tbuckley/cabot-search huggingface dataset:
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA
Authors: W. Barry Wood, Edwin N. Irons
Journal: The Journal of Experimental Medicine (1946)

Experimental pneumococcal pneumonia was produced in albino rats by intrabronchial inoculation of Type I pneumococci suspended in mucin. The resulting pneumonia was uniformly fatal in untreated rats. Eighty per cent of the animals so infected and treated with sulfonamide drugs 6 hours after inoculation survived the pneumonia. At the end of 1 week the surviving animals were sacrificed, and examination of the lungs showed sharply demarcated localized pulmonary lesions containing no pneumococci. Microscopic study of the lungs of treated animals sacrificed at 6, 18, 42, 66, 96, and 168 hours after the start of treatment revealed the following sequence of events. During the first 18 hours the drug apparently had little effect upon the pneumonic lesion, but at the end of 18 hours pneumococci in the edema zone began to show striking changes in their morphology, indicating bacteriostesis. Forty-two hours after the start of treatment the edema zone had disappeared, the pneumonia had ceased to spread, and the pneumococci at the margin of the lesion had been overtaken by leucocytes. Careful examination of the exudate in the periphery of the lesion revealed definite phagocytosis of pneumococci. By the 4th day no pneumococci could be found in the stained sections, and after 1 week there remained only macrophages in the rapidly clearing alveoli. In order to demonstrate the phagocytic reaction more clearly the effect of sulfonamide drugs was studied in pneumonic rats previously rendered leucopenic by exposure to x-ray. The pneumonia in these animals was relatively acellular, and the few macrophages present in each alveolus could be seen to have phagocyted large numbers of pneumococci after 18 to 42 hours of treatment. The macrophages not only phagocyted the pneumococci but ultimately destroyed them, the pneumonic lesion later going on to complete resolution. The fact that this phagocytic reaction was observed in the lungs of animals with bacteremia suggests that the phagocytosis is independent of circulating type-specific opsonins.
A study of matrix metalloproteinase expression and activity in atopic dermatitis using a novel skin wash sampling assay for functional biomarker analysis
Authors: J.I. Harper, H. Godwin, A. Green, L.E. Wilkes, N.J. Holden, M. Moffatt, W.O. Cookson, G. Layton, S. Chandler
Journal: British Journal of Dermatology (2009)

Atopic dermatitis (AD) is a chronic inflammatory skin condition that is characterized by a defective skin barrier. Despite the well-recognized role of proteases in skin barrier maintenance, relatively little is known of the contribution made by matrix metalloproteinases (MMPs) to the inflammatory process in AD.To test a simple, novel ex vivo bioassay technique in an analysis of the MMPs present in wash samples taken from the skin surface of patients with AD.Saline wash samples were collected from eczematous and unaffected areas of the skin of patients with AD and from the skin of normal controls. Wash samples were analysed for their MMP content using a functional peptide cleavage assay, gelatin zymography and an antibody array.Using a functional substrate cleavage assay, skin wash samples from AD lesions were shown to contain 10- to 24-fold more MMP activity than those from normal control skin (P < 0.02) and fivefold more than those from unaffected AD skin (P < 0.05); this activity was inhibited by a broad-spectrum MMP inhibitor Ro 31-9790. Gelatin zymography and antibody array analysis revealed substantial levels of MMP-8 (neutrophil collagenase) and MMP-9 (92-kDa gelatinase) in AD skin wash samples as well as lower levels of MMP-10 (stromelysin 2) and tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2; low levels of MMP-1 (fibroblast collagenase), MMP-3 (stromelysin 1) and TIMP-4 were also detected.A simple skin wash technique suitable for the quantitative and functional analysis of biomolecules in AD is described. Using this method we show that MMPs, and in particular MMP-8 and MMP-9, represent an important potential component of the pathology of AD. The method is expected to prove useful in advancing our understanding of AD and in identifying biomarkers for the evaluation of new therapies.
Maturation, Activation, and Protection of Dendritic Cells Induced by Double-stranded RNA
Authors: Marina Cella, Mariolina Salio, Yoichi Sakakibara, Hanno Langen, Ilkka Julkunen, Antonio Lanzavecchia
Journal: The Journal of Experimental Medicine (1999)

The initiation of an immune response is critically dependent on the activation of dendritic cells (DCs). This process is triggered by surface receptors specific for inflammatory cytokines or for conserved patterns characteristic of infectious agents. Here we show that human DCs are activated by influenza virus infection and by double-stranded (ds)RNA. This activation results not only in increased antigen presentation and T cell stimulatory capacity, but also in resistance to the cytopathic effect of the virus, mediated by the production of type I interferon, and upregulation of MxA. Because dsRNA stimulates both maturation and resistance, DCs can serve as altruistic antigen-presenting cells capable of sustaining viral antigen production while acquiring the capacity to trigger naive T cells and drive polarized T helper cell type 1 responses.
Decay-accelerating factor modulates induction of T cell immunity
Authors: Peter S. Heeger, Peter N. Lalli, Feng Lin, Anna Valujskikh, Jinbo Liu, Nasima Muqim, Yuanyuan Xu, M. Edward Medof
Journal: The Journal of Experimental Medicine (2005)

Decay-accelerating factor (Daf) dissociates C3/C5 convertases that assemble on host cells and thereby prevents complement activation on their surfaces. We demonstrate that during primary T cell activation, the absence of Daf on antigen-presenting cells (APCs) and on T cells enhances T cell proliferation and augments the induced frequency of effector cells. The effect is factor D- and, at least in part, C5-dependent, indicating that local alternative pathway activation is essential. We show that cognate T cell–APC interactions are accompanied by rapid production of alternative pathway components and down-regulation of Daf expression. The findings argue that local alternative pathway activation and surface Daf protein function respectively as a costimulator and a negative modulator of T cell immunity and explain previously reported observations linking complement to T cell function. The results could have broad therapeutic implications for disorders in which T cell immunity is important.
Exercises to improve function of the rheumatoid hand (SARAH): a randomised controlled trial
Authors: Sarah E Lamb, Esther M Williamson, Peter J Heine, Jo Adams, Sukhdeep Dosanjh, Melina Dritsaki, Matthew J Glover, Joanne Lord, Christopher McConkey, Vivien Nichols, Anisur Rahman, Martin Underwood, Mark A Williams
Journal: The Lancet (2014)
The Sequel to a Case of Excision of the Two Principal Joints of the Upper Extremity
Authors: W. Mac Cormac
Journal: BMJ (1876)

IN the Medico-Chirurgical Transactions for 1872, vol.55, will be found some particulars of, I believe, an unique case, in which, during the war of I870-7I, I performed resection of the shoulder-and elbow-joints in the same arm.The patient, a man called St. Aubin, was one of the corps Chasseurs d'Afrique, the third regiment of which took an active part in the battle of Sedan, under the command of the Marquis de Galliffet.
Is a Single Time Point C-Reactive Protein Predictive of Outcome in Peritoneal Dialysis Patients?
Authors: Angela Yee-Moon Wang, Jean Woo, Christopher Wai-Kei Lam, Mei Wang, Mandy Man-Mei Sea, Siu-Fai Lui, Philip Kam-Tao Li, John Sanderson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. C-reactive protein is the prototype marker of inflammation and has been shown to predict mortality in hemodialysis patients. However, it remains uncertain as to whether a single C-reactive protein level has similar prognostic significance in peritoneal dialysis patients. A single high-sensitivity C-reactive protein (hs-CRP) level was measured in 246 continuous ambulatory peritoneal dialysis patients without active infections at study baseline together with indices of dialysis adequacy, echocardiographic parameters (left ventricular mass index, left ventricular dimensions, and ejection fraction), nutrition markers (serum albumin, dietary intake, and subjective global assessment) and biochemical parameters (hemoglobin, lipids, calcium, and phosphate). The cohort was then followed-up prospectively for a median of 24 mo (range, 2 to 34 mo), and outcomes were studied in relation to these parameters. Fifty-nine patients died (36 from cardiovascular causes) during the follow-up period. The median hs-CRP level was 2.84 mg/L (range, 0.20 to 94.24 mg/L). Patients were stratified into tertiles according to baseline hs-CRP, namely those with hs-CRP ≤ 1.26 mg/L, 1.27 to 5.54 mg/L, and ≥ 5.55 mg/L. Those with higher hs-CRP were significantly older (<i>P</i> &lt; 0.001), had greater body mass index (<i>P</i> &lt; 0.001), higher prevalence of coronary artery disease (<i>P</i> = 0.003), and greater left ventricular mass index (<i>P</i> &lt; 0.001). One-year overall mortality was 3.9% (lower) <i>versus</i> 8.8% (middle) <i>versus</i> 21.3% (upper tertile) (<i>P</i> &lt; 0.0001). Cardiovascular death rate was 2.7% (lower) <i>versus</i> 5.2% (middle) <i>versus</i> 16.2% (upper tertile) (<i>P</i> &lt; 0.0001). Multivariable Cox regression analysis showed that every 1 mg/L increase in hs-CRP was independently predictive of higher all-cause mortality (hazard ratio [HR], 1.02; 95% CI, 1.01 to 1.04; <i>P</i> = 0.002) and cardiovascular mortality (HR, 1.03; 95% CI, 1.01 to 1.05; <i>P</i> = 0.001) in peritoneal dialysis patients. Other significant predictors for all-cause mortality included age (HR, 1.07; 95% CI, 1.04 to 1.10), gender (HR, 0.49; 95% CI, 0.27 to 0.90), atherosclerotic vascular disease (HR, 2.65; 95% CI, 1.46 to 4.80), left ventricular mass index (HR, 1.01; 95% CI, 1.00 to 1.01) and residual GFR (HR, 0.53; 95% CI, 0.38 to 0.75). Age (HR, 1.06; 95% CI, 1.02 to 1.10), history of heart failure (HR, 3.31; 95% CI, 1.36 to 8.08), atherosclerotic vascular disease (HR, 3.20; 95% CI, 1.43 to 7.13), and residual GFR (HR, 0.57; 95% CI, 0.38 to 0.86) were also independently predictive of cardiovascular mortality. In conclusion, a single, random hs-CRP level has significant and independent prognostic value in PD patients. E-mail: awang@cuhk.edu.hk
A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke
Authors: Olvert A. Berkhemer, Puck S.S. Fransen, Debbie Beumer, Lucie A. van den Berg, Hester F. Lingsma, Albert J. Yoo, Wouter J. Schonewille, Jan Albert Vos, Paul J. Nederkoorn, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, L. Jaap Kappelle, Rob H. Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, H. Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Aad van der Lugt, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel
Journal: New England Journal of Medicine (2014)

In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking.
Chemokine receptor CX3CR1 contributes to macrophage survival in tumor metastasis
Authors: Jiao Zheng, Min Yang, Jianghua Shao, Yanju Miao, Jiahuai Han, Jie Du
Journal: Molecular Cancer (2013)

Abstract Background Macrophages, the key component of the tumor microenvironment, are differentiated mononuclear phagocyte lineage cells that are characterized by specific phenotypic characteristics that have been implicated in tumor growth, angiogenesis, and invasion. CX3CR1, the chemoattractant cytokine CX3CL1 receptor, plays an important role in modulating inflammatory responses, including monocyte homeostasis and macrophage phenotype and function. However, the role of CX3CR1 in the regulation of the tumor inflammatory microenvironment is not fully understood. Methods Using in vivo hepatic metastasis model, human colon carcinoma specimens, immunohistochemical staining, TUNEL staining, flow cytometry analysis, Western blotting assay and co-culture in three-dimensional peptide gel, we determined the effects of CX3CR1 on angiogenic macrophage survival and tumor metastasis. Results In this study, we found that CX3CR1 was expressed in human colon carcinomas in a histologic grade- and stage-dependent manner, and CX3CR1 upregulation in TAMs was correlated with poor prognosis. Furthermore, we showed that in a microenvironment lacking CX3CR1, the liver metastasis of colon cancer cells was significantly inhibited. The underlying mechanism is associated with decrease accumulation of angiogenic macrophages that can be partly attributed to increased apoptosis in the tumor microenvironment, thus leading to impaired tumor angiogenesis in the liver and suppressed tumor metastasis. Conclusions Our results suggest a role of CX3CR1 in angiogenic macrophage survival in the tumor microenvironment contributing to tumor metastasis.
Further Evidence for a Humoral Natriuretic Factor
Authors: W. B. BLYTHE, D. D'AVILA, H. J. GITELMAN, L. G. WELT, L. LEE
Journal: Circulation Research (1971)

This chapter provides biochemical evidences for a humoral natriuretic factor. The regulation of salt excretion is among the most important determinants that modifies the concentration of sodium in the extracellular fluid and, hence, its osmolality and that of the intracellular fluid; modifies the distribution of fluid between the major compartments; modifies the volume of the extracellular phase; and perhaps most significant of all, in turn, plays a vital role in the circulation of the blood and all the conditions attendant on this remarkable phenomenon. It is possible that the increased sodium excretion in the donor dogs might have been due to factors other than a humoral natriuretic substance. Thus, it seems quite clear that a highly significant natriuresis obtains in a nonexpanded dog when this particular cross circulation technique is employed. It is also possible that a natriuretic factor is elaborated but its effect on the kidney might not be seen in the absence of dilution of the extravascular fluid.
Problematic Variation in Local Institutional Review of a Multicenter Genetic Epidemiology Study
Authors: Rita McWilliams
Journal: JAMA (2003)

Sequencing of the human genome provides an immense resource for studies correlating DNA variation and epidemiology. However, appropriately powered genetic epidemiology studies often require recruitment from multiple sites.To document the burden imposed by review of multicenter studies and to determine the variability among local institutional review boards (IRBs) in the approval of a multicenter genetic epidemiology study.A PubMed search was performed to determine the frequency of citations of multicenter studies by 5-year intervals from 1974 through 2002. A 7-question survey was sent to all participating study centers to obtain information on frequency of IRB meetings, dates for submission and approval, use/nonuse of a specific consent form, type of review performed, types of consent forms required, preparation time, and number of changes requested by the IRB at each center. Centers also provided a copy of all consent forms they generated and IRB correspondence regarding the study.Thirty-one of 42 cystic fibrosis care centers in this single US multicenter genetic epidemiology study of cystic fibrosis replied, yielding a 74% response rate.Frequency of published research studies and consistency among IRBs.The number of all published single-center studies has increased 1.3-fold since 1985, while the number of published epidemiology and genetic epidemiology multicenter studies increased by 8- and 9-fold, respectively, during this same period. Evaluation of the risk of the same genetic epidemiology study by 31 IRBs ranged from minimal to high, resulting in 7 expedited reviews (23%) and 24 full reviews (77%). The number of consents required by the IRBs ranged from 1 to 4; 15 IRBs (48%) required 2 or more consents, while 10 (32%) did not require assent for children. The most common concern (52%) of IRBs pertained to the genetic aspects of the study.Review of a protocol for a multicenter genetic epidemiology study by local IRBs was highly variable. Lack of uniformity in the review process creates uneven human subjects protection and incurs considerable inefficiency. The need for reform, such as the proposed centralized review, is underscored by the ever increasing rate of genetic discoveries facilitated by the Human Genome Project and the unprecedented opportunity to assess the relevance of genetic variation to public health.
NKT cell-dependent leukemia eradication following stem cell mobilization with potent G-CSF analogs
Authors: E. S. Morris
Journal: Journal of Clinical Investigation (2005)

NKT cells have pivotal roles in immune regulation and tumor immunosurveillance. We report that the G-CSF and FMS-like tyrosine kinase 3 ligand (Flt-3L) chimeric cytokine, progenipoietin-1, markedly expands the splenic and hepatic NKT cell population and enhances functional responses to α-galactosylceramide. In a murine model of allogeneic stem cell transplantation, donor NKT cells promoted host DC activation and enhanced perforin-restricted CD8+ T cell cytotoxicity against host-type antigens. Following leukemic challenge, donor treatment with progenipoietin-1 significantly improved overall survival when compared with G-CSF or control, attributable to reduced graft-versus-host disease mortality and paradoxical augmentation of graft-versus-leukemia (GVL) effects. Enhanced cellular cytotoxicity was dependent on donor NKT cells, and leukemia clearance was profoundly impaired in recipients of NKT cell–deficient grafts. Enhanced cytotoxicity and GVL effects were not associated with Flt-3L signaling or effects on DCs but were reproduced by prolonged G-CSF receptor engagement with pegylated G-CSF. Thus, modified G-CSF signaling during stem cell mobilization augments NKT cell–dependent CD8+ cytotoxicity, effectively separating graft-versus-host disease and GVL and greatly expanding the potential applicability of allogeneic stem cell transplantation for the therapy of malignant disease.
Thoughts from the Transition Zone
Authors: J. Terrance Davis
Journal: New England Journal of Medicine (2006)

I got the call earlier today. A teenager has been on life support at our hospital while awaiting a heart transplant. She was running out of time when we got the offer of a heart, and it was my job to recover the organ. Before I knew it, I was arriving at a suburban hospital 600 miles away, accompanied by my resident and a procurement technician. When we drove in, it seemed like any other emergency department at night.But as we walked through the emergency room (ER), all grew quiet. There were eyes upon us, and as people stepped . . .
An Autopsy Study of Maternal Mortality in Mozambique: The Contribution of Infectious Diseases
Authors: Clara Menéndez, Cleofé Romagosa, Mamudo R Ismail, Carla Carrilho, Francisco Saute, Nafissa Osman, Fernanda Machungo, Azucena Bardaji, Llorenç Quintó, Alfredo Mayor, Denise Naniche, Carlota Dobaño, Pedro L Alonso, Jaume Ordi
Journal: PLoS Medicine (2008)

Background Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios. Methods and Findings We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths. Conclusions In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement.