tbuckley/cabot-search huggingface dataset:
Abstract 5128: Identification of osteosarcoma driver genes by integrative analysis of copy number and gene expression data
Authors: Marieke L. Kuijjer, Halfdan Rydbeck, Stine H. Kresse, Emilie P. Buddingh, Helene Roelofs, Horst Bürger, Ola Myklebost, Pancras CW Hogendoorn, Leonardo A. Meza-Zepeda, Anne-Marie Cleton-Jansen
Journal: Cancer Research (2012)

Abstract High-grade osteosarcoma is a tumor with a complex genomic profile, occurring primarily in adolescents. The extensive genomic alterations obscure the identification of genes driving tumorigenesis in osteosarcoma progenitor cells. In order to identify such driver genes, we integrated DNA copy number profiles (Affymetrix SNP 6.0) of 32 diagnostic biopsies with 84 expression profiles (Illumina Human-6 v2.0) of osteosarcoma as compared with its putative progenitor cells, i.e. mesenchymal stem cells (n=12) or osteoblasts (n=3). In addition, we performed paired analyses between copy number and expression profiles of a subset of 29 patients for which we had both DNA and mRNA profiles. Integrative analyses were performed in Nexus Copy Number Software and statistical language R. Paired analyses were performed on all probes which were significantly differentially expressed in corresponding LIMMA analyses. For both non-paired and paired analyses, copy number aberration frequency was set to &amp;gt;35%. Non-paired integrative analyses resulted in 45 genes that were present in both analyses using different control sets, i.e. MSCs and osteoblasts. 101 genes overlapped between the two paired integrative analyses. Paired analyses detected &amp;gt;90% of all genes found with the corresponding non-paired analyses. Remarkably, approximately twice as many genes as found in the corresponding non-paired analyses were detected. Affected genes were compared with differential expression in osteosarcoma cell lines. An overrepresentation of altered cell division related genes was found, such as MCM4 and LATS2, suggesting that deregulation of the cell cycle is an initial driver of osteosarcomagenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5128. doi:1538-7445.AM2012-5128
Hong Kong University turns down tobacco money
Authors: S. Mayor
Journal: BMJ (1997)

The University of Hong Kong has decided to turn down the offer of a substantial donation. from a tobacco company. The decision comes in the wake of the decision by other universities, including Cambridge and Shanghai, to accept controversial tobacco sponsorship.

The vice chancellor, Professor Cheng Yiu Chung, recently revealed that he and university staff had turned down a financial offer from a major tobacco company, which was made on the condition that it be given public recognition.

Professor Judith Mackay, director of the Asian Consultancy on Tobacco Control, said: “One …
Brochures on Seafood Safety for People With Certain Diseases
Authors: Stuart L. Nightingale
Journal: JAMA (1994)

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
Inhibition of presenilin 1 expression is promoted by p53 and p21WAF-1and results in apoptosis and tumor suppression
Authors: Jean-Pierre Roperch, Véronique Alvaro, Sylvie Prieur, Marcel Tuynder, Mona Nemani, Florence Lethrosne, Laurence Piouffre, Marie-Claude Gendron, David Israeli, Jean Dausset, Moshe Oren, Robert Amson, Adam Telerman
Journal: Nature Medicine (1998)
Stem cell researchers claim some reviewers hamper publication of high quality research
Authors: S. Mayor
Journal: BMJ (2010)

Leading stem cell researchers have expressed concern that some reviewers may be hampering publication of high quality research in the field and are calling for a more open process of review to prevent this.

Their concerns echo those expressed in a letter sent last summer to the editors of science journals by 10 stem cell researchers from around the world. The letter claimed that “papers that are scientifically flawed or comprise only modest technical increments often attract undue profile. At the same time publication of truly original findings may be delayed or rejected” (http://eurostemcell.org/commentanalysis/peer-review).

The letter followed a major conference, the EuroSyStem/European Molecular Biology Organisation Conference on Advances in Stem Cell Research, at which researchers shared their frustration at sometimes receiving what they considered to be “unreasonable or obstructive reviews.” To improve the situation, they proposed that when a paper is published, the reviews, response to reviews and associated editorial correspondence could be provided as supplementary information, while preserving anonymity of the referees.

Speaking to the BBC about the issue this week, Austin Smith, director of the Wellcome Trust Centre for Stem Cell …
INOCULATION IN THE INCUBATION STAGE OF PLAGUE
Authors: A. M. Corthorn
Journal: BMJ (1902)

caused by its being torn away from any other structure.It is always present in fresh specimens.Its function I do not know.I believe the function of this bulb has not been definitely settled; still its position and structure would lead one to sup- pose that it was suctorial.In Bermuda I frequently caught specimens that had just fed, and mounting them quickly, found blood corpuscles in the epipharynx, but I never found anv in the bulb itself.This bulb is also present in the head of the male Culex, but is perhaps not quite so well developed.In the male the hypopharynx lies on the sheath or labium, and more or less coalesces with it, especially at the pointed distal part be- tween the lateral labellae.The mandibles and maxillae are practically absent.The fine central canal or groove in the hypopharynx terminates, as in the female, in a small sac at its basal end, from which runs a fine-ringed salivary duct.It would therefore, I think, be very interesting to know the minute anatomy of those few male species that are credited with the power of biting and sucking blood, for if the same arrangement of the mouth parts exists in them as in the male specimens (Culex) that I have examined, I should not think that they could possibly perform the operation satisfactorily.
Cardiomyopathy: Presenting Symptom of Progressive Muscular Dystrophy
Authors: Irwin M. Siegel
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The heredofamilial myopathic disorders, progressive muscular dystrophy and dystrophia myotonica, are frequently complicated by cardiomyopathy.<sup>1,2</sup>Perloff et al described diagnostic electrocardiographic patterns for these conditions in an excellent review that included a detailed prospective study of cardiomyopathy in a variety of dystrophic types.<sup>3</sup>Nonetheless, cardiac expression in muscular dystrophy often occurs late in the disease, and occult cardiac involvement frequently goes unrecognized.<sup>4</sup> This report describes a case of progressive muscular dystrophy in which the initial major clinical manifestation was cardiomyopathy. <h3>Report of a Case.—</h3> The patient, a 22-year-old white man, was an only child. His birth and developmental history were normal. His history revealed no serious illness, and there was no family history of neuromuscular disease. He did not smoke or drink alcohol. He had never been athletic, and late in adolescence he noticed mild weakness when ascending stairs and moderate fatigue after vigorous
Importance of Obtaining Independent Measures of Insulin Secretion and Insulin Sensitivity During the Same Test
Authors: Devjit Tripathy, Ylva Wessman, Monica Gullström, Tiinamaija Tuomi, Leif Groop
Journal: Diabetes Care (2003)

OBJECTIVE—To validate and apply a method for independent assessment of insulin secretion and insulin sensitivity (SI) during the same test; that is, an intravenous glucose tolerance test followed by a euglycemic-hyperinsulinemic clamp, also called the Botnia clamp. This test was then applied to nondiabetic subjects with (FH+) and without (FH−) a first-degree family history of diabetes. RESEARCH DESIGN AND METHODS—The Botnia clamp measures the first-phase insulin response (FPIR) to 0.3g/kg glucose i.v. and insulin sensitivity (M-value) from a 2-h euglycemic clamp begun 60 min after the glucose bolus. The M-value obtained during the Botnia clamp was compared with M-values obtained during a regular euglycemic clamp without prior glucose bolus. Repeated tests were performed in random order in subjects with normal and abnormal glucose tolerance. Finally, the test was applied to subjects with and without a family history of type 2 diabetes. RESULTS—SI and insulin secretion from this test showed a high degree of reproducibility, and the M-value obtained with the Botnia clamp correlated strongly with the M-value from a euglycemic clamp without prior glucose bolus (r = 0.953, P &amp;lt; 0.005). FH+ subjects showed decreased SI (P = 0.02), but similar FPIR, compared with FH− subjects. However, insulin secretion adjusted for the degree of insulin resistance was significantly impaired (P = 0.04). CONCLUSIONS—In conclusion, the Botnia clamp provides reliable and independent measures of SI and β-cell function during the same test. As illustrated above, knowledge of the degree of SI is mandatory when presenting data on insulin secretion.
Chemotherapy Alters Monocyte Differentiation to Favor Generation of Cancer-Supporting M2 Macrophages in the Tumor Microenvironment
Authors: Eveline M. Dijkgraaf, Moniek Heusinkveld, Bart Tummers, Lisa T.C. Vogelpoel, Renske Goedemans, Veena Jha, Johan W.R. Nortier, Marij J.P. Welters, Judith R. Kroep, Sjoerd H. van der Burg
Journal: Cancer Research (2013)

Current therapy of gynecologic malignancies consists of platinum-containing chemotherapy. Resistance to therapy is associated with increased levels of interleukin (IL)-6 and prostaglandin E2 (PGE(2)), 2 inflammatory mediators known to skew differentiation of monocytes to tumor-promoting M2 macrophages. We investigated the impact of cisplatin and carboplatin on 10 different cervical and ovarian cancer cell lines as well as on the ability of the tumor cells to affect the differentiation and function of cocultured monocytes in vitro. Treatment with cisplatin or carboplatin increased the potency of tumor cell lines to induce IL-10-producing M2 macrophages, which displayed increased levels of activated STAT3 due to tumor-produced IL-6 as well as decreased levels of activated STAT1 and STAT6 related to the PGE(2) production of tumor cells. Blockade of canonical NF-κB signaling showed that the effect of the chemotherapy was abrogated, preventing the subsequent increased production of PGE(2) and/or IL-6 by the tumor cell lines. Treatment with the COX-inhibitor indomethacin and/or the clinical monoclonal antibody against interleukin-6 receptor (IL-6R), tocilizumab, prevented M2-differentiation. Importantly, no correlation existed between the production of PGE(2) or IL-6 by cancer cells and their resistance to chemotherapy-induced cell death, indicating that other mechanisms underlie the reported chemoresistance of tumors producing these factors. Our data suggest that a chemotherapy-mediated increase in tumor-promoting M2 macrophages may form an indirect mechanism for chemoresistance. Hence, concomitant therapy with COX inhibitors and/or IL-6R antibodies might increase the clinical effect of platinum-based chemotherapy in otherwise resistant tumors.
Salicylate intoxication in the elderly due to benorylate.
Authors: T R Beringer
Journal: BMJ (1984)

6 observations chez des malades âges. Le benorylate est metabolise en acide salicylique et paracetamol. L'excretion d'acide salicylique peut etre reduite en cas de troubles fonctionnels renaux, frequents chez le vieillard
Murine laminin binds to Histoplasma capsulatum. A possible mechanism of dissemination.
Authors: J P McMahon, J Wheat, M E Sobel, R Pasula, J F Downing, W J Martin
Journal: Journal of Clinical Investigation (1995)

Histoplasmosis, an increasingly important opportunistic infection in immunosuppressed subjects, is characterized by hematogenous dissemination of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracellular matrix, is known to mediate the attachment of various invasive pathogens to host tissues. In the current study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid, specific, and saturable manner. Scatchard analysis with 125I-labeled laminin revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent Kd for laminin binding of 1.6 x 10(-9) M. Laminin binding to H. capsulatum was decreased from 62 +/- 1 to 17 +/- 1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin. A 50-kD H. capsulatum laminin-binding protein was demonstrated using an 125I-Ln blot of H. capsulatum cell wall proteins. The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related. This study proposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traverse the basement membrane.
Lessons from the Wiskott–Aldrich Syndrome
Authors: Jennifer M. Puck, Fabio Candotti
Journal: New England Journal of Medicine (2006)

The Wiskott–Aldrich syndrome is a well-recognized triad of eczema, bleeding diathesis, and recurrent infections that occurs in boys. Although it is rare (with an estimated incidence of less than 1 in 100,000 births), the syndrome offers rich historical, clinical, and scientific lessons.In a typical case of severe Wiskott–Aldrich syndrome, petechiae (see figure), bruising, and bloody diarrhea may develop in the first days of life owing to thrombocytopenia with small platelets (low platelet volume). Unusually prolonged bleeding after circumcision often leads to the discovery of the thrombocytopenia. Eczema — which may be severe — ensues, and throughout childhood there may . . .
Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control
Authors: Donald E. Kohan, Paola Fioretto, Weihua Tang, James F. List
Journal: Kidney International (2013)

In patients with diabetes, glycemic improvement by sodium-glucose cotransporter-2 inhibition depends on the kidney's ability to filter glucose. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces hyperglycemia in patients with diabetes and normal or mildly impaired renal function. In this randomized, double-blind, placebo-controlled study we assessed daily treatment with dapagliflozin in 252 patients with inadequately controlled type 2 diabetes and moderate renal impairment. The primary endpoint, the mean change in HbA1c, was not statistically different from placebo after 24 weeks (-0.41% and -0.44% for 5- and 10-mg doses, respectively, and -0.32% for placebo). The mean weight change from baseline was -1.54 and -1.89 kg for the 5- and 10-mg doses, respectively, and +0.21 kg for placebo. The mean systolic and diastolic blood pressure decreased in the dapagliflozin groups compared to placebo. Through 104 weeks, 13 patients receiving dapagliflozin and no patients receiving placebo experienced bone fracture. At 1 week, the mean serum creatinine increased with dapagliflozin 5 mg (+0.13 mg/dl) and 10 mg (+0.18 mg/dl) and did not change further after 104 weeks. Mean serum electrolytes did not change in any group, and there were fewer episodes of hyperkalemia with dapagliflozin than placebo. Thus, in patients with moderate renal impairment, dapagliflozin did not improve glycemic control, but reduced weight and blood pressure.
Pakistan’s doctors call for clarity on cause of Bhutto’s death
Authors: Ashfaq Yusufzai
Journal: BMJ (2008)

The Pakistan Medical Association has expressed concern over the conflicting medical reports regarding the death of former prime minister Benazir Bhutto and has asked for an international tribunal to be formed to ascertain the real causes of her death.

Umer Ayub Khan, the association’s president, said that the report compiled by the doctors at the Rawalpindi General Hospital had merely mentioned that Ms Bhutto died of temporal fracture, which he said was not enough.

The association says that the conflicting medical reports are sending the wrong messages among the medical community.

“It is important …
Bias in Treatment Assignment in Controlled Clinical Trials
Authors: Thomas C. Chalmers, Paul Celano, Henry S. Sacks, Harry Smith
Journal: New England Journal of Medicine (1983)

Abstract Controlled clinical trials of the treatment of acute myocardial infarction offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment. A group of 145 papers was divided into those in which the randomization process was blinded (57 papers), those in which it may have been unblinded (45 papers), and those in which the controls were selected by a nonrandom process (43 papers). At least one prognostic variable was maldistributed (P<0.05) in 14.0 per cent of the blinded-randomization studies, in 26.7 per cent of the unblinded-randomization studies, and in 58.1 per cent of the nonrandomized studies. Differences in case-fatality rates between treatment and control groups (P<0.05) were found in 8.8 per cent of the blinded-randomization studies, 24.4 per cent of the unblinded-randomization studies, and 58.1 per cent of the nonrandomized studies. These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration. (N Engl J Med 1983; 309:1358–61.)
Abstract 3051: CDC28 protein kinase subunit 1B (CKS1B) is a potential therapeutic target in esophageal adenocarcinomas overexpressing the CDK inhibitor p21Cip1/Waf1
Authors: Amin Ismail, Santhoshi Bandla, Liana Toia, Tony Godfrey
Journal: Cancer Research (2012)

Abstract Background: The incidence of adenocarcinoma of the esophagus and gastroesophageal junction (EAC) has grown faster than any tumor type in the United States and westernized countries, outpacing the next closest cancer by almost 3 times. This rising incidence of EAC is associated with the increasing prevalence of obesity and gastroesophageal reflux disease (GERD). Due to the limited effect of current chemotherapy for this cancer, the search for new therapeutic targets is disparately needed. Chromosomal amplification is one mechanism by which cancer cells acquire and maintain neoplastic phenotype and genes that are amplified and overexpressed may represent potential therapeutic targets. Methods: DNA and RNA from a cohort of 116 patients were analyzed using SNP and mRNA expression microarrays respectively. Gene amplification was explored for correlation with expression and patient survival. Results: 25% of tumors harbor amplification at chromosome 1q which is significantly associated with poor survival. Although the amplicon is non-focal spanning almost the entire arm of chromosome 1q, only a subset of amplified genes (including The CDC28 protein kinase subunit 1B, CKS1B) are significantly overexpressed. CKS1B is an auxiliary protein required for ubiquitination and cytosomal degradation of the CDK inhibitors p27Kip1 and p21Cip1/Waf1 by the SCFSKP2 E3 ubiquitin ligase complex. Both p27Kip1 and p21Cip1/Waf1 inhibits CDK2/Cyclin E complex during the G1/S cell cycle transition. The endogenous protein expression of p27Kip1 is low among EAC cell lines. However the expression of p21Cip1/Waf1 is differential being very high in a subset of cells and low or undetectable in others. Knocking down CKS1B by siRNA in six EAC cell lines results in accumulation of p27 Kip1 with little or no effect on p21Cip1/Waf1 expression. CKS1B knockdown inhibits monolayer cell proliferation only in cells with high endogenous expression of p21Cip1/Waf1. Conclusion: We suggest that the combined action of accumulation of p27 Kip1 and the endogenously highly expressed p21Cip1/Waf1 triggers the response to CKS1B knockdown in EAC cell lines. We thus propose the potential use of CKS1B as a novel therapeutic target in esophageal adenocarcinomas with high p21Cip1/Waf1 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3051. doi:1538-7445.AM2012-3051
Disorders of Higher Nervous Activity
Authors: James F. Toole
Journal: JAMA (1969)

Volume 3 of the<i>Handbook</i>surveys the borderlands that lie between neurology and psychiatry. It considers subjects for which no precise tools for measurement exist and no common terminology has been devised. Intelligence, the mind-brain relationship, consciousness, orientation, attention, and the time sense are covered by separate chapters contributed by recognized experts in the field. MacDonald Critchley provides an introductory chapter studded with pithy remarks—one of which, in my opinion, characterizes the difficulties that the entire field has experienced in the past: It is a wry thought that so many of the classical writers on the topic of highest level cerebral function and dysfunction have shown a singular defect in self-expression. Clarity of diction, which after all is the mirror of clear thinking, is only too often fogged over by the verbiage of the pedant. At times, this volume suffers from the defect which Dr. Critchley decries. However, the majority