EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008
Ditza Levin
Abstract We examined TCR:MHC/peptide interactions and in vivo epitope availability to explore the Th1- or Th2-like phenotype of autoimmune disease in two TCR Tg mouse models of autoimmune gastritis (AIG). The TCR of strains A23 and A51 recognize distinct IAd -restricted peptides from the gastric parietal cell H/K-ATPase. Both peptides form extremely stable MHC/peptide (MHC/p) complexes. All A23 animals develop a Th1-like aggressive, inflammatory AIG early in life, while A51 mice develop indolent Th2-like AIG at 6,8,wk with incomplete penetrance. A51 T cells were more sensitive than A23 to low doses of soluble antigen and to MHC/p complexes. Staining with IAd/peptide tetramers was only detectable on previously activated T cells from A51. Thus, despite inducing a milder AIG, the A51 TCR displays a higher avidity for its cognate IAd/peptide. Nonetheless, in vivo proliferation of adoptively transferred A51 CFSE-labeled T cells in the gastric lymph node was relatively poor compared with A23 T cells. Also, DC from WT gastric lymph node, presenting processed antigen available in vivo, stimulated proliferation of A23 T cells better than A51. Thus, the autoimmune potential of these TCR in their respective Tg lines is strongly influenced by the availability of the peptide epitope, rather than by differential avidity for their respective MHC/p complexes. [source]

The CD1d-binding glycolipid ,-galactosylceramide enhances humoral immunity to T-dependent and T-independent antigen in a CD1d-dependent manner

IMMUNOLOGY, Issue 1 2006
Gillian A. Lang
Summary Specific interaction of class II/peptide with the T-cell receptor (TCR) expressed by class II-restricted CD4+ T helper (Th) cells is essential for in vivo production of antibodies reactive with T-dependent antigen. In response to stimulation with CD1d-binding glycolipid, V,14+ TCR-expressing, CD1d-restricted natural killer T (NKT) cells may provide additional help for antibody production. We tested the hypothesis that the CD1d-binding glycolipid ,-galactosylceramide (,-GC) enhances production of antibodies reactive with T-dependent antigen in vivo. ,-GC enhanced antibody production in vivo in a CD1d-dependent manner in the presence of class II-restricted Th cells and induced a limited antibody response in Th-deficient mice. ,-GC also led to alterations in isotype switch, selectively increasing production of immunoglobulin G2b. Further analysis revealed that ,-GC led to priming of class II-restricted Th cells in vivo. Additionally, we observed that ,-GC enhanced production of antibodies reactive with T-independent antigen, showing the effects of NKT cells on B cells independently of Th cells. Our data show that NKT cells have multiple effects on the induction of a humoral immune response. We propose that NKT cells could be exploited for the development of novel vaccines where protective antibody is required. [source]

Availability of autoantigenic epitopes controls phenotype, severity, and penetrance in TCR Tg autoimmune gastritis

PLASMA BRAIN NATRIURETIC PEPTIDE MEASURED IN STABLE CONDITIONS IS RELATED TO MORTALITY IN FRAIL AND VERY OLD PATIENTS

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2009
Franck Lebourgeois MD
No abstract is available for this article. [source]

BRAIN NATRIURETIC PEPTIDE IN HEART FAILURE

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2006
Article first published online: 6 FEB 200
No abstract is available for this article. [source]

Screening for Asymptomatic Left Ventricular Dysfunction Using B-Type Natriuretic Peptide

CONGESTIVE HEART FAILURE, Issue 2008
Theresa A. McDonagh MD
Asymptomatic left ventricular dysfunction (ASLVD), a known precursor phase of heart failure, fulfills the essential criteria that should be met before screening for a disease. It is common and associated with reduced longevity and quality of life. Left untreated, it progresses to heart failure, which incurs a mortality greater than most cancers as well as significant morbidity rates. In addition, we now have several population-based studies that demonstrate that both B-type natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NTproBNP) can accurately exclude left ventricular systolic dysfunction. More recent work shows that this can be done cost-effectively. There is also a wealth of evidence from randomized controlled trials indicating that the treatment of ASLVD can reduce both morbidity and mortality and slow progression to the heart failure state. The main stumbling block to implementation of screening, in addition to the perceived cost, may well be the lack of a randomized study showing that screening the population for ASLVD really does alter the natural history of the condition, something that other screening strategies have so far failed to do. Congest Heart Fail. 2008;14(4 suppl 1):5,8. ©2008 Le Jacq [source]

Invasive and Noninvasive Correlations of B-Type Natriuretic Peptide in Patients With Heart Failure Due to Chagas Cardiomyopathy

CONGESTIVE HEART FAILURE, Issue 3 2008
Fábio Vilas-Boas MD
Heart failure due to Chagas cardiomyopathy (HFCC) differs from failure with other etiologies because of the occurrence of intense inflammatory infiltrate and right ventricle compromise. This article investigates correlations of B-type natriuretic peptide (BNP) levels with parameters of severity in HFCC. Twenty-eight patients and 8 normal controls underwent heart catheterization and clinical and laboratory analyses. BNP levels were higher in patients with HFCC (P<.0001) and correlated with New York Heart Association (NYHA) class; right atrial pressure; wedge pressure; cardiac output; levels of serum sodium, hemoglobin, urea, and tumor necrosis factor-,; and ejection fraction. Interferon-, and transforming growth factor-, did not correlate with BNP level. The authors conclude that BNP levels are elevated in patients experiencing HFCC, irrespective of NYHA class, and that the occurrence of HFCC correlates with severity of disease. [source]

Clinical and Hemodynamic Effects of Nesiritide (B-Type Natriuretic Peptide) in Patients With Decompensated Heart Failure Receiving , Blockers

CONGESTIVE HEART FAILURE, Issue 2 2005
William T. Abraham MD
The use of , blockers in congestive heart failure presents a therapeutic challenge for patients with acute episodes of decompensation. Such patients may be less responsive to positive inotropic agents, whereas the beneficial effects of nesiritide, which are not dependent on the ,-adrenergic receptor signal-transduction pathway, may be preserved. This analysis of the Vasodilation in the Management of Acute CHF trial evaluated the safety and efficacy of nesiritide in decompensated congestive heart failure patients receiving , blockers. The Vasodilation in the Management of Acute CHF trial was a multicenter, randomized, controlled evaluation of nesiritide in 489 hospitalized patients with decompensated congestive heart failure. One hundred twenty-three patients were on chronic ,-blocker therapy at enrollment (31 randomized to placebo, 50 to nesiritide, and 42 to nitroglycerin). Primary end points included pulmonary capillary wedge pressure and dyspnea evaluation at 3 hours. Patients receiving nesiritide, but not IV nitroglycerin, had significantly reduced pulmonary capillary wedge pressure vs. placebo at 3 hours regardless of ,-blocker use. The use of , blockers did not alter the beneficial effects of nesiritide on systemic blood pressure, heart rate, or dyspnea evaluation. In nesiritide-treated subjects, safety profiles were similar regardless of ,-blocker use. Thus, the clinical and hemodynamic benefits and safety of nesiritide are preserved in decompensated congestive heart failure patients receiving chronic , blockade. [source]

Brain Natriuretic Peptide and Diastolic Dysfunction in the Elderly: Influence of Gender

CONGESTIVE HEART FAILURE, Issue 2 2005
Chanwit Roongsritong MD
Diastolic heart failure is common in the elderly, particularly women. Previous studies on the value of brain natriuretic peptide in diastolic dysfunction have been largely limited to male subjects. The authors found that female gender, in addition to diastolic function, is an independent predictor of brain natriuretic peptide levels in the elderly without systolic ventricular dysfunction. The authors' data indicate that an optimal threshold of brain natriuretic peptide for detecting diastolic dysfunction should be qender-specific. [source]

Usefulness of B-Type Natriuretic Peptide as a Predictor of Treatment Outcome in Pulmonary Arterial Hypertension

CONGESTIVE HEART FAILURE, Issue 5 2004
Myung H. Park MD
We examined the utility of early modulation B-type natriuretic peptide (BNP) levels in 20 pulmonary arterial hypertension patients as a marker of response to epoprostenol therapy. The baseline BNP level was 828±217 pg/mL. A total of 19 hospitalizations and one death occurred in nine patients during 11.0±1.8 months. At baseline, a trend toward higher BNP level was observed among the event-free (Group A) as compared with clinical event patients (Group B) (1090±372 vs. 510±235 pg/mL, respectively; p=0.08). After 3 months on epoprostenol, a significant reduction among Group A occurred while Group B demonstrated an increase (288±92 vs. 610±121 pg/mL, p=0.04). A comparison of percent reduction in BNP level demonstrated a ,70±7% change among Group A and an 11±19% increase in Group B (p=0.005). A decrease in BNP level of ,50% during the first 3 months on epoprostenol was strongly predictive of event-free survival (p=0.003). This investigation establishes the utility of BNP for predicting response to epoprostenol therapy in pulmonary arterial hypertension. [source]

Effect of Bisoprolol on Right Ventricular Function and Brain Natriuretic Peptide in Patients With Heart Failure

CONGESTIVE HEART FAILURE, Issue 3 2004
Luís Beck-da-Silva MD
Beta-blocker use improves left ventricular ejection fraction (LVEF) in patients with heart failure. A similar effect of , blockers on right ventricular function has been proposed, although the effect of bisoprolol, a highly selective ,-1 blocker, on right ventricular function has not been assessed. This study investigated the short-term effect of bisoprolol on right ventricular function in chronic heart failure patients. A cohort of 30 heart failure patients who were not taking , blockers at baseline was studied prospectively. Right ventricular ejection fraction (RVEF) and LVEF were measured at both baseline and 4 months by radionuclide angiography. Bisoprolol was up-titrated during four monthly visits by a preestablished protocol to a target dose of 10 mg/d. The dose of vasodilators was not changed. Quality of life and brain natriuretic peptide level were assessed. Mean age was 62.7±14.3 years. Baseline RVEF was 30.7%±6.3% and baseline LVEF was 21.7%±9.4%. Mean bisoprolol dose reached was 5.3±3.9 mg daily. At 4 months, RVEF significantly increased by 7.1 % (95% confidence interval, 3.9,10.2; p=0.0001) and LVEF also increased significantly by 7.9% (95% confidence interval, 4.0%,11.9%p=0.0003). Quality-of-life score improved from 42.8 to 30.8 (p=0.047). No correlation was found between brain natriuretic peptide levels and RVEF. Bisoprolol treatment for 4 months resulted in a significant improvement of RVEF, which paralleled the improvement of LVEF. [source]

Gastrin-Releasing Peptide, a Bombesin-like Neuropeptide, Promotes Cutaneous Wound Healing

DERMATOLOGIC SURGERY, Issue 4 2002
Yuji Yamaguchi MD
Background. Little is known about the effects of neuropeptides on wound healing. Objective. To investigate the effect of gastrin-releasing peptide (GRP), one of the bombesin-like neuropeptides, on wound healing. Methods. The effects of GRP on cultured keratinocyte proliferation and migration were measured by BrdU uptake and in vitro scratch assay, respectively. Various concentrations of GRP ointments (0, 10,9, 10,8, 10,7, 10,6 M) were topically applied to 1.0 mm wounds on porcine flanks. Results. GRP stimulated keratinocyte growth and locomotion in a dose-dependent manner. Topical administration of GRP accelerated macroscopic epidermal regeneration in a dose-dependent manner, as measured by planimetry. Histologic studies also showed that GRP promoted reepithelialization, including epidermal thickness as well as superficial skin coverage. conclusion. Topical use of GRP may clinically accelerate wound healing of burns, injuries, chronic ulcers, and skin graft donor sites through the enhancement of keratinocyte growth and spreading. [source]

Accuracy of Tissue Doppler Echocardiography in the Diagnosis of New-Onset Congestive Heart Failure in Patients with Levels of B-Type Natriuretic Peptide in the Midrange and Normal Left Ventricular Ejection Fraction

ECHOCARDIOGRAPHY, Issue 8 2006
Stephane Arques M.D.
Background: Based on the hypothesis that it reflects left ventricular (LV) diastolic pressures, B-type natriuretic peptide (BNP) is largely utilized as first-line diagnostic complement in the emergency diagnosis of congestive heart failure (HF). The incremental diagnostic value of tissue Doppler echocardiography, a reliable noninvasive estimate of LV filling pressures, has been reported in patients with preserved LV ejection fraction and discrepancy between BNP levels and the clinical judgment, however, its clinical validity in such patients in the presence of BNP concentrations in the midrange, which may reflect intermediate, nondiagnostic levels of LV filling pressures, is unknown. Methods: 34 patients without history of HF, presenting with acute dyspnea at rest, BNP levels of 100,400 pg/ml and normal LV ejection fraction were prospectively enrolled (17 with congestive HF and 17 with noncardiac cause). Tissue Doppler echocardiography was performed within 3 hours after admission. Results: unlike BNP (P = 0.78), Boston criteria (P = 0.0129), radiographic pulmonary edema (P = 0.0036) and average E/Ea ratio (P = 0.0032) were predictive of congestive HF by logistic regression analysis. In this clinical setting, radiographic pulmonary edema had a positive predictive value of 80% in the diagnosis of congestive HF. In patients without evidence of radiographic pulmonary edema, average E/Ea > 10 was a powerful predictor of congestive HF (area under the ROC curve of 0.886, P < 0.001, sensitivity 100% and specificity 78.6%). Conclusion: by better reflecting LV filling pressures, bedside tissue Doppler echocardiography accurately differentiates congestive HF from noncardiac cause in dyspneic patients with intermediate, nondiagnostic BNP levels and normal LV ejection fraction. [source]

Peptide Modified Electrodes as Electrochemical Metal Ion Sensors

ELECTROANALYSIS, Issue 15 2006
Edith Chow
Abstract Sensors for the detection of metal ions are of considerable importance for enabling the monitoring of environmental samples for metal ion contamination directly in the field. This review outlines the use of peptides and amino acids as the recognition element of electrochemical sensors for metal ion detection. Initially the complexation of metals by peptides is discussed followed by the immobilization of peptides on electrode surfaces. Subsequently, the application of peptide modified electrodes for detecting metals is reviewed and finally challenges and future prospects are outlined. [source]

Synthesis, Solution Structure and Biological Activity of Val-Val-Pro-Gln,a Bioactive Elastin Peptide

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 8 2005
Caterina Spezzacatena
Abstract Val-Val-Pro-Gln (valyl-valyl-prolyl-glutamine) is a small but highly conserved sequence present in all elastins. We describe its synthesis by mixed anhydride solution chemistry as an alternative to solid-phase peptide synthesis (SPPS). The molecular structure of the tetrapeptide in solution was investigated by classical spectroscopy, such as circular dichroism (CD), nuclear magnetic resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). The biological activity of Val-Val-Pro-Gln was evaluated by a bromodeoxyuridine (BrdU) incorporation assay with normal human dermal fibroblasts. This small peptide may play a critical role in control of matrix metabolism through its release from the elastin polypeptide chain during periods of tissue breakdown and remodelling. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]

Solvent-Dependent Conformational Behaviour of Model Tetrapeptides Containing a Bicyclic Proline Mimetic

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2004
Andrea Trabocchi
Abstract Two model tetrapeptides containing bicyclic analogues of either D - or L -proline were synthesised and their conformational properties were studied by NMR in different solvent systems and by molecular modelling techniques. Compound 1, with the bicyclic D -proline mimetic in the i+1 position, generated a unique trans isomer, and the peptide showed a well organised structure, in accordance with the tendency of D -proline to act as a good turn inducer with respect to its enantiomer. Peptide 2 displayed structures equilibrating from type I,II to type VI ,-turns, thus confirming the hypothesised relationship between the chirality of BGS/Bgs and proline enantiomers on nucleating compact turns. Moreover, such behaviour suggested a tool for peptidomimetic design of reverse turn peptides containing BGS/Bgs bicyclic proline mimetics, as the choice of chirality might influence the generation either of compact ,- and ,-turns or of flexible equilibrating reverse turn structures. The effect of solvent on conformational behaviour was also studied. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source]

Adrenomedullin and Proadrenomudullin N-Terminal 20 Peptide (PAMP) are Present in Human Colonic Epithelia and Exert an Antimicrobial Effect

EXPERIMENTAL PHYSIOLOGY, Issue 5 2001
K. Marutsuka
The hypotensive and vasorelaxing peptides adrenomedullin (AM) and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), were found to be distributed on the surface of the colonic mucosa. AM and PAMP showed dose-dependent antimicrobial activity against E. coli. The results suggest that the novel vasoactive peptides AM and PAMP play an important role in mucosal defence. [source]

Involvement of Calmodulin in Glucagon-Like Peptide 1(7-36) Amide-Induced Inhibition of the ATP-Sensitive K+ Channel in Mouse Pancreatic ,-Cells

EXPERIMENTAL PHYSIOLOGY, Issue 3 2001
W. G. Ding
The present investigation was designed to examine whether calmodulin is involved in the inhibition of the ATP-sensitive K+ (KATP) channel by glucagon-like peptide 1(7-36) amide (GLP-1) in mouse pancreatic ,-cells. Membrane potential, single channel and whole-cell currents through the KATP channels, and intracellular free Ca2+ concentration ([Ca2+]i) were measured in single mouse pancreatic ,-cells. Whole-cell patch-clamp experiments with amphotericin-perforated patches revealed that membrane conductance at around the resting potential is predominantly supplied by the KATP channels in mouse pancreatic ,-cells. The addition of 20 nM GLP-1 in the presence of 5 mM glucose significantly reduced the membrane KATP conductance, accompanied by membrane depolarization and the generation of electrical activity. A calmodulin inhibitor N -(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7, 20 ,M) completely reversed the inhibitory actions of GLP-1 on the membrane KATP conductance and resultant membrane depolarization. Cell-attached patch recordings confirmed the inhibition of the KATP channel activity by 20 nM GLP-1 and its restoration by 20 ,M W-7 or 10 ,M calmidazolium at the single channel level. Bath application of 20 ,M W-7 also consistently abolished the GLP-1-evoked increase in [Ca2+]i in the presence of 5 mM glucose. These results strongly suggest that the mechanisms by which GLP-1 inhibits the KATP channel activity accompanied by the initiation of electrical activity in mouse pancreatic ,-cells include a calmodulin-dependent mechanism in addition to the well-documented activation of the cyclic AMP-protein kinase A system. [source]

Self-Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation, Release and In Vitro Delivery

ADVANCED FUNCTIONAL MATERIALS, Issue 1 2009
Shan Yu Fung
Abstract The self-assembling peptide EAK16-II is capable of stabilizing hydrophobic compounds to form microcrystal suspensions in aqueous solution. Here, the ability of this peptide to stabilize the hydrophobic anticancer agent ellipticine is investigated. The formation of peptide-ellipticine suspensions is monitored with time until equilibrium is reached. The equilibration time is found to be dependent on the peptide concentration. When the peptide concentration is close to its critical aggregation concentration, the equilibration time is minimal at 5,h. With different combinations of EAK16-II and ellipticine concentrations, two molecular states (protonated or cyrstalline) of ellipticine could be stabilized. These different states of ellipticine significantly affect the release kinetics of ellipticine from the peptide-ellipticine complex into the egg phosphatidylcholine vesicles, which are used to mimic cell membranes. The transfer rate of protonated ellipticine from the complex to the vesicles is much faster than that of crystalline ellipticine. This observation may also be related to the size of the resulting complexes as revealed from the scanning electron micrographs. In addition, the complexes with protonated ellipticine are found to have a better anticancer activity against two cancer cell lines, A549 and MCF-7. This work forms the basis for studies of the peptide-ellipticine suspensions in vitro and in vivo leading to future development of self-assembling peptide-based delivery of hydrophobic anticancer drugs. [source]

, -Peptide Conjugates: Syntheses and CD and NMR Investigations of ,/, -Chimeric Peptides, of a DPA- , -Decapeptide, and of a PEGylated , -Heptapeptide

HELVETICA CHIMICA ACTA, Issue 12 2009
James Gardiner
Abstract ,3 -Peptides consisting of six, seven, and ten homologated proteinogenic amino acid residues have been attached to an , -heptapeptide (all d- amino acid residues; 4), to a hexaethylene glycol chain (PEGylation; 5c), and to dipicolinic acid (DPA derivative 6), respectively. The conjugation of the , -peptides with the second component was carried out through the N-termini in all three cases. According to NMR analysis (CD3OH solutions), the (M)- 314 -helical structure of the , -peptidic segments was unscathed in all three chimeric compounds (Figs.,2, 4, and 5). The , -peptidic section of the ,/, -peptide was unstructured, and so was the oligoethylene glycol chain in the PEGylated compound. Thus, neither does the appendage influence the , -peptidic secondary structure, nor does the latter cause any order in the attached oligomers to be observed by this method of analysis. A similar conclusion may be drawn from CD spectra (Figs.,1, 3, and 5). These results bode well for the development of delivery systems involving , -peptides. [source]

Molecular Recognition of a Peptide by the Nickel(II) Complex of 1,4,7,10-Tetraazacyclododecane-2,9-dione

HELVETICA CHIMICA ACTA, Issue 3 2003
Jian Gao
The nickel(II) complex of the macrocycle 1,4,7,10-tetraazacyclododecane-2,9-dione (dota) was found to be efficient in the recognition of the dipeptide, glycyl-glycine (Gly-Gly) in aqueous solution. This (dota)NiII complex serves as a targeting molecule to form a stable ternary complex with the dipeptide at pH,8.3 in aqueous solution. The recognition constant (log K=19.20) and the recognition mechanism were investigated based on the potentiometric method. The single-crystal of a six-coordinated (dota)2NiII complex is also reported. [source]

Different hepatitis C virus nonstructural protein 3 (Ns3)-DNA,expressing vaccines induce in HLA-A2.1 transgenic mice stable cytotoxic T lymphocytes that target one major epitope

HEPATOLOGY, Issue 6 2001
Carine Brinster
The immunogenicity of the Hepatitis C virus (HCV) nonstructural protein 3 (NS3) was investigated using different DNA-based strategies and a preclinical mouse model transgenic for the HLA-A2.1 molecule. Plasmids expressing NS3 either as a wild-type protein, as a fusion with murine lysosome-associated-membrane protein-1 specific sequences, or under the control of the Semliki Forest virus replicase were evaluated in vitro and in vivo. All plasmids were shown to express the expected size protein. These 3 NS3-expressing vaccines induced overall comparable levels of CTLs when measured at different times postvaccination although mice injected with the NS3-LAMP expressing plasmid showed a particularly homogeneous and overall vigorous response (specific lysis ranged from 60% to 90 % for an E:T ratio of 33.3:1 with a mean CTL precursor frequency of 1:2.105 cells). Out of the four HLA-A2.1-restricted NS3 epitopes previously described in HCV infected patients (aa 1073-1081, aa 1406-1415; aa 1169-1177 and aa 1287-1296), the NS3-DNA generated CTLs were predominantly targeted at the aa 1073-1081 epitope. Peptide-based immunization showed that the mouse repertoire was intact for all epitopes tested except one (aa 1287-1296). In conclusion, the 3 NS3-DNA vaccines although based on different mode of action, shared a comparable efficacy at inducing CTL. Surprisingly, the breadth of such response was restricted to a single, major epitope. [source]

Peptide-,2-microglobulin-major histocompatibility complex expressing cells are potent antigen-presenting cells that can generate specific T cells

IMMUNOLOGY, Issue 1 2007
Sonja Obermann
Summary Adoptive T-cell therapy represents a promising therapeutic approach for the treatment of cancer. Successful adoptive immunotherapy depends on the ex vivo priming and expansion of antigen-specific T cells. However, the in vitro generation of adequate numbers of functional antigen-specific T cell remains a major obstacle. It is important to develop efficient and reproducible methods to generate high numbers of antigen-specific T cells for adoptive T-cell transfer. We have developed a new artificial antigen-presenting cell (aAPC) by transfection of major histocompatibility (MHC) class I negative Daudi cells with a peptide-,2-microglobulin,MHC fusion construct (single-chain aAPC) ensuring presentation of the peptide,MHC complex of interest. Using this artificial antigen-presenting cell, we could generate up to 9·2 × 108 antigen-specific cytotoxic CD8+ T cells from 10 ml blood. In vitro generated T cells lysed endogenously presented antigens. Direct comparison of the single-chain aAPC with autologous monocyte-derived dendritic cells demonstrated that these cells were equally efficient in stimulation of T cells. Finally, we were able to generate antigen-specific T cell lines from perpheral blood mononuclear cells of patients receiving cytotoxic chemotherapy. The use of single-chain aAPC represent a promising option for the generation of antigen-specific CD8+ T cells, which could be used for adoptive T-cell therapy. [source]

Bioinspired Materials: Oligothiophene Versus , -Sheet Peptide: Synthesis and Self-Assembly of an Organic Semiconductor-Peptide Hybrid (Adv. Mater.

ADVANCED MATERIALS, Issue 16 2009
16/2009)
A first representative of a novel class of bioinspired materials, a fully symmetric hybrid between an oligothiophene and a , -sheet peptide, is introduced in work by Peter Bäuerle and co-workers on p. 1562. The conjugate can be synthesized via click-chemistry and employs a switch-peptide segment to gain control over the self-assembly motif of the peptide part. [source]

Oligothiophene Versus , -Sheet Peptide: Synthesis and Self-Assembly of an Organic Semiconductor-Peptide Hybrid

ADVANCED MATERIALS, Issue 16 2009
Eva-Kathrin Schillinger
A first representative of a novel class of bioinspired materials is introduced, a fully symmetric hybrid between an oligothiophene and a , -sheet peptide. The conjugate is synthesized via "click chemistry", and employs a switch-peptide segment to gain control over the self-assembly motif of the peptide part. The self-organization properties of the hybrid are investigated. [source]

Identification of a Highly Specific Hydroxyapatite-binding Peptide using Phage Display,

ADVANCED MATERIALS, Issue 10 2008
Marc D. Roy
A peptide sequence SVSVGMKPSPRP that selectively recognizes hydroxyapatite (HA) is identified by using a phage display approach. The engineered sequence exhibits chemical and structural specificity for HA over calcium carbonate and HA's amorphous calcium phosphate precursor. In situ binding to HA in a tooth cross section further demonstrates the sequence specificity and utility in nondestructive imaging applications. [source]

Covalent Attachment of Low Molecular Weight Poly(ethylene imine) Improves Tat Peptide Mediated Gene Delivery,

ADVANCED MATERIALS, Issue 16 2006
F. Alexis
A polymer-peptide hybrid biomaterial synthesized by coupling poly(ethylene imine) directly to resin-supported Tat peptide takes advantage of the unique features associated with the two original cationic materials and functions as a novel gene-delivery vector with good biocompatibility. The figure shows cells transfected with green fluorescent protein (GFP) using complexes of the polymer-peptide hybrid and GFP (scale bar: 100,,m). [source]

Rapid, Room-Temperature Formation of Crystalline Calcium Molybdate Phosphor Microparticles via Peptide - Induced Precipitation,

ADVANCED MATERIALS, Issue 13 2006
G. Ahmad
A phage display method has been used for the first time to identify peptides that bind to, and induce the rapid formation of, a pure crystalline binary metal oxide compound, CaMoO4, at room temperature from a soluble aqueous precursor solution (see figure). This demonstration opens the door to the biosculpting (peptide patterning, then localized peptide-induced mineralization) of functional synthetic crystalline multicomponent compounds onto or with low-temperature or chemically dissimilar materials. [source]

Vakzinationstherapie kutaner T-Zell-Lymphome

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 12 2002
Vaccination therapy for cutaneous T-cell lymphoma
primary cutaneous T cell lymphomas (CTCL); vaccination; antigenic targets Zusammenfassung: Primär kutane T-Zell-Lymphome (CTCL) sind definiert als klonale Proliferation hautinfiltrierender T-Lymphozyten. Unabhängig von der Heterogenität dieser Krankheitsgruppe besteht derzeit keine kurative Therapiemöglichkeit, was zur Entwicklung verschiedener Behandlungsstrategien, einschließlich der Vakzination, führte. Dieser Artikel gibt eine Übersicht über den Entwicklungsstand der Vakzinationstherapie für Lymphome mit besonderer Rücksicht auf die CTCL. Da bisher kein universelles Tumorantigen identifiziert wurde, sind verschiedenste antigene Agenzien (komplette Tumorzellen, Idiotypen, Cancer/Testis-Antigene, Proteine aus tumorassoziierten Mutationen und Mimotope) hinsichtlich ihrer Eignung für die Vakzinationstherapie von CTCL untersucht worden. Die antigene Information dieser Präparationen kann dem körpereigenen Immunsystem über verschiedene Wege (Carrier) dargeboten werden, bisher sind dazu mit Tumorzellen fusionierte dendritische Zellen, Idiotyp-Proteine oder -Peptide sowie DNA- und RNA-Präparationen eingesetzt worden. Da die verwendeten Antigene allesamt schwache Immunogene darstellen, sind Adjuvanzien (dendritische Zellen, immunogene Peptide, Oligonukleotide, Zytokine, virale Vektoren) notwendig, um eine suffiziente Antigenpräsentation und Aktivierung des Immunsystems zu erreichen. Erste klinische Daten bestätigen die prinzipielle Wirksamkeit einer Vakzinationstherapie bei CTCL. Die große Anzahl bisher verwendeter Antigene, Carrier, Adjuvanzien und Applikationsschemen macht die Identifizierung eines optimalen Protokolls jedoch nahezu unmöglich. Da auch die Wechselwirkungen zwischen Lymphom und Immunsystem sehr komplex und nicht vollständig verstanden sind, ist bis zur Einführung der Vakzinationstherapie in die klinische Praxis noch großer Forschungsaufwand nötig. Summary: Primary cutaneous T,cell lymphomas (CTCL) are defined as clonal proliferation of skin-infiltrating T lymphocytes. Despite their heterogeneity, CTCL are generally incurable, which lead to the development of various treatment strategies including vaccination. Here, the attempts to vaccinate against lymphoma will be reviewed with special emphasis on CTCL. Since an universal tumour antigen is not available so far, different targets, including whole tumour cells, idiotypes, cancer/testis antigens, proteins derived from tumour-associated mutations, and mimotopes, have been investigated for their applicability in CTCL vaccination. The antigenic information can be delivered in different ways. So far, tumour cells fused to dendritic cells, idiotypic proteins/peptides and DNA/RNA preparations have been applied in lymphoma. Since most targets are weak immunogens, adjuvants and other helpers, including dendritic cells, immunogenic peptides and oligonucleotides, cytokines, and viral vectors, are required to enable proper presentation of the antigens and sufficient activation of the immune system. Although first data from CTCL patients prove the suitability of vaccination in CTCL therapy, the number of available antigens, carriers, adjuvants and application schemes creates a multitude of vaccine formulations and identification of the best-suited approach difficult. Furthermore, the relationship between lymphoma and the host immune system is complex and still not completely understood. In consequence, CTCL vaccination requires a lot of research to be done before its breakthrough. [source]

B-Type Natriuretic Peptide Is Associated with Mortality in Older Functionally Impaired Patients

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2005
Miles D. Witham BM
Objectives: To determine the predictive power of B-type natriuretic peptide (BNP) regarding death in older, functionally impaired patients with multiple comorbidity. Design: Prospective cohort study. Setting: Specialist geriatric assessment clinic and day hospital. Participants: Two hundred ninety-nine older, functionally impaired patients, mean age 79 at enrollment. Measurements: Full clinical history and examination, baseline BNP, and echocardiography. Date and cause of death were ascertained from Scottish death records. Kaplan-Meier survival curves were constructed for quartiles of log (BNP), and the contribution of BNP to prediction of death was investigated. Results: The follow-up period ranged from 3.9 to 5.2 years (mean 4.4 years). BNP was a powerful independent predictor of all-cause and cardiovascular mortality. BNP was a more powerful predictor than blood pressure, diabetes mellitus, smoking, echocardiographic left ventricular hypertrophy, left ventricular systolic dysfunction, or age. BNP predicted death in those with and without a previous cardiovascular event at baseline. Conclusion: BNP has significant predictive power for death in older, functionally impaired patients. [source]