tbuckley/cabot-search huggingface dataset:
Increased IgA production by B-cells in COPD<i>via</i>lung epithelial interleukin-6 and TACI pathways
Authors: Maha Zohra Ladjemi, Marylène Lecocq, Birgit Weynand, Holly Bowen, Hannah J. Gould, Jacques Van Snick, Bruno Detry, Charles Pilette
Journal: European Respiratory Journal (2014)

Despite their relevance to mucosal defense, production of IgA and the function of lung B-cells remain unknown in chronic obstructive pulmonary disease (COPD). We assessed IgA synthesis in the lungs of COPD (n=28) and control (n=21) patients, and regulation of B-cells co-cultured with in vitro-reconstituted airway epithelium. In COPD lung tissue, synthesis of IgA1 was increased, which led to its accumulation in subepithelial areas. In vitro, the COPD bronchial epithelium imprinted normal human B-cells for increased production of IgA (mainly IgA1) and maturation into CD38(+) plasma cells. These effects were associated with upregulation of TACI (transmembrane activator and CAML interactor) and were observed under resting conditions, while being partly inhibited upon stimulation with cigarette smoke extract. Interleukin (IL)-6 and BAFF (B-cell activating factor)/APRIL (a proliferation-inducing ligand) were upregulated in the COPD epithelium and lung tissue, respectively; the IgA-promoting effect of the COPD bronchial epithelium was inhibited by targeting IL-6 and, to a lower extent, by blocking TACI. These data show that in COPD, the bronchial epithelium imprints B-cells with signals promoting maturation into IgA-producing plasma cells through the action of two epithelial/B-cell axes, namely the IL-6/IL-6 receptor and BAFF-APRIL/TACI pathways, while cigarette smoke partly counteracts this IgA-promoting effect.
Career paths for doctors: Disabled doctor forced to retire
Authors: N. W Lees
Journal: BMJ (1993)

Mutations in the genes encoding collagen VI (<i>COL6A1</i>, <i>COL6A2</i>, and <i>COL6A3</i>) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two conditions which were previously believed to be completely separate entities. BM is a relatively mild dominantly inherited disorder characterised by proximal weakness and distal joint contractures. UCMD was originally described as an autosomal recessive condition causing severe muscle weakness with proximal joint contractures and distal hyperlaxity. Here we review the clinical phenotypes of BM and UCMD and their diagnosis and management, and provide an overview of the current knowledge of the pathogenesis of collagen VI related disorders.
TRAIL and doxorubicin combination enhances anti-glioblastoma effect based on passive tumor targeting of liposomes
Authors: Liangran Guo, Li Fan, Zhiqing Pang, Jinfen Ren, Yulong Ren, Jingwei Li, Jie Chen, Ziyi Wen, Xinguo Jiang
Journal: Journal of Controlled Release (2011)
Governments failing to invest in education and health
Authors: Z. Kmietowicz
Journal: BMJ (2003)

Young people, especially in the developing world, are being short-changed because continuing under-investment in their health and education is stripping them of prospects for their future, says a report from the United Nations.

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Two children sniff glue in Nairobi, Kenya

Credit: AP PHOTO/SAYYID AZIM

The world faces the largest ever generation of children on the brink of adulthood: an estimated 1.2 billion people aged between 10 and 19 years, according to the United Nations Population Fund. This surge in the number of young people …

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Histology after placement of β-particle emitting stents: Insights into inhibition of neointimal formation
Authors: Andrew J. Carter, John R. Laird, Timothy G. Hoopes, Lynn R. Balley, Andrew Farb, Robert E. Fischell, David R. Fischell, Renu Virmani, Tim A. Fischell
Journal: Journal of the American College of Cardiology (1996)
Dorzolamide/timolol combination versus concomitant administration of brimonidine and timolol
Authors: Kenneth N Sall, Linda J Greff, Lisa R Johnson-Pratt, Paul T DeLucca, Adam B Polis, Andrea H Kolodny, Charlena A Fletcher, Deborah A Cassel, Denise R Boyle, Franck Skobieranda
Journal: Ophthalmology (2003)
Electricity, Safety, and the Patient
Authors: Nicholas G. Bircher
Journal: JAMA (1991)

This is a truly remarkable book. Not only does it make for enjoyable and informative reading, it makes otherwise tedious topics entertaining. The vigorous writing is complemented by thorough research on the part of the authors, amply reflected in the citation of references. The first of 11 chapters, "Electricity, the Basics," concisely and completely reviews the pertinent concepts for medical readers. "Fundamentals of Electrical Safety" considers microshock and macroshock hazards and how to avoid them, particularly in the hospital setting. The chapter "Electronic Instrumentation" details the history of monitors and other electrical equipment in the hospital. "Cardiac Excitability" provides a thorough treatment of this topic, and the chapters on pacemakers and electrosurgery are useful references. The real gem in this book is the incisive critique of the highly convoluted development of electrical safety standards. "The History and Epidemiology of Electrical Injuries in Hospitals" offers a rational perspective on the real
SUICIDE; WITH SOME ILLUSTRATIVE CASES.
Authors: JOHN L. DAVIS
Journal: JAMA (1904)

The alarming increase of suicide in recent years in this country is sufficient warrant for calling your attention to the subject to-day. The gifted editor of the<i>Chicago Tribune</i>, Mr. Upton, recently contributed some statistics to the<i>Independent</i>illustrating this lamentable fact. He showed that in twelve years there have been over 77,000 suicides recorded in the United States, the number increasing annually from about 3,500 in 1891 to 8,600 in 1903. Doubtless many cases failed to reach public knowledge, and doubtless many others recognized as suicides were officially reported under other causes of death. Had all these been noted properly, without doubt our country would show a loss at this time of fully 10,000 a year from self-destruction. The<i>Medical News</i><sup>1</sup>of New York says: "There have been 50 per cent. more suicides in Chicago in 1903 than in 1902." The same journal states that in Philadelphia for 1902
TCT-850 Early Clinical Outcome of Transcatheter Valve-In Valve Implantation in The Nordic Countries
Authors: Leo Ihlberg, Alexander Wahba, Henrik Nissen, Nielsen Niels-Henrik, Andreas Ruck, Rolf Busund, Kaj-Erik Klaaborg, Lars Soendergaard, Jan Harnek, Heikki Miettinen, Markku Eskola, Mika Laine
Journal: Journal of the American College of Cardiology (2012)
Clinical Guidelines for Lumbar Radiographs for Patients With Low Back Pain-Reply
Authors: Maria E. Suarez-Almazor, Anthony S. Russell, Elaine Belseck
Journal: JAMA (1997)

Although it may appear that the results reported by Dr Gutierrez and colleagues contradict our findings, we actually believe they are quite similar. Our study involved only primary care physicians, whereas theirs also included internists, surgeons, and chiropractors. In their health insurance company, Gutierrez et al report that lumbar radiograph utilization by family practitioners was 16%, which is similar to the utilization rate in our study (13%). Higher rates were observed for surgeons and chiropractors. After implementing the AHCPR guidelines to educate clinicians in their health insurance company, utilization in the overall group was reduced by 20%, but it is unclear whether this decrease occurred in all groups of clinicians or just those with prior high utilization (especially surgeons). In this group, a decrease of only 20% still would result in substantial use. We agree that prospective studies are necessary to evaluate fully the effect of these (and other) clinical
The Costs of Doctoring, the Distribution of Physicians, and Caring for the Underinsured
Authors: Robert C. Wallach
Journal: JAMA (1991)

To the Editor.  —Two articles 1,2 and a related editorial 3 in a recent issue of JAMA discussed the cost of medical care in Canada and the cost impact of the number of physicians produced by our training systems.  It is most surprising that in these three articles, neither the differences between Canada and the United States in respect to the medical care needs of indigent patients or the needs within the United States for expanding the care of underserved groups were considered.  Clearly, the employment levels of the two countries are major factors in the structure of medical care systems and should not be overlooked in these types of evaluations.
Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex
Authors: Jukka Kero, Matti Poutanen, Fu-Ping Zhang, Nafis Rahman, Anne Marie McNicol, John H. Nilson, Ruth A. Keri, Ilpo T. Huhtaniemi
Journal: Journal of Clinical Investigation (2000)

Transgenic (TG) female mice expressing bLHbeta-CTP (a chimeric protein derived from the beta-subunit of bovine luteinizing hormone [LH] and a fragment of the beta-subunit of human chorionic gonadotropin [hCG]) exhibit elevated serum LH, infertility, polycystic ovaries, and ovarian tumors. In humans, increased LH secretion also occurs in infertility and polycystic ovarian syndrome, often concomitant with adrenocortical dysfunction. We therefore investigated adrenal function in LH overexpressing bLHbeta-CTP female mice. The size of their adrenals was increased by 80% with histological signs of cortical stimulation. Furthermore, adrenal steroid production was increased, with up to 14-fold elevated serum corticosterone. Primary adrenal cells from TG and control females responded similarly to ACTH stimulation, but, surprisingly, the TG adrenals responded to hCG with significantly increased cAMP, progesterone, and corticosterone production. LH receptor (LHR) expression and activity were also elevated in adrenals from female TG mice, but gonadectomized TG females showed no increase in corticosterone, suggesting that the dysfunctional ovaries of the intact TG females promote adrenocortical hyperfunction. We suggest that, in intact TG females, enhanced ovarian estrogen synthesis causes increased secretion of prolactin (PRL), which elevates LHR expression. Chronically elevated serum LH, augmented by enhanced PRL production, induces functional LHR expression in mouse adrenal cortex, leading to elevated, LH-dependent, corticosterone production. Thus, besides polycystic ovaries, the bLHbeta-CTP mice provide a useful model for studying human disorders related to elevated LH secretion and adrenocortical hyperfunction.
Tree that provides paclitaxel is put on list of endangered species
Authors: S. Mayor
Journal: BMJ (2011)

Overharvesting of one of the trees that are sources of paclitaxel, a chemotherapy drug used to treat several cancers, has led to its classification as endangered in the latest global list of threatened species, published last week.

The tree, Taxus contorta , a yew that grows in Afghanistan, India, and Nepal, has been classified as endangered by the International Union for Conservation of Nature and Natural Resources, a non-profit organisation funded by governments and other organisations, in its latest “red list” of species at risk of extinction.

Its conservation status has changed from vulnerable to endangered because the …
Risks of Consumption of Contaminated Seafood: The Quincy Bay Case Study
Authors: Charles B. Cooper, Mary E. Doyle, Katrina Kipp
Journal: Environmental Health Perspectives (1991)

A recent EPA-sponsored study of sediment and seafood contamination in Quincy Bay revealed elevated levels of several complex organic pollutants frequently of concern in human health assessments. A seafood consumption risk assessment was conducted using data from samples collected in Quincy Bay in the methodology developed for EPA's Office of Marine and Estuarine Protection for such assessments. Results showed estimated plausible, upperbound excess cancer risks in the 10(-5) to 10(-2) range. These results are comparable to those found in other seafood contamination risk assessments for areas where consumption advisories and fishing restrictions were implemented. Regulatory response included consumption advisories for lobster tomalley (hepatopancreas) and other types of locally caught seafood. Uncertainties inherent in seafood risk assessment in general and for the Quincy Bay case are discussed, along with implications for further action.
Placental Growth Factor Regulates Cardiac Inflammation Through the Tissue Inhibitor of Metalloproteinases-3/Tumor Necrosis Factor-α–Converting Enzyme Axis
Authors: Daniela Carnevale, Giuseppe Cifelli, Giada Mascio, Michele Madonna, Mauro Sbroggiò, Cinzia Perrino, Maria Grazia Persico, Giacomo Frati, Giuseppe Lembo
Journal: Circulation (2011)

Heart failure is one of the leading causes of mortality and is primarily the final stage of several overload cardiomyopathies, preceded by an early adaptive hypertrophic response and characterized by coordinated cardiomyocyte growth, angiogenesis, and inflammation. Therefore, growth factors and cytokines have to be critically regulated during cardiac response to transverse aortic constriction. Interestingly, the dual properties of placental growth factor as an angiogenic factor and cytokine make it a candidate to participate in cardiac remodeling in response to hemodynamic overload.After transverse aortic constriction, placental growth factor knockout mice displayed a dysregulation of cardiac remodeling, negatively affecting muscle growth. Molecular insights underscored that this effect was ascribable mainly to a failure in the establishment of adequate inflammatory response owing to an impaired activity of tumor necrosis factor-α-converting enzyme. Interestingly, after transverse aortic constriction, placental growth factor knockout mice had strongly increased levels of tissue inhibitor of metalloproteinases-3, the main natural TACE inhibitor, thus indicating an unbalance of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-α-converting enzyme axis. Strikingly, when we used an in vivo RNA interference approach to reduce tissue inhibitor of metalloproteinases-3 levels in placental growth factor knockout mice during transverse aortic constriction, we obtained a complete phenotype rescue of early dilated cardiomyopathy.Our results demonstrate that placental growth factor finely tunes a balanced regulation of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-α-converting enzyme axis and the consequent TNF-α activation in response to transverse aortic constriction, thus allowing the establishment of an inflammatory response necessary for adaptive cardiac remodeling.
In vivo targeting of adoptively transferred T-cells with antibody- and cytokine-conjugated liposomes
Authors: Yiran Zheng, Matthias T. Stephan, S. Annie Gai, Wuhbet Abraham, Adrianne Shearer, Darrell J. Irvine
Journal: Journal of Controlled Release (2013)

In adoptive cell therapy (ACT), autologous tumor-specific T-cells isolated from cancer patients are activated and expanded ex vivo, then infused back into the individual to eliminate metastatic tumors. A major limitation of this promising approach is the rapid loss of ACT T-cell effector function in vivo due to the highly immunosuppressive environment in tumors. Protection of T-cells from immunosuppressive signals can be achieved by systemic administration of supporting adjuvant drugs such as interleukins, chemotherapy, and other immunomodulators, but these adjuvant treatments are often accompanied by serious toxicities and may still fail to optimally stimulate lymphocytes in all tumor and lymphoid compartments. Here we propose a novel strategy to repeatedly stimulate or track ACT T-cells, using cytokines or ACT-cell-specific antibodies as ligands to target PEGylated liposomes to transferred T-cells in vivo. Using F(ab′)2 fragments against a unique cell surface antigen on ACT cells (Thy1.1) or an engineered interleukin-2 (IL-2) molecule on an Fc framework as targeting ligands, we demonstrate that > 95% of ACT cells can be conjugated with liposomes following a single injection in vivo. Further, we show that IL-2-conjugated liposomes both target ACT cells and are capable of inducing repeated waves of ACT T-cell proliferation in tumor-bearing mice. These results demonstrate the feasibility of repeated functional targeting of T-cells in vivo, which will enable delivery of imaging contrast agents, immunomodulators, or chemotherapy agents in adoptive cell therapy regimens.
Textbook of the fundus of the eye.
Authors: David Shoch
Journal: JAMA (1963)

Since the invention of the ophthalmoscope by Helmholz, in 1851, examination of the fundus of the eye has become a part of every general physical examination. Indeed, within a year of this invention the first atlas of ophthalmoscopy appeared. Since this time, numerous atlases and texts have been published which describe the fundus in various pathologic states. The atlases have the common failing of including rather scanty text material. To remedy this, a series of textbooks has been written which correlate the eye findings with local or systemic disease. The classic example is volume 3 of<i>Duke-Elder's Textbook of Ophthalmology</i>— but this is too detailed for the non-ophthalmologist. Elwyn's<i>Diseases of the Retina</i>is a more concise presentation, but the title precisely defines its limitations. This new book is the best compromise published to date. It is magnificently written and beautifully illustrated. Chapter 1, on instrumentation, will interest chiefly
Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group
Authors: Trudy D. Buitenkamp, Shai Izraeli, Martin Zimmermann, Erik Forestier, Nyla A. Heerema, Marry M. van den Heuvel-Eibrink, Rob Pieters, Carin M. Korbijn, Lewis B. Silverman, Kjeld Schmiegelow, Der-Cheng Liang, Keizo Horibe, Maurizio Arico, Andrea Biondi, Giuseppe Basso, Karin R. Rabin, Martin Schrappe, Gunnar Cario, Georg Mann, Maria Morak, Renate Panzer-Grümayer, Veerle Mondelaers, Tim Lammens, Hélène Cavé, Batia Stark, Ithamar Ganmore, Anthony V. Moorman, Ajay Vora, Stephen P. Hunger, Ching-Hon Pui, Charles G. Mullighan, Atsushi Manabe, Gabriele Escherich, Jerzy R. Kowalczyk, James A. Whitlock, C. Michel Zwaan
Journal: Blood (2013)
Fatal pulmonary hypertension and rheumatoid vasculitis
Authors: VP Balagopal, P da Costa, MA Greenstone
Journal: European Respiratory Journal (1995)

A 51 year old man with mild rheumatoid arthritis developed pulmonary hypertension in the absence of interstitial lung disease. A cutaneous vasculitis subsequently responded to immunosuppressive therapy, but the lung disease was refractory to treatment. In patients with rheumatoid arthritis, dyspnoea should be investigated at an early stage, even in the absence of obvious pleural or interstitial lung disease.
Congenital Anomalies Probably Induced by Cyclophosphamide
Authors: Lowell H. Greenberg, Palos Verdes, Kouichi R. Tanaka
Journal: JAMA (1964)

A child showing multiple congenital anomalies was born to a woman with Hodgkin's disease who was treated with cyclophosphamide during pregnancy. It is probable that the alkylating agent administered during the first trimester played a significant teratogenic role. Alkylating agents act as teratogens in animals but have not been demonstrated previously as a cause of fetal abnormalities in humans.
The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections
Authors: Michael D. Howell, Peisong Gao, Byung Eui Kim, Leighann J. Lesley, Joanne E. Streib, Patricia A. Taylor, Daniel J. Zaccaro, Mark Boguniewicz, Lisa A. Beck, Jon M. Hanifin, Lynda C. Schneider, Tissa R. Hata, Richard L. Gallo, Mark H. Kaplan, Kathleen C. Barnes, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2011)
OBSERVATIONS ON THE RELATION OF THE EYE TO IMMUNITY IN EXPERIMENTAL SYPHILIS
Authors: Alan M. Chesney, Alan C. Woods, Alexander D. Campbell
Journal: The Journal of Experimental Medicine (1939)

Three experiments are reported in which an attempt has been made to determine the extent to which the eye participates in the general resistance which develops in rabbits during the course of syphilitic infection. Rabbits treated with arsphenamine well after the period when they would be expected to be immune to intratesticular or intracutaneous inoculations were reinoculated with the homologous strain of T. pallidum, the organisms being injected into either the cornea itself or the anterior chamber. Altogether in the three experiments 43 presumably immune animals were injected, 25 into the cornea itself and 18 into the anterior chamber. 41 normal animals were used as controls. In the immune animals 27 or 62 per cent showed lesions in the cornea. 14 of the 43 test animals were inoculated simultaneously in the cornea and in the skin of the back. In 9 of these 14, lesions developed in the cornea although no lesions developed in the skin. The lesions developing in the corneas of the "immune" animals had a longer incubation period on the average, were often of longer duration, and in some instances were more severe than the lesions developing in the control animals. In the case of some animals, also, they showed a greater tendency to recur. The immediate reactions in both the normal and the "immune" animals were entirely comparable and there was no evidence of an accelerated reaction in the test animals. It is concluded that the eye of the syphilitic rabbit does not share to the same extent as other tissues in the general resistant state which develops in that animal during the course of syphilitic infection. Possible explanations for this finding are discussed.
Spermagglutinating Activity and Female Infertility
Authors: Jose C. Pacheco-Romero
Journal: JAMA (1973)

Because of reports suggesting that spermagglutinins may be involved in female infertility, we tested serum and genital tract secretions over a three-year period. Initial studies of serums from 42 infertile patients showed a similar frequency of spermagglutinating activity in those with primary infertility (not due to detectable disease) and other forms of infertility. Analysis of serum, uterine, and vaginal secretions from another 31 infertile women showed that spermagglutinating activity was less frequent in the genital tract secretions than in serum. Among the total group of 73 women with various types of infertility, no significant difference in serum spermagglutinating activity was found. Our results do not encourage belief that spermagglutinating activity plays an important role in female infertility.
Hemodynamic and Body Composition Changes Following Bilateral Nephrectomy in Chronic Renal Failure
Authors: CONSTANTINE L. HAMPERS, ROBERT M. ZOLLINGER, JOHN J. SKILLMAN, J. ROBERT W. GUMPERT, GEORGE L. BAILEY, JOHN P. MERRILL
Journal: Circulation (1969)

Six patients with severe chronic renal failure and hypertension were evaluated before and again 1 and 4 months following bilateral nephrectomy while being maintained with regular hemodialysis. Hemodynamic function and body composition were measured by isotope dilution with each study. The mean femoral artery blood pressure (B.P.) of 142 mm Hg fell to 136 mm Hg ( P , ns ) at 1 month and to 120 mm Hg at 4 months ( P &lt; 0.005). This was mainly reflected in a drop in mean diastolic pressure of 13 mm Hg at 4 months ( P &lt;0.025). Total peripheral resistance tended to decrease, whereas, cardiac index was unchanged. Four months after nephrectomy, however, ability to raise both cardiac output and mean B.P. with standardized exercise had increased ( P &lt;0.005). Changes in exchangeable Na + , K + , extracellular fluid, and total body water did not correlate with the change in B.P. Plasma volume showed a slight tendency to fall with the decrease in mean B.P. after nephrectomy despite constant body weight ( P &lt;0.1). It is concluded that bilateral nephrectomy has a salutary effect on the hypertension of chronic renal failure (CRF), that this effect may not be immediately apparent, and that the fall in B.P. is independent of marked changes in extracellular fluid and exchangeable Na + and plasma volume.