tbuckley/cabot-search huggingface dataset:
The Effects of Volatile Salivary Acids and Bases on Exhaled Breath Condensate pH
Authors: Richard M. Effros, Richard Casaburi, Jennifer Su, Marshall Dunning, John Torday, Julie Biller, Reza Shaker
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Recent studies have reported acidification of exhaled breath condensate (EBC) in inflammatory lung diseases. This phenomenon, designated "acidopnea," has been attributed to airway inflammation.To determine whether salivary acids and bases can influence EBC pH in chronic obstructive pulmonary disease (COPD).Measurements were made of pH, electrolytes, and volatile bases and acids in saliva and EBC equilibrated with air in 10 healthy subjects and 10 patients.The average EBC pH in COPD was reduced (normal, 7.24 +/- 0.24 SEM; range, 6.11-8.34; COPD, 6.67 +/- 0.18; range, 5.74-7.64; p = 0.079). EBCs were well buffered by NH(4)(+)/NH(3) and CO(2)/HCO(3)(-) in all but four patients, who had NH(4)(+) concentrations under 60 micromol/L, and acetate concentrations that approached or exceeded those of NH(4)(+). Saliva contained high concentrations of acetate (approximately 6,000 micromol/L) and NH(4)(+) (approximately 12,000 micromol/L). EBC acetate increased and EBC NH(4)(+) decreased when salivary pH was low, consistent with a salivary source for these volatile constituents. Nonvolatile acids did not play a significant role in determining pH of condensates because of extreme dilution of respiratory droplets by water vapor (approximately 1:12,000). Transfer of both acetic acid and NH(3) from the saliva to the EBC was in the gas phase rather than droplets.EBC acidification in COPD can be affected by the balance of volatile salivary acids and bases, suggesting that EBC pH may not be a reliable marker of airway acidification. Salivary acidification may play an important role in acidopnea.
The Characterization, Molecular Cloning, and Expression of a Novel Hematopoietic Cell Antigen From CD34+ Human Bone Marrow Cells
Authors: Nobuko Uchida, Zhi Yang, Jesse Combs, Olivier Pourquié, Megan Nguyen, Rajeev Ramanathan, Joan Fu, Annemarie Welply, Shirley Chen, Greg Weddell, Arun K. Sharma, Kevin R. Leiby, Domna Karagogeos, Beth Hill, Laurent Humeau, William B. Stallcup, Ron Hoffman, Ann S. Tsukamoto, David P. Gearing, Bruno Péault
Journal: Blood (1997)
Surgery versus Physiotherapy for Stress Urinary Incontinence
Authors: Julien Labrie, Bary L.C.M. Berghmans, Kathelijn Fischer, Alfredo L. Milani, Ileana van der Wijk, Dina J.C. Smalbraak, Astrid Vollebregt, René P. Schellart, Giuseppe C.M. Graziosi, J. Marinus van der Ploeg, Joseph F.G.M. Brouns, E. Stella M. Tiersma, Annette G. Groenendijk, Piet Scholten, Ben Willem Mol, Elisabeth E. Blokhuis, Albert H. Adriaanse, Aaltje Schram, Jan-Paul W.R. Roovers, Antoine L.M. Lagro-Janssen, Carl H. van der Vaart
Journal: New England Journal of Medicine (2013)

Physiotherapy involving pelvic-floor muscle training is advocated as first-line treatment for stress urinary incontinence; midurethral-sling surgery is generally recommended when physiotherapy is unsuccessful. Data are lacking from randomized trials comparing these two options as initial therapy.We performed a multicenter, randomized trial to compare physiotherapy and midurethral-sling surgery in women with stress urinary incontinence. Crossover between groups was allowed. The primary outcome was subjective improvement, measured by means of the Patient Global Impression of Improvement at 12 months.We randomly assigned 230 women to the surgery group and 230 women to the physiotherapy group. A total of 49.0% of women in the physiotherapy group and 11.2% of women in the surgery group crossed over to the alternative treatment. In an intention-to-treat analysis, subjective improvement was reported by 90.8% of women in the surgery group and 64.4% of women in the physiotherapy group (absolute difference, 26.4 percentage points; 95% confidence interval [CI], 18.1 to 34.5). The rates of subjective cure were 85.2% in the surgery group and 53.4% in the physiotherapy group (absolute difference, 31.8 percentage points; 95% CI, 22.6 to 40.3); rates of objective cure were 76.5% and 58.8%, respectively (absolute difference, 17.8 percentage points; 95% CI, 7.9 to 27.3). A post hoc per-protocol analysis showed that women who crossed over to the surgery group had outcomes similar to those of women initially assigned to surgery and that both these groups had outcomes superior to those of women who did not cross over to surgery.For women with stress urinary incontinence, initial midurethral-sling surgery, as compared with initial physiotherapy, results in higher rates of subjective improvement and subjective and objective cure at 1 year. (Funded by ZonMw, the Netherlands Organization for Health Research and Development; Dutch Trial Register number, NTR1248.).
Predictors of late mortality following ablative new-device angioplasty in native coronary arteries
Authors: Simon R. Redwood, Jeffrey J. Popma, Kenneth M. Kent, Augusto D. Pichard, Lowell F. Satler, Gary S. Mintz, Mun K. Hong, Theresa A. Bucher, Alan J. Merritt, Martin B. Leon
Journal: Journal of the American College of Cardiology (1996)
PREVENTING YOUTH VIOLENCE: What Works?
Authors: Arthur L. Kellermann, Dawna S. Fuqua-Whitley, Frederick P. Rivara, James Mercy
Journal: Annual Review of Public Health (1998)

▪ Abstract Between 1985 and 1992, serious youth violence in the United States surged to unprecedented levels. The growing use of firearms to settle disputes has contributed to this phenomenon. Youth are most often victimized by one of their peers. In response to this problem, a wide variety of programs have been implemented in an attempt to prevent youth violence or reduce its severity. Few have been adequately evaluated. In general, interventions applied between the prenatal period and age 6 appear to be more effective than interventions initiated in later childhood or adolescence. Community-based programs that target certain high-risk behaviors may be beneficial as well. A sustained commitment to evaluation research is needed to identify the most effective approaches to youth violence prevention.
Rapid Prototyping of Concave Microwells for the Formation of 3D Multicellular Cancer Aggregates for Drug Screening
Authors: Ting‐Yuan Tu, Zhe Wang, Jing Bai, Wei Sun, Weng Kung Peng, Ruby Yun‐Ju Huang, Jean‐Paul Thiery, Roger D. Kamm
Journal: Advanced Healthcare Materials (2013)

Microwell technology has revolutionized many aspects of in vitro cellular studies from 2D traditional cultures to 3D in vivo‐like functional assays. However, existing lithography‐based approaches are often costly and time‐consuming. This study presents a rapid, low‐cost prototyping method of CO 2 laser ablation of a conventional untreated culture dish to create concave microwells used for generating multicellular aggregates, which can be readily available for general laboratories. Polymethylmethacrylate (PMMA), polydimethylsiloxane (PDMS), and polystyrene (PS) microwells are investigated, and each produces distinctive microwell features. Among these three materials, PS cell culture dishes produce the optimal surface smoothness and roundness. A549 lung cancer cells are grown to form cancer aggregates of controllable size from ≈40 to ≈80 μm in PS microwells. Functional assays of spheroids are performed to study migration on 2D substrates and in 3D hydrogel conditions as a step towards recapitulating the dissemination of cancer cells. Preclinical anti‐cancer drug screening is investigated and reveals considerable differences between 2D and 3D conditions, indicating the importance of assay type as well as the utility of the present approach.
Chemogenomic Profiling Provides Insights into the Limited Activity of Irreversible EGFR Inhibitors in Tumor Cells Expressing the T790M EGFR Resistance Mutation
Authors: Martin L. Sos, Haridas B. Rode, Stefanie Heynck, Martin Peifer, Florian Fischer, Sabine Klüter, Vijaykumar G. Pawar, Cecile Reuter, Johannes M. Heuckmann, Jonathan Weiss, Lars Ruddigkeit, Matthias Rabiller, Mirjam Koker, Jeffrey R. Simard, Matthäus Getlik, Yuki Yuza, Tzu-Hsiu Chen, Heidi Greulich, Roman K. Thomas, Daniel Rauh
Journal: Cancer Research (2010)

Reversible epidermal growth factor receptor (EGFR) inhibitors are the first class of small molecules to improve progression-free survival of patients with EGFR-mutated lung cancers. Second-generation EGFR inhibitors introduced to overcome acquired resistance by the T790M resistance mutation of EGFR have thus far shown limited clinical activity in patients with T790M-mutant tumors. In this study, we systematically analyzed the determinants of the activity and selectivity of the second-generation EGFR inhibitors. A focused library of irreversible as well as structurally corresponding reversible EGFR-inhibitors was synthesized for chemogenomic profiling involving over 79 genetically defined NSCLC and 19 EGFR-dependent cell lines. Overall, our results show that the growth-inhibitory potency of all irreversible inhibitors against the EGFR(T790M) resistance mutation was limited by reduced target inhibition, linked to decreased binding velocity to the mutant kinase. Combined treatment of T790M-mutant tumor cells with BIBW-2992 and the phosphoinositide-3-kinase/mammalian target of rapamycin inhibitor PI-103 led to synergistic induction of apoptosis. Our findings offer a mechanistic explanation for the limited efficacy of irreversible EGFR inhibitors in EGFR(T790M) gatekeeper-mutant tumors, and they prompt combination treatment strategies involving inhibitors that target signaling downstream of the EGFR.
The use of heated citric acid for dialyzer reprocessing.
Authors: N W Levin, S L Parnell, H N Prince, F Gotch, H D Polaschegg, R Levin, A Alto, A M Kaufman
Journal: Journal of the American Society of Nephrology (1995)

Dialyzer reprocessing with heated water (100 to 105 degrees C) for 20 h can be used safely in lieu of chemical methods for disinfection. All infective agents including spores are destroyed and depyrogenation may occur. However, these temperatures may result in structural damage to the dialyzer, limiting reuse. Dialyzer reprocessing by using 1.5% citric acid heated to 95 degrees C for 20 h is an alternative method that produces equivalent microbiologic effects. Citric acid is well known as a disinfecting agent used for dialysis equipment. Because there is little structural damage to dialyzer components at 95 degrees C, reuse statistics are improved (mean reuse increased to 12.8). Both small and large molecule clearances and the sieving coefficient for protein are insignificantly altered by the process. Whereas the procedure is relatively simple, quality-assurance indicators are essential. The method has appeal because it avoids the use of chemical germicides. However, at present it has only been tested thoroughly in polysulfone dialyzers with heat-resistant polycarbonate casings and polyurethane resin. The clinical experience is favorable.
The concentration-response relation between PM(2.5) and daily deaths.
Authors: Joel Schwartz, Francine Laden, Antonella Zanobetti
Journal: Environmental Health Perspectives (2002)

Particulate air pollution at commonly occurring concentrations is associated with daily deaths. Recent attention has focused on the shape of the concentration-response curve, particularly at low doses. Several recent articles have reported that particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) was associated with daily deaths with no evidence of a threshold. These reports have used smoothing or spline methods in individual cities and pooled the results across multiple cities to obtain estimates that are more robust. To date, fine particulate matter (aerodynamic diameter Less than or equal to 2.5 microm; PM(2.5)), a component of PM(10), has not been examined in this regard. We examined this association in a hierarchical model in six U.S. cities. In the first stage, we fit log-linear models including smooth functions of PM(2.5) in each city, controlling for season, weather, and day of the week. These smooth functions allowed for nonlinearities in the city-specific associations. We combined the estimated curves across cities using a hierarchical model that allows for heterogeneity. We found an essentially linear relationship down to 2 microg/m(3). The same approach was applied to examine the concentration response to traffic particles, controlling for particles from other sources. Once again, the association showed no sign of a threshold. The magnitude of the association suggests that controlling fine particle pollution would result in thousands of fewer early deaths per year.
Report ON THE RADIUM TREATMENT AT THE ROYAL INFIRMARY, EDINBURGH, DURING THE YEAR 1914
Authors: D. Turner
Journal: BMJ (1915)

SIXTY-THREE patients attended for radium treatment dutring the past year; of these, were in-patients, 27 were out-patients; 34 of the patients all but 1 case, inoperable malignant from carcinoma, and 11 fromn sarcom-ia.There 12 cases of rodent ulcer, 6 of exoplithalmic otoselerosis, 1 of middle-ear deafness,1 Paget's 1 recurrent wen, 1 sirmple tumour, 1 naevuLs, leucoplakia, warty turmour, 1 hypertrophied Thouglh a cure was not effected in any cases, nor, considering their advanced nature, expected, yet in practically all of those whlo were treated
Tumor Suppressor HLJ1 Binds and Functionally Alters Nucleophosmin via Activating Enhancer Binding Protein 2α Complex Formation
Authors: Tzu-Pei Chang, Sung-Liang Yu, Sheng-Yi Lin, Yi-Jing Hsiao, Gee-Chen Chang, Pan-Chyr Yang, Jeremy J.W. Chen
Journal: Cancer Research (2010)

Abstract HLJ1, a member of the heat shock protein 40 chaperone family, is a newly identified tumor suppressor that has been implicated in tumorigenesis and metastasis in non–small cell lung cancer. However, the mechanism of HLJ1 action is presently obscure. In this study, we report that HLJ1 specifically interacts with the nuclear protein nucleophosmin (NPM1), forming a multiprotein complex that alters the nucleolar distribution and oligomerization state of NPM1. Enforced accumulation of NPM1 oligomers by overexpression in weakly invasive but high HLJ1-expressing cells induced the activity of signal transducer and activator of transcription 3 (STAT3) and increased cellular migration, invasiveness, and colony formation. Furthermore, silencing HLJ1 accelerated NPM1 oligomerization, inhibited the activity of transcription corepressor activating enhancer binding protein 2α (AP-2α), and increased the activities of matrix metalloproteinase-2 (MMP-2) and STAT3. Our findings suggest that HLJ1 switches the role of NPM1, which can act as tumor suppressor or oncogene, by modulating the oligomerization of NPM1 via HLJ1-NPM1 heterodimer formation and recruiting AP-2α to the MMP-2 promoter. Cancer Res; 70(4); 1656–67
Autoregulation of Serotonin Neurons: Role in Antidepressant Drug Action
Authors: Graciela Piñeyro, Pierre Blier
Journal: Pharmacological Reviews (1999)

The existence of an endogenous vasoconstrictor in blood serum ([Stevens and Lee, 1984][1]; [Brodie, 1900][2]) and the presence in the gut of a substance that increases intestinal motility ([Vialli and Ersparmer, 1933][3]) had been known to scientists since the beginning of the century. However, it
Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids
Authors: Yoshihiro Kanemitsu, Hisako Matsumoto, Kenji Izuhara, Yuji Tohda, Hideo Kita, Takahiko Horiguchi, Kazunobu Kuwabara, Keisuke Tomii, Kojiro Otsuka, Masaki Fujimura, Noriyuki Ohkura, Katsuyuki Tomita, Akihito Yokoyama, Hiroshi Ohnishi, Yasutaka Nakano, Tetsuya Oguma, Soichiro Hozawa, Tadao Nagasaki, Isao Ito, Tsuyoshi Oguma, Hideki Inoue, Tomoko Tajiri, Toshiyuki Iwata, Yumi Izuhara, Junya Ono, Shoichiro Ohta, Mayumi Tamari, Tomomitsu Hirota, Tetsuji Yokoyama, Akio Niimi, Michiaki Mishima
Journal: Journal of Allergy and Clinical Immunology (2013)
Cardiovascular Safety Profile of Combretastatin A4 Phosphate in a Single-Dose Phase I Study in Patients with Advanced Cancer
Authors: Matthew M. Cooney, Tomas Radivoyevitch, Afshin Dowlati, Beth Overmoyer, Nathan Levitan, Kelly Robertson, Sandra L. Levine, Kathleen DeCaro, Carol Buchter, Anne Taylor, Bruce S. Stambler, Scot C. Remick
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of our study was to review and determine the cardiovascular safety profile of combretastatin A4 phosphate (CA4P) in a Phase I study in 25 patients with advanced solid tumors. Experimental Design: CA4P was administered in a dose-escalating fashion starting at 18 mg/m2 i.v. every 21 days, and the maximal dosage was 90 mg/m2. Continuous evaluation included bedside blood pressure and pulse monitoring, 12-lead electrocardiogram (ECG) at fixed time points for measured QT interval determination, determination of the corrected QT interval (QTc) using Bazett’s formula QTc = QT/(R-R interval)1/2, and chart review. Pharmacodynamic correlations of CA4P dose, CA4P/CA4 area under the curve, and Cmax versus heart rate (HR), blood pressure, QT, and QTc intervals, over the first 4 h postdosing were analyzed. Results: After CA4P administration, there were significant increases in QTc interval at the 3-h and 4-h time points [27.2 ms (P &amp;lt; 0.0001) and 30.8 ms (P &amp;lt; 0.0001), respectively] and HR at the 3- and 4-h time points [13.2 beats per minute (bpm; P &amp;lt; 0.01) and 15.1 bpm (P &amp;lt; 0.001), respectively]. Three of 25 patients had prolonged QTc intervals at baseline, whereas 15 (60%) of 25 and 18 (75%) of 24 patients had prolonged QTc intervals at 3 and 4 h. The slope of HR and QTc increasing as a function of time during the first 4 h was correlated to dose (in milligrams) of CA4P (P = 0.01 and r = 0.49 for HR, P = 0.005 and r = 0.55 for QTc) and to CA4 area under the curve (P = 0.04 and r = 0.41 for HR, P = 0.02 and r = 0.44 for QTc); blood pressure and uncorrected QTc interval dose-response correlations were not significant. Two patients had ECG changes consistent with an acute coronary syndrome within 24 h of CA4P infusion. Conclusions: CA4P prolongs the QTc interval. There was a temporal relationship with the CA4P infusion and with ECG changes consistent with an acute coronary syndrome in two patients. It is advisable that future trials with CA4P have eligibility guidelines limiting patients with known coronary artery disease or those with multiple coronary artery disease risk factors until more experience is gained regarding potential cardiovascular toxicity with this agent.
Fatality of Future Coronary Events Is Related to Inflammation-Sensitive Plasma Proteins
Authors: Gunnar Engström, Bo Hedblad, Lars Stavenow, Patrik Tydén, Peter Lind, Lars Janzon, Folke Lindgärde
Journal: Circulation (2004)

Approximately 40% of men suffering a first acute coronary event die the first day; most of them never reach hospital. It is largely unknown whether a low-grade inflammation in healthy men predicts the fatality of future coronary events.Five inflammation-sensitive plasma proteins (ISPs; fibrinogen, orosomucoid, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin) were measured in 6075 apparently healthy men, 680 of whom had a first coronary event [nonfatal myocardial infarction (MI) or death from coronary heart disease (CHD)] over a mean follow-up of 19 years. Of the 680 men who had a coronary event, 197 died the first day and 228 died within 28 days. Elevated ISPs were significantly associated with both nonfatal MI and CHD death, but the relative risks for CHD death were higher than for nonfatal MI. Among men who subsequently had a coronary event, the proportion of fatal events was related to the number of elevated ISPs at the baseline examination. The proportions who died the first day were 26%, 25%, 29%, and 35%, respectively, among men with 0, 1, 2, and > or =3 elevated ISPs (trend: P=0.01, adjusted for risk factors). The corresponding proportions who died within 28 days were 30%, 31%, 34%, and 38%, respectively (trend: P=0.03).Men who have been exposed to a low-grade inflammation many years earlier have higher fatality in future coronary events, with a higher proportion of CHD deaths and less nonfatal MI. This relation should be regarded when inflammatory markers are considered for risk assessment in primary prevention.
Thrombocytosis in rheumatoid arthritis. Recurrent arterial thromboembolism and death.
Authors: M Ehrenfeld, S Penchas, M Eliakim
Journal: Annals of the Rheumatic Diseases (1977)

A patient with rheumatoid arthritis complicated by excessive thrombocytosis and recurrent thromboembolic events is presented. The platelet count correlated well with disease activity and thrombosis occurred when thrombocytosis was marked. The patient died from massive thrombosis of the aorta despite treatment with anticoagulants, corticosteroids, and azathioprine.
Conflicting Finding on Intramucosal Colon Cancers Based on National Survival Outcomes Data
Authors: Yuan-Tzu Lan, Shung-Haur Yang, Anna Fen-Yau Li, Jen-Kou Lin
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: The article by Gunderson et al provides powerful evidence to support the revised staging system in the seventh edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for colon cancer. The case numbers of national-based survival data are large enough to explore significant subtle staging factors. However, an interesting point about Tis colon cancers is worthy of deeper discussion, which was not mentioned in the article. We found the contents both in Table 1 and Table 2 in this article showed that a proportion of Tis colon cancers had lymph node metastasis, with a very low incidence. A total of 5,939 patients had Tis colon cancer, and 95 patients (1.6%) had N1 disease and 19 patients (0.32%) had N2 disease. This finding challenges our previous general rule that colon cancer confined to the mucosa has no chance of metastasis and thus no further treatment is needed. According to the previous AJCC consensus in 2000, colon tumors invading the lamina propria up to and including the muscularis mucosae have no associated risk of regional lymph node metastasis. However, recent data using immunohistochemical marker D2-40 have shown the presence of lymphatic channels extending to the colonic mucosa in neoplastic and inflammatory conditions. Literature on the subject of metastatic risk in intramucosal colorectal carcinoma is extremely limited. Only one patient with poorly differentiated intramucosal rectal cancer had recurrence after surgical resection. We reviewed the patient group in our hospital. In total, there were 3,196 patients with colorectal cancer who received treatment at our hospital during 1999 to 2005. Among the 118 patients receiving regional resection for Tis tumors, no lymph node metastasis was found, except in one patient with a polypoid lesion. The pathology slides of this patient were reviewed carefully, and the tumor was actually a T2 lesion that invaded the superficial muscle layer. In fact, certain types of intramucosal cancer can have lymph node metastasis in gastric cancer. In colorectal cancer, data are still lacking regarding lymph node metastasis in intramucosal tumors. We suggest that all pathologic slides of these intramucosal colon cancers with lymph node metastasis in this article should be reviewed carefully, if possible, to certify the actual invasion depth of the tumor. If it is true that lymph node metastasis could occur in intramucosal colon cancer, it will provide us with a new point of view concerning the treatment of this type of tumor. As a result of recent advances for endoscopic procedures, such as endoscopic mucosal resection or endoscopic submucosal dissection, local treatment for early colorectal cancers is generally accepted and widely applied. If intramucosal colon cancers could have risk of metastasis, additional investigation is warranted to define the high-risk group before applying local treatment for these patients.