tbuckley/cabot-search huggingface dataset:
Abstract 4600: Analysis of clonal evolution in cancer using whole exome sequence data reveals that subclonal driver mutations predict poor prognosis in chronic lymphocytic leukemia.
Authors: Scott L. Carter, Dan-Avi Landau, Petar Stojanov, Aaron McKenna, Kristian Cibulskis, Michael S. Lawrence, Jens Lohr, Kristen Stevenson, Donna Neuberg, Matthew Meyerson, Catherine J. Wu, Gad Getz
Journal: Cancer Research (2013)

Abstract Clonal evolution is a key feature of cancer progression and relapse. We present a computational technique for analyzing whole exome sequence data to measure the fraction of cancer cells harboring each somatic mutation and resolve subclonal cell populations. We applied our methods to 149 chronic lymphocytic leukemia (CLL) samples to classify driver mutations as predominantly clonal or subclonal, corresponding to initiating and progression events in CLL evolution. We identified driver mutations as predominantly clonal (e.g., MYD88, trisomy 12 and del(13q)) or subclonal (e.g., SF3B1, TP53), corresponding to earlier and later events in CLL evolution. We sampled leukemia cells from 18 patients at two timepoints and found that 10 of 12 CLL cases treated with chemotherapy (but only 1 of 6 without treatment) underwent clonal evolution, predominantly involving subclones with driver mutations (e.g., SF3B1, TP53) that expanded over time. Furthermore, presence of a subclonal driver mutation was an independent risk factor for rapid disease progression. Our methods uncover patterns of clonal evolution in cancer, providing insights into its stepwise transformation and linking the presence of subclones with adverse clinical outcome. Because our methods require only whole exome sequence data, they are readily applicable to a large corpus of approximately 6,000 sequenced cancer exomes, and are ideally suited for application in future exome-based clinical cancer sequencing pipelines. We present additional application of our methods to analysis of prostate cancer, multiple myeloma, and glioblastoma multiforme datasets. Citation Format: Scott L. Carter, Dan-Avi Landau, Petar Stojanov, Aaron McKenna, Kristian Cibulskis, Michael S. Lawrence, Jens Lohr, Kristen Stevenson, Donna Neuberg, Matthew Meyerson, Catherine J. Wu, Gad Getz. Analysis of clonal evolution in cancer using whole exome sequence data reveals that subclonal driver mutations predict poor prognosis in chronic lymphocytic leukemia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4600. doi:10.1158/1538-7445.AM2013-4600
Arteritis of the arms.
Authors: G A Missen
Journal: BMJ (1981)

Background/Aim: Activated Wnt signaling in cancer cells leads to cell proliferation. It has been shown that the Wnt pathway is activated in pancreatic adenocarcinoma cells. Therefore, we tested the effect of Wnt inhibitors in human and murine pancreatic cancer cell lines. Materials and Methods: The Wnt inhibitors ethacrynic acid (EA), ciclopirox olamine (CIC), piroctone olamine (PO) and griseofulvin (GF) were tested in murine and human pancreatic cancer cell lines with the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: We showed that the Wnt inhibitors significantly reduced cell viability in murine, as well as human pancreatic cancer cell lines. Conclusion: These results may lead to a new therapeutic option with Wnt inhibitors for patients with pancreatic adenocarcinoma.
P3-07-33: Are Single Node Metastases More Common in Patients with Breast Cancer in the Sentinel Node Era?
Authors: G Shetty, S Randhawa, I Mohammed, S Harries, L Jones, D Clarke
Journal: Cancer Research (2011)

Abstract Background: The axillary recurrence rate after axillary lymph node dissection has been reported as approximately 3%. Since the introduction of sentinel node biopsy (SNB), it has become apparent that, there is a significant decrease in axillary recurrence, ranging from 0.26% to 0.9% in published literature. One of the concerns that arises from this data is that, the sentinel node may have been missed when routine axillary node clearance were being performed. The aim of this study was to compare the results of a cohort of patients who had an axillary staging procedure prior to the introduction of SNB (axillary clearance) with patients after the introduction of SNB in relation to the number who had only one positive node in the axilla. Methods: From June 2003 to November 2010 data was collected on demographics, histopathology and procedure performed. All patients with invasive breast cancer prior to April 2005 had an axillary node clearance (ANC) with either wide local excision or mastectomy. Since April 2005 all patients with invasive breast cancer had a SNB and patients with a positive sentinel node (SN) underwent ANC. Patients with a negative SNB had no further axillary surgery. Results: 702 patients had axillary node surgery between June 2003 and November 2010. 251 patients had axillary node clearance (pre SN period) and 451 had SNB (SN period). Average age was 57 years. 509 patients (156 in pre SNB period and 353 in post SNB period) had no nodal metastases. Amongst the 193 node positive patients, 100 had single node involvement. In the pre SNB period 33 (34.7%) patients had single node involvement, compared to 67 (68.3%) in SNB period. The histopathological type of cancer did not vary significantly between the one node positive, multiple node positive and node negative groups. Conclusion: Our study confirms a significant rise in patients with a single node positive in the sentinel node period. This could be due to the SLN being “missed” during surgery when an axillary node clearance was performed, which would explain the reported higher axillary recurrence rates in the pre sentinel node period compared to the sentinel node period. Another possibility is that the SN is undergoing more detailed histopathological assessment as there are fewer number of lymph nodes to be examined. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-33.
Typing Streptococci in Renal Disease
Authors: CHARLES H. RAMMELKAMP
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 July 1981Typing Streptococci in Renal DiseaseCHARLES H. RAMMELKAMP, M.D.CHARLES H. RAMMELKAMP, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-1-125_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Gibney and colleagues (1) recently suggested that it would be interesting to ascertain the serologic type of streptococcus isolated from an infection in a patient whose renal disease was not classic acute poststreptococcal glomerulonephritis. Indeed, such data are both interesting and helpful in managing such patients.In 1956 during a very large epidemic of streptococcal infections and nephritis in Japan (2), type 12 streptococci were isolated from the oropharynx of patients with an initial attack of classical nephritis, whereas several different non-nephritogenic types and only occasionally type 12 were recovered from patients whose history, urine examination, and...References1. GIBNEYREINECKBANNAYANSTEIN RHGJ. Renal lesions in acute rheumatic fever. Ann Intern Med. 1981;94:322-6. LinkGoogle Scholar2. KODAMATMIYAMOTOKOTAKE YI. Ochiais: epidemic nephritis in Japan. Yokahama Med Bull. 1958;9:105-18. MedlineGoogle Scholar3. STETSONRAMMELKAMPKRAUSEKOHENPERRY CCRRW. Epidemic acute nephritis: studies on etiology, natural history and prevention. Medicine (Baltimore). 1955;34:431-50. CrossrefMedlineGoogle Scholar4. RAMMELKAMP C. Acute poststreptococcal glomerulonephritis. In: READ SW, ZABRISKIE JB, eds. Streptococcal Disease and the Immune Response. New York: Academic Press; 1980:43-51. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Case Western Reserve University Cleveland, OH 44106 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1981Volume 95, Issue 1Page: 125-125KeywordsGlomerulonephritisInfectious diseasesNephritisOropharynxRenal diseasesStreptococcal infectionsStreptococcusUrine Issue Published: 1 July 1981 PDF DownloadLoading ...
TOXIC JAUNDICE, WITH ATROPHY OF LIVER, FOLLOWED BY REGENERATION AND RECOVERY
Authors: B. G. R. Crawford
Journal: BMJ (1918)

attributes his success to special precautions with regard to intervals between doses, etc.Lieut.-Colonel Harrison, officer commanding Rochester Row Hospital, writes: "Jaundice occurs during treatment of syphilis with arsenical compounds in 0.6 per cent. of cases, and this symptom may last for four or five months."In neither of the cases here reported was arsenic detected in the urine.
Implantable Biosensors: Towards Smart Tattoos: Implantable Biosensors for Continuous Glucose Monitoring (Adv. Healthcare Mater. 1/2013)
Authors: Yun Jung Heo, Shoji Takeuchi
Journal: Advanced Healthcare Materials (2013)

Glowing glucose sensors, or so-called smart tattoos, have garnered attention because the sensors implanted under the skin can help people with diabetes monitor their blood glucose levels in a convenient, less-invasive manner. If the sensors meet their promise, life for diabetic patients can be significantly improved. Shoji Takeuchi and Yun Jung Heo review on page 43 the efforts to develop glucose biosensors and discuss their current status and future prospects.
THE INTERVERTEBRAL DISK
Authors: EMIL S. GEIST
Journal: JAMA (1931)

The past five years has seen a greater increase in knowledge of the pathologic changes of the spine than that of the half century preceding. This is due to Professor Schmorl of the Dresden Pathologic Institute, who, in his researches up to now, did not achieve his object of demonstrating the cause of scoliosis but who indicated the anatomy, physiology and pathologic anatomy of that hitherto neglected organ the intervertebral disk. Schmorl removes the spine at every autopsy and during the past five years has studied more than 5,000 spines. His investigations and observations are those of the pathologist. A considerable literature has already sprung up in Germany as a result of Schmorl's work, while in this country it has received practically no attention. It was my privilege to spend a few days at Professor Schmorl's institute during the month of October, 1930. The spine is an organ of many
Outcome of Budd-Chiari syndrome: A multivariate analysis of factors related to survival including surgical portosystemic shunting
Authors: Guy Zeitoun, Sylvie Escolano, Antoine Hadengue, Nabih Azar, Mustapha El Younsi, Alain Mallet, Marie-Jeanne Boudet, Jean-Marie Hay, Serge Erlinger, Jean-Pierre Benhamou, Jacques Belghiti, Dominique Valla
Journal: Hepatology (1999)

The aim of this study was to assess the factors, including surgical portosystemic shunts, which affect survival in adults with Budd-Chiari syndrome. Multivariate retrospective analysis was performed using characteristics recorded at the time of diagnosis in 120 patients admitted from 1970 to 1992, of whom 82 were treated with surgical portosystemic shunts and 38 received only medical therapy. The 1-, 5-, and 10-year survival rates were 77 ± 4%, 64 ± 5%, and 57 ± 6%, respectively. Survival was significantly better in the subgroup of patients diagnosed after versus before 1985. In both subgroups, and in patients with, as well as in patients without surgical shunts, 4 factors were found to be inversely and independently related to survival: age, response of ascites to diuretics, Pugh score, and serum creatinine. In patients diagnosed since 1985, an index combining these 4 factors allowed to differentiate patients with a good outcome (5-year survival 95%) from those with a poor outcome (5-year survival 62%; P &lt; .05). There was no statistically significant and independent influence of surgical portosystemic shunts on survival. In conclusion, age, severity of liver failure, and presence of refractory ascites are the main prognostic factors in Budd-Chiari syndrome. Increased survival in recent years is consistent with improved management of hypercoagulable states as well as improved general care. It is uncertain whether surgical portosystemic shunting favorably modifies survival. Therefore, we recommend that surgical shunting should be restricted to management of refractory ascites or variceal bleeding in patients with otherwise good prognostic factors.
Immunoglobulins and the X-chromosome
Authors: K. Rhodes, R. L. Markham, P. M. Maxwell, M. E. Monk-Jones
Journal: BMJ (1969)

Serum levels of immunoglobulins (Ig) G, M, and A were determined in 28 women with an additional X-chromosome (XXX), and in equal numbers of age-matched normal women and men. Mean IgM levels were found to be highest in the XXX group, intermediate in normal women, and lowest in men; these differences were statistically significant. Mean IgM values obtained from seven XXY and three XXXY cases were almost identical with those of normal women and XXX women respectively. No such sex linkage was observed for IgA and IgG levels. These results support the suggestion that the serum level of IgM is related to the number of X chromosomes present.
Polyunsaturated Fatty Acids Ameliorate Hepatic Steatosis in Obese Mice by Srebp–1 Suppression
Authors: Motohiro Sekiya, Naoya Yahagi, Takashi Matsuzaka, Yuho Najima, Masanori Nakakuki, Ryozo Nagai, Shun Ishibashi, Jun-ichi Osuga, Nobuhiro Yamada, Hitoshi Shimano
Journal: Hepatology (2003)

Leptin–deficient ob/ob mice show many characteristics of obesity, including excess peripheral adiposity as well as severe hepatic steatosis, at least in part, due to increased hepatic lipogenesis. Polyunsaturated fatty acids (PUFAs) are not only ligands for peroxisome proliferator–activated receptor (PPAR) α but are also negative regulators of hepatic lipogenesis, which is thought to be mediated by the repression of sterol regulatory element–binding protein (SREBP)–1. We have previously shown that the disruption of SREBP–1 in ob/ob mice decreased their liver triglyceride storage. To examine whether PUFAs could reduce hepatic triglyceride deposition, we challenged ob/ob mice with dietary PUFA. It is demonstrated that PUFA markedly decreased the mature form of SREBP–1 protein and thereby reduced the expression of lipogenic genes such as fatty acid synthase (FAS) and stearoyl–CoA desaturase 1 (SCD1) in the livers of ob/ob mice. Consequently, the liver triglyceride content and plasma alanine aminotransferase (ALT) levels were decreased. Furthermore, both hyperglycemia and hyperinsulinemia in ob/ob mice were improved by PUFA administration, similar to the effect of PPARα activators. In conclusion, PUFAs ameliorate obesity–associated symptoms, such as hepatic steatosis and insulin resistance, presumably through both down–regulation of SREBP–1 and activation of PPARα.
Micropenis: an important early sign of congenital hypopituitarism.
Authors: D M Salisbury, J V Leonard, C A Dezateux, M O Savage
Journal: BMJ (1984)

Micropenis is an important sign in neonates, since it may be the only clue to the diagnosis of panhypopituitarism, a potentially lethal but eminently treatable condition. Case reportsCase 1-A boy infant was delivered at 37 weeks' gestation after an uncomplicated pregnancy.Birth weight was 2200 g.He was asphyxiated and successfully resuscitated but remained hypotonic.Jaundice developed on the third day of life and persisted.At 3 weeks of age hypothyroidism was diagnosed (plasma thyroxine concentration 54 nmol/l (4-2 /ig/lOO ml), thyroid stimulating hormone concentration 8-5 mU/l).Despite thyroxine replacement he failed to thrive and developed abdominal distension and vomiting.Laparotomy showed milk curd obstruction of the small intestine, and postoperatively he was ventilated for three days.Twelve days later he collapsed and had a hypoglycaemic convulsion.For the next three months he was fed intravenously and became hypoglycaemic when attempts were made to restart oral feeds.At the age of 4 months the diagnosis of hypopituitarism was suggested because of his micropenis.During a hypoglycaemic episode (blood glucose concentration 10 mmol/l; 18 mg/100 ml) the plasma cortisol value was noted to be low at 100 nmoll1 (3-6 Ag/lOO ml) and concentrations of both plasma adrenocorticotrophic hormone (93 ng/l) and growth hormone (7-0 mU/l) were inappropriately low, consistent with hypopituitarism.The hypoglycaemia resolved rapidly with hydrocortisone replacement and did not recur.Growth hormone deficiency was confirmed by a glucagon stimulation test and appreciable penile growth occurred after three injections of depot testosterone.His jaundice, which had persis- ted despite thyroxine replacement, resolved after initiation of the hydrocortisone.Case 2-A boy infant (birth weight 3650 g) was delivered normally after an uncomplicated pregnancy.Shortly after birth he became hypothermic and hypoglycaemic and micropenis was noted.Three days after birth he became severely jaundiced with raised plasma transaminase activities, which persisted.Plasma thyroxine concentra- tion was 16 nmol/1 (12 kg/lOO ml) without the appropriate thyroid stimulating hormone response (5-0 mU/l), indicating hypothyroidism of pituitary origin.Thyroid replacement was started but was in- adequate.At 3 weeks of age he had several hypoglycaemic convulsions, and a normal blood glucose concentration could be maintained only Hospital for Sick Children, Great
Health-related quality of life in patients with chronic hepatitis C and advanced fibrosis
Authors: Herbert L. Bonkovsky, Kristin K. Snow, Peter F. Malet, Carla Back-Madruga, Robert J. Fontana, Richard K. Sterling, Clark C. Kulig, Adrian M. Di Bisceglie, Timothy R. Morgan, Jules L. Dienstag, Marc G. Ghany, David R. Gretch
Journal: Journal of Hepatology (2006)
730-3 “Directional” Coronary Atherectomy Removes Atheroma More Effectively from Concentric than Eccentric Lesions: Intravascular Ultrasound Predictors of Lesional Success
Authors: Anthony C. De Franco, E. Murat Tuzcu, David J. Moliterno, Russell E. Raymond, Irving Franco, Skip Guyer, Stephen G. Ellis, Patrick L. Whitlow, Steven E. Nissen
Journal: Journal of the American College of Cardiology (1995)
A CARRIER STATE OF MUMPS VIRUS IN HUMAN CONJUNCTIVA CELLS
Authors: Duard L. Walker, Harry C. Hinze
Journal: The Journal of Experimental Medicine (1962)

Mumps virus in a carrier culture of human conJunctiva cells (C-M cultures) persisted through 5(1/2) months of cultivation in a medium containing sufficient specific antiserum to keep the fluid free of infectious virus. Cells from the C-M cultures were cloned under antiserum with an efficiency equal to control, uninfected cultures (40 to 100 per cent). Of 269 C-M cell clones examined, the cells of 262 contained antigen. Eight infected clones were grown into cultures sufficiently large to demonstrate that they released infectious virus and adsorbed erythrocytes in a manner similar to the original C-M cultures. Two uninfected clones were as susceptible to the effects of a cytopathogenic line of mumps virus as were uninfected control cells. In healthy, growing cultures of C-M cells 0.1 to 1.0 per cent of cells adsorbed erythrocytes to their surfaces, suggesting that these cells were releasing virus. Reduction of serum content of the medium to less than 3 per cent, depletion of the medium, or crowding of cultures resulted in hemadsorption by 50 to 90 per cent of cells and an increase of virus in the medium. In growing cultures hemadsorbing cells did not appear damaged. It was observed that cells could simultaneously exhibit hemadsorption and mitosis.
Etiology of Liver Disease in Renal-Transplant Patients
Authors: Athol J. Ware, James P. Luby, Blaine Hollinger, Edwin H. Eigenbrodt, Jennifer A. Cuthbert, Carolyn R. Atkins, James Shorey, Alan R. Hull, Burton Combes
Journal: Annals of Internal Medicine (1979)

The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation.
Strategies and prospects for finding insulin resistance genes
Authors: Michael P. Stern
Journal: Journal of Clinical Investigation (2000)

In this paper I review the evidence that human sensitivity to insulin is influenced by heredity, in particular by one or more genes with relatively large effects. Even granting the existence of such genes, however, the best route toward identifying them — and the related genes that are presumed to affect an individual’s risk of obesity or type 2 diabetes — remains unclear. Thus, the phenotype of insulin resistance can be assessed either directly, with techniques such as the euglycemic hyperinsulinemic clamp, or indirectly, using various proxy measures such as serum insulin concentrations. In addition, several different genotyping strategies might be employed. These alternatives raise both practical and theoretical questions: Which of the available phenotypic traits offers the most promising approach to identifying insulin resistance genes? Which methodologies are most powerful, and which best exploit the anticipated continued successes of the Human Genome Project? Finally, is it more realistic to search for genes influencing “intermediate” phenotypes such as insulin sensitivity, or to seek the related disease genes directly?
Calcium signaling inhibits interleukin-12 production and activates CD83+ dendritic cells that induce Th2 cell development
Authors: Mark B. Faries, Isabelle Bedrosian, Shuwen Xu, Gary Koski, James G. Roros, Mirielle A. Moise, Hung Q. Nguyen, Friederike H. C. Engels, Peter A. Cohen, Brian J. Czerniecki
Journal: Blood (2001)
Identification of T-cell epitopes of Lol p 9, a major allergen of ryegrass (Lolium perenne) pollen☆, ☆☆, ★, ★★
Authors: B BLAHER, C SUPHIOGLU, R KNOX, M SINGH, J MCCLUSKEY, J ROLLAND
Journal: Journal of Allergy and Clinical Immunology (1996)
Cloned calves are grown from cultured cells
Authors: S. Mayor
Journal: BMJ (2000)

Six cloned calves have been created from cells cultured in vitro for up to three months, confirming previous work showing that relatively “old” cells can be used to clone whole animals.

The achievement confirms the possibility of being able to carry out targeted genetic manipulations in vitro—taking out specific genes and replacing them with other ones—because this requires prolonged culture of nuclear donor cells.

A research team working in Japan and the …