tbuckley/cabot-search huggingface dataset:
Effects of Repetition and Competition on Activity in Left Prefrontal Cortex during Word Generation
Authors: Sharon L. Thompson-Schill, Mark D'Esposito, Irene P. Kan
Journal: Neuron (1999)

Neuroimaging studies have revealed an association between word generation and activity in the left inferior frontal gyrus (IFG) that is attentuated with item repetition. The experiment reported here examined the effects of repeated word generation, under conditions in which completion was either decreased or increased, on activity measured during whole-brain echoplanar functional magnetic resonance imaging. Activity in left IFG decreased during repetition conditions that reduced competition but increased during repetition conditions that increased competition; this pattern was contrasted to repetition effects observed in other cortical areas, specifically regions of left temporal cortex. The increase in left IFG activity, which is not predicted by a simple semantic retrieval account of prefrontal function, is consistent with the hypothesis that left IFG subserves the selection of semantic knowledge among competing alternatives.
Platelet-mediated cytotoxicity. Role of antibody and C3, and localization of the cytotoxic system in membranes.
Authors: S Slezak, D E Symer, H S Shin
Journal: The Journal of Experimental Medicine (1987)

Platelets are one of several cell types capable of mediating antibody-dependent cellular cytotoxicity. We have developed a plasma-free system in which washed mouse platelets lyse washed antibody and complement-sensitized SRBC targets in the presence of EDTA. The dose-response curve is concave to the abscissa, indicating that lysis is a one-hit reaction. Determination of the actual number of platelets required to lyse a target shows that each platelet could lyse a single target. A limited degree of lysis is observed when platelets are incubated with SRBC sensitized with monoclonal IgG2a alone, but no lysis occurs with SRBC bearing comparable amounts of other isotypes. In the presence of C1 through C3, but not C1 through C2, efficient lysis is triggered by complement-fixing monoclonal IgG2a, IgG2b, and IgG3. In contrast, IgM and non-complement-fixing IgG1 and IgE are inactive. To achieve efficient lysis, it appears that platelets require both target cell-bound antibody and C3 fragments in close proximity. It is unlikely that proteases, pore-forming proteins, or toxic oxygen metabolites are involved in platelet-mediated lysis. Freezing and thawing of platelets, sonication, or sonication followed by hypotonic shock causes severe depletion of cytoplasmic and granular contents, as shown by electron microscopy and marker assays. However, the membrane fraction of these preparations retains cytolytic activity. When platelets are treated with trypsin or heated, lytic activity is eliminated, indicating that at least one component of this system is protein. These findings, as well as the fact that platelets do not lyse unsensitized innocent bystander SRBC, suggest that the complete cytotoxic system of platelets capable of specific recognition and lysis resides in their membranes.
Chronomodulated capecitabine in combination with short-time oxaliplatin: a Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil
Authors: C. Qvortrup, M. Yilmaz, D. Ogreid, A. Berglund, L. Balteskard, J. Ploen, T. Fokstuen, H. Starkhammar, H. Sørbye, K. Tveit, P. Pfeiffer
Journal: Annals of Oncology (2008)
Twist1 Induces CCL2 and Recruits Macrophages to Promote Angiogenesis
Authors: Janine M. Low-Marchelli, Veronica C. Ardi, Edward A. Vizcarra, Nico van Rooijen, James P. Quigley, Jing Yang
Journal: Cancer Research (2013)

Abstract The transcription factor Twist1 induces epithelial–mesenchymal transition and extracellular matrix degradation to promote tumor metastasis. Although Twist1 also plays a role in embryonic vascular development and tumor angiogenesis, the molecular mechanisms that underlie these processes are not as well understood. Here, we report a novel function for Twist1 in modifying the tumor microenvironment to promote progression. We found that expression of Twist1 in human mammary epithelial cells potently promoted angiogenesis. Surprisingly, Twist1 expression did not increase the secretion of the common proangiogenic factors VEGF and basic fibroblast growth factor but rather induced expression of the macrophage chemoattractant CCL2. Attenuation of endogenous Twist1 in vivo blocked macrophage recruitment and angiogenesis, whereas exogenous CCL2 rescued the ability of tumor cells lacking Twist1 to attract macrophages and promote angiogenesis. Macrophage recruitment also was essential for the ability of Twist1-expressing cells to elicit a strong angiogenic response. Together, our findings show that how Twist1 recruits stromal macrophages through CCL2 induction to promote angiogenesis and tumor progression. As Twist1 expression has been associated with poor survival in many human cancers, this finding suggests that anti-CCL2 therapy may offer a rational strategy to treat Twist1-positive metastatic cancers. Cancer Res; 73(2); 662–71. ©2012 AACR.
In vivo and in vitro clonal deletion of double-positive thymocytes.
Authors: N J Vasquez, J Kaye, S M Hedrick
Journal: The Journal of Experimental Medicine (1992)

To study the processes of thymic development, we have established transgenic mice expressing and alpha/beta T cell antigen receptor (TCR) specific for cytochrome c associated with class II major histocompatibility complex (MHC) molecules. The transgenic TCR chains are expressed by most of the thymocytes in these mice, and these cells have been shown to efficiently mature in association with Ek- and Ab-encoded class II MHC molecules. This report describes a characterization of the negative selection of these transgenic thymocytes in vivo that is associated with the expression of As molecules. Negative selection by As molecules appears to result in the deletion of a late stage of CD4/CD8 double-positive thymocytes in that there is a virtual absence of transgenic TCR bearing CD4 single-positive thymocytes. This phenotype is accompanied by the appearance of CD4/CD8 double-negative thymocytes and peripheral T cells that are functionally antigen reactive. The process of negative selection has also been investigated using an in vitro culture system. Upon presentation of cytochrome c by Eb-expressing nonthymic antigen-presenting cells, there occurs an antigen dose-dependent deletion of the majority of CD4/CD8 double-positive thymocytes. In contrast, presentation of Staphylococcal enterotoxin A by Eb in vitro results in minimal deletion of double-positive thymocytes. In addition, we use this in vitro model to examine the effects of cyclosporin A on negative selection. In contrast to its effects on mature T cells, and the findings of others in vivo, cyclosporin A does not inhibit antigen-induced deletion of double-positive thymocytes. Finally, a comparison of the antigen dose responses for thymocyte deletion and for peripheral T cell activation indicates that double-positive thymocyte recognition is more sensitive than mature T cells to antigen recognition.
Multiple downstream proarrhythmic targets for calmodulin kinase II: Moving beyond an ion channel-centric focus
Authors: Mark E. Anderson
Journal: Cardiovascular Research (2006)

The multifunctional Ca2+ calmodulin-dependent protein kinase II (CaMKII) has emerged as a pro-arrhythmic signaling molecule. CaMKII can participate in arrhythmia signaling by effects on ion channel proteins, intracellular Ca2+ uptake and release, regulation of cell death, and by activation of hypertrophic signaling pathways. The pleuripotent nature of CaMKII is reminiscent of another serine–threonine kinase, protein kinase A (PKA), which shares many of the same protein targets and is the downstream kinase most associated with β-adrenergic receptor stimulation. The ability of CaMKII to localize and coordinate activity of multiple protein targets linked to Ca2+ signaling set CaMKII apart from other "traditional" arrhythmia drug targets, such as ion channel proteins. This review will discuss some of the biology of CaMKII and focus on work that has been done on molecular, cellular, and whole animal models that together build a case for CaMKII as a pro-arrhythmic signal and as a potential therapeutic target for arrhythmias and structural heart disease.
Seasonal Variations in Clinical and Laboratory Variables among Chronic Hemodialysis Patients
Authors: Alfred K. Cheung, Guofen Yan, Tom Greene, John T. Daugirdas, Johanna T. Dwyer, Nathan W. Levin, Daniel B. Ornt, Gerald Schulman, Garabed Eknoyan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Seasonal variations in BP among chronic hemodialysis patients have been reported. It was hypothesized that other characteristics of these patients might also vary with the seasons. Twenty-one clinical and laboratory variables were examined for seasonal variations among 1445 patients enrolled in the Hemodialysis Study, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Mixed-effects models were applied to longitudinal changes (up to 45 mo) for individual patients for 19 of the 21 variables, which were measured at least twice each year, to determine the seasonal component of each variable. Seasonal variations in the other two variables, i.e., protein and energy intakes determined from annual dietary records, were assessed in cross-sectional comparisons of intakes of patients entering the study at different time points. Thirteen of the 21 variables examined demonstrated statistically significant (P < 0.01) seasonal components in their longitudinal variations. Predialysis blood urea nitrogen concentrations peaked in March, which coincided approximately with the peak protein catabolic rates, as well as protein and energy intakes (determined by dietary recall). Predialysis systolic and diastolic BP values were highest in winter and lowest in summer, corroborating previous reports. In addition, the lower predialysis BP values in summer were associated with higher outdoor temperatures and less interdialytic fluid gain. The mean predialysis hematocrit values were highest in July, which could not be attributed solely to the estimated changes in plasma volume. Seasonal variations in clinical and laboratory variables occur commonly among chronic hemodialysis patients. The reasons for most of these variations are not apparent and require further investigation. Nonetheless, failure to consider these variations might lead to biases in the interpretation of clinical studies. In addition, awareness of these variations might facilitate the interpretation of laboratory results and the clinical treatment of these patients.
Effect of wearing an ice cooling jacket on repeat sprint performance in warm/humid conditions
Authors: R Duffield, B Dawson, D Bishop, M Fitzsimons, S Lawrence
Journal: British Journal of Sports Medicine (2003)

Objective: To examine the effect of cooling the skin with an ice jacket before and between exercise bouts (to simulate quarter and half time breaks) on prolonged repeat sprint exercise performance in warm/humid conditions. Methods: After an initial familiarisation session, seven trained male hockey players performed two testing sessions (seven days apart), comprising an 80 minute intermittent, repeat sprint cycling exercise protocol inside a climate chamber set at 30°C and 60% relative humidity. On one occasion a skin cooling procedure was implemented (in random counterbalanced order), with subjects wearing an ice cooling jacket both before (for five minutes) and in the recovery periods (2 × 5 min and 1 × 10 min) during the test. Measures of performance (work done and power output on each sprint), heart rates, blood lactate concentrations, core (rectal) and skin temperatures, sweat loss, perceived exertion, and ratings of thirst, thermal discomfort, and fatigue were obtained in both trials. Results: In the cooling condition, chest (torso) skin temperature, thermal discomfort, and rating of thirst were all significantly lower (p&lt;0.05), but no significant difference (p&gt;0.05) was observed between conditions for measures of work done, power output, heart rate, blood lactate concentration, core or mean skin temperature, perceived exertion, sweat loss, or ratings of fatigue. However, high effect sizes indicated trends to lowered lactate concentrations, sweat loss, and mean skin temperatures in the cooling condition. Conclusions: The intermittent use of an ice cooling jacket, both before and during a repeat sprint cycling protocol in warm/humid conditions, did not improve physical performance, although the perception of thermal load was reduced. Longer periods of cooling both before and during exercise (to lower mean skin temperature by a greater degree than observed here) may be necessary to produce such a change.
Accuracy of diagnostic tools for the management of nosocomial respiratory infections in mechanically ventilated patients
Authors: A Torres
Journal: European Respiratory Journal (1991)

This article reviews the medical literature concerning available diagnostic tools for managing nosocomial respiratory infections in mechanically ventilated patients. The first part deals with the reliability of the clinical criteria used in diagnosing nosocomial pneumonia in such patients and the accuracy of simple markers of pneumonia such as elastin fibres stain and antibody-coated bacteria. The second part reviews the presently available non-invasive and invasive methods for diagnosing pulmonary infections acquired during mechanical ventilation. With regard to invasive methods, protected specimen brush and bronchoalveolar lavage are extensively discussed in view of the different results in the literature. At the present time, these two methods seem to be the most accurate techniques available. The fact that bronchoalveolar lavage may combine the cytological examination and the quantitative culture of the sample obtained is noted. The role of percutaneous lung needle aspiration is also mentioned. Finally, histological diagnosis of pneumonia and pulmonary postmortem biopsy cultures are reviewed as "gold-standard" reference methods for investigation in this field. Future directions for further clinical research are addressed.
Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement
Authors: Yu Sun, Beata Bak, Nadia Schoenmakers, A S Paul van Trotsenburg, Wilma Oostdijk, Peter Voshol, Emma Cambridge, Jacqueline K White, Paul le Tissier, S Neda Mousavy Gharavy, Juan P Martinez-Barbera, Wilhelmina H Stokvis-Brantsma, Thomas Vulsma, Marlies J Kempers, Luca Persani, Irene Campi, Marco Bonomi, Paolo Beck-Peccoz, Hongdong Zhu, Timothy M E Davis, Anita C S Hokken-Koelega, Daria Gorbenko Del Blanco, Jayanti J Rangasami, Claudia A L Ruivenkamp, Jeroen F J Laros, Marjolein Kriek, Sarina G Kant, Cathy A J Bosch, Nienke R Biermasz, Natasha M Appelman-Dijkstra, Eleonora P Corssmit, Guido C J Hovens, Alberto M Pereira, Johan T den Dunnen, Michael G Wade, Martijn H Breuning, Raoul C Hennekam, Krishna Chatterjee, Mehul T Dattani, Jan M Wit, Daniel J Bernard
Journal: Nature Genetics (2012)
Expression Profile of Malignant and Nonmalignant Lesions of Esophagus and Stomach: Differential Activity of Functional Modules Related to Inflammation and Lipid Metabolism
Authors: Luciana I. Gomes, Gustavo H. Esteves, Alex F. Carvalho, Elier B. Cristo, Roberto Hirata, Waleska K. Martins, Sarah M. Marques, Luiz P. Camargo, Helena Brentani, Adriane Pelosof, Cláudia Zitron, Rubens A. Sallum, André Montagnini, Fernando A. Soares, E. Jordão Neves, Luiz F.L. Reis
Journal: Cancer Research (2005)

Abstract Adenocarcinomas of stomach and esophagus are frequently associated with preceding inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of the gastric mucosa is associated with higher risk of malignization, Barrett's disease is a risk factor for adenocarcinoma of the esophagus. Barrett's disease is characterized by the substitution of the squamous mucosa of the esophagus by a columnar tissue classified histopathologically as intestinal metaplasia. Using cDNA microarrays, we determined the expression profile of normal gastric and esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both organs. Data were explored to define functional alterations related to the transformation from squamous to columnar epithelium and the malignant transformation from intestinal metaplasia to adenocarcinomas. Based on their expression profile, adenocarcinomas of the esophagus showed stronger correlation with intestinal metaplasia of the stomach than with Barrett's mucosa. Second, we identified two functional modules, lipid metabolism and cytokine, as being altered with higher statistical significance. Whereas the lipid metabolism module is active in samples representing intestinal metaplasia and inactive in adenocarcinomas, the cytokine module is inactive in samples representing normal esophagus and esophagitis. Using the concept of relevance networks, we determined the changes in linear correlation of genes pertaining to these two functional modules. Exploitation of the data presented herein will help in the precise molecular characterization of adenocarcinoma from the distal esophagus, avoiding the topographical and descriptive classification that is currently adopted, and help with the proper management of patients with Barrett's disease.
Treatment of High-Risk Neuroblastoma With Triple-Tandem High-Dose Therapy and Stem-Cell Rescue: Results of the Chicago Pilot II Study
Authors: Morris Kletzel, Howard M. Katzenstein, Paul R. Haut, Alice L. Yu, Elaine Morgan, Marleta Reynolds, Grant Geissler, Maryanne H. Marymount, Dachao Liu, John A. Kalapurakal, Richard M. Shore, Diana M.E. Bardo, Jennifer Schmoldt, Alfred W. Rademaker, Susan L. Cohn
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To investigate whether intensive induction therapy followed by triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue and local irradiation will improve event-free survival for patients with high-risk neuroblastoma. PATIENTS AND METHODS: From August 1995 to January 2000, 25 consecutive newly diagnosed high-risk neuroblastoma patients and one child with recurrent MYCN-amplified disease were enrolled onto the Chicago Pilot II Protocol. After induction therapy and surgery, peripheral-blood stem cells were mobilized with three cycles of high-dose cyclophosphamide and granulocyte colony-stimulating factor. Patients then underwent triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue followed by radiation to the primary site. RESULTS: Twenty-two of the 26 patients successfully completed induction therapy and were eligible for the triple-tandem consolidation high-dose therapy. Sufficient numbers of peripheral-blood stem cells were collected in all but one patient. Seventeen patients were able to complete all three cycles of high-dose therapy and peripheral-blood stem-cell rescue, two patients completed two cycles, and three patients completed one cycle. There was one toxic death, and one patient died from complications of treatment for graft failure. With a median follow-up of 38 months, the 3-year event-free survival and survival rates are 57% ± 11% and 79% ± 10%, respectively. CONCLUSION: The results of this pilot study demonstrate that it is feasible to intensify consolidation with triple-tandem high-dose chemotherapy and peripheral-blood stem-cell rescue and local irradiation, and suggest that this treatment strategy may lead to improved survival for patients with high-risk neuroblastoma.
Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs
Authors: Jianbing Mu, Rachel A Myers, Hongying Jiang, Shengfa Liu, Stacy Ricklefs, Michael Waisberg, Kesinee Chotivanich, Polrat Wilairatana, Srivicha Krudsood, Nicholas J White, Rachanee Udomsangpetch, Liwang Cui, May Ho, Fengzhen Ou, Haibo Li, Jianping Song, Guoqiao Li, Xinhua Wang, Suon Seila, Sreng Sokunthea, Duong Socheat, Daniel E Sturdevant, Stephen F Porcella, Rick M Fairhurst, Thomas E Wellems, Philip Awadalla, Xin-zhuan Su
Journal: Nature Genetics (2010)
Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling
Authors: V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, K. R. Sipido
Journal: Cardiovascular Research (2007)

In the cardiac dyad, sarcolemmal L-type Ca2+ channels (LCCs) and sarcoplasmic reticulum (SR) Ca2+ release channels (RyR) are structurally in close proximity. This organization provides for an efficient functional coupling, tuning SR Ca2+ release for optimal contraction of the myocyte. Given that LCC are regulated by the prevailing [Ca2+], this structural organization is the setting for feedback mechanisms and crosstalk. A defective coupling of Ca2+ influx via LCC to activation of RyR has been implicated in reduced SR Ca2+ release in heart failure. Both functional changes in LCC properties and structural re-organization of LCC in T-tubules could be involved. LCC are regulated by cytosolic Ca2+, and crosstalk with SR Ca2+ handling occurs on a long-term basis, i.e. during steady-state changes in heart rate, on an intermediate-term basis, i.e. on a beat-to-beat basis during sudden rate changes, and on a very short- or immediate-term basis, i.e. during a single heartbeat. We review the properties and consequences of these different feedback mechanisms and the changes in heart failure and cardiac hypertrophy that have thus far been studied.
Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report
Authors: A. John Rush, Madhukar H. Trivedi, Stephen R. Wisniewski, Andrew A. Nierenberg, Jonathan W. Stewart, Diane Warden, George Niederehe, Michael E. Thase, Philip W. Lavori, Barry D. Lebowitz, Patrick J. McGrath, Jerrold F. Rosenbaum, Harold A. Sackeim, David J. Kupfer, James Luther, Maurizio Fava
Journal: American Journal of Psychiatry (2006)

Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of ≤5 on the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR 16 ) (equivalent to ≤7 on the 17-item Hamilton Rating Scale for Depression [HRSD 17 ]) defined remission; a QIDS-SR 16 total score of ≥11 (HRSD 17 ≥14) defined relapse. Results: The QIDS-SR 16 remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. Conclusions: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.