tbuckley/cabot-search huggingface dataset:
Clinical, Radiographic, and Biochemical Characterization of Multiple Myeloma Patients with Osteonecrosis of the Jaw
Authors: Noopur Raje, Sook-Bin Woo, Karen Hande, Jeffrey T. Yap, Paul G. Richardson, Sonia Vallet, Nathaniel Treister, Teru Hideshima, Niall Sheehy, Shweta Chhetri, Brendan Connell, Wanling Xie, Yu-Tzu Tai, Agnieszka Szot-Barnes, Mei Tian, Robert L. Schlossman, Edie Weller, Nikhil C. Munshi, Annick D. Van Den Abbeele, Kenneth C. Anderson
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Osteonecrosis of the jaw (ONJ) has been reported in patients with a history of aminobisphosphonate use. This study was conducted in order to define ONJ clinically and radiographically and gain insights into its pathophysiology. Experimental Design: Eleven multiple myeloma (MM) patients with ONJ were included in the study. Patients underwent clinical, biochemical, radiographic, and molecular profiling. Ten MM patients on aminobisphosphonates without ONJ and five healthy volunteers were used as controls for biochemical and molecular studies. Results: MM patients with ONJ were treated with either pamidronate (n = 3), zoledronate (n = 4), or both agents sequentially (n = 4) for a mean of 38.7 months. Radiographic studies showed bone sclerosis and fragmentation on plain films and computerized tomography. Quantitative regional analysis of NaF-PET and FDG-PET scans confirmed an increased standardized uptake value (SUVmax) in areas of ONJ. The target to background ratio of SUVmax was significantly greater for NaF-PET compared with FDG-PET scan. Biochemical bone marker data and transcriptional profiling studies showed that genes and proteins involved in osteoblast and osteoclast signaling cascades were significantly down-regulated in patients with ONJ. Conclusions: ONJ was associated with a mean duration of 38.7 months of aminobisphosphonate exposure. Radiographic and functional imaging confirmed sites of clinically established ONJ. Gene and protein studies are consistent with altered bone remodeling, evidenced by suppression of both bone resorption and formation.
Molecular Imaging of the Paracrine Proangiogenic Effects of Progenitor Cell Therapy in Limb Ischemia
Authors: Jae Choon Ryu, Brian P. Davidson, Aris Xie, Yue Qi, Daogang Zha, J. Todd Belcik, Evan S. Caplan, Juliana M. Woda, Catherine C. Hedrick, Richard N. Hanna, Nicholas Lehman, Yan Zhao, Anthony Ting, Jonathan R. Lindner
Journal: Circulation (2013)

Background— Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPCs) promotes recovery of blood flow through the recruitment of proangiogenic monocytes. Methods and Results— Hind-limb ischemia was produced in mice by iliac artery ligation, and MAPCs were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPCs indicated that cells survived for 1 week. Contrast-enhanced ultrasound on days 3, 7, and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX 3 CR-1-positive monocytes were significantly higher in MAPC-treated mice than in the control groups at days 3 and 7 after arterial ligation. Muscle immunohistology showed a &gt;10-fold-greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or tumor necrosis factor-α–treated cremaster muscle demonstrated that MAPCs migrate to perimicrovascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14 + monocytes was 10-fold greater in response to MAPC-conditioned than basal media. Conclusions— In limb ischemia, MAPCs stimulate the recruitment of proangiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond the MAPC lifespan, suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype.
A follow-up study of recurrence and cosmesis in completely responding superficial and nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-based photodynamic therapy alone and with prior curettage
Authors: A.M. Soler, T. Warloe, A. Berner, K.E. Giercksky
Journal: British Journal of Dermatology (2001)

Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA.To assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment.Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2-4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g(-1) was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm(-2). Fibrosis was assessed histologically in 23 biopsies.The overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies.We conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.
THE EFFECT OF HYDROCORTISONE AND X-IRRADIATION ON THE LYMPHOCYTOSIS INDUCED BY BORDETELLA PERTUSSIS
Authors: Stephen I. Morse
Journal: The Journal of Experimental Medicine (1966)

1. In mice rendered lymphocytopenic by X-irradiation or hydrocortisone acetate, pertussis vaccine evoked both lymphocytosis and polymorphonuclear leukocytosis. 2. When mice with lymphocytosis induced by pertussis vaccine were X-irradiated, prompt and extensive destruction of circulating as well as tissue small lymphocytes occurred. The devitalized circulating cells were cleared from the blood primarily by the Kupffer's cells of the hepatic sinusoids. 3. Hydrocortisone acetate administered to mice with lymphocytosis did not cause acute lymphopenia nor was there any evidence of destruction of circulating small lymphocytes. However, destruction of these cells within lymphoid tissues was apparent. These observations suggested that adrenal cortical hormones are not "lymphocytolytic" with respect to circulating lymphocytes.
Vaccination of Patients With Advanced Non–Small-Cell Lung Cancer With an Optimized Cryptic Human Telomerase Reverse Transcriptase Peptide
Authors: Irini Bolonaki, Athanassios Kotsakis, Elsa Papadimitraki, Despoina Aggouraki, George Konsolakis, Aphrodite Vagia, Charalambos Christophylakis, Irini Nikoloudi, Elefterios Magganas, Athanassios Galanis, Paul Cordopatis, Kostas Kosmatopoulos, Vassilis Georgoulias, Dimitris Mavroudis
Journal: Journal of Clinical Oncology (2007)

To evaluate the immunological and clinical response as well as the safety of the optimized peptide telomerase reverse transcriptase p572Y (TERT572Y) presented by HLA-A*0201 in patients with advanced non-small-cell lung cancer (NSCLC).Twenty-two patients with advanced NSCLC and residual (n = 8) or progressive disease (PD; n = 14) following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide administered every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay and/or TERT572Y pentamer staining.Twelve (54.5%) of 22 patients completed the vaccination program. Toxicity consisted primarily of local skin reactions. TERT572-specific CD8+ cells were detected in 16 (76.2%) of 21 patients after the second vaccination, and 10 (90.9%) of 11 patients after the sixth vaccination. Stable disease (SD) occurred in eight (36.4%) of 22 vaccinated patients, with three (13.6%) having had PD before entering the study. The median duration of SD was 11.2 months. After a median follow-up of 10.0 months, patients with early developed immunological response (n = 16) had a significantly longer time to progression and overall survival (OS) than nonresponders (n = 5; log-rank tests P = .046 and P = .012, respectively). The estimated median OS was 30.0 months (range, 2.8 to 40.0 months) and 4.1 months (range, 2.4 to 10.9 months) for responders and nonresponders, respectively.TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. Immunological response is associated with prolonged survival. These results are encouraging and warrant further evaluation in a randomized study.
Management of Cutaneous and Extracutaneous Side Effects of Smoothened Inhibitor Therapy for Advanced Basal Cell Carcinoma
Authors: Shalini V. Mohan, Anne Lynn S. Chang
Journal: Clinical Cancer Research (2015)

Smoothened inhibitors represent the first class of targeted drugs approved for use in advanced and metastatic basal cell carcinoma. For many patients with limited treatment options, this drug class has led to significant clinical improvements, but is not without side effects. In this review, we outline the basic mechanism of smoothened inhibitors and the most commonly observed cutaneous and extracutaneous side effects. We also highlight possible mechanisms for these adverse events and current management strategies.
PIK3CA Mutation Uncouples Tumor Growth and Cyclin D1 Regulation from MEK/ERK and Mutant KRAS Signaling
Authors: Ensar Halilovic, Qing-Bai She, Qing Ye, Raymond Pagliarini, William R. Sellers, David B. Solit, Neal Rosen
Journal: Cancer Research (2010)

Abstract Mutational activation of KRAS is a common event in human tumors. Identification of the key signaling pathways downstream of mutant KRAS is essential for our understanding of how to pharmacologically target these cancers in patients. We show that PD0325901, a small-molecule MEK inhibitor, decreases MEK/ERK pathway signaling and destabilizes cyclin D1, resulting in significant anticancer activity in a subset of KRAS mutant tumors in vitro and in vivo. Mutational activation of PIK3CA, which commonly co-occurs with KRAS mutation, provides resistance to MEK inhibition through reactivation of AKT signaling. Genetic ablation of the mutant PIK3CA allele in MEK inhibitor–resistant cells restores MEK pathway sensitivity, and re-expression of mutant PIK3CA reinstates the resistance, highlighting the importance of this mutation in resistance to therapy in human cancers. In KRAS mutant tumors, PIK3CA mutation restores cyclin D1 expression and G1-S cell cycle progression so that they are no longer dependent on KRAS and MEK/ERK signaling. Furthermore, the growth of KRAS mutant tumors with coexistent PIK3CA mutations in vivo is profoundly inhibited with combined pharmacologic inhibition of MEK and AKT. These data suggest that tumors with both KRAS and phosphoinositide 3-kinase mutations are unlikely to respond to the inhibition of the MEK pathway alone but will require effective inhibition of both MEK and phosphoinositide 3-kinase/AKT pathway signaling. Cancer Res; 70(17); 6804–14. ©2010 AACR.
Should Group Education Classes Be Separated by Type of Diabetes?
Authors: Arlene Smaldone, Om P. Ganda, Sheila McMurrich, Keri Hannagan, Susan Lin, A. Enrique Caballero, Katie Weinger
Journal: Diabetes Care (2006)

Although the rising prevalence of type 2 diabetes and economic factors have resulted in more group diabetes education (1–4), little research has examined the effective use of group education or composition of groups. Regardless of group or individual education format, attention to individual learning needs through assessment of attitudes, health beliefs, motivation, and levels of self-care remain critical to tailoring programs to the adult learner. To maximize the benefit of the group format, educators must identify commonalities among group members to foster engagement and participation (5); however, this process can be difficult if participants vary in type of diabetes. In clinical practice, emphasis is typically on filling classes without attention to homogeneity; thus, assessing and addressing the needs of each group participant can be difficult (6). In this study, we examined whether adults with type 1 or type 2 diabetes requiring diabetes education differ in medical treatment issues, lifestyle, self-management, and psychosocial characteristics that may impact how they are educated in groups.

We evaluated the baseline data of 208 adults (type 1 diabetes, n = 101; type 2 diabetes, n = 107) enrolled in a longitudinal diabetes education study. The Committee on Human Subjects reviewed the study, and subjects provided informed written consent.

Subjects were eligible for the study if aged 18–75 years, if they had been diagnosed with type 1 or type 2 diabetes for ≥2 years, and if they had HbA1c (A1C) ≥7.6 and ≤14%. To be eligible, type 2 diabetic subjects needed to be treated with oral …
The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis
Authors: S. Debette, H. S. Markus
Journal: BMJ (2010)

Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death. Design Systematic review and meta-analysis. Data sources PubMed from 1966 to 23 November 2009. Study selection Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death. Data extraction Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome. Data synthesis 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested. Conclusion White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.
A Pilot Comparison of Standardized Online Surgical Curricula for Use in Low- and Middle-Income Countries
Authors: Seth D. Goldstein, Dominic Papandria, Allison Linden, Georges Azzie, Eric Borgstein, James Forrest Calland, Samuel R. G. Finlayson, Pankaj Jani, Mary Klingensmith, Mohamed Labib, Frank Lewis, Mark A. Malangoni, Eric O’Flynn, Stephen Ogendo, Robert Riviello, Fizan Abdullah
Journal: JAMA Surgery (2014)

<h3>Importance</h3> Surgical conditions are an important component of global disease burden, due in part to critical shortages of adequately trained surgical providers in low- and middle-income countries. <h3>Objectives</h3> To assess the use of Internet-based educational platforms as a feasible approach to augmenting the education and training of surgical providers in these settings. <h3>Design, Setting, and Participants</h3> Access to two online curricula was offered to 75 surgical faculty and trainees from 12 low- and middle-income countries for 60 days. The Surgical Council on Resident Education web portal was designed for general surgery trainees in the United States, and the School for Surgeons website was built by the Royal College of Surgeons in Ireland specifically for the College of Surgeons of East, Central and Southern Africa. Participants completed an anonymous online survey detailing their experiences with both platforms. Voluntary respondents were daily Internet users and endorsed frequent use of both print and online textbooks as references. <h3>Main Outcomes and Measures</h3> Likert scale survey questionnaire responses indicating overall and content-specific experiences with the Surgical Council on Resident Education and School for Surgeons curricula. <h3>Results</h3> Survey responses were received from 27 participants. Both online curricula were rated favorably, with no statistically significant differences in stated willingness to use and recommend either platform to colleagues. Despite regional variations in practice context, there were few perceived hurdles to future curriculum adoption. <h3>Conclusions and Relevance</h3> Both the Surgical Council on Resident Education and School for Surgeons educational curricula were well received by respondents in low- and middle-income countries. Although one was designed for US surgical postgraduates and the other for sub-Saharan African surgical providers, there were no significant differences detected in participant responses between the two platforms. Online educational resources have promise as an effective means to enhance the education of surgical providers in low- and middle-income countries.
ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in acute promyelocytic leukemia cells
Authors: J Nigten, M C Breems-de Ridder, C A J Erpelinck-Verschueren, G Nikoloski, B A van der Reijden, S van Wageningen, P B van Hennik, T de Witte, B Löwenberg, J H Jansen
Journal: Leukemia (2005)
Transfer of hematopoietic stem cells encoding autoantigen prevents autoimmune diabetes
Authors: Raymond J. Steptoe, Janine M. Ritchie, Leonard C. Harrison
Journal: Journal of Clinical Investigation (2003)

Bone marrow or hematopoietic stem cell transplantation is a potential treatment for autoimmune disease. The clinical application of this approach is, however, limited by the risks associated with allogeneic transplantation. In contrast, syngeneic transplantation would be safe and have wide clinical application. Because T cell tolerance can be induced by presenting antigen on resting antigen-presenting cells (APCs), we reasoned that hematopoietic stem cells engineered to express autoantigen in resting APCs could be used to prevent autoimmune disease. Proinsulin is a major autoantigen associated with pancreatic β cell destruction in humans with type 1 diabetes (T1D) and in autoimmune NOD mice. Here, we demonstrate that syngeneic transplantation of hematopoietic stem cells encoding proinsulin transgenically targeted to APCs totally prevents the development of spontaneous autoimmune diabetes in NOD mice. This antigen-specific immunotherapeutic strategy could be applied to prevent T1D and other autoimmune diseases in humans.
Antitumor Effects of a Novel Phenylbutyrate-Based Histone Deacetylase Inhibitor, (<i>S</i>)-HDAC-42, in Prostate Cancer
Authors: Samuel K. Kulp, Chang-Shi Chen, Da-Sheng Wang, Ching-Yu Chen, Ching-Shih Chen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To assess the antitumor effects of a novel phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, (S)-HDAC-42, vis-à-vis suberoylanilide hydroxamic acid (SAHA) in in vitro and in vivo models of human prostate cancer. Experimental Design: The in vitro effects of (S)-HDAC-42 and SAHA were evaluated in PC-3, DU-145, or LNCaP human prostate cancer cell lines. Cell viability, apoptosis, and indicators of HDAC inhibition were assessed. Effects on Akt and members of the Bcl-2 and inhibitor of apoptosis protein families were determined by immunoblotting. Immunocompromised mice bearing established s.c. PC-3 xenograft tumors were treated orally with (S)-HDAC-42 (50 mg/kg q.o.d. or 25 mg/kg q.d.) or SAHA (50 mg/kg q.d.) for 28 days. In vivo end points included tumor volumes and intratumoral changes in histone acetylation, phospho-Akt status, and protein levels of Bcl-xL and survivin. Results: (S)-HDAC-42 was more potent than SAHA in suppressing the viability of all cell lines evaluated with submicromolar IC50 values. Relative to SAHA, (S)-HDAC-42 exhibited distinctly superior apoptogenic potency, and caused markedly greater decreases in phospho-Akt, Bcl-xL, and survivin in PC-3 cells. The growth of PC-3 tumor xenografts was suppressed by 52% and 67% after treatment with (S)-HDAC-42 at 25 and 50 mg/kg, respectively, whereas SAHA at 50 mg/kg suppressed growth by 31%. Intratumoral levels of phospho-Akt and Bcl-xL were markedly reduced in (S)-HDAC-42-treated mice, in contrast to mice treated with SAHA. Conclusions: (S)-HDAC-42 is a potent orally bioavailable inhibitor of HDAC, as well as targets regulating multiple aspects of cancer cell survival, which might have clinical value in prostate cancer chemotherapy and warrants further investigation in this regard.
US ban on "partial birth" abortions could outlaw other forms as well
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Both the US Senate and the House of Representatives have passed bills banning “partial birth abortion.” When minor differences between the bills are resolved, President George Bush will sign the law. While travelling in Asia, he told the New York Times that the bill was “very important legislation that will end an abhorrent practice and continue to build a culture of life in America.”

Doctors who violate the law may be imprisoned for up to two years and also be fined.

The bills define “partial birth abortion” as a procedure in which the physician “deliberately and intentionally vaginally delivers a living fetus until, in the case of a headfirst presentation, the …
Mutations in the Mevalonate Kinase (MVK) Gene Cause Nonsyndromic Retinitis Pigmentosa
Authors: Anna M. Siemiatkowska, L. Ingeborgh van den Born, P. Martin van Hagen, Monique Stoffels, Kornelia Neveling, Arjen Henkes, Mieke Kipping-Geertsema, Lies H. Hoefsloot, Carel B. Hoyng, Anna Simon, Anneke I. den Hollander, Frans P.M. Cremers, Rob W.J. Collin
Journal: Ophthalmology (2013)
Reply to: “CCL3L1 and HIV/AIDS susceptibility” and “Experimental aspects of copy number variant assays at CCL3L1”
Authors: Weijing He, Hemant Kulkarni, John Castiblanco, Chisato Shimizu, Una Aluyen, Robert Maldonado, Andrew Carrillo, Madeline Griffin, Amanda Lipsitt, Lisa Beachy, Ludmila Shostakovich-Koretskaya, Andrea Mangano, Luisa Sen, Robert J B Nibbs, Caroline T Tiemessen, Hector Bolivar, Michael J Bamshad, Robert A Clark, Jane C Burns, Matthew J Dolan, Sunil K Ahuja
Journal: Nature Medicine (2009)