tbuckley/cabot-search huggingface dataset:
Polymorphic <i>TP53BP1</i> and <i>TP53</i> Gene Interactions Associated with Risk of Squamous Cell Carcinoma of the Head and Neck
Authors: Kexin Chen, Zhibin Hu, Li-E Wang, Wei Zhang, Adel K. El-Naggar, Erich M. Sturgis, Qingyi Wei
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Tumor protein 53-binding protein 1 (TP53BP1) and TP53 interact during TP53-mediated transcriptional activation and during checkpoint activation in response to DNA damage. Because suboptimal repair of tobacco-induced DNA damage is associated with risk of squamous cell carcinoma of the head and neck (SCCHN), we hypothesized that potentially functional polymorphisms in TP53BP1 and TP53 may contribute jointly to SCCHN risk. Experimental Design: In a case-control study, DNA samples from age- and sex-matched SCCHN patients (n = 818) and cancer-free controls (n = 821) were genotyped for the presence of three variants of TP53BP1 (T-885G, Glu353Asp, and Gln1136Lys) and three variants of TP53 (Arg72Pro, PIN3, and MspI). Multivariate logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Results: Although none of these six genetic variants alone was associated with SCCHN risk, the combined TP53BP1 genotypes were associated with a significant, dose response–dependent decrease in SCCHN risk among carriers of TP53Pro72Pro, TP53PIN3del/del, and TP53Msp1AA genotypes (trend test: P = 0.024, 0.016, and 0.016, respectively). Furthermore, TP53BP1 variant haplotype GGC carriers who were also TP53 variant homozygotes had a significantly lower risk of SCCHN than did TP53BP1 haplotype TCA carriers (adjusted OR, 0.48; 95% CI, 0.25-0.94 for TP53Pro72Pro; adjusted OR, 0.17; 95% CI, 0.04-0.69 for TP53PIN3del/de; and adjusted OR, 0.16; 95% CI, 0.04-0.65 for TP53Msp1AA). There was statistical evidence of interaction between TP53BP1 and TP53 diplotypes (P = 0.017). Conclusion: Our data suggest that TP53BP1 variants may have protective effects on SCCHN risk but such effects were confined to TP53 variant allele/haplotype carriers.
NIK-dependent RelB Activation Defines a Unique Signaling Pathway for the Development of Vα14<i>i</i> NKT Cells
Authors: Dirk Elewaut, Raziya B. Shaikh, Kirsten J. L. Hammond, Hilde De Winter, Andrew J. Leishman, Stephane Sidobre, Olga Turovskaya, Theodore I. Prigozy, Lisa Ma, Theresa A. Banks, David Lo, Carl F. Ware, Hilde Cheroutre, Mitchell Kronenberg
Journal: The Journal of Experimental Medicine (2003)

A defect in RelB, a member of the Rel/nuclear factor (NF)-κB family of transcription factors, affects antigen presenting cells and the formation of lymphoid organs, but its role in T lymphocyte differentiation is not well characterized. Here, we show that RelB deficiency in mice leads to a selective decrease of NKT cells. RelB must be expressed in an irradiation-resistant host cell that can be CD1d negative, indicating that the RelB expressing cell does not contribute directly to the positive selection of CD1d-dependent NKT cells. Like RelB-deficient mice, aly/aly mice with a mutation for the NF-κB–inducing kinase (NIK), have reduced NKT cell numbers. An analysis of NK1.1 and CD44 expression on NKT cells in the thymus of aly/aly mice reveals a late block in development. In vitro, we show that NIK is necessary for RelB activation upon triggering of surface receptors. This link between NIK and RelB was further demonstrated in vivo by analyzing RelB+/− × aly/+ compound heterozygous mice. After stimulation with α-GalCer, an antigen recognized by NKT cells, these compound heterozygotes had reduced responses compared with either RelB+/− or aly/+ mice. These data illustrate the complex interplay between hemopoietic and nonhemopoietic cell types for the development of NKT cells, and they demonstrate the unique requirement of NKT cells for a signaling pathway mediated by NIK activation of RelB in a thymic stromal cell.
Anti-VEGF Therapy Revived by c-Met Inhibition, but Is c-Met the Answer?
Authors: Kristi D. Lynn, Rolf A. Brekken
Journal: Cancer Discovery (2012)

Abstract A new study by Sennino and colleagues demonstrates that selective VEGF inhibition via the use of an anti-VEGF antibody is sufficient to increase invasion and metastasis in a c-Met–dependent manner. Anti-VEGF therapy induced tumor hypoxia, hypoxia-inducible factor 1α, and c-Met activation in the RIP-Tag2 model of neuroendocrine pancreatic cancer. Selective c-Met inhibition was sufficient to block these effects, providing a potential mechanism for and solution to overcome increased invasion in the face of anti-VEGF therapy. Cancer Discovery; 2(3); 211–3. ©2012 AACR. Commentary on Sennino et al., p. 270.
Acute hepatitis B in a healthcare worker: A case report of genuine vaccination failure
Authors: Hein J. Boot, Laurens A. van der Waaij, Jurjen Schirm, Cees G.M. Kallenberg, Jim van Steenbergen, Bert Wolters
Journal: Journal of Hepatology (2008)

BackgroundIndividuals who reach the antibody threshold level of 10 IU/l against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection.Case reportHere we describe an acute hepatitis B infection in a patient who received five hepatitis B vaccinations. Although his initial response to vaccination was moderate, he finally reached an excellent hepatitis B surface antibody level (anti-HBs) titres of more than 1000 IU/l in response to a booster vaccination with a recombinant DNA vaccine. Nevertheless, he developed full-blown acute hepatitis due to an HBV infection 14 years after this booster vaccination. A DNA analysis of the surface protein encoding region followed by phylogenetic analysis showed that our patient was infected with a normal HBV strain that is circulating among men who have sex with men. To our knowledge, this is the first report of a genuine hepatitis B vaccination failure in someone who acquired a high anti-HBs level in response to a recombinant DNA hepatitis B vaccine.ConclusionHealthcare workers whose response to the initial hepatitis B vaccination is moderate might be vulnerable to hepatitis B virus infection. Individuals who reach the antibody threshold level of 10 IU/l against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection. Here we describe an acute hepatitis B infection in a patient who received five hepatitis B vaccinations. Although his initial response to vaccination was moderate, he finally reached an excellent hepatitis B surface antibody level (anti-HBs) titres of more than 1000 IU/l in response to a booster vaccination with a recombinant DNA vaccine. Nevertheless, he developed full-blown acute hepatitis due to an HBV infection 14 years after this booster vaccination. A DNA analysis of the surface protein encoding region followed by phylogenetic analysis showed that our patient was infected with a normal HBV strain that is circulating among men who have sex with men. To our knowledge, this is the first report of a genuine hepatitis B vaccination failure in someone who acquired a high anti-HBs level in response to a recombinant DNA hepatitis B vaccine. Healthcare workers whose response to the initial hepatitis B vaccination is moderate might be vulnerable to hepatitis B virus infection.
Sorafenib-Related Hand-Foot Skin Reaction Improves, Not Worsens, with Continued Treatment
Authors: Keith T. Flaherty, Marcia S. Brose
Journal: Clinical Cancer Research (2009)

To the Editor: In the February issue of Clinical Cancer Research , Azad and colleagues report on their experience with sorafenib and hand-foot skin reaction (HFSR; ref. [1][1]). Understanding the relationship between toxicity and the primary molecular targets of an agent is important. However, we
Multi-platform characterization of the human cerebrospinal fluid metabolome: a comprehensive and quantitative update
Authors: Rupasri Mandal, An Chi Guo, Kruti K Chaudhary, Philip Liu, Faizath S Yallou, Edison Dong, Farid Aziat, David S Wishart
Journal: Genome Medicine (2012)

Human cerebral spinal fluid (CSF) is known to be a rich source of small molecule biomarkers for neurological and neurodegenerative diseases. In 2007, we conducted a comprehensive metabolomic study and performed a detailed literature review on metabolites that could be detected (via metabolomics or other techniques) in CSF. A total of 308 detectable metabolites were identified, of which only 23% were shown to be routinely identifiable or quantifiable with the metabolomics technologies available at that time. The continuing advancement in analytical technologies along with the growing interest in CSF metabolomics has led us to re-visit the human CSF metabolome and to re-assess both its size and the level of coverage than can be achieved with today's technologies.
A pulmonary rehabilitation program at a public hospital in Buenos Aires, Argentina
Authors: Clarisa Boim, Miguel Storni, Cortiñaz Marta, Monti Fernanda, Chiervo Sandra, Caberloto Oscar
Journal: European Respiratory Journal (2013)

Introduction: Respiratory rehabilitation is a therapeutic strategy for improving quality of life in patients with chronic respiratory disease. Maintaining a pulmonary rehabilitation program in a public hospital poses a challenge.  Objective: To share our experience and assess the impact of a pulmonary rehabilitation program on both quality of life and the six minute walking test.  Method: Pulmonary rehabilitation program was carried out between May 1996 and December 2011, 382 patients were interviewed for admission to pulmonary rehabilitation program of whom 102 subsequently completed the sixteen week program. Patients attended the bi-weekly program which consisted of education, physical training, psychological support and nutritional counseling. Patients were assessed with the Chronic Respiratory Questionnaire (CRQ) and the six minute walking test (6MWT) before initiating and after concluding the program.  Results: Sixty nine of the 102 patients completing the pulmonary rehabilitation program were males; mean age was 63.85±9; mean force expiratory volume in 1 second was 39.06%±7.  Prior to pulmonary rehabilitation program the mean 6MWT was 338.69±21 and post pulmonary rehabilitation it was 405.94±105mts. The sum of the four CRQ domains was 83.39±19 prior to rehabilitation and 100.82±19 after the pulmonary rehabilitation, indicating improved quality of life.  Conclusion: Pulmonary rehabilitation led to improvements in the six minute walking test and a quality of life; however, patient compliance was low.
P13.04 * A STUDY ON DOSIMETRIC PERFORMANCE OF 5 MM MLCS FOR VMAT BASED STEREOTACTIC RADIOSURGERY
Authors: M. Robinson, S. Padmanaban, F. Van den Heuvel, C. Blesing
Journal: Neuro-Oncology (2014)

OBJECTIVE: In stereotactic radiosurgery (SRS), the high resolution multileaf collimator (HR-MLC) (i.e. 1 to 3mm leaf width) has the potential to provide improved dose conformity to target volume and lower doses to critical structures compared to the more prevalent standard MLCs (5 mm), when used in a classic conformal manner. In this study we investigate the dosimetric performance of standard 5 mm MLC for SRS targets of various sizes, when using a VMAT technique, to determine the limitations and/or need to increase planning complexity. METHODS AND MATERIALS: Spherical planning target volumes (PTV) were delineated in a test patient with diameters ranging from 1 to 3 cm in increments of 0.4 cm in an Eclipse treatment planning system. RapidArc plans using 6 MV photons were produced for each PTV using two coplanar arcs. Plan optimization and plan normalization was to obtain better PTV dose coverage (min V90 = 100% and medium PTV dose >100%) and dose fall-off controlled by the normal tissue objective and a ring structure 1 cm clear of PTV with an aim for dose of 40% of prescribed. PTV coverage was prioritized over dose fall off. All plans were calculated using Anisotropic Analytical Algorithm (AAA) with 1mm grid size. The plans were evaluated using dose conformity defined by the ratio of the percentage dose volume to volume of PTV for 100, 90, 80, 60 and 40 percent of prescribed (R100-40). Dosimetric machine accuracy is assessed using high resolution (0.1mm) GafChromic film analysis, an added limitation was to provide increased dose homogeneity compared to classical radiosurgery. RESULTS: Conformity index R100-40 was lower in plans with 1.8 cm diameter (volume <2.9 cc) or lower (R100 = 2.81, 1.84, 1.54, 1.39, 1.29, and 1.36 for target volumes with increasing diameter as defined above). Plotting the plan conformity and the calculated conformity given a defined fixed distance to dose fall off against PTV volume shows the two to be divergent at small volumes indicating the point at which conformity is compromised with 5 mm MLC. Gafchromic film analysis based on direct dose calibration showed good agreement for all volume sizes, showing that the planning system correctly predicts the dose variations even at this high resolution. CONCLUSIONS: Single plane RA-SRS using 5mm MLC is feasible down to target sizes of 2.9cc, while a clinical planning system allows accurate prediction of the dose. In future work the impact of multiple plane RA-SRS on feasibility will be presented.
Exercise, Hypertension, and Left Ventricular Mass
Authors: L. Julian Haywood
Journal: JAMA (1990)

To the Editor.—  The study by Kelemen et al 1 showing that exercise is equivalent to exercise plus drug therapy with either propranolol or diltiazem in controlling hypertension is interesting and important.  Left ventricular mass increased in all three study groups without a change in diastolic function. This finding begs the question of whether there is a good increase in left ventricular mass that results from exercise and a bad increase in left ventricular mass that results from hypertension untreated. One might argue that a desired result of treatment of hypertension is prevention of an increase in left ventricular mass or reduction in left ventricular mass if it has already increased.  Because the study period lasted only 10 weeks, I question whether the conclusion that exercise had no deleterious effects is valid for longer periods. Studies to evaluate the efficacy of longer trials of exercise for control of high blood
Metastatic Behavior of Breast Cancer Subtypes
Authors: Hagen Kennecke, Rinat Yerushalmi, Ryan Woods, Maggie Chon U. Cheang, David Voduc, Caroline H. Speers, Torsten O. Nielsen, Karen Gelmon
Journal: Journal of Clinical Oncology (2010)

Prognostic and predictive factors are well established in early-stage breast cancer, but less is known about which metastatic sites will be affected.Patients with early-stage breast cancer diagnosed between 1986 and 1992 with archival tissue were included. Subtypes were defined as luminal A, luminal B, luminal/human epidermal growth factor receptor 2 (HER2), HER2 enriched, basal-like, and triple negative (TN) nonbasal. Distant sites were classified as brain, liver, lung, bone, distant nodal, pleural/peritoneal, and other. Cumulative incidence curves were estimated for each site according to competing risks methods. Association between the site of relapse and subtype was assessed in multivariate models using logistic regression.Median follow-up time among 3,726 eligible patients was 14.8 years. Median durations of survival with distant metastasis were 2.2 (luminal A), 1.6 (luminal B), 1.3 (luminal/HER2), 0.7 (HER2 enriched), and 0.5 years (basal-like; P < .001). Bone was the most common metastatic site in all subtypes except basal-like tumors. In multivariate analysis, compared with luminal A tumors, luminal/HER2 and HER2-enriched tumors were associated with a significantly higher rate of brain, liver, and lung metastases. Basal-like tumors had a higher rate of brain, lung, and distant nodal metastases but a significantly lower rate of liver and bone metastases. TN nonbasal tumors demonstrated a similar pattern but were not associated with fewer liver metastases.Breast cancer subtypes are associated with distinct patterns of metastatic spread with notable differences in survival after relapse.
High-Dimensional Single-Cell Monitoring of Circulating Cells in Allergic Asthmatics Infected with Rhinovirus Reveals Dynamic Flux in Diverse Immune Cells
Authors: Lyndsey Muehling, Cara Wogsland, Rachana Agrawal, Peter W. Heymann, Jonathan M. Irish, Judith A. Woodfolk
Journal: Journal of Allergy and Clinical Immunology (2015)
Widespread use of serological tests for tuberculosis: data from 22 high-burden countries
Authors: J. Grenier, L. Pinto, D. Nair, K. Steingart, D. Dowdy, A. Ramsay, M. Pai
Journal: European Respiratory Journal (2012)

In summary, we show for the first time that the absence of a trident peak at 7 ppm in NMR spectra of EBC, related to ammonium, is associated with asthma.The loss of ammonium reflects reduced ammonia synthesis due to downregulation of glutaminase, leading to impaired acid neutralisation.Surprisingly, despite a very strong association in our study, this signature was not noted in the seminal study by CARRARO et al.[2], who first described the use of NMR spectroscopy of EBC in asthma.Only spectra between 1 and 4 ppm were shown in their study.One possibility for the observed differences is that CARRARO et al.[2] used a reusable collection system.It is possible, as suggested by , that the use of disinfectants in reusable collection systems may create artefacts, cleaning of which may in turn obscure some parts of the spectra.As we use a completely disposable tube for EBC collection, with only a chilled external metal sleeve being reused, there is no possibility of such contamination in our data.It was additionally confirmed that EBC spectra including the 7 ppm peaks were distinct from deuterated water condensate collected from identical tubes.Furthermore, independent previous reports of ammonia and ammonium being reduced in asthma corroborate our findings [5, 9].The small number of controls in our study, particularly of children, limits our study and further studies are needed to establish the usefulness of our finding.Also, it appears likely that the ammonium signature is enhanced by acidic load on the airway, which may vary across geographical regions.This study was conducted in Delhi, India, where ambient air contains high sulphuric and nitric oxides.Applicability of our finding to less polluted regions needs to be tested.However, despite this, our data hopefully removes the need for any further debate regarding whether valid and useful NMR spectra can be obtained for EBC [4].This nascent field holds much potential for translation, and concerted efforts of many investigators are needed.
Diagnostic Imaging for Low Back Pain: Advice for High-Value Health Care From the American College of Physicians
Authors: Roger Chou
Journal: Annals of Internal Medicine (2011)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Diagnostic imaging is indicated for patients with low back pain only if they have severe progressive neurologic deficits or signs or symptoms that suggest a serious or specific underlying condition. In other patients, evidence indicates that routine imaging is not associated with clinically meaningful benefits but can lead to harms. Addressing inefficiencies in diagnostic testing could minimize potential harms to patients and have a large effect on use of resources by reducing both direct and downstream costs. In this area, more testing does not equate to better care. Implementing a selective approach to low back imaging, as suggested by the American College of Physicians and American Pain Society guideline on low back pain, would provide better care to patients, improve outcomes, and reduce costs.
Effects of dextran sulphate sodium on intestinal epithelial cells and intestinal lymphocytes.
Authors: J Ni, S F Chen, D Hollander
Journal: Gut (1996)

BACKGROUND AND AIMS: The effects of dextran sulphate sodium (DSS) on mouse intestinal epithelial cells and intraepithelial lymphocytes were analysed to investigate the mechanism by which DSS induces colitis and tumours in mice. Cytotoxicity of DSS towards intestinal epithelial cells and intestinal intraepithelial lymphocyte hybridomas or fresh intestinal intraepithelial lymphocytes seems to have concentration, time, and cell type dependency with increasing concentrations and time causing increased cytotoxicity. RESULTS: Integrin alpha 4 expression was marginally down regulated by 0.5% of DSS, while alpha M290 expression was up regulated. DSS inhibits the binding of 9.1 gamma delta cells to both extracellular matrix (ECM) and epithelial cells. Conversely at high concentrations it increases binding to all ECM except poly-L-lysine. Various cytokines including TGF beta, interleukin 2, and tumour necrosis factor alpha as well as prostaglandin alter the expression of the integrin alpha 4 and M290 subunits at the cell surface, and also alter the adhesion of 9.1 gamma delta cells to epithelial monolayers. The expression of a large number of cell adhesion molecules expressed on intraepithelial lymphocytes is affected by a combination of the abundant gut cytokine TGF beta and DSS, suggesting that DSS induced colitis may ultimately arise from a combination of gut cytokine and DSS. DSS also triggers intraepithelial lymphocyte aggregation on all ECM coated plate tested. CONCLUSIONS: These data suggest that the potential roles of DSS induced colitis may be: (a) direct cytotoxicity; (b) interference with the normal interaction between intestinal lymphocytes, epithelial cells, and ECMs; (c) aberrant modulation of the expression of the integrin beta 7 receptors, other cell receptors, and their functions.
The Sarcoplasmic Reticulum Ca2+ Channel/Ryanodine Receptor: Modulation by Endogenous Effectors, Drugs and Disease States
Authors: Riccardo Zucchi, Simonetta Ronca-Testoni
Journal: Pharmacological Reviews (1997)

### A. The ryanodine receptor

The ryanodine receptor (RyR)c corresponds to the sarcoplasmic reticulum (SR) Ca2+ channel ([Inui et al., 1987][1]; [Imagawa et al., 1987][2]). Its structure and function have been reviewed recently ([Fleischer and Inui, 1989][3]; [Lai and Meissner, 1989][4];[McPherson