tbuckley/cabot-search huggingface dataset:
Vaccines against gut pathogens
Authors: P MASTROENI, F BOWE, R CAHILL, C SIMMONS, G DOUGAN
Journal: Gut (1999)

Many infectious agents enter the body using the oral route and are able to establish infections in or through the gut. For protection against most pathogens we rely on immunity to prevent or limit infection. The expression of protective immunity in the gut is normally dependent both on local (mucosal) and systemic mechanisms. In order to obtain full protection against some pathogens, particularly non-invasive micro-organisms such as Vibrio cholerae, mucosal immunity may be particularly important. There is a need to take these factors into account when designing vaccines targeting gut pathogens. Conventional parenteral vaccines (injected vaccines) can induce a degree of systemic immunity but are generally poor stimulators of mucosal responses. Thus, a basic prerequisite for designing novel vaccines against gut associated pathogens may be the requirement to induce mucosal and potentially systemic immunity.1 The most effective way to induce local immunity against infectious agents has so far proved to be direct application of vaccine antigens to mucosal surfaces (oral or intranasal delivery).2 The fact that we have so few effective oral vaccines shows that the induction of protective immunity through oral immunisation is not an easy goal to achieve as many antigens are poor oral immunogens. Here we will focus, using bacterial pathogens as examples, on some recent approaches being used to generate novel oral vaccines.

Oral vaccines can be based on either live or non-living antigens. The generation of modern live oral vaccines involves the construction of genetically defined attenuated micro-organisms capable of inducing immunity in a non-harmful way. The recent improved understanding of bacterial virulence associated gene function offers the possibility of introducing multiple, defined, attenuating and stable mutations into the genome of bacterial pathogens. Furthermore, the use of precisely attenuated bacterial vectors as carriers for recombinant heterologous antigens can lead to the generation of …
Microvascular effects of atrial natriuretic factor: interaction with alpha 1- and alpha 2-adrenoceptors.
Authors: J E Faber, D R Gettes, D P Gianturco
Journal: Circulation Research (1988)

The cremaster skeletal muscle of anesthetized rats was denervated and extended with intact circulation into a tissue bath. Intravital microscopy was used to measure microvessel diameter at three different anatomical levels within the microcirculation: large distributing arterioles (x control diameter = 100 +/- 7 micron), large capacitance venules (147 +/- 8 micron), and small terminal arterioles (17 +/- 1 micron). Norepinephrine (NE) was added to the cremaster bath to produce intermediate reductions in diameter of large arterioles and venules (55% and 38% of maximum constriction, respectively). In the presence of NE tone, bath-added atrial natriuretic factor (ANF) produced concentration-dependent dilation of both arterioles and venules. Arteriolar IC25 = 18 pmol and IC50 = 1.2 X 10(-10) M; venules exhibited similar sensitivity. However, the highest ANF concentration examined (10(-7) M) only reversed NE-induced tone by 70%. In a second large vessel group ANF completely reversed constriction induced by the alpha 1-adrenoceptor agonist, phenylephrine, in the presence of 5 X 10(-7) M yohimbine. However, vessels constricted with the alpha 2-receptor agonist UK-14,304 (in the presence of 10(-8) M prazosin) were insensitive to ANF. A third group of terminal arterioles, which possess considerable spontaneous "intrinsic" tone, were studied in the absence of alpha-receptor agonists. Significant dilation occurred at greater than 10(-7) M, and the maximal response was only 25% of complete dilation with adenosine. These data indicate that ANF exhibits a high potency and selectivity for reversal of alpha 1-adrenoceptor-mediated constriction of large arterioles and venules. Constriction produced by alpha 2-adrenoceptor occupation or by nonadrenergic "intrinsic" mechanisms appears to be insensitive to ANF. We propose that the ability of ANF to reduce microvascular resistance depends on the relative contribution of alpha 1-, alpha 2-, and intrinsic vasoconstrictor components to the prevailing level of smooth muscle tone. Differences in these components among regional circulations and between arterial and venous smooth muscle may contribute to the systemic hemodynamic pattern produced by ANF.
Systemic Lupus Erythematosus Developing in Patients with Primary Biliary Cirrhosis
Authors: STEPHEN HALL
Journal: Annals of Internal Medicine (1984)

Three patients with biopsy-proven primary biliary cirrhosis subsequently developed a multisystem disorder and serologic abnormalities consistent with systemic lupus erythematosus. In one patient, antimitochondrial antibody titers fell to undetectable levels after the development of the extrahepatic manifestations. No patient had been exposed to D-penicillamine or other drugs capable of inducing a lupus-like condition. These patients further emphasize the difficulties in disease classification and underline the systemic nature of chronic liver diseases such as primary biliary cirrhosis.
Antiarrhythmic Effects of Acute Hyperkalemia through Altered Intraventricular Conduction.
Authors: Philip O. Ettinger
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Antiarrhythmic Effects of Acute Hyperkalemia through Altered Intraventricular Conduction.Philip O. Ettinger, M.D., F.A.C.P., Henry A. Oldewurtel, Timothy J. Regan, M.D.Philip O. Ettinger, M.D., F.A.C.P.Search for more papers by this author, Henry A. OldewurtelSearch for more papers by this author, Timothy J. Regan, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-863_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPotassium has been used as an antiarrhythmic agent, but its value has been thought to be limited by its prolongation of intraventricular conduction. To investigate the effects of hyperkalemia on the ventricular specialized conduction system, isotonic potassium chloride was infused into intact anesthetized dogs. Fluoroscopically placed electrode catheters recorded His bundle and left anterior false-tendon electrograms simultaneously with the peripheral electrocardiogram. Arterial and coronary sinus potassium (K+) were sequentially monitored. Delays in all segments of conduction pathways (His-false tendon, false tendon-Q, QRS) were progressive and related directly to potassium increments. False tendon-Q and QRS segments were more affected by increasing... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Newark, N.J. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 863-863KeywordsCathetersElectrocardiographyElectrode recordingElectrophysiological techniquesIsotonicityPotassiumPotassium chlorideTendons Issue Published: 1 May 1972 PDF DownloadLoading ...
Phospholamban-mediated stimulation of Ca2+ uptake in sarcoplasmic reticulum from normal and failing hearts.
Authors: M A Movsesian, J Colyer, J H Wang, J Krall
Journal: Journal of Clinical Investigation (1990)

Studies in animal models have suggested that alterations affecting phospholamban-mediated stimulation of Ca2+ uptake by sarcoplasmic reticulum are involved in the pathophysiology of heart disease. A monoclonal antibody that binds to phospholamban and stimulates Ca2+ uptake was used to characterize phospholamban-mediated effects in human cardiac sarcoplasmic reticulum and to compare these effects in tissue from normal and failing hearts. Stimulation of Ca2+ uptake by anti-phospholamban monoclonal antibody simulated the effect of phosphorylation of phospholamban by cAMP-dependent protein kinase. Binding of anti-phospholamban antibody reduced the K0.5 of the Ca2(+)-transporting ATPase from 0.53 microM [( Ca2+]) to 0.29 microM [( Ca2+]), without affecting Vmax or nHill. At 0.2 microM Ca2+, stimulation was 1.93-fold in sarcoplasmic reticulum prepared from normal human left ventricular myocardium and 1.94-fold in sarcoplasmic reticulum prepared from the left ventricular myocardium of patients with heart failure resulting from idiopathic dilated cardiomyopathy. Stimulation of Ca2+ uptake in canine cardiac sarcoplasmic reticulum under identical conditions was 1.89-fold. Phospholamban-mediated stimulation of Ca2+ uptake in human cardiac sarcoplasmic reticulum is thus comparable in magnitude to that observed in other species and results from an increase in the apparent affinity of the Ca2(+)-transporting ATPase for Ca2+. The pathogenesis of heart failure in idiopathic dilated cardiomyopathy does not, however, appear to involve intrinsic alterations of this mechanism.
Physician-Patient Communication
Authors: Patricia C. Franco
Journal: JAMA (1981)

<h3>To the Editor.—</h3> "Therapeutic Talk" by John P. Callan, MD (1980;244:2202), sorely missed defining true communication, which has two distinct components: listening and responding, not merely talking to a patient. As a hospital-based oncology counselor, a major part of my role is to facilitate communication between the physician and his patient. From the time of diagnosis through rehabilitation or death, the physician and others on the treatment team who are truly able to communicate with the patient and his family enhance the treatment process immeasurably. The physician who is able to "hear" the spoken and unspoken fears regarding a disease as threatening as cancer and to respond in a realistic, yet supportive manner may at times be offering the most potent tool in his medicine chest. He is not the physician who takes a defensive posture, who distances himself from the patient to "retain his effectiveness," who does not
Europe launches 12 point plan to tackle antimicrobial resistance
Authors: R. Watson
Journal: BMJ (2011)

The European Commission presented its first action plan to tackle antimicrobial resistance to drugs on 17 November, as new research that was based on Europe-wide surveillance data confirmed that carbapenem resistant Klebsiella pneumoniae is on the rise.

Announcing the initiative, the health and consumer policy commissioner, John Dalli, said, “We need to take swift and determined action if we do not want to lose antimicrobial medicines as essential treatment against bacterial infections in both humans and animals.”

He emphasised the scale of the problem by pointing out that some 25 000 patients die each year in the …
POIKILODERMA-LIKE CHANGES ON THE SKIN FOLLOWING ARSPHENAMINE DERMATITIS
Authors: Joseph M. Shelton
Journal: JAMA (1942)

<h3>To the Editor:—</h3> I was interested to note in the article "Poikiloderma-like Changes in the Skin Following Arsphenamine Dermatitis," by Dr. A. Benson Cannon and his associates, appearing in the January 10 issue ofThe Journal, that the possibility of Jacobi's original case of poikiloderma atrophicans vasculare having been due to previously administered arsphenamine was mentioned. On page 128 in the middle of the first paragraph the authors state: "One wonders whether if Jacobi had examined his patient for arsenic or if he had followed him over a long period he too might not have been able to classify the condition as being due to a postarsphenamine dermatitis. This is a surprising statement in view of the fact that Jacobi's case was presented in 1906 and that arsphenamine (salvarsan) was not announced by Ehrlich until 1910. Of course the arsenic could have been introduced in some other form, but the
Cardiac Enlargement in Chronic Severe Anemia
Authors: L. M. SANGHVI, S. N. MISRA, K. BANERJEE
Journal: Circulation (1960)

One hundred and fifty patients with chronic severe anemia were studied to determine the nature of cardiac enlargement and its relation to various factors. Enlargement was present in 120 patients. It showed no consistent relation to the hemoglobin level on admission. A significant increase in the cardiac size and incidence of failure was observed with increased severity of anemia, and in female as compared to male patients. The incidence of enlargement showed no relation to the age and sex of the patient and the duration or the etiologic factor of anemia. With correction of the anemia, enlargement disappeared rapidly in 92 patients, indicating that it was due to dilatation alone. Some enlargement persisted in 28 patients, and it is believed to be associated with cardiac hypertrophy. Pericardial effusion due to heart failure in 2 patients contributed to a small extent to the enlargement of the cardiac shadow.
Visual Loss in Pregnant Women with Pituitary Adenomas
Authors: Mark J. Kupersmith
Journal: Annals of Internal Medicine (1994)

Objective: To investigate the potential risk for developing visual loss during single or multiple pregnancies in women with pituitary adenomas. Design: Cohort study. Setting: Referral center of a neuro-ophthalmology service. Patients: 65 consecutive women with pituitary adenomas who had not been previously treated with surgery or radiation were monitored during 111 pregnancies. Sixty had increased levels of serum prolactin or growth hormone and 5 did not. Main Outcome Measures: Visual field or acuity loss was compared with the baseline size of the adenoma measured on the coronal view of the computed tomographic or magnetic resonance image. Results: Computed tomography or magnetic resonance imaging showed a definitive tumor (>0.3 cm, vertical height) in 57 patients, 8 of whom had macroadenomas (≥ 1.1 cm). Visual field loss occurred in 6 of 8 primiparous patients, all with adenomas greater than 1.1 cm (range, 1.2 to 2.5 cm). None of the 57 patients (95% CI, 0% to 6.3%) with a microadenoma or presumed microadenoma of 1 cm or smaller developed visual loss after as many as four full-term pregnancies. Conclusions: The risk for developing visual loss during single or multiple pregnancies in patients with microadenomas was small. Six of eight pregnant women with macroadenomas, however, developed visual field loss during pregnancy.
Effect of hypertrophy induced by pressure overload or volume overload on reperfusion induced arrhythmias in anaesthetised rats
Authors: E. Robertson, R. P Hof, W. Zierhut
Journal: Cardiovascular Research (1993)

The aim was to determine the effect of myocardial hypertrophy on the incidence and severity of arrhythmias following reperfusion after experimental coronary artery occlusion, and to establish if the effect differed between pressure overload hypertrophy and volume overload hypertrophy.The experiments were performed in rats. Pressure overload hypertrophy was induced by aortic banding, and volume overload hypertrophy by perforation of the aortic valve. Four weeks after surgery, coronary artery occlusion and reperfusion experiments were performed.Both pressure and volume overloaded hearts exhibited a similar degree of left ventricular hypertrophy of about 45% weight gain compared to control animals. The total number of ventricular premature beats during reperfusion was not significantly increased in either model of hypertrophy. In contrast to volume overload, the incidence of reperfusion induced ventricular fibrillation was significantly increased in pressure overloaded hearts. Furthermore, there was a significant correlation between number of ventricular premature beats and degree of left ventricular hypertrophy, as well as between duration of ventricular tachycardia and degree of hypertrophy in the pressure overloaded group. Such correlations were not observed in hypertrophy due to volume overload. Neither volume nor pressure overload hypertrophy significantly increased mortality from ventricular fibrillation.An increase in cardiac mass per se does not necessarily aggravate reperfusion arrhythmias. The susceptibility to arrhythmias in this model seems to be critically dependent on the nature of the stimulus triggering left ventricular hypertrophy.
The mutant eisai hyperbilirubinemic rat is resistant to bile acid–induced cholestasis and cytotoxicity
Authors: Makoto Hoshino, Tomihiro Hayakawa, Asamitsu Hirano, Yasutaka Kamiya, Takayuki Ohiwa, Akitaka Tanaka, Tomoyuki Kumai, Takanori Inagaki, Makoto Miyaji, Toshihiko Takeuchi
Journal: Hepatology (1994)

We investigated bile flow and biliary excretion of bile acids in the Eisai hyperbilirubinemic rat, a Sprague–Dawley mutant rat with conjugated hyperbilirubinemia, using both in vivo and in vitro models. In vivo bile flow was lower in Eisai hyperbilirubinemic rats than in the control rats before and after taurocholate was infused. After taurocholate was infused, bile acid output was similar in the Eisai hyperbilirubinemic rats and control rats. In the isolated perfused rat liver, biliary excretion of bile acids was higher in the Eisai hyperbilirubinemic rats than in the control rats after a high–dose infusion of taurocholate (0.33 μmol/min/gm liver). Infusion of taurochenodeoxycholate (0.22 μmol/min/gm liver) did not produce cholestasis and did not reduce the biliary excretion of bile acids in the Eisai hyperbilirubinemic rats. Taurochenodeoxycholate significantly increased the phospholipid/bile acid molar ratio and slightly reduced bile acid-induced alkaline phosphatase output into bile. The release of lactate dehydrogenase from the perfused liver 30 min after the start of the taurochenodeoxycholate infusion was 10 times lower in the Eisai hyperbilirubinemic rats than in the control rats (2.0 ± O.8 vs. 28.7 ± 6.8 mU/min/gm liver). When the isolated perfused rat liver was infused with a 1–min pulse of horseradish peroxidase (25 mg), we observed an early and late peak of biliary excretion of horseradish peroxidase. The Eisai hyperbilirubinemic rats showed a significant increase in the late peak. Although taurochenodeoxycholate produced dose–dependent increases in lactate dehydrogenase levels in the medium at 3 hr in primary cultured hepatocytes from both strains, the increase was significantly smaller in the Eisai hyperbilirubinemic rat. The intracellular content of taurochenodeoxycholate in the Eisai hyperbilirubinemic rat was 11.7 ± 1.5 nmol/mg protein, half that seen in the control rats. These findings indicate that the Eisai hyperbilirubinemic rat is resistant to bile acid-induced cholestasis and liver injury and that this resistance may be related, in part, to a reduction in the intracellular accumulation of bile acids. This phenomenon might be explained by an increased intrahepatic microtubule–dependent vesicle transport of bile acids in the mutant rats. (Hepatology 1994;20:932-939).
Priming with synthetic oligonucleotides attenuates pressure overload-induced inflammation and cardiac hypertrophy in mice
Authors: Markus Velten, Georg D. Duerr, Thilo Pessies, Julia Schild, Ralph Lohner, Jan Mersmann, Oliver Dewald, Kai Zacharowski, Sven Klaschik, Tobias Hilbert, Andreas Hoeft, Georg Baumgarten, Rainer Meyer, Olaf Boehm, Pascal Knuefermann
Journal: Cardiovascular Research (2012)

Inflammation and Toll-like receptor (TLR) signalling have been linked to the development of cardiac hypertrophy following transverse aortic constriction (TAC). In the present study, we investigated whether pre-treatment with the synthetic TLR9 ligands 1668-thioate or 1612-thioate modulates the progression of TAC-induced cardiac inflammation and hypertrophy.C57BL/6N-mice were pre-treated with 1668-thioate, 1612-thioate (0.25 nmol/g, i.p.), or phosphate-buffered saline 16 h prior to TAC or sham surgery. Heart-weight/body-weight ratio (HW/BW), cardiomyocyte cell size, cellular macrophage accumulation, myofibroblast differentiation, and collagen deposition were investigated for up to 28 days. Cardiac function was monitored using a pressure-volume catheter and M-mode echocardiography. Inflammatory gene expression in the heart was analysed via gene array, while the time course of mRNA expression of key inflammatory mediators was assessed via RT-qPCR. TAC increased the HW/BW ratio and cardiomyocyte cell size and induced macrophage accumulation, myofibroblast differentiation, and collagen deposition. These changes were accompanied by cardiac inflammation and a significant loss of left ventricular function. Pre-treatment with cytosine-phosphate-guanine (CpG)-containing 1668-thioate attenuated the inflammatory response, the progression of cardiac hypertrophy, and cardiac remodelling, which resulted in a prolonged preservation of left ventricular function. These changes were induced to a smaller extent by the use of the non-CG-containing oligodeoxynucleotide 1612-thioate.Pre-treatment with 1668-thioate attenuated cardiac hypertrophy following pressure overload, possibly by modifying the hypertrophy-induced inflammatory response, thereby reducing cardiac growth and fibrosis as well as delaying loss of cardiac function.
The angiogenesis induced by HIV–1 Tat protein is mediated by the Flk–1/KDR receptor on vascular endothelial cells
Authors: Adriana Albini, Raffaella Soldi, Daniela Giunciuclio, Enrico Giraudo, Roberto Benelli, Luca Primo, Douglas Noonan, Mariolina Salio, Giovanni Camussi, Wolfang Rock, Federico Bussolino
Journal: Nature Medicine (1996)
Beta-adrenergic receptor number and adenylate cyclase function in denervated transplanted and cardiomyopathic human hearts.
Authors: A R Denniss, J D Marsh, R J Quigg, J B Gordon, W S Colucci
Journal: Circulation (1989)

To test the hypothesis that there is up-regulation of beta-adrenergic receptor density or supersensitivity of beta-adrenergic receptor-stimulated adenylate cyclase in the denervated transplanted human heart, we studied myocardium from transplanted, normal, and failing hearts. Myocardium was obtained from 10 patients 9 +/- 3 months after cardiac transplantation, from 10 patients without cardiac disease, and from eight patients with symptomatic congestive heart failure due to idiopathic cardiomyopathy. beta-Adrenergic receptor density in transplanted myocardium (15 +/- 3 fmol/mg protein, 1.20 +/- 0.14 fmol/mg DNA) was not different from that in normal myocardium (22 +/- 3 fmol/mg protein, 1.46 +/- 0.13 fmol/mg DNA; p = NS for both). In myocardium from cardiomyopathic hearts, beta-adrenergic receptor density was markedly reduced (8 +/- 2 fmol/mg protein, 0.84 +/- 0.13 fmol/mg DNA; p less than 0.05 and p less than 0.01 vs. normal myocardium, respectively). Likewise, the response of adenylate cyclase to isoproterenol in transplanted myocardium was not significantly different from that in normal myocardium, but the response was markedly depressed in cardiomyopathic myocardium. Although forskolin-stimulated adenylate cyclase activity was similar in all three groups, guanine nucleotide-stimulated adenylate cyclase activity was markedly reduced in transplanted myocardium (20 +/- 17 vs. 78 +/- 13 pmol/mg/min for normal myocardium, p less than 0.01) and to a lesser degree in cardiomyopathic myocardium (39 +/- 14 pmol/mg/min, p less than 0.03 vs. normal myocardium). Thus, there is no evidence of beta-adrenergic receptor up-regulation or supersensitivity in denervated transplanted human myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)