tbuckley/cabot-search huggingface dataset:
The Central Role of Sinusoidal Endothelial Cells in Hepatic Hypoxia–Reoxygenation Injury in the Rat
Authors: D A Samarasinghe, G C Farrell
Journal: Hepatology (1996)

The role of individual cell types in hepatic hypoxia–reoxygenation (reperfusion) injury has not been completely defined. We therefore examined the effects of hypoxia and hypoxia–reoxygenation on the viability of rat hepatocytes, Kupffer cells, and sinusoidal endothelial cells (SECs) in primary culture and whether direct exposure to hypoxia followed by reoxygenation activated Kupffer cells. Cultures of hepatocytes (purity &gt; 99%), Kupffer cells (97%), and endothelial cells (&gt; 93%) were established as single–cell types and as cocultures. Hypoxia was achieved by culturing cells under 95% N2/5% CO2, and cell viability was estimated by lactate dehydrogenase (LDH) leakage and Trypan blue exclusion. Kupffer cells and endothelial cells were more resistant to hypoxia than hepatocytes. Following 4–8 hours of hypoxia, reoxygenation accentuated cell death in endothelial cells. In contrast, reoxygenation did not accentuate cell death in hepatocytes or in resting Kupffer cells. The activation of Kupffer cells by the addition of lipopolysaccharide failed to alter their response to hypoxia–reoxygenation. The addition of phorbol myristate acetate to Kupffer cells stimulated the production of superoxide as expected, and the medium from these activated cells augmented the cellular injury of hypoxic hepatocytes. In contrast, hypoxia–reoxygenation did not stimulate Kupffer cells to produce superoxide or other hepatotoxic products. Moreover, Kupffer cells in coculture with hepatocytes did not augment hepatocyte injury after hypoxia–reoxygenation. Likewise, in cocultures of Kupffer cells and SECs, the presence of the Kupffer cell failed to enhance endothelial injury following hypoxia–reoxygenation, and these cocultures did not produce superoxide after reoxygenation. Thus, despite other evidence that Kupffer cells are activated in the intact liver during reperfusion injury, when present in isolation, only endothelial cells possess the innate capacity to undergo hypoxia–reoxygenation injury. Furthermore, changes in oxygen tension alone are not sufficient to activate Kupffer cells to secrete superoxides or other cell products that are toxic to hepatocytes or endothelial cells. It is concluded that SECs play a central role in hypoxia–reoxygenation injury, and the factors that activate Kupffer cells in vivo require further study.
“Rights” and “Fruit of Knowledge”
Authors: Adam Possner
Journal: Journal of Clinical Oncology (2013)

Adam Possner, General Internal Medicine, George Washington University, Washington, DC. Submitted July 11, 2013; accepted July 11, 2013; published online ahead of print at www.jco.org on September 9, 2013. Corresponding author: Adam Possner, MD, Assistant Professor, General Internal Medicine, Medical Faculty Associates, George Washington University, 2150 Pennsylvania Ave NW, Suite 5-416 North, Washington, DC 20037; e-mail: apossner@mfa.gwu.edu. JOURNAL OF CLINICAL ONCOLOGY A R T O F O N C O L O G Y VOLUME 31 NUMBER 30 OCTOBER 2
1137-97 Soluble CD40 ligand in predicting coronary artery disease and long-term outcomes in stable patients with angiographically defined disease states
Authors: Jason M Lappe, John F Carlquist, Jeffrey L Anderson, Matthew J Kolek, Benjamin D Horne, Bryant M Whiting, Heath U Jones, Robert R Pearson, Johnny Walker, Joseph B Muhlestein
Journal: Journal of the American College of Cardiology (2004)
B Cell Signaling and Tumorigenesis
Authors: Hassan Jumaa, Rudolf W. Hendriks, Michael Reth
Journal: Annual Review of Immunology (2004)

▪ Abstract The proliferation and differentiation of lymphocytes are regulated by receptors localized on the cell surface. Engagement of these receptors induces the activation of intracellular signaling proteins that transmit the receptor signals to distinct targets and control the cellular responses. The first signaling proteins to be discovered in higher organisms were the products of oncogenes. For example, the kinases Src and Abelson (Abl) were originally identified as oncogenes and were later characterized as important proteins for signal transduction in various cell types, including lymphocytes. Now, as many cellular signaling molecules have been discovered and ordered into certain pathways, we can better understand why particular signaling proteins are associated with tumorigenesis. In this review, we discuss recent progress in unraveling the molecular mechanisms of signaling pathways that control the proliferation and differentiation of early B cells. We point out the concepts of auto-inhibition and subcellular localization as crucial aspects in the regulation of B cell signaling.
Abstract 2441: mTOR complex 2 modulates glycosylation of CD147 via the hexosamine biosynthetic pathway
Authors: Chang-Chih Wu, Thomas Lynch, Joseph Moloughney, Aixa Navia, Olufunmilola Ibironke, Po-Chien Chou, Nicole M. Vega-Cotto, Sisi Zhang, Joshua Rabinowitz, Guy Werlen, Estela Jacinto
Journal: Cancer Research (2014)

Abstract Cell surface proteins transduce extracellular signals into the cell to control metabolism and growth. In turn, their expression is linked to nutrient availability and other growth signals by mechanisms that are poorly understood. The mammalian target of rapamycin (mTOR) regulates cell growth and metabolism and is part of two distinct protein complexes, mTOR complex 1 (mTORC1) and mTORC2. We found that mTORC2 is involved in the processing and maturation of cell surface receptors such as CD147. CD147 is a highly glycosylated receptor that has been linked to tumor progression via its role in activating matrix metalloproteinases and maturation of lactate transporters. In breast cancer cells, CD147 glycosylation is highly sensitive to glucose starvation and mTOR inhibition. In mTORC2-disrupted cells CD147 is misprocessed and occurs predominantly in a low glycosylated form. CD147 misprocessing can be partly rescued by addition of exogenous UDP-GlcNAc, the end product of the hexosamine biosynthetic pathway (HBP). However, UDP-GlcNAc cannot restore the abnormal growth and metabolism in mTORC2-disrupted cells due to defects in expression of other key metabolic enzymes in these cells. Our findings define a role for mTORC2 in regulating receptor glycosylation via the HBP and reveal a broader role for mTORC2 in controlling other biosynthetic pathways that become deregulated in cancer. Citation Format: Chang-Chih Wu, Thomas Lynch, Joseph Moloughney, Aixa Navia, Olufunmilola Ibironke, Po-Chien Chou, Nicole M. Vega-Cotto, Sisi Zhang, Joshua Rabinowitz, Guy Werlen, Estela Jacinto. mTOR complex 2 modulates glycosylation of CD147 via the hexosamine biosynthetic pathway. [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 2441. doi:10.1158/1538-7445.AM2014-2441
Whiskey Barrel Explosions— A Newly Discovered Danger
Authors: David W. Becker
Journal: JAMA (1980)

<h3>To the Editor.—</h3> A 9-year-old girl and her older sister were playing in the backyard when they became curious about the contents of a used whiskey barrel purchased that day by their father as a decorative yard ornament. A match was ignited to further illuminate the object. The explosion that followed was heard at the end of the block. The lid of the whiskey barrel was blown over the house into the front yard. The 9-year-old girl suffered first-, second-, and third-degree burns over her face, the anterior portion of her chest, and both hands. On the same day, two other children were seen in another emergency room in the same town for injuries received when a similar whiskey barrel exploded, throwing them against a fence. Neither of these children was seriously injured. I had previously been unaware of the hazard presented by used whiskey barrels, which are seen with
Effect of Breast Cancer After Ovarian Cancer on Mortality for<i>BRCA</i>Mutation Carriers
Authors: Alexander Liede, Ping Sun, Steven Narod
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
Innateness versus expectation in human fears: Causal versus maintaining factors?
Authors: Robert J. Edelmann
Journal: Behavioral and Brain Sciences (1995)

Abstract This commentary focuses upon two issues raised by Davey's target article: (1) whether there are certain core features of stimuli we learn to fear, rather than specific types of objects or situations, which implies some element of innateness; and (2) whether expectancy biases serve to maintain rather than generate anxiety.
Concise Textbook of Medicine
Authors: Frank D. Gray
Journal: JAMA (1991)

Textbooks serve medical education by closing the gaps in information gleaned from conferences, ward rounds, lecture courses, and medical journals. Usually the modern textbook can be contained in a single volume. However, the expansive and frequent changes in medical information have engendered colossal texts of several thousand pages. Cramming all of our knowledge of internal medicine into a single volume has become as difficult as stuffing all of the afflictions of the universe back into a mythological Pandora's box! By way of obviating this situation, an array of medical textbooks has appeared with titles intended to modify our expectations of the books' contents.<i>Concise Textbook of Medicine</i>is a revision and presumably a condensation of Kochar's earlier<i>Textbook of General Medicine</i>. The adjective<i>concise</i>purportedly defines the structure of the text so that we expect it to be shorter than standard. Other words that have been used to indicate shortened
Molecular Testing in Thyroid Cancer
Authors: Anne R. Cappola, Susan J. Mandel
Journal: JAMA (2013)

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
Antibiotic use with cholesterol lowering drugs may increase risk of cataracts
Authors: D. Spurgeon
Journal: BMJ (2002)

A study on rats, published in the November early release, online edition of the Journal of Lipid Research (www.jlr.org), confirms findings of a previous study in the Archives of Internal Medicine (2001;161:2021-6) that a single 10 day course of erythromycin taken concurrently with the cholesterol lowering drug simvastatin can double or triple the risk of cataracts.

“The take-home message for ophthalmologists is that they should enquire whether their patients are taking statins, and also one of the several drugs that are known to inhibit …
Management of Breast Cancer
Authors: George B. Sanders
Journal: JAMA (1975)

To the Editor.—  I read with great pleasure Dr Ralph Johnson's letter to the editor (230:1387, 1974). Dr Johnson has very accurately stated the case for considered judgment and thoughtful procrastination in the physician management of early, operable breast cancer.  Since most clinically detected breast cancers have been present in occult or semioccult form for many months, the helter-skelter approach from biopsy to mastectomy is not only unnecessary but in many cases harmful.  Until recent years the policy at one of our greatest midwestern surgical clinics, was to operate on all patients with a histologic diagnosis of breast cancer—regardless of stage, provided the patient could withstand the anesthesia and the operation. Thankfully, that period is past, but from the failure of radical operations in advanced stages of breast cancer, we have learned a great deal that we now put to good use.  Unfortunately, in many areas throughout the United States,
PKCθ promotes c-Rel–driven mammary tumorigenesis in mice and humans by repressing estrogen receptor α synthesis
Authors: Karine Belguise, Gail E. Sonenshein
Journal: Journal of Clinical Investigation (2007)

The vast majority of primary human breast cancer tissues display aberrant nuclear NF-κB c-Rel expression. A causal role for c-Rel in mammary tumorigenesis has been demonstrated using a c-Rel transgenic mouse model; however, tumors developed with a long latency, suggesting a second event is needed to trigger tumorigenesis. Here we show that c-Rel activity in the mammary gland is repressed by estrogen receptor α (ERα) signaling, and we identify an epigenetic mechanism in breast cancer mediated by activation of what we believe is a novel PKCθ-Akt pathway that leads to downregulation of ERα synthesis and derepression of c-Rel. ERα levels were lower in c-Rel–induced mammary tumors compared with normal mammary gland tissue. PKCθ induced c-Rel activity and target gene expression and promoted growth of c-Rel- and c-RelxCK2α–driven mouse mammary tumor–derived cell lines. RNA expression levels of PKCθ and c-Rel target genes were inversely correlated with ERα levels in human breast cancer specimens. PKCθ activated Akt, thereby inactivating forkhead box O protein 3a (FOXO3a) and leading to decreased synthesis of its target genes, ERα and p27Kip1. Thus we have shown that activation of PKCθ inhibits the FOXO3a/ERα/p27Kip1 axis that normally maintains an epithelial cell phenotype and induces c-Rel target genes, thereby promoting proliferation, survival, and more invasive breast cancer.
A COMPARATIVE STUDY OF LYMPH AND SERUM FERMENTS DURING PROTEIN SHOCK REACTIONS
Authors: Benjamin F. Davis, William F. Petersen
Journal: The Journal of Experimental Medicine (1917)

The relation of two phenomena involved in the mechanism of recovery following protein shock therapy is shown in these experiments to be due to changes that concern the lymph rather than the serum. The first of these, the increase in the rate of flow of the lymph, has been suggested by Teague and McWilliams as a possible factor in recovery from infection when due to bacteria proliferating in the lymph spaces and inaccessible to the antibodies of the serum (typhoid). By means of the protein shock, antibody-rich fluids (serum) are forced into the lymph channels. That the antibodies of the serum are augmented following the shock has been demonstrated by Culver (4). With this possibility in mind it is to be expected that bacterial infection not confined to the lymph spaces will not be influenced by shock therapy to the same extent. How far this holds true we are unable to state, although von Decastello (5) has called attention to the fact that while he was able to cause rapid lysis or a crisis in typhoid patients following the shock reaction, the injection of a similar amount of vaccine in typhus fever was without effect. The second factor, the great increase in the antiferment, is clearly due to the amount of the antiferment entering the general circulation through the lymph stream. This accounts for the marked fluctuations observed in the titer of the serum antiferment in patients following protein shock. If, for instance, the original titer of the lymph is less than that of the blood, the first flushing of the lymphatic current into the blood channel will tend to lower the titer of the serum, but with the increased amount in the lymph after the shock the titer of the serum will also increase. Bacteria proliferate best where the antiferment is absent, as Wright (6) has noted in his studies on war wounds, a fact that is also commonly applied in bacteriological technique when we employ ascitic fluids, containing relatively little antiferment, preferably to serum, in culture media. The increased lymph flow that follows the shock reaction would have value then, not only in forcing specific antibodies into the lymph channels, but 'in increasing the antiferment there as well, which would aid in checking the growth of bacteria.
STUDIES WITH THE ELECTRON MICROSCOPE OF VIRUS-HOST RELATIONSHIPS IN EHRLICH ASCITES TUMOR CELLS
Authors: Marlene Friedlaender, Dan H. Moore, Hilary Koprowski
Journal: The Journal of Experimental Medicine (1955)

Evidence is presented suggesting that anopheles A virus in the Ehrlich ascites tumor cell is harbored and propagated within the endoplasmic reticulum which in this system consists of an extensive canalicular network. The organization and differentiation of endoplasmic reticulum within the cell are described and the significance of such a location of virus is discussed.
A risk adapted approach to the governance of clinical trials
Authors: R. L. Smyth
Journal: BMJ (2011)

The research community needs to support a new initiative to reduce the regulatory burden

Over the past three to five years, there has been a barrage of criticism and dissent about the complex and bureaucratic systems that govern clinical research in the United Kingdom. This has culminated in sweeping recommendations, made in a report by the UK’s Academy of Medical Sciences,1 which have been endorsed by government.2 However, many of these recommendations (such as revision of the European Union Clinical Trials Directive and establishment of a health research regulatory agency) will take time and require new legislation, so initiatives to tackle these problems now are timely and welcome.

One such initiative is the implementation, since April 2011, by the Medicines and Healthcare Products Regulatory Agency (MHRA) of a risk adapted approach to the regulation of clinical trials of investigational medicinal products.3 This approach defines three types of trial according to the risks associated with the product—none (A), some (B), and markedly higher (C) than for standard medical care. A type A trial would typically investigate products used according to their licensed indications in the EU. A type B trial might be of a product, licensed in …
Long-Chain Fatty Acid Analogues Suppress Breast Tumorigenesis and Progression
Authors: Udi Gluschnaider, Rachel Hertz, Sarit Ohayon, Elia Smeir, Martha Smets, Eli Pikarsky, Jacob Bar-Tana
Journal: Cancer Research (2014)

Obesity and type 2 diabetes (T2D) are associated with increased breast cancer incidence and mortality, whereas carbohydrate-restricted ketogenic diets ameliorate T2D and suppress breast cancer. These observations suggest an inherent efficacy of nonesterified long-chain fatty acids (LCFA) in suppressing T2D and breast tumorigenesis. In this study, we investigated novel antidiabetic MEDICA analogues consisting of methyl-substituted LCFA that are neither β-oxidized nor esterified to generate lipids, prompting interest in their potential efficacy as antitumor agents in the context of breast cancer. In the MMTV-PyMT oncomouse model of breast cancer, in which we confirmed that tumor growth could be suppressed by a carbohydrate-restricted ketogenic diet, MEDICA treatment suppressed tumor growth, and lung metastasis, promoting a differentiated phenotype while suppressing mesenchymal markers. In human breast cancer cells, MEDICA treatment attenuated signaling through the STAT3 and c-Src transduction pathways. Mechanistic investigations suggested that MEDICA suppressed c-Src-transforming activity by elevating reactive oxygen species production, resulting in c-Src oxidation and oligomerization. Our findings suggest that MEDICA analogues may offer therapeutic potential in breast cancer and overcome the poor compliance of patients to dietary carbohydrate restriction.
Egregious Errors in the Management of Hypertension
Authors: Irvine H. Page
Journal: JAMA (1976)

NOW that hypertension has come of age and everyone is an expert, it is time to correct some common and often egregious errors in therapeutic management. These errors are, for the most part, simple and well known, but are frequently overlooked. The result: a considerable increase in the number of hypertensive persons is caused by false measurements and slipshod treatment of those who have hypertension. Few measurements are made more often than blood pressure, since the introduction of the auscultatory method in 1905. It is such a simple technique that results are seldom suspected of being inaccurate. We are now in the middle of a massive campaign to "identify" hypertensive persons. The federal government has pulled out all the stops, with scary statistics, threats, and importunings, to persuade our people that hypertension is the second greatest killer. "No one, not even you, is exempt." It also has racial overtones in
DOES EXERCISE FITNESS ATTENUATE THE OBESITY PARADOX?
Authors: Seth Uretsky, Azhar Supariwala, Supraja R. Yeturi, Gargi Thotakura, Pranitha Mantrala, Niriksha Sathyanarayana, Salim Memon, Deepa B. Iyer, Sirisha Kanneganti, Alan Rozanski
Journal: Journal of the American College of Cardiology (2011)
Salivary oestriol to progesterone ratio in relation to spontaneous labour
Authors: H. H G McGarriagle, G. C L Lachelin
Journal: BMJ (1984)

all original.I Indeed, this has been the conclusion of all previous studies, and that it is also observed in saliva can hardly be described as surprising.Thirdly, the only way in which it would be possible to prove any direct relation between the oestriol to progesterone ratio and the initiation of
THE DIAGNOSIS AND MANAGEMENT OF HEAD INJURIES
Authors: FRANCIS R. HOLBROOK
Journal: JAMA (1924)

Until a few years ago, the subject of cranial injuries resolved itself very largely into a discussion of fractures of the skull. At this time, fractures of the skull were thought to be an exceedingly grave condition. Many patients died, thereby supplying incontrovertible evidence in favor of this opinion. But, on the other hand, not a few recovered, and, be it known, at times these were apparently more seriously injured than some of those who died. The question naturally arises, "Why was this so?" In the light of our present-day knowledge of this subject, the answer to our question is not difficult. We now know that a fracture of the skull per se is not particularly serious and that it becomes a thing of real moment only when complicated by injury to the intracranial structures. This being so, in discussing the subject of head injuries, we must place special emphasis