tbuckley/cabot-search huggingface dataset:
Abstract 2289: MRJ(L) reverts mesenchymal phenotype and restricts malignancy by inhibiting Wnt/β-catenin signaling
Authors: Rajeev S. Samant, Aparna Mitra, Mitchell E. Menezes, Lalita A. Shevde
Journal: Cancer Research (2010)

Abstract Expression of MRJ (Hsp40/DNAJB6) is lost in advanced infiltrating ductal carcinoma. We found that ectopic expression of the large isoform of MRJ, MRJ(L), is functionally capable of retarding tumor growth. Our continuing efforts towards understanding the effect of MRJ(L) expression on cancer cells revealed that MRJ(L) caused morphological changes indicative of epithelial-like appearance. It decreased the expression of several mesenchymal markers such as N-cadherin, Twist, Slug, vimentin and up regulated epithelial marker, Keratin 18. However, most noticeable was the loss of β-catenin protein upon MRJ(L) expression. Differential-proteomic analysis of the secretome showed that MRJ(L) expression elevated DKK1 (Dickkopf1), a secreted inhibitor of Wnt/β-catenin signaling. Increased DKK1 levels enhanced proteosome mediated degradation of β-catenin and reduced Wnt/β-catenin signaling as measured by the TCF/LEF reporter activity in MRJ(L) expressors. Furthermore we found that silencing MRJ(L) from immortalized mammary epithelial cell line, MCF10A, led to decreased DKK1 and E-cadherin levels, with concomitant increase of β-catenin protein. We also found that silencing DKK1 from the MRJ(L) overespressing cancer lines led to increased malignant behavior as measured by foci formation, growth in soft agar and wound healing capacity. Overall, our findings lead us to conclude that MRJ(L) maintains the epithelial phenotype and restricts malignant behavior of tumor cells by inhibiting Wnt/β-catenin pathway. 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 2289.
STUDY OF THE ADSORPTION ON AND DESORPTION FROM POLYSTYRENE-HUMAN SERUM ALBUMIN CONJUGATES OF RABBIT ANTI-HUMAN SERUM ALBUMIN ANTIBODIES HAVING DIFFERENT SPECIFICITIES
Authors: Tom Webb, Claude Lapresle
Journal: The Journal of Experimental Medicine (1961)

An insoluble specific adsorbent for anti-human serum albumin antibodies was prepared by coupling human serum albumin (H.S.A.) to polystyrene by azo bonds. Rabbit anti-H.S.A. immune serum was passed through a column of the adsorbent. It was shown that different volumes of the immune serum were required for the saturation of the different determinant groups of H.S.A. by their corresponding antibodies. The elution of the anti-H.S.A. antibodies adsorbed on the column was achieved by passing successively through the column an acetate buffer pH 3.0 and a solution of 0.1 N HCl in 0.15 M NaCl. The antibodies were eluted in three different fractions, each of which was composed of gamma-globulins only. These three fractions contained different proportions of antibodies of different specificities.
Author's Reply: Breast Cancer in Black Women
Authors: L. D. Leffall
Journal: CA A Cancer Journal for Clinicians (1982)

If postmastectomy lymphangiosarcomadoes not occur in the absence of lymphede ma, then the prevention of lymphedema should in fact be essential in the prevention of lymphangiosarcoma, but also in the pre vention of painful, distressing, recurrent lymphangitis and cellulitis.
S136 Pre- and Post-Specific Inhalational Challenge Measurements of Fractional Exhaled Nitric Oxide (FENO) in the Diagnosis of Occupational Asthma
Authors: GI Walters, VC Moore, PS Burge
Journal: Thorax (2012)

<h3>Introduction</h3> The interpretation of Specific Inhalation Challenge (SIC) can be equivocal, particularly for late asthmatic reactions. It has been suggested that increases in FE<sub>NO</sub> 24-hours post-challenge might help separate positive from negative challenges. <h3>Methods</h3> We reviewed all positive and equivocal SIC tests with occupational agents between March 2008 and June 2012 from our tertiary referral centre. FENO was measured pre- and 24-hours post control and active challenges using a Niox Mino handheld machine at 50 ml/sec, compliant with ERS/ATS recommendations. Post-challenge changes &gt;20% for FENO &gt;50 ppb, or &gt;10 ppb for &lt;50 ppb, were counted as per ATS guidelines for a clinically significant change (1). <h3>Results</h3> 24 patients had complete data related to control and active challenges, which were positive in 15 and equivocal in 9 cases. 13/24 patients had raised pre-control challenge FENO (mean=31.3) after adjusting for smoking and inhaled corticosteroid use. Increases in FENO, more than the minimum clinically relevant difference, were seen after 13/24 control challenges: including 6/7 exposures to cleaning agents or hand gels and 2/6 unused metalworking fluids. 5/24 patients had a clinically significant increase in FENO after positive or equivocal challenges: including 1/4 challenges with isocyanates, 1/6 cleaning agents or hand gels, and 2/3 with used metalworking fluids. There was no statistically significant difference in mean percentage change in FENO between control and active challenges. <h3>Conclusions</h3> The previously defined minimum clinically relevant difference for FENO was seen as commonly following control as active challenges. Measuring changes in FENO pre- and 24-hours post challenge to the diverse range of low molecular weight agents tested did not provide useful additional information for interpreting SIC responses. <h3>Reference</h3> Dweik RA et al. An Official ATS Clinical Practise Guideline: Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. Am J Respir Crit Care Med 2011; 184:602–15.
Human Life in the Balance
Authors: Sidney C. Roberts
Journal: JAMA (1992)

"We are clearly in a state of chaos about the status of human life in our society," writes David C. Thomasma in his book<i>Human Life in the Balance</i>. This is a well-thought-out, well-researched, and incredibly well-referenced plea for each of us to begin to affirm the value of human life and then to participate in social action in support of those views. It is not a call for civil disobedience (an excellent discussion of this can be found in Francis Schaeffer's<i>A Christian Manifesto</i>) but a cry for dialogue. Thomasma's "nightmare" is "no consensus about the status of human life." He persuades that a "baseline commitment to an irreducible value inherent in human beings" does not confine us to one particular moral, political, or religious position. In the process, he outlines three possible positions that we, as individuals and as a society, can take and still have a baseline
Warming feeds is unnecessary and hazardous
Authors: E. Thomas
Journal: BMJ (2000)

<h3>Abstract</h3> Variant interpretation remains a central challenge for precision medicine. Missense variants are particularly difficult to understand as they change only a single amino acid in protein sequence yet can have large and varied effects on protein activity. Numerous tools have been developed to identify missense variants with putative disease consequences from protein sequence and structure. However, biological function arises through higher order interactions among proteins and molecules within cells. We therefore sought to capture information about the potential of missense mutations to perturb protein interaction networks by integrating protein structure and interaction data. We developed 16 network-based annotations for missense mutations that provide orthogonal information to features classically used to prioritize variants. We then evaluated them in the context of a proven machine-learning framework for variant effect prediction across multiple benchmark datasets to demonstrate their potential to improve variant classification. Interestingly, network features resulted in larger performance gains for classifying somatic mutations than for germline variants, possibly due to different constraints on what mutations are tolerated at the cellular versus organismal level. Our results suggest that modeling variant potential to perturb context-specific interactome networks is a fruitful strategy to advance <i>in silico</i> variant effect prediction.
Glucorrhea Revisited
Authors: Harry F. Hull
Journal: JAMA (1975)

Glucose oxidase test strips were used to evaluate the presence of glucose in nasal secretions and tears in a group of normal children. Substantial amounts of glucose were present in 15 of 17 samples of nasal discharge and 10 of 15 samples of tears. The use of glucose oxidase test strips for diagnosis of cerebrospinal fluid rhinorrhea, therefore, is without merit. (<i>JAMA</i>234:1052-1053, 1975)
Some Speculations about Prions, Amyloid, and Alzheimer's Disease
Authors: Stanley B. Prusiner
Journal: New England Journal of Medicine (1984)

The causes of most degenerative diseases are unknown; however, the causes of three degenerative disorders of the central nervous system have been defined by their transmissibility to animals. These diseases are kuru, Creutzfeldt–Jakob disease, and the Gerstmann-Straüssler syndrome.1 , 2 The slow infectious agents that cause these diseases appear to be different from viruses but similar to the agent that causes scrapie, a neurologic disorder of sheep and goats.1 , 3 The term "prion" has been introduced to denote this slow infectious agent, with its unusual properties.3 Studies of the molecular structure of scrapie prions in highly purified preparations indicate that they contain one . . .
P192 Fibreoptic bronchoscopic insertion of the Gianturco stent for tracheobronchial obstruction in patients with cancer at a lung cancer tertiary referral centre: 20 year experience
Authors: A. Collins, T. Jordan, M. Ledson, M. Walshaw
Journal: Thorax (2010)

<h3>Background</h3> Lung cancer is the commonest form of malignant disease in the Western World, and 95% of patients die within 5 years of presentation. Palliation of symptoms is therefore an important aspect of the treatment: up to 30% will develop large airway obstruction due to tumour with ensuing distressing breathlessness and this may be life threatening. Protection of the airway by stenting may be difficult and is traditionally carried out under general anaesthesia and fluoroscopy. In our regional unit we have developed a service for the insertion of self-expanding Gianturco stents under local anaesthesia using the fibreoptic bronchoscope (FOB) and direct vision for the treatment of malignant airway tumours, and we now report our 20-year experience. <h3>Methods</h3> A review of all stenting procedures carried out in our unit between 1990 and 2009, looking for tumour type, number and site of stents, procedure complications, and survival. <h3>Results</h3> 236 patients (mean age 64 years (range 21–89)) had 414 stents inserted during 242 procedures (mean 1.7 stents/procedure (1–4)); 184 patients for primary lung tumours (49% squamous cell, 25% small cell, 15% adenocarcinoma, 11% unknown), 33 for secondary malignancy, and four for benign conditions (following fully informed consent). There were no operative deaths, but four patients developed a pneumothorax, three haemoptysis, and two procedure-related chest infections. Mean survival of patients with primary lung cancer improved from 103 days (range 1–488) between 1990 and 1999 to 150 days (5–910) between 2000 and 2009. <h3>Conclusion</h3> We conclude that Gianturco stents are safe in relieving malignant airway obstruction, with a low complication rate: higher complication rates reported in others studies may be due to poor patient selection or stent placement. Survival improved in our patients over time, suggesting better patient selection or improvement in coexisting treatment modalities (eg, oral chemotherapy and palliative care). Our technique of endobronchial stent insertion using FOB is simple and effective without the need for thoracic surgical facilities, and we therefore recommend its use to other clinicians who are charged with treating patients with this common and distressing disease.
The Area under the Curve
Authors: Mark Linzer
Journal: New England Journal of Medicine (1999)

To the Editor: Dr. Darouiche and colleagues (Jan.7 issue) 1 conclude that the use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of catheter-related bloodstream infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.They defined a catheter-related bloodstream infection by the isolation of the same organism from the vascular catheter and from peripheral blood in a patient with sepsis and no other apparent source of bloodstream infection.However, residual antimicrobial activity in the removed catheter sufficient to prevent growth from the cultured catheter segments would substantially reduce the apparent rate of catheter-related bloodstream infections (since a catheter-related bloodstream infection cannot occur on the basis of this definition if no growth is recorded from the cultured catheter segments).The authors found no significant difference between groups in the proportion of catheters removed for suspected infection (14 percent of minocycline-rifampin catheters and 13 percent of chlorhexidine-silver sulfadiazine catheters), the proportion receiving vancomycin (23 percent vs. 25 percent), or the mean duration of stay in the intensive care unit (8.7 vs. 8.6 days).Thus, could it be that use of minocycline-rifampin impregnation prevents growth from catheters in the microbiology laboratory but does not eliminate the clinical syndrome of catheter-related bloodstream infection?
FAMILY DIET COEFFICIENTS
Authors: M. L. Clark
Journal: BMJ (1933)

rMLED1CAL;jOPURXAL 132 aged 12+, and 101 aged 13+ would range from FAMILY DIET COEFFICIENTS so60 men per-100 boys (Atwater scale) to 87 men per 100 boys (Inter-Allied scale), and the catering might be BY adequate or inadequate for the needs of the boys according
Should Physicians Counsel Patients to Drink Alcohol?
Authors: Enoch Gordis
Journal: JAMA (1995)

<h3>To the Editor.</h3> —We agree with the recent Editorial by Dr Pearson and Mr Terry<sup>1</sup>that certain patients, such as pregnant women, should abstain entirely from alcohol. However, we wish to comment on their suggestion that physicians might advise other population subgroups to initiate moderate alcohol consumption. Epidemiological findings indicate that although women are less likely to drink, drink less heavily, and develop fewer alcohol-related problems than men, they develop alcohol dependence more rapidly.<sup>2</sup>Women metabolize alcohol less efficiently than men, probably because of reduced first-pass metabolism. Together with less ethanol dilution attributable to lower body water content, this metabolic difference increases bioavailability of alcohol and may enhance sensitivity to alcohol-induced physiological impairment. There also seems to be a greater risk for liver cirrhosis for women than men at comparable consumption levels; and women contract pancreatic disease after shorter periods of consumption and liver disease at lower consumption
Intraventricular conduction in man studied with an endocardial electrode catheter mapping technique. Patients with normal QRS and right bundle branch block.
Authors: J A Kastor, B N Goldreyer, E N Moore, J C Shelburne, J H Manchester
Journal: Circulation (1975)

The sequence of intraventricular conduction has been studied in a total of 60 patients, 38 of whom had normal QRS morphology and 37 of whom had right bundle branch block (RBBB) either present continuously or produced as functional aberrant RBBB by the introduction of atrial premature depolarizations or by rapid atrial pacing. Activation times were measured by intracardiac electrode catheters positioned at the right ventricular inflow tract (RVIT), right ventricular apex (RVA), right ventricular outflow tract (RVOT), left ventricular apex (LVA) and left ventricular outflow tract (LVOT). The activation after beginning of QRS in milliseconds plus or minus 1 SD and the number of patients studied at each location were: RVIT--normal 23 plus or minus 13 (15 patients); RVIT-RBBB 49 plus or minus 16 (15 patients); RVA--normal 18 plus or minus 9 (28 patients); RVA-RBBB 54 plus or minus 16 (30 patients); RVOT--normal 40 plus or minus 10 (28 patients); RVOT-RBBB 78 plus or minus 21 (30 patients);LVA--normal 9 plus or minus 9 (18 patients); LVA-RBBB 6 plus or minus 10 (10 patients); LVOT--normal 45 plus or minus 13 (10 patients); LVOT-RBBB 32 plus or minus 9 (7 patients). Significant differences observed were: RVA-normal versus RVA-RBBB P smaller than 0.001; RVOT-RBBB P smaller than 0.001; RVA-normal versus LVA-normal P smaller than 0.005; LVA-normal versus LVA-RBBB NS, LVOT-normal versus LVOT-RBBB P smaller than 0.05. The LVOT change was unexpected and suggests changes in left ventricular depolarization may occur when right bundle branch block develops. In patients with RBBB the activation of the RVA (r equals 0.82) and of the RVOT (r equals 0.68) was directly related to the duration of QRS. Changes in activation time when RBBB was induced by rapid atrial pacing or by introduction of atrial premature depolarizations were: RVA (7 patients) 19 plus or minus 11 to 56 plus or minus 16 (P smaller than 0.001); RVOT (9 patients) 41 plus or minus 10 to 77 plus or minus 22 (P SMALLER THAN 0.001); LVA (5 patients) and LVOT (2 patients), small insignigicant changes. These data indicate that endocardial activation changes can be evaluated in the catheterization laboratory, that right ventricular conduction becomes slower in RBBB as a direct function of total QRS and that left ventricular conduction may be affected when RBBB develops.
Crying in infants
Authors: Carolina de Weerth, Susana Fuentes, Willem M de Vos
Journal: Gut Microbes (2013)

Up to around a quarter of all infants cry excessively and unsoothably during their first months of life. This phenomenon has been termed "infant colic." In most cases, physicians are unable to determine the cause of the colicky behavior. In a recent study, and by means of comprehensive and deep analyses of more than 1000 intestinal phylotypes, we found that infants with colic showed lower microbiota diversity and stability than control infants in the first weeks of life. Colic-control differences in the abundance of certain bacteria were also found at 2 weeks. These microbial signatures possibly explain the colic phenotype. In this addendum we discuss other recent publications on the subject and present previously unpublished analyses of our own. We address possible mechanisms behind the links between microbiota and crying, and present future directions that could further help elucidate the hypothesized relations between intestinal microbiota and infant colic.
Letter by Kaplan Regarding Article, “Bacteremia Associated With Toothbrushing and Dental Extraction”
Authors: Edward L. Kaplan
Journal: Circulation (2009)

revised recommendations for antibiotic prophylaxis for prevention of bacterial endocarditis. 2The authors should be commended for undertaking this study, which must have been difficult to carry out; however, before these data can be put into appropriate perspective, several questions require thought.
Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice
Authors: James O. McNamara, Despina Kolonias, Fernando Pastor, Robert S. Mittler, Lieping Chen, Paloma H. Giangrande, Bruce Sullenger, Eli Gilboa
Journal: Journal of Clinical Investigation (2008)

4-1BB is a major costimulatory receptor that promotes the survival and expansion of activated T cells. Administration of agonistic anti–4-1BB Abs has been previously shown to enhance tumor immunity in mice. Abs are cell-based products posing significant cost, manufacturing, and regulatory challenges. Aptamers are oligonucleotide-based ligands that exhibit specificity and avidity comparable to, or exceeding, that of Abs. To date, various aptamers have been shown to inhibit the function of their cognate target. Here, we have described the development of an aptamer that binds 4-1BB expressed on the surface of activated mouse T cells and shown that multivalent configurations of the aptamer costimulated T cell activation in vitro and mediated tumor rejection in mice. Because aptamers can be chemically synthesized, manufacturing and the regulatory approval process should be substantially simpler and less costly than for Abs. Agonistic aptamers could therefore represent a superior alternative to Abs for the therapeutic manipulation of the immune system.
Economic Assessment of Platelet Glycoprotein IIb/IIIa Receptor Blockade With Abciximab and Low-Dose Heparin During Percutaneous Coronary Revascularization
Authors: A. Michael Lincoff, Daniel B. Mark, James E. Tcheng, Robert M. Califf, Mohan V. Bala, Keaven M. Anderson, Linda Davidson-Ray, J. David Knight, Catherine F. Cabot, Eric J. Topol
Journal: Circulation (2000)

Background —In the EPILOG trial (Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade), abciximab administered with weight-adjusted heparin diminished the risk of ischemic complications within 30 days by 56% among patients undergoing percutaneous coronary revascularization, without increased bleeding complications. Methods and Results —A prospective economic assessment was performed in the 2792 patients enrolled in EPILOG. Patients were randomized to receive placebo with standard-dose weight-adjusted heparin, abciximab with low-dose weight-adjusted heparin, or abciximab with standard-dose weight-adjusted heparin during percutaneous coronary intervention. Hospital billing data for the baseline hospitalization were collected for 2581 patients (92.4% of total) and imputed for the remainder, with physician fees estimated from the Medicare Fee Schedule. For the baseline hospitalization, medical costs (hospitalization and physician fees) averaged $9632 for the placebo arm compared with $8758 ( P =0.005) and $9092 ( P =0.176) for the abciximab with low-dose and standard-dose heparin arms, respectively. Inclusive of average drug cost ($1454 to $1457), the net incremental baseline cost of these 2 abciximab strategies was $583 with low-dose weight-adjusted heparin and $914 with standard-dose weight-adjusted heparin. During 6-month follow-up, average hospital costs were not significantly different in the 3 treatment groups; cumulative net incremental costs were $1236 and $1268 in the abciximab with low-dose and standard-dose heparin groups, respectively. Conclusions —Treatment with abciximab and low-dose, weight-adjusted heparin during percutaneous coronary revascularization reduces ischemic events and associated costs, thereby offsetting some of the cost of the drug. The suppression of bleeding complications associated with this agent by heparin dose reduction optimizes the economic attractiveness of this treatment strategy.