tbuckley/cabot-search huggingface dataset:
WHO reaffirms commitment to women's health
Authors: S. Kirwin
Journal: BMJ (1998)

The World Health Organization (WHO) has reiterated its goal of reducing maternal mortality by 50% by 2000, and celebrated the 10th anniversary of its Safe Motherhood Initiative on April 7. The initiative is a coalition formed by the WHO, UNICEF, the World Bank, the UN Population Fund, and other nongovernmental organizations to encourage countries to look at the position of women in society and improve their health care. About 1600 women die every day due to complications in pregnancy and childbirth, mostly in Asia and Africa. Of all the health statistics monitored by the WHO, maternal mortality is the one with the largest discrepancy between developed and developing countries; the level of maternal mortality in the developing world is almost 18 times higher than that in the developed world and up to one third of all deaths among women of reproductive age in many developing countries are the result of complications of pregnancy or childbirth. The WHO claims that providing care from conception to delivery, including family planning and neonatal care, would cost only about $3 per woman, an important social and economic investment. China, Sri Lanka, Iran, and Cuba have had considerable success in reducing their levels of maternal mortality through a combination of commitment to the initiative and improved health care.
Review: Continuous glucose monitoring reduces HbA<sub>1c</sub>more than self-monitoring in type 1 diabetes
Authors: A.C. Felix Burden
Journal: Annals of Internal Medicine (2013)

Source Citation Yeh HC, Brown TT, Maruthur N, et al. Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med. 2012;157:336-47. 22777524
Targeting cancer with kinase inhibitors
Authors: Stefan Gross, Rami Rahal, Nicolas Stransky, Christoph Lengauer, Klaus P. Hoeflich
Journal: Journal of Clinical Investigation (2015)

Kinase inhibitors have played an increasingly prominent role in the treatment of cancer and other diseases. Currently, more than 25 oncology drugs that target kinases have been approved, and numerous additional therapeutics are in various stages of clinical evaluation. In this Review, we provide an in-depth analysis of activation mechanisms for kinases in cancer, highlight recent successes in drug discovery, and demonstrate the clinical impact of selective kinase inhibitors. We also describe the substantial progress that has been made in designing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing strategies for combining kinase inhibitors in the clinic. Last, there are numerous prospects for the discovery of novel kinase targets, and we explore cancer immunotherapy as a new and promising research area for studying kinase biology.
International Labour Organisation tackles work related injuries
Authors: John Zarocostas
Journal: BMJ (2005)

Every year about 2.2 million people die from unintentional injuries at work and work related diseases, estimates the International Labour Organisation (ILO). The latest findings based on 2001 figures, the latest year with internationally comparable data, represents a 10% increase over similar measurements that used 1998 data.

Jukka Takala, director of the ILO's safe work programme, and author of the report, told the BMJ that he believes that the current death rate “would be at least 5-10% higher over the 2001 figures.”

The ILO report cautions that the numbers may be “vastly” under estimated since under-reporting is common in …
Medicine as a Social Instrument: The Hospital and the Community
Authors: Paul R. Hawley
Journal: New England Journal of Medicine (1951)

THE relation of the hospital to the community has undergone great changes in the last four centuries. It is scarcely an exaggeration to say that hospitals were set up initially for the primary purpose of abating a nuisance, and that they were operated accordingly for many years. The sick, the crippled, the insane — especially those unable to pay for private care — were public nuisances. The provision of asylum for such unfortunates was as much in the public interest as in the patients' own interest, if not more so. The deplorable conditions in most hospitals, which have obtained almost . . .
Socioeconomic evaluation of well‐characterized allergy to staple foods in adults
Authors: S.‐A. Jansson, J. L. P. Protudjer, M. Arnlind Heibert, U. Bengtsson, I. Kallström‐Bengtsson, B. Marklund, R. J. M. Middelveld, G. Rentzos, A. C. Sundqvist, J. Åkerström, E. Östblom, S.‐E. Dahlén, S. Ahlstedt
Journal: Allergy (2014)

Abstract Background The aim of the present study was to evaluate if total, direct, indirect, and intangible costs differ between a cohort of adults with well‐characterized allergy to staple foods (‘cases’) and controls. Methods Swedish adults with objectively diagnosed food allergy to cow′s milk, hen′s egg, and/or wheat were recruited at an outpatient allergy clinic. Controls age‐ and sex‐matched to cases were recruited from the same geographic area. For assessing the household costs of food allergy, a disease‐specific socioeconomic questionnaire, developed within E uro P revall, was utilized. Results Overall annual total costs at the household level were significantly higher among adults with food allergy compared with controls (the difference amounted to 8164 €), whereas direct costs did not differ between cases and controls. However, household healthcare costs and costs for medicines were significantly higher for cases vs controls. Furthermore, indirect costs were significantly higher for households with food‐allergic adults vs households without food‐allergic adults. Specifically, more time was spent on performing domestic tasks due to a family member's food‐allergy‐related illness, as well as shopping and preparing food, and seeking food‐allergy‐related information. Presence of food allergy also affected intangible costs. Adults with food allergy experienced overall lower health status compared with controls. Conclusions Swedish adults with allergy to staple foods have higher total costs determined as direct, indirect, and intangible costs using the disease‐specific socioeconomic questionnaire. Thus, total costs were 8164 € higher per year in households with at least one adult allergic to staple foods compared with controls.
Evolutionary Origin and Functions of Retrogene Introns
Authors: M. Fablet, M. Bueno, L. Potrzebowski, H. Kaessmann
Journal: Molecular Biology and Evolution (2009)

Retroposed genes (retrogenes) originate via the reverse transcription of mature messenger RNAs from parental source genes and are therefore usually devoid of introns. Here, we characterize a particular set of mammalian retrogenes that acquired introns upon their emergence and thus represent rare cases of intron gain in mammals. We find that although a few retrogenes evolved introns in their coding or 3′ untranslated regions (untranslated region, UTR), most introns originated together with untranslated exons in the 5′ flanking regions of the retrogene insertion site. They emerged either de novo or through fusions with 5′ UTR exons of host genes into which the retrogenes inserted. Generally, retrogenes with introns display high transcription levels and show broader spatial expression patterns than other retrogenes. Our experimental expression analyses of individual intron-containing retrogenes show that 5′ UTR introns may indeed promote higher expression levels, at least in part through encoded regulatory elements. By contrast, 3′ UTR introns may lead to downregulation of expression levels via nonsense-mediated decay mechanisms. Notably, the majority of retrogenes with introns in their 5′ flanks depend on distant, sometimes bidirectional CpG dinucleotide–enriched promoters for their expression that may be recruited from other genes in the genomic vicinity. We thus propose a scenario where the acquisition of new 5′ exon–intron structures was directly linked to the recruitment of distant promoters by these retrogenes, a process potentially facilitated by the presence of proto-splice sites in the genomic vicinity of retrogene insertion sites. Thus, the primary role and selective benefit of new 5′ introns (and UTR exons) was probably initially to span the often substantial distances to potent CpG promoters driving retrogene transcription. Later in evolution, these introns then obtained additional regulatory roles in fine tuning retrogene expression levels. Our study provides novel insights regarding mechanisms underlying the origin of new introns, the evolutionary relevance of intron gain, and the origin of new gene promoters.
Prevalence of Mitochondrial 1555A→G Mutation in European Children
Authors: Maria Bitner-Glindzicz, Marcus Pembrey, Andrew Duncan, Jon Heron, Susan M. Ring, Amanda Hall, Shamima Rahman
Journal: New England Journal of Medicine (2009)

To the Editor: Aminoglycoside antibiotics are used worldwide to treat gram-negative sepsis. Since these drugs are ototoxic and nephrotoxic, drug levels are closely monitored. However, their effect ...
Authors' reply to Kundi and Davis and colleagues
Authors: M. P. Little, P. Rajaraman, R. E. Curtis, S. S. Devesa, P. D. Inskip, D. P. Check, M. S. Linet
Journal: BMJ (2012)

We clearly state in the statistical methods that, while the figures are based on a specific reference group (men aged 60-64, Los Angeles registry), the entire dataset was used to estimate these rates.1 2 3 The reference group was chosen purely for statistical reasons, to minimise the variance of estimates: choosing a different group …
Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor
Authors: RN Germain, ME Dorf, B Benacerraf
Journal: The Journal of Experimental Medicine (1975)

After appropriate in vivo or in vitro immunization, cytotoxic T lymphocytes (CTL) are generated which efficiently kill cells bearing particular membrane antigens in common with the immunizing cell (reviewed in reference 1). Such CTL have been most thoroughly studied in mice, employing alloimmunization with cells differing at the major histocompatibility locus, H-2. in such cases, the predominant cell surface antigens recognized by the CTL appear to be the molecules carrying the serologically defined H-2 specificities, coded for by the K and D regions of the H-2 complex (2). In other syngeneic models of cell-mediated specific cytolysis, involving lymphocyte chariomeningitis (LCM) virus- or ectromelia virus-infected cells or TNP-modified lymphoid cells, thymus-derived cells also constitute the main effector cell type. The CTL generated in these latter systems function most efficiently when virus-infected or TNP-modified target cells share identitites at the H-2K or H-2D loci with the effector CTL and stimulator cells (3-5). Another set of experimental systems in which CTL are generated and play a significant biological role is that of immunity to tumor-associated antigens (TAA) (6). The nature of the TAA which the CTL recognize is only beginning to be understood. Several recent reports indicated the existence of physiochemical and/or antigenic relationships between TAA and H-2 antigens (7,8). These relationships, together with the genetic restrictions cited above in the generation of CTL involving products of the H-2K or H-2D loci suggested the possibility that in certain tumor systems, the TAA which are able to most effectively stimulate CTL responses might be structurally similar to, or linked with, the H-2K or H- 2D molecules on the tumor surface. It has been previously demonstrated in allogenic models that antisera specific for the appropriate H-2K or H-2D products present on a target cell could specifically block CTL-mediated lysis (1,9). This report demonstrates that certain anti-H-2 alloantisera specific for the target tumor cells can block lysis of those target cells mediated by syngeneic tumor-specific CTL effector cells.
FOREIGN BODY IN THE BRONCHUS.
Authors: H. H. GERMAIN
Journal: JAMA (1905)

Since 1897, when Killian of Freiburg reported his method of examining the bronchi by means of long tubes inserted through the mouth or through a tracheotomy wound, it has been extensively used. This procedure is largely confined to the location and removal of foreign bodies, but it has frequently been of value in localizing compression of the trachea from goiter and mediastinal tumors.  Up to August, 1904, there had been thirty-two successful removals of foreign bodies reported and there have been many more since that time. Under expectant treatment, these cases present a mortality variously given at from 56 to 80 per cent. Treated by tracheotomy, this rate is lowered to about 30 per cent. since a much better opportunity is furnished for spontaneous expulsion. These figures are more or less fallacious, as many of the fatal cases are probably not reported and some others considered cured probably die later
Tenascin-C Is Expressed in Macrophage-Rich Human Coronary Atherosclerotic Plaque
Authors: Kurt Wallner, Chen Li, Prediman K. Shah, Michael C. Fishbein, James S. Forrester, Sanjay Kaul, Behrooz G. Sharifi
Journal: Circulation (1999)

Background —Tenascin is a large extracellular matrix glycoprotein generally found in adult tissues undergoing active remodeling such as healing wounds and tumors. To determine the potential role of tenascin-C (TN-C) in the pathophysiology of atherosclerosis, we investigated the pattern of expression of TN-C in human coronary atherosclerotic plaques. Methods and Results —Immunohistochemical staining and in situ hybridization demonstrated minimal and random expression of TN-C in fibrotic but lipid-poor atherosclerotic plaques. In contrast, all plaques with an organized lipid core or ruptured intimal surface strongly expressed TN-C, which was preferentially concentrated around the lipid core, shoulder regions, and ruptured area of the plaques but not in the fibrous cap. TN-C was not detected in normal arterial tissue. To identify the cellular source of TN-C, the plaques were stained with smooth muscle cell– and macrophage-specific antibodies. TN-C expression correlated with the infiltration of macrophages. Northern blot and immunoprecipitation analysis showed that macrophages expressed 7.0-kb TN-C mRNA and 220-kDa protein. Reverse transcription–polymerase chain reaction of total RNA derived from macrophages showed that they express the small isoform of TN-C. Zymogram analysis revealed that macrophages markedly increased MMP-9 expression. Conclusions —This study demonstrates that the level of TN-C expression correlates with the degree of inflammation present, not with plaque size. In addition, cultured macrophages have the capacity to express the TN-C gene. These findings suggest the significance of macrophages in the remodeling of atherosclerotic plaque matrix composition.
FUNCTION OF MACROPHAGES IN ANTIGEN RECOGNITION BY GUINEA PIG T LYMPHOCYTES
Authors: Ethan M. Shevach, Alan S. Rosenthal
Journal: The Journal of Experimental Medicine (1973)

A number of recent studies have suggested that the main functional role of the product of the immune response (Ir) genes is in the process of antigen recognition by the T lymphocyte. The observation in the accompanying report that the interaction of macrophage-associated antigen with immune T lymphocytes requires that both cells share histocompatibility antigens raised the question as to whether the macrophage played a role in the genetic control of the immune response or even if the macrophage were the primary cell in which the product of the Ir gene is expressed. In the current study, parental macrophages were pulsed with an antigen, the response to which is controlled by an Ir gene lacking in that parent; these macrophages were then mixed with T cells derived from the (nonresponder x responder)F(1) and the resultant stimulation was measured. No stimulation was seen when column-purified F(1) lymph node lymphocytes were mixed with antigen-pulsed macrophages from the nonresponder parent. However, when the highly reactive peritoneal exudate lymphocyte population was used as the indicator cells, parental macrophages pulsed with an antigen whose Ir gene they lacked were capable of initiating F(1) T-cell proliferation. The magnitude of stimulation was approximately 1/10 that seen when macrophages from either the responder parent or the F(1) were used. In order to explain this observation, we hypothesize that antigen recognition sites on the T lymphocyte are physically related to a macrophage-binding site and both are linked to the serologically determined histocompatibility antigens. Thus, parental macrophages pulsed with an antigen, whose Ir gene they lack, activate F(1) cells poorly because the recognition sites for the antigen are physically related to the macrophage-binding site of the responder parent while the main contacts between the cells are at the nonresponder binding sites. Experiments performed with alloantisera lend support to this hypothesis. Thus, when parental macrophages are pulsed with any antigen and added to F(1) T cells, an alloantiserum directed against parental histocompatibility antigens reacts with both the lymphocyte and the macrophage and thereby inhibits macrophage-lymphocyte interaction and abolishes antigen-induced lymphocyte transformation. When the alloantisera are directed at determinants present solely on the T lymphocyte, they only inhibit the recognition of antigens controlled by the Ir gene linked to the histocompatibility antigen against which they are directed. We conclude from these studies that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.
Effect of VDR gene polymorphisms on osteocalcin secretion in calcitriol-stimulated human osteoblasts
Authors: Manuel Naves, Daniel Álvarez-Hernández, José L. Fernández-Martín, José Paz-Jiménez, Pedro García-Prado, Teresa Fernández-Coto, Íñigo Santamaría, Jorge Cannata-Andía
Journal: Kidney International (2003)
Primary cutaneous anaplastic large cell lymphoma in an elderly patient with cryoglobulinaemic hepatitis C virus infection
Authors: T. Kawakami, Y. Soma, K. Kaminishi, S. Kimura, Y. Tutumi, M. Mizoguchi
Journal: British Journal of Dermatology (2004)

Journal Article Primary cutaneous anaplastic large cell lymphoma in an elderly patient with cryoglobulinaemic hepatitis C virus infection Get access T. Kawakami, T. Kawakami Department of Dermatology, St Marianna University School of Medicine, 2‐16‐1 Sugao, Miyamae‐ku, Kawasaki, Kanagawa 216‐8511, Japan E‐mail: tami@marianna‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Soma, Y. Soma Department of Dermatology, St Marianna University School of Medicine, 2‐16‐1 Sugao, Miyamae‐ku, Kawasaki, Kanagawa 216‐8511, Japan E‐mail: tami@marianna‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Kaminishi, K. Kaminishi Department of Dermatology, St Marianna University School of Medicine, 2‐16‐1 Sugao, Miyamae‐ku, Kawasaki, Kanagawa 216‐8511, Japan E‐mail: tami@marianna‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Kimura, S. Kimura Department of Dermatology, St Marianna University School of Medicine, 2‐16‐1 Sugao, Miyamae‐ku, Kawasaki, Kanagawa 216‐8511, Japan E‐mail: tami@marianna‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Tutumi, Y. Tutumi Department of Dermatology, St Marianna University School of Medicine, 2‐16‐1 Sugao, Miyamae‐ku, Kawasaki, Kanagawa 216‐8511, Japan E‐mail: tami@marianna‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar M. Mizoguchi M. Mizoguchi Department of Dermatology, St Marianna University School of Medicine, 2‐16‐1 Sugao, Miyamae‐ku, Kawasaki, Kanagawa 216‐8511, Japan E‐mail: tami@marianna‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 4, 1 October 2004, Pages 941–943, https://doi.org/10.1111/j.1365-2133.2004.06232.x Published: 01 October 2004
Space mission aims to increase understanding of the nervous system
Authors: D. Josefson
Journal: BMJ (1998)

Seven astronauts and more than 2000 other creatures were launched into space aboard the space shuttle Columbia last week in a massive effort to study the effect of microgravity on the development and function of the nervous system.

The 16 day shuttle mission, known as Neurolab, is the first devoted exclusively to the neurosciences and the last launch of the century dedicated to the life sciences. Neurolab has cost $99m (£62m) so far, but the research is expected to lay the groundwork for long term space travel by providing insight into the neurological mechanisms of adaptions that the body makes in space. Earth based medicine is also likely to benefit from such research.

Prominent problems currently encountered by astronauts include space motion sickness, orthostatic intolerance, insomnia, and muscle atrophy. Longer space missions will impose additional demands on a nervous system already confused by the microgravity environment. Moreover, if people are …
Review: Low-molecular-weight heparin is better than unfractionated heparin to prevent VTE after ischemic stroke
Authors: Ken Uchino
Journal: Annals of Internal Medicine (2008)

Source Citation Shorr AF, Jackson WL, Sherner JH, Moores LK. Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis. Chest. 2008;133:149-55. 17925410
Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors
Authors: Steven C. Katz, Venu G. Pillarisetty, Joshua I. Bleier, T. Peter Kingham, Umer I. Chaudhry, Alaap B. Shah, Ronald P. DeMatteo
Journal: Hepatology (2005)

The contribution of intrahepatic conventional T cells to the unique immunologic properties of the liver has not been clearly defined. We isolated bulk and CD4 T cells from mouse liver and compared their functions with each other and with their splenic counterparts. Unlike bulk spleen T cells, bulk liver T cells reacted minimally to allogeneic or antigen-loaded syngeneic dendritic cells. However, after exclusion of natural killer T cells (NKTs) and γδ T cells by FACS, liver and spleen CD4 T cells actually proliferated to a similar extent upon allogeneic or antigen-specific stimulation. Liver CD4 T cells were more sensitive to interleukin 2 (IL-2) than were spleen CD4 T cells, but had a similar proliferative potential based on their response to CD3 ligation. In addition, activated liver CD4 T cells produced higher levels of IL-4, IL-5, IL-10, and interferon gamma (IFN-γ) than did splenic CD4 T cells. Therefore, liver CD4 T cells are intrinsically different from spleen CD4 T cells. In vitro, liver or spleen NKTs and γδ T cells suppressed liver and spleen CD4 T-cell proliferation in a dose-dependent fashion. In conclusion, unconventional T cells constrain liver CD4 T-cell function. Our findings have implications for pathological conditions of the liver that involve the response of conventional CD4 T lymphocytes. (HEPATOLOGY 2005;42:293–300.)
Alcohol and drug services have been patient centred for years
Authors: R. MacQueen
Journal: BMJ (2001)

EDITOR—Stewart's summary of and enthusiasm for a patient centred approach is most welcome.1 I believe that one additional feature of this approach should be added—namely, that it acknowledges the reality of patients accepting or rejecting our advice or treatment. Clinicians working with patients with alcohol and other drug problems, particularly those working in the harm reduction model, have known this for years.

The …
OCID 2987: A Novel, Chemically Distinct Orally Active PDE4 Inhibitor
Authors: S. Narayanan, S. Vishwakarma, S. Saxena, S. Honnegowda, K. Ganesan, F.A. Ahamed, N. Surendran, S. Narayanan, S. Rajagopal, G. Balasubramaniam
Journal: Journal of Allergy and Clinical Immunology (2010)