tbuckley/cabot-search huggingface dataset:
Abstract 4570: Using laser capture microdissection functionally coupled with mass spectrometry for an enhanced study of solid tumor heterogeneity via tissue proteomics
Authors: Donald J. Johann, Sumana Mukherjee, Jaime Rodriquez-Canales, Jeffrey Hanson, DaRue Prieto, Timothy D. Veenstra, Michael Emmert-Buck, Josip Blonder
Journal: Cancer Research (2010)

Abstract Introduction Examining solid tumor heterogeneity using a tissue proteomics approach, which relies on a functional coupling between Laser Capture Microdissection (LCM) and biological mass spectrometry (MS), is the purpose of this research study. A common characteristic of solid tumors is a heterogeneous architecture, which enables distinct cellular morphologies and molecular behaviors. This diverse composition of cells, specifically cancer cells proper along with both modified and unmodified stromal elements, collectively forms a microenvironment that serves to nurture the malignant process. Methods Using LCM, homogeneous regions of cells exhibiting uniform histology were isolated and captured from fresh frozen tissue specimens, which were obtained from a human lesion of breast carcinoma metastasis. All slides were reviewed by a pathologist and the LCM session planned. Multiple specimens each containing ∼ 50,000 cells were collected by LCM. Specimens were processed directly on LCM caps, using sonication in buffered methanol to lyse captured cells, solubilize, and digest extracted proteins. Preliminary results Prepared samples were analyzed by LC-MS/MS resulting in more than 500 unique protein identifications. High confidence measures were employed by including only proteins identified by ≥ 2 unique peptides. Decoy database searching revealed a false-positive rate between 5 and 10%. Machine learning methods assisted with molecular profiling activities to better discern the concurrent expression of multiple cellular phenotypes due to the heterogeneity of the solid tumor. Cross validation via Western Blot analysis confirmed specific linkage of 12 validated proteins to underlying pathology and their potential role in solid tumor heterogeneity. Summary and conclusion Solid tumors are composed of an assortment of cell types, which have diverse morphologies, as well as distinct molecular phenotypes. Tumor heterogeneity may be viewed as a memory of the malignant process and thus a novel proteomic study may yield insights regarding cancer development and more effective treatment. The biological background of such heterogeneity is not well understood. With continued research and optimization of this method including analysis of additional clinical specimens, this approach may lead to an improved understanding of tumor heterogeneity, and serve as a platform for solid tumor biomarker discovery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4570.
STRESS ECHOCARDIOGRAPHY INCORPORATED INTO AN ACUTE CHEST PAIN SERVICE PROVIDES EXCELLENT FEASIBILITY, RAPID ASSESSMENT WITH EARLY TRIAGING AND ACCURATE RISK STRATIFICATION OF PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME BUT NON-DIAGNOSTIC ECG AND NEGATIVE 12-HR TROPONIN
Authors: Benoy Shah, Gothandaraman Balaji, Abdalla Al Hajiri, Ihab Ramzy, Shahram Ahmadvazir
Journal: Journal of the American College of Cardiology (2012)
Doctors face two year pay freeze if Conservatives gain power
Authors: N. Timmins
Journal: BMJ (2009)

GPs face a two year pay freeze and hospital doctors a tiny rise followed by a freeze if the Conservative Party gains power at the next general election.

This is the likely outcome of two days of intensive politicking around the Conservative Party conference, which started on 5 October, as Labour tried to trump any Tory announcement on pay and as George Osborne, the shadow chancellor, started to spell out what a Conservative government would do to cut the United Kingdom’s massive deficit.

For months it has been clear that the public sector in general and the NHS in particular will face a sustained period of pain …
Having electronic preprints is logical
Authors: J. McConnell, R. Horton
Journal: BMJ (1998)

EDITOR— Delamothe asks what the policy of journals should be on publication on the internet of electronic preprints (“eprints”).1He points out that some journals, including the New England Journal of Medicine and, currently, the BMJ , reject papers whose substance has already appeared as an eprint because they regard this manoeuvre as prior publication. This policy is illogical and impossible to police. What is the difference between the published abstract of a study presented at a conference and an eprint? The only …
P41 DOES THE GUT MICROBIOTA MODULATE THE INFLAMMATORY STATE IN CIRRHOTIC HOST?
Authors: V. Giannelli, V. Di Gregorio, C. Lucidi, V. Iebba, F. Santangelo, A.F. Attili, O. Riggio, S. Schippa, M. Merli
Journal: Journal of Hepatology (2014)
NCI Awards Jackson Lab $9.5 Million To Rebuild
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article NCI Awards Jackson Lab $9.5 Million To Rebuild Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 21, 7 November 1990, Page 1674, https://doi.org/10.1093/jnci/82.21.1674 Published: 07 November 1990
Psychological consequences of segregation resulting from chronic Burkholderia cepacia infection in adults with CF
Authors: A J A Duff
Journal: Thorax (2002)

Patients with CF segregated because of Burkholderia cepacia infection must be helped to assemble coherent structures for social relationships if they are to adapt successfully to such management.

In 1997 the median life expectancy for individuals with cystic fibrosis (CF) was 31.5 years in the UK1 and it has been suggested that those born today can expect to live well into their mid 40s.2 However, there is huge variability in the physical condition of adults with CF. While malabsorption, osteoporosis, diabetes, and liver failure all contribute to incapacity, lung disease is the main cause of morbidity and mortality. Some patients have near normal levels of lung function. Others, however, are debilitated by dyspnoea and dependent on oxygen.

Lung disease in CF is primarily due to the consequences of infection. In the first decade of life Staphylococcus aureus and Haemophilus influenzae are the predominant organisms in sputum, while in older children and adults Pseudomonas aeruginosa is most common.3 In the past 15 years some CF centres have had epidemics of Burkholderia cepacia infection. Although patients respond to standard antibiotic treatment,4 most become chronically infected and experience a more rapid decline in lung function. The reasons for this are still unclear, although recent microbiological findings suggest that there are different pathogenic potentials of various B cepacia genomovars.5 In the UK prevalence rates vary between centres but increase significantly if spread from patient to patient is not prevented. In this respect, B cepacia differs from other bacteria in that it is usually caught through close or frequent contact with another B cepacia positive CF patient.5,6

In most UK adult CF centres it is now accepted practice to separate patients who are infected with B cepacia from those who are not. Guidelines on cross infection effectively mean …
Does Delayed Childbearing Increase Risk?-Reply
Authors: Heinz W. Berendes
Journal: JAMA (1993)

In Reply.  —We thank Berkowitz et al for their comments. Women who delay childbearing in both countries are well-educated, married, healthy, smoke less, and attend prenatal care early. In our study, 49% of women aged 30 years and older had a college education or more, which is identical to that quoted for the United States (written communication, S. J. Ventura, National Center for Health Statistics, Hyattsville, Md, October 25,1989). Cigarette smoking among women who delay childbearing was 24% in Sweden and 26% in the United States among white females aged 13 to 15 years, and 16.4% in those with 16 or more years of education. By contrast, in the Mount Sinai study, 94% of the women had attended college—a rate about twice as high as that in the United States and Sweden. Smoking was reported for 3.6%, which is only a fraction of the rate reported for the United States
Cannabis: the next villain on the lung cancer battlefield?
Authors: C. Brambilla, M. Colonna
Journal: European Respiratory Journal (2008)

Lung cancer epidemics arose and spread in western countries when the tobacco industry created the manufactured cigarette and realised that nicotine addiction was the most adaptable way to increase and secure long-term sales 1. In spite of well-known toxicity of tobacco smoke 2 and the proven relationship of tobacco smoking with lung cancer incidence 3, the tobacco industry took advantage of the lack of response by western governments, concerning the alarms raised by physicians and citizen associations, and set up a very powerful marketing process directed at smokers, adult males and nonsmokers, females and adolescents with devastating effects. In all western countries the percentage of smokers increased, and the age at which the first cigarette was smoked decreased. Since susceptibility of females to tobacco carcinogens is higher, lung cancer in females equalled or exceeded lung cancer in males in different countries 4, even in females with a lower, but regular, cigarette consumption. The age of lung cancer occurrence followed the age that people started smoking. In the 1950s, the average ages for the first cigarette smoked and for lung cancer onset were 20–30 yrs and ≥60 yrs, respectively, but at the turn of the 20th century these were <12 yrs and ≥40 yrs, respectively. The electroshock was the revelation of the tobacco industry’s …
Media coverage of the Child B case
Authors: V. A Entwistle, I. S Watt, R. Bradbury, L. J Pehl
Journal: BMJ (1996)

The case of a girl with leukaemia, known as Child B, hit the headlines in March 1995 when her father refused to accept the advice of doctors who counselled against further treatment and took Cambridge and Huntingdon Health Authority to court for refusing to fund chemotherapy and a second bone transplant for her in the private sector. British national newspapers varied greatly in the way they covered the case. Some paid little attention to clinical considerations and presented the case as an example of rationing based on financial considerations. Their selective presentations meant that anyone reading just one newspaper would have received only limited and partial information. If members of the public are to participate in debates about treatment decisions and health care rationing, means other than the media will need to be found to inform and involve them.
The Visual Fields: Text and Atlas of Clinical Perimetry
Authors: Benjamin Hendrik Ticho
Journal: JAMA (1990)

The visual field is a map of the visual system, from the optic nerve through the optic chiasm and optic tracts, to the visual cortex. Ever since Hippocrates described hemianopic field defects during the fifth century BCE, physicians have used this map in navigating the waters of ophthalmology and neurology. Defects in recognition of light stimulation at various positions and intensities can be useful in localizing pathological conditions, including glaucoma, optic neuritis, pituitary adenomas, and intracerebral aneurysms. Improved radiological imaging (especially computed tomographic and magnetic resonance scanning) has supplanted some of the importance of the visual field as a localizing tool. Nonetheless, familiarity with the techniques and interpretation of field data is important for both diagnosis and follow-up of neuro-ophthalmologic conditions. This textbook is a classic in the clinical perimetry literature. The first edition appeared in 1956, when perimetry was coming into widespread use, thanks in large part to the
The prevalence of clinically significant sleep apnoea syndrome in the Netherlands
Authors: A K. Neven, H A M Middelkoop, B Kemp, H A C Kamphuisen, M P Springer
Journal: Thorax (1998)

Figures for the prevalence of sleep apnoea syndrome range from 0.3% to 8.5%. These widely ranged estimates are probably due to differences in the definitions used, study designs, and study populations. A study was undertaken to determine the lower limit of the prevalence of clinically significant sleep apnoea syndrome.A cross sectional survey by postal questionnaire was carried out in a general practice of a small town in which three doctors serve 93% of its population of 6747 inhabitants of all ages. All men aged 35 and over and women aged 50 and over were invited to fill in a specially designed questionnaire on snoring and sleep. All men and women whose answers suggested the possible occurrence of sleep apnoea were invited to undergo further investigation. Oronasal thermistry was performed in the subjects' homes and the results were scored to provide an apnoea index (AI). Those subjects with an AI of > or = 5 were referred to a sleep laboratory for investigation by polysomnography.Of the 2466 questionnaires issued, 2182 (88.5%) were completed and returned. The occurrence during the previous three months of regular snoring, together with daytime sleepiness and/or partners' observation of interruptions in breathing at night, was reported by 194 subjects (169 men, 25 women). In 173 subjects oronasal thermistry applied in their homes provided satisfactory recordings and, of these, 24 men and one woman had an AI of > or = 5. Analysis of the polysomnographic findings showed that 14 men and one woman met the criteria for sleep apnoea syndrome. Scrutiny of their case records disclosed that in seven men this was clinically significant.Our findings suggest that the prevalence of clinically significant sleep apnoea syndrome in men aged 35 and over is at least 0.45%. Extrapolation to the population of the Netherlands suggests that at least 16,000 men suffer from sleep apnoea syndrome that should be relieved by medical care. A large proportion of these subjects remains to be diagnosed.
Docetaxel prolongs life in men with hormone refractory prostate cancer
Authors: Scott Gottlieb
Journal: BMJ (2004)

Within the past three decades, extensive research has been carried out with the aim to prevent graft rejection by minimizing the side effects related to the use of immunosuppressants. The major goal in transplantation research remains the development of strategies that would allow one to achieve a state of donor-specific unresponsiveness in order to promote a condition of true tolerance without the need of immunosuppressants. Recent evidence has been provided that this is a pursuing goal, at least in experimental animals. The thymus plays the major role in the development of self-tolerance, and initial work in the late 1960s indicated that the thymus also plays a critical role in the induction of acquired tolerance to exogenous antigens. Recently, the interest in acquired thymic tolerance has been renewed by the observation that, in the rat, the thymus is an immunologically privileged site in which isolated pancreatic islets can be engrafted and survive indefinitely. Moreover, intrathymic injection of the islets induced donor-specific unresponsiveness, which allowed survival of a second donor-strain islet cell allograft transplanted into an extrathymic site. These findings on cellular allografts have been extended to vascularized organ allografts.(ABSTRACT TRUNCATED AT 250 WORDS)
Medical Consultation for Surgical Cases in the Era of Value-Based Care
Authors: Gulshan Sharma
Journal: JAMA Internal Medicine (2014)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 Internal Medicine journal
Molecular modeling studies suggest that zinc ions inhibit HIV-1 protease by binding at catalytic aspartates.
Authors: D M York, T A Darden, L G Pedersen, M W Anderson
Journal: Environmental Health Perspectives (1993)

Human immunodeficiency virus type 1 protease is inhibited in vitro by zinc ions at neutral pH. The binding site of these ions is not known; however, experimental data suggest that binding may occur in the active site. To examine the possibility of zinc binding in the active site, molecular dynamics simulations in the presence and absence of zinc have been carried out to 200 psec. The results are compared with the 2.8-A crystallographic structures of a synthetic HIV-1 protease, and a zinc binding site at the catalytic aspartate residues (Asp-25, Asp-25') is proposed. Molecular dynamics simulations show that the zinc ion remains stably bound in this region, coordinating the carboxylate side chains of both aspartate residues. Interaction with zinc does not disrupt the dimeric structure of the protein or significantly alter the structure of the active site. These data are consistent with experimental studies of HIV-1 protease inhibition by zinc and give strong evidence that this is the binding site that leads to inactivation.
Distribution of body water in patients with cirrhosis: The effect of liver transplantation
Authors: Darrell H. G. Crawford, June W. Halliday, W. G. E. Cooksley, Therese L. Murphy, Suzanne D. Golding, Jennifer D. Wallace, Ross C. Cuneo, Steven V. Lynch, Russell J. Strong, Lawrie W. Powell
Journal: Hepatology (1993)

We compared total body water and intracellular-extracellular distribution of body water between male patients with mild liver disease without ascites (n = 9), male patients with severe liver disease and gross ascites (n = 6) and a group of age-, sex-, height- and weight- matched controls (n = 6). In addition, we documented the effects of liver transplantation on intracellular, extracellular and total body water in 12 patients (6 men and 6 women) by means of deuterium oxide dilution and whole-body potassium counting. We saw no significant difference in total body water between the healthy controls, patients without ascites and patients with ascites (46.5 +/- 9.2 kg, 45.4 +/- 6.6 kg and 50.4 +/- 5.1 kg, respectively), although, as expected, extracellular water was increased in patients with ascites compared with healthy controls and cirrhotic patients without ascites (36.9 +/- 6.5 kg vs. 25.4 +/- 4.4 kg, p = 0.005; and 36.9 +/- 6.5 kg vs. 27.0 +/- 5.3 kg, p = 0.002, respectively). We found no difference between non-ascitic patients and healthy controls (25.4 +/- 4.4 kg vs. 27.0 +/- 5.3 kg). However, intracellular water was significantly reduced in patients with severe liver disease compared with that in controls (13.6 +/- 3.3 kg vs. 21.5 +/- 4.2 kg, p = 0.005) or patients without ascites (13.6 +/- 3.3 kg vs. 18.3 +/- 2.9 kg, p = 0.01). The reduction of intracellular water appears to be due to loss of body cell mass.(ABSTRACT TRUNCATED AT 250 WORDS)
SOX5 Is a Candidate Gene for Chronic Obstructive Pulmonary Disease Susceptibility and Is Necessary for Lung Development
Authors: Craig P. Hersh, Edwin K. Silverman, Jody Gascon, Soumyaroop Bhattacharya, Barbara J. Klanderman, Augusto A. Litonjua, Véronique Lefebvre, David Sparrow, John J. Reilly, Wayne H. Anderson, David A. Lomas, Thomas J. Mariani
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Chromosome 12p has been linked to chronic obstructive pulmonary disease (COPD) in the Boston Early-Onset COPD Study (BEOCOPD), but a susceptibility gene in that region has not been identified.We used high-density single-nucleotide polymorphism (SNP) mapping to implicate a COPD susceptibility gene and an animal model to determine the potential role of SOX5 in lung development and COPD.On chromosome 12p, we genotyped 1,387 SNPs in 386 COPD cases from the National Emphysema Treatment Trial and 424 control smokers from the Normative Aging Study. SNPs with significant associations were then tested in the BEOCOPD study and the International COPD Genetics Network. Based on the human results, we assessed histology and gene expression in the lungs of Sox5(-/-) mice.In the case-control analysis, 27 SNPs were significant at P ≤ 0.01. The most significant SNP in the BEOCOPD replication was rs11046966 (National Emphysema Treatment Trial-Normative Aging Study P = 6.0 × 10(-4), BEOCOPD P = 1.5 × 10(-5), combined P = 1.7 × 10(-7)), located 3' to the gene SOX5. Association with rs11046966 was not replicated in the International COPD Genetics Network. Sox5(-/-) mice showed abnormal lung development, with a delay in maturation before the saccular stage, as early as E16.5. Lung pathology in Sox5(-/-) lungs was associated with a decrease in fibronectin expression, an extracellular matrix component critical for branching morphogenesis.Genetic variation in the transcription factor SOX5 is associated with COPD susceptibility. A mouse model suggests that the effect may be due, in part, to its effects on lung development and/or repair processes.
MORBIDITY, VASCULAR EVENTS AND INTERVENTIONAL THERAPY FOR FIBROMUSCULAR DYSPLASIA: A REPORT OF THE FIBROMUSCULAR DYSPLASIA PATIENT REGISTRY
Authors: Heather L. Gornik, James B. Froehlich, Xiaokui Gu, J. Michael Bacharach, Bruce Gray, Mark A. Grise, Soo Hyun Kim, Eva Kline-Rogers, Pamela D. Mace, Robert McBane, Jeffrey W. Olin
Journal: Journal of the American College of Cardiology (2011)
Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans
Authors: Kara L O'Brien, Jinyan Liu, Sharon L King, Ying-Hua Sun, Joern E Schmitz, Michelle A Lifton, Natalie A Hutnick, Michael R Betts, Sheri A Dubey, Jaap Goudsmit, John W Shiver, Michael N Robertson, Danilo R Casimiro, Dan H Barouch
Journal: Nature Medicine (2009)
Food intolerance and the irritable bowel syndrome.
Authors: R Nanda, R James, H Smith, C R Dudley, D P Jewell
Journal: Gut (1989)

Two hundred patients (156 women) with the irritable bowel syndrome were treated with dietary exclusion for three weeks. Of the 189 who completed this study, 91 (48.2%) showed symptomatic improvement. Subsequent challenge with individual foods showed that 73 of these 91 responders were able to identify one or more food intolerances and 72 remained well on a modified diet during the follow up period (mean (SD), 14.7 (7.98) months). Of the 98 patients who showed no symptomatic improvement after three weeks of strict exclusion only three were symptomatically well at follow up (mean (SD), 12.48 (8.09 months). There was no close correlation between response and symptom complex. There was a wide range of food intolerance. The majority (50%) identified two to five foods which upset them (range 1-14). The foods most commonly incriminated were dairy products (40.7%) and grains (39.4%).