minimal or overt hepatic encephalopathy.
Gradually Increasing Doses of Prednisone in Myasthenia Gravis
Authors: Marjorie E. Seybold, Daniel B. Drachman
Journal: New England Journal of Medicine (1974)

ACTH and adrenal corticosteroids are effective in the treatment of myasthenia gravis. However, increased weakness may occur early in treatment, posing a considerable risk for the patient. To determine whether the early weakening could be avoided by use of a gradually increasing dosage schedule, we started treatment with 25 mg of prednisone on alternate days, and gradually increased the dose to 100 mg on alternate days. Anticholinesterase medication was maintained. No increased weakness developed in any of 12 patients on this regimen. Seven patients had good to excellent improvement in strength, returning to normal activity. Four patients had moderate improvement, and one did not benefit. The greater safety of this treatment regimen extends the usefulness of steroid therapy to a larger group of myasthenic patients than would otherwise be feasible. (N Engl J Med 290:81–84, 1974)
The Intracellular B30.2 Domain of Butyrophilin 3A1 Binds Phosphoantigens to Mediate Activation of Human Vγ9Vδ2 T Cells
Authors: Andrew Sandstrom, Cassie-Marie Peigné, Alexandra Léger, James E. Crooks, Fabienne Konczak, Marie-Claude Gesnel, Richard Breathnach, Marc Bonneville, Emmanuel Scotet, Erin J. Adams
Journal: Immunity (2014)
The Evolution of R Factor
Authors: Charles E. Davis, Jeraldine Anandan
Journal: New England Journal of Medicine (1970)

Although the therapeutic use of antibiotics favors the selection of bacteria that contain R factor, it does not necessarily follow that man-made antibiotics have induced the evolution of R factor. We have obtained evidence that R factor evolved before the advent of the antibiotic era. Cultures of fecal flora were taken from 128 people living in an "antibiotic-virgin" community in north Borneo. The total experience of this entire community with antibiotics consisted of 19 injections of penicillin given in 1959 during a yaws-eradication program. Six strains of Escherichia coli isolated from four subjects were found to possess transferable drug resistance. This multiple-antibiotic resistance was shown to be due to R factor by serial transfer through several recipients, by the absence of transfer from cell-free filtrates, and by the occurrence of transfer independently of the chromosome.
Low-Dose Oral Propranolol Could Reduce Brown Adipose Tissue F-18 FDG Uptake in Patients Undergoing PET Scans
Authors: Oscar Parysow, Ana M. Mollerach, Victor Jager, Silvina Racioppi, Jose San Roman, Victor H. Gerbaudo
Journal: Clinical Nuclear Medicine (2007)

Fluorine-18 fluoro-2-deoxy-D-glucose (FDG) uptake in brown adipose tissue (BAT) may generate FDG-PET scan misinterpretation. Recent studies have shown reduced FDG uptake in BAT in rats treated with high doses of the beta-blocker propranolol. The aim of this observational study was to present a cohort of patients with high FDG uptake in BAT who underwent a second scan after receiving a low dose of propranolol, to determine whether the use of this premedication could improve the diagnostic confidence of FDG-PET scans by inhibition FDG uptake in BAT, and also whether administration of this drug affects tracer uptake in tumors.Twenty-six cancer patients, presenting with increased BAT FDG uptake, were selected prospectively. On a different day, patients were given propranolol 20 mg orally 60 minutes prior to FDG administration 185-277.5 MBq (5-7.5 mCi) and were scanned again. Basal and postpropranolol BAT SUVmax, and tumor SUVmax (when present) were measured.Mean basal BAT SUVmax was 5.52+/-2.3. Mean postpropranolol SUVmax was 1.39+/-0.42 (P<0.0001). In 11 patients, the basal mean tumor SUVmax was 8.07+/-6.4, and 7.88+/-5.9 in postpropranolol scans (P=0.53). Nine patients showed mediastinal FDG uptake in the basal scan, affecting image interpretation. This was not observed in postpropranolol scans. No adverse effects due to propranolol were encountered.In this patient cohort, there was significant reduction of FDG uptake in BAT following propranolol administration, allowing for adequate interpretation of FDG-PET and software-fused FDG-PET with CT images, particularly in the mediastinal area, without affecting tumor tracer uptake.
The Michigan Medical Legislation League.
Authors: E. L. Shurly
Journal: JAMA (1896)

Detroit, Mich., Aug. 10, 1896. <h3>To the Editor:</h3> —I hope you will permit me to occupy a little more space in theJournalfor a few remarks concerning the Michigan Medical Legislation League. Of course, there is no use of continuing a controversy upon a subject when the participants are so widely apart in their premises; but I can not see wherein the " Regular " members of the League merit any censure! On the contrary, they deserve commendation for their patriotism and liberality of spirit in putting aside, for the moment, special ethical scruples for a broader code of human ethics which embraces the welfare, not only of the craft, but of all their fellow human beings. As already pointed out, the Michigan Medical Legislation League is merely a<i>political</i>organization. This controversy illustrates curiously the romance of history. Twenty years ago Dr. Donald Maclean and his colleagues of the Faculty
Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing
Authors: A. Patruno, P. Amerio, M. Pesce, G. Vianale, S. Di Luzio, A. Tulli, S. Franceschelli, A. Grilli, R. Muraro, M. Reale
Journal: British Journal of Dermatology (2009)

Background Extremely low frequency (ELF) electromagnetic fields (EMF) are known to produce a variety of biological effects. Clinical studies are ongoing using EMF in healing of bone fractures and skin wounds. However, little is known about the mechanisms of action of ELF-EMF. Several studies have demonstrated that expression and regulation of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) are vital for wound healing; however, no reports have demonstrated a direct action of ELF-EMF in the modulation of these inflammatory molecules in human keratinocytes. Objectives The present study analysed the effect of ELF-EMF on the human keratinocyte cell line HaCaT in order to assess the mechanisms of action of ELF-EMF and to provide further support for their therapeutic use in wound healing. Methods Exposed HaCaT cells were compared with unexposed control cells. At different exposure times, expression of inducible NOS (iNOS), endothelial NOS (eNOS) and COX-2 was evaluated by Western blot analysis. Modulation of iNOS and eNOS was monitored by evaluation of NOS activities, production of nitric oxide (NO) and O2− and expression of activator protein 1 (AP-1). In addition, catalase activity and prostaglandin (PG) E2 production were determined. Effects of ELF-EMF on cell growth and viability were monitored. Results The exposure of HaCaT cells to ELF-EMF increased iNOS and eNOS expression levels. These ELF-EMF-dependent increased expression levels were paralled by increased NOS activities, and increased NO production. In addition, higher levels of AP-1 expression as well as a higher cell proliferation rate were associated with ELF-EMF exposure. In contrast, ELF-EMF decreased COX-2 expression, PGE2 production, catalase activity and O2− production. Conclusions Mediators of inflammation, such as reactive nitrogen and PGE2, and keratinocyte proliferation are critical for the tissue regenerative processes. The ability of ELF-EMF to upmodulate NOS activities, thus nitrogen intermediates, as well as cell proliferation, and to downregulate COX-2 expression and the downstream intermediate PGE2, highlights the potential therapeutic role of ELF-EMF in wound healing processes.
N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs: Endocytosis, exocytosis and drug release
Authors: Ji Sun Park, Tae Hee Han, Kuen Yong Lee, Sung Soo Han, Jung Jin Hwang, Dae Hyuk Moon, Sang Yoon Kim, Yong Woo Cho
Journal: Journal of Controlled Release (2006)
Heparan Sulfate Proteoglycans Provide a Signal to Plasmodium Sporozoites to Stop Migrating and Productively Invade Host Cells
Authors: Alida Coppi, Rita Tewari, Joseph R. Bishop, Brandy L. Bennett, Roger Lawrence, Jeffrey D. Esko, Oliver Billker, Photini Sinnis
Journal: Cell Host & Microbe (2007)
Textbook of Rheumatology
Authors: George E. Ehrlich
Journal: JAMA (1993)

Little progress was made in the understanding of the rheumatic diseases between Sydenham and Musgrave, writing in the 17th century, and the modern epoch in 1948, heralded by rheumatoid factor, the LE cell, and corticosteroids. The 1927 edition of Cecil's classic medical textbook devotes 10 lines to lupus erythematosus and a page and a half to scleroderma, the former under diseases of the mouth, the latter under skin. Boyd's<i>Pathology</i>of 1934 says nothing about either disease. Even the 1940 edition of Comroe's<i>Arthritis</i>devotes but 13 lines to lupus, 13 to scleroderma, and 13 to periarteritis. Epiphenomena were described, connections were not even speculated about (except erroneously to tuberculosis), and underlying mechanisms remained unknown. O, brave new world! This is the fourth edition of one of the standards of the now recognized specialty of rheumatology to be published in just 12 years. Although a couple of pages shorter than
MicroRNA Mediation of Endothelial Inflammatory Response to Smooth Muscle Cells and Its Inhibition by Atheroprotective Shear Stress
Authors: Li-Jing Chen, Li Chuang, Yi-Hsuan Huang, Jing Zhou, Seh Hong Lim, Chih-I Lee, Wei-Wen Lin, Ting-Er Lin, Wei-Li Wang, Linyi Chen, Shu Chien, Jeng-Jiann Chiu
Journal: Circulation Research (2015)

In atherosclerotic lesions, synthetic smooth muscle cells (sSMCs) induce aberrant microRNA (miR) profiles in endothelial cells (ECs) under flow stagnation. Increase in shear stress induces favorable miR modulation to mitigate sSMC-induced inflammation.To address the role of miRs in sSMC-induced EC inflammation and its inhibition by shear stress.Coculturing ECs with sSMCs under static condition causes initial increases of 4 anti-inflammatory miRs (146a/708/451/98) in ECs followed by decreases below basal levels at 7 days; the increases for miR-146a/708 peaked at 24 hours and those for miR-451/98 lasted for only 6 to 12 hours. Shear stress (12 dynes/cm(2)) to cocultured ECs for 24 hours augments these 4 miR expressions. In vivo, these 4 miRs are highly expressed in neointimal ECs in injured arteries under physiological levels of flow, but not expressed under flow stagnation. MiR-146a, miR-708, miR-451, and miR-98 target interleukin-1 receptor-associated kinase, inhibitor of nuclear factor-κB kinase subunit-γ, interleukin-6 receptor, and conserved helix-loop-helix ubiquitous kinase, respectively, to inhibit nuclear factor-κB signaling, which exerts negative feedback control on the biogenesis of these miRs. Nuclear factor-E2-related factor (Nrf)-2 is critical for shear-induction of miR-146a in cocultured ECs. Silencing either Nrf-2 or miR-146a led to increased neointima formation of injured rat carotid artery under physiological levels of flow. Overexpressing miR-146a inhibits neointima formation of rat or mouse carotid artery induced by injury or flow cessation.Nrf-2-mediated miR-146a expression is augmented by atheroprotective shear stress in ECs adjacent to sSMCs to inhibit neointima formation of injured arteries.
Rapid Exclusion of Acute Myocardial Infarction in Patients With Undetectable Troponin Using a High-Sensitivity Assay
Authors: Richard Body, Simon Carley, Garry McDowell, Allan S. Jaffe, Michael France, Kennedy Cruickshank, Christopher Wibberley, Michelle Nuttall, Kevin Mackway-Jones
Journal: Journal of the American College of Cardiology (2011)