tbuckley/cabot-search huggingface dataset:
S100 Proteinase-activated Receptor 1 Signalling Contributes To Neutrophilic Inflammation And Alveolar Barrier Disruption In Streptococcus Pneumoniae Pneumonia
Authors: R. Jose, A. Williams, M. Sulikowski, D. Brealey, J. Brown, R. Chambers
Journal: Thorax (2014)

<h3>Introduction</h3> <i>Streptococcus pneumoniae</i> is the most common cause of community-acquired pneumonia (CAP) and is associated with excessive neutrophilic inflammation. The high-affinity thrombin receptor, proteinase-activated receptor (PAR)-1, has been implicated in mediating the interplay between coagulation and inflammation. However, its role during <i>S. pneumoniae</i>-induced neutrophilic inflammation and the mechanisms for neutrophil recruitment in this context are poorly understood. <h3>Methods and Results</h3> The role of neutrophilic inflammation and PAR-1 was investigated in two models of murine pneumococcal pneumonia (serotype 2 (D39) and serotype 19F (EF3030)) by using the most clinically advanced PAR-1 antagonist, SCH530348. Neutrophil depletion and chemokine neutralisation studies were also performed. Samples were analysed by immunohistochemistry, cytology, flow cytometry, ELISA and microbiological techniques. Our models were characterised by evidence of intra-alveolar coagulation, increased neutrophil recruitment to areas of bacterial infection and increased PAR-1 expression (demonstrated by quantitative image-analysis). Neutrophil depletion protected mice against barrier disruption but resulted in compromised host defence. In contrast, PAR-1 antagonist treatment significantly reduced neutrophil recruitment to the bronchoalveolar space without being detrimental to host defence. Markers of alveolar leak, coagulation activation and pro-inflammatory cytokines and chemokines (IL-1β, CXCL1, CCL2 and CCL7) were also attenuated. Neutralisation studies demonstrated that IL-1β and CCL7, but not CXCL1 and CCL2, played a key role in neutrophil recruitment to the airspaces in this model. Translational studies were performed to examine by flow cytometry the CXC and CC chemokine receptor expression on neutrophils from blood and BALF of mechanically ventilated CAP-induced ARDS patients and controls. CXCR1 and CXCR2 expression on BALF neutrophils was higher in CAP-ARDS patients compared to controls. Additionally, chemokine expression patterns on neutrophils from CAP-ARDS patients changed within different compartments, evidenced by decreased expression of CXCR1 and increased expression of CXCR2, CCR1, CCR2 and CCR3 on neutrophils from BALF compared with blood. <h3>Conclusion</h3> These data provide preclinical proof-of-concept that recently developed PAR-1 antagonists may offer a novel therapeutic approach for controlling or preventing alveolar barrier dysfunction and excessive neutrophilic inflammation in pneumococcal pneumonia without compromising host defence. Furthermore, they highlight a role for chemokine receptor switching in CAP-ARDS with important implications for future targeting of these chemokine receptors.
Hypoxia and Heat Inhibit Inducible Nitric Oxide Synthase Gene Expression by Different Mechanisms in Rat Hepatocytes
Authors: Tomohisa Inoue, A-Hon Kwon, Michio Oda, Masaki Kaibori, Yasuo Kamiyama, Mikio Nishizawa, Seiji Ito, Tadayoshi Okumura
Journal: Hepatology (2000)

Ischemia/reperfusion contributes to the hepatic injury in resection and transplantation of the liver. However, the precise mechanisms involved in hypoxia stress remain to be clarified. Pro–inflammatory cytokines including interleukin 1β (IL–1β) induce a gene expression of inducible nitric oxide synthase (iNOS) and produce nitric oxide, which exerts either a cytoprotective or toxic effect. In this report, we found that hypoxia and heat markedly inhibited the induction of nitric oxide production stimulated by IL–1β in rat cultured hepatocytes. Both treatments also abolished the induction of iNOS protein and mRNA. However, hypoxia could not prevent either degradation of an inhibitory protein (IκBα) of nuclear factor–κB (NF–κB) or translocation of NF–κB to the nucleus, whereas heat inhibited both of the IκBα degradation and NF–κB translocation. Transfection experiments with iNOS promoter construct revealed that hypoxia as well as heat significantly inhibited the transactivation of iNOS gene. Further, a hypoxia–response element located in the promoter was not involved in the inhibition of iNOS induction by hypoxia. These results indicate that hypoxia and heat suppress iNOS gene induction at the transcriptional level through different mechanisms. Reduction of nitric oxide production under hypoxic conditions may be implicated in the cellular damage or protection during hepatic ischemia/reperfusion.
Wound Infections Following Potentially Contaminated Operations
Authors: Harvey R. Bernard
Journal: JAMA (1963)

THESE EXPERIMENTS were designed to test whether delayed primary wound closure would effect a significant reduction in the incidence of wound infection following abdominal operations (eg, intestinal anastomoses, gastric resections, operations on the biliary tract) which are potentially contaminated by bacteria. This technique was suggested by Coller and Valk<sup>1</sup>22 yr ago in the treatment of contaminated civilian wounds and has been used extensively by military surgeons since World War I as a method of treating contaminated war wounds. In the present study, the incidence of wound infection following delayed primary closure of the skin and subcutaneous tissues was compared with that of wounds closed primarily. The patients were from a women's surgical ward at the Barnes Hospital during a period from July, 1960, through June, 1961. The study included 95 intra-abdominal operations. A simple, uncomplicated system of patient selection was used which decreed that all patients assigned an
Entrapment Neuropathy From Baker's Cyst
Authors: Kenneth K. Nakano
Journal: JAMA (1978)

BAKER'S cysts occur when the gastrocnemius-semimembranous bursa communicates with the knee joint and an effusion leads to a popliteal cyst. Rheumatoid synovitis may produce bursal swelling, distension, and eventually a Baker's cyst. If the cyst ruptures, this causes extravasation of the fluid into the compartments of the calf and produces symptoms and signs mimicking thrombophlebitis. On the other hand, if the cyst enlarges without rupturing, pressure may be exerted on branches of the low sciatic nerve and produce a neuropathy. I report the cases of five patients, each with an entrapment neuropathy secondary to Baker's cysts. <h3>Report of Cases</h3> The five patients included three men and two women ranging in age from 51 to 66 years. Four patients had classical rheumatoid arthritis, while foot-drop developed in one man after trauma to the knee. In all five patients, a painful palpable enlargement in the popliteal area became most symptomatic with the
On Ulcerative Inflammation of the Valves of the Heart, as a Cause of Pyaemia
Authors: W. S. Kirkes
Journal: BMJ (1863)

At that time he was in a nervous, tremulous condition, the result of intemperance; besides which, the ordinary symptomns of jaundice were present, though not in a severe form.They had existed about a montlh or five weeks.The abdomen was full and distended.He had some pain, chiefly marked under the right ribs, and occasioually at the pit of the stomach.There had been much nausea and vomiting when the jaundice first appeared, but they had since subsided.He had had a previous attack, five years before.The stools were rather loose, quite clay-coloured; the urine high co- loured, slhowing the purple colour in a marked degree with thie acid test, indicating the presence of bile-acids.He was ordered two compound colocynth pills occasion- ally, and a dose of a mixture containing solution of acetate of ammonia, tincture of orange.peel,and chloric ether, tlhree times a day; common diet, and half a pint of porter daily.He quiickly improved, lost his yellow colour and trem- bling conidition, and was discharged cured on June 15th.CASE Ix.B. D., aged 50, female, was admitted on May 14th, 186i3, with symptoms of jaundice to an ex- treme degree.The skin was of an intense greenislh yellow hue, dry and harsh ; urine as black as porter, de- positing sediment; bowels costive.She did not com- plain of any pain, but was in a very low, weak state.The jauindice had been coming on about two months, an(d hald been preceded by an attack of " slow" fever.She lhad vomited very much at first, but not latterly.Slhe had not had a previous attack of jaundice.The urine, with the suilphuric acid test, showed distinictly the presence of bile-acids.Slhe was ordered to take a grain of podophyllin, and two grains of extract of henbane in a pill, twice a day; and to have milk diet, and three ounces of wine daily.
Diagnostic paracentesis in the acute abdomen.
Authors: W. N. Baker, D. B. Mackie, J. F. Newcombe
Journal: BMJ (1967)

The first comprehensive study of the technique was carried out by Neuhof and Cohen (1926), who reported enthusiastically on its use as a diagnostic aid in the evaluation of closed abdominal injuries, acute pancreatitis, and primary pneumo coccal or streptococcal peritonitis. Though no cases were reported in their paper, they also predicted a wider use for the test in the diagnosis of ruptured hollow viscera and bleeding ectopic pregnancies.
Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells
Authors: Xueliang Du, Takeshi Matsumura, Diane Edelstein, Luciano Rossetti, Zsuzsanna Zsengellér, Csaba Szabó, Michael Brownlee
Journal: Journal of Clinical Investigation (2003)

In this report, we show that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron transport chain activates the three major pathways of hyperglycemic damage found in aortic endothelial cells by inhibiting GAPDH activity. In bovine aortic endothelial cells, GAPDH antisense oligonucleotides activated each of the pathways of hyperglycemic vascular damage in cells cultured in 5 mM glucose to the same extent as that induced by culturing cells in 30 mM glucose. Hyperglycemia-induced GAPDH inhibition was found to be a consequence of poly(ADP-ribosyl)ation of GAPDH by poly(ADP-ribose) polymerase (PARP), which was activated by DNA strand breaks produced by mitochondrial superoxide overproduction. Both the hyperglycemia-induced decrease in activity of GAPDH and its poly(ADP-ribosyl)ation were prevented by overexpression of either uncoupling protein–1 (UCP-1) or manganese superoxide dismutase (MnSOD), which decrease hyperglycemia-induced superoxide. Overexpression of UCP-1 or MnSOD also prevented hyperglycemia-induced DNA strand breaks and activation of PARP. Hyperglycemia-induced activation of each of the pathways of vascular damage was abolished by blocking PARP activity with the competitive PARP inhibitors PJ34 or INO-1001. Elevated glucose increased poly(ADP-ribosyl)ation of GAPDH in WT aortae, but not in the aortae from PARP-1–deficient mice. Thus, inhibition of PARP blocks hyperglycemia-induced activation of multiple pathways of vascular damage.
The footballer's fracture
Authors: H R Cattermole, J R W Hardy, P J Gregg
Journal: British Journal of Sports Medicine (1996)

Objective To describe the typical tibial diaphyseal fracture (“footballer's fracture”) and to clarify the circumstances and mechanism of the injury. Methods In an attempt to obtain a detailed analysis of the types of injury suffered, and thereby highlight areas for prevention, 100 consecutive adult football players with a tibial diaphyseal fracture were studied prospectively. Details of the circumstances and mechanism of injury were collected using a questionnaire (response rate 85%). Treatments depended on the Gustilo classification, displacement, and axial stability. Long term follow up was performed until clinical healing to define the overall prognosis. Results 61% of players suffered a fracture of both the tibia and the fibula. Ninety five percent of the tibial fractures were transverse or short oblique and were caused by impact during a tackle. Radiographic evidence of bridging callus was better than a classification of the bony injury for predicting weeks to clinical healing. The delayed union and non-union incidence following this injury is low. One patient suffered symptomatic shortening. One patient suffered symptomatic angulation and two patients with non-union required bone grafting. Conclusions Tibial fracture is an expensive injury. It prevents a young population from being employed and takes up valuable NHS resources. As 85% of players were wearing shin guards, it is likely that improvements in shin guard design could reduce the rate of tibial fracture.
Notes on Traumatic Tetanus
Authors: A. W. Hare
Journal: BMJ (1884)

complex composition.It contains creasote, turpentine, paraffin, and eupione, and is obtained by the destructive distillation of Pinus Syl- vestris.Carbolic acid has largely taken the place of this cruder com- pound; but Dr. Whitla says that there are virtues possessed by tar which are not equally enjoyed by its more fashionable rivals.In oakum we have a form of tar-dressing which I heartily recommend to those engaged in hospital-work.
Colonic mucosa-specific “pro-antedrugs” for oral treatment of ulcerative colitis: design, synthesis and fate of methyl 20-glucopyranosyloxyprednisolonates
Authors: Toshikiro Kimura, Takehiro Yamaguchi, Kumi Usuki, Yuji Kurosaki, Taiji Nakayama, Yukiko Fujiwara, Yasuyuki Matsuda, Katsuo Unno, Toshio Suzuki
Journal: Journal of Controlled Release (1994)
"Mesenteric Vascular Insufficiency" in Myocardial Infarction, Cardiac Failure, Cardiac Arrhythmias, and Shock States.
Authors: E. Corday
Journal: Annals of Internal Medicine (1961)

s1 May 1961"Mesenteric Vascular Insufficiency" in Myocardial Infarction, Cardiac Failure, Cardiac Arrhythmias, and Shock States.E. Corday, M.D., F.A.C.P., D. W. Irving, M.D., H. Gold, M.D., (Assoc.), H. Bernstein, M.D., J. H. Williams, M.D.E. Corday, M.D., F.A.C.P.Search for more papers by this author, D. W. Irving, M.D.Search for more papers by this author, H. Gold, M.D., (Assoc.)Search for more papers by this author, H. Bernstein, M.D.Search for more papers by this author, J. H. Williams, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1033_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptExperimental and clinical evidence will be presented to explain ischemic changes in the gastrointestinal tract resulting from remote extra-mesenteric circulatory disturbances such as hemorrhagic and traumatic shock, arrhythmias, myocardial infarction, and cardiac decompensation. The blood flow of the mesenteric circulation was measured during the various pathological states with the new accurate electromagnetic flowmeter and electronic integrator-computer. The mesenteric circulation decreases markedly during shock states, cardiac arrhythmias, and congestive heart failure. The resistance of the mesenteric circulation increases considerably due to a vasoconstriction. This results in ischemia and necrosis of the gastrointestinal tract. Findings at autopsy have been correlated with direct... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1033-1033KeywordsArrhythmiaBlood flowGastrointestinal tractHeart failureIschemiaMyocardial infarctionNecrosisShockVascular insufficiencyVasoconstriction ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
Heredity of Cancer Elucidated by a Study of Unselected Twins
Authors: Bent Harvald, Mogens Hauge
Journal: JAMA (1963)

In an unselected sample of 6,893 Danish twin pairs, a total of 1,038 cases of cancer were found. In the group of identical twins (1,528), 143 cancer probands had unaffected partners, 8 had partners with cancer of the same site, and 13 had partners with cancer of other localizations. In the same-sexed fraternal twins (2,609), the corresponding numbers were 292, 9, and 39. Thus the concordance rates in the two groups do not differ significantly, indicating that gene differences can only to a limited extent explain the diversity in the population with regard to the occurrence of malignant growth.
Sodium and potassium intake and blood pressure.
Authors: H Trowell
Journal: BMJ (1980)

this might not be the whole story: "The answer may well be more complicated."A very recent review' of the epidemiology of heart disease supports both comments.In the course of the review I analyse the sex and age pattems of mortality from "ischaemic heart disease" (8th ICD 410-414) in five populations: England and Wales, Scotland, US whites, US non-whites, and Japan.Defined in this way, ischaemic heart disease is heterogeneous, comprising three main components.Most deaths over the age range 30-75 years can, however, be attributed to one component, "acute myocardial infarction" (8th ICD 410).I deduce that genetic factors play two distinctive roles where acute myocardial infarction is concemed.
Histamine H<sub>4</sub> receptors modulate dendritic cell migration through skin – immunomodulatory role of histamine
Authors: W. Bäumer, S. Wendorff, R. Gutzmer, T. Werfel, D. Dijkstra, P. Chazot, H. Stark, M. Kietzmann
Journal: Allergy (2008)

Background: Dendritic cells (DC) are the major antigen‐presenting cells and play a key role in adaptive immunity as they are able to activate naive T cells. It was recently described, that the histamine H 4 receptor (H4R) is present on human monocyte‐derived DC and that chemotaxis and T‐helper (Th)1–Th2 polarization is mediated by this receptor. However, the distribution of histamine receptors on murine DC has not been studied yet. Methods: The histamine receptor expression on murine bone marrow (BM)‐derived DC and effects of histamine and H4R agonism on DC migration through skin were studied. As it was demonstrated in scratching experiments that NMRI mice are more susceptible to H4R‐mediated itch than BALB/c mice, DC function of NMRI and BALB/c mice was compared. Results: The mRNA of the H1R, H2R and H4R could be detected in murine BM‐derived DC, while mRNA of the H3R was found to be low or undetectable. There were no distinct differences in mRNA expression and in H4R protein level (flow cytometry) between NMRI compared with BALB/c mice indicating, that a higher susceptibility is not associated with a generally higher H4R expression in all cell types. Histamine as well as the H4R agonist clobenpropit induced an enhanced chemotaxis in the skin DC migration assay. The enhanced chemotaxis was blocked by the H4R antagonist JNJ7777120. This finding was confirmed by in vitro migration experiments with BM‐derived DC. Conclusion: Referring to DC migration, blocking the H4R on inflammatory cells might be a promising anti‐inflammatory, immunomodulatory strategy.
Angiopoietin-2 Promotes Disease Progression of Neuroendocrine Tumors
Authors: Katharina M. Detjen, Svenja Rieke, Antje Deters, Petra Schulz, Annett Rexin, Sonja Vollmer, Peter Hauff, Bertram Wiedenmann, Marianne Pavel, Arne Scholz
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Inhibition of angiogenesis represents a promising therapeutic strategy in neuroendocrine tumors. Angiopoietin-2 (Ang-2), a ligand of the endothelial tyrosine kinase Tie-2, is emerging as a key regulator of vascular remodeling during tumorangiogenesis. We therefore addressed the expression and biological significance of Ang-2 in human neuroendocrine tumors. Experimental Design: Surgical specimens and serum from neuroendocrine tumor patients were used to determine Ang-2 expression by in situ hybridization or ELISA (circulating Ang-2). Ang-2 biological effects were evaluated following stable transfection into BON human pancreatic neuroendocrine tumor cells. BON clones were grown as orthotopic xenografts in nude mice to determine tumor growth and abdominal metastatic spread. Further analyses included microvessel density, lymphatic vessel density, and nodal invasion. Results: Specimens from pancreatic neuroendocrine tumors and nontransformed pancreatic tissue revealed uniform expression of Ang-2 mRNA in endothelial cells. In contrast, epithelial expression of Ang-2 mRNA occurred exclusively in neuroendocrine tumors. Overexpression of Ang-2 in BON orthotopic xenografts did not affect primary tumor growth, although successful Ang-2 induction was confirmed from elevated serum levels. However, increased microvessel density and enhanced lymphatic metastasis were evident in Ang-2–expressing tumors, indicating a functional role of Ang-2 in experimental neuroendocrine tumors. Consistent with this notion, circulating Ang-2 was significantly elevated in neuroendocrine tumor patients compared with healthy controls. Circulating Ang-2 furthermore correlated with metastatic versus localized disease. The highest Ang-2 concentrations occurred in patients with liver metastasis, and concentrations ≥75th percentile predicted shorter survival (P = 0.0003). Conclusion: Induction of Ang-2 in neuroendocrine tumors represents a clinically relevant pathomechanism of disease progression and constitutes an adverse prognostic marker. Clin Cancer Res; 16(2); 420–9.
Early pregnancy factor in liver regeneration after partial hepatectomy in rats: Relationship with chaperonin 10
Authors: Kathryn A. Quinn, Alice C. Cavanagh, Narelle C. Hillyard, Dorothy A. McKay, Halle Morton
Journal: Hepatology (1994)

Early pregnancy factor is not only a product of dividing embryonic and neoplastic cells, as demonstrated previously, but also of normal proliferating cells. Eight hours after partial hepatectomy in rats, early pregnancy factor was detected in serum. It rose to a peak by 48 hr. Neutralization of early pregnancy factor in vivo by passive immunization with specific antibodies, 18 hr after partial hepatectomy, resulted in a significant decrease in the uptake of [3H]thymidine by the liver remnant, measured 4 to 6 hr later. These results suggest that during liver regeneration, early pregnancy factor is essential to the sequence of events that culminates in DNA synthesis and cell division. Recently we purified early pregnancy factor from human platelets and determined by mass spectrometry a precise molecular mass of 10,843 Da. Amino acid sequencing (approximately 72% of the molecule) demonstrated that early pregnancy factor is highly homologous with chaperonin 10, a stress-inducible mitochondrial protein, and that platelet-derived early pregnancy factor and rat chaperonin 10 share similar biochemical and immunological properties. In this study we show that early pregnancy factor, purified from regenerating rat liver and from serum taken 24 hr after hepatectomy, shares these properties. In addition, antibodies to early pregnancy factor, effective in passive immunization studies, recognize chaperonin 10, whereas chaperonin 10 antibodies bind to early pregnancy factor from regenerating liver and posthepatectomy serum. We propose that early pregnancy factor/chaperonin 10 is selectively released from proliferating cells and, in an autocrine or paracrine mode (or both) is involved in DNA synthesis.
Blueberry Rakers' Tendinitis
Authors: Shiro Tanaka, Cheryl Fairfield Estill, Stephen C. Shannon
Journal: New England Journal of Medicine (1994)

To the Editor: Annually, from late July through early September, thousands of seasonal workers harvest wild blueberries in Maine and the eastern provinces of Canada. Maine's crop in 1993 was approximately 30 million kg1. The harvesting is done mostly by manual raking through the low-lying bushes (height, <25 cm). In response to reports of tendinitis among blueberry rakers, we conducted a survey in August 1993, consisting of a questionnaire about symptoms, physical examinations of the hands and wrists, and an ergonomic assessment of raking. The participants in the study were 134 rakers who volunteered on site; 73 percent were . . .