tbuckley/cabot-search huggingface dataset:
Concurrent Chemotherapy-Radiotherapy Compared With Radiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma: Progression-Free Survival Analysis of a Phase III Randomized Trial
Authors: A.T.C. Chan, P.M.L. Teo, R.K. Ngan, T.W. Leung, W.H. Lau, B. Zee, S.F. Leung, F.Y. Cheung, W. Yeo, H.H. Yiu, K.H. Yu, K.W. Chiu, D.T. Chan, T. Mok, K.T. Yuen, F. Mo, M. Lai, W.H. Kwan, P. Choi, P.J. Johnson
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho’s N2 or N3 stage or N1 stage with nodal size ≥ 4 cm were randomized to receive cisplatin 40 mg/m 2 weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P = .10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho’s stage T3 (P = .0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P = .016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.
A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia
Authors: Sohela Shah, Kasmintan A Schrader, Esmé Waanders, Andrew E Timms, Joseph Vijai, Cornelius Miething, Jeremy Wechsler, Jun Yang, James Hayes, Robert J Klein, Jinghui Zhang, Lei Wei, Gang Wu, Michael Rusch, Panduka Nagahawatte, Jing Ma, Shann-Ching Chen, Guangchun Song, Jinjun Cheng, Paul Meyers, Deepa Bhojwani, Suresh Jhanwar, Peter Maslak, Martin Fleisher, Jason Littman, Lily Offit, Rohini Rau-Murthy, Megan Harlan Fleischut, Marina Corines, Rajmohan Murali, Xiaoni Gao, Christopher Manschreck, Thomas Kitzing, Vundavalli V Murty, Susana C Raimondi, Roland P Kuiper, Annet Simons, Joshua D Schiffman, Kenan Onel, Sharon E Plon, David A Wheeler, Deborah Ritter, David S Ziegler, Kathy Tucker, Rosemary Sutton, Georgia Chenevix-Trench, Jun Li, David G Huntsman, Samantha Hansford, Janine Senz, Tom Walsh, Ming Lee, Christopher N Hahn, Kathryn G Roberts, Mary-Claire King, Sarah M Lo, Ross L Levine, Agnes Viale, Nicholas D Socci, Katherine L Nathanson, Hamish S Scott, Mark Daly, Steven M Lipkin, Scott W Lowe, James R Downing, David Altshuler, John T Sandlund, Marshall S Horwitz, Charles G Mullighan, Kenneth Offit
Journal: Nature Genetics (2013)
Transplacental immunization of the human fetus to tetanus by immunization of the mother.
Authors: T J Gill, C F Repetti, L A Metlay, B S Rabin, F H Taylor, D S Thompson, A L Cortese
Journal: Journal of Clinical Investigation (1983)

Experimental studies in rats showed that immunization of the pregnant female led to the transplacental immunization of her fetuses. The possibility that this also occurred in humans was explored by immunizing 42 pregnant women with tetanus toxoid (2.5 or 5 Lf) in the fifth and eighth months of pregnancy and comparing the immune responses of their offspring with the responses of the offspring of 25 unimmunized mothers. Only the offspring of the immunized mothers were sensitized to tetanus. IgM antitetanus antibodies were in their blood before immunization with diphtheria, pertussis, tetanus vaccine (DPT), they had a more rapid (P less than 0.01) response to DPT immunization, and they were still highly sensitized (P less than 0.01) to tetanus 13 mo after birth. In addition, pregnancy had no immunosuppressive effect (P less than 0.05) on the responses of the mothers to tetanus toxoid. Thus, transplacental immunization occurs in humans; it enhances the response of the offspring to subsequent immunization, and it could be used to circumvent the necessity for immunization in early neonatal life.
Gene Therapy for Repair of Cardiac Fibrosis
Authors: Maurits Allessie, Ulrich Schotten, Sander Verheule, Erik Harks
Journal: Circulation (2005)

ecause of the increase in life expectancy and a high survival rate after myocardial infarction, cardiac fibrosis is becoming one of the most important problems in cardiology.It is characterized by excessive accumulation of fibrillar collagen in the extracellular space, either because of a loss of cardiomyocytes (replacement fibrosis) and/or as an interstitial response to various chronic cardiovascular diseases such as hypertension, myocarditis, and congestive heart failure (reactive fibrosis). 1In humans, cardiac fibrosis is universal in the aging heart.Activated fibroblasts play a pivotal role in the formation and maintenance of fibrous tissue by the production of various extracellularmatrix proteins, including collagen and fibronectin.It is now recognized that even in areas with long-standing fibrosis, such as postinfarction scars, fibroblasts remain metabolically active. 2 Their activity is regulated by various autocrine and paracrine factors, such as angiotensin II, aldosterone, endothelins, cytokines, and growth factors. 3The renin-angiotensin-aldosterone system is considered to be of major importance for the regulation of cardiac fibrosis.Increased tissue levels of angiotensin II have shown to promote, and ACE inhibitors are able to delay the development of, cardiac fibrosis. 4,
Human epithelial cells establish direct antifungal defense through TLR4-mediated signaling
Authors: Günther Weindl, Julian R. Naglik, Susanne Kaesler, Tilo Biedermann, Bernhard Hube, Hans Christian Korting, Martin Schaller
Journal: Journal of Clinical Investigation (2007)

Mammalian TLRs are central mediators of the innate immune system that instruct cells of the innate and adaptive response to clear microbial infections. Here, we demonstrate that human epithelial TLR4 directly protected the oral mucosa from fungal infection via a process mediated by polymorphonuclear leukocytes (PMNs). In an in vitro epithelial model of oral candidiasis, the fungal pathogen Candida albicans induced a chemoattractive and proinflammatory cytokine response but failed to directly modulate the expression of genes encoding TLRs. However, the addition of PMNs to the C. albicans–infected model strongly upregulated cytoplasmic and cell-surface epithelial TLR4 expression, which correlated directly with protection against fungal invasion and cell injury. C. albicans invasion and cell injury was restored by the addition of TLR4-specific neutralizing antibodies and knockdown of TLR4 using RNA interference, even in the presence of PMNs, demonstrating the direct role of epithelial TLR4 in the protective process. Furthermore, treatment with neutralizing antibodies specific for TNF-α resulted in strongly reduced TLR4 expression accompanied by augmented epithelial cell damage and fungal invasion. To our knowledge, this is the first description of such a PMN-dependent, TLR4-mediated protective mechanism at epithelial surfaces, which may provide significant insights into how microbial infections are managed and controlled in the oral mucosa.
Elevated Serum Amylase Levels after Seizures
Authors: W. Robert Graham
Journal: Annals of Internal Medicine (1997)

Letters1 January 1997Elevated Serum Amylase Levels after SeizuresW. Robert Graham, MD, Yair Lotan, MS, and Todd Painton, MSW. Robert Graham, MDBaylor College of Medicine; Houston, TX 77030Search for more papers by this author, Yair Lotan, MSBaylor College of Medicine; Houston, TX 77030Search for more papers by this author, and Todd Painton, MSBaylor College of Medicine; Houston, TX 77030Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-1-199701010-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:A 65-year-old man was brought to our emergency department after a seizure. The patient was lethargic and confused when he arrived. The medication he had been prescribed, Dilantin (Parke-Davis, Morris Plains, New Jersey), was not present in his blood. Results of physical examination of the patient's abdomen were normal. His serum amylase level was 9.19 µkat/L (normal, 0.57 to 2.03 µkat/L). This elevation prompted physicians to do computed tomography of the abdomen. No abnormality was detected in the pancreas. The patient was admitted to the hospital for observation. His mental status became normal, he ate, and he ... Author, Article, and Disclosure InformationAuthors: W. Robert Graham, MD; Yair Lotan, MS; Todd Painton, MSAffiliations: Baylor College of Medicine; Houston, TX 77030 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHyperamylasemia Following Lipid Resuscitation 1 January 1997Volume 126, Issue 1Page: 89KeywordsAbdominal painAlcoholismBloodChartsComputed axial tomographyEmergency departmentEpileptic seizuresPancreasPancreatitisRenal failure ePublished: 15 August 2000 Issue Published: 1 January 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Deaths from drug poisoning in English and Welsh men reach five year peak
Authors: A. O'Dowd
Journal: BMJ (2008)

Almost 2000 men died from drug poisoning last year in England and Wales, the highest number for five years, the latest statistics from the Office for National Statistics (ONS) show.

Deaths linked to heroin and morphine accounted for the largest amount of the total number of 2640 deaths from drug poisoning in men and women in 2007, but one of the sharpest rises in deaths involved methadone.

The figures showed that 1914 deaths of men were related to drug poisoning, the highest recorded number since 2002—and a rise of 7% from the 1782 deaths recorded in 2006.

Deaths among women, however, were at their lowest recorded annual number since the ONS drug poisoning database was begun …
Effects of long-term training on neutrophil function in male university judoists
Authors: Y Yamamoto, S Nakaji, T Umeda, M Matsuzaka, I Takahashi, M Tanabe, K Danjo, A Kojima, T Oyama
Journal: British Journal of Sports Medicine (2008)

Objectives: To clarify the effects of high-intensity and high-frequency long-term/chronic training on neutrophil function and serum levels of myogenic enzymes in male university judoists. Methods: The subjects were 24 male judoists who had stopped judo training for 6 months and then restarted their training. The following parameters were examined before and after a 2 h unified exercise loading (UEL) at the beginning of the restarted quotidian training (pre-training) and at 2 months, 4 months and 6 months thereafter: myogenic enzymes, neutrophil and leucocyte counts, and neutrophil phagocytic activity (PA) and oxidative burst activity as a measure of reactive oxygen species (ROS) production capability. Results: Myogenic enzymes that were measured after UEL at all four points significantly increased except for creatine kinase at the 2-month point (p&lt;0.01 in each) and neutrophil counts significantly increased after UEL at the pre-training, 2-month and 4-month points (p&lt;0.01 in each), but these changes became smaller from the 2-month point. PA significantly decreased after UEL at the pre-training and 2-month points (p&lt;0.01 in each), but no change was seen at the 4-month and 6-month points. On the other hand, no change in ROS production per cell after UEL was seen at the pre-training point, but it significantly increased after UEL at the 2-month, 4-month and 6-month points (p&lt;0.01 in each). Conclusion: The changing rate of the levels of UEL-mediated myogenic enzymes, neutrophil mobilisation and neutrophil function was seen to decrease at the 2-month, 4-month and 6-month assessments, compared with the pre-training point: these may comprise at least some of the long-term training effects.
Air Pollution Exposure During Pregnancy, Ultrasound Measures of Fetal Growth, and Adverse Birth Outcomes: A Prospective Cohort Study
Authors: Edith H. van den Hooven, Frank H. Pierik, Yvonne de Kluizenaar, Sten P. Willemsen, Albert Hofman, Sjoerd W. van Ratingen, Peter Y.J. Zandveld, Johan P. Mackenbach, Eric A.P. Steegers, Henk M.E. Miedema, Vincent W.V. Jaddoe
Journal: Environmental Health Perspectives (2011)

Air pollution exposure during pregnancy might have trimester-specific effects on fetal growth.We prospectively evaluated the associations of maternal air pollution exposure with fetal growth characteristics and adverse birth outcomes in 7,772 subjects in the Netherlands.Particulate matter with an aerodynamic diameter < 10 μm (PM10) and nitrogen dioxide (NO2) levels were estimated using dispersion modeling at the home address. Fetal head circumference, length, and weight were estimated in each trimester by ultrasound. Information on birth outcomes was obtained from medical records.In cross-sectional analyses, NO2 levels were inversely associated with fetal femur length in the second and third trimester, and PM10 and NO2 levels both were associated with smaller fetal head circumference in the third trimester [-0.18 mm, 95% confidence interval (CI): -0.24, -0.12 mm; and -0.12 mm, 95% CI: -0.17, -0.06 mm per 1-μg/m3 increase in PM10 and NO2, respectively]. Average PM10 and NO2 levels during pregnancy were not associated with head circumference and length at birth or neonatally, but were inversely associated with birth weight (-3.6 g, 95% CI: -6.7, -0.4 g; and -3.4 g, 95% CI: -6.2, -0.6 g, respectively). Longitudinal analyses showed similar patterns for head circumference and weight, but no associations with length. The third and fourth quartiles of PM10 exposure were associated with preterm birth [odds ratio (OR) = 1.40, 95% CI: 1.03, 1.89; and OR = 1.32; 95% CI: 0.96, 1.79, relative to the first quartile]. The third quartile of PM10 exposure, but not the fourth, was associated with small size for gestational age at birth (SGA) (OR = 1.38; 95% CI: 1.00, 1.90). No consistent associations were observed for NO2 levels and adverse birth outcomes.Results suggest that maternal air pollution exposure is inversely associated with fetal growth during the second and third trimester and with weight at birth. PM10 exposure was positively associated with preterm birth and SGA.
Tissue-Based Research in Kidney Cancer: Current Challenges and Future Directions
Authors: Sabina Signoretti, Gennady Bratslavsky, Frederick M. Waldman, Victor E. Reuter, John Haaga, Maria Merino, George V. Thomas, Michael R. Pins, Towia Libermann, John Gillespie, Joseph E. Tomaszewski, Carolyn C. Compton, Andrew Hruszkewycz, W. Marston Linehan, Michael B. Atkins
Journal: Clinical Cancer Research (2008)

Abstract The past several years have seen unprecedented advances in the application of various therapeutic strategies for the treatment of patients with renal cancer. The availability of active immunotherapy, antiangiogenic therapy, and targeted therapy for this disease has brought front and center issues related to choosing the appropriate treatment for particular patient populations. It is increasingly evident that the most promising treatment selection strategies will incorporate identifying specific features of the tumor itself. To facilitate this move toward personalized medicine, it is critically important to establish some standard principles for renal cancer tissue collection, preparation, and analysis for translational research studies. In this article, we identify and discuss some critical issues related to tissue-based kidney cancer research. We focus on five major areas as follows: (a) surgical and image-guided techniques for tissue collection; (b) quality control of specimen collection, processing, storage, and review; (c) issues related to analysis of paraffin embedded tissues; (d) genomic studies; and (e) assessment of reproducibility of assays across institutions. In addition, some practical implementation strategies are proposed. Although many of the topics discussed are specific for renal cancer, several are also relevant to tissue based biomarker investigations in a broad array of malignancies.
Upregulated response to chemokines in oxidative metabolism of eosinophils in asthma and allergic rhinitis
Authors: S. Sannohe, T. Adachi, K. Hamada, K. Honda, Y. Yamada, N. Saito, C‐H. Cui, H. Kayaba, K. Ishikawa, J. Chihara
Journal: European Respiratory Journal (2003)

Reactive oxygen species (ROS) from eosinophils are known to cause tissue damage in allergic inflammation. CC chemokines, especially eotaxin and regulated on activation, normal T‐cell expressed and secreted (RANTES), are involved not only in chemotaxis but also in eosinophil activation, such as ROS production. It has been shown that eosinophils from allergic patients are not functionally equivalent to those from normal subjects. In the present study, the characteristics of chemokine­primed ROS production in eosinophils from allergic patients and normal controls were compared. After pretreatment with chemokines, eosinophils were stimulated with calcium ionophore A23187. ROS production by eosinophils was measured using luminol­dependent chemiluminescence. Both RANTES and eotaxin exhibited a priming effect on calcium ionophore­induced ROS production from eosinophils. Despite there being no difference in expression of CC chemokine receptor 3, the priming effect of RANTES and eotaxin was significantly enhanced in eosinophils from the patients. Interleukin‐5 further enhanced the priming effect of chemokines in eosinophils from normal subjects, but not those from allergic subjects. The present results suggest an upregulated response to chemokines in eosinophils from allergic patients, and that interleukin‐5 can induce a similar phenotype to that found in vivo in allergic patients.
Isolation from Rat Diaphragm of a Calcium-Protein Complex Involved in Excitation-Contraction Coupling
Authors: Stephen Hajdu, Christian J. Posner, Edward J. Leonard
Journal: Circulation Research (1971)

Rat diaphragms depleted of calcium involved in excitation-contraction (E-C calcium) coupling were tagged with 45 Ca Seventy percent of the 45 Ca was extracted by a 25 m M NaHCO 3 -50% glycerol solution. Treatment of the muscles with caffeine, shown previously to release E-C calcium, decreased extractable 45 Ca to about one-fourth of that of control muscles, indicating that a large fraction of the extracted 45 Ca is involved in E-C coupling. On gel filtration, only 10% of the extracted 45 Ca was bound to protein. This figure increased to 30% when procaine (which stabilizes E-C calcium) was present in the extraction solution; total extracted 45 Ca remained unchanged. The results suggest that E-C calcium is extracted from the muscle as a calcium-protein complex and is readily dissociated from the protein unless prevented in part by procaine. Cadmium-115, which is shown to replace 45 Ca at the sites involved in E-C coupling, binds more strongly than 45 Ca When 115 Cd muscles were extracted with glycerol solution containing procaine, all the extracted ll5 Cd was in protein-bound form. One of the extracted proteins formed a precipitin line which was immunochemicaliy identical with rat plasma cardioglobulin-C when tested in gel against an anti-cardioglobulin-C antiserum. This supports our hypothesis that cardioglobulin is the circulating form of a cell membrane calcium transport system.
Distinctive growth requirements and gene expression patterns distinguish progenitor B cells from pre-B cells.
Authors: E A Faust, D C Saffran, D Toksoz, D A Williams, O N Witte
Journal: The Journal of Experimental Medicine (1993)

Long-term bone marrow cultures have been useful in determining gene expression patterns in pre-B cells and in the identification of cytokines such as interleukin 7 (IL-7). We have developed a culture system to selectively grow populations of B lineage restricted progenitors (pro-B cells) from murine bone marrow. Pro-B cells do not grow in response to IL-7, Steel locus factor (SLF), or a combination of the two. c-kit, the SLF receptor, and the IL-7 receptor are both expressed by pro-B cells, indicating that the lack of response is not simply due to the absence of receptors. Furthermore, SLF is not necessary for the growth of pro-B cells since they could be expanded on a stromal line derived from Steel mice that produces no SLF. IL-7 responsiveness in pre-B cells is associated with an increase in n-myc expression and is correlated with immunoglobulin (Ig) gene rearrangements. Although members of the ets family of transcription factors and the Pim-1 kinase are expressed by pro-B cells, n-myc is not expressed. Pro-B cells maintain Ig genes in the germline configuration, which is correlated with a low level of recombination activating genes 1 and 2 (Rag-1 and 2) mRNA expression, but high expression of sterile mu and terminal deoxynucleotidyl transferase. Pro-B cells are unable to grow separated from the stromal layer by a porous membrane, indicating that stromal contact is required for growth. These results suggest that pro-B cells are dependent on alternative growth signals derived from bone marrow stroma and can be distinguished from pre-B cells by specific patterns of gene expression.
Feeling Unreal: A PET Study of Depersonalization Disorder
Authors: Daphne Simeon, Orna Guralnik, Erin A. Hazlett, Jacqueline Spiegel-Cohen, Eric Hollander, Monte S. Buchsbaum
Journal: American Journal of Psychiatry (2000)

The goal of this study was to assess brain glucose metabolism and its relationship to dissociation measures and clinical symptoms in DSM-IV depersonalization disorder.Positron emission tomography scans coregistered with magnetic resonance images of eight subjects with depersonalization disorder were compared to those of 24 healthy comparison subjects. The two groups did not differ in age, sex, education, performance on a baseline neuropsychological battery, or performance on a verbal learning task administered during [(18)F]fluorodeoxyglucose uptake. A cortical analysis by individual Brodmann's areas was performed.Compared to the healthy subjects, subjects with depersonalization disorder showed significantly lower metabolic activity in right Brodmann's areas 22 and 21 of the superior and middle temporal gyri and had significantly higher metabolism in parietal Brodmann's areas 7B and 39 and left occipital Brodmann's area 19. Dissociation and depersonalization scores among the subjects with depersonalization disorder were significantly positively correlated with metabolic activity in area 7B.Depersonalization appears to be associated with functional abnormalities along sequential hierarchical areas, secondary and cross-modal, of the sensory cortex (visual, auditory, and somatosensory), as well as areas responsible for an integrated body schema. These findings are in good agreement with the phenomenological conceptualization of depersonalization as a dissociation of perceptions as well as with the subjective symptoms of depersonalization disorder.