tbuckley/cabot-search huggingface dataset:
Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene.
Authors: M J McPhaul, M Marcelli, S Zoppi, C M Wilson, J E Griffin, J D Wilson
Journal: Journal of Clinical Investigation (1992)

We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminization, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90%) cluster in two regions that account for approximately 35% of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-beta) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex.
Diuretics, Potassium, and Ventricular Arrhythmias
Authors: Vasilios Papademetriou
Journal: JAMA (1992)

To the Editor.  —It was interesting to read the article by Siegel et al in the February 26 issue ofThe Journal.1We have repeatedly shown that diuretic-induced hypokalemia does not in fact cause arrhythmias in patients with uncomplicated mild to moderate hypertension.  I was pleased and reassured that their data in a large population confirmed our observations. In the last 9 years, we have performed studies in hypertensive patients with or without left ventricular hypertrophy and in patients2with mild3and moderate or severe left ventricular hypertrophy.4We assessed the effect of exercise5on ventricular arrhythmias in diuretic-treated patients and the effect of potassium correction in seriously hypokalemic patients.6These studies included over 130 patients and yet we found no evidence that hypokalemia aggravates ventricular arrhythmias. In that respect we are in agreement with Siegel et al. However, we differ on their finding
Soy Isoflavones Augment Radiation Effect by Inhibiting APE1/Ref-1 DNA Repair Activity in Non-small Cell Lung Cancer
Authors: Vinita Singh-Gupta, Michael C. Joiner, Lindsay Runyan, Christopher K. Yunker, Fazlul H. Sarkar, Steven Miller, Shirish M. Gadgeel, Andre A. Konski, Gilda G. Hillman
Journal: Journal of Thoracic Oncology (2011)
Ionising radiation in infancy and adult cognitive function
Authors: Lynn Howard Ehrle
Journal: BMJ (2004)

Editor—Hall et al say that little is known about the effects of low doses of radiation or a possible threshold value, ignoring a large body of scientific evidence.1

Muller said in 1955 that radiation produces permanent changes, mutations, no matter how long or how short a time the total dose was received—more than 99% are harmful, causing some functional impairment.2 A survey by Stewart et al followed in 1958, the first human study documenting cancer and leukaemia in children whose mothers had been exposed to in utero x ray of only 1-2 rad.3 In 1969-70 Gofman presented several studies to congressional committees dealing with low dose issues and authored five books on human health effects, the latest linking at least 50% of cancers and ischaemic heart disease to the primary co-action of medical x rays.4 Recently 15 cancer experts published a review confirming these earlier warnings, indicating there is good evidence for cancer risk in the 1-5 rad range.

US journalist Laurie Garrett observed that scientists who independently studied the human health impacts of low level radiation would be vilified, their reputations smeared.5 Many researchers have been scientifically shunned and subjected to attacks on their person. History will show that much substantial low dose research is still hidden.
An 82-Year-Old Woman With Mood Changes Following a Stroke
Authors: Robert G. Robinson
Journal: JAMA (2000)

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
Detection of p53 gene mutations in cytopathology and biopsy specimens from patients with lung cancer.
Authors: I Murakami, Y Fujiwara, N Yamaoka, K Hiyama, S Ishioka, M Yamakido
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

In order to ascertain the feasibility of detecting p53 gene mutations in patients with lung cancer in a nonsurgical diagnostic setting before starting treatment, we screened for p53 gene mutations in tumor specimens obtained using diagnostic methods such as fiberoptic bronchoscopy, thoracentesis, and percutaneous needle aspiration. We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiroshima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis technique. p53 gene mutations were found in 64 of 159 (40%) cytologically positive specimens, but in none of 47 cytologically negative specimens. The PCR-based assay did not increase the sensitivity of the cytopathologic examination in detecting malignant cells. The type and location of the p53 gene mutation was the same in cytologically positive specimens obtained by different methods, but from the same patient. Of the 66 patients, p53 gene mutations were found in 27 (41%) at the time of the first nonsurgical diagnostic examination: 7 of 12 (58%) with small cell carcinoma, 9 of 20 (45%) with squamous cell carcinoma, and 11 of 34 (32%) with adenocarcinoma of the lung. The incidence of p53 gene mutation for each histologic subtype was comparable to previously published data examining surgically and/or autopsy-obtained specimens. These results indicate that detection of p53 gene mutations in a nonsurgical, diagnostic setting is feasible. This technique will make it possible to assess the significance of p53 gene mutations in relation to survival and response to therapy before starting treatment, in future prospective studies.
Response of the Arterial Po<sub>2</sub>to Oxygen Administration in Chronic Pulmonary Disease
Authors: JOHN C. MITHOEFER
Journal: Annals of Internal Medicine (1971)

In 34 patients with emphysema, 12 patients with pulmonary insufficiency from other causes, and 14 normal subjects, arterial Po2, Pco2, and pH were measured when inspired oxygen concentration was 21%, 24%, 28%, 35%, 40%, and 100%, The dead space to tidal volume ratio was measured during ambient air breathing in all, as was venous admixture in 21 patients and 8 normals. An explanation based on variability of the abnormality of alveolar ventilation to blood flow ratio is offered for the known wide variation in the response of arterial Po2 to inspired O2 concentrations among patients with pulmonary disease. Linear regressions are described that allow estimation of response to a given oxygen concentration based on measurement of arterial Po2 during air breathing. These regressions apply to a variety of chronic lung diseases, suggesting similarities in the distribution of low ratios of alveolar ventilation to blood flow in chronic pulmonary disease regardless of etiology.
New polyps, old tricks: controversy about removing benign bowel lesions
Authors: G. Hoff, M. Bretthauer, K. Garborg, T. J. Eide
Journal: BMJ (2013)

Colorectal cancer screening programmes have increased the number of benign lesions being detected. <b>Geir Hoff and colleagues</b> argue that we need more evidence about their malignant potential to be sure that the risks of following current recommendations for removal do not outweigh the benefits of screening
Primary Sjogren's syndrome and aplastic anaemia
Authors: I. QUIQUANDON, P. MOREL, J.-L. LAI, F. BAUTERS, C. DRESCH, E. GLUCKMAN, F. SIGAUX, A. JANIN
Journal: Annals of the Rheumatic Diseases (1997)

Primary Sjogren’s syndrome (SS) is an autoimmune disease characterised by the presence of xerostomia and xerophthalmia without evidence of another systemic autoimmune disease. It has a wide clinical spectrum, extending from exocrinopathy to systemic autoimmune disease and to B cell lymphoma. The association of SS with aplastic anaemia (AA) has rarely been reported1 2 and only in patients with lymphoma. We report here an exceptional case of primary SS and severe AA without lymphoma who had cytogenetic and immunological abnormalities, which might give clues to the pathogenesis of ‘idiopathic’ AA.

A 28 year old white man was referred in February 1990 for lymphadenopathies and pancytopenia. He complained of xerostomia and ocular burning. Xerophthalmia was confirmed by an abnormal Schirmer’s test (right eye 2 mm, left eye 1 mm after 10 mn) and a punctate keratitis on slit lamp examination after Rose-Bengal staining was observed. Labial salivary gland biopsy examination showed features of SS (grade 4 according to Chisholm’s focus score 3).

A polyclonal hypergammaglobulinaemia with a low level of IgA was present and fluorescent antinuclear antibodies were positive in a titre of 1: 640 with a …
A conceptual framework may be of limited value
Authors: Geoff Norman
Journal: BMJ (2004)

Straus et al provide a conceptual framework for evaluation of strategies for teaching evidence based medicine (EBM).1 They correctly state that there is little evidence of effectiveness of teaching EBM, a deficiency frequently identified by critics.2,3 The authors' assumption is that provision of a conceptual framework will lead to better studies. But will it? Is it really the case that a conceptual framework leads naturally to well designed studies? If so, this represents a reorientation of the first author, who previously stated that “no investigative team has yet overcome the problems of sample size, contamination and blinding that such a trial raises,”3 which puts the problem squarely in the court of methodology. And I think she is at least partially right.4 It is well nigh impossible to conceive of an effective educational intervention where the teachers were standardised and participants were blinded, hence unaware that they had received the intervention.

This does not preclude the possibility that a conceptual framework may help. But it seems to me that the major consequence may be to so impress upon potential researchers the daunting nature of the task facing them that it may stimulate abandonment of research rather than initiation. A quick calculation from Straus et al's table 1 shows that, if you were serious about doing a study aimed at “doers,” you would have to get reliable and valid information from each of 5×5 = 25 cells. And that is a substantial problem. While the authors claim that the article's focus is on “psychometrically strong measurements,” that is the last time that psychometric issues are raised. Others have suggested that EBM studies suffer from a “lack of validated outcome measures,” particularly those that focus on learner behaviours,5 but there is no mention of that here.

In the end, I suspect that if a trial, using good design and psychometrically defensible instruments, showed that those who had a course in EBM actually delivered better care than those who did not, all the assessment of attitudes, knowledge, and skills elucidated in this article would probably be viewed as irrelevant. I await the day.
287 ICAM-1 AND VCAM-1 EXPRESSION IN HEPATOCYTE IS REGULATED BY NOD1 PATHWAY
Authors: G. Lassailly, A. Cannesson, A. Louvet, F. Artru, E. Gantier, F. Maggiotto, S. Dharancy, P. Mathurin, L. Dubuquoy
Journal: Journal of Hepatology (2013)
Gender-specific reference M-mode values in adults: Population-derived values with consideration of the impact of height
Authors: Michael S. Lauer, Martin G. Larson, Daniel Levy
Journal: Journal of the American College of Cardiology (1995)

The purpose of this investigation was to derive population-based reference values for M-mode echocardiographic dimensions that can be applied in epidemiologic studies, clinical trials and clinical practice and to determine optimal methods for adjusting these dimensions for body size.M-mode echocardiography remains an important modality for studying cardiovascular disease; this is especially true with regard to detecting target organ damage in systemic hypertension. Most previously published reference values were derived from hospital-based series or relatively small samples and were not gender specific.Using a sample of 288 men and 524 women who were between 20 and 45 years of age and who were free of cardiovascular disease, reference values were derived for end-diastolic and end-systolic left ventricular internal dimensions, left ventricular wall thickness and left atrial dimension. The relations between these dimensions and height, a measure of body size relatively independent of obesity, were investigated using various regression models.Nomograms for mean and 95th percentile values in men and women were constructed on the basis of linear regression models relating echocardiographic dimensions to height. Adjustment for body surface area greatly attenuated associations between obesity and cardiac dimensions in a separate healthy but less restricted sample of 411 men and 503 women.Gender-specific M-mode reference values and nomograms, with mean and 95th percentile values for echocardiographic dimensions as a function of height, are reported. The use of body surface area as means of body size adjustment is called into question.
Guanine Nitration in Idiopathic Pulmonary Fibrosis and Its Implication for Carcinogenesis
Authors: Yasuhiro Terasaki, Teruo Akuta, Mika Terasaki, Tomohiro Sawa, Takeshi Mori, Tatsuya Okamoto, Masakazu Ozaki, Motohiro Takeya, Takaaki Akaike
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Nitric oxide (NO)-induced nitrative stress of nucleic acids, as evidenced by guanine nitration, appears to be involved in inflammation-induced carcinogenesis. A high incidence of lung cancer in idiopathic pulmonary fibrosis (IPF) is the major reason for poor prognosis in patients with IPF.We immunohistochemically analyzed the formation and localization of 8-nitroguanine in lung tissues from control subjects, patients with IPF, and patients with lung cancer.Immunohistochemical analysis of control smoker and nonsmoker lungs showed weak immunoreactivity for 8-nitroguanine, mainly in cytoplasm of bronchial epithelial cells. In addition to the bronchial epithelial cells, metaplastic regenerated epithelial cells overlying dense fibrotic lesions in IPF showed strong 8-nitroguanine staining in the cytoplasm. The staining in these metaplastic cells colocalized with staining of inducible and endothelial NO synthases and 8-oxodeoxyguanosine, as evidenced by double-immunostaining analysis. Confocal and immunoelectron microscopy revealed localization of 8-nitroguanine in metaplastic epithelial cytoplasm, mostly in mitochondria. Appreciable 8-nitroguanine immunostaining was also observed in both nuclei and cytoplasm of malignant epithelial cells in squamous cell carcinoma. No significant difference was found in the epithelial 8-nitroguanine formation between control smokers and nonsmokers, but much higher guanine nitration was observed in patients with IPF than in control subjects and patients with lung cancer, via a quantitative immunofluorescence image analysis.The present study indicates that not only oxidative stress but also nitrative stress induced by NO may participate in the pathogenesis of epithelial cell damage and aberrant regeneration occurring in IPF. Thus, guanine nitration may be a major risk factor for lung cancer development in IPF.
IL-6-Encoding Tumor Antigen Generates Potent Cancer Immunotherapy Through Antigen Processing and Anti-apoptotic Pathways
Authors: Chang-Yao Hsieh, Chi-An Chen, Chia-Yen Huang, Ming-Cheng Chang, Chien-Nan Lee, Yi-Ning Su, Wen-Fang Cheng
Journal: Molecular Therapy (2007)

A naked DNA vaccine delivered by gene gun into antigen-presenting cells (APCs) has emerged as an attractive strategy for antigen-specific cancer immunotherapy. However, APCs have a limited lifespan, hindering their long-term ability to prime antigen-specific T cells. Furthermore, the potency of DNA vaccines is limited by their inability to process and present antigens. Interleukin-6 (IL-6) could play a role in immunity and cell apoptosis. We explored how the DNA vaccine encodes IL-6 to a model tumor antigen, human papilloma virus type-16 (HPV-16) E7. Mice vaccinated with IL-6/E7 DNA exhibited dramatic increases in E7-specific T-cell immunities, anti-E7 antibody responses, and impressive anti-tumor effects against E7-expressing tumors. The in vitro results revealed that IL-6 enhances DNA vaccine potency through the major histocompatibility complex class I pathway via direct and cross-priming effects. In addition, the delivery of IL-6/E7 DNA prolonged the survival of transduced dendritic cells (DCs) in vivo. Our results indicated that the IL-6/E7 DNA vaccine combined the mechanisms of enhancing antigen processing and presentation with prolonging the survival of DCs. Using IL-6 represents an innovative approach to enhancing DNA vaccine potency and holds promise for cancer prevention and immunotherapy. A naked DNA vaccine delivered by gene gun into antigen-presenting cells (APCs) has emerged as an attractive strategy for antigen-specific cancer immunotherapy. However, APCs have a limited lifespan, hindering their long-term ability to prime antigen-specific T cells. Furthermore, the potency of DNA vaccines is limited by their inability to process and present antigens. Interleukin-6 (IL-6) could play a role in immunity and cell apoptosis. We explored how the DNA vaccine encodes IL-6 to a model tumor antigen, human papilloma virus type-16 (HPV-16) E7. Mice vaccinated with IL-6/E7 DNA exhibited dramatic increases in E7-specific T-cell immunities, anti-E7 antibody responses, and impressive anti-tumor effects against E7-expressing tumors. The in vitro results revealed that IL-6 enhances DNA vaccine potency through the major histocompatibility complex class I pathway via direct and cross-priming effects. In addition, the delivery of IL-6/E7 DNA prolonged the survival of transduced dendritic cells (DCs) in vivo. Our results indicated that the IL-6/E7 DNA vaccine combined the mechanisms of enhancing antigen processing and presentation with prolonging the survival of DCs. Using IL-6 represents an innovative approach to enhancing DNA vaccine potency and holds promise for cancer prevention and immunotherapy.
Combined Liver and Heart Transplantation for End-Stage Iron-Induced Organ Failure in an Adult with Homozygous Beta-Thalassemia
Authors: Nancy F. Olivieri, Peter P. Liu, Graham D. Sher, Paul A. Daly, Paul D. Greig, Patricia J. McCusker, Anne F. Collins, William H. Francombe, Douglas M. Templeton, Jagdish Butany
Journal: New England Journal of Medicine (1994)

Most patients with homozygous β-thalassemia require red-cell transfusions to survive beyond the first decade of life. Although this intervention clearly prolongs survival,1 it also results in the accumulation of iron in tissue, which is itself fatal without iron-chelating therapy2. Before the introduction of deferoxamine, iron-induced cardiac dysfunction was a predictable outcome in thalassemia,3 and it is still the leading cause of death, followed in incidence by hepatic disease1. Despite the successes with deferoxamine,4–7 many patients still have serious complications, because of either advanced age at the start of therapy or erratic compliance8–14. To date, the . . .
Circulating activation markers of severe atopic dermatitis following ultraviolet A1 cold light phototherapy: eosinophil cationic protein, soluble interleukin-2 receptor and soluble interleukin-4 receptor
Authors: G von Kobyletzki, C Pieck, S Höxtermann, M Freitag, P Altmeyer
Journal: British Journal of Dermatology (1999)
Proteins and Protein Pattern Differences between Glioma Cell Lines and Glioblastoma Multiforme
Authors: Timothy W. Vogel, Zhengping Zhuang, Jie Li, Hiroaki Okamoto, Makoto Furuta, Youn-Soo Lee, Weifen Zeng, Edward H. Oldfield, Alexander O. Vortmeyer, Robert J. Weil
Journal: Clinical Cancer Research (2005)

Abstract Introduction: Research into the pathogenesis, molecular signaling, and treatment of glioblastoma multiforme (GBM) has traditionally been conducted using cell lines derived from malignant gliomas. We compared protein expression patterns between solid primary GBMs and GBM cell lines to identify proteins whose expression may be altered in cell culture. Methods: We cultured cell lines U87, U118, U251, and A172 and used tissue-selective microdissection of eight primary GBMs to obtain pure populations of tumor cells, which we studied using two-dimensional gel electrophoresis (2DGE) and examined using differential expression software. Select protein targets expressed differentially between GBM tumors and GBM cell lines were sequenced using tandem mass spectrometry. Results: Analysis of the primary GBM tumor samples (n = 8) and the GBM cell lines revealed reproducibly similar proteomic patterns for each group, which distinguished tumors from the cell lines. Gels contained up to 500 proteins that were consistently identified in the pH 4 to 7 range. Comparison of proteins identified in the GBM tumors and in the cell lines showed ∼160 proteins that were gained and 60 proteins that were lost on culture. Using normalized intensity patterns from the 2DGE images, ANOVA tests were done and statistically significant spots were identified. Seven proteins found in the cell lines were significantly increased when compared with the GBM tumors (P &amp;lt; 0.05), whereas 10 proteins were significantly decreased from cell lines compared with the GBM tumors. Proteins identified included transcription factors, tumor suppressor genes, cytoskeletal proteins, and cellular metabolic proteins. Conclusion: Global protein and proteomic differences were identified between primary GBM tumor samples and GBM cell lines. The proteins identified by 2DGE analysis elucidate some of the selection pressures of in vitro culture, help accentuate the advantages and limitations of cell culture, and may aid comprehension of gliomagenesis and enhance development of new therapeutics.