tbuckley/cabot-search huggingface dataset:
Abstract 3305: Trim3, the human homolog of Drosophila brat, regulates asymmetric division in glioblastoma stem cells
Authors: Gang Chen, Y Rong, F Rahman, C Tucker-Burden, C Hadjipanayis, E G. Van Meir, D J. Brat
Journal: Cancer Research (2011)

Abstract Glioblastoma (GBM) is the most common and malignant primary brain tumor. The recently described stem cell component of malignant gliomas is biologically critical, yet mechanisms that underlie its regulation are not understood. Mutations in Drosophila Brain tumor (brat) result in a massively enlarged fly brain that consists of a neuroblast cell population with neoplastic growth properties that has lost the ability to divide asymmetrically. Brat has been shown to promote asymmetric cell division and direct neural differentiation at least partially through its translational suppression of Myc. Here we investigated the role of brat homologs for their regulation of glioma behavior, especially as related to asymmetric division of glioma stem cells. We found that the human brat homolog, Trim3, is highly expressed in normal brain and that a substantial subset of GBMs (25-30%) show loss of heterozygosity (LOH) of chromosome 11p15.5, the site of Trim3. Trim3 expression was markedly reduced in human GBM cell lines compared to human astrocytes and reduced in human GBMs specimens compared to normal brain, consistent with results from mining existing gene expression data sets (oncomine). Since Drosophila brat is critical to neural differentiation and regulates Myc, we explored whether human Trim3 might regulate glioma stem cell properties by its regulation of Myc. We found that the forced expression of Trim3 in human GBM cell lines led to reduced Myc protein expression. This inverse relationship between Trim3 and Myc also held true in GBM samples. We used a lentiviral system to stably express Trim3 in GBM cell lines and neurospheres and found that Trim3 expression reduced glioma proliferation and colony formation in vitro and also led to smaller and less frequent neuropheres. In vivo, Trim3 suppressed tumor growth in an orthotopic xenograft model and led to prolonged survival. Trim3 expression was associated with reduced expression of nestin and CD133 by GBM neurosphere cultures, suggesting that its loss may enrich the stem cell compartment. Moreover, Trim3 expression by neurosphere stem cells favored a pattern of asymmetric cell division in GBM. Thus, Trim3 appears to direct asymmetric cell division in glioma stem cells and its loss is associated with stem cell enrichment and greater biologic potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3305. doi:10.1158/1538-7445.AM2011-3305
Tolbutamide: Men from Mars
Authors: GEORGE F. BROCKMAN
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 December 1971Tolbutamide: Men from MarsGEORGE F. BROCKMAN III, M.D.GEORGE F. BROCKMAN III, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-6-974_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Schwartz's account, "The Tolbutamide Controversy: A Personal Perspective" (Ann Intern Med 75:303-306, 1971), is a valuable insight for the thousands of us who do not specialize in diabetes but who undertake to care for patients with maturity-onset diabetes. With the diabetologists sharply divided into two armed camps, physicians whom we know to be sincere and competent are engaged in rancorous public debate bearing little resemblance to reasoned scientific discourse. It is refreshing to find this reasonable presentation by a physician of judgment and maturity, writing as a physician of judgment and maturity.Anyone who has attempted... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Greenville Clinic Greenville, Ky. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1971Volume 75, Issue 6Page: 974-975KeywordsCyclic adenosine monophosphatePatientsType 2 diabetes Issue Published: 1 December 1971 PDF DownloadLoading ...
INFANTILE CONVULSIONS: THEIR FREQUENCY AND IMPORTANCE
Authors: D. A. Thom
Journal: American Journal of Psychiatry (1927)

1. Infantile convulsions do not occur in a group of unselected cases more frequently than once in every 10 to 14 cases. 2. There seems to be no prognostic value to the pathological, physiological or psychological factors with which the first convulsion is associated. 3. Those cases where the convulsions occur without any apparent exciting factor (that is without trauma, teething, gastro-intestinal upsets, etc.) are invariably more significant and the prognosis should be more guarded than those cases where the convulsion is associated with some definite etiology. 4. In a fairly large group of cases, the convulsion is but a symptom of an unstable nervous system, one that is unable to withstand the ordinary vicissitudes to which the normal child is subjected. 5. There is undoubtedly a fairly large group of convulsive disorders in childhood where the convulsions are symptoms of an undiagnosed meningitis or encephalitis, which leaves behind irreparable damage to the nervous system. 6. The convulsion itself, though not associated with any devastating disease, such as meningitis, or encephalitis, may produce damage from which the brain never recovers, as seen in: (a) Some of the spastic conditions which follow immediately upon a series of convulsions. (b) Those cases following convulsions without neurological signs, but which have to adjust on a very much lower mental level. 7. The convulsions associated with rickets and tetany may leave behind very definite damage to the nervous system. 8. There is reason to believe that if the infantile convulsions associated with rickets, gastro-intestinal upsets, and acute infections were looked upon more seriously, and a greater effort made to prevent their occurrence during early life, much epilepsy and mental deficiency might be prevented.
Abstract LB-11: Discovery, synthesis, and structure-activity relationship of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against non-small cell lung cancer
Authors: Thomas S. Dexheimer, Andrew S. Rosenthal, Diane Luci, Qin Liang, Mark A. Villamil, Ajit Jadhav, Anton Simeonov, Zhihao Zhuang, David J. Maloney
Journal: Cancer Research (2014)

Abstract Protein ubiquitination is a dynamic and reversible post-translational modification that has been linked to many essential cellular processes in eukaryotes. In addition, deregulation of ubiquitin conjugation or deconjugation has been implicated in the pathogenesis of many human diseases, including cancer. For example, the deubiquitinating enzyme USP1 (ubiquitin-specific protease 1) in association with its WD40-repeat protein binding partner, UAF1 (USP1-associated factor 1), is a known regulator of DNA damage tolerance and repair and has been proposed as a promising target for anticancer therapy. To further evaluate the USP1/UAF1 complex as a therapeutic target, we conducted a quantitative high throughput screen of &amp;gt;400,000 compounds and subsequent medicinal chemistry optimization in pursuit of small molecules that inhibit the deubiquitinating activity of USP1/UAF1. These efforts lead to the identification of ML323 and a series of N-benzyl-2-phenylpyrimidin-4-amine derivatives, which possess nanomolar USP1/UAF1 inhibition and exhibit excellent selectivity over related proteases. Moreover, we demonstrate a strong correlation between compound IC50 values for USP1/UAF1 inhibition in vitro and activity in non-small cell lung cancer cells, specifically increasing the level of ubiquitinated-PCNA and decreasing cell survival. Taken together, our results establish the druggability of the USP1/UAF1 deubiquitinase complex and its potential as molecular target for anticancer therapies. Citation Format: Thomas S. Dexheimer, Andrew S. Rosenthal, Diane Luci, Qin Liang, Mark A. Villamil, Ajit Jadhav, Anton Simeonov, Zhihao Zhuang, David J. Maloney. Discovery, synthesis, and structure-activity relationship of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against non-small cell lung cancer. [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-11. doi:10.1158/1538-7445.AM2014-LB-11
ALLOGRAFT REJECTION IN C'6 DEFECTIVE RABBITS
Authors: Ursula Rother, Donald L. Ballantyne, Carl Cohen, Klaus Rother
Journal: The Journal of Experimental Medicine (1967)

27 skin allografts were transplanted in duplicate to 13 rabbits defective in the sixth component (C'6) of complement (C'). 14 were rejected within the normal period of time and 9 only after a significant delay. In four grafts, no rejection was observed. Grafts exchanged between C' active and C' defective littermates tended to persist viable longer on the C' defective partners. It is concluded that in a species of higher vertebrates, the rabbit, allograft rejection can proceed in the absence of C'6 and the biological functions depending on it. This includes the cytotoxic function of complement. However, the prolonged survival in C'6 defective rabbits of some allografts strongly suggests that two pathways may be operative in the rejection reaction. The results are consistent with the view that a mechanism independent of C'6 was alone fully effective in the majority of the donor-host combinations. A C'6-dependent mechanism became influential only in some specific donor-host combinations.
The Role of Na-K-Activated Adenosine Triphosphatase in Potassium Adaptation. STIMULATION OF ENZYMATIC ACTIVITY BY POTASSIUM LOADING
Authors: Patricio Silva, John P. Hayslett, Franklin H. Epstein
Journal: Journal of Clinical Investigation (1973)

The specific activity of sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) in homogenates of rat kidneys increases when the dietary intake of potassium is chronically increased. The effect is seen first and is most prominent in the outer medulla, but large loads of potassium elicit an increase in the cortex as well. Levels of Na-K-ATPase in brian, liver, and muscle, by contrast, are unaffected by potassium loading. Although the changes in enzyme activity in the kidney resemble those reportedly produced by aldosterone, they are not induced by experimental sodium deprivation, and they can be evoked by potassium loading in the absence of the adrenal glands. The results suggest that Na-K-ATPase of renal tubular cells, presumably in the distal tubules and collecting ducts, plays an important role in the phenomenon of potassium adaptation and in the process by which potassium is excreted into the urine.
Post-Heart Transplant Diastolic Dysfunction Is a Risk Factor for Mortality
Authors: José A. Tallaj, James K. Kirklin, Robert N. Brown, Barry K. Rayburn, Robert C. Bourge, Raymond L. Benza, Laura Pinderski, Salpy Pamboukian, David C. McGiffin, David C. Naftel
Journal: Journal of the American College of Cardiology (2007)
Failed asylum seekers in Wales will get free health care from mid-July
Authors: D. Cohen
Journal: BMJ (2009)

Failed asylum seekers in Wales will be able to get free health care from 15 July this year, as a result of changes to the National Health Service (Wales) Act 2006. The changes mean that people whose application for asylum has failed will not be charged for services forming part of the health service and that they will be entitled to the same health services as someone ordinarily resident in the United Kingdom.

This is in contrast to England, where failed asylum seekers and people not ordinarily resident in the UK are liable for healthcare costs, although trusts have discretion to provide treatment even when a patient has no means of paying.

Edwina Hart, minister for health and social services in the Welsh Assembly government, announced her intention to change the regulations in May 2008 and has since been consulting with the NHS and church leaders on the proposals. …
Referral patterns to an ophthalmic outpatient clinic by general practitioners and ophthalmic opticians and the role of these professionals in screening for ocular disease.
Authors: R. J. Harrison, J. M. Wild, A. J. Hobley
Journal: BMJ (1988)

Case notes of 1113 consecutive new patients referred to a consultant ophthalmologist at a district general hospital were reviewed to determine the source and efficacy of referrals and the current screening practices of general practitioners and ophthalmic opticians. General practitioners initiated referral in 546 cases (49%) and ophthalmic opticians referral in 439 (39%). Visual loss or visual disturbance was the most important single reason for referral (345 cases; 31%), followed by suspected glaucoma (145 cases; 13%), abnormalities of binocular vision (140; 12.5%), disorders of eyelids or ocular adnexa (127; 11%), and red eye (86; 8%). General practitioners referred many more patients with disorders of the eyelids and adnexa and ophthalmic opticians many more patients with suspected glaucoma. Ophthalmic opticians were far more likely than general practitioners to refer patients with suspected glaucoma correctly. A total of 180 patients (16%) were referred from ocular screening, in 149 cases by ophthalmic opticians and in 10 by general practitioners. Seventy patients had glaucoma or incomplete features of glaucoma, all of them referred by ophthalmic opticians. Of eight diabetic patients referred by ophthalmic opticians, three had asymptomatic disease and in two diabetes was diagnosed as a result of ocular screening. No patient was referred for asymptomatic diabetic retinopathy from screening by general practitioners. Ophthalmic opticians were more likely than general practitioners to diagnose retinopathy requiring photocoagulation. Use of a community based service to screen for glaucoma could save unnecessary consultant outpatient appointments. A similar service could facilitate detection of diabetic retinopathy at a stage when treatment is most effective.
Standardization of Drug Names
Authors: Frank M. Allan
Journal: JAMA (1974)

The use of multiple names for the same medicinal agent is confusing to physicians, pharmacists, nurses, and students. Products that appear to be entirely different may possess the same active ingredients. There may be hazard to patients; an individual allergic to a drug may inadvertently receive it when it is disguised under an unfamiliar name. Legislation has been enacted or is under consideration in the US Congress and other legislative bodies to abolish proprietary names for drugs and to require the use of a single official name for each drug product. The objectives are to minimize confusion, to guard against risks, and to reduce costs. (<i>JAMA</i>229:541-543, 1974)
Monomeric IgE enhances human mast cell chemokine production: IL-4 augments and dexamethasone suppresses the response
Authors: K MATSUDA, A PILIPONSKY, M IIKURA, S NAKAE, E WANG, S DUTTA, T KAWAKAMI, M TSAI, S GALLI
Journal: Journal of Allergy and Clinical Immunology (2005)
In-111 Pentetreotide Accumulation in a Teratoma
Authors: ALBERT T. LAMBERT, MIKE McBILES, KIMBERLY J. HUMULOCK, DANIEL T. TELL
Journal: Clinical Nuclear Medicine (1996)

An In-111 pentetreotide scan (Octreoscan) was performed as part of an investigational study on a 42-year-old man who had a large anterior mediastinal mass. Both whole-body planar and chest SPECT images revealed uptake in the mass. Pathology revealed an immature teratoma with malignant neuroblastoma-like and chondrosarcoma-like foci. Although primitive neuroectodermal components are observed in teratoma, uptake of In-111 pentetreotide in a teratoma has never been described.
From Sea to Shining Sea: A Report on the American Environment—Our Natural Heritage
Authors: William A. Thomas
Journal: JAMA (1969)

Intelligent people are aware that civilization is now capable of destroying itself, if not by warfare, then by neglect of its environment. This publication is unique in that it does not merely catalog our environmental ills but provides extensive information about what can be done to alleviate them. The body of the book, about equally divided between nontechnical prose and halftones, cites hundreds of examples of how cooperation between citizen groups and government provided the impetus to overcome specific environmental problems. The overall theme is that of local and regional planning, coordinated within the framework of ecological theory and empirical knowledge. The Council emphasizes certain problem areas by making about 65 proposals for executive or legislative action on federal or state and local levels. Many of these recommendations should be acted upon promptly to enhance the quality of our surroundings; others are so vague or so politically untenable that they
K-lymphocytes (killer-cells) in Crohn's disease and acute virus B-hepatitis.
Authors: R Eckhardt, P Kloos, M P Dierich, K H Meyer zum Buschenfelde
Journal: Gut (1977)

Total lymphocyte counts, B-, T-, C'3 receptor-bearing lymphocytes, and K-cell activity were studied in peripheral blood in patients with Crohn's disease and inflammatory liver disease. Patients with active untreated Crohn's disease and acute virus B hepatitis exhibited a markedly increased K-cell activity measured in a plaque assay when compared with normal controls (P less than 0.01). Patients with immunosuppressive treated Crohn's disease, HBsAg-positive chronic active hepatitis, and cirrhosis of the liver showed only a slight increase of K-cell activity (P less than 0.01). In the postacute phase of hepatitis (four to 12 weeks from onset) K-cell activity fell to normal levels. The number of B-lymphocytes showed a relative and absolute decrease in all groups of patients. With the exception of patients with acute HBsAg-positive hepatitis and the post-acute phase of hepatitis all the other groups showed statistically decreased absolute numbers for C'3 receptor-bearing lymphocytes. The significant decrease in K-cell activity and the number of T-lymphocytes in Crohn's disease treated with immunosuppressive drugs was interpreted as an effect of azathioprine and prednisone on these lymphocyte subpopulations.
Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters
Authors: François Lemonnier, Lucile Couronné, Marie Parrens, Jean-Philippe Jaïs, Marion Travert, Laurence Lamant, Olivier Tournillac, Therese Rousset, Bettina Fabiani, Rob A. Cairns, Tak Mak, Christian Bastard, Olivier A. Bernard, Laurence de Leval, Philippe Gaulard
Journal: Blood (2012)
The Hinman Syndrome Nonneurogenic Neurogenic Urinary Bladder—Renal Scintigraphic Findings
Authors: B. CHANDRAMOULY, R. SCARLATA, R. AGRAVAT
Journal: Clinical Nuclear Medicine (1994)

The Hinman Syndrome is applied to a group of neurologically normal children presenting with clinical and radiological findings strongly suggestive of a primary neuropathic process. The authors report a radionuclide renal study demonstrating massive dilatation of the urinary bladder with marked changes in shape and position of the bladder in supine and standing positions. The clinical findings and renal scintigraphy were consistent with the Hinman Syndrome.
Verapamil and tiapamil in prevention of ventricular fibrillation in pigs with coronary ligation. Comparative effects on left ventricular function.
Authors: C A Muller, L H Opie, C W Hamm, M Peisach, C A Pineda, F T Thandroyen
Journal: Circulation (1988)

Antiarrhythmic and hemodynamic effects of the calcium channel antagonist verapamil were compared with those of tiapamil, a congener, in open-chest pigs with anterior descending coronary artery ligation. Tiapamil (6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 4 of 10 versus 22 of 25 in controls (p less than 0.05) and maintained left ventricular dP/dtmax after ligation (predrug value: 2,312 +/- 112 mm Hg/sec; 20 minutes after ligation: 2,139 +/- 229 mm Hg/sec). Tiapamil increased blood flow in the peripheral ischemic zone (24 +/- 3.2% vs. 16.9 +/- 1.6% of preligation value in controls, p less than 0.05) as well as in the peri-ischemic and nonischemic zones (153.9 +/- 12.7% and 186.3 +/- 17.1%, respectively; both p less than 0.0001 vs. 97.9 +/- 5% and 91.3 +/- 4.7% in controls). Verapamil (0.6 mg/kg i.v.) decreased the incidence of ventricular fibrillation to 0 of 7 versus 22 of 25 in controls (p less than 0.005); left ventricular dP/dtmax decreased from 2,062 +/- 144 to 1,060 +/- 168 mm Hg/sec (p less than 0.0001). Verapamil did not change blood flow in the peripheral, peri-ischemic, or nonischemic zones. Thus, tiapamil, and not verapamil, decreased ischemic ventricular fibrillation while maintaining left ventricular mechanical function. Verapamil congeners warrant further evaluation as antiarrhythmic agents in acute myocardial ischemia.
Leucine 7 to Proline 7 Polymorphism in the Preproneuropeptide Y Is Associated With Proteinuria, Coronary Heart Disease, and Glycemic Control in Type 1 Diabetic Patients
Authors: Kim Pettersson-Fernholm, Matti K. Karvonen, Jaana Kallio, Carol M. Forsblom, Markku Koulu, Ullamari Pesonen, Johan A. Fagerudd, Per-Henrik Groop
Journal: Diabetes Care (2004)

OBJECTIVE—Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabetic patients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population. RESULTS—The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P &amp;lt; 0.05). Patients with the Pro7 allele had worse glycemic control (HbA1c 8.8 vs. 8.5%, P &amp;lt; 0.005), more coronary heart disease (CHD) (14 vs. 8%, P &amp;lt; 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P &amp;lt; 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA1c (P &amp;lt; 0.001), proteinuria (P &amp;lt; 0.01), and CHD (P &amp;lt; 0.01) in multiple regression analyses. CONCLUSIONS—We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabetic patients, possibly by influencing glycemic control and triglycerides.
Review: New oral anticoagulants reduced stroke and systemic embolism compared with warfarin in AF
Authors: Liviu Klein
Journal: Annals of Internal Medicine (2012)

Source Citation Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol. 2012;110:453-60. 22537354