tbuckley/cabot-search huggingface dataset:
Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway.
Authors: I Y Gluzman, S E Francis, A Oksman, C E Smith, K L Duffin, D E Goldberg
Journal: Journal of Clinical Investigation (1994)

The human malaria parasite, Plasmodium falciparum, de- grades nearly all its host cell hemoglobin during a short seg- ment of its intraerythrocytic development.This massive cata- bolic process occurs in an acidic organelle, the digestive vacu- ole.Aspartic and cysteine proteases have been implicated in this pathway.We have isolated three vacuolar proteases that account for most of the globin-degrading activity of the diges- tive vacuole.One is the previously described aspartic hemoglo- binase that initiates hemoglobin degradation.A second aspartic protease is capable of cleaving hemoglobin with an overlapping specificity, but seems to prefer acid-denatured globin.The third is a cysteine protease that does not recognize native hemoglobin but readily cleaves denatured globin.It is synergistic with the aspartic hemoglobinase, both by in vitro assay of hemoglobin degradation, and by isobologram analysis of protease inhibitor-treated parasites in culture.The cysteine protease is highly sensitive to chloroquine-heme complex, suggesting a possible mechanism of 4-aminoquinoline antimalarial action.The data suggest an ordered pathway of hemoglobin catabolism that presents an excellent target for chemotherapy. (
Evasion of inflammasome activation by microbial pathogens
Authors: Tyler K. Ulland, Polly J. Ferguson, Fayyaz S. Sutterwala
Journal: Journal of Clinical Investigation (2015)

Activation of the inflammasome occurs in response to infection with a wide array of pathogenic microbes. The inflammasome serves as a platform to activate caspase-1, which results in the subsequent processing and secretion of the proinflammatory cytokines IL-1β and IL-18 and the initiation of an inflammatory cell death pathway termed pyroptosis. Effective inflammasome activation is essential in controlling pathogen replication as well as initiating adaptive immune responses against the offending pathogens. However, a number of pathogens have developed strategies to evade inflammasome activation. In this Review, we discuss these pathogen evasion strategies as well as the potential infectious complications of therapeutic blockade of IL-1 pathways.
The short life of a terminal care support team
Authors: A. Herxheimer, R. Begent, I. Walton
Journal: BMJ (1985)

should not deter other groups who want to see such a team established in their own area.It does make the point, however, that support teams need to be set up with great care, with adequate funding and proper commitment, if they are to be successful.There needs to be a single consultant in charge, with at least one other doctor and, wherever possible, a full time social worker plus at least two nursing sisters.We believe that the appointment of a single unsupported nurse, instead of a properly funded team, will inevitably prove a recipe for disaster.
Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study
Authors: Rakesh Amin, Barry Widmer, A Toby Prevost, Phillip Schwarze, Jason Cooper, Julie Edge, Loredana Marcovecchio, Andrew Neil, R Neil Dalton, David B Dunger
Journal: BMJ (2008)

<b>Objectives</b> To describe independent predictors for the development of microalbuminuria and progression to macroalbuminuria in those with childhood onset type 1 diabetes. <b>Design</b> Prospective observational study with follow-up for 9.8 (SD 3.8) years. <b>Setting</b> Oxford regional prospective study. <b>Participants</b> 527 participants with a diagnosis of type 1 diabetes at mean age 8.8 (SD 4.0) years. <b>Main outcome measures</b> Annual measurement of glycated haemoglobin (HbA<sub>1c</sub>) and assessment of urinary albumin:creatinine ratio. <b>Results</b> Cumulative prevalence of microalbuminuria was 25.7% (95% confidence interval 21.3% to 30.1%) after 10 years of diabetes and 50.7% (40.5% to 60.9%) after 19 years of diabetes and 5182 patient years of follow-up. The only modifiable adjusted predictor for microalbuminuria was high HbA<sub>1c</sub> concentrations (hazard ratio per 1% rise in HbA<sub>1c</sub> 1.39, 1.27 to 1.52). Blood pressure and history of smoking were not predictors. Microalbuminuria was persistent in 48% of patients. Cumulative prevalence of progression from microalbuminuria to macroalbuminuria was 13.9% (12.9% to 14.9%); progression occurred at a mean age of 18.5 (5.8) years. Although the sample size was small, modifiable predictors of macroalbuminuria were higher HbA<sub>1c</sub> levels and both persistent and intermittent microalbuminuria (hazard ratios 1.42 (1.22 to 1.78), 27.72 (7.99 to 96.12), and 8.76 (2.44 to 31.44), respectively). <b>Conclusion</b> In childhood onset type 1 diabetes, the only modifiable predictors were poor glycaemic control for the development of microalbuminuria and poor control and microalbuminuria (both persistent and intermittent) for progression to macroalbuminuria. Risk for macroalbuminuria is similar to that observed in cohorts with adult onset disease but as it occurs in young adult life early intervention in normotensive adolescents might be needed to improve prognosis.
60 SILEN-C1: SUSTAINED VIROLOGIC RESPONSE (SVR) AND SAFETY OF BI201335 COMBINED WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN (P/R) IN TREATMENT-NAIVE PATIENTS WITH CHRONIC GENOTYPE 1 HCV INFECTION
Authors: M.S. Sulkowski, E. Ceasu, T. Asselah, F.A. Caruntu, J. Lalezari, P. Ferenci, A. Streinu-Cercel, H. Fainboim, H. Tanno, L. Preotescu, B. Leggett, F. Bessone, S. Mauss, J.O. Stern, C. Häfner, Y. Datsenko, G. Nehmiz, W. Böcher, G. Steinmann
Journal: Journal of Hepatology (2011)
Prevalence of preclinical and clinical heart failure in the elderly. A population‐based study in Central Italy
Authors: Gian Francesco Mureddu, Nera Agabiti, Vittoria Rizzello, Francesco Forastiere, Roberto Latini, Giulia Cesaroni, Serge Masson, Giuseppe Cacciatore, Furio Colivicchi, Massimo Uguccioni, Carlo Alberto Perucci, Alessandro Boccanelli
Journal: European Journal of Heart Failure (2012)
Fitness, unfitness, and phosphate.
Authors: G Dale, J A Fleetwood, A Weddell, R D Ellis, J R Sainsbury
Journal: BMJ (1987)

The occurrence of chronic lymphocytic leukaemia in this patient contemporaneous with his antibody positivity may be coincidental, but it also raised the possibility of various causal associations.There is evidence that other retroviruses that infect T cells can also integrate into and transform B cells in a clonal fashion.4Furthermore, B lymphoblastoid cell lines transformed by Epstein-Barr virus have been shown to be permissive to HIV infection.5Our use of the anti-HIV serum detected no viral antigens in the neoplastic B cells.Such evidence cannot, however, exclude the possibility of non-transcribed genomic integration of the virus in the cellular DNA.Such analysis will require the use of viral recombinant cDNA genotyping of the leukaemia B cells.We thank the Grampian Health Board for financial support, Dr Margaret Moffat, departnent ofbacteriology (virology), for viral antibody assays, and Miss Ann Mackay for typing the manuscript.
Postoperative exercise response in the evaluation of the physiologic status after coronary bypass surgery.
Authors: S H Rahimtoola
Journal: Circulation (1982)

Many studies have demonstrated that coronary artery bypass surgery combined with medical therapy produces a greater degree of improvement in the symptomatic state and in the functional class of the patients with severe coronary artery disease than does medical therapy alone. This can be objectively documented by an improvement in the exercise capacity and by an increase in heart rate and blood pressure attained at the higher level of exercise. The improvement is the result of relief of exercise-induced (and resting) myocardial ischemia documented by increases in heart rate and blood pressure, greater lactate extraction across the myocardium, improvement in left ventricular dysfunction, abolition of exertional hypotension, and by reversal of exercise-induced and of resting thallium-201 defects. Results of coronary bypass surgery performed during 1974-1979 are better than those during 1969-1973.
Fatal Infection with Influenza A (H5N1) Virus in China
Authors: Qing-Yu Zhu, None E-De Qin, Wei Wang, Jun Yu, Bo-Hua Liu, Yi Hu, Jian-Fei Hu, Wu-Chun Cao
Journal: New England Journal of Medicine (2006)

To the Editor: A 24-year-old man had pneumonia and respiratory distress in November 2003 and died four days after being hospitalized. Because the clinical manifestations were consistent with those ...
Trimethoprim-Sulfamethoxazole for Meningitis
Authors: JOHN A. ROBINSON
Journal: Annals of Internal Medicine (1976)

Comments and Correction1 May 1976Trimethoprim-Sulfamethoxazole for MeningitisJOHN A. ROBINSON, M.D.JOHN A. ROBINSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-5-613_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: On reason that there is an increasing frequency of collisions between ethicists and physicians might be illustrated by the letter from Farid and associates (1), who used trimethoprim-sulfamethoxazole for the treatment of pneumococcal and meningococcal meningitis. Since the overwhelmingly proved drug of choice for either disease is penicillin G, and since meningitis is not an innocuous disease, one wonders whether any semblance of informed consent was obtained from relatives ("three patients were drowsy and two were unconscious"). Since the authors state that the patients had not responded to "routine therapy," either they are reporting five cases of...Reference References1. FARIDGIRGISYASSIN ZNW: Trimethoprim-sulfamethoxazole and bacterial meningitis. Ann Intern Med 84:50-51, 1976 LinkGoogle Scholar1. HASSANABDEL WAHABFARID AMZ: Acute pyogenic meningitis in Cairo, Egypt 1961-1966. J Trop Med Hyg 74:141-144, 1971 MedlineGoogle Scholar2. LAFAIX C: Proceedings of the 7th International Congress of Chemotherapy. Prague, 1 1227, 1971 Google Scholar3. SABELBRANDBERG KA: Treatment of meningitis and septicemia in infancy with a sulphamethoxazole/trimethoprim combination. Acta Paediatr Scand 64:25-32, 1975 CrossrefMedlineGoogle Scholar4. GREENETHOMASALFORD BPR: Trimethoprim-sulfamethoxazole and brain abscess. Ann Intern Med 82:812-813, 1975 LinkGoogle Scholar5. INGELFINGER F: The unethical in medical ethics. Ann Intern Med 83:264-269, 1975 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Clinical Immunology Section Department of Medicine Loyola University-Foster G. McGaw Hospital Maywood, IL 60153 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1976Volume 84, Issue 5Page: 613-614KeywordsDrugsMeningitisPenicillin Issue Published: 1 May 1976 PDF DownloadLoading ...
Reports cite cardiovascular risks of COX 2 inhibitors and NSAIDs
Authors: Janice Hopkins Tanne
Journal: BMJ (2006)

Cyclo-oxygenase-2 (COX 2) inhibitors and some other non-steroidal anti-inflammatory drugs (NSAIDs) may present cardiovascular and renal risks, say two papers published online ahead of print publication in JAMA .

And an accompanying editorial by David Graham, a Food and Drug Administration employee and whistleblower, criticises studies of COX …
“Roadmap” Aids Malaria Vaccine Efforts
Authors: Bridget M. Kuehn
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Project to decode genomes in cancer samples promises new treatments
Authors: A. Gulland
Journal: BMJ (2010)

Scientists from across the globe have launched a collaboration to decode the genomes from 25 000 samples of cancer cells, which will then be made freely available to researchers, it was announced last week.

Organisations in 10 countries, including Australia, Canada, China, India, Japan, and the United States, and two European consortiums are conducting cancer genome projects under the umbrella of the International Cancer Genome Consortium. The consortium describes the latest venture as “one of the most ambitious biomedical research efforts since the human genome project.”

The consortium, which is open to new members, will help to coordinate current and future large scale projects to understand the genomic changes in cancer, once thought of …
CLONAL CHARACTER OF F1 HYBRID LYMPHOCYTE SUBSET RECOGNITION OF PARENTAL CELLS IN ONE-WAY MIXED LYMPHOCYTE CULTURES
Authors: Bryan M. Gebhardt, Yoshinobu Nakao, Richard T. Smith
Journal: The Journal of Experimental Medicine (1974)

Proliferation of F(1) hybrid lymphocytes in mixed lymphocyte cultures is stimulated by mitomycin-blocked parental cells. The demonstration of this phenomenon using F(1) hybrids derived from congenic lines of mice establishes that the stimulation is controlled by genes in or closely linked to the major histocompatibility locus chromosome region. In agreement with the finding that tumor-bearing mice have an increased capacity for primary alloantigen recognition, it was observed that the F(1) hybrid response to parent was also augmented by tumor bearing. Chromosomal analysis of dividing cells in one-way mixed cultures confirms that F(1) cells, and not the blocked parental cells, enter mitosis. Stimulation of F(1) cells by a soluble mediator liberated by the parental cells was not observed and mitomycin blocking of parental cells seems to be a completely effective blocking agent ensuring that parental cells can not enter DNA synthesis. The specificity and clonal nature of F(1) recognition of parent was demonstrated using a 5-bromodeoxyuridine-suicide procedure. Distinct clones of lymphocytes in F(1) spleen cell populations seem to recognize one or the other parent, but not both, in such experiments. These observations and others in tumor systems suggest that most or all heterozygous organisms may possess potentially self-reactive clones of lymphocytes.
Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study
Authors: Giancarlo Agnelli, Gualberto Gussoni, Carlo Bianchini, Melina Verso, Mario Mandalà, Luigi Cavanna, Sandro Barni, Roberto Labianca, Franco Buzzi, Giovanni Scambia, Rodolfo Passalacqua, Sergio Ricci, Giampietro Gasparini, Vito Lorusso, Erminio Bonizzoni, Maurizio Tonato
Journal: The Lancet Oncology (2009)
Placental transmission of thyroid-stimulating immunoglobulins.
Authors: S M Dirmikis, D S Munro
Journal: BMJ (1975)

Long-acting thyroid stimulator (LATS) and LATS protector (LATS-P) were assayed at or near delivery in serum from 18 pregnant women with a history of past or present thyrotoxicosis. The results suggested that neonatal thyrotoxicosis may be predicted prenatally if maternal serum LATS and LATS-P concentrations near delivery are above certain levels.
Statin Use May Stop When Illness Is Terminal, Study Says
Authors: Rebecca Voelker
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A large case-control study on the predictability of hepatitis B surface antigen levels three years before hepatitis B surface antigen seroclearance
Authors: Wai-Kay Seto, Danny Ka-Ho Wong, James Fung, Ivan Fan-Ngai Hung, Daniel Yee-Tak Fong, John Chi-Hang Yuen, Teresa Tong, Ching-Lung Lai, Man-Fung Yuen
Journal: Hepatology (2012)

The kinetics of hepatitis B surface antigen (HBsAg) levels preceding spontaneous HBsAg seroclearance has not been fully investigated. The kinetics of HBsAg and hepatitis B virus (HBV) DNA of 203 treatment-naïve, hepatitis B e antigen (HBeAg)-negative patients with spontaneous HBsAg seroclearance were compared with 203 age- and sex-matched HBeAg-negative controls. Serum samples at 3 years, 2 years, 1 year, and 6 months before HBsAg seroclearance and at the time of HBsAg loss were tested. Median HBsAg levels at these respective time points before HBsAg seroclearance were 23.5, 3.51, 0.524, and 0.146 IU/mL. For all time points, patients with HBsAg seroclearance had significantly lower median HBsAg and HBV DNA levels, compared to those of the controls (all P < 0.001). Median HBsAg and HBV DNA levels declined significantly until HBsAg seroclearance (P < 0.001). Although median HBsAg levels also decreased significantly with time (P = 0.006) in controls, median HBV DNA levels remained similar (P = 0.414). Serum HBsAg levels, followed by HBsAg log reduction, were the best predictors of HBsAg seroclearance, with an area under the receiving operator characteristic (AUROC) of 0.833 (95% confidence interval [CI]: 0.792-0.873) and 0.803 (95% CI: 0.755-0.849), respectively. The optimal cut-off HBsAg level and HBsAg reduction to predict HBsAg seroclearance were <200 IU/mL (sensitivity, 84.2%; specificity, 73.4%) and 0.5 log IU/mL/year (sensitivity, 62.8%; specificity, 88.7%), respectively. For patients with HBsAg levels ≥ 200 IU/mL, an annual 0.5-log reduction was highly predictive of subsequent HBsAg seroclearance (AUROC, 0.867; 95% CI: 0.778-0.956). To conclude, serum HBsAg <200 IU/mL and 0.5-log reduction in HBsAg were predictive of HBsAg seroclearance within 3 years of follow-up. These parameters may serve as good indicators for the consideration of treatment duration and cessation for chronic hepatitis B.
Atrioventricular Junctional Premature and Escape Beats with Altered QRS and Fusion
Authors: ALBERT D. KISTIN
Journal: Circulation (1966)

The interval between an ectopic QRS and a retrograde P wave measured in simultaneous esophageal and other leads may help to identify beats which originate in the atrio-ventricular (A-V) junction. In six cases beats which seem to originate in the A-V junction are associated with a QRS which differs in configuration from the QRS of sinus origin, and in each case atrial premature systoles which give rise to normal QRS complexes occur in tracings which contain the A-V junctional beats also. Comparison of the QRS of the atrial premature systoles with the QRS of the A-V junctional beats with respect to the time of occurrence in the cardiac cycle and the duration of the preceding cycle makes it seem unlikely that the altered QRS of the A-V junctional beats can be explained by aberrant conduction during incomplete recovery. In five of the cases, fusion QRS complexes occur, suggesting activation of the ventricles partly by an impulse of sinus origin and partly by the impulse of A-V junctional origin. These observations support the interpretation previously made by others that impulses of A-V junctional origin may reach the ventricles by pathways other than the usual A-V pathway. If such beats as are described here occur at all frequently, then the diagnostic value of fusion, heretofore considered an almost conclusive criterion of a ventricular focus, may be impaired.
In vitro effect of plasmin on human platelet function in plasma. Inhibition of aggregation caused by fibrinogenolysis.
Authors: I Gouin, T Lecompte, M C Morel, J Lebrazi, P W Modderman, C Kaplan, M M Samama
Journal: Circulation (1992)

Plasmin has been reported both to activate platelets and to inhibit platelet functions. The latter effect was thought to be caused by proteolysis of the main membrane glycoproteins.We found that incubation of citrated human platelet-rich plasma with streptokinase (SK) (300 IU/ml) does not produce any detectable activation but leads to a time-dependent inhibition of ADP-induced aggregation accompanied by substantial fibrinogenolysis. These effects were abrogated by previous addition of a plasmin inhibitor, aprotinin. Crossover experiments (SK-treated or control platelets mixed with SK-treated or control plasma) demonstrated that the platelets remained functional and that the aggregation defect was caused by fibrinogenolysis. Further experiments (addition of purified fibrinogen to fibrinogen-depleted plasma with either SK or thrombin) suggested that in addition to the low residual level of fibrinogen, fibrinogen degradation products had an inhibitory effect. Under the same conditions, tissue-type plasminogen activator (t-PA) (3,000 ng/ml) had no effect on platelet aggregation, and plasma fibrinogen was not significantly lowered. The effects on glycoproteins IIb-IIIa of incubation with SK, t-PA, or plasmin were assessed with immunoblots with murine monoclonal antibodies directed against either part of the complex, which is the receptor for fibrinogen. Proteolysis was detected only in the presence of EDTA, a potent chelator of divalent cations.The incubation of human platelets in citrated plasma with SK concentrations obtained during therapy leads to an aggregation defect that is related to the decrease in fibrinogen, the adhesive protein involved in this function, and to the impeding effect of fibrinogen degradation products on its binding onto platelets but not to an alteration of the corresponding platelet receptor, the heterodimer glycoproteins IIb-IIIa.