tbuckley/cabot-search huggingface dataset:
Abstract 435: Targeted exome sequencing to understand tumor progression and identify targeted therapies
Authors: Danielle Greenawalt, James Hardwick, Theresa Zhang, Mark Ferguson, Patrick Lewis, Shane Hunstman, Shawn O'Brien, Zhidong Tu, Sergey Lezhnin, Andrey Loboda, Cathy Kerzner, Timothy J. Yeatman, William Dalton, Hongyue Dai
Journal: Cancer Research (2012)

Abstract There is a large effort in the public domain to systematically perform DNA and RNA sequencing on large numbers of tumor samples. These efforts will bring us to a greater understanding of tumor biology and lead to identification of new tumor drivers. However, these efforts may fall short in allowing us to understand the progression of tumor resistance, relapse and metastasis, factors which make tumors difficult to treat and increase mortality rates. We are currently performing targeted DNA sequencing on 4000 tumor samples. We have selected 1321 genes, 5 GB of the genome to sequence. Genes were selected through a thorough review of the literature, mutation databases and key pathways in tumorigenesis such as growth factor signaling, DNA damage, p53 signaling, cell cycle and apoptosis. Our effort not only includes a diverse panel of breast, colon, ovarian, and kidney tumors but we have also sequenced pancreatic, liver, esophageal, cervix, endometrial, melanoma, CLL, DLBCL and carcinoid tumors. Our dataset also includes approximately 300 matched tumor-metastatic pairs and an additional 550 metastatic samples. Clinical phenotypes, treatment information, gene expression profiling and copy number variation data is available for all samples. To achieve the next level of care for cancer patients we must understand the biology of the tumors we are trying to treat, which are often metastatic and standard of care resistant. We believe that increasing our efforts in targeted DNA sequencing of key tumor and metastatic samples will allow us to achieve these goals. 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 435. doi:1538-7445.AM2012-435
Intramural Pseudodiverticulosis of the Esophagus: A Case Series
Authors: B. Herter, H.-J. Dittler, A. Wuttge-Hannig, J. R. Siewert
Journal: Endoscopy (1997)

Intramural pseudodiverticulosis of the esophagus is a rare benign disease of the esophageal wall, with dilation of the submucosal glands, and the predominant symptom is dysphagia. In the literature, 191 cases have been described so far. Along with a short review of the literature, the present report describes six cases of this disorder, including a patient in whom intramural pseudodiverticulosis of the esophagus was secondary to laser therapy and endoluminal afterloading of an esophageal squamous-cell carcinoma.
Anaphylaxis to a Component of Isoetharine (Sodium Bisulfite)
Authors: Frank J. Twarog
Journal: JAMA (1982)

ADVERSE reactions to preservatives used in foods and medications are being recognized with increasing frequency. We have recently seen an asthmatic patient in whom wheezing and anaphylactoid symptoms developed after the administration of isoetharine hydrochloride and metoclopramide hydrochloride on separate occasions. The purpose of this report is to document that these hypersensitivity reactions resulted from sodium bisulfite, a preservative, used in the vehicles of these two drugs. <h3>Report of a Case</h3> The patient was an 18-year-old woman who had had perennial asthma since the age of 15 years. The first episode of wheezing occurred in 1974 while she was vacationing in Europe. While eating lunch, consisting of a hamburger and french fries, diffuse urticaria and wheezing developed and she required emergency therapy. She had eaten similar meals on previous occasions without difficulty. After her return to the United States, the patient experienced recurrent episodes of wheezing while eating restaurant meals.
Phospholamban Is Present in Endothelial Cells and Modulates Endothelium-Dependent Relaxation
Authors: Roy L. Sutliff, James B. Hoying, Vivek J. Kadambi, Evangelia G. Kranias, Richard J. Paul
Journal: Circulation Research (1999)

Abstract —Vascular endothelial cells regulate vascular smooth muscle tone through Ca 2+ -dependent production and release of vasoactive molecules. Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca 2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca 2+ ] i and contractility in these muscles. In the present study, we report the existence of PLB in the vascular endothelium, a nonmuscle tissue, and provide functional data on PLB regulation of vascular contractility through its actions in the endothelium. Endothelium-dependent relaxation to acetylcholine was attenuated in aorta of PLB-deficient (PLB-KO) mice compared with wild-type (WT) controls. This effect was not due to actions of nitric oxide on the smooth muscle, because sodium nitroprusside–mediated relaxation in either denuded or endothelium-intact aortas was unaffected by PLB ablation. Relative to denuded vessels, relaxation to forskolin was enhanced in WT endothelium-intact aortas. The endothelium-dependent component of this relaxation was attenuated in PLB-KO aortas. To investigate whether these changes were due to PLB, WT mouse aorta endothelial cells were isolated. Both reverse transcriptase–polymerase chain reaction and Western blot analyses revealed the presence of PLB in endothelial cells, which were shown to be &gt;98% pure by diI-acetylated LDL uptake and nuclear counterstaining. These data indicate that PLB is present and modulates vascular function as a result of its actions in endothelial cells. The presence of PLB in endothelial cells opens new fields for investigation of Ca 2+ regulatory pathways in nonmuscle cells and for modulation of endothelial-vascular interactions.
UK doctors' revalidation should be linked to registration
Authors: L. Beecham
Journal: BMJ (1999)

A steering group set up by the UK's General Medical Council (GMC) has concluded that an effective system of revalidation can be set up and has recommended that the system should be linked with registration. The group said that using the council's existing performance procedures would be the best way to review a doctor's registration in cases where there is evidence of poor performance.

The group has also …
The BMJ's stance on collaboration with industry
Authors: F. Godlee
Journal: BMJ (2013)

Goldacre asks how so many health organisations signed misleading guidelines for collaboration with the drug industry.1 Let me explain how this happened at the BMJ .

We asked the Association of the British Pharmaceutical Industry (ABPI) to sponsor two co-branded seminars—on access to clinical trial data and the role of industry in medical education. Working in partnership with a commercial sponsor was new for the BMJ . Both meetings went well, with lively debate from an invited audience.

The BMJ was not a member of the Ethical Standards in Health and Life Sciences Group (ESHLSG), had published an …
Urinary incontinence. GPs lack confidence.
Authors: J V Jolleys, J V Wilson
Journal: BMJ (1993)

The costs of implementing the Code of Practice for the Prevention of Infection in Clinical Laboratories appear to have been inflated in various ways. These include: alterations and improvements not required by the Code; rehabilitation of neglected buildings to conform with the requirements of the Health and Safety at Work Act; correction of poor design in recently built laboratories; suboptimal management and courses of instruction; and numerous committees.
Florbetapir-PET Imaging and Postmortem β-Amyloid Pathology—Reply
Authors: Christopher M. Clark
Journal: JAMA (2011)

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
Tailor-Made Monoclonal Antibodies
Authors: Ronald A. DePINHO, Lori B. Feldman, Matthew D. Scharff
Journal: Annals of Internal Medicine (1986)

Monoclonal antibodies, potentially powerful diagnostic and therapeutic reagents, are having a significant impact in basic and clinical research. Some persisting problems must be solved, however, in order to realize the potential of this technology. We review the basic biology of antibody molecules and the genes that encode them, and discuss how this knowledge can be applied to make more effective monoclonal antibodies.
Immunologic Specificity of Transfer Factor
Authors: Kenneth S. Zuckerman, James A. Neidhart, Stanley P. Balcerzak, Albert F. LoBuglio
Journal: Journal of Clinical Investigation (1974)

This study examined the immunologic specificity of transfer factor using a chromatographically purified transfer factor preparation. The specificity of transfer was examined utilizing immunity to keyhole limpet hemocyanin (KLH) and tuberculin. Transfer factor prepared from a donor immune to KLH successfully transferred KLH skin test reactivity to 10 out of 10 recipients. In contrast, comparable amounts of transfer factor from two donors not immune to KLH failed to transfer immunity to KLH in 11 recipients despite evidence for successful transfer of tuberculin reactivity. Unlike prior studies with a variety of antigens, the immunity to KLH in recipients of KLH immune transfer factor appeared comparable to that of the donor since both could be elicited with the same skin test antigen dose. These observations indicate that transfer factor can initiate a specific immune response to an antigen not previously encountered by the recipient and that in certain circumstances this immune response can be comparable to that of the donor. These observations on specificity and potency of transfer factor have important implications for the clinical use of this material.
The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement
Authors: M A Hussein, F D Vrionis, R Allison, J Berenson, S Berven, E Erdem, S Giralt, S Jagannath, R A Kyle, S LeGrand, R Pflugmacher, N Raje, S V Rajkumar, L Randall, D Roodman, D Siegel, R Vescio, J Zonder, B G M Durie
Journal: Leukemia (2008)
Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8.
Authors: E DiMango, H J Zar, R Bryan, A Prince
Journal: Journal of Clinical Investigation (1995)

Respiratory epithelial cells play a crucial role in the inflammatory response during Pseudomonas aeruginosa infection in the lungs of patients with cystic fibrosis. In this study, we determined whether the binding of specific Pseudomonas gene products (pilin, flagellin) to their receptors on respiratory epithelial cells would result in production of the neutrophil chemoattractant IL-8. Piliated wild-type organisms, purified pili, or antibody to the pilin receptor (asialoGM1) evoked significant production of IL-8 by immortalized airway epithelial cells, whereas nonpiliated organisms were less able to bind to respiratory epithelial cells and stimulated much less IL-8 secretion (P < 0.01). A piliated, nonflagellated strain was also associated with decreased binding and a diminished level of IL-8 production when compared to wild-type organisms. Isogenic, nonadherent rpoN mutants, lacking pilin and flagellin, did not bind or elicit an IL-8 response. In addition, the IL-8 response was four-fold higher in a cystic fibrosis cell line compared with its corrected cell line. The Pseudomonas autoinducer, an exoproduct secreted during chronic infection, was found to stimulate IL-8 in a dose-dependent manner. P. aeruginosa adhesins, which are necessary for initial infection, directly stimulate IL-8 production by respiratory epithelial cells and therefore play a major role in the pathogenesis of Pseudomonas infection in patients with cystic fibrosis. The inflammatory response is subsequently perpetuated by Pseudomonas autoinducer which is secreted during chronic infection.
Major alterations in relaxation during cardiac hypertrophy induced by aortic stenosis in guinea pig.
Authors: Y Lecarpentier, A Waldenström, M Clergue, D Chemla, P Oliviero, J L Martin, B Swynghedauw
Journal: Circulation Research (1987)

Left ventricular hypertrophy (LVH) was produced in guinea pigs after aortic stenosis (AS). The percentage of LVH in AS was determined by normalizing left ventricular (LV) weight by the mean LV weight of sham-operated controls (n = 12). After 3 weeks of cardiac overload, a mild LVH (30 +/- 3%) was induced in 17 animals and a relatively severe LVH (56 +/- 3%) was induced in 7 animals. LV papillary muscles were rapidly excised for mechanical studies. No significant differences were observed between control and mild hypertrophy groups. In contrast, a marked decrease in myocardial performance was seen in the more severe cardiac hypertrophy group and was expressed as a percentage of sham-operated levels (Vmax, 22%; active isometric force/mm2, 23%; +dF/dt max/mm2, 26%). Relaxation in this group was still more impaired than contraction (peak lengthening velocity, 14%; -dF/dt max/mm2, 19%). Moreover, the load sensitivity of relaxation was present in both sham-operated controls and mild hypertrophy but almost disappeared in more severe hypertrophy. Isometric relaxation was delayed in the latter group, as shown by the 15% increase of the half-time of the decline of isometric relaxation (t 1/2). On the other hand, acute hypoxia (95% N2-5% CO2 for 20 minutes) also induced a fall in contractility and the disappearance of the load sensitivity of relaxation but with a 67% decrease of t 1/2. Thus, the mechanical analysis of relaxation allows the effects of chronic overload in relatively severe cardiac hypertrophy to be separated from those of acute hypoxia. Moreover, in severe cardiac hypertrophy, the impairment of the load sensitivity of relaxation with increased t 1/2 strongly suggests alterations of the sarcoplasmic reticulum, especially since the moderate decrease in the myofibrillar ATPase activity, which has been observed previously in guinea pig pressure overload, cannot account completely for the marked fall in myocardial performance.
ATM Acts Downstream of ATR in the DNA Damage Response Signaling of Bystander Cells
Authors: Susanne Burdak-Rothkamm, Kai Rothkamm, Kevin M. Prise
Journal: Cancer Research (2008)

Abstract This study identifies ataxia-telangiectasia mutated (ATM) as a further component of the complex signaling network of radiation-induced DNA damage in nontargeted bystander cells downstream of ataxia-telangiectasia and Rad3-related (ATR) and provides a rationale for molecular targeted modulation of these effects. In directly irradiated cells, ATR, ATM, and DNA-dependent protein kinase (DNA-PK) deficiency resulted in reduced cell survival as predicted by the known important role of these proteins in sensing DNA damage. A decrease in clonogenic survival was also observed in ATR/ATM/DNA-PK–proficient, nonirradiated bystander cells, but this effect was completely abrogated in ATR and ATM but not DNA-PK–deficient bystander cells. ATM activation in bystander cells was found to be dependent on ATR function. Furthermore, the induction and colocalization of ATR, 53BP1, ATM-S1981P, p21, and BRCA1 foci in nontargeted cells was shown, suggesting their involvement in bystander DNA damage signaling and providing additional potential targets for its modulation. 53BP1 bystander foci were induced in an ATR-dependent manner predominantly in S-phase cells, similar to γH2AX foci induction. In conclusion, these results provide a rationale for the differential modulation of targeted and nontargeted effects of radiation. [Cancer Res 2008;68(17):7059–65]
Congenital Heart Disease and Brain Injury
Authors: Michael V. Johnston
Journal: New England Journal of Medicine (2007)

During the past 25 years, remarkable progress has been made in the surgical treatment and survival of infants with congenital heart disease.1 Recent data have shown that in-hospital death rates for neonates were less than 10% for the treatment of transposition of the great arteries with the arterial-switch procedure and less than 20% for the treatment of hypoplastic left heart syndrome with aortic arch reconstruction using the Norwood procedure.2 Before the development of the Norwood procedure in 1980, the vast majority of infants with hypoplastic left heart syndrome died.3 On the other hand, several studies have shown that many children . . .
Bone metabolism during methylprednisolone pulse therapy in rheumatoid arthritis.
Authors: J W Bijlsma, S A Duursma, O Huber-Bruning
Journal: Annals of the Rheumatic Diseases (1986)

The deleterious effects of corticosteroids (CS) on bone are well known, but probably differ depending on duration and dosage of CS therapy. Presently huge amounts of CS are given over a short period of time in different rheumatic conditions. Not much is known about the effect of this kind of CS treatment on bone metabolism. Twenty patients with persistently active rheumatoid arthritis were treated with 1 g methylprednisolone (MP) three times on alternate days over a five day period. Twenty four hours after the first MP pulse serum calcium was increased and the values of parathyroid hormone and 1,25-dihydroxyvitamin D tended to increase. After the second MP pulse, however, these values had returned to the starting values. The urinary calcium excretion increased during MP pulse therapy and returned to the initial value immediately after the pulse therapy. The hydroxyproline excretion tended to decrease during therapy and stayed decreased immediately afterwards, indicating a decrease in bone resorption. It is concluded that bone metabolism is not seriously affected during MP pulse therapy.
Assessment of care of children with sickle cell disease: implications for neonatal screening programmes.
Authors: R I Milne
Journal: BMJ (1990)

OBJECTIVE--To assess the quality of care provided by hospitals for young children with sickle cell disease. DESIGN--Retrospective survey. SETTING--Teaching hospital in London. PATIENTS--31 Children (mean age 4 years 4 months, range 4 months to 7 years 5 months) born with sickle cell disease between 1978 and 1985 identified from Hospital Activity Analysis data, an outpatient diagnostic register, and registers of the haematology department. Eight had been diagnosed on neonatal screening and at least four of these had not been followed up. MAIN OUTCOME MEASURES--Aspects of quality of outpatient care (blood testing, clinic attendance, and prophylactic drug treatment) and family care (adequate support and carers9 knowledge about the disease) as assessed by reviewing the notes and administering a semistructured questionnaire to the carers, in relation to a devised list of standards deemed necessary to ensure achievement of the aims of screening. RESULTS--There were 93 outpatient attendances during the previous 12 months, but 13 children had not attended at least every six months and four not at all for more than a year. Only eight children had had three of the blood tests considered to be necessary for good care; three had had none. Prophylactic treatment with penicillin and folic acid was erratic; three children with sickle cell anaemia were not receiving regular prophylactic penicillin. IMPLICATION--Diagnosis of sickle cell disease on neonatal screening must be linked with follow up to ensure optimal management.
Roentgenographic Observations in the Zollinger-Ellison Syndrome
Authors: John R. Amberg, Edwin H. Ellison, Stuart D. Wilson, F. Frank Zboralske
Journal: JAMA (1964)

A severe ulcer diathesis may be caused by a hormone secreted by the non-beta cells of the pancreatic islets. This hormone stimulates the parietal cells to hypersecrete. Secondary changes observed by roentgenography consist of increased bowel fluid, ulceration, edema, dilatation, gastric and duodenal hypomotility, and jejunal hypermotility. These changes are often distinct enough to suggest the diagnosis of Zollinger-Ellison syndrome. An accurate preoperative diagnosis of this condition is important if the proper ablative therapy is to be carried out.
C1-07: IPI-504, a novel HSP90 inhibitor is effective in EGFR T790M and Non-T790M Gefitinib-resistant Lung Cancer Cell Lines.
Authors: Joon Oh Park, Feng Zhao, Kreshnik Zejnullahu, Emmanuel Normant, Jeffrey A. Engelman, Bruce E. Johnson, Pasi A. Jänne
Journal: Journal of Thoracic Oncology (2007)
Only the Shadow Knows
Authors: M. J. Zerbe
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Only the Shadow Knows Get access Michael J. Zerbe Michael J. Zerbe Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 10, 16 May 1990, Page 821, https://doi.org/10.1093/jnci/82.10.821 Published: 16 May 1990
A national ethics committee
Authors: K Korlipara
Journal: BMJ (1989)

and the screening study (0-6% of the entire adult population v 3-5% of the 2000 screened subjects visiting a primary care centre) is not surprising.A much larger fraction of patients visiting a primary care unit will be taking thyroxine than in the general population.Furthermore, the prevalence found in patients visiting the primary care centre agrees with our previous findings in subjects seeking hospital care.'
Evaluation of Patients with Chronic Diarrhea
Authors: Mark Donowitz, Freddy T. Kokke, Roxan Saidi
Journal: New England Journal of Medicine (1995)

Patients who report having diarrhea for more than four weeks should be evaluated for chronic diarrheal diseases, since most infectious enteritides and other causes of acute diarrhea generally resolve spontaneously within this period.13 We suggest a two-stage outpatient evaluation, which relies initially on the history and physical examination to direct studies and then on a systematic outpatient evaluation, followed, if necessary, by a third-stage inpatient evaluation. This approach should lead to a diagnosis in approximately 90 percent of patients. Patients with diarrhea experience a change in the consistency or frequency of their bowel movements. Diarrheal diseases are almost always . . .
A Comparison of Real-Time Compression Ultrasonography with Impedance Plethysmography for the Diagnosis of Deep-Vein Thrombosis in Symptomatic Outpatients
Authors: Harriet Heijboer, Harry R. Buller, Anthonie Lensing, Alexander Turpie, Louisa P. Colly, Jan Wouter ten Cate
Journal: New England Journal of Medicine (1993)

Impedance plethysmography performed serially over a one-week period has been shown to be an effective diagnostic strategy for patients with clinically suspected acute deep-vein thrombosis. Compression ultrasonography has a high sensitivity and specificity for the detection of proximal-vein thrombosis. The clinical value of repeated ultrasonography in the management of symptomatic deep-vein thrombosis is unknown.