tbuckley/cabot-search huggingface dataset:
Increased lung deposition and biological effect of methacholine by use of a drying device for bronchial provocation tests
Authors: P Malmberg, K Larsson, S Thunberg
Journal: European Respiratory Journal (1991)

A simple device aiming to increase deposition of nebulized methacholine in the lower airway was studied. The device controlled inspiratory flow and volume and dried the aerosol. The effect of drying on deposition in the throat and lower airways was studied in six subjects given an aerosol of 99mTechnetium-diethylenetriamine pentaacetate (DTPA) in saline with the device and with a reference device giving the same inspiratory flow and volume but no drying. Drying reduced throat deposition from 46 (range 26-61) to 13 (range 6-22)% (p less than 0.05) of the inhaled and retained dose. The effect of drying on the biological effect of nebulized methacholine was studied in 21 subjects who underwent three provocation tests on different days with doubling concentrations of methacholine from 0.5 to a maximum of 64 mg.ml-1, one with the reference device and two with the drying device. The percentage change in forced expiratory volume in one second (%FEV1) per cumulative dose of methacholine changed from -1.0 (2.6) %FEV1.mumol-1 (geom. mean and SD) with the reference device to -1.6 (3.6) with the drying device p less than 0.02. In an additional study 20 subjects underwent four provocation tests on different days, two with a different version of the drying device and two with the reference device. The slope changed from -1.1 (3.1) to -1.6 (3.3), p less than 0.02. The reproducibility of duplicate measurements did not improve with the drying device. Thus, the drying device decreased throat deposition and increased the biological effect of nebulized methacholine.
Histologic and Transplantation Studies on Preleukemic Thymus of the AKR Mouse&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Donald Metcalf
Journal: JNCI Journal of the National Cancer Institute (1966)

A histologic survey of 264 thymuses from high-leukemia strain AKR mice, age 2–14 months, revealed that abnormal morphologic changes preceded the development of thymic lymphomas by at least several months. These changes were narrowing of the cortex with a selective depletion of cortical small lymphocytes and enlargement of the medulla by follicular aggregates of lymphoid cells, frequently with germinal centers. In its extreme form (cortical inversion), small lymphocytes were almost completely absent from the thymus cortex. Similar changes were only rarely observed in thymuses from low-leukemia strain mice of the same age. Transplantation tests failed to reveal the presence of lymphoma cells in AKR thymuses showing preleukemic changes. Neonatal or 1-week-old AKR thymus grafts in preleukemic mice showed normal morphology 1 month after grafting and exhibited normal Coulter Counter cell-distribution patterns despite the abnormal morphology of the host thymus. Neonatal AKR thymus grafts did develop cortical thinning and medullary lymphoid aggregates if left in host animals for 6 months. Preleukemic thymuses grafted to young hosts gave rise to thymus grafts which reproduced the morphologic abnormalities of the donor thymus. These results implicate the thymic epithelial and reticulum cells as being responsible in part for the preleukemic changes in the thymus.
Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing
Authors: Jiang Wu, Fujie Xu, Li Lu, Min Lu, Liang Miao, Ting Gao, Wenyan Ji, Luodan Suo, Donglei Liu, Rui Ma, Rui Yu, Jiazi Zhangzhu, Weixiang Liu, Yang Zeng, Xiaomei Li, Xuechun Zhang, Xinghuo Pang, Ying Deng
Journal: New England Journal of Medicine (2010)

After the first monovalent 2009 pandemic influenza A (H1N1) vaccine became available in September 2009, Chinese officials conducted a mass vaccination program in Beijing. We evaluated the safety and effectiveness of the vaccine.
The ratio of leptin to adiponectin can be used as an index of insulin resistance
Authors: Naohisa Oda, Shigeo Imamura, Takashi Fujita, Yuka Uchida, Kazumichi Inagaki, Hiroaki Kakizawa, Nobuki Hayakawa, Atsushi Suzuki, Jun Takeda, Yukio Horikawa, Mitsuyasu Itoh
Journal: Metabolism (2008)
Selective effects of cyclophosphamide therapy on activation, proliferation, and differentiation of human B cells.
Authors: L P Zhu, T R Cupps, G Whalen, A S Fauci
Journal: Journal of Clinical Investigation (1987)

The immune function of B lymphocytes from 12 patients with nonneoplastic immune-mediated diseases receiving chronic low-dose (2 mg/kg per d) cyclophosphamide (CY) was evaluated. There was a selective and differential suppressive effect of CY therapy on the various stages of the B cell cycle including activation, proliferation, and differentiation. The proliferative responses to Staphylococcus aureus Cowan strain I (SAC) and mitogenic concentrations of anti-mu were suppressed. In contrast, B cells that have been presumably activated in vivo proliferated with a normal pattern when exposed to B cell growth factor in vitro. Chronic low-dose CY therapy also suppressed B cell differentiation. Secretion of immunoglobulin by B cells following in vitro triggering with SAC and a T cell supernatant was suppressed in CY-treated patients. Moreover, differentiation of the large in vivo-activated B cells (which do not require an in vitro activation signal) in the presence of appropriate T lymphocyte supernatant was also suppressed. This selective suppression of B cell function at multiple points in the B cell cycle may be responsible for the efficacy of CY therapy in certain antibody and immune complex-mediated diseases.
Voltage dependence of beta-adrenergic modulation of conduction in the canine Purkinje fiber.
Authors: T M Munger, S B Johnson, D L Packer
Journal: Circulation Research (1994)

Although recent voltage-clamp and microelectrode studies have demonstrated beta-adrenergic modulation of Na+ current (INa) the modulation of conduction by catecholamines and the voltage dependence of that process have not been elucidated. To determine whether voltage-dependent modulation of conduction occurs in the presence of a beta-adrenergic agonist, the effect of 1 mumol/L isoproterenol on impulse propagation in canine Purkinje fibers was examined by using a dual-microelectrode technique. At physiological membrane potentials ([K+]o 5.4 mmol/L), isoproterenol increased squared conduction velocity [theta 2, 0.39 +/- 0.25 (m/s)2 (mean +/- SD)] from 3.46 +/- 0.86 to 3.85 +/- 0.98 (m/s)2 (P &lt; .011), an 11% change, without altering the maximum first derivative of the upslope of phase 0 of the action potential (Vmax, 641 +/- 50 versus 657 +/- 47 V/s, P = NS). At transmembrane potential of -65 mV, produced by 12 mmol/L [K+]o titration, theta 2 declined 79% to 0.73 +/- 0.44 (m/s)2 as Vmax decreased 85% to 95 +/- 43 V/s (P &lt; .02). The addition of isoproterenol further decreased theta 2 to 0.49 +/- 0.33 (m/s)2 (P = .02) in parallel with a further decline in Vmax to 51 +/- 25 V/s (P &lt; .05). Isoproterenol produced a 3-mV hyperpolarizing shift of apparent Na+ channel availability curves generated from both theta 2 and Vmax, used as indexes of the fast inward INa, without changing the slopes of the relation. The relation between normalized theta 2 and Vmax over a range of depolarized potentials was linear and was not appreciably altered by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)
The Growing Arsenal of ATP-Competitive and Allosteric Inhibitors of BCR–ABL
Authors: Oliver Hantschel, Florian Grebien, Giulio Superti-Furga
Journal: Cancer Research (2012)

Abstract The BCR–ABL fusion kinase is the driving mutation of chronic myelogenous leukemias and is also expressed in a subset of acute lymphoblastic leukemias. Recent advances in elucidating the structure, regulation, and signaling of BCR–ABL have led to the identification of allosteric sites that are distant from the ATP-binding pocket and are critical for BCR–ABL–dependent oncogenic transformation. Here, we review the available data regarding the molecular mechanism of action and the specificity of ATP-competitive tyrosine kinase inhibitors targeting BCR–ABL. In addition, we discuss how targeting of allosteric sites could provide new opportunities to inhibit resistant BCR–ABL mutants, either alone or in combination with conventional ATP-competitive inhibitors. Cancer Res; 72(19); 4890–5. ©2012 AACR.
Percutaneous pulmonary valve replacement: autologous tissue-engineered valved stents
Authors: A. Metzner, U. A. Stock, K. Iino, G. Fischer, T. Huemme, J. Boldt, J. H. Braesen, B. Bein, J. Renner, J. Cremer, G. Lutter
Journal: Cardiovascular Research (2010)

Percutaneous implantation has already been used clinically and is a great option for treating young patients. The use of autologous tissue-engineered valved stents might solve the problem of degeneration and limited durability of biological heart valves. Porcine pulmonary heart valves and small intestinal submucosa were obtained from a slaughterhouse. The intestinal submucosa was used to cover the inside of the porcine pulmonary valved stents. Endothelial cells (ECs) and autologous myofibroblasts (MFs) were used from carotid artery segments of juvenile sheep. After MF seeding, constructs were placed in a dynamic bioreactor system and cultured for 16 days. After additional EC seeding, tissue-engineered valved stents were percutaneously deployed into the annulus of the pulmonary valve (n = 9). Angiography was performed at implantation and 4-week follow-up. Constructs were analysed radiographically, by post-mortem examination, and microscopically. In all but one case, orthotopic positioning of the stents (n = 6) at the time of implantation and explantation was observed angiographically, macroscopically, and by computer tomography scan and demonstrated normal valve function (n = 7). Gross morphology confirmed excellent opening and closure characteristics of all leaflets after 4 weeks (n = 7). Strong expression of α-smooth muscle actin in neo-interstitial cells and of von Willebrand factor and PECAM-1 in ECs was revealed by immunocytochemistry. Good functioning and morphological characteristics were observed after percutaneous tissue-engineered valved stent implantation with autologous cells. This implantation of autologous tissue-engineered valved stents will become a valid future option in adolescents.
Is Response Rate Relevant to the Phase II Trial Design of Targeted Agents?
Authors: Afshin Dowlati, Pingfu Fu
Journal: Journal of Clinical Oncology (2008)

Afshin Dowlati, Department of Medicine, Case Western Reserve and University Hospitals Ireland Cancer Center and the Developmental Therapeutics Program, Case Comprehensive Cancer Center, Cleveland, OH Pingfu Fu, Department of Epidemiology & Biostatistics, Case Western Reserve University and University Hospitals Ireland Cancer Center and the Developmental Therapeutics Program, Case Comprehensive Cancer Center, Cleveland, OH
Characterizing biobank organizations in the U.S.: results from a national survey
Authors: Gail E Henderson, R Jean Cadigan, Teresa P Edwards, Ian Conlon, Anders G Nelson, James P Evans, Arlene M Davis, Catherine Zimmer, Bryan J Weiner
Journal: Genome Medicine (2013)

Abstract Background Effective translational biomedical research hinges on the operation of 'biobanks,' repositories that assemble, store, and manage collections of human specimens and related data. Some are established intentionally to address particular research needs; many, however, have arisen opportunistically, in a variety of settings and with a variety of expectations regarding their functions and longevity. Despite their rising prominence, little is known about how biobanks are organized and function beyond simple classification systems (government, academia, industry). Methods In 2012, we conducted the first national survey of biobanks in the U.S., collecting information on their origins, specimen collections, organizational structures, and market contexts and sustainability. From a list of 636 biobanks assembled through a multi-faceted search strategy, representatives from 456 U.S. biobanks were successfully recruited for a 30-minute online survey (72% response rate). Both closed and open-ended responses were analyzed using descriptive statistics. Results While nearly two-thirds of biobanks were established within the last decade, 17% have been in existence for over 20 years. Fifty-three percent listed research on a particular disease as the most important reason for establishment; 29% listed research generally. Other reasons included response to a grant or gift, and intent to centralize, integrate, or harmonize existing research structures. Biobank collections are extraordinarily diverse in number and types of specimens and in sources (often multiple) from which they are obtained, including from individuals, clinics or hospitals, public health programs, and research studies. Forty-four percent of biobanks store pediatric specimens, and 36% include postmortem specimens. Most biobanks are affiliated in one or multiple ways with other entities: 88% are part of at least one or more larger organizations (67% of these are academic, 23% hospitals, 13% research institutes). The majority of biobanks seem to fill a particular 'niche' within a larger organization or research area; a minority are concerned about competition for services, although many are worried about underutilization of specimens and long-term funding. Conclusions Effective utilization of biobank collections and effective policies to govern their use will require understanding of the immense diversity found in organizational features, including the very different history and primary goals that many biobanks have.
STUDIES ON A-AVITAMINOSIS IN CHICKENS
Authors: Oskar Seifried
Journal: The Journal of Experimental Medicine (1930)

1. The principal tissue changes in the respiratory tract of chickens caused by a vitamin A deficiency in the food are, first, an atrophy and degeneration of the lining mucous membrane epithelium as well as of the epithelium of the mucous membrane glands. This process is followed or accompanied by a replacement or substitution of the degenerating original epithelium of these parts by a squamous stratified keratinizing epithelium. This newly formed epithelium develops from the primitive columnar epithelium and divides and grows very rapidly. The process appears to be one of substitution rather than a metaplasia, and resembles the normal keratinization of the skin or even more closely the incomplete keratinization of the mucous membranes (e.g., the esophagus or certain parts of the tongue of chickens). In this connection findings have been described which not only afford an interesting insight into the complicated mechanism of keratinization, but also show probable relations between keratinization and the development of Guarnieri's inclusion bodies. Balloon and reticular degeneration of the upper layers of the new stratified epithelium has been frequently observed. All parts of the respiratory tract are about equally involved in the process; and the olfactory region as well, so that the sense of smell may be lost. The lesions, which first take place on the surface epithelium and then in the glands, show only minor differences. 2. The protective mechanism inherent in the mucous membranes of the entire respiratory tract is seriously damaged or even entirely destroyed by the degeneration of the ciliated cells at the surface and the lack of secretion with bactericidal. properties. Secondary infections are frequently found, and nasal discharge and various kinds of inflammatory processes are common, including purulent ones, especially in the upper respiratory tract, communicating sinuses, eyes and trachea. The development of the characteristic histological process is not dependent upon the presence of these infections, since it also takes place in the absence of infection. 3. The specific histological lesions make it possible to differentiate between A-avitaminosis and some infectious diseases of the respiratory tract. These studies we hope will serve as a basis for further investigations on the relationship between A-avitaminosis and infection in general.
Delayed Disease Progression after Allogeneic Cell Vaccination in Hormone-Resistant Prostate Cancer and Correlation with Immunologic Variables
Authors: Agnieska Michael, Graham Ball, Nadine Quatan, Fatima Wushishi, Nick Russell, Joe Whelan, Prabir Chakraborty, David Leader, Michael Whelan, Hardev Pandha
Journal: Clinical Cancer Research (2005)

Abstract Purpose: There are a significant number of patients with asymptomatic hormone-resistant prostate cancer who have increasing prostate-specific antigen (PSA) levels but little or no evaluable disease. The immunogenicity and minimal toxicity associated with cell-based vaccine therapy makes this approach attractive for these patients. Experimental Design: We have evaluated a vaccine comprising monthly intradermal injection of three irradiated allogeneic prostate cell lines (8 × 106 cells each) over 1 year. The first two doses were supplemented with bacille Calmette-Guérin as vaccine adjuvant. Twenty-eight hormone-resistant prostate cancer patients were enrolled. Patients were assessed clinically and PSA levels were measured monthly. Radiologic scans (X-ray, computed tomography, and bone scan) were taken at baseline and at intervals throughout the treatment period. Comprehensive monthly immunologic monitoring was undertaken including proliferation studies, activation markers, cytokine protein expression, and gene copy number. This longitudinal data was analyzed through predictive modeling using artificial neural network feed-forward/back-propagation algorithms with multilayer perceptron architecture. Results: Eleven of the 26 patients showed statistically significant, prolonged decreases in their PSA velocity (PSAV). None experienced any significant toxicity. Median time to disease progression was 58 weeks, compared with recent studies of other agents and historical control values of around 28 weeks. PSAV-responding patients showed a titratable TH1 cytokine release profile in response to restimulation with a vaccine lysate, while nonresponders showed a mixed TH1 and TH2 response. Furthermore, immunologic profile correlated with PSAV response by artificial neural network analysis. We found predictive power not only in expression of cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but also the method of analysis (qPCR measurement of IFN-γ &amp;gt; qPCR measurement tumor necrosis factor-α &amp;gt; protein expression of IFN-γ &amp;gt; protein expression of interleukin 2). Conclusions: Whole cell allogeneic vaccination in hormone-resistant prostate cancer is nontoxic and improves the natural history of the disease. Longitudinal changes in immunologic function in vaccinated patients may be better interpreted through predictive modeling using tools such as the artificial neural network rather than periodic “snapshot” readouts.
A fiber-modified adenoviral vector interacts with immunoevasion molecules of the B7 family at the surface of murine leukemia cells derived from dormant tumors
Authors: Elodie Grellier, Katia Lécolle, Sophie Rogée, Cyril Couturier, Jean-Claude D'Halluin, Saw-See Hong, Pascal Fender, Pierre Boulanger, Bruno Quesnel, Morvane Colin
Journal: Molecular Cancer (2011)

Abstract Tumor cells can escape the immune system by overexpressing molecules of the B7 family, e.g. B7-H1 (PD-L1 or CD86), which suppresses the anti-tumor T-cell responses through binding to the PD-1 receptor, and similarly for B7.1 (CD80), through binding to CTLA-4. Moreover, direct interactions between B7-H1 and B7.1 molecules are also likely to participate in the immunoevasion mechanism. In this study, we used a mouse model of tumor dormancy, DA1-3b leukemia cells. We previously showed that a minor population of DA1-3b cells persists in equilibrium with the immune system for long periods of time, and that the levels of surface expression of B7-H1 and B7.1 molecules correlates with the dormancy time. We found that leukemia cells DA1-3b/d365 cells, which derived from long-term dormant tumors and overexpressed B7-H1 and B7.1 molecules, were highly permissive to Ad5FB4, a human adenovirus serotype 5 (Ad5) vector pseudotyped with chimeric human-bovine fibers. Both B7-H1 and B7.1 were required for Ad5FB4-cell binding and entry, since (i) siRNA silencing of one or the other B7 gene transcript resulted in a net decrease in the cell binding and Ad5FB4-mediated transduction of DA1-3b/d365; and (ii) plasmid-directed expression of B7.1 and B7-H1 proteins conferred to Ad5FB4-refractory human cells a full permissiveness to this vector. Binding data and flow cytometry analysis suggested that B7.1 and B7-H1 molecules played different roles in Ad5FB4-mediated transduction of DA1-3b/d365, with B7.1 involved in cell attachment of Ad5FB4, and B7-H1 in Ad5FB4 internalization. BRET analysis showed that B7.1 and B7-H1 formed heterodimeric complexes at the cell surface, and that Ad5FB4 penton, the viral capsomere carrying the fiber projection, could negatively interfere with the formation of B7.1/B7-H1 heterodimers, or modify their conformation. As interactors of B7-H1/B7.1 molecules, Ad5FB4 particles and/or their penton capsomeres represent potential therapeutic agents targeting cancer cells that had developed immunoevasion mechanisms.
Bone mineral density and body composition in adult patients with cystic fibrosis.
Authors: A B Grey, R W Ames, R D Matthews, I R Reid
Journal: Thorax (1993)

BACKGROUND--Cystic fibrosis is a multisystem disease characterised by chronic pulmonary sepsis and malnutrition. To ascertain whether osteoporosis is a feature of cystic fibrosis in adult patients, total body and regional bone mineral density (BMD) was measured in a group of eight men and eight women aged 17-42 years. METHODS--Total body and regional BMD (lumbar spine L2-L4, femoral neck, trochanteric, and Ward9s triangle), as well as total body fat and lean mass, were measured by dual energy x ray absorptiometry. A range of biochemical, lifestyle, and anthropometric variables was also assessed. RESULTS--Patients with cystic fibrosis had significantly reduced bone density at all sites compared with normal young adults. The mean reductions ranged from 7% at Ward9s triangle to 13% at the trochanter. Body mass index (BMI) was positively correlated with BMD at four sites and disease severity negatively correlated with BMD at two sites. Other biochemical and anthropometric variables were not predictive of bone density. Total body fat mass was reduced by 30% compared with normal young adults. CONCLUSIONS--Bone density is decreased in adult patients with cystic fibrosis and BMI and disease severity are independent predictors of bone density.
CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells
Authors: Ulrike Erb, Amelie Pajip Megaptche, Xiaoyu Gu, Markus W Büchler, Margot Zöller
Journal: Journal of Hematology & Oncology (2014)

A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10).