tbuckley/cabot-search huggingface dataset:
APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa
Authors: Bertrand Huard, Thomas McKee, Carine Bosshard, Stéphane Durual, Thomas Matthes, Samir Myit, Olivier Donze, Christophe Frossard, Carlo Chizzolini, Christiane Favre, Rudolf Zubler, Jean Philippe Guyot, Pascal Schneider, Eddy Roosnek
Journal: Journal of Clinical Investigation (2008)

The bone marrow constitutes a favorable environment for long-lived antibody-secreting plasma cells, providing blood-circulating antibody. Plasma cells are also present in mucosa-associated lymphoid tissue (MALT) to mediate local frontline immunity, but how plasma cell survival there is regulated is not known. Here we report that a proliferation-inducing ligand (APRIL) promoted survival of human upper and lower MALT plasma cells by upregulating expression of the antiapoptotic proteins bcl-2, bcl-xL, and mcl-1. The in situ localization of APRIL was consistent with such a prosurvival role in MALT. In upper MALT, tonsillar epithelium produced APRIL. Upon infection, APRIL production increased considerably when APRIL-secreting neutrophils recruited from the blood infiltrated the crypt epithelium. Heparan sulfate proteoglycans (HSPGs) retained secreted APRIL in the subepithelium of the infected zone to create APRIL-rich niches, wherein IgG-producing plasma cells accumulated. In lower MALT, neutrophils were the unique source of APRIL, giving rise to similar niches for IgA-producing plasmocytes in villi of lamina propria. Furthermore, we found that mucosal humoral immunity in APRIL-deficient mice is less persistent than in WT mice. Hence, production of APRIL by inflammation-recruited neutrophils may create plasma cell niches in MALT to sustain a local antibody production.
Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer
Authors: M.M. Kim, P. Allen, A.M. Gonzalez-Angulo, W.A. Woodward, F. Meric-Bernstam, A.U. Buzdar, K.K. Hunt, H.M. Kuerer, J.K. Litton, G.N. Hortobagyi, T.A. Buchholz, E.A. Mittendorf
Journal: Annals of Oncology (2013)
Exposure to Concentrated Ambient Particles Does Not Affect Vascular Function in Patients with Coronary Heart Disease
Authors: Nicholas L. Mills, Simon D. Robinson, Paul H. B. Fokkens, Daan L. A. C. Leseman, Mark R. Miller, David Anderson, Evelyn J. Freney, Mathew R. Heal, Robert J. Donovan, Anders Blomberg, Thomas Sandström, William MacNee, Nicholas A. Boon, Ken Donaldson, David E. Newby, Flemming R. Cassee
Journal: Environmental Health Perspectives (2008)

BackgroundExposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans.ObjectivesWe conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction.MethodsTwelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures.ResultsParticulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 μg/m3) were higher than ambient levels (31 ± 8 μg/m3) and levels in filtered air (0.5 ± 0.4 μg/m3; p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group.ConclusionsDespite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans.
Large-Volume Microfluidic Cell Sorting for Biomedical Applications
Authors: Majid Ebrahimi Warkiani, Lidan Wu, Andy Kah Ping Tay, Jongyoon Han
Journal: Annual Review of Biomedical Engineering (2015)

Microfluidic cell-separation technologies have been studied for almost two decades, but the limited throughput has restricted their impact and range of application. Recent advances in microfluidics enable high-throughput cell sorting and separation, and this has led to various novel diagnostic and therapeutic applications that previously had been impossible to implement using microfluidics technologies. In this review, we focus on recent progress made in engineering large-volume microfluidic cell-sorting methods and the new applications enabled by them.
Lck regulates the tyrosine phosphorylation of the T cell receptor subunits and ZAP-70 in murine thymocytes.
Authors: N S van Oers, N Killeen, A Weiss
Journal: The Journal of Experimental Medicine (1996)

The Src-family and Syk/ZAP-70 family of protein tyrosine kinases (PTK) are required for T cell receptor (TCR) functions. We provide evidence that the Src-family PTK Lck is responsible for regulating the constitutive tyrosine phosphorylation of the TCR zeta subunit in murine thymocytes. Moreover, ligation of the TCR expressed on thymocytes from Lck-deficient mice largely failed to induce the phosphorylation of TCR-zeta, CD3 epsilon, or ZAP-70. In contrast, we find that the TCR-zeta subunit is weakly constitutively tyrosine phosphorylated in peripheral T cells isolated from Lck-null mice. These data suggest that Lck has a functional role in regulation of TCR signal transduction in thymocytes. In peripheral T cells, other Src-family PTKs such as Fyn may partially compensate for the absence of Lck.
Prognostic value of preoperatively obtained clinical and laboratory data in predicting survival following orthotopic liver transplantation
Authors: Valentin Cuervas-Mons, Isabel Millan, Judith S. Gavaler, Thomas E. Starzl, David H. van Thiel
Journal: Hepatology (1986)

Twenty-seven clinical and laboratory data and the subsequent clinical course of 93 consecutive adult patients who underwent orthotopic liver transplantation for various chronic advanced liver diseases were analyzed retrospectively to assess the risk factors of early major bacterial infection and death after the procedure. Forty-one patients (44%) had early major bacterial infection during hospitalization for orthotopic liver transplantation. The mortality rate was 70.7% in patients with early major bacterial infection and was 7.7% in patients without early major bacterial infection (p < 0.001). Total serum bilirubin, total white blood cell count and polymorphonuclear cell count, IgG (all p < 0.05) and plasma creatinine level (p < 0.001) were higher in patients that developed early major bacterial infection than in those who did not. By step-wise discriminant analysis, the strongest risk factor for early major bacterial infection was the serum creatinine level, which achieved an accuracy of 69% for a creatinine level greater than 1.58 mg per dl. Seven variables (ascites, hepatic encephalopathy, elevated white blood and polymorphonuclear cell count, decreased helper to suppressor T cell ratio and elevated plasma creatinine and bilirubin levels) were associated with a significant increased risk for death. A step-wise discriminant analysis of these seven factors resulted in the demonstration of serum creatinine as the greatest risk factor for mortality. A preoperative serum creatinine either less than or greater than 1.72 mg per dl accurately predicts survival or death, respectively, in 79% of cases. These data suggest that the baseline preoperative serum creatinine level provides the best indication of the short-term prognosis after liver transplantation than does any other preoperatively obtained index of the patient's status.
Identification and characterization of receptors specific for human pancreatic secretory trypsin inhibitor.
Authors: T Niinobu, M Ogawa, A Murata, J Nishijima, T Mori
Journal: The Journal of Experimental Medicine (1990)

Specific binding sites for human pancreatic secretory trypsin inhibitor (PSTI) on 3T3 Swiss albino cells were studied using radioiodinated recombinant PSTI. Some ion species, pH, and temperature significantly influenced the binding of 125I-PSTI. Kinetic studies showed that the binding of 125I-PSTI to 3T3 Swiss albino cells reached the maximum level within 120 min at 4 degrees C, with a slow dissociation rate. The half-maximal inhibition (ID50) of 125I-PSTI binding by unlabeled PSTI occurred at 1.0 x 10(-10) M. On Scatchard analysis of the competitive binding data, linear plots indicated a single class of receptors with high affinity (Kd = 5.3 x 10(-10) M) on 3T3 Swiss albino cells, the number of receptors being 5,400 per cell. Treatment of surface-bound radiolabeled PSTI with a chemical crosslinker (disuccinimidyl suberate) led to the identification of a membrane polypeptide of Mr 140,000 to which PSTI was crosslinked. The formation was inhibited by an excess amount of unlabeled PSTI in a dose-dependent manner. The binding of 125I-PSTI to 3T3 Swiss albino cells was competitively inhibited by unlabeled PSTI but not by other peptide hormones, such as epidermal growth factor (EGF), bovine fibroblast growth factor, insulin-like growth factor, transforming growth factor alpha, platelet-derived growth factor, and tumor necrosis factor, indicating the presence of receptors specific for PSTI. Various protease inhibitors had no or only a little effect, and mercaptoethanol and dithiothreitol strongly decreased the binding of 125I-PSTI. Incubation at 37 degrees C resulted in rapid internalization of cell-bound 125I-PSTI, followed by the appearance of trichloroacetic acid-soluble 125I-radioactivity in the culture medium, due to degradation of internalized PSTI. In addition, PSTI stimulated [3H]thymidine incorporation into DNA on 3T3 Swiss albino cells in a dose-dependent manner. The combined addition of PSTI and EGF stimulated [3H]thymidine incorporation to an extent greater than that seen with either agent alone. These results indicated that the biological effect of PSTI was mediated by high affinity plasma membrane receptors, which were not a cell-surface proteinase(s). Specific binding of 125I-PSTI was noted with the following cells: WI-38, 3T3 Swiss albino, HUVE, BDC-1, and H4-II-E-C3.
Hyperphosphorylation of Na-Pump Contributes to Defective Renal Dopamine Response in Old Rats
Authors: MOHAMMAD ASGHAR, VIKRAM KANSRA, TAHIR HUSSAIN, MUSTAFA F. LOKHANDWALA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Dopamine D 1 -like receptor activation causes phosphorylation and inhibition of Na,K-ATPase (Na-pump) activity in the proximal tubules, which is associated with an increase in sodium excretion. It has been shown that dopamine and SKF 38393, a D 1 -like receptor agonist, caused inhibition of Na,K-ATPase activity in the proximal tubules of adult (6 mo) but not of old (24 mo) Fischer 344 rats. The present study demonstrated that SKF 38393 and PDBu, a phorbol ester and protein kinase C (PKC) activator, increased phosphorylation of the α 1 -subunit of Na,K-ATPase in adult but not in old rats. In adult rats, SKF 38393-mediated phosphorylation was antagonized by SCH 23390, a D 1 -like receptor antagonist. Similarly, Na,K-ATPase activity was inhibited by SKF 38393 and PDBu in adult but not in old rats. The basal activity of Na,K-ATPase was decreased and the basal phosphorylation state of the enzyme was increased in old compared with adult rats. Basal activity of PKC was higher in old compared with adult rats, and SKF 38393 and PDBu stimulated PKC activity in adult but not in old rats. The conclusion is that the failure of D 1 -like receptor agonist and phorbol ester to stimulate PKC and inhibit Na,K-ATPase activity in old rats is due, at least in part, to the higher basal PKC activity and Na,K-ATPase phosphorylation in old compared with adult rats.
Photodynamic therapy of cancer: An update
Authors: Patrizia Agostinis, Kristian Berg, Keith A. Cengel, Thomas H. Foster, Albert W. Girotti, Sandra O. Gollnick, Stephen M. Hahn, Michael R. Hamblin, Asta Juzeniene, David Kessel, Mladen Korbelik, Johan Moan, Pawel Mroz, Dominika Nowis, Jacques Piette, Brian C. Wilson, Jakub Golab
Journal: CA A Cancer Journal for Clinicians (2011)

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.
PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR
Authors: James B. Murphy, Ernest Sturm, Albert Claude, Oscar M. Helmer
Journal: The Journal of Experimental Medicine (1932)

By two methods a protein fraction can be separated out from a Chicken Tumor I extract, which carries all the tumor-producing agent. The precipitate can be dissolved and reprecipitated a number of times without loss of activity. The agent can be largely dissociated from the protein as shown by the fact that aluminum hydroxide will adsorb the protein from an extract and leave the agent behind. This purified material has a very low protein content, if any, as shown by both chemical and biological tests.
Rome II: the Functional Gastrointestinal Disorders. Diagnosis, Pathophysiology and Treatment: a Multinational Consensus
Authors: R. SPILLER
Journal: Gut (2000)

Rome II: the Functional Gastrointestinal Disorders. Diagnosis, Pathophysiology and Treatment: a Multinational Consensus . 2nd edn. Edited by Drossman DA, Corazziari E, Talley J, et al . (Pp 800; illustrated; $79.95) USA: Degnon Associates, 2000. ISBN 0965683729 (PB).

While medical students can confidently hold forth on the mechanisms of the Zollinger-Ellison syndrome, a condition affecting one in a million of the population, they rarely have much to say about functional GI disorders (FGIDs), which can affect up to a quarter of the population at some stage in their life. Part of the reason is that this is a complex area, which requires the integration of pathophysiology with psychology, and even sociology. FGIDs also suffer from having no objective measurable abnormalities, so that classifications must of necessity be symptom based. The Rome process is a valiant attempt to make this area of study less confused, more consistent, and scientifically respectable. As such, it undoubtedly has had a major impact, and Rome criteria are now used for the entry into most clinical trials …
Passive Smoking on Commercial Airline Flights
Authors: M E Mattson, G Boyd, D Byar, C Brown, J F Callahan, D Corle, J W Cullen, J Greenblatt, N J Haley, K Hammond
Journal: JAMA (1989)

In-flight exposure to nicotine, urinary cotinine levels, and symptom self-reports were assessed in a study of nine subjects (five passengers and four attendants) on four routine commercial flights each of approximately four hours' duration. Urine samples were collected for 72 hours following each flight. Exposures to nicotine measured during the flights using personal exposure monitors were found to be variable, with some nonsmoking areas attaining levels comparable to those in smoking sections. Attendants assigned to work in nonsmoking areas were not protected from smoke exposure. The type of aircraft ventilation was important in determining the levels of in-flight nicotine exposure. The environmental tobacco smoke levels that occurred produced measurable levels of cotinine (a major metabolite of nicotine) in the urine of passengers and attendants. Passengers who experienced the greatest smoke exposure had the highest levels of urinary cotinine. Changes in eye and nose symptoms between the beginning and end of the flights were significantly related both to nicotine exposure during the flight and to the subsequent urinary excretion of cotinine. In addition, subjects' perceptions of annoyance and smokiness in the airplane cabin were also related to in-flight nicotine exposure and urinary excretion measures.
Youth Violence Prevention Comes of Age: Research, Training and Future Directions
Authors: Kara Williams, Lourdes Rivera, Robert Neighbours, Vivian Reznik
Journal: Annual Review of Public Health (2007)

Youth violence is recognized as a major public health problem in the United States and the world. Over the past ten years, progress has been made in documenting the factors that contribute to violent behavior. Emerging research is deepening our understanding of the individual and societal influences that contribute to and protect against youth violence. However, much work still remains to be done in this field, both in examining potential causes and in designing effective intervention strategies. This chapter highlights specific dimensions of youth violence prevention selected by the authors because these dimensions are the focus of public attention, are emerging as critical issues in the study of youth violence, or have a unique place in the current political and social context. We focus on the developmental pathways to violence, factors that mediate and moderate youth violence, the role of culture and media in youth violence, school-based violence such as school shootings and bullying, and the training of health care professionals.
Determinants of fatigue in patients with bronchial asthma
Authors: Deniz Inal-Ince, Sema Savci, Naciye Vardar-Yagli, Melda Saglam, Ebru Calik, Meral Bosnak-Guclu, Hulya Arikan, Gul Karakaya, Fuat Kalyoncu
Journal: European Respiratory Journal (2013)

Purpose:  Fatigue is a common symptom for chronic respiratory disease. The aim of this study was to investigate the determinants of fatigue in patients with bronchial asthma.   Methods:  Fifty-two patients with bronchial asthma participated in this study. Pulmonary function testing was performed. Respiratory muscle strength (MIP and MEP) and hand grip strength were measured. Dyspnea perception (Medical Research Council dyspnea scale, MMRC), general and disease specific quality of life (Nottingham Health Profile, NHP, and Asthma Quality of Life Questionnaire, AQLQ, respectively), anxiety (State Trait Anxiety Inventory, STAI), depression (Beck Depression Inventory, BDI), stress management (Health Promotion Scale, HPS) were evaluated. Exercise capacity was assessed using six-minute walk test. Fatigue perception was determined using the Fatigue Severity Scale (FSS).   Results:  The FSS score was significantly related with FEV 1  (r=-0.30), MEP (r=-0.42), %6MWT distance (r=-0.32), dominant hand grip strength (r=-0.33), MMRC (r=0.32), NHP-energy level (r=0.56), NHP-pain (r=0.31), NHP-emotional reactions (r=0.34), NHP-physical mobility (r=0.33), NHP-social isolation (r=0.31) and NHP-total (r=0.51) scores, AQLQ- activity (r=-0.44) and AQLQ-environmental (r=-0.29) scores, BDI (r=0.37), STAI- trait anxiety (r=0.29), and HPS-stress management (r=-0.40) scores (p 2 =0.087), NHP-energy level (r 2 =0.353), HPS-stress management (r 2 =0.102) and BDI scores (r 2 =0.044) explained 59% of the variance in the FSS score (r 2 =0.586, F (1-42) =4.91, p   Conclusion:  Expiratory muscle strength, quality of life, depression, and stress management ability are the determinants of fatigue perception in bronchial asthma.
Cardiovascular Risk and Events in 17 Low-, Middle-, and High-Income Countries
Authors: Salim Yusuf, Sumathy Rangarajan, Koon Teo, Shofiqul Islam, Wei Li, Lisheng Liu, Jian Bo, Qinglin Lou, Fanghong Lu, Tianlu Liu, Liu Yu, Shiying Zhang, Prem Mony, Sumathi Swaminathan, Viswanathan Mohan, Rajeev Gupta, Rajesh Kumar, Krishnapillai Vijayakumar, Scott Lear, Sonia Anand, Andreas Wielgosz, Rafael Diaz, Alvaro Avezum, Patricio Lopez-Jaramillo, Fernando Lanas, Khalid Yusoff, Noorhassim Ismail, Romaina Iqbal, Omar Rahman, Annika Rosengren, Afzalhussein Yusufali, Roya Kelishadi, Annamarie Kruger, Thandi Puoane, Andrzej Szuba, Jephat Chifamba, Aytekin Oguz, Matthew McQueen, Martin McKee, Gilles Dagenais
Journal: New England Journal of Medicine (2014)

More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown.We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years.The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001).Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).