tbuckley/cabot-search huggingface dataset:
Abstract 2941: Rapid changes in chromatin structure in response to extracellular signals
Authors: Alfonso G. Fernandez, Lijun Di, Jung Byun, Temesgen Fufa, Kevin Gardner
Journal: Cancer Research (2010)

Abstract Immediate early genes (IEGs) are well known to be rapidly and transiently induced at high levels of expression in response to various extracellular signals such as growth factors. These rapid changes in the transcriptional state of this class of genes raised questions regarding the role of higher order chromatin structure in this transient event of inducible gene expression. In these studies, we compared the degree of chromatin condensation in Jurkat cells before and after mitogen stimulation of c-fos, a well-known IEG. Soluble chromatin obtained from unstimulated and stimulated cells were collected for a sucrose gradient sedimentation assay in order to separate chromatin fibers by means of size and more importantly by the extent of structural condensation of the chromatin. Real time-PCR analysis of c-fos was then used as a tool to quantify the distribution of open and closed chromatin fibers across the collected fractions obtained from the sucrose gradients. The results suggested a major decondensation of the chromatin fiber at the c-fos gene upon stimulation. The unfolding of the chromatin structure upon stimulation is paired with a dramatic increase in histone acetylation as detected by chromatin immunoprecipiation (ChIP) at the promoter region. Histone hyperacetylation is known to cause destabilization of the higher order chromatin structure leading to an increase in chromatin accessibility as clearly shown in our DNase hypersensitivity studies. Taken together, we have detected a rapid decondensation of the chromatin fiber, which is believed to facilitate the rapid transcriptional response to extracellular signals. Our current interest lies in obtaining further information regarding the molecular events that are more directly related to destabilization of the higher order chromatin structure upon mitogen stimulation. Testing of various molecular candidates involved in chromatin destabilizing events include phosphorylation of linker histone H1, recruitment of histone variants and dramatic histone modications such as ADP-polyribosylation at the c-fos promoter region. A more detailed understanding on the rapid decondensation of the chromatin fiber would provide valuable information regarding the cascade of events that must take place in response to stress or extracellular signals. 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 2941.
Abstract 4816: Development of an integrated analysis platform of circulating melanoma cells for PD-L1 expression as a predictive biomarker
Authors: Benjamin K. Gibbs, Lindsay N. Strotman, Stephanie M. Thiede, Jamie M. Sperger, Benjamin P. Casavant, Scott M. Berry, David J. Beebe, Joshua M. Lang
Journal: Cancer Research (2014)

Abstract Novel therapies that target the PD-1/PD-L1 axis have shown great potential to improve survival for patients with advanced melanoma. However, there are limited predictive biomarkers to identify patients who may respond to this class of agents. Previous studies suggest that a subset of responders to PD-1/PD-L1 targeting therapies have expression of PD-L1 in tumor biopsies. The development of these predictive biomarkers is complicated by intratumoral heterogeneity across primary and metastatic lesions for PD-L1 expression. Circulating tumor cells (CTCs) are one potential source of tumor samples for serial analysis. An integrated CTC capture and analysis technology known as the VERSA (Versatile Exclusion-based Rare Sample Analysis) platform permits evaluation of CTCs at the protein, DNA and mRNA level for biomarkers of both therapeutic response and resistance. Using this platform, we have developed a method to isolate circulating tumor cells from patients with advanced melanoma. Using a cocktail of capture monoclonal antibodies including targets of CD146, GD2 and NG2, we have recovered cells across multiple cell lines with high efficiency. Using single antibody capture of SK-Mel-28 cells, capture was 52%, 54%, and 45% with CD146, GD2 and NG2 targets respectively. However, when using a cocktail of capture antibodies containing CD146, GD2 and NG2, capture increased to 92%. Similar results were obtained with other melanoma cell lines including, 624 and M21 cell lines. Cells were also stained for PD-L1 as a potential predictive biomarker of response to PD-L1 and PD-1 targeting immunotherapies. We are now collecting patient samples with this capture platform to identify CTCs expressing PD-L1 as a potential predictive biomarker to PD-1/PD-L1 targeting therapies. Citation Format: Benjamin K. Gibbs, Lindsay N. Strotman, Stephanie M. Thiede, Jamie M. Sperger, Benjamin P. Casavant, Scott M. Berry, David J. Beebe, Joshua M. Lang. Development of an integrated analysis platform of circulating melanoma cells for PD-L1 expression as a predictive biomarker. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4816. doi:10.1158/1538-7445.AM2014-4816
Croonian Lectures on Disease and its Medical Treatment
Authors: J. S. Bristowe
Journal: BMJ (1872)

MR. PRESIDENT AND GENTLEMEN,-In my former lecture I endea- voured to explain what I understood by the word "disease," and, by reference to various complex diseases, to show in what sense, as applied to them, it might be regarded as including within its scope the various phenomena which flow, immediately or mediately, from the primary cause, and in what sense again it is applicable to each or certain of these various phenomena.I ventured, also, to make some kind of arrangement of diseases in groups; and, guided by this arrangement, to discuss the processes by which diseases affect the body injuriously, and those by ,which their cure or alleviation is accomplished.To-day I enter upon the subject of the treatment of disease.The art of prescribing is unquestionably a very important medical art.I recollect when, some years ago now, I read that fascinating work, the Pharma- sologia of the late Dr. Paris, I was struck with the logical (I had almost said plausible) way in which he classifies the objects which we should en- deavour to obtain, by mixing and combining medicinal substances.He arranges them under five heads, and under each head includes several subdivisions.The five heads are as follows :-I.To promote the action of the basis or principal medicine ; 2. To correct the operation of the basis by obviating any unpleasant effects it might be likely to occasion, and which would prevent its intended action, and defeat the objects of its exhibition; 3. To obtain the joint action of two or more medicines ; 4. To obtain a new and active remedy, not afforded by any single sub- stance; and 5. To afford an eligible form.Now, I suppose that each one of us has endeavoured, according to his lights, to carry some such principles as these into operation; at all events, every one will admit lat it is in many points of view not immaterial that our combinations of drupsKshould yield "elegant" results; and, still more, that the drugs which we administer together should neither neutralise one another che- mically, nor aim at producing incompatible results within the body.But, admitting all this, it must also be admitted, I conceive, that such rules are more adapted for those who thoroughly understand, or who believe they understand, the actions of medicines in relation to the processes of disease, than for those who are investigators of the actions of drugs, and
Mithramycin Therapy in Disseminated Germinal Testicular Cancer
Authors: Norman W. Ream
Journal: JAMA (1968)

Mithramycin, an antibiotic, was used in the treatment of 30 patients with disseminated germinal testicular cancer. The antitumor effect of mithramycin was evaluable in 26. Nine patients experienced an objective antitumor response, which has been complete in two. The major responses occurred in patients with embryonal carcinoma with pulmonary metastases. No significant response was observed in patients with advanced retroperitoneal or hepatic metastases from embryonal carcinoma or in the six patients with teratocarcinoma. The toxicity of mithramycin encountered in this investigation does not preclude employing this agent as a primary treatment of metastases from embryonal carcinoma of the testis.
The nose, paranasal sinuses, and ears in childhood.
Authors: J. Charles Drooker
Journal: JAMA (1963)

Professor Proctor presents a contemporary short monograph which reflects his personal clinical management of the areas listed in the title. His teachers and colleagues are graciously acknowledged for his educational background in this work. The Johns Hopkins point of view in otolaryngologic disease is thereby strongly emphasized. For example, the use of the monel metal radium applicator to eradicate lymphoid tissue about the eustachian tubes is strongly advocated.  The book is written in large print in a large but thin volume and the material is very well documented by a generous bibliography. The bibliography following the chapter on the history of otolaryngology is of particular reference value. The illustrations are large and abundant. The text is written in an editorial, first-person narrative manner and short case histories from the author's experience are liberally used to emphasize the practical aspects of the management of the clinical entities discussed.  The necessity for
THE "MEDICAL INTERPRETER"
Authors: M. W. Ireland
Journal: JAMA (1930)

<h3>To the Editor:</h3> —Kindly give publicity to the following: Under date of April 13, 1930, I received a letter from Dr. Arthur F. Stotts, Colonel, Medical Reserve Corps, Galesburg, Ill., stating that a representative of the<i>Medical Interpreter</i>had informed him that the<i>Medical Interpreter</i>was published in conjunction with the Public Health Service and the Army Medical Library, and requesting information in regard to the matter. Under date of September 2 I had a similar letter from Dr. W. L. Casler, Marquette, Mich., and under date of October 13, a similar one from Dr. Ewald Hermann. These letters suggest that there is a systematic effort to make it appear that the<i>Medical Interpreter</i>bears an official relationship to the public health services and especially to the Army Medical Library. The facts are that two employees of the<i>Medical Interpreter</i>, women without medical training so far as I know, utilize
Automania the New Disease.
Authors: J. W. Clemmer
Journal: JAMA (1906)

Columbus, Ohio, April 25, 1906. <h3>To the Editor:</h3> —The number of diseases produced by occupation is being augmented by the complexity of modern life. Medical men are acquainted with the ordinary forms of occupation diseases, such as the necrosis of match-makers, the cataract of blacksmiths, the colic of painters and the like. I wish to call attention to a disease of this class of recent origin. The new disease is so prevalent as to have attracted the attention of many physicians, and I learned fromThe Journal, April 21, that not a few physicians have had a personal experience. The new disease is a functional neurosis and spreads through a community, like chorea, by imitation. The disease is known as motor fever, chauffeur mania and automobiliousness. The spread of the disease is limited only by the confines of civilization and the quarantine enforced by poverty. The disease has followed the
P431Evaluation of tpe-te interval and tpe-te/QTc ratio in patients with coronary artery ectasia:
Authors: K Karaagac, O C Yontar, E Tenekecioglu, F Vatansever, O Arican Ozluk, A Tutuncu, P Yagcioglu, M Yilmaz
Journal: Cardiovascular Research (2014)

Aim: Coronary artery ectasia (CAE) is commonly defined as local or generalized dilatation of a coronary vessel up to 1,5 times the diameter of an adjacent vessel. Tp-Te interval and Tp-Te/QT ratio have emerged as a novel electrocardiographic (ECG) markers of increased dispersion of ventricular repolarization. The aim of this study was to evaluate ventricular repolarization by using Tp-Te interval and Tp-Te/QT ratio in patients with CAE.
Help the medicine go down
Authors: G. Jones
Journal: BMJ (2003)

Taking medicine, the theme of this week's BMJ , is an experience shared by all of us at some point in our lives. For the lucky, medicine taking is confined to the odd painkiller. For others it involves accommodating complex and inflexible medication regimes into their daily lives (p 837). Assuming the right drug is prescribed in the first place, the success of medication relies …
CXC Chemokine Receptor 3 Expression by Activated CD8+ T cells Is Associated with Survival in Melanoma Patients with Stage III Disease
Authors: Irene M. Mullins, Craig L. Slingluff, Jae K. Lee, Courtney F. Garbee, Jianfen Shu, Sara G. Anderson, Melanie E. Mayer, William A. Knaus, David W. Mullins
Journal: Cancer Research (2004)

Abstract Despite the presence of tumor Ag-specific CD8+ T cells in the peripheral blood, metastatic melanoma often evades immune-mediated destruction. Even after therapeutic efforts to expand Ag-specific T-cell populations, the correlation between magnitude of response and clinical efficacy has been weak. Because the migratory phenotype of tumor Ag-specific effector T cells may determine their ability for tumor control, we hypothesized that the expression of CC or CXC chemokine receptor (CCR) molecules on activated CD8+ T cells may define phenotypes associated with more effective control of melanoma progression and prolonged survival. In a retrospective evaluation of patient isolates, CCR expression was determined for activated CD8+ T cells derived from the peripheral blood or tumor-involved lymph nodes of 52 patients with stage III or IV metastatic melanoma. In patients with stage III disease, expression of CXCR3 by CD8+CD45RO+ cells was significantly associated with enhanced survival. This was a stage-specific effect, because it was not observed in patients with stage IV disease. In addition, CCR4 and CXCR3 were highly coexpressed and associated with enhanced survival in stage III patients; however, CXCR3 seems to be the dominant receptor associated with clinical outcome. These findings support the hypothesis that the host immune system affects cancer progression and control, and that measures of CCR status of circulating lymphocytes may have prognostic value.
Effects of a carbohydrate-restricted diet with and without supplemental soluble fiber on plasma low-density lipoprotein cholesterol and other clinical markers of cardiovascular risk
Authors: Richard J. Wood, Maria Luz Fernandez, Matthew J. Sharman, Ricardo Silvestre, Christine M. Greene, Tosca L. Zern, Sudeep Shrestha, Daniel A. Judelson, Ana L. Gomez, William J. Kraemer, Jeff S. Volek
Journal: Metabolism (2006)
Defining consensus leukemia-associated immunophenotypes for detection of minimal residual disease in acute myeloid leukemia in a multicenter setting
Authors: N Feller, V H J van der Velden, R A Brooimans, N Boeckx, F Preijers, A Kelder, I de Greef, G Westra, J G te Marvelde, P Aerts, H Wind, M Leenders, J W Gratama, G J Schuurhuis
Journal: Blood Cancer Journal (2013)

Flow-cytometric detection of minimal residual disease (MRD) has proven in several single-institute studies to have an independent prognostic impact. We studied whether this relatively complex approach could be performed in a multicenter clinical setting. Five centers developed common protocols to accurately define leukemia-associated (immuno)phenotypes (LAPs) at diagnosis required to establish MRD during/after treatment. List mode data files were exchanged, and LAPs were designed by each center. One center, with extensive MRD experience, served as the reference center and coordinator. In quarterly meetings, consensus LAPs were defined, with the performance of centers compared with these. In a learning (29 patients) and a test phase (35 patients), a mean of 2.2 aberrancies/patient was detected, and only 1/63 patients (1.6%) had no consensus LAP(s). For the four centers without (extensive) MRD experience, clear improvement could be shown: in the learning phase, 39-63% of all consensus LAPs were missed, resulting in a median 30% of patients (range 21-33%) for whom no consensus LAP was reported; in the test phase, 27-40% missed consensus LAPs, resulting in a median 16% (range 7-18%) of 'missed' patients. The quality of LAPs was extensively described. Immunophenotypic MRD assessment in its current setting needs extensive experience and should be limited to experienced centers.
Abstract 1961: Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype.
Authors: Jae Yun Lim, Sun Och Yoon, So-Young Seol, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Ju-Seog Lee, Jae Yong Cho
Journal: Cancer Research (2013)

Abstract Background: Gastric cancer is composed of disease subgroups with heterogeneous clinical and biological behaviors. A previous study identified two subgroups with distinct gene-expression profiles strongly associated with prognosis. To identify molecular biologic differences between these two subgroups, we performed an integrative analysis of mRNA, microRNA, and protein expression. Methods: Array technologies were used to generate microRNA and protein expression profiles of frozen tissue samples from 60 patients with gastric cancer. All patients underwent curative gastric resection in 2005 and distributed from stage I to IV and their clinical characteristics were collected. BRB-ArrayTools were used for microarray data analysis. Data was compared between gastric cancer tissue and normal gastric tissue and also between two different prognostic groups. Aberrantly expressed microRNA and associated mRNA in patients with poor-prognosis gastric cancer were validated by quantitative RT-PCR and tissue microarray, respectively. Results: Four microRNAs were aberrantly expressed in gastric cancer tissue, especially poor prognostic group (P &amp;lt; 0.05). In the poor-prognosis subgroup, miR-196b showed the most significantly high expression patterns and also miR-135b, miR-93. On the contrary, miR-29c* was down-regulated. MiR-196b expression was positively correlated with HOXA10 expression (r = 0.726; P &amp;lt; 0.001), which was significantly increased in poor-prognosis patients (P &amp;lt; 0.001). HOXA10 protein-positive expression was identified in 56 of 368 gastric cancer tissue microarray samples. In reverse-phase protein array, 46/124 proteins were expressed differently (P &amp;lt; 0.05); COX2 (P &amp;lt; 0.001) and cyclin B1 (P = 0.017) were clearly over-expressed in the poor-prognosis group. Conclusion: Integrative analysis of RNA and protein expression profile facilitates interpretation of the molecular biologic heterogeneity of cancer. Co-activation of miR-196b and HOXA10 characterized a poor-prognosis subgroup of patients with gastric cancer. As HOXA10 is involved in the proliferation of hematopoietic stem cells and progenitor cells, the relevance of hematopoietic progenitor cell and gastric cancer development/progression should be further investigated. Citation Format: Jae Yun Lim, Sun Och Yoon, So-Young Seol, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Ju-Seog Lee, Jae Yong Cho. Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1961. doi:10.1158/1538-7445.AM2013-1961
Novartis faces growing pressure to drop patent case against Indian government
Authors: Sally Hargreaves
Journal: BMJ (2007)

The Swiss drug company Novartis is under growing pressure from all sides as its long awaited High Court case against the Indian government began last month in Chennai.

Novartis is challenging the government's refusal of a patent for the leukaemia treatment imatinib (Glivec) and also section 3(d) of the Indian Patent Act, which restricts drug patents to innovative drugs. The law was designed to make it easier for poor patients to get cheaper generic drugs. If Novartis succeeds in the case, it would signal the start of more stringent patent laws in India and an end to the current trend of lower prices.

“People living with HIV from Lesotho to Laos depend on India …
Determinants of Regional Cerebral Oxygenation in Children with Sleep-disordered Breathing
Authors: Maha Abou Khadra, Keith McConnell, Rhonda VanDyke, Virend Somers, Matthew Fenchel, Syed Quadri, Jenny Jefferies, Aliza P. Cohen, Michael Rutter, Raouf Amin
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: An association between neurocognitive deficits and pediatric sleep-disordered breathing has been suggested; however, weak correlations between disease severity and functional outcomes underscore the lack of knowledge regarding factors modulating cognitive morbidity of sleep-disordered breathing.Objectives: To identify the parameters affected by sleep-disordered breathing that modulate cerebral oxygenation, an important determinant of cognition. A further objective was to use these parameters with demographic data to develop a predictive statistical model of pediatric cerebral oxygenation.Methods: Ninety-two children (14 control subjects, 32 with primary snoring, and 46 with obstructive sleep apnea) underwent polysomnography with continuous monitoring of cerebral oxygenation and blood pressure. Analysis of covariance was used to relate the blood pressure, sleep diagnostic parameters, and demographic characteristics to regional cerebral oxygenation.Measurements and Main Results: To account for anatomic variability, an index of cerebral oxygenation during sleep was derived by referencing the measurement obtained during sleep to that obtained during wakefulness. In a repeated measures model predicting the index of cerebral oxygenation, mean arterial pressure, rapid eye movement (REM) sleep, female sex, age, and oxygen saturation had a positive effect on cerebral oxygenation levels, whereas arousal index and non-REM (NREM) sleep had a negative effect.Conclusions: Increasing mean arterial pressure, age, oxygen saturation, and REM sleep augment cerebral oxygenation, while sleep-disordered breathing, male sex, arousal index, and NREM sleep diminish it. The proposed model may explain the sources of variability in cognitive function of children with sleep-disordered breathing.
Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention
Authors: Barbara E Tardiff, Robert M Califf, James E Tcheng, A.Michael Lincoff, Kristina N Sigmon, Robert A Harrington, Kenneth W Mahaffey, E.Magnus Ohman, Paul S Teirstein, James C Blankenship, Michael M Kitt, Eric J Topol
Journal: Journal of the American College of Cardiology (1999)
Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds
Authors: C. POPP, A.M KLIGMAN, T.J. STOUDEMAYER
Journal: British Journal of Dermatology (1995)

Pretreatment of skin with all‐trans retinoic acid (tretinoin) has been shown to enhance wound healing. Previous studies have mainly used animal models to demonstrate this effect. We wanted to determine whether pretreatment could promote wound healing in severely photoaged dorsal forearm skin.
The Acute Phase Response in Sicilian Patients with Boutonneuse Fever Admitted to Hospitals in Palermo, 1992–1997
Authors: G. Vitale, S. Mansueto, G. Gambino, C. Mocciaro, A. Spinelli, G.B. Rini, M. Affronti, N. Chifari, C. La Russa, S. Di Rosa, P. Colletti, C. Barbera, M. La Rosa, G. Di Bella, V. Ferlazzo, S. Milano, P. D'Agostino, E. Cillari
Journal: Journal of Infection (2001)