tbuckley/cabot-search huggingface dataset:
Acupuncture for Postchemotherapy Fatigue: A Phase II Study
Authors: Andrew J. Vickers, David J. Straus, Bertha Fearon, Barrie R. Cassileth
Journal: Journal of Clinical Oncology (2004)

To determine whether improvement in postchemotherapy fatigue following acupuncture treatment is substantial enough to warrant a controlled trial.We accrued patients at Memorial Sloan-Kettering Cancer Center who had completed cytotoxic chemotherapy but experienced persisting fatigue. Patients with severe anemia, clinical depression, or Karnofsky performance status score less than 70 were excluded. Thirty-seven patients were registered in two cohorts; 31 provided follow-up data. Patients received acupuncture either twice per week for 4 weeks (25 patients) or once per week for 6 weeks (12 patients). The primary end point was change in score on the Brief Fatigue Inventory between baseline and 2 weeks after the final treatment. A baseline Brief Fatigue Inventory score of four or greater was an eligibility requirement for the trial.Patients had completed cytotoxic chemotherapy an average of more than 2 years previously. Baseline fatigue scores were high, with approximately half of the sample scoring in the "severe" range. Mean improvement following acupuncture was 31.1% (95% CI, 20.6% to 41.5%), meeting our prespecified criterion for declaring acupuncture worthy of further study. Increasing age was associated with poorer response and failure to complete the study. There was no important difference in improvement following once-weekly and twice-weekly treatments.Acupuncture is worthy of further study in the treatment of postchemotherapy fatigue.
Constitutive nuclear factor-kappaB activity in human upper airway tissues and nasal epithelial cells
Authors: I. Ramis, G. Bioque, J. Lorente, P. Jares, P. Quesada, J. Rosello-Catafau, E Gelpi, O Bulbena
Journal: European Respiratory Journal (2000)

Respiratory epithelial cells are actively involved in the host defence and inflammatory reactions of the airways. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a pivotal role in many cellular responses to environmental changes. The inducible nitric oxide synthase (iNOS) isoform has been implicated in airway inflammation as well as in normal airway function. In this study, the hypothesis that NF-kappaB may be associated with iNOS expression in airway epithelium, not only in inflammatory processes but also under physiological conditions was examined. NF-kappaB deoxyribonucleic acid-binding activity was assayed by means of electrophoretic mobility shift assay (EMSA) and iNOS expression examined using immunohistochemical techniques in healthy nasal mucosa and chronically inflamed nasal polyps. Further NF-kappaB activity was assayed; by means of EMSA, in nasal epithelial cells isolated from both tissues. NF-kappaB was activated in nasal polyps, but also to the same extent in healthy nasal mucosa. Uniform iNOS expression was localized within the airway epithelium in both inflamed and noninflamed tissues. Along with iNOS expression, concomitant NF-kappaB activation was found in nasal epithelial cells obtained from both tissues and no differences were observed when nasal mucosa and nasal polyp were compared. These results suggest that constitutive nuclear factor-kappaB and concurrent inducible nitric oxide synthase expression in epithelial cells may play a physiological role in airway function.
Developmentally Regulated Switching of Titin Size Alters Myofibrillar Stiffness in the Perinatal Heart
Authors: Christiane A. Opitz, Mark C. Leake, Irina Makarenko, Vladimir Benes, Wolfgang A. Linke
Journal: Circulation Research (2004)

Before birth, the compliance of the heart is limited predominantly by extracardiac constraint. Reduction of this constraint at birth requires that myocardial compliance be determined mainly by the heart's own constituents. Because titin is a principal contributor to ventricular passive tension (PT), we studied the expression and mechanics of cardiac-titin isoforms during perinatal rat heart development. Gel electrophoresis and immunoblotting revealed a single, 3.7-MDa, N2BA isoform present 6 days before birth and an additional, also previously unknown, N2BA isoform of 3.5 to 3.6 MDa expressed in the near-term fetus. These large isoforms rapidly disappear after birth and are replaced by a small N2B isoform (3.0 MDa) predominating in 1-week-old and adult rats. In addition, neonatal pig hearts showed large N2BA-titin isoforms distinct from those present in the adult porcine myocardium. By quantitative reverse transcriptase-polymerase chain reaction, developmentally expressed titin-mRNA species were detected in rat heart. Titin-based PT was much lower (approximately 15 times) in fetal than adult rat cardiomyocytes, and measured PT levels were readily predictable with a model of worm-like chain titin elasticity. Immunofluorescence microscopy showed the extensibility of the differentially spliced molecular spring regions of fetal/neonatal titin isoforms in isolated rat cardiomyofibrils. Whereas the titin-isoform shift by 700 kDa ensures high passive stiffness of the postnatal cardiac myofibrils, the expression of specific fetal/neonatal cardiac-titin isoforms may also have important functions for contractile properties, myofibril assembly or turnover, and myocardial signaling during perinatal heart development.
‘Surgical’ causes of benign intracranial hypertension
Authors: Peter Alwyn Bodkin, Md Faizul Hassan, Philip John Kane, Nick Brady, Ian Roger Whittle
Journal: Journal of the Royal Society of Medicine (2008)

Summary Benign intracranial hypertension is a clinical diagnosis linked to a number of medical and surgical disorders. A common aetiology has not yet been established. It would seem, however, that many, if not all, of these cases can be related to some degree of cerebral venous outflow obstruction. We present here a series of patients with extraluminal compression of the cerebral venous sinuses that has been amenable to surgical resection. These ‘surgical’ causes of BIH illustrate an important subset of the disease and inform us about the possible pathophysiological principles underlying the disorder.
Transesophageal Echocardiographic Assessment of Mitral Valve Position and Pulmonary Venous Flow During Cardiopulmonary Resuscitation in Humans
Authors: Matthew Huei-Ming Ma, Juey-Jen Hwang, Ling-Ping Lai, Shih-Ming Wang, Guan-Tarn Huang, Kou-Gi Shyu, Yu-Lin Ko, Jiunn-Lee Lin, Wen-Jone Chen, Kwan-Lih Hsu, Jin-Jer Chen, Peiliang Kuan, Yung-Zu Tseng, Wen-Pin Lien
Journal: Circulation (1995)

Background The mechanisms of blood flow during closed-chest cardiopulmonary resuscitation (CPR) in humans have been debated since the technique was first described in 1960. Two competing models, the cardiac pump theory and the thoracic pump theory, have been proposed, and some investigators have used mitral valve position during the downstroke of chest compression to distinguish between them. Previous studies using either transthoracic or transesophageal echocardiography have yielded conflicting results, and there have been few, if any, hemodynamic or echocardiographic studies on pulmonary venous flow (PVF) during CPR. Methods and Results In this study, transesophageal two-dimensional and pulsed Doppler echocardiography were used to study mitral valve position and flow, together with PVF, in 20 adult patients undergoing manual CPR. In the 17 patients who could be analyzed, the mitral valve closed in 5 patients (group 1) during chest compression but stayed open or opened further in the remaining 12 patients (group 2). Peak forward mitral flow occurred during the release phase in group 1 but during the compression phase in group 2. During chest compression, PVF occurred in the forward direction (from the pulmonary vein to the left atrium) in 8 of the group 2 patients (group 2a) and in the backward direction (from the left atrium to the pulmonary vein) in all group 1 patients and the remaining 4 patients in group 2 (group 2b). The downtime (time from collapse to CPR) was significantly shorter ( P &lt;.05) for those in group 1 (7.0±4.4 minutes) than in groups 2a (19.8±7.7 minutes) and 2b (17.8±6.8 minutes). Conclusions Transesophageal echocardiography performed during manual CPR in humans disclosed three different patterns of mitral valve position and PVF during chest compression. The presence of an opened mitral valve with forward mitral flow and backward pulmonary venous flow during chest compression in a small number of subjects underscores this heterogeneity in blood flow and suggests the possible existence of a “left atrium pump” in addition to the currently known “left ventricle pump” and “chest pump” mechanisms.
Directing the future of lung health: the European Respiratory Roadmap
Authors: Y. Sibille, M. Decramer, L.P. Nicod, P. Palange, B. Nemery, G.F. Joos, K-H. Carlsen, B. Ward, N. Kamel, P. Powell
Journal: European Respiratory Journal (2011)

One of the missions of the European Respiratory Society (ERS) is to raise public and political awareness of lung disease. A major initiative to help achieve this goal was the 2010 Year of the Lung; a year dedicated to promoting lung health. A particular highlight of the year was a global lung function testing event, the first-ever World Spirometry Day which was held on October 14, 2010 [1]. Another major initiative was the ERS pre-ministerial conference on “Chronic respiratory diseases – exploring solutions in the EU” held on October 19, 2010, in partnership with the Belgian presidency of the Council of the EU. The ERS was invited to present its recommendations on chronic diseases at the ministerial conference on October 20, 2010 [2]. The official Council conclusions reflected the collective efforts of the ERS to raise the profile of chronic diseases [3]. As a continuation and expansion of these actions, the ERS has embarked on the publication of the European Respiratory Roadmap [4].

“A roadmap provides an extended look at the future of a chosen field of inquiry composed from the collective knowledge and imagination of the brightest drivers of change in that field” [5]. The European Respiratory Roadmap (hereafter “roadmap”), the first of its kind, seeks to serve as a basis for the respiratory community to communicate with key decision and policy makers on the importance of a focused strategy for respiratory medicine. It aims to outline, in four main chapters, the future needs of respiratory medicine in terms of changes in clinical practice, patient empowerment, expected new models of care delivery, and prevention strategies. It highlights the major research challenges that still persist, and how the training and education of health professionals will need to change and adapt …
A requirement for CD45 distinguishes Ly49D-mediated cytokine and chemokine production from killing in primary natural killer cells
Authors: Nicholas D. Huntington, Yuekang Xu, Stephen L. Nutt, David M. Tarlinton
Journal: The Journal of Experimental Medicine (2005)

Engagement of receptors on the surface of natural killer (NK) cells initiates a biochemical cascade ultimately triggering cytokine production and cytotoxicity, although the interrelationship between these two outcomes is currently unclear. In this study we investigate the role of the cell surface phosphatase CD45 in NK cell development and intracellular signaling from activating receptors. Stimulation via the major histocompatibility complex I–binding receptor, Ly49D on CD45−/− primary NK cells resulted in the activation of phosphoinositide-3-kinase and normal cytotoxicity but failed to elicit a range of cytokines and chemokines. This blockage is associated with impaired phosphorylation of Syk, Vav1, JNK, and p38, which mimics data obtained using inhibitors of the src-family kinases (SFK). These data, supported by analogous findings after CD16 and NKG2D stimulation of CD45−/− primary NK cells, place CD45 upstream of SFK in NK cells after stimulation via immunoreceptor tyrosine-based activation motif-containing receptors. Thus we identify CD45 as a pivotal enzyme in eliciting a precise subset of NK cell responses.
In Vivo Identification of Glycolipid Antigen–Specific T Cells Using Fluorescent Cd1d Tetramers
Authors: Kamel Benlagha, Angela Weiss, Andrew Beavis, Luc Teyton, Albert Bendelac
Journal: The Journal of Experimental Medicine (1999)

The CD1 family of major histocompatibility complex (MHC)-like molecules specializes in presenting lipid and glycolipid antigens to α/β T lymphocytes, but little is known about the size of the CD1-restricted T cell population or the frequency of T lymphocytes specific for a given glycolipid antigen. Here, we report the generation and use of mouse CD1d1–glycolipid tetramers to visualize CD1d-restricted T cells. In contrast with previous BIAcore-based estimates of very short half-lives for CD1d–glycolipid complexes, we found that the dissociation rate of several different CD1d–glycolipid complexes was very slow. Fluorescent tetramers of mouse CD1d1 complexed with α-galactosylceramide (αGalCer), the antigen recognized by mouse Vα14-Jα281/Vβ8 and human Vα24-JαQ/Vβ11 natural killer T (NKT) cell T cell receptors (TCRs), allowed us for the first time to accurately describe, based on TCR specificity, the entire population of NKT cells in vivo and to identify a previously unrecognized population of NK1.1-negative “NKT” cells, which expressed a different pattern of integrins. In contrast, natural killer (NK) cells failed to bind the tetramers either empty or loaded with αGalCer, suggesting the absence of a CD1d-specific, antigen-nonspecific NK receptor. Mouse CD1d1–αGalCer tetramers also stained human NKT cells, indicating that they will be useful for probing a range of mouse and human conditions such as insulin-dependent diabetes mellitus, tumor rejection, and infectious diseases where NKT cells play an important role.
Immediate implants at fresh extraction sockets: from myth to reality
Authors: Fabio Vignoletti, Mariano Sanz
Journal: Periodontology 2000 (2014)

In recent years, immediate implant placement has become a common clinical therapeutic protocol representing an alternative to the classical delayed surgical protocol of implant placement. This protocol, however, has not been fully validated, either in terms of fully understanding the influence of implant placement on the socket-healing process or on the clinical outcomes. This narrative review evaluates the different experimental studies in humans and animals assessing the bone-healing dynamics of the socket after tooth extraction and the dimensional changes occurring at the socket bone walls. These experimental studies describe, in detail, the hard- and soft-tissue healing of implants placed into fresh extraction sockets, demonstrating that marked morphological changes of the alveolar ridge will occur, independently of the implant installation, thus demonstrating that postextraction bone loss is an inevitable biological process. This evidence has also been corroborated in clinical studies in humans, demonstrating the risk of significant peri-implant tissue loss, mainly in the areas of high esthetic demand. There is a lack of long-term evidence on the impact of this protocol on the preservation of the peri-implant tissues. In conclusion, despite the obvious advantages of this surgical protocol, it also has limitations and is more technically demanding than placing an implant into a healed crest. When selecting this protocol, clinicians should always consider: (a) the gingival biotype of the patient; (b) the thickness and integrity of the socket bony walls; (c) the implant selection as well as the adequate vertical and horizontal position of the implant; and (d) the ideal patient (a nonsmoker with good plaque control).
Epidermal growth factor-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting tubule cells. Regulation by G protein, calcium, and protein kinase C.
Authors: I Teitelbaum, A Strasheim, T Berl
Journal: Journal of Clinical Investigation (1990)

Epidermal growth factor (EGF) exhibits specific saturable binding to cultured rat inner medullary collecting tubule cells and stimulates inositol trisphosphate (IP3) production by these cells in a dose-dependent fashion. EGF-stimulated IP3 production is enhanced by GTP gamma s or AIF4- and is inhibited by GDP beta s or pertussis toxin. Alterations in extracellular Ca2+ have no effect on either basal or EGF-stimulated IP3 production. Similarly, treatment with EGTA which decreases cytosolic Ca2+ is without effect. In contrast, treatment with ionomycin which increases cytosolic Ca2+ has no effect on basal IP3 production but enhances the response to EGF. Activation of protein kinase C inhibits IP3 production in response to either EGF or AIF4-. These studies demonstrate the occurrence of EGF-stimulated phospholipase C activity in the rat inner medullary collecting duct. Stimulation by EGF is transduced by a pertussis toxin-sensitive G protein, unaffected by alterations in extracellular Ca2+, insensitive to a decrement in cytosolic Ca2+, enhanced by an increase in cytosolic Ca2+, and inhibited by protein kinase C.
Targeting Natural Killer Cells to Acute Myeloid Leukemia<i>In Vitro</i>with a CD16 × 33 Bispecific Killer Cell Engager and ADAM17 Inhibition
Authors: Andres Wiernik, Bree Foley, Bin Zhang, Michael R. Verneris, Erica Warlick, Michelle K. Gleason, Julie A. Ross, Xianghua Luo, Daniel J. Weisdorf, Bruce Walcheck, Daniel A. Vallera, Jeffrey S. Miller
Journal: Clinical Cancer Research (2013)

The graft versus leukemia effect by natural killer (NK) cells prevents relapse following hematopoietic stem cell transplantation. We determined whether a novel bispecific killer cell engager (BiKE) signaling through CD16 and targeting CD33 could activate NK cells at high potency against acute myelogenous leukemia (AML) targets.We investigated the ability of our fully humanized CD16 × CD33 (CD16 × 33) BiKE to trigger in vitro NK cell activation against HL60 (CD33(+)), RAJI (CD33(-)), and primary AML targets (de novo and refractory) to determine whether treatment with CD16 × 33 BiKE in combination with an ADAM17 inhibitor could prevent CD16 shedding (a novel inhibitory mechanism induced by NK cell activation) and overcome inhibition of class I MHC recognizing inhibitory receptors.NK cell cytotoxicity and cytokine release were specifically triggered by the CD16 × 33 BiKE when cells were cultured with HL60 targets, CD33(+) de novo and refractory AML targets. Combination treatment with CD16 × 33 BiKE and ADAM17 inhibitor resulted in inhibition of CD16 shedding in NK cells, and enhanced NK cell activation. Treatment of NK cells from double umbilical cord blood transplant (UCBT) recipients with the CD16 × 33 BiKE resulted in activation, especially in those recipients with cytomegalovirus reactivation.CD16 × 33 BiKE can overcome self-inhibitory signals and effectively elicit NK cell effector activity against AML. These in vitro studies highlight the potential of CD16 × 33 BiKE ± ADAM17 inhibition to enhance NK cell activation and specificity against CD33(+) AML, which optimally could be applied in patients with relapsed AML or for adjuvant antileukemic therapy posttransplantation.
Temozolomide for the Treatment of Brain Metastases Associated With Metastatic Melanoma: A Phase II Study
Authors: Sanjiv S. Agarwala, John M. Kirkwood, Martin Gore, Brigitte Dreno, Nicholas Thatcher, Beate Czarnetski, Michael Atkins, Antonio Buzaid, Dimosthenis Skarlos, Elaine M. Rankin
Journal: Journal of Clinical Oncology (2004)

Temozolomide is a well-tolerated oral alkylating agent with activity in the CNS. A multicenter, open-label, phase II study was conducted to assess the safety and efficacy of temozolomide in patients with brain metastases from metastatic melanoma (MM) who did not require immediate radiotherapy.Eligible patients had histologically confirmed MM to the brain, and no prior radiotherapy or radiosurgery for brain metastases. Previously untreated patients received temozolomide at 200 mg/m(2)/d x 5 days; previously treated patients received 150 mg/m(2)/d x 5 days every 28 days. Treatment continued for 1 year or until disease progression or unacceptable toxicity.Of 151 patients enrolled, 117 had received no prior systemic chemotherapy, and 34 had received prior chemotherapy for MM. Among previously untreated patients, 25% had more than four brain lesions, eight (7%) achieved an objective response (one complete and seven partial), and 34 (29%) had stable disease in brain metastases. Median overall survival was 3.5 months. Among previously treated patients, 21% had more than four brain lesions, one had a partial response, and six (18%) had stable disease in brain metastases. Median overall survival was 2.2 months. Temozolomide was well tolerated, with four (3%) patients discontinuing because of adverse events. Grade 3/4 hematologic toxicities included thrombocytopenia (3%), neutropenia (2%), and leukopenia (1%). Headache (9%) and vomiting (8%) were the most common nonhematologic grade 3/4 adverse events.Temozolomide was well tolerated and demonstrated activity in the treatment of brain metastases from MM. Further evaluation of temozolomide combination therapy is warranted.
Thrombotic Thrombocytopenic Purpura
Authors: Paul B. Goldenfarb
Journal: JAMA (1973)

Five of seven patients with thrombotic thrombocytopenic purpura have survived from 1 to 10.5 years from the time of diagnosis. In four cases, treatment consisted of high doses of corticosteroids followed by splenectomy. Three patients so treated were cured, and are still well 1, 1.5, and 7 years after therapy. Another patient, treated with low doses of steroids and splenectomy, has had chronic active disease for 10.5 years. In two of three cases, bedside biopsy of gingival tissue provided rapid histological confirmation of the clinical diagnosis. Thrombotic thrombocytopenic purpura is a potentially curable illness whose clinical spectrum ranges from a rapidly fatal disorder to chronic smoldering illness. Histological diagnosis can be made quickly and accurately by gingival biopsy.