tbuckley/cabot-search huggingface dataset:
Mortality Risk From Squamous Cell Skin Cancer
Authors: Gary L. Clayman, J. Jack Lee, F. Christopher Holsinger, Xian Zhou, Madeleine Duvic, Adel K. El-Naggar, Victor G. Prieto, Evelyn Altamirano, Susan L. Tucker, Sara S. Strom, Margaret L. Kripke, Scott M. Lippman
Journal: Journal of Clinical Oncology (2005)

Purpose To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality. Patients and Methods Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality. Results We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions ≥ 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor. Conclusion Lesion size ≥ 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.
Development of biodegradable crosslinked urethane-doped polyester elastomers
Authors: Jagannath Dey, Hao Xu, Jinhui Shen, Paul Thevenot, Sudershan R. Gondi, Kytai T. Nguyen, Brent S. Sumerlin, Liping Tang, Jian Yang
Journal: Biomaterials (2008)
The MRC OX-62 antigen: a useful marker in the purification of rat veiled cells with the biochemical properties of an integrin.
Authors: M Brenan, M Puklavec
Journal: The Journal of Experimental Medicine (1992)

A mouse immunoglobulin G1 monoclonal antibody (mAb), MRC OX-62 (OX-62), was raised against density gradient-enriched rat veiled (dendritic) cells obtained from lymph. In suspensions of lymphoid cells, the OX-62 mAb only labeled cells with the characteristics of veiled cells. The OX-62 mAb was used with a magnetic cell sorter to enrich or deplete veiled cells, and the enriched veiled cells were potent stimulators in the primary allogeneic mixed leukocyte reaction. Immunohistochemical staining of tissue sections showed that the OX-62 mAb did not label all classical dendritic cells and was not restricted to this cell type. In lymphoid tissues, the labeling correlated with dendritic cells, but in skin, major histocompatibility complex class II+ cells were OX-62-, while another CD3+ cell with dendritic morphology was strongly OX-62+. It seems that the OX-62 mAb may be restricted to dendritic cells and probably to gamma/delta T cells. The OX-62 mAb will be of use in delineating minor subsets of cells with dendritic morphology in various tissues. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of veiled cell-enriched populations immunoprecipitated with the OX-62 mAb gave bands with the biochemical characteristics of an integrin. The OX-62 mAb recognized the alpha-like subunit.
OC-136 Changes in the practice of liver resection for colorectal liver metastases over a 15-year period in a high-volume UK hepatobiliary unit
Authors: C Macutkiewicz, C D Briggs, E Hidalgo, G J Toogood, J P A Lodge, K R Prasad
Journal: Gut (2012)

<h3>Introduction</h3> Colorectal cancer remains the second most common cause of cancer-related death in Europe and North America. More than 50% of patients develop liver metastases within their lifetime and liver resection remains their only chance of cure. Recent trends in liver surgery have favoured parenchyma-preserving liver surgery over traditional major hepatectomies.<sup>1</sup> The aim of this study was to investigate the trend in approach to liver surgery over a 15-year period at a high-volume hepatobiliary unit. <h3>Methods</h3> A prospectively maintained database containing data for the resection of colorectal liver metastases was analysed from 1995 to 2010. Demographic data were extracted together with data on types of liver resection, morbidity and mortality rates, and major vs minor hepatectomies. Minor hepatectomy was defined as any resection up to three segments and major hepatectomy was more than three segments resected. Data displayed compare the three 5-year periods from: 1995 to 1999, 2000 to 2004 and 2005 to 2009. <h3>Results</h3> A total of 1414 hepatectomies were undertaken from 1995 up to 2010. 172 resections were performed in 1995–1999, 570 in 2000–2004 and 672 in 2005–2009. Median age and range were as follows: 61 years (36–80 years) in 1995–1999, 65 years (32–87 years) in 2000–2004, and 65 years (23–91 years) in 2005–2009. Major vs minor hepatectomy ratio were as follows: 55:45 in 1995–1999, 45:55 in 2000–2004, and 33:67 in 2005–2009. Complication rates were as follows: 29.1% in 1995–1999, 23.5% in 2000–2004, and 15.9% in 2005–2009. Mortality rates were significantly reduced from 9.3% in 1995–1999, and 3.3% in 2000–2004, to 1.9% in 2005–2009 (P <h3>Conclusion</h3> The trend in liver resection has been towards more segmentectomies and metastasectomies rather than the more traditional major anatomical resections. This has been associated with a decreased complication rate and a significantly reduced mortality rate. This may reflect not only improvements in technique and critical care management but also in the paradigm shift towards parenchyma-preserving liver surgery. Local recurrence and survival rates will dictate whether this is the optimal treatment. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>von Heesen M</b>, Schuld J, Sperling J, <i>et al.</i> Parenchyma-preserving hepatic resection for colorectal liver metastases. <i>Langenbecks Arch Surg</i> 2011.
The Diabetes Network Internet-Based Physical Activity Intervention
Authors: H. Garth McKay, Diane King, Elizabeth G. Eakin, John R. Seeley, Russell E. Glasgow
Journal: Diabetes Care (2001)

OBJECTIVE—Because of other competing priorities, physical activity (PA) is seldom addressed in a consistent way in either primary care or diabetes education . This 8-week pilot study evaluated the short-term benefits of an Internet-based supplement to usual care that focused on providing support for sedentary patients with type 2 diabetes to increase their PA levels. RESEARCH DESIGN AND METHODS—A total of 78 type 2 diabetic patients (53% female, average age 52.3 years) were randomized to the Diabetes Network (D-Net) Active Lives PA Intervention or an Internet information-only condition. The intervention condition received goal-setting and personalized feedback, identified and developed strategies to overcome barriers, received and could post messages to an on-line “personal coach,” and were invited to participate in peer group support areas. Key outcomes included minutes of PA per week and depressive symptomatology. RESULTS—There was an overall moderate improvement in PA levels within both intervention and control conditions, but there was no significant improvement in regard to condition effects. There was substantial variability in both site use and outcomes within the intervention and control conditions. Internal analyses revealed that among intervention participants, those who used the site more regularly derived significantly greater benefits, whereas those in the control condition derived no similar benefits with increased program use. CONCLUSIONS—Internet-based self-management interventions for PA and other regimen areas have great potential to enhance the care of diabetes and other chronic conditions. We conclude that greater attention should be focused on methods to sustain involvement with Internet-based intervention health promotion programs over time.
Non–Q-Wave Infarction and Ostial Left Coronary Obstruction Due to Giant Lambl’s Excrescences of the Aortic Valve
Authors: George Dangas, Felix G. Dailey-Sterling, Samin K. Sharma, Selvakumar Chockalingham, James R. Albanese, David L. Reich, Jose Meller, John T. Fallon
Journal: Circulation (1999)
Protein Kinase C δ Overexpressing Transgenic Mice Are Resistant to Chemically but not to UV Radiation–Induced Development of Squamous Cell Carcinomas: A Possible Link to Specific Cytokines and Cyclooxygenase-2
Authors: Moammir H. Aziz, Deric L. Wheeler, Bhushan Bhamb, Ajit K. Verma
Journal: Cancer Research (2006)

Abstract Protein kinase C δ (PKCδ), a Ca2+-independent, phospholipid-dependent serine/threonine kinase, is among the novel PKCs (δ, ε, and η) expressed in mouse epidermis. We reported that FVB/N transgenic mice that overexpress (∼8-fold) PKCδ protein in basal epidermal cells and cells of the hair follicle are resistant to the development of both skin papillomas and squamous cell carcinoma (SCC) elicited by 7,12-dimethylbenz(a)anthracene initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion protocol. We now present that PKCδ overexpression in transgenic mice failed to suppress the induction of SCC developed by repeated exposures to UV radiation (UVR), the environmental carcinogen linked to the development of human SCC. Both TPA and UVR treatment of wild-type mice (a) increased the expression of proliferating cell nuclear antigen (PCNA) and apoptosis; (b) stimulated the expression of cytokines tumor necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte CSF (G-CSF); and (c) increased cyclooxygenase-2 (COX-2) expression and expression of phosphorylated Akt (p-Akt), p38, extracellular signal-regulated kinase-1 (ERK1), and ERK2. PKCδ overexpression in transgenic mice enhanced TPA-induced but not UVR-induced apoptosis and suppressed TPA-stimulated but not UVR-stimulated levels of cell PCNA, cytokines (TNF-α, G-CSF, and GM-CSF), and the expression of COX-2, p-Akt, and p38. The results indicate that UVR-mediated signal transduction pathway to the induction of SCC does not seem to be sensitive to PKCδ overexpression. The proapoptotic activity of PKCδ coupled with its ability to suppress TPA-induced expression of proinflammatory cytokines, COX-2 expression, and the phosphorylation of Akt and p38 may play roles in the suppression of TPA-promoted development of SCC. (Cancer Res 2006; 66(2): 713-22)
Mutational Spectrometry in Animal Toxicity Testing
Authors: W G Thilly
Journal: The Annual Review of Pharmacology and Toxicology (1990)

The microbial geneticists who pioneered the study of mutational spectra have shown us how rich a source of mutagen-specific information it can be for the pharmacologist and toxicologist. Contributions by physical chemists and molecular biologists have led to a practical means to observe mutation spectra directly from the DNA of cultured human cells and this review suggests that the same methodology may be applied successfully to the study of mutations and mutational spectra in tissues of experimental animals and humans. In toxicological testing, the new field of mutational spectrometry offers a previously unattainable level of sensitivity and specificity as well as new tools for dissecting mechanisms of pharmacologic and toxic action.
Gray platelet syndrome. Demonstration of alpha granule membranes that can fuse with the cell surface.
Authors: J P Rosa, J N George, D F Bainton, A T Nurden, J P Caen, R P McEver
Journal: Journal of Clinical Investigation (1987)

Platelets from patients with the gray platelet syndrome have decreased recognizable alpha granules and are markedly deficient in some alpha-granule secretory proteins. Using immunocytochemical techniques with antibodies to an alpha-granule membrane protein, GMP-140, we identified the membranes of intracellular vesicles in gray platelets as alpha-granule membranes. Gray platelets contained normal amounts of GMP-140 as measured by electroimmunoassay. The activation of gray platelets with thrombin caused GMP-140 to be redistributed to the plasma membrane surface, as in normal platelets. In agreement with previous studies, an endogenously synthesized secretory protein, platelet factor 4, was undetectable in gray platelets. However, the alpha-granule proteins albumin and IgG, which are thought to be derived from endocytosis of plasma proteins into megakaryocytes, were present in substantial quantities and were secreted efficiently from gray platelets. Therefore, the fundamental defect in the gray platelet syndrome may be in the targeting of endogenously synthesized secretory proteins to developing alpha granules in megakaryocytes.
Telomerase Reverse Transcriptase Promoter Mutations in Bladder Cancer: High Frequency Across Stages, Detection in Urine, and Lack of Association with Outcome
Authors: Yves Allory, Willemien Beukers, Ana Sagrera, Marta Flández, Miriam Marqués, Mirari Márquez, Kirstin A. van der Keur, Lars Dyrskjot, Irene Lurkin, Marcel Vermeij, Alfredo Carrato, Josep Lloreta, José A. Lorente, Enrique Carrillo-de Santa Pau, Roy G. Masius, Manolis Kogevinas, Ewout W. Steyerberg, Angela A.G. van Tilborg, Cheno Abas, Torben F. Orntoft, Tahlita C.M. Zuiverloon, Núria Malats, Ellen C. Zwarthoff, Francisco X. Real
Journal: European Urology (2013)
BACTERICIDAL ACTION OF HISTONE
Authors: James G. Hirsch
Journal: The Journal of Experimental Medicine (1958)

The arginine-rich fraction of calf thymus histone (histone B) exerts bactericidal activity on various coliform bacilli and micrococci under certain conditions in vitro. Final concentrations of less than 1 µg. histone per ml. kill susceptible microbes without detectable morphological alteration or lysis. Among the microorganisms highly susceptible to histone are Escherichia, Salmonella, Shigella, Pseudomonas, Klebsiella, and Micrococcus pyogenes var. albus. Less susceptible or completely resistant are Proteus, Serratia, Micrococcus pyogenes var. aureus, and various types of hemolytic streptococci. Coliforms grown on solid media are much more resistant to the lethal effect of histone than are those cultured in liquid media. This difference is apparently related to the physiological state of the bacteria; agar grown microorganisms washed with water remain resistant to histone, whereas incubation in broth rapidly renders them more susceptible. Histone is adsorbed onto heat-killed E. coli K-12 under conditions suitable for lethal action on this organism. The bactericidal activity of histone is but little affected by pH of the test system, but ionic strength of the medium exerts a marked influence, the lethal action being reduced or blocked as the salt concentration reaches levels higher than that of 0.15–0.2 M NaCl. Relatively high concentrations of rabbit serum or of bovine plasma albumin reduce the bactericidal activity of histone in a medium at pH 7; these serum preparations are, however, essentially without effect in the test system at pH 5.6. The bactericidal effect of histone is antagonized by addition to the medium of small amounts of certain basic substances (protamine, spermine), or of various acid polysaccharides (heparin, nucleic acid, bacterial lipopolysaccharides). The rate of killing of E. coli K-12 by histone increases as the temperature and the concentration of histone are raised. Within the limits studied, this rate also appears to be directly proportional to the concentration of bacteria in the system.
Are Implantable Cardioverter Defibrillator Shocks a Surrogate for Sudden Cardiac Death in Patients With Nonischemic Cardiomyopathy?
Authors: Kenneth A. Ellenbogen, Joseph H. Levine, Ronald D. Berger, James P. Daubert, Stephen L. Winters, Eugene Greenstein, Alaa Shalaby, Andi Schaechter, Haris Subacius, Alan Kadish
Journal: Circulation (2006)

Background— Ventricular tachyarrhythmias long enough to cause implantable cardioverter defibrillator (ICD) shocks are generally thought to progress to cardiac arrest. In previous ICD trials, shocks have been considered an appropriate surrogate for sudden cardiac death (SCD) because the number of shocks has been thought to be equivalent to the mortality excess in patients without ICDs. The practice of equating ICD shocks with mortality is controversial and has not been validated critically. Methods and Results— The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial was a prospective, randomized, multicenter trial of ICD therapy in 458 patients with nonischemic cardiomyopathy. Patients were randomized to receive standard medical therapy (STD) or STD plus an ICD. Shock electrograms were reviewed, and the cause of death was evaluated by a separate blinded events committee. There were 15 SCD or cardiac arrests in the STD group and only 3 in the ICD arm. In contrast, of the 229 patients randomized to an ICD, 33 received 70 appropriate ICD shocks. Patients in the ICD arm were more likely to have an arrhythmic event (ICD shock plus SCD) than patients in the STD arm (hazard ratio 2.12, 95% CI 1.153 to 3.893, P =0.013). The number of arrhythmic events when one includes syncope as a potential arrhythmic event was similar in both groups (hazard ratio 1.20, 95% CI 0.774 to 1.865, P =0.414). Approximately the same number of total events was noted in each arm when we compared syncope plus SCD/cardiac arrest in the STD arm with SCD plus ICD shocks plus syncope in the ICD arm. Conclusions— Appropriate ICD shocks occur more frequently than SCD in patients with nonischemic cardiomyopathy. This suggests that episodes of nonsustained ventricular tachycardia frequently terminate spontaneously in such patients.
Translational pain research: Lessons from genetics and genomics
Authors: Sulayman D. Dib-Hajj, Stephen G. Waxman
Journal: Science Translational Medicine (2014)

Pharmacological, surgical, psychological, and alternative medicine approaches for the treatment of chronic pain, including neuropathic pain, provide only partial relief for most patients, with the efficacy of existing medications often blunted by dose-limiting side effects arising from drug actions on cells outside the pain-signaling axis. The development of more effective treatments for pain--particularly chronic pain states such as neuropathic pain--has been hampered by lack of predictive animal models and biomarkers, variation in pain characteristics between patients or on a day-to-day basis for single patients, patient stratification on the basis of symptoms rather than mechanism, and a high rate of placebo responses. We discuss genetic and genomic approaches to translational pain research. We review examples of the identification and validation of human pain targets through rodent genome-wide association studies (GWAS) and global mRNA expression studies, functional screening in flies and mice, human GWAS and whole-exome sequencing studies, and the targeted candidate gene approach. These and other emerging genetic and genomic strategies are likely to facilitate the development of new, more effective pain therapeutics.
Basigin is a druggable target for host-oriented antimalarial interventions
Authors: Zenon A. Zenonos, Sara K. Dummler, Nicole Müller-Sienerth, Jianzhu Chen, Peter R. Preiser, Julian C. Rayner, Gavin J. Wright
Journal: The Journal of Experimental Medicine (2015)

Plasmodium falciparum is the parasite responsible for the most lethal form of malaria, an infectious disease that causes a large proportion of childhood deaths and poses a significant barrier to socioeconomic development in many countries. Although antimalarial drugs exist, the repeated emergence and spread of drug-resistant parasites limit their useful lifespan. An alternative strategy that could limit the evolution of drug-resistant parasites is to target host factors that are essential and universally required for parasite growth. Host-targeted therapeutics have been successfully applied in other infectious diseases but have never been attempted for malaria. Here, we report the development of a recombinant chimeric antibody (Ab-1) against basigin, an erythrocyte receptor necessary for parasite invasion as a putative antimalarial therapeutic. Ab-1 inhibited the PfRH5-basigin interaction and potently blocked erythrocyte invasion by all parasite strains tested. Importantly, Ab-1 rapidly cleared an established P. falciparum blood-stage infection with no overt toxicity in an in vivo infection model. Collectively, our data demonstrate that antibodies or other therapeutics targeting host basigin could be an effective treatment for patients infected with multi-drug resistant P. falciparum.
Evidence-Based Tuberculosis Diagnosis
Authors: Madhukar Pai, Andrew Ramsay, Richard O'Brien
Journal: PLoS Medicine (2008)

There is great excitement in the tuberculosis (TB) scientific community over the introduction of new tools into TB control activities. The development of new tools is an important component of the Global Plan to Stop TB and the World Health Organization's new global Stop TB Strategy [1,2]. Anticipating the introduction of new tools, the Stop TB Partnership has established a Retooling Task Force to develop a framework for engaging policy makers to foster accelerated adoption and implementation of new tools into TB control programs [3].
Associations of promoter region polymorphisms in the tumour necrosis factor-? gene and early-onset psoriasis vulgaris in a northern Polish population
Authors: B. Nedoszytko, A. Szczerkowska-Dobosz, M. Zabłotna, J. Gleń, K. Rębała, J. Roszkiewicz
Journal: British Journal of Dermatology (2007)

Tumour necrosis factor (TNF)-alpha is considered to be an important mediator in the pathogenesis of psoriasis. Increased levels and activity of this cytokine have been observed in blood and skin of patients with psoriasis. As certain allelic variants of the TNF-alpha gene are associated with increased or decreased production of TNF-alpha, the disturbed cytokine balance may be under genetic control.To investigate the potential association of TNF-alpha promoter alleles within subtypes of psoriasis compared with healthy controls in a northern Polish population.We analysed 166 patients with psoriasis vulgaris (134 with type I and 32 with type II) and 65 healthy controls. The polymorphisms -238G/A and -308G/A in the promoter region of the TNF-alpha gene were typed using the amplification refractory mutation system-polymerase chain reaction method.We found that the TNF-alpha-308A allele frequency was significantly decreased among patients with early-onset psoriasis in comparison with control subjects (7.5% vs. 15.4%, P = 0.022), whereas in the same patients the frequency of the TNF-alpha-238A allele was significantly increased as compared with the controls (16.8% vs. 3.1%, P = 0.000017, odds ratio 8.79, 95% confidence interval 2.606-29.678). Patients with early-onset psoriasis with -238 genotype GA or AA were found more often among those with age at onset < 25 years in comparison with those with genotype GG (31.7% vs. 9.1%, P = 0.0312). We also found that the mean +/- SD age at onset among -238A carriers was significantly lower in comparison with that associated with the -238GG genotype (13.5 +/- 7.4 vs. 19.2 +/- 9.9 years, P = 0.0132).Our study confirming the association between -238 G/A TNF-alpha promoter polymorphism and early-onset psoriasis vulgaris in the northern Polish population suggests that the -238A variant may contribute not only to a predisposition to psoriasis vulgaris but also to the disease phenotype.