tbuckley/cabot-search huggingface dataset:
Growth Assessment of Hepatic Venous Malformations—Reply
Authors: Hani Y. Hasan, J. Louis Hinshaw, Emily R. Winslow
Journal: JAMA Surgery (2015)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Retroviral vector-mediated hypoxia-regulated neurotrophin-3 gene transfer reduces apoptosis induced by hypoxia in PC12 cells
Authors: Junfeng Zhang, Qindong Shi, Xinlin Chen, Pengbo Yang, Cunfang Qi, Jianshui Zhang, Haixia Lu, Lingyu Zhao, Bingqiao Zhao, Ping Zheng, Yong Liu
Journal: Molecular Neurodegeneration (2012)

Background Gene therapy for ischemic diseases is a prospective strategy. However, excessive expression of therapeutic genes may produce undesired side effects. Recently, multiple copies hypoxia response elements (HRE) were developed to conditionally regulate gene expression under hypoxia. As a nerve growth factor, Neurotrophin3 (NT-3) possesses neural protect effects either in vitro or in vivo. To explore hypoxia-controlled NT-3 expression, we constructed a recombinant retrovirus vector with 5HRE and NT-3, and generated a gene transferred cell line PC12-5HRE-NT3 to determine effects of conditionally expressed NT-3 on apoptosis induced by hypoxia in PC12 cells.
Stable transfectants of human MCF-7 breast cancer cells with increased levels of the human folate receptor exhibit an increased sensitivity to antifolates.
Authors: K N Chung, Y Saikawa, T H Paik, K H Dixon, T Mulligan, K H Cowan, P C Elwood
Journal: Journal of Clinical Investigation (1993)

A major problem in cancer therapy is tumor drug resistance such as is found with antifolates (e.g., methotrexate [MTX]). We are specifically interested in the role of the human folate receptor (hFR) in MTX resistance. To investigate whether transfection of hFR results in increased MTX uptake and increased drug sensitivity, human mammary carcinoma (MCF-7) cells and Chinese hamster ovary cells (CHO) (cells which do not express detectable levels of hFR) were transfected with hFR cDNA. Stable human mammary carcinoma and Chinese hamster ovary transfectants expressing high levels of hFR were selected for further analysis. Transfected cells which express increased levels of hFR grow more rapidly than mock transfected or wild type cells in media containing physiologic concentrations of folates. The hFR expressed by these cells is sorted to the plasma membrane and is functional as determined by cell surface binding of a radiolabeled folic acid derivative and by internalization of [3H]methotrexate. The stable transfectants that express increased levels of hFR are also more sensitive to MTX in physiologic concentrations of folates. We conclude that increased expression of hFR by human mammary carcinoma and Chinese hamster ovary cells cultured under these conditions results in an enhanced growth rate, increased folic acid binding, and increased MTX uptake and cytotoxicity.
FLUOROSCOPY ASSISTED SCORING OF MYOCARDIAL HYPOPERFUSION AS NOVEL PREDICTOR OF MORTALITY AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH ST ELEVATION MYOCARDIAL INFARCTION
Authors: Stefan Biesbroek, Sebastiaan Roos, Jack van der Gragt, Paul Teunissen, Max van Hout, Otto Kamp, Niels Van Royen
Journal: Journal of the American College of Cardiology (2014)
G-Protein–Coupled Receptor Kinase Interacting Protein-1 Is Required for Pulmonary Vascular Development
Authors: Jinjiang Pang, Ryan Hoefen, Gloria S. Pryhuber, Jing Wang, Guoyong Yin, R. James White, Xiangbin Xu, Michael R. O'Dell, Amy Mohan, Heidi Michaloski, Michael P. Massett, Chen Yan, Bradford C. Berk
Journal: Circulation (2009)

Background— The G-protein–coupled receptor kinase interacting protein-1 (GIT1) is a multidomain scaffold protein that participates in many cellular functions including receptor internalization, focal adhesion remodeling, and signaling by both G-protein–coupled receptors and tyrosine kinase receptors. However, there have been no in vivo studies of GIT1 function to date. Methods and Results— To determine essential functions of GIT1 in vivo, we generated a traditional GIT1 knockout mouse. GIT1 knockout mice exhibited ≈60% perinatal mortality. Pathological examination showed that the major abnormality in GIT1 knockout mice was impaired lung development characterized by markedly reduced numbers of pulmonary blood vessels and increased alveolar spaces. Given that vascular endothelial growth factor (VEGF) is essential for pulmonary vascular development, we investigated the role of GIT1 in VEGF signaling in the lung and cultured endothelial cells. Because activation of phospholipase-Cγ (PLCγ) and extracellular signal-regulated kinases 1/2 (ERK1/2) by angiotensin II requires GIT1, we hypothesized that GIT1 mediates VEGF-dependent pulmonary angiogenesis by modulating PLCγ and ERK1/2 activity in endothelial cells. In cultured endothelial cells, knockdown of GIT1 decreased VEGF-mediated phosphorylation of PLCγ and ERK1/2. PLCγ and ERK1/2 activity in lungs from GIT1 knockout mice was reduced postnatally. Conclusions— Our data support a critical role for GIT1 in pulmonary vascular development by regulating VEGF-induced PLCγ and ERK1/2 activation.
Bioluminescent Imaging of HPV-Positive Oral Tumor Growth and Its Response to Image-Guided Radiotherapy
Authors: Rong Zhong, Matt Pytynia, Charles Pelizzari, Michael Spiotto
Journal: Cancer Research (2014)

The treatment paradigms for head and neck squamous cell cancer (HNSCC) are changing due to the emergence of human papillomavirus (HPV)-associated tumors possessing distinct molecular profiles and responses to therapy. Although patients with HNSCCs are often treated with radiotherapy, preclinical models are limited by the ability to deliver precise radiation to orthotopic tumors and to monitor treatment responses accordingly. To better model this clinical scenario, we developed a novel autochthonous HPV-positive oral tumor model to track responses to small molecules and image-guided radiation. We used a tamoxifen-regulated Cre recombinase system to conditionally express the HPV oncogenes E6 and E7 as well as a luciferase reporter (iHPV-Luc) in the epithelial cells of transgenic mice. In the presence of activated Cre recombinase, luciferase activity, and by proxy, HPV oncogenes were induced to 11-fold higher levels. In triple transgenic mice containing the iHPV-Luc, K14-CreER(tam), and LSL-Kras transgenes, tamoxifen treatment resulted in oral tumor development with increased bioluminescent activity within 6 days that reached a maximum of 74.8-fold higher bioluminescence compared with uninduced mice. Oral tumors expressed p16 and MCM7, two biomarkers associated with HPV-positive tumors. After treatment with rapamycin or image-guided radiotherapy, tumors regressed and possessed decreased bioluminescence. Thus, this novel system enables us to rapidly visualize HPV-positive tumor growth to model existing and new interventions using clinically relevant drugs and radiotherapy techniques.
Smad2 Protects against TGF-β/Smad3-Mediated Renal Fibrosis
Authors: Xiao Ming Meng, Xiao Ru Huang, Arthur C.K. Chung, Wei Qin, Xinli Shao, Peter Igarashi, Wenjun Ju, Erwin P. Bottinger, Hui Yao Lan
Journal: Journal of the American Society of Nephrology (2010)

Smad2 and Smad3 interact and mediate TGF-β signaling. Although Smad3 promotes fibrosis, the role of Smad2 in fibrogenesis is largely unknown. In this study, conditional deletion of Smad2 from the kidney tubular epithelial cells markedly enhanced fibrosis in response to unilateral ureteral obstruction. <i>In vitro</i>, Smad2 knockdown in tubular epithelial cells increased expression of collagen I, collagen III, and TIMP-1 and decreased expression of the matrix-degrading enzyme MMP-2 in response to TGF-β1 compared with similarly treated wild-type cells. We obtained similar results in Smad2-knockout fibroblasts. Mechanistically, Smad2 deletion promoted fibrosis through enhanced TGF-β/Smad3 signaling, evidenced by greater Smad3 phosphorylation, nuclear translocation, promoter activity, and binding of Smad3 to a collagen promoter (COL1A2). Moreover, deletion of Smad2 increased autoinduction of TGF-β1. Conversely, overexpression of Smad2 attenuated TGF-β1–induced Smad3 phosphorylation and collagen I matrix expression in tubular epithelial cells. In conclusion, in contrast to Smad3, Smad2 protects against TGF-β–mediated fibrosis by counteracting TGF-β/Smad3 signaling.
The Role of the Registered Nurse
Authors: Allan J. Ryan
Journal: JAMA (1966)

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
Abstract 2274: RIP1-mediated sensitivity to SN38 induced by TNF in colon adenocarcinoma cell lines
Authors: Lucia Cabal-Hierro, Peter J. O'Dwyer
Journal: Cancer Research (2014)

Abstract BACKGROUND: TNF is a dual role cytokine involved both in cell death and survival that is expressed in the tumor microenvironment. However, little is known about the molecular events that mark the biological outcomes of such opposite biological events. Recently, the protein kinase RIP1 has been identified as a new intermediate involved in the responses activated after DNA damage induction. PURPOSE: In this study we investigated how TNF modulates the sensitivity to SN38 in colon cancer cell lines. We focused further on HT29- and HCT116-derived cell lines in which RIP1 or RIP3 proteins expression were stably downregulated. RESULTS: We found that TNF increases cellular sensitivity to different chemotherapeutic drugs under both normoxic and hypoxic conditions over a panel of different colon adenocarcinoma cell lines. Combinations with SN38 were highly synergistic. In HT29 and HCT116 cell lines (TNF resistant and TNF sensitive respectively), we analyzed this interaction by studying P-H2-AX induction, cell proliferation (clonogenic assays and BrdU incorporation) and cell cycle distribution. To study the role of RIP1 and RIP3 on the biological responses triggered by SN38, HT29- and HCT116-derived cell lines expressing low levels of RIP1 and RIP3 were analyzed. While knockdown of RIP3 had no effect on SN38 cytotoxicity, RIP1 down regulation produced a 2.5-fold increased resistance to SN38 under hypoxic conditions. This change in SN38 sensitivity also correlated with a reduction in the levels of P-H2-AX in the presence of TNF, suggesting dependence of DNA damage induction by SN38 on RIP1. CONCLUSIONS: These data suggest that RIP1 may be a key intermediate in determining cell death following SN38 treatment. Additional studies in tumor samples are in progress. Citation Format: Lucia Cabal-Hierro, Peter J. O'Dwyer. RIP1-mediated sensitivity to SN38 induced by TNF in colon adenocarcinoma cell lines. [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 2274. doi:10.1158/1538-7445.AM2014-2274
AMPK, insulin resistance, and the metabolic syndrome
Authors: Neil B. Ruderman, David Carling, Marc Prentki, José M. Cacicedo
Journal: Journal of Clinical Investigation (2013)

Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic syndrome, as are central adiposity, dyslipidemia, and a predisposition to type 2 diabetes, atherosclerotic cardiovascular disease, hypertension, and certain cancers. Regular exercise and calorie restriction have long been known to increase insulin sensitivity and decrease the prevalence of these disorders. The subsequent identification of AMP-activated protein kinase (AMPK) and its activation by exercise and fuel deprivation have led to studies of the effects of AMPK on both IR and metabolic syndrome–related diseases. In this review, we evaluate this body of literature, with special emphasis on the hypothesis that dysregulation of AMPK is both a pathogenic factor for these disorders in humans and a target for their prevention and therapy.
Use of a guideline based questionnaire to audit hospital care of acute asthma.
Authors: D Bell, A J Layton, J Gabbay
Journal: BMJ (1991)

OBJECTIVES--To design an audit questionnaire and pilot its use by an audit assistant to monitor inpatient management of acute asthma and to compare the care given by chest physicians and general physicians. DESIGN--Retrospective review by a chest physician and audit assistant of a random sample of 76 case records of patients by a criterion based questionnaire developed from hospital guidelines on management of acute asthma. SETTING--One district general hospital. PATIENTS--76 adult patients with acute asthma: 38 admitted with a relevant primary diagnosis between April 1988 and March 1989 and a further 38 admitted through the accident and emergency department between April 1989 and March 1990. MAIN OUTCOME MEASURES--Conformity with recognised standards for assessment and management of acute asthma before and after the audit and by chest physicians and general physicians. RESULTS--Age and sex did not differ significantly between the different groups of patients. Overall, deviations from the guidelines occurred in recording measures of severity of asthma, emergency treatment with beta 2 agonists (60/76, 79%) and steroids (43/76, 57%), and prescription of antibiotics in accordance with at least one criterion of the guidelines (29/45, 64%). Chest physicians were more rigorous than general physicians in recording severity measures, especially serum potassium concentration (chi 2 = 3.6, df = 1, p = 0.06), emergency steroid treatment within the correct period (chi 2 = 3.9, df = 1, p = 0.05), and referral for follow up at an outpatient chest clinic. Recording of arterial blood gas tensions improved significantly between the 1988-9 and 1989-90 samples (chi 2 = 7.0, df = 1, p = 0.08). CONCLUSIONS--The questionnaire proved easy to use for both doctor and audit assistant. The audit improved few standards of care and emphasises the need for further reinforcement and feedback.
Funding for Research
Authors: Marjorie A. Bowman
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The report of the results of the recent Society of Teachers of Family Medicine and North American Primary Care Research Group survey of family medicine residencies and university academic units (1983;249:63) provides interesting and useful data for the field of family medicine, which is attempting to develop a stronger research base. I previously researched a similar topic, using different methods but getting similar results.<sup>1</sup>A computer search of Public Health Service research grants disclosed that funding for research in the departmental focus of family medicine activity at medical schools came from 11 different organizational entities within the PHS, with 41 projects funded in 1980, thirty-three of which were supported by the National Institutes of Health (NIH). Another five projects were funded by the National Center for Health Services Research. Fifteen different medical schools received funds in 1979 or 1980 in the amount of about $4 million
Intracranial extramedullary hematopoiesis in β°-thalassemia/hemoglobin E disease
Authors: Suthat Fucharoen, Chalermchai Tunthanavatana, Dhira Sonakul, Prawase Wasi
Journal: American Journal of Hematology (1981)

Abstract A 27‐year‐old woman with β‐thalassemia/hemoglobin E disease presented with an intracranial mass of 10 × 9 × 1.2 cm firmly attached to the dura and the falx cerebri extending over the central part of both hemispheres, with pressure atrophy of the underlying brain. Histopathologic examination revealed that the mass consisted entirely of hematopoietic cells. We have seen 1,315 cases with β‐thalassemia/hemoglobin E, but this was the first case with intracranial extramedullary hematopoietic mass.
Delayed Arterial Healing and Increased Late Stent Thrombosis at Culprit Sites After Drug-Eluting Stent Placement for Acute Myocardial Infarction Patients
Authors: Gaku Nakazawa, Aloke V. Finn, Michael Joner, Elena Ladich, Robert Kutys, Erik K. Mont, Herman K. Gold, Allen P. Burke, Frank D. Kolodgie, Renu Virmani
Journal: Circulation (2008)

The long-term safety of drug-eluting stents (DES) for acute myocardial infarction (AMI) remains uncertain. Using autopsy data, we evaluated the pathological responses of the stented segment in patients treated with DES for AMI and compared with patients with stable angina.From the CVPath Registry of 138 DES autopsies, we identified 25 patients who presented with AMI and had an underlying necrotic core with a ruptured fibrous cap. Twenty-six patients who had stable angina with thick-cap fibroatheroma treated by DES were selected as controls. Histomorphometric analysis was performed in patients with >30-day stent duration. We compared the response to stenting at the culprit site in these 2 groups and to nonculprit sites within each stent. Late stent thrombosis was significantly less frequent in stable (11%) than in AMI (41%; P=0.04) patients. Although neointimal thickness in the AMI culprit site was significantly less (median, 0.04 mm; interquartile range [IQR], 0.02 to 0.09 mm), the prevalence of uncovered struts (49%; IQR, 16% to 96%), fibrin deposition (63+/-28%), and inflammation (35%; IQR, 27% to 49%) were significantly greater compared with the culprit site in stable patients (neointimal thickness: 0.11 mm [IQR, 0.07 to 0.21 mm], P=0.008; uncovered struts: 9% [IQR, 0% to 39%], P=0.01; fibrin: 36+/-27%, P=0.008; inflammation, 17% [IQR, 7% to 25%], P=0.003) and the nonculprit site within each stent.Vessel healing at the culprit site in AMI patients treated with DES is substantially delayed compared with the culprit site in patients receiving DES for stable angina, emphasizing the importance of underlying plaque morphology in the arterial response to DES. Our data suggest an increased risk of thrombotic complications in patients treated with DES for AMI.
349 INCIDENCE OF APBEC3B GENE DELETION IN JAPANESE POPULATION AND SIGNIFICANCE IN HEPATITIS B VIRUS INFECTION AND G TO A HYPERMUTATION OF THE VIRUS GENOME
Authors: H. Abe, H. Ochi, T. Maekawa, M. Tsuge, M. Imamura, N. Hiraga, S. Takahashi, Y. Fujimoto, K. Chayama
Journal: Journal of Hepatology (2009)
Derrick Henry Randall
Authors: W. Leigh
Journal: BMJ (2015)

Derrick Henry Randall was born in Luton, the second son of Joseph and Rose Randall. His elder brother, Frederick James (“Jim”) was killed in action during the Fall of Singapore in 1942. Derrick won a scholarship to Ashton Grammar School in Dunstable and, on leaving, decided to study medicine. He started his preclinical studies at King’s College London in September 1938 and his clinical training at Westminster Hospital in September 1940, and was evacuated for part of this time to Glasgow. By taking and passing the conjoint examination, rather than waiting for his university degree, he was able to qualify six months early, in April 1943.

Once qualified, he was called up for the army and in November 1943 was awarded his commission with the Black Watch, later transferring to the 1st Airlanding Anti-Tank Battery as regimental medical officer.

After preparing for numerous operations, which were aborted at the last minute, he first saw action in “Operation Market Garden,” when he was airlifted into Arnhem, hitching a lift on a jeep loaded in a Horsa glider. He ended up, at the age of just 23, running a divisional HQ regimental aid post in the basement of the Hartenstein Hotel in Oosterbeek from the beginning to the end of the battle. …
Durability of ceramic and novel man-made mineral fibers.
Authors: I C Alexander, R C Brown, G A Jubb, P Pickering, J A Hoskins
Journal: Environmental Health Perspectives (1994)

In vitro solubility testing is an important means of assessing the likely behavior of fibers that are respired and accumulate in the lung. The problem has been that such tests often do not mirror the dissolution and removal mechanisms seen in vivo. Comparison of iron and silica solubility values of various types of mineral fiber showed no obvious correlation. Treating a mineral fiber containing high levels of calcium with normal balanced salt solutions produces a precipitate of calcium phosphate on the fiber surface. This deposit was not seen in fibers isolated from the lung of exposed animals. New solutions have been developed and with variations in the methods of exposing fibers, results similar to those seen in vivo have been obtained. Suitable fluid phases have been examined in static and flow-through systems. The relationship of solubility to biological activity is discussed.
Detection of Invasive Colon Cancer Using a Novel, Targeted, Library-Derived Fluorescent Peptide
Authors: Kimberly Kelly, Herlen Alencar, Martin Funovics, Umar Mahmood, Ralph Weissleder
Journal: Cancer Research (2004)

Abstract Sensitive methods to detect the earliest forms of colorectal cancers remain a challenge despite the development of serum and stool biomarkers. We reasoned that fluorescent affinity ligands derived from library screens can be developed to improve the detection and localization of early malignant lesions by endoscopy. We have developed an imaging agent for real-time endoscopic tumor detection in a murine model using a previously identified phage library-derived colon cancer-specific cyclic peptide and fluorescent moieties. The modified peptide had a 24 minute blood half life and tumoral accumulation was 6.9% of injected dose/g, ∼7-fold higher than a scrambled control peptide. Orthotopic colonic tumors (HT29) were readily detectable by fluorescence endoscopy even when tumors were submucosal. These results show proof-of-principle that disease-specific library-derived fluorescent probes can be rapidly developed for use in the early detection of cancers by optical means.