tbuckley/cabot-search huggingface dataset:
Role of cytokines and their inhibitors in acute pancreatitis.
Authors: A Kingsnorth
Journal: Gut (1997)

Leading articleRole of cytokines and their inhibitors in acute pancreatitis Acute pancreatitis is a disease with considerable lethality for which there is no specific therapy beyond supportive treatment.Epidemiological data on the disease are sparse, but the incidence in Western countries is in the region of 10-20 per 10' population. - There are probably up to 10 000 cases of acute pancreatitis annually in Britain and as the mortality is approximately 8-12%, overall mortality may approach 1000.In Finland the incidence has increased by 50% between 1970 and 1989.4Hospital discharges with the final diagnosis of pancreatitis correlate with alcohol consumption in men and with gallstone disease in women.The early pathophysiology of the disease is not well understood.After the initial acinar cell injury, inflamma- tory cells migrate into the interstitium by adhering to endothelium and escaping from the microcirculation.The mechanisms by which inflammatory cells adhere to endothelial cells are determined by a variety of mediators or cytokines released at sites of tissue damage.Cytokines hold the key to both the local and the systemic inflamma- tory response in acute pancreatitis.New therapeutic approaches aim to modulate these pathways.5 6Infection Deaths after the first week of the disease are likely to be related to infection.'8Necrotic pancreatic tissue becomes contaminated with Gram negative bacteria, particularly Leading articles express the views of the author and not those of the editor and editorial board.
Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin
Authors: Kevin G. Leong, Kyle Niessen, Iva Kulic, Afshin Raouf, Connie Eaves, Ingrid Pollet, Aly Karsan
Journal: The Journal of Experimental Medicine (2007)

Aberrant expression of Jagged1 and Notch1 are associated with poor outcome in breast cancer. However, the reason that Jagged1 and/or Notch overexpression portends a poor prognosis is unknown. We identify Slug, a transcriptional repressor, as a novel Notch target and show that elevated levels of Slug correlate with increased expression of Jagged1 in various human cancers. Slug was essential for Notch-mediated repression of E-cadherin, which resulted in β-catenin activation and resistance to anoikis. Inhibition of ligand-induced Notch signaling in xenografted Slug-positive/E-cadherin–negative breast tumors promoted apoptosis and inhibited tumor growth and metastasis. This response was associated with down-regulated Slug expression, reexpression of E-cadherin, and suppression of active β-catenin. Our findings suggest that ligand-induced Notch activation, through the induction of Slug, promotes tumor growth and metastasis characterized by epithelial-to-mesenchymal transition and inhibition of anoikis.
23–valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial
Authors: N French, J Nakiyingi, LM Carpenter, E Lugada, C Watera, K Moi, M Moore, D Antvelink, D Mulder, EN Janoff, J Whitworth, CF Gilks
Journal: The Lancet (2000)
IL-1β and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system
Authors: Yun Xia, Hong-Zhen Hu, Sumei Liu, Jun Ren, Dimiter H. Zafirov, Jackie D. Wood
Journal: Journal of Clinical Investigation (1999)

Conventional intracellular microelectrodes and injection of biocytin were used to study the actions of IL-1β and IL-6 on electrical and synaptic behavior in morphologically identified guinea pig small intestinal submucous neurons. Exposure to nanomolar concentrations of either IL-1β or IL-6 stimulated neuronal excitability. The excitatory action consisted of depolarization of the membrane potential, decreased membrane conductance, and increased discharge of action potentials. Excitatory action of IL-1β was suppressed by the natural IL-1β human receptor antagonist. Electrical stimulation of sympathetic postganglionic axons evoked inhibitory postsynaptic potentials (IPSPs), and stimulation of cholinergic axons evoked nicotinic fast excitatory postsynaptic potentials (EPSPs). Both kinds of synaptic potentials occurred in neurons with uniaxonal morphology believed to be secretomotor neurons. Either IL-1β or IL-6 suppressed the noradrenergic IPSPs and the fast EPSPs, and the two acted synergistically when applied in combination. Suppression of the IPSP resulted from presynaptic inhibition of the release of norepinephrine from sympathetic nerves. The results suggest that the presence of either or both inflammatory cytokines will release the sympathetic brake from secretomotor neurons to the intestinal crypts and from nicotinic synapses in the integrative microcircuits, where norepinephrine is known to have a presynaptic inhibitory action. This, in concert with excitation of secretomotor neurons, may lead to neurogenic secretory diarrhea.
Modulation of Synaptic Plasticity and Memory by Reelin Involves Differential Splicing of the Lipoprotein Receptor Apoer2
Authors: Uwe Beffert, Edwin J. Weeber, Andre Durudas, Shenfeng Qiu, Irene Masiulis, J. David Sweatt, Wei-Ping Li, Giselind Adelmann, Michael Frotscher, Robert E. Hammer, Joachim Herz
Journal: Neuron (2005)
Ampicillin levels in sputum, serum, and saliva
Authors: S. M. Stewart, M. Fisher, J. E. Young, W. Lutz
Journal: Thorax (1970)

The ampicillin levels in sputum, serum, and saliva from 40 patients receiving a dose of 250 mg., 26 patients receiving a dose of 500 mg., and 11 patients receiving a dose of 1 g. were estimated. The ampicillin was given orally four times daily. The 1-2 hour and 2-3 hour sputum levels were similar in individual patients. There was no difference in the range or mean sputum or saliva levels between specimens from patients receiving 250 mg. and 500 mg., but the levels were significantly higher after the 1 g. dose. The mean serum level showed a small increase after 500 mg. ampicillin as compared with the 250 mg. dose and a big increase after the 1 g. dose: only the latter difference was significant. The sputum levels were approximately 30 to 40 times lower than the corresponding serum levels. There was considerable scatter in the sputum level for any level of ampicillin in the serum: in only two of the 1-2 hour sputum specimens was there no detectable ampicillin. There was no correlation between the sputum levels and either the body weight or the dose in milligrams per kilogram. There was no evidence that corticosteroids or diuretics affected the sputum level. It was not possible to demonstrate any relationship between the purulence of the sputum and the level of ampicillin after doses of 250 mg. or 500 mg., but higher levels were found in the more purulent specimens after 1 g. doses.
Plantaris excision in the treatment of non-insertional Achilles tendinopathy in elite athletes
Authors: James D F Calder, Richard Freeman, Noel Pollock
Journal: British Journal of Sports Medicine (2014)

Achilles tendinopathy is a serious and frequently occurring problem, especially in elite athletes. Recent research has suggested a role for the plantaris tendon in non-insertional Achilles tendinopathy.To assess whether excising the plantaris tendon improved the symptoms of Achilles tendinopathy in elite athletes.This prospective consecutive case series study investigated 32 elite athletes who underwent plantaris tendon excision using a mini-incision technique to treat medially located pain associated with non-insertional Achilles tendinopathy. Preoperative and postoperative visual analogue scores (VAS) for pain and the foot and ankle outcome score (FAOS) as well as time to return to sport and satisfaction scores were assessed.At a mean follow-up of 22.4 months (12-48), 29/32 (90%) of athletes were satisfied with the results. Thirty of the 32 athletes (94%) returned to sport at a mean of 10.3 weeks (5-27). The mean VAS score improved from 5.8 to 0.8 (p<0.01) and the mean FAOS improved in all domains (p<0.01). Few complications were seen, four athletes experienced short-term stiffness and one had a superficial wound infection.The plantaris tendon may be responsible for symptoms in some athletes with non-insertional Achilles tendinopathy. Excision carries a low risk of complications and may provide significant improvement in symptoms enabling an early return to elite-level sports.
A CURRENT VIEW OF THE RABIES PROBLEM
Authors: J. Casals
Journal: Annals of Internal Medicine (1945)

Article1 July 1945A CURRENT VIEW OF THE RABIES PROBLEMJ. CASALS, M.D.J. CASALS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-23-1-74 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFor the past 15 years the number of human cases of rabies in this country has averaged 55 per year. In animals, incomplete data obtained from state departments of health1 would indicate that for the period 1936-1940, the number is over ten thousand per year. The incidence of the disease in man and lower animals is greatest in the Southern and East-North-Central states, and in California.Owing to its relatively high incidence in domestic and wild animals as well as to its dreadful clinical reaction, rabies, even though infrequent as a cause of death in man, constitutes an important public...Bibliography1. WEBSTER LT: Rabies, 1942, The Macmillan Company, New York. Google Scholar2. KOCH J: Lyssa. In KOLLE, W., and VON WASSERMANN, A.: Handbuch der pathogenen Mikroorganismen, Jena, G. Fischer, 3rd edition (edited by KOLLE, W., KRAUS, R., and UHLENHUTH, P.), 1929, viii, 547-694. Google Scholar3. WEBSTERDAWSON LTJR: Early diagnosis of rabies by mouse inoculation. Measurement of humoral immunity to rabies by mouse protection test, Proc. Soc. Exper. Biol. and Med., 1935, xxxii, 570-573. CrossrefGoogle Scholar4. JOHNSON HN: Rabies. Oxford Loose-leaf Medicine, 1943, Oxford University Press, New York. Google Scholar5. WEBSTER LT: The immunizing potency of antirabies vaccines. A critical review, Am. Jr. Hyg., 1939, xxx (Sec. B), 113-134. Google Scholar6. MCKENDRICK AG: A ninth analytical review of reports from Pasteur Institutes on the results of anti-rabies treatment, Bull. of the Health Organization of the League of Nations, 1940, ix, 31-78. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Read at the Meeting of the American College of Physicians, New York, October 20, 1944.From the Laboratories of the Rockefeller Institute for Medical Research, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1945Volume 23, Issue 1Page: 74-78KeywordsRabies ePublished: 1 December 2008 Issue Published: 1 July 1945 PDF downloadLoading ...
No association between HLA-B and cutaneous reactions to sulphonamides in human immunodeficiency virus-infected patients
Authors: Z.G. Vitezica, P. Wolkenstein, C. Lonjou, M. Eliaszewicz, X. Sicard, J.-C. Roujeau, A. Hovnanian
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, Sulphonamides are commonly used antibiotic drugs. The sulphonamide family includes drugs used to treat the most common opportunistic infections in patients with AIDS. Their use is complicated by the unusually high rate of cutaneous drug reactions (CDR).1 The frequency of CDR to sulphonamides is approximately 5% in the general population and 10 times greater in human immunodeficiency virus (HIV)‐infected patients.2 Increasing evidence shows that CDR are genetically determined. Most of the studied polymorphisms in drug metabolism are not risk factors for sulphamide reactions.3, 4 More recent studies focusing on immunological rather than metabolic factors have demonstrated the involvement of HLA markers in the susceptibility to hypersensitive reactions to abacavir and nevirapine.5, 6 In this study, associations between HLA polymorphisms and CDR to sulphonamides were explored in the Epitox cohort of patients with AIDS. From 1995 to 1997, 136 HIV‐infected patients treated with sulfamethoxazole/trimethoprim for Pneumocystis carinii pneumonia or with sulfadiazine for cerebral toxoplasmosis were prospectively included in the study and followed up for 30 days. Patients with CDR to sulphonamides during this period were compared with patients without CDR. Participants were included according to the French laws governing participation in biomedical research and with approval of the local Ethics Committee. Each participant provided informed consent. The elapsed time between the initial Epitox study and this new genotyping study is due to a new hypothesis about the involvement of HLA in the susceptibility to CDR.5, 6 The Epitox cohort of patients with AIDS was used to evaluate HLA‐B polymorphism as a risk factor for CDR to sulphonamides. The number of patients genotyped for HLA‐B was limited by DNA quantity and quality. This subgroup of patients was not different from the entire cohort for its main characteristics. Twenty‐two individuals had developed CDR and 26 individuals did not show evidence of CDR to sulphonamides. All patients and controls were typed for HLA‐B locus. Low‐resolution HLA‐B genotyping was performed by polymerase chain reaction with sequence‐specific primers (GenoVision; Qiagen, Valencia, CA, U.S.A.).
The oxidative metabolism of circulating phagocytes in ankylosing spondylitis: determination by whole blood chemiluminescence
Authors: K.-J. Ho
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> Superoxide anion radicals within the human body are regarded as a major cause of inflammation. However, their role in the pathogenesis of ankylosing spondylitis (AS) has not been well identified. This study aimed at investigating the relation between AS and the oxidative metabolism of phagocytes in whole blood. <h3>METHODS</h3> 24 patients with classic AS were examined to determine their clinical status; complete blood count, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were determined, and levels of the superoxide anion radicals in the patients with AS and 21 healthy subjects were assessed by the ultraweak chemiluminescence method. Subsequently, the relation between this disease and phagocytes was examined by using<i>N</i>-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol-12-myristate-13-acetate (PMA) stimulants. <h3>RESULTS</h3> In clinical assessments, patients with AS had abnormally raised serum CRP (&gt;10 mg/l) and ESR (&gt;15 mm/1st h) levels. In contrast with healthy subjects, patients with AS had significantly increased rates of superoxide anion radical production in their whole blood either in the resting state or with either fMLP or PMA stimulation. In addition, chemiluminescence maximum light intensity was significantly higher in patients with AS than in healthy subjects after fMLP or PMA stimulation. <h3>CONCLUSIONS</h3> Our results suggest that the phagocytes of patients with AS are partly activated in the resting state, and are sensitive to fMLP or PMA stimulation. The priming of phagocytes in the bloodstream is likely to be a causative factor in the onset of AS.
IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells
Authors: JiChu Li, Gail Huston, Susan L. Swain
Journal: The Journal of Experimental Medicine (2003)

After transfer to adoptive hosts, in vitro–generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown. We find that low doses of interleukin (IL) 7 enhance survival of effectors in vitro without driving their division. When in vitro–generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype. CD4 effectors generated from wild-type versus IL-7 receptor−/− mice were transferred to adoptive hosts, including intact mice and those deficient in IL-7. In each case, the response to IL-7 was critical for good recovery of donor cells after 5–7 d. Recovery was also IL-7–dependent in Class II hosts where division was minimal. Blocking antibodies to IL-7 dramatically decreased short-term recovery of transferred effectors in vivo without affecting their division. These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.
HER-2/<i>neu</i> Analysis in Archival Tissue Samples of Human Breast Cancer: Comparison of Immunohistochemistry and Fluorescence In Situ Hybridization
Authors: Annette Lebeau, Daniela Deimling, Christine Kaltz, Andrea Sendelhofert, Anette Iff, Beate Luthardt, Michael Untch, Udo Löhrs
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany). RESULTS: HER-2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification. CONCLUSION: The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification.
Use the Duodenum, It’s Right There
Authors: J. Bart Rose, Phillip Bilderback, Tal Raphaeli, William Traverso, Scott Helton, John A. Ryan, Thomas Biehl
Journal: JAMA Surgery (2013)

This is the largest series to date comparing end-to-side biliary reconstruction for all indications performed using either the duodenum or jejunum and with at least 2-year follow-up.To demonstrate that duodenal anastomoses for biliary reconstruction are at least as safe and effective as Roux-en-Y jejunal anastomoses, with the benefits of operative simplicity and ease of postoperative endoscopic evaluation.Retrospective record review with telephone survey of patients undergoing nonpalliative biliary reconstruction in the hepatopancreatobiliary surgery division of a high-volume tertiary care facility.Biliary reconstruction via either end-to-side Roux-en-Y jejunal anastomosis or direct duodenal anastomosis.The primary end points were anastomosis-related complications (leak, cholangitis, bile gastritis, or stricture), and the secondary end points were overall complications, endoscopic or radiologic interventions, readmissions, and death.Ninety-six nonpalliative biliary reconstructions were performed between February 1, 2000, and November 23, 2011 for bile duct injury, cholangiocarcinoma, choledochal cysts, or benign strictures; the procedures included 59 duodenal reconstructions and 37 Roux-en-Y jejunal reconstructions. The groups were similar with regard to demographics, operative indications, postoperative length of stay, and mortality rates. However, anastomosis-related complications (leaks, cholangitis, or strictures) were fewer in the duodenal than the jejunal cohort (7 patients [12%] vs 13 [35%]; P = .009). Of patients with stricture, 5 of 9 in the jejunal cohort required percutaneous transhepatic access for management compared with only 1 of 2 in the duodenal cohort.Duodenal anastomosis is a safe, simple, and often preferable method for biliary reconstruction. This anastomosis can successfully be performed to all levels of the biliary tree with low rates of leak, stricture, cholangitis, and bile gastritis. When anastomotic complications do occur, there is less need for transhepatic intervention because of easier endoscopic access.
Multiple extra-medullary plasmacytomas of the skin
Authors: L. STANKLER, J. F. DAVIDSON
Journal: British Journal of Dermatology (1974)

Multiple plasma cell tumours of the skin may, on rare occasions, precede clinical, radiological and laboratory evidence of systemic myelomatosis. A man presented with several plasma cell tumours of the skin but with no detectable evidence of the disseminated myelomatosis to which he succumbed 16 months later. Multiple cutaneous extra‐medullary plasmacytomas should be regarded as a cutaneous expression of multiple myelomatosis.
Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence
Authors: Giulio Genovese, Anna K. Kähler, Robert E. Handsaker, Johan Lindberg, Samuel A. Rose, Samuel F. Bakhoum, Kimberly Chambert, Eran Mick, Benjamin M. Neale, Menachem Fromer, Shaun M. Purcell, Oscar Svantesson, Mikael Landén, Martin Höglund, Sören Lehmann, Stacey B. Gabriel, Jennifer L. Moran, Eric S. Lander, Patrick F. Sullivan, Pamela Sklar, Henrik Grönberg, Christina M. Hultman, Steven A. McCarroll
Journal: New England Journal of Medicine (2014)

Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent.
Creatine: Endogenous Metabolite, Dietary, and Therapeutic Supplement
Authors: John T. Brosnan, Margaret E. Brosnan
Journal: Annual Review of Nutrition (2007)

Creatine and phosphocreatine serve not only as an intracellular buffer for adenosine triphosphate, but also as an energy shuttle for the movement of high-energy phosphates from mitochondrial sites of production to cytoplasmic sites of utilization. The spontaneous loss of creatine and of phosphocreatine to creatinine requires that creatine be continuously replaced; this occurs by a combination of diet and endogenous synthesis. Vegetarians obtain almost no dietary creatine. Creatine synthesis makes major demands on the metabolism of glycine, arginine, and methionine. Large doses of creatine monohydrate are widely taken, particularly by athletes, as an ergogenic supplement; creatine supplements are also taken by patients suffering from gyrate atrophy, muscular dystrophy, and neurodegenerative diseases. Children with inborn errors of creatine synthesis or transport present with severe neurological symptoms and a profound depletion of brain creatine. It is evident that creatine plays a critical, though underappreciated, role in brain function.