tbuckley/cabot-search huggingface dataset:
In vitro binding of L-triiodothyronine to receptors in rat liver nuclei. Kinectics of binding, extraction properties, and lack of requirement for cytosol proteins.
Authors: M I Surks, D H Koerner, J H Oppenheimer
Journal: Journal of Clinical Investigation (1975)

Isolated hepatic nuclei from euthyroid rats were incubated with tracer (125I)L-triiodothyronine (T3) and increasing doses of nonradioactive T3 for 30 min at 37degrees C. The T3 bound specifically to nuclear sites increased with increasing T3 doses to a plateau, which represented the nuclear binding capacity, M. Addition of 1 mM KCN, NaF, dinitrophenol, oriodoacetate did not affect nuclear binding, indicating that active metabolism was not required. Kinetic studies showed that the nuclear sites were equilibrated with T3 within 30 min of incubation (one-half maximal binding at 3 min) and that the rate of release of T3 in vitro (0.058 min-1) was the same for endogenous T3 or for T3 bound to nuclei in vitro. Nuclear T3 resisted extraction with 0.14 M NaC1 buffered at pH 7.5, but both endogenous hormone and T3 bound in vitro were readily extracted by 0.4 M KC1 at pH 8.0. The elution profiles of endogenous and in vitro-bound T3 from Sephadex G-100 columns showed a common protein peak with a molecular weight of 60-65,000, assuming a globular protein. Scatchard analysis of in vitro displacement studies showed a single class of binding sites. Mean M equals 0.23 times 10-9 M or 0.85 ng T3 for nuclei isolated from 1 g of liver. Mean M closely corresponded to that anticipated from reported in vivo studies. The apparent association constant Ka for the nuclear sites, 5.55 times 108 M-1, was lower than in studies in vivo, probably attributable to the different ionic milieu of nuclei in the incubation buffer and in the intact cell. Thus, the identity of the nuclear T3 binding sites studied in vitro to those reported for endogenous hormone is demonstrated by similar binding capacities, release rates, analogue binding affinities (previously reported), and localization to chromatin nonhistone proteins of comparable molecular weight. The role of cytosol protein in nuclear binding was assessed by comparing binding parameters for extensively washed nuclei and nuclei incubated either with contaminating or added cytosol. No difference in Ka or M was found. Moreover, it was unlikely that specific cytosol proteins were already present in nuclei and functioned during incubation as a shuttle for T3, since Ka and M for nuclei obtained from athyreotic rats were similar to Ka and M for nuclei from euthyroid animals. Thus, an initial interaction between T3 and specific cytosol proteins does not appear to be a prerequisite for translocation of T3 to nuclear sites.
DIAGNOSIS OF DRUNKENNESS FROM THE EXCRETION OF ALCOHOL
Authors: S. Smith, C. P. Stewart
Journal: BMJ (1932)

method of chloroform anaesthesia has not been applied to diphtheria, in spite of the suggestive experiments of Billard in this connexion.Silnce February, 1930, we have tried the method in six cases, four without any success.We must frankly adnmit, however, that the treatment was applied only when the -patients were in extremis, so that no really satisfactory conclusions can be drawn from these cases.It is absolutely necessary to intervene early if the method is to be applied at all.As soon as nervous complications begin to appear chloroform anaesthesia should be at once combined with the administration of large doses of anti- diphtheritic serum, following the same technique as for tetanus, and giving the serum subcutaneously, intra- muscularly, or even, in the hypertoxic cases, intravenously.The intraspinal route might also be employed, although this, to our knowledge, has not yet been tried in diphtheria.Such are the general indications which we advise, and which we shall ourselves follow in the future.Encephalomyelitis and Poliomyelitis.-The phylactic method of chloroform anaesthesia might, by analogy, be used in encephalitis and poliomyelitis, but it would be necessary to have at our disposal corresponding specific serums.As far as poliomyelitis is concerned, Petit's anti- poliomyelitis serum might well be employed in this way, and may possibly give far better results than those obtained hitherto.Against encephalomyelitis there is, as yet, no specific serum, but it is interesting to note that urotropine, which was quickly found to have a favourable therapeutic effect in this condition, probably acts in the same phylactic way as chloroform.Urotropine becomes decomposed in the tissues and gives rise to formaldehyde, which displaces the toxins from the nerve centres and becomes fixed to the Lipoids of the cells.Billard's experiments with urotropine suggest this conclusion.
The Death of the Cancer Cell
Authors: Carlos Sonnenschein, Ana M. Soto
Journal: Cancer Research (2011)

For a century, the perception that there are qualitative differences between a normal cell and a cell belonging to a tumor has dominated discussions aimed at explaining cancer. However, an analysis of the experimental evidence suggests that individual normal cells and individual cancer cells share the same two fundamental behavioral properties, namely, proliferation and motility. Each individual cancer cell carries no recognizable molecules or structures that make them consistently distinguishable from normal cells. Herein, we argue that the differences between normal and cancerous states are instead identifiable at the tissue level of biological organization, and therefore, the search for identification of a cancer cell should be abandoned.
Celebrities help promote campaign to destigmatise mental illness
Authors: L. Eaton
Journal: BMJ (2009)

An £18m (€19; $24) campaign to tackle the discrimination and stigma that surrounds mental health appeared on television screens and in newspapers in England on Wednesday.

The Time to Change initiative is funded by Comic Relief and the National Lottery. Its aim is to tell the public that it is no longer acceptable to discriminate against people with a mental illness. The campaign includes an advertisement on the prime time television, during Coronation Street , which will continue to be shown on ITV for three weeks.

A series of press advertisements involving celebrities who have …
Grand Challenges in Global Mental Health: Integration in Research, Policy, and Practice
Authors: Pamela Y. Collins, Thomas R. Insel, Arun Chockalingam, Abdallah Daar, Yvonne T. Maddox
Journal: PLoS Medicine (2013)

This is one article in a five-part series providing a global perspective on integrating mental health.The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies.
T cell proliferation induced by anti-self-I-A-specific T cell hybridomas. Evidence of a T cell network.
Authors: D W Kennedy, C Russo, Y T Kim, M E Weksler
Journal: The Journal of Experimental Medicine (1986)

Allo-I-A-reactive T cell hybridomas were generated from MLR-activated lymphoblasts. Cloned hybridomas T1.203, T1.321, and T1.426 were stimulated by I-Ab determinants, as shown by their ability to secrete IL-2 in response to a panel of MHC-recombinant mice. T2.146, T2.205, and T3.116 were found to be specific for I-Ak determinants using a similar panel of MHC-recombinant mice. Inhibition of IL-2 secretion by anti-I-A mAb confirmed these data. Some I-Ab-specific hybrids stimulated the proliferation of T cells from C57BL/6 (H-2b) mice. Similarly, some I-Ak-specific hybrids stimulated the proliferation of T cells from C3H/HeJ (H-2k) mice. These hybrids expressed no detectable surface I-A, and stimulation of T cells was not inhibited by anti-I-A mAb. These results are consistent with the hypothesis that normal mice possess a population of T cells responsive to idiotypic determinants on anti-MHC class II T cell receptors.
Omega-3 Fatty Acids
Authors: Kenneth L. Radack
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 July 1988Omega-3 Fatty AcidsKenneth L. Radack, MDKenneth L. Radack, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-1-81 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:We read with interest Dr. von Schacky's (1) excellent perspective on marine omega-3 fatty acids. In general, we agree with his review but believe that one statement needs proper clarification. In discussing the difficulty with the choice of placebo controls in fish oil studies, Dr. von Schacky stated that olive oil can lower blood lipids, implying that olive oil may not be a suitable placebo. Unfortunately, the statement is a misleading generalization out of its original context, in which olive oil was used in very large dosages. This statement best applies to studies on large doses of...References1. von Schacky C. Prophylaxis of atherosclerosis with marine omega-3 fatty acids. Ann Intern Med. 1987;107:890-9. LinkGoogle Scholar2. MattsonGrundy FC. Comparison of effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in men. J Lipid Res. 1985;26:194-202. CrossrefMedlineGoogle Scholar3. Grundy C. Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cholesterol. N Engl J Med. 1986;314:745-8. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Kenneth L. Radack, MDAffiliations: University of Cincinnati Medical Center Cincinnati, OH 45267-0535 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEffects of fish oil supplementation in late pregnancy on blood pressure: a randomised controlled trialRandomised controlled trial of effect of fish-oil supplementation on pregnancy duration 1 July 1988Volume 109, Issue 1Page: 81-82KeywordsArmed forcesBloodFatty acidsLipidsOils ePublished: 1 December 2008 Issue Published: 1 July 1988 PDF downloadLoading ...
Abstract LB-322: The senescence-associated Sin3B protein promotes inflammation and pancreatic cancer progression
Authors: Maite Rielland, David Cantor, Richard Graveline, Cristina Hadju, Lisa Mara, George Miller, Gregory David
Journal: Cancer Research (2014)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We have previously demonstrated that the histone deacetylase associated SIN3B protein is essential for oncogene-induced senescence in cultured cells. Here we report that SIN3B is required for activated KRAS-induced senescence in vivo using a mouse model of pancreatic cancer. Surprisingly, impaired senescence caused by genetic inactivation of Sin3B is associated with delayed PDAC progression, correlating with an impaired inflammatory response. At the molecular level, SIN3B mediates KRAS-induced Il-1a production in a cell autonomous and senescence dependent manner. These results indicate for the first time that senescence-associated inflammation positively correlates with PDAC progression and identify SIN3B as a therapeutic target to inhibit inflammation-driven tumorigenesis. Citation Format: Maite Rielland, David Cantor, Richard Graveline, Cristina Hadju, Lisa Mara, George Miller, Gregory David. The senescence-associated Sin3B protein promotes inflammation and pancreatic cancer progression. [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 LB-322. doi:10.1158/1538-7445.AM2014-LB-322
Extracellular accumulation of bioactive substances during preparation and storage of various platelet concentrates
Authors: Lisbeth Edvardsen, Ellen Taaning, Bettina Dreier, Lisa Dalh Christensen, Tommie Mynster, Hans Jørgen Nielsen
Journal: American Journal of Hematology (2001)

Abstract Background Side effects of platelet transfusion may be associated with infusion of bioactive substances. We therefore studied extracellular accumulation of histamine, plasminogen activator inhibitor (PAI)‐1, vascular endothelial growth factor (VEGF), and interleukin (IL)‐6 during preparation and storage of various platelet concentrates. Methods Twenty buffy‐coat‐derived platelet pools (BCPC) were prepared and stored in platelet additive solutions (PAS). Twelve apheresis platelet (APC) units were prepared using the COBE Spectra LRS, and 14 were prepared using the Fenwal Amicus Separator. After preparation half of the content was drawn from each APC unit. The normal ranges of the substances were determined in plasma from all donors, and the extracellular concentrations of the substances were determined in supernatants collected on days 0, 1, 3, 5, and 7 of storage from all platelet preparations. Results The platelet counts were not significantly different in BCPC units and APC units. The BCPC units had a significantly higher white cell count than the APC units ( P &lt; 0.0001), but the count was significantly higher in the Amicus APC units than in the COBE APC units ( P &lt; 0.0001). The extracellular histamine concentration was significantly ( P &lt; 0.001) increased in BCPC units after preparation and without further increase during storage, while there was no accumulation of histamine in APC units. After preparation the PAI‐1 concentration was significantly ( P &lt; 0.02) higher in BCPC units than in APC units, but during storage PAI‐1 increased significantly ( P &lt; 0.05) more in APC units than in BCPC units. Similarly, VEGF concentration was significantly ( P &lt; 0.05) higher in BCPC units than in APC units after preparation. During storage, however, VEGF increased more in BCPC units compared with COBE Spectra APC units ( P &lt; 0.05), but compared with Amicus Separator APC units only for the first 3 days of storage. At days 5 and 7 of storage the VEGF concentration was significantly higher in the Amicus APC units than in the COBE APC units ( P &lt; 0.05). IL‐6 was not detectable in any of the concentrates after preparation or during storage. Conclusion Platelet concentrates prepared by the apheresis method may contain less white cell derived bioactive substances than platelet concentrates prepared by the buffy‐coat method. However, a substantial storage time dependent platelet derived bioactive substance accumulation takes place in all platelet concentrates tested, presumably due to platelet disintegration. Am. J. Hematol. 67:157–162, 2001. © 2001 Wiley‐Liss, Inc.
Metabolic actions of FGF21: molecular mechanisms and therapeutic implications
Authors: Xuan Ge, Yu Wang, Karen SL Lam, Aimin Xu
Journal: Acta Pharmaceutica Sinica B (2012)

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor alpha (PPARα). A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.
Abstract 1048: Homogenous, bioluminescent and HTS formatted assay for quantization of ADP production in kinase and ATPase reactions
Authors: Said Goueli, Kevin Hsiao, Marina Zdanovoskaia, Jolanta Vidugiriene, Hicham Zegzouti
Journal: Cancer Research (2010)

Abstract Because of its versatility (all types of substrates), robustness (Z’&amp;gt;0.8), rapid performance, and its ease of use, the luminescence based Kinase GloTM assays platform have gained wide acceptance in many drug screening programs for protein kinase inhibitors. We have attempted to extend our strategy by now monitoring ADP product formation in the kinase reaction. The new assay we developed (ADP Glo) maintains all the positive features of Kinase GloTM such as universality, and applicability to all kinds of kinase substrates regardless of their nature with no prior modification (peptides, protein, polymer, lipids, and sugars) but In stead of measuring ATP depletion, it monitors ADP production. It detects ADP at early stages of enzyme reactions with very high signal to background (SB) ratio. It can be run at a wide range of ATP concentrations (low micromolar to millimolar), is sensitive to low ADP concentrations (0.1 pmol), and it can be carried out in high density plate formats. This assay is robust and homogenous, and does not require antibodies or custom synthesized substrates. It is ideal to search for optimal substrates in a collection of peptides, proteins, or lipids in a single assay format, and to screen for ATP competitive and Non competitive inhibitors. Because of the high dynamic range and more importantly, the high SB values even at low % ATP to ADP conversion, the assay allows the use of low amounts of enzyme during high-throughput screening. Evaluation of this assay in a screen of a large chemical library showed minimal false hits attesting to the quality of this system. The ADP-GloTM assay is applicable to all types of kinases, ATPases, multidrug resistant proteins such as MDR1-Pgp, helicases, topoisomerases, and heat shock proteins and as well as many other ADP producing enzyme reactions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1048.
Liver acid sphingomyelinase inhibits growth of metastatic colon cancer
Authors: Yosuke Osawa, Atsushi Suetsugu, Rie Matsushima-Nishiwaki, Ichiro Yasuda, Toshiji Saibara, Hisataka Moriwaki, Mitsuru Seishima, Osamu Kozawa
Journal: Journal of Clinical Investigation (2013)

Acid sphingomyelinase (ASM) regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate (S1P). These sphingolipids regulate carcinogenesis and proliferation, survival, and apoptosis of cancer cells. However, the role of ASM in host defense against liver metastasis remains unclear. In this study, the involvement of ASM in liver metastasis of colon cancer was examined using Asm-/- and Asm+/+ mice that were inoculated with SL4 colon cancer cells to produce metastatic liver tumors. Asm-/- mice demonstrated enhanced tumor growth and reduced macrophage accumulation in the tumor, accompanied by decreased numbers of hepatic myofibroblasts (hMFs), which express tissue inhibitor of metalloproteinase 1 (TIMP1), around the tumor margin. Tumor growth was increased by macrophage depletion or by Timp1 deficiency, but was decreased by hepatocyte-specific ASM overexpression, which was associated with increased S1P production. S1P stimulated macrophage migration and TIMP1 expression in hMFs in vitro. These findings indicate that ASM in the liver inhibits tumor growth through cytotoxic macrophage accumulation and TIMP1 production by hMFs in response to S1P. Targeting ASM may represent a new therapeutic strategy for treating liver metastasis of colon cancer.
A Father's Letter to a New Intern
Authors: M. G. Jacoby
Journal: JAMA (1981)

Dear Dave,  Your mother and I are very glad to know that you are now settled in and enjoying your work. I can understand why you have lost weight. At least your 100-hour week will give you a maximal clinical exposure and will be good training for you when you get out into practice. It's what medicine is made of.  Are you talking at your patients or are you letting them talk to you? Difficult, isn't it, to give them all the time they need, difficult when your training has been to be dynamic, to do, to produce, rather than to adopt a passive role? Please do not try bluff heartiness as a substitute for genuine concern, although we all do so at times. It is difficult to sit and listen but it works. If you ask questions that demand little more than yes or no as an answer, you
Molecular Signatures of Breast Cancer — Predicting the Future
Authors: Anne Kallioniemi
Journal: New England Journal of Medicine (2002)

Breast cancer affects about 10 percent of women in Western countries and is still a major cause of illness and death. Most patients with lymph-node–negative disease (i.e., with no evidence that cancer cells have spread beyond the primary tumor) can be effectively treated with surgery and local radiation. Patients with more aggressive disease can benefit from adjuvant chemotherapy or hormone therapy and are currently identified according to a combination of criteria1,2: age, the size of the tumor, axillary-node status, the histologic type and pathological grade of cancer, and hormone-receptor status. The ability of these criteria to predict disease . . .
T‐cell receptor gamma and delta gene rearrangements and junctional region characteristics in south Indian patients with T‐cell acute lymphoblastic leukemia
Authors: Natarajan Sudhakar, Nirmala Karunakaran Nancy, Kamalalayam Raghavan Rajalekshmy, Ganapathi Ramanan, Thangarajan Rajkumar
Journal: American Journal of Hematology (2006)

Abstract Clonal T‐cell receptor (TCR) gamma and delta gene rearrangements were studied in 40 T‐ALL cases (pediatrics, 29; adults, 11) using PCR with homo‐heteroduplex analysis. At least one clonal TCRG or TCRD rearrangement was detected in 34 (85%) cases. TCR gamma ( TCRG ) rearrangement was detected in 25 (62.5%) cases that included 16 (55%) pediatrics and 9 (81.8%) adults. TCR delta (T CRD ) rearrangement was detected in 14/40 (35%) cases, which included 12 (41%) pediatrics and 2 (18%) adults. The frequency of VγI‐Jγ1.3/2.3 was significantly more in adults than pediatrics (81.8% vs. 41.3%, P = 0.02). In TCRD , Vδ1‐Jδ1 was rearranged in 10 (25%) cases. The surface membrane CD3 positive cases are significantly associated with absence of TCRD rearrangements (surface membrane CD3+ TCRδ− 84% vs. surface membrane CD3− TCRδ− 48%, P value = 0.03). Junctional region sequence analyzed with 10 cases each, of TCRG and TCRD , revealed an average junctional region of 7.4 nucleotides (range 2–18 nucleotides) in TCRG and 27 nucleotides (range 14–42 nucleotides) in TCRD‐ complete rearrangements. In TCRG , trimming at the ends of Vγ and Jγ germline nucleotides resulted in deletion, on an average of 9.2 nucleotides. In TCRD , deletion of nucleotides of the Vδ and Jδ gene segments on an average was 3.5 nucleotides. The junctional region of TCRD is more diverse than TCRG; nevertheless, the frequency of TCRG was more than that of TCRD and hence we rely more on TCRG clonal markers to quantitate the minimal residual disease in T‐ALL. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
Effects of pH-neutral, bicarbonate-buffered dialysis fluid on peritoneal transport kinetics in children
Authors: Claus P. Schmitt, Börje Haraldsson, Rouven Doetschmann, Mirjam Zimmering, Christine Greiner, Michael Böswald, Günter Klaus, Jutta Passlick-Deetjen, Franz Schaefer
Journal: Kidney International (2002)