tbuckley/cabot-search huggingface dataset:
Conditions influencing release of granule contents from human platelets in citrated plasma induced by ADP or the thrombin receptor activating peptide SFLLRN: Direct measurement of percent release of β-thromboglobulin and assessment by flow cytometry of P-selectin expression
Authors: Margaret L. Rand, Dennis W. Perry, Marian A. Packham, Cynthia H. Gemmell, Erik L. Yeo, Raelene L. Kinlough-Rathbone
Journal: American Journal of Hematology (1996)

Contrary to a recent report [Rinder et al.: Blood 82:505, 1993], aspirin does inhibit the release of α-granule contents as well as inhibiting the release of dense granule contents by human platelets during ADP-induced aggregation in citrated platelet-rich plasma (PRP). Measurements were: percent release of 14C-serotonin from prelabeled platelets, radio-immunoassay of β-thromboglobulin (βTG), and expression on the platelet surface of the α-granule constituent, P-selectin, by flow cytometry. During the second phase of ADP-induced aggregation, 69.0 ± 8.3% of βTG and 54.1 ± 4.6% of 14C-serotonin were released (means ± SEM, n = 13); aspirin treatment reduced these values to 6.0 ± 1.2 and 1.0 ± 0.3%, respectively. In contrast, incubation of platelets with ADP without stirring caused only 6.7 ± 1.7% release of βTG and 2.1 ± 0.4% release of 14C-serotonin; these low values were not appreciably affected by aspirin. During ADP-induced primary aggregation in PRP anticoagulated with FPRCH2Cl (PPACK), only 4.7 ± 0.9% release of βTG and no detectable release of 14C-serotonin occurred; aspirin had no effect. In both stirred and unstirred PRP, the thrombin receptor activating peptide, SFLLRN (50 μM), caused at least 75% release of the contents of both granules, which was partially inhibited by aspirin. Upon incubation of platelets with ADP (2–10 μM), the mean fluorescence intensity due to P-selectin was <14% of that induced by SFLLRN. In this unstirred system used for flow cytometry, aspirin treatment caused no significant inhibition of P-selectin expression. Thus, under conditions in which ADP does not cause secondary aggregation (physiological Ca2??? concentration or unstirred citrated PRP) release of the contents of both types of granules is less than 7% and aspirin is not inhibitory; the P-selectin expression associated with this low percent release is also unaffected by aspirin. However, aspirin does strongly inhibit the extensive release of both α-granule and dense granule contents during ADP-induced secondary aggregation in citrated PRP. © 1996 Wiley-Liss, Inc.
Administration of imatinib after allogeneic hematopoietic stem cell transplantation may improve disease-free survival for patients with Philadelphia chromosome-positive acute lymphobla stic leukemia
Authors: Huan Chen, Kai-yan Liu, Lan-ping Xu, Dai-hong Liu, Yu-hong Chen, Xiang-yu Zhao, Wei Han, Xiao-hui Zhang, Yu Wang, Yuan-yuan Zhang, Ya-zhen Qin, Yan-rong Liu, Xiao-jun Huang
Journal: Journal of Hematology & Oncology (2012)

Abstract Background Maintenance therapy with imatinib during the post-transplant period has been used for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); however, its efficacy has not been demonstrated. A study was designed to investigate the safety of imatinib and its efficacy in preventing hematological relapse and improving disease-free survival (DFS) when administered after allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods Patients with Ph + ALL that received allo-HCT were enrolled in the study. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were &gt; 1.0 × 10 9 /L and platelet counts were &gt; 50.0 × 10 9 /L, or if they displayed either elevated BCR-ABL transcript levels in two consecutive tests, or a BCR-ABL transcript level ≥ 10 -2 after initial engraftment. Patients receiving imatinib after relapse were assigned to the non-imatinib group. The imatinib treatment was scheduled for 3–12 months, until BCR-ABL transcript levels were negative at least for three consecutive tests or complete molecular remission was sustained for at least 3 months. Results A total of 82 patients were enrolled. Sixty-two patients initiated imatinib therapy post-HCT. Imatinib therapy was initiated at a median time of 70 days post-HCT. Grade 3–4 adverse events (AEs) occurred in 17.7% of patients. Ten patients (16.1%) terminated imatinib therapy owing to AEs. Among the patients in imatinib and non-imatinib groups, the estimated 5-year relapse rate was 10.2% and 33.1% (p = 0.016), and the 5-year probability of DFS was 81.5% and 33.5% (p = 0.000) with the median follow-up of 31 months (range, 2.5-76 months) and 24.5 months (range, 4–72 months), respectively. Multivariate analysis identified imatinib maintenance therapy post-HCT as an independent prognostic factor for DFS (p = 0.000, hazard ratio [HR] =4.8) and OS (p = 0.000, HR = 6.2). Conclusions These results indicate that relapse rate can be reduced and DFS may be improved in Ph + ALL patients with imatinib maintenance therapy after HCT. BCR-ABL monitoring by qRT-PCR can guide maintenance therapy with imatinib including initiation time and treatment duration after allo-HCT.
Giant-cell Pneumonia in an Adult
Authors: E. M. McConnell
Journal: BMJ (1961)

Fourteen of the specimens were taken three to six days after vaccination, 13 after 7 to 13 days, and the remainder after 14 to 21 days.The specimens, after neutralization of the vaccine poliovirus with specific antiserum, were inoculated into vervet-monkey-kidney cultures.No vacuolating agent was found in any of the 34 specimens.
Sex-related genes, directional sexual selection, and speciation
Authors: A. Civetta, R. S. Singh
Journal: Molecular Biology and Evolution (1998)

Reproductive isolation and speciation can result from the establishment of either premating or postmating barriers that restrict gene flow between populations. Recent studies of speciation have been dominated by a molecular approach to dissect the genetic basis of hybrid male sterility, a specific form of postmating reproductive isolation. However, relatively little attention has been paid to the evolution of genes involved in premating isolation and genes generally involved in other sex-related functions (e.g., mating behavior, fertilization, spermatogenesis, sex determination). We have assembled DNA sequences from 51 nuclear genes and classified them based on their functional characteristics. The proportion of nonsynonymous to synonymous nucleotide substitutions were compared between Drosophila melanogaster, Drosophila simulans, and Drosophila pseudoobscura, as well as between Caenorhabditis elegans and Caenorhabditis briggsae. We found a high ratio of nonsynonymous to synonymous substitutions for sex-related genes (i.e., genes involved in mating behavior, fertilization, spermatogenesis, or sex determination). The results suggest that directional sexual selection has shaped the evolution of sex-related genes and that these changes have more likely occurred during the early stages of speciation. It is possible that directional selection becomes relaxed after reproductive isolation has been completed between more distantly related species (e.g., D. melanogaster and D. pseudoobscura). However, a saturation in the number of nucleotide substitutions since the time of species separation may mask any sign of directional selection between more distantly related species.
Decrease of physical activity in patients with COPD in the course of the disease
Authors: Benjamin Waschki, Miriam Schaper, Anna-Lena Sack, Olaf Holz, Anne Kirsten, Thorsten Meyer, Klaus F. Rabe, Helgo Magnussen, Henrik Watz
Journal: European Respiratory Journal (2012)

Background: COPD is a progressive lung disease that affects physical activity of patients. Little is known about the changes of physical activity in the course of the disease.  Methods: We measured total daily energy expenditure, the physical activity level (total daily energy expenditure divided by resting metabolic rate), and steps per day by a multisensory armband over a period of 5 to 6 consecutive days in 26 patients with chronic bronchitis and 137 COPD patients (GOLD stage I - IV) at baseline and at follow-up.  Results: During a median follow-up of 2.8 years (range, 1.8 - 3.5) total daily energy expenditure decreased from 2708 kcal (SD 590) to 2518 kcal (SD 536) resulting in an annual rate of decline of 68 kcal (P   Conclusion: Physical activity decreases across all severity stages of COPD in the course of the disease with relative changes being most prominent in severe stages.
Phase II Study of Temozolomide in Relapsed or Refractory High-Risk Neuroblastoma: A Joint Société Française des Cancers de l’Enfant and United Kingdom Children Cancer Study Group–New Agents Group Study
Authors: Hervé Rubie, Julia Chisholm, Anne Sophie Defachelles, Bruce Morland, Caroline Munzer, Dominique Valteau-Couanet, Véronique Mosseri, Christophe Bergeron, Clare Weston, Carole Coze, Anne Auvrignon, Latifa Djafari, Rachel Hobson, Christiane Baunin, Fiona Dickinson, Hervé Brisse, Kieran McHugh, Lorenzo Biassoni, Francesco Giammarile, Gilles Vassal
Journal: Journal of Clinical Oncology (2006)

To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population.A multicenter, phase II evaluation of an oral, daily schedule of TMZ (200 mg/m2/d x 5 days every 28 days) was undertaken in children with refractory or relapsed high-risk NB (metastatic or localized with Myc-N amplification). Response assessment was based on imaging with two-dimentional measurement of disease and meta-iodobenzylguanidine (MIBG) score. Activity was defined by a reduction in lesion size or isotope uptake at anytime. Methodology included a two-step design using Fleming's method with a first step of 15 patients and a second of 10 additional patients if two to four responses had been observed in the first cohort. All data was centrally reviewed by a panel.Twenty-five assessable patients were recruited over a 14-month period in 14 centers and received 94 cycles of chemotherapy. Twenty-three patients had metastatic NB either refractory (n = 9) or in relapse (n = 14). Grade 3 or 4 thrombocytopenia was the most frequent toxicity (16% of cycles). Myelosuppression resulted in treatment delays and dose reductions (24% and 21% of cycles, respectively). Response (complete response, very good partial response, or partial response) was observed in five patients (RR = 20% +/- 8%) with a median duration of 6 months and an objective or mixed response in five additional patients.Temozolomide shows activity in heavily pretreated patients with NB, and deserves further evaluation in combination with another drug.
Methods of sputum processing for cell counts, immunocytochemistry and in situ hybridisation
Authors: Q. Hamid, M.M. Kelly, M. Linden, R. Louis, M.M.M. Pizzichini, E. Pizzichini, C. Ronchi, F. Van Overveld, R. Djukanović
Journal: European Respiratory Journal (2002)

Since the first attempts to use standardised methods for sampling induced airways sputum, two methods for processing the expectorate have evolved. The first involves selecting all viscid or denser portions from the expectorated sample with the aid of an inverted microscope 1, 2. This method has been extensively evaluated and reported in detail 2–4. The second approach involves processing the entire expectorate, comprising sputum plus variable amounts of saliva 5. Recent modifications to this method include collecting saliva and sputum separately in order to reduce salivary contamination 6–8. Both methods have advantages and disadvantages.

The advantages of using selected sputum are: squamous cell contamination is  20% of all recovered cells 4. There is conflicting data as to whether or not differential cell counts (DCCs) differ between the two methods. One study reported a higher percentage of eosinophils in sputum processed by the selection method compared to the entire expectorate 9 but this has not been confirmed in other studies 2, 6, 10. Although, both the selected …
Autocrine Production of Amphiregulin Predicts Sensitivity to Both Gefitinib and Cetuximab in <i>EGFR</i> Wild-type Cancers
Authors: Kimio Yonesaka, Kreshnik Zejnullahu, Neal Lindeman, Alison J. Homes, David M. Jackman, Feng Zhao, Andrew M. Rogers, Bruce E. Johnson, Pasi A. Jänne
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, lead to significant tumor regressions in 10% to 15% of non-small cell lung cancer (NSCLC) patients with EGFR activating mutations. However, 30% to 40% of NSCLC patients, majority of whom are EGFR wild-type, develop stable disease following EGFR tyrosine kinase inhibitor therapy. EGFR-directed antibodies (cetuximab) are effective treatments for head and neck squamous cell carcinomas, which seldom contain EGFR mutations. The determinant(s) of efficacy of EGFR-targeted therapies in EGFR wild-type cancers is not well defined. Experimental Design: We examined the relationship of EGFR ligands, EGF, transforming growth factor-α,and amphiregulin and the efficacy of gefitinib and cetuximab in EGFR wild-type NSCLC (n = 10) and head and neck squamous cell carcinoma (n = 4) cell lines. We compared amphiregulin expression using immunohistochemistry in EGFR wild-type NSCLC patients (n = 24) that developed either stable or progressive disease following erlotinib or gefitinib treatment. Results: Cell lines which produced ≥20 pmol/L amphiregulin, as detected by an ELISA, were significantly more likely to be growth inhibited by both gefitinib and cetuximab than those that produced minimal or no amphiregulin. In these cell lines, both cetuximab and gefitinib led to cell cycle arrest at the G1-S boundary and was associated with preferential inhibition of extracellular signal-regulated kinase 1/2 but not Akt signaling. Amphiregulin expression was significantly higher in NSCLC patients that developed stable disease compared with those that developed disease progression following gefitinib or erlotinib treatment. Conclusions: Amphiregulin expression may help select EGFR wild-type patients who are likely to develop stable disease from EGFR-targeted therapies.
PML-RARα and Its Phosphorylation Regulate PML Oligomerization and HIPK2 Stability
Authors: Yutaka Shima, Yuki Honma, Issay Kitabayashi
Journal: Cancer Research (2013)

The PML gene is frequently fused to the retinoic acid receptor α (RARα) gene in acute promyelocytic leukemia (APL), generating a characteristic PML-RARα oncogenic chimera. PML-RARα disrupts the discrete nuclear speckles termed nuclear bodies, which are formed in PML, suggesting that nuclear body disruption is involved in leukemogenesis. Nuclear body formation that relies upon PML oligomerization and its stabilization of the hypoxia-inducible protein kinase (HIPK)-2 is disrupted by expression of the PML-RARα chimera. Here, we report that disruption of nuclear bodies is also mediated by PML-RARα inhibition of PML oligomerization. PKA-mediated phosphorylation of PML-RARα blocked its ability to inhibit PML oligomerization and destabilize HIPK2. Our results establish that both PML oligomerization and HIPK2 stabilization at nuclear bodies are important for APL cell differentiation, offering insights into the basis for the most common prodifferentiation therapies of APL used clinically.
Thomas McMahon: A Dedication in Memoriam
Authors: Robert D. Howe, Richard E. Kronauer
Journal: Annual Review of Biomedical Engineering (2001)

Thomas A. McMahon (1943-1999) was a pioneer in the field of biomechanics. He made primary contributions to our understanding of terrestrial locomotion, allometry and scaling, cardiac assist devices, orthopedic biomechanics, and a number of other areas. His work was frequently characterized by the use of simple mathematical models to explain seemingly complex phenomena. He also validated these models through creative experimentation. McMahon was a successful inventor and also published three well-received novels. He was raised in Lexington, Massachussetts, attended Cornell University as an undergraduate, and earned a PhD at MIT. From 1970 until his death, he was a member of the faculty of Harvard University, where he taught biomedical engineering. He is fondly remembered as a warm and gentle colleague and an exemplary mentor to his students.
Personalized risk prediction for event‐free survival at 24 months in patients with diffuse large B‐cell lymphoma
Authors: Matthew J. Maurer, Jean‐Philippe Jais, Hervé Ghesquières, Thomas E. Witzig, Fangxin Hong, Corinne Haioun, Carrie A. Thompson, Catherine Thieblemont, Ivana N. Micallef, Luis F. Porrata, Vincent Ribrag, Gregorz S. Nowakowski, Olivier Casasnovas, Serge Bologna, Franck Morschhauser, Vicki A. Morrison, Bruce A. Peterson, William R. Macon, Christiane Copie‐Bergman, Andrew L. Feldman, Sergei I. Syrbu, Paul J. Kurtin, Randy D. Gascoyne, Hailun Li, Cristine Allmer, Brad S. Kahl, Stephen M. Ansell, Susan L. Slager, Brian K. Link, Gilles Salles, Thomas M. Habermann, Hervé Tilly, James R. Cerhan
Journal: American Journal of Hematology (2015)

We recently defined event‐free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age‐ and sex‐matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline‐based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability ( c ‐statistic = 0.671) in the validation dataset compared to the IPI ( c ‐statistic = 0.649) or the NCCN‐IPI ( c ‐statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12–88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps. Am. J. Hematol. 91:179–184, 2016. © 2015 Wiley Periodicals, Inc.
Lowering LDL Cholesterol
Authors: Antonio M. Gotto, Scott M. Grundy
Journal: Circulation (1999)

Abstract —The benefit of cholesterol-lowering therapy in the prevention of coronary heart disease (CHD) is well established. The secondary prevention Scandinavian Simvastatin Survival Study (4S) and the primary prevention West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated that lipid lowering with a statin can dramatically and cost-effectively reduce CHD morbidity and mortality with no increase in noncardiovascular mortality. The Cholesterol and Recurrent Events (CARE) trial extended benefit to CHD patients without high cholesterol. Post hoc analyses of data from these large trials are contributing to speculation, driven by subset analyses and meta-analyses, about whether cholesterol intervention should be target based, as current guidelines recommend. Whereas CARE data support the importance of baseline LDL cholesterol (LDL-C), with greatest clinical event risk reduction in the upper part of the LDL-C range in the trial, 4S found no difference in outcome according to baseline LDL-C in a quartile analysis, and WOSCOPS found no linear relation between decrease in LDL-C and decrease in relative risk for CHD. Furthermore, WOSCOPS showed no additional clinical benefit with LDL-C lowering beyond ≈24%. Questions raised by such analyses require answers from prospective, hypothesis-based data, and at present there is no compelling argument for moving away from LDL-C targets. The hypothesis-based findings of 4S, CARE, and WOSCOPS support current clinical guidelines, and lowering LDL-C may reduce risk more substantially than might have been predicted.
Evolving Treatment Strategies for Inflammatory Breast Cancer: A Population-Based Survival Analysis
Authors: Miguel Panades, Ivo A. Olivotto, Caroline H. Speers, Tamara Shenkier, Theodora A. Olivotto, Lorna Weir, Sharon J. Allan, Pauline T. Truong
Journal: Journal of Clinical Oncology (2005)

Purpose To determine if mastectomy (Mx) use, chemotherapy (CT) intensity, or treatment sequence of CT, radiation therapy (RT), and Mx have improved outcome for inflammatory breast cancer (IBC). Patients and Methods A retrospective analysis of 485 patients with IBC diagnosed in British Columbia between 1980 and 2000 analyzed locoregional relapse-free survival (LRFS) and breast cancer–specific survival (BCSS) by treatment intent and treatment received. Curative intent was defined as delivery of more than four cycles of anthracycline-based CT plus locoregional RT in patients without distant metastases. Results Median follow-up among survivors was 6.5 years. Median BCSS was 1.0 and 3.2 years for patients with distant metastases at diagnosis or those who were curatively treated, respectively. Among patients treated curatively (n = 308), there were no significant differences in LRFS or BCSS with timing of Mx before or after CT/RT, time between diagnosis and RT, or the sequence of RT and CT. Patients receiving more intensive CT had improved 10-year BCSS compared with standard CT (43.7% v 26.3%; P = .04). Ten-year LRFS for patients having Mx after CT, Mx before CT, and without Mx was 62.8%, 58.6%, and 34.4%, respectively (P = .0001); the corresponding 10-year BCSS was 36.9%, 19.9%, and 22.5%, respectively (P = .005). On multivariate analysis, Mx was associated with improved LRFS (P = .04). Independent prognostic factors for BCSS were menopausal status (P = .02), estrogen receptor status (P = .02), and CT type (P = .05). Conclusion This retrospective analysis suggested that mastectomy, in conjunction with CT and RT, seemed to enhance locoregional control, whereas modern CT regimens seemed to improve BCSS.
Revision of the American Joint Committee on Cancer Staging System for Breast Cancer
Authors: S. Eva Singletary, Craig Allred, Pandora Ashley, Lawrence W. Bassett, Donald Berry, Kirby I. Bland, Patrick I. Borgen, Gary Clark, Stephen B. Edge, Daniel F. Hayes, Lorie L. Hughes, Robert V.P. Hutter, Monica Morrow, David L. Page, Abram Recht, Richard L. Theriault, Ann Thor, Donald L. Weaver, H. Samuel Wieand, Frederick L. Greene
Journal: Journal of Clinical Oncology (2002)

To revise the American Joint Committee on Cancer staging system for breast carcinoma.A Breast Task Force submitted recommended changes and additions to the existing staging system that were (1) evidence-based and/or consistent with widespread clinical consensus about appropriate diagnostic and treatment standards and (2) useful for the uniform accrual of outcome information in national databases.Major changes included the following: size-based discrimination between micrometastases and isolated tumor cells; identifiers to indicate usage of innovative technical approaches; classification of lymph node status by number of involved axillary lymph nodes; and new classifications for metastasis to the infraclavicular, internal mammary, and supraclavicular lymph nodes.This revised staging system will be officially adopted for use in tumor registries in January 2003.