bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracoronary stenting without coumadin: One month results of a French multicenter study
Authors: Morice Marie C. , Zemour Gilles , Benveniste Edgar , Biron Yves , Bourdonnec Claude , Faivre René , Fajadet Jean , Gaspard Philippe , Glatt Bernard , Joly Patrick , Labrunie Pierre , Lienhart Yves , Marco Jean , Petiteau Pierre Y. , Royer Thierry , Valeix Bernard
Published: March 2007

In order to simplify post‐coronary stenting treatment and to obtain a lower rate of complications, especially in bailout situations, seven French institutions treated 246 stented patients with 0.25 g/day of ticlopidine, 0.1 g/day of IV aspirin, and 2 days of heparin followed by low‐molecular‐weight heparin for 1 month. Fifty percent of patients had a planned stenting procedure, and 50% had an unplanned procedure, including 29 (11.8%) in bailout situations. Subacute occlusion occurred in three (1.2%) patients (one death, two non‐Q‐wave infarctions). During the 1 month follow‐up period, another death was reported (non‐stent‐related), two elective coronary artery bypass grafts were performed, and three additional patients presented with non‐Q‐wave myocardial infarctions. Nine (3.7%) patients had a groin complication that required blood transfusion or surgical repair. These results suggest that while waiting for the technological advancements of stents, postprocedural treatment that includes a low dosage of ticlopidine, aspirin, and low‐molecular‐weight heparin is a very effective alternative to conventional poststenting therapy. © 1995 Wiley‐Liss, Inc.
Comparison of bedside and hospital laboratory coagulation studies during and after coronary intervention
Authors: Blumenthal Roger S. , Carter Andrew J. , Resar Jon R. , Coombs Vicki , Gloth Sean T. , Dalal Jyostna , Brinker Jeffrey A.
Published: March 2007

The activated clotting time is routinely used to monitor anticoagulation during coronary intervention, whereas the hospital laboratory APTT guides pre‐ and postprocedure heparin therapy. An optimal coagulation test for patients undergoing percutaneous revascularization would provide a rapid and accurate assessment of anticoagulation throughout a broad range of heparin therapy. We studied the relationships of the bedside whole blood APTT, ACT, and the laboratory APTT in 166 patients undergoing coronary intervation. The whole blood APTT correlated closely with the laboratory APTT (range 18‐80 sec) (r = .75), whereas the ACT and laboratory APTT had only a fair correlation (r = .42). Also, the whole blood APTT demonstrated a strong correlation with the ACT throughout the range of heparin therapy for intervention (r = .81). The diagnostic accuracy of the whole blood APTT, based on the receiver operating characteristic curve, was significantly better than that for the ACT in determining the anticoagulation status. The whole blood APTT obtained by bedside monitoring provides a rapid and accurate assessment of anticoagulation throughout the range of heparin dosing associated with coronary intervention. In situations in which an adequate assessment of residual anticoagulation is necessary, the whole blood APTT is superior to the ACT and probably should be the method of choice. © 1995 Wiley‐Liss, Inc.
The forgotten chamber: The importance of the right ventricle
Authors: Rigolin Vera H. , Robiolio Paul A. , Wilson John S. , Harrison J. Kevin , Bashore Thomas M.
Published: March 2007

Historically, the right heart was viewed as less important than the left heart in the maintenance of normal overall hemodynamic performance. However, there is now considerable evidence that emphasizes the significance of intact right ventricular (RV) function. The RV's anatomy and physiology are reviewed in order to provide insight into how changes in volume can be accommodated within a low‐pressure environment and how this contributes to hemodynamic stability. The interdependent relationship between the right and left ventricles is also explored.

The contribution of RV performance to overall hemodynamics is best exemplified when the RV becomes diseased. RV infarction, atrial septal defect, and cor pulmonale are used as examples to illustrate the dramatic sequelae associated with RV dysfunction, as well as to identify the RV's specific adaptive mechanisms. © 1995 Wiley‐Liss, Inc.
Controversies in balloon mitral valvuloplasty: The when (timing for intervention), what (choice of valve), and how (selection of technique)
Authors: Lau Kean‐Wah , Hung Jui‐Sung , Ding Zee‐Pin , Johan Abdullah
Published: March 2007

Despite the established role of percutaneous balloon mitral valvuloplasty (BMV) in the treatment of mitral stenosis, major controversial issues in the realm of BMV persist. With increased operator experience, BMV has now been extended to include various controversial scenarios, such as mild mitral stenosis, adverse valve morphologies, and highrisk patients with concomitant anatomic distortions which are technically demanding. In skilled hands, however, BMV has yielded a favorable outcome in these settings. Furthermore, the debate on whether the Inoue or the double‐balloon approach is superior continues. Studies to date have shown equal efficacy of the two BMV methods in terms of valve enlargement although the Inoue approach is clearly simpler to execute and may potentially be associated with a lower risk of creating severe mitral regurgitation. Last, because of the lack of consensus on optimal balloon sizing for BMV, perhaps the best method to adopt at this stage is one that is simple and safe to apply across a broad spectrum of valve anatomy. © 1995 Wiley‐Liss, Inc.
Coronary artery fistulas in adults: Incidence, angiographic characteristics, natural history
Authors: Vavuranakis Manolis , Bush Charles A. , Boudoulas Harisios
Published: March 2007

The incidence, angiographic characteristics, and natural history of coronary artery fistulas in patients undergoing diagnostic cardiac catheterization have not been well defined. Of 33,600 patients who had diagnostic cardiac catheterization, 34 (0.1%) had coronary artery fistula. Nineteen fistulas originated from the right, 11 from the left anterior descending, and 4 from the circumflex coronary arteries, respectively. The mean ratio of pulmonary to systemic flow was 1.19 ± 0.33. Only one patient with coexistent atrial septal defect had a pulmonic to systemic flow ratio >1.5. Right and left heart pressures, with the exception of three patients in whom left ventricular end‐diastolic pressure was >12 mm Hg, were within normal limits. During a mean follow‐up period of 6.3 years (range 2–14 years), there were no complications related to coronary artery fistula.

It was concluded that the incidence of coronary artery fistulas detected during diagnostic coronary angiography is very low. Coronary artery fistulas originate predominantly from the right coronary artery and are not associated with hemodynamic abnormalities or other congenital heart diseases. The prognosis of coronary artery fistulas in adults is good. © 1995 Wiley‐Liss, Inc.
Intracoronary ST‐T alternans during coronary balloon angioplasty
Authors: Kwan Tak , Feit Alan , Chadow Hal , Chio Francisco , Huber Michael S. , Chebaclo Mohamed , Breitbart Sheldon , Stein Richard A.
Published: March 2007

To evaluate the presence and clinical significance of electrical alternans during PTCA, intracoronary electrocardiography (ic‐ECG) was performed in 65 consecutive lesions. ST‐T alternans, defined as a beat‐to‐beat difference in the ST elevation ⩾1 mm, was present in five lesions (7.7%), all in the proximal left anterior descending (LAD) coronary artery. The phenomenon was seen only after 130 sec (mean 174 ± 57) of balloon inflation. Only two of the five showed ST‐T alternans simultaneously on both surface and ic‐ECG. One of five patients had premature ventricular contractions following ST‐T alternans. Three of these five lesions required a second balloon inflation with duration of ⩾ 300 sec; there was no ST‐T alternans on the second inflation in any of these lesions. We conclude: (1) the detection of ST‐T alternans during PTCA is enhanced by use of ic‐ECG, (2) electrical alternans during PTCA was seen only in proximal LAD lesions, implicating a large amount of ischemic myocardium as a requisite for the phenomenon, (3) electrical alternans is not immediate, requiring a certain duration of balloon occlusion and hence ischemia to occur, and (4) the absence of ST‐T alternans during second balloon inflations suggests ischemic preconditioning may abolish this phenomenon.
Successful intravenous streptokinase treatment of a child with Kawasaki disease complicated by acute myocardial infarction
Authors: Liang Chi‐Di , Huang Song‐Chei , Su Wen‐Jen , Chen Hui‐Yung , Lee Chiang‐Hsuan
Published: March 2007

A 9‐year‐old boy developed ischemic cardiac symptoms 1 year after he presented with Kawasaki disease. The myocardial infarction was confirmed by the typical changes of electrocardiograms, echocardiograms, cardiac enzymes, thallium myocardial scintigrams, and angiograms. With successful intravenous streptokinase therapy, he remained well during the following 4 months. © 1995 Wiley‐Liss, Inc.
Radiation‐induced mitral and tricuspid regurgitation with severe ostial coronary artery disease: A case report with successful surgical treatment
Authors: Raviprasad G. S. , Salem Bakr I. , Gowda Siddhesh , Leidenfrost Ronald
Published: March 2007

A 71‐year‐old woman presented with congestive heart failure due to severe mitral and tricuspid regurgitations. In addition, she had significant ostial right coronary stenosis. She received radiation therapy following left radical mastectomy for carcinoma of breast in the past. She underwent successful combined mitral valve replacement, tricuspid annuloplasty, and coronary artery bypass graft for radiation‐induced heart disease. © 1995 Wiley‐Liss, Inc.
Functional characteristics of a new coronary perfusion balloon: Comparison with the flowtrack 40 in closed chest swine
Authors: Lambert Charles R. , Bikkina Mahesh
Published: March 2007

This study was designed to compare a new investigational coronary perfusion balloon (Wave, Scimed Life Systems Inc.) with that of an approved, widely used, current generation device (Flowtrack 40, Advanced Cardiovascular Systems). Domestic swine were anesthetized with pentobarbital and instrumented using standard percutaneous technique. Left ventricular contractile function (dP/dt) was monitored using a micromanometer while intracoronary and surface ECGs were also recorded. Eight target vessels were studied (4 LAD and 4 Cx) in random order. The perfusion balloons were kept inflated for 10 min. Complete coronary occlusion with a standard angioplasty balloon produced marked decreases in mean aortic pressure, left ventricular developed pressure, peak + dP/dt, peak ‐dP/dt, and significant ST segment elevation in both intracoronary and surface ECG at 30 seconds. Neither the Wave or Flowtrack 40 produced any change in heart rate or mean aortic pressure. Both catheters caused a drop in left ventricular developed pressure immediately after balloon inflation. At 10 min, however, there was a small but significant decrease only with the Flowtrack 40. Similarly, peak + dP/dt was slightly depressed during Flowtrack 40 inflation at 10 min but not with the Wave catheter. Both catheters produced ST segment elevation on the surface and intracoronary electrocardiographic records. These changes were significantly greater with the Flowtrack 40 system. Thus, both the Flowtrack 40 and Wave perfusion balloons are effective in preventing ischemia during coronary occlusion in swine; however, the latter system may be more effective in this model. © 1995 Wiley‐Liss, Inc.
Angiographic diagnosis of true and false LV aneurysms after inferior wall myocardial infarction
Authors: Al‐Saadon K. , Walley V. M. , Green M. , Beanlands D. S.
Published: March 2007

False aneurysms of the left ventricle are rare complications of myocardial infarction. In this unusual case, a 57‐year‐old male patient had a false aneurysm, that took origin from a true aneurysm in the inferior wall, both discovered 7 years postinfarct. The aneurysms were demonstrable by ventriculography and were resected because of ventricular tachycardia. © 1995 Wiley‐Liss, Inc.
Balloon expandable stent implantation after latrogenic arterial dissection of the left subclavian artery
Authors: Galli Mario , Goldberg Steven L. , Zerboni Santoni , Almagor Yaron
Published: March 2007

A patient undergoing attempted angioplasty of a left internal mammary artery graft to left anterior descending coronary artery developed an iatrogenic dissection of the left subclavian artery, with symptoms of left arm claudication. A balloon expandable stent was inserted with an excellent angiopgraphic result. The patient has remained free of symtoms or signs of decreased arm flow, with a patent subclavian artery demonstrate on angiography 8 months later. The excellent early‐to‐moderate term clinical and angiographic results support the efficacy of this technical approach. © 1995 Wiley‐Liss, Inc.
Guide wire extension may not be essential to pass an over‐the‐wire balloon catheter
Authors: Ahmad Tanvir , Webb John G. , Carere Ronald G. , Dodek Arthur
Published: March 2007

The ability to pass an angioplasty balloon catheter over a regular length free guidewire can be advantageous in certain circumstances. This procedure was performed successfully in 99 consecutive patients without any complications. There was improved tactile sense of the lesion and improved dye delivery without the necessity of resorting to the use of extension wires or magnet exchange device. When performed while observing the required precautions this is a safe procedure.
Percutaneous balloon pericardiotomy: A double‐balloon technique
Authors: Iaffaldano Robert A. , Jones Paul , Lewis Bruce E. , Eleftheriades Elias G. , Johnson Sarah A. , McKiernan Thomas L.
Published: March 2007

We describe a double‐balloon technique for performing a percutaneous balloon pericardiotomy. This technique was employed when the large, single dilation balloon customarily used for this procedure failed to fully inflate across the parietal pericardium. Two smaller balloons were advanced through the same skin tract and simultaneously inflated, thus producing an adequate pericardial window. This double‐balloon technique allowed for the more secure anchoring of the balloons across the pericardium and for the delivery of greater dilation pressures. © 1995 Wiley‐Liss, Inc.
Morphologic characteristics of restenotic lesions following coronary interventions: Balloon angioplasty versus directional atherectomy: Can we speculate about the mechanism of restenosis from morphologic analysis?
Authors: Moreu Jose , Silver Marc T. , Palacios Igor F. , Jang Ik‐Kyung
Published: March 2007

In order to compare the processes of restenosis after balloon angioplasty as compared to that after directional coronary atherectomy, we performed qualitative and quantitative analysis of 72 lesions in 68 patients with recurrent ischemia following a successful initial procedure. For each lesion, we reviewed the pre‐intervention, immediate post‐intervention, and restenosis angiograms. The morphology of the restenotic lesions could not be predicted from pre‐ or post‐intervention angiograms. The restenotic lesions after directional atherectomy, as compared to balloon angioplasty, did not show a statistically significant difference, although there was a trend to more eccentric narrowing. © 1995 Wiley‐Liss, Inc.
Juxtaposed “kissing” stents as a technique to preserve both limbs of a bifurcating renal artery
Authors: Avula Surendra , Dorros Gerald
Published: March 2007

Percutaneous revascularization with balloon expandable stent placement and/or balloon angioplasty has been proven to be an effective alternative for renal artery bypass surgery for management of renal artery stenosis. Endovascular stent deployment has been proven to be superior to balloon angioplasty alone, especially for ostial lesions in terms of maintaining long‐term patency. Here we describe a case report for deployment of two Palmaz stents with simultaneous utilization of brachial and femoral routes. Technical aspects for this procedure, especially adaptation of coronary guide wire systems in management of renal artery stenosis were discussed. © 1995 Wiley‐Liss, Inc.
Method of preparing, mounting, and implanting a palmaz‐schatz coronary half‐stent from the stent delivery system
Authors: Koh Tian‐Hai
Published: March 2007

Full‐length 15 mm Palmaz‐Schatz coronary stents currently come premounted in a specially designed stent delivery system. A method is described for obtaining a bare half‐stent from this system and mounting it onto a balloon catheter. The technique of half‐stent delivery and implantation is discussed and is illustrated by a case example. © 1995 Wiley‐Liss, Inc.
Percutaneous transvenous mitral commissurotomy using inoue balloon catheter: A left femoral vein approach
Authors: Patel Tejas M. , Dani Sameer I. , Rawal Jayesh R. , Shah Sanjay C. , Patel Thakorebhai K.
Published: March 2007

Percutaneous transvenous mitral commissurotomy by the Inoue technique is usually recommended from right femoral vein approach only. We report an unusual patient in whom the left femoral vein approach was used successfully. We believe that the left femoral vein approach can be reserved as a last resort in certain cases. © 1995 Wiley‐Liss, Inc.
Predictors of short term clinical and angiographic outcome after coronary angioplasty for acute myocardial infarction
Authors: Zimarino Marco , Corcos Thierry , Favereau Xavier , Garcia Elias , Tamburino Corrado , Guérin Yves
Published: March 2007

Coronary angioplasty is an effective method to achieve myocardial reperfusion in acute myocardial infarction (AMI). We reviewed our experience in 132 patients (pts) who underwent percutaneous transluminal coronary angioplasty (PTCA) of a totally occluded infarct‐related artery (IRA) within 24 h after the onset of symptoms (mean delay 10±7 h), in order to identify the predictors of primary success and of major complications. PTCA was successfully performed in 113 patients (86%). Failure without complications occurred in 12 patients (8.4%); untoward events (death and emergency CABG) occurred in seven patients (5.3%). Pts in the failure group were more likely to have cardiogenic shock (53 vs. 8.8%, P<.0005), longer time to reperfusion (15±6 vs. 9±6 h, P<.0005), lower ejection fraction (EF) (42±16 vs. 54±12%, P<.0005), multivessel disease (74 vs. 43%, P<.03), and a smaller IRA diameter (2.8±0.6 vs. 3.1± 0.6 mm, P<.03). Sex, age, previous bypass surgery, previous thrombolytic treatment, IRA, and infarct location were similar in both groups. Absence of cardiogenic shock (P<.0001), decreasing time to reperfusion (P<.005) and increasing EF (P<.02) were independent predictors of successful PTCA. Presence of cardiogenic shock (P<.0001) and decreasing EF (<.05) were independent predictors of untoward events. Repeat angiography was performed 24 h after the procedure in the success group. Angiographic deterioration (stenosis ⩾ 50% and/or TIMI flow grade ⩽ 1) was present in 18 pts (16%), among whose 5 pts (4.4%) had re‐occlusion of the IRA. Pts with early angiographic deterioration were more likely to have a lower IRA diameter (2.8±0.5 vs. 3.1±0.6 mm, P<.02). Conclusion: Emergency PTCA is an effective method for establishing reperfusion in AMI. Pts with high‐risk baseline characteristics show the highest rate of untoward events, but are the most likely to benefit from aggressive reperfusion therapy. © 1995 Wiley‐Liss, inc.
Late development of dissecting aneurysm following balloon angioplasty of native aortic coarctation
Authors: Aydogan Umrah , Dindar Aygun , Gurgan Lerzan , Cantez Talat
Published: March 2007

Acute aortic dissection during balloon angioplasty for coarctation of the aorta or aneurysm formation during follow‐up are well‐known complications of this procedure. Dissecting aneurysm development during long‐term follow‐up after balloon angioplasty of a native coarctation has not been previously reported. We report a case in which a huge dissecting aneurysm developed 3 years after the native coarctation angioplasty procedure. The aneurysm required surgical repair. © 1995 Wiley‐Liss, Inc.
Transcatheter embolization coil closure of patent ductus arteriosus ‐modified delivery for enhanced control during coil positioning
Authors: Kuhn Micheal A. , Latson Larry A.
Published: March 2007

The use of Gianturco coils (Cook, Inc., Bloomington, IN) has been recently described as a method of occluding restrictive patent ductus arteriosus (PDA). Precise control of the coil during positioning or withdrawal is difficult. We designed an inexpensive and readily available system to control the coil during delivery and repositioning. A 5 French Mallincrodt vertebral catheter was heat tapered to allow slight, but definite resistance of a 0.035″ guide wire when it was passed through the catheter. The delivery system has been used to successfully coil occlude restrictive PDAs in seven patients. The system has added no additional costs to the procedure and has provided improved control of the coil position prior to release of the coil. © 1995 Wiley‐Liss, Inc.
Efficacy of angioscopy in determining the effectiveness of intracoronary urokinase and TEC atherectomy thrombus removal from an occluded saphenous vein graft prior to stent implantation
Authors: Kaplan Barry M. , Safian Robert D. , Goldstein James A. , Grines Cindy L. , O'Neill William W.
Published: March 2007

Percutaneous revascularization of thrombus containing saphenous vein grafts is associated with a high incidence of acute complications. This case report describes successful revascularization of an occluded vein graft employing angioscopically guided sequential urokinase infusion, TEC atherectomy and stent implantation. © 1995 Wiley‐Liss, Inc.
Coronary angioplasty of branch vessels associated with an extreme angle take‐off
Authors: Gershony Gary , Hussain Hassan , Rowan William
Published: March 2007

Stenoses in branch vessels which originate at an acute angle to the main vessel represent a technically challenging anatomy for the performance of balloon angioplasty [PTCA]. We report a novel technique utilizing a distally placed perfusion balloon that facilitated guidewire placement and subsequent balloon angioplasty of a branch vessel stenosis. © 1995 Wiley‐Liss, Inc.
Evidence for dynamic coronary vasoconstriction of non‐infarct vessels during acute myocardial infarction
Authors: Kahn Joel K.
Published: March 2007

The role of coronary vasoconstriction in acute myocardial infarction is controversial. Two patients are presented who were studied with angiography during the early hours of acute myocardial infarction and in whom reversible spasm of non‐infarct vessels was observed. A tendency towards coronary vasospasm may be a generalized phenomenon during acute myocardial infarction. © 1995 Wiley‐Liss, Inc.
Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation
Authors: Wu Li , Vremec David , Ardavin Carlos , Winkel Ken , Süss Gabriele , Georgiou Harry , Maraskovsky Eugene , Cook Wendy , Shortman Ken
Published: March 2007

The early thymus precursor population of adult mice has the capacity to generate T cells, B cells and dendritic cells (DC). These precursors were injected into the thymus of irradiated recipients in order to follow the kinetics of thymic DC development. The resultant cohort of T‐lineage cells developing in the thymus was accompanied by a parallel cohort of DC, present at 103‐fold lower frequency. The intrathymic lifespan of these DC was as short as that of T‐lineage thymocytes. As the thymic DC matured, some markers characteristic of the original precursor population gradually declined (Ly‐5, c‐kit, Sca‐2) whereas markers characteristic of thymic DC appeared and were maintained (major histocompatibility complex class II, CD11c, NLDC‐145 and CD8α). Some thymic DC expressed the early B‐cell marker BP‐1, and BP‐1 mRNA, throughout their maturation. The surface markers on thymic DC could be divided into two groups. Some markers, including class I and class II MHC, CD8α and BP‐1, appeared to be integral components of the DC surface. In contrast, other markers, including Thy‐1, CD4 and CD8β, had probably been picked up from associated thymocytes.
Precursor B cells of mouse bone marrow express two different complexes with the surrogate light chain on the surface
Authors: Winkler Thomas H. , Rolink Antonius , Melchers Fritz , Karasuyama Hajime
Published: March 2007

Two monoclonal antibodies raised against the complex of μ heavy (H) chain and Vpre‐B/λ5 surrogate light (L) chains recognize surrogate L chain in different conformations on normal pre‐B cells. One, LM34 recognizes free λ5 protein and free λ5/Vpre‐B surrogate L chains and binds to surrogate L chains on the surface of early, pro‐B and pre‐B‐I cells where the surrogate L chain is associated with a gp130/gp35–65 complex of proteins. It also recognizes the surrogate L chain associated with the μH chain on pre‐B‐II cells. The other monoclonal antibody, SL156, does not recognize free surrogate L chain or its components, nor its complex with gp130/gp35–65 on pro‐B and pre‐B‐I cells. However, it does bind to a conformational epitope on the surrogate light chain/μH chain complex on a subpopulation of pre‐B‐II cells and on μH chain‐positive pre‐B cell lines. On mouse precursor B cells prepared ex vivo on ice, expression of the surrogate L chain is very low and almost undetectable. Incubation of the precursor cells for 1 h at 37 °C up‐regulates the surface expression of surrogate L chain associated with gp130/gp35–65 (early complex) as well as the μH chain/surrogate L chain complex. These results reconcile some of the apparently discrepant results on surface expression of the surrogate L chain obtained with human and mouse bone marrow pre‐B cells, and show that a surrogate L chain/μH chain‐containing pre‐B cell receptor can be expressed also on the surface of mouse pre‐B‐II cells.
Distribution of HLA class II molecules in epidermal Langerhans cells in situ
Authors: Mommaas A. Mieke , Mulder Aat A. , Out Coby J. , Girolomoni Giampiero , Koerten Henk K. , Vermeer Bert J. , Koning Frits
Published: March 2007

We performed immunoelectron microscopic studies to investigate the expression of HLA class II molecules in Langerhans cells (LC). In the epidermis, LC expressed class II molecules on the plasma membrane of the dendrites, resulting in a class II positive reticulo‐epithelial network, but not on the surface of the cell body. In contrast, isolated LC as well as activated LC in situ displayed an even and strong expression of class II molecules on their entire cell surface. Therefore, isolation and/or activation results in redistribution and up‐regulation of class II molecules on the cell surface. In addition, double‐labeling experiments were carried out with monoclonal antibodies to class II antigens and to LAMP‐1, CD63 and α‐glucosidase, specific markers for organelles of the endosomal/lysosomal system. The results show expression of class II molecules on intracellular, electron‐dense vesicular structures, and co‐localization of class II molecules and the markers for late endosomes and early lysosomes in human LC in situ. Expression of these markers was not found on Birbeck granules, an LC‐specific organelle.
Carbohydrate‐dependent, HLA class II‐restricted, human T cell response to the bee venom allergen phospholipase A2 in allergic patients
Authors: Dudler Thomas , Altmann Friedrich , Carballido José M. , Blaser Kurt
Published: March 2007

The T cell‐independent antibody response to polysaccharide antigen (Ag) is believed to result from their inability to bind major histocompatibility complex (MHC) restriction elements. However, recent studies using glycosylated analogues of known immunogenic peptides revealed that glycopeptides can interact with MHC molecules and are able to elicit specific T cell responses in experimental animals. This raises questions about the possible role which carbohydrates can play in T cell responses following natural exposure to glycoprotein antigens. Analyzing the fine specificity of the human T cell response against the major bee venom allergen phospholipase A2 (PLA), a 16–20‐kDa protein glycosylated at a single site (Asn13), we have identified several T cell clones which proliferate in response to the glycoprotein but not to its non‐glycosylated variants. Neither the carbohydrate moiety alone nor the combination of carbohydrate and nonglycosylated protein could substitute for the intact glycoprotein. Antibody directed against the carbohydrate moiety inhibited Ag‐induced proliferation of these clones whereas control clones with known peptide specificity were not affected, providing additional evidence for the involvement of carbohydrates in T cell recognition. Moreover, peripheral blood mononuclear cells of two individuals from whom glycosylation‐dependent T cell clones have been isolated showed significantly higher proliferation in response to glycosylated compared to non‐glycosylated Ag, suggesting that glycosylation can contribute in some cases extensively to the immunogenicity of a glycoprotein Ag. Thus, this report shows that glycosylation‐dependent Ag recognition by T cells can also occur following natural exposure to a glycoprotein.
Regulation of an anti‐polysaccharide immune response in BALB/c mice through a tight T and B lymphocyte idiotypic connection
Authors: Rademaekers André , Kölsch Eckehart
Published: March 2007

The isotype expression in the J558 idiotype‐associated humoral immune response against α(1 → 3)‐dextran in BALB/c mice is controlled by idiotype‐specific T cells which silence in situ B lymphocytes primed and committed to an IgG response. This leads to a restriction of the type II thymus‐independent response to the sole production of IgM antibodies. The availability of the T cell receptor (TcR) α and β sequences for such a regulatory T cell clone allows the investigation of the degree of heterogeneity of the TcR usage of these T cells. It is found that all α(1 → 3)‐dextran‐primed BALB/c mice use a very similar, possibly identical TcR. This suggests a tight, possibly genetically programmed, interaction between the J558 idiotype‐bearing dextran‐specific B cells and their idiotype‐specific regulatory T cell counterparts.
The nude mutation results in impaired primary antibody repertoire
Authors: Kaushik Azad , Kelsoe Garnett , Jaton Jean‐Claude
Published: March 2007

We have studied the effect of the nude mutation and/or T lymphocytes on the development of V gene germ‐line repertoire in neonatal athymic (nu/nu) and euthymic (+/nu) littermates. A total of 2.35 × 106 and 1.47 × 106 B lymphocyte clones from nu/nu and +/nu neonates, respectively, were examined for the expression of select VH (J558, J606, S107, 36–60, 7183 and Q52) and Vx (1, 2, 8 and 9) gene families as well as VH (J558, S107) + Vx (1, 9) associations. Data showed that the nude mutation, whether homozygous or heterozygous, significantly affects VH and Vx gene expression as well as VH and Vx pairings and, thus, provide evidence for a defective development of B cell repertoire in both athymic nude (nu/nu) and euthymic (+/nu) mice. In addition, an analysis of 3.34 × 106 B lymphocyte clones from adult C57BL/6 mice showed non‐stochastic association between VHJ558 + Vx1 gene families that suggests restrictions on clonal population in order to maintain homeostasis in the immune system. Studies outlined here, therefore, describe an hitherto unknown defect in the development of B lymphocyte repertoire as a result of the nude mutation which is independent of thymic dysgenesis.
Comparison of lymphokine secretion and mRNA expression in the CD45RA+ and CD45RO+ subsets of human peripheral blood CD4+ and CD8+ lymphocytes
Authors: Conlon Kevin , Osborne Jennifer , Morimoto Chikao , Ortaldo John R. , Young Howard A.
Published: March 2007

Flow cytometric analysis of human peripheral blood T lymphocytes demonstrated that the majority of the CD4+ cells were CD29+ or CD45RO+ “mature” cells while the CD8+ cells were primarily CD45RA+ “naive” cells. After an initial separation into CD4+ and CD8+ cells and a secondary separation into CD45 subsets, lymphokine secretion was assessed after phorbol 12‐myristate 13‐acetate and ionomycin or fixed anti‐CD3 stimulation. Within the respective CD45 subsets, CD4+ cells produced more interleukin (IL)‐2, IL‐4, and IL‐6; but the CD8+ cells secreted more interferon‐γ and granulocyte/macrophage‐colony‐stimulating factor. Tumor necrosis factor‐α secretion was similar in the matched CD45 subsets. Northern analysis revealed a parallel pattern of lymphokine mRNA expression in the four lymphocyte subsets. These results suggest that human CD8+ peripheral blood lymphocytes have a significant capacity to secrete lymphokines, and that the low lymphokine production observed in unseparated CD8+ cells reflects the higher percentage of less functional CD45RA+ cells.
Heparin inhibits the antiparasitic and immune modulatory effects of human recombinant interferon‐γ
Authors: Däubener Walter , Nockemann Susanne , Gutsche Marc , Hadding Ulrich
Published: March 2007

Interferon‐γ (IFN‐γ) is a potent immune regulatory cytokine and is, in addition, involved in the induction of antiparasitic effector mechanisms in different cell types. The first step of IFN‐γ action is its binding to a specific receptor. Furthermore, it has been shown that IFN‐γ binds with a great affinity to the heparin‐like structure of heparan sulfate, which is localized in basement membranes and on cell surfaces. In this study, we analyze the effect of heparin and heparan sulfate on three different IFN‐γ‐mediated activities inducible in human glioblastoma cells (87HG31 and 86HG39).

We find firstly that heparin is able to inhibit IFN‐γ‐mediated induction of major histocompatibility complex (MHC) class II antigen expression on 87HG31 cells, an effect which can be abrogated by protamine. Secondly, we show that heparin inhibits the IFN‐γ‐induced toxoplasmostasis within 86HG39 cells in a dose‐dependent fashion, and thirdly that heparin inhibits the IFN‐γ‐mediated induction of the tryptophan‐degrading enzyme indoleamine 2,3‐dioxygenase. In contrast to IFN‐γ‐induced effects, the activity of other cytokines, such as interleukin (IL)‐1, IL‐2 and IL‐6, is not influenced by heparin. The possible mechanism of heparin‐induced inhibition of IFN‐γ is discussed.
Role of the thymus in the generation of skin‐homing αβ and γδ virgin T cells
Authors: Washington Elizabeth A. , Kimpton Wayne G. , Holder Joanne E. , Cahill Ross N. P.
Published: March 2007

Current models of lymphocyte traffic suggest that homing specificities of T cells to tissues such as skin are generated outside the thymus as a result of activation of naive T cells by antigen in lymph nodes. Virgin T cells are thought to home to high endothelial venules in lymph nodes, but are thought to be unable to home to extra‐lymphoid tissues such as skin. We used the technique of in situ labeling of the thymus with fluorescein isothiocyanate to examine the homing specificities of authentically naive T cells in vivo, immediately after their export from the thymus. We report that homing specificities for skin as well as lymph node are imprinted on T cells inside the thymus, independent of antigen. We also show that both αβ and γδ emigrant T cells exhibit homing patterns to skin and lymph nodes which are identical to those of mature T cells. Our findings demonstrate a key role for the thymus in the induction of skin‐homing specificities on T cells indicating that skin‐homing specificities of T cells are not generated solely outside the thymus as a result of the activation of virgin T cells by antigen. The migration of thymic emigrants to extra‐lymphoid tissues within a few hours of leaving the thymus may have implications for mechanisms of peripheral self‐tolerance. This pathway provides an opportunity for direct virgin T cell interactions with self components only expressed in the periphery at a time when emigrants may be more susceptible to tolerance induction than mature circulating T cells.
CD8+ and CD45RA+ human peripheral blood lymphocytes are potent sources of macrophage inflammatory protein 1α, interleukin‐8 and RANTES
Authors: Conlon Kevin , Lloyd Andrew , Chattopadhyay Utpala , Lukacs Nicholas , Kunkel Stephen , Schall Thomas , Taub Dennis , Morimoto Chikao , Osborne Jennifer , Oppenheim Joost , Young Howard , Kelvin David , Ortaldo John
Published: March 2007

The chemokines macrophage inflammatory protein 1α (MIP 1α), interleukin‐8 (IL‐8) and RANTES are potent regulators of leukocyte trafficking. Examination of chemokine secretion by human peripheral blood lymphocytes after stimulation with anti‐CD3 or phorbol 12, 13 myristate acetate and ionomycin showed CD8+ cells were the dominant source of MIP 1α and RANTES. Although production of MIP 1α and IL‐8 were similar in pharmacologically stimulated CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ CD45RA+ cells, the largest amounts of MIP 1α and RANTES were secreted by CD8+ CD45RO+ lymphocytes. A parallel pattern of prolonged chemokine mRNA expression for at least 18 h after activation was observed in the T cell subsets. These results confirm that human T lymphocytes have a unique capacity for secretion of these three chemokines. In addition, CD8+ cells have an unrecognized role in recruiting cells to sites of inflammation, and adult human CD45RA+ cells have a physiologically significant secretory capacity.
Limited development capacity of the earliest embryonic murine thymus
Authors: Amagai Takashi , Itoi Manami , Kondo Yuichi
Published: March 2007

Previous studies have demonstrated that murine thymus separates from the pharynx during 11.5–12 days of gestation, and that the proliferation of thymic cells starts at this age. We characterized embryonic day 12 thymus in terms of the surface phenotype of the thymus cells, the function of the lobe in supporting T cell development in organ culture, and the precursor activity of the thymus cells in a mixed culture with deoxyguanosine‐treated lobes.

The phenotype of the major population of embryonic day 12 thymus cells was HSA+, CD44+, c‐kit+, Thy‐1−, CD25−, CD4−, CD8−, TcR−, and Sca‐1−. In organ culture of embryonic day 12 thymus lobes, most of the lobes did not develop well and failed to generate CD4+CD8+, CD4+CD8−, or CD4−CD8+ cells, even when embryonic day 14 thymus cells were added. However, thymus cells on embryonic day 12 contained T cell precursors that developed into mature T cells in co‐culture with deoxyguanosine‐treated fetal thymic lobes. The majority of the stromal cells in deoxyguanosine‐treated embryonic day 14 thymus lobes expressed the surface molecules I‐A and H‐2D, whereas these cells in embryonic day 12 thymus lobes were negative for these surface molecules. Thus, our findings suggest that the embryonic day 12 thymus lobe contains T cell precursors, but that the undeveloped thymic stromal cells are insufficient to support full T cell development.
The non‐histone chromosomal protein HMG‐I(Y) contributes to repression of the immunoglobulin heavy chain germ‐line ε RNA promoter
Authors: Kim Jinny , Reeves Ray , Rothman Paul , Boothby Mark
Published: March 2007

The rate of germ‐line RNA transcription correlates with the rate of immunoglobulin heavy chain isotype switching. A promoter element for the transcription of RNA from the germ‐line mouse immunoglobulin ε heavy chain constant region gene is induced by interleukin(IL)‐4 and lipopolysaccharide, and is bound at its transcription initiation sites by an IL‐4‐inducible nuclear protein, NF‐BRE. To examine the function of the binding site for this IL‐4‐inducible complex, substitution mutations were introduced in the promoter. These binding site mutations increased promoter activity and decreased binding of NF‐BRE. To investigate the paradox of an IL‐4‐inducible protein binding to a repressor site in an IL‐4‐inducible promoter, we determined that the non‐histone chromosomal protein HMG‐I(Y) binds at the transcription initiation sites of the germ‐line epsilon promoter. Assays with antisera against HMG‐I(Y) revealed monomeric HMG‐I(Y) in nuclear extracts. Cotransfection of an expression construct directing the synthesis of anti‐sense HMG‐I(Y) RNA also increased promoter activity, consistent with a repressor function of HMG‐I(Y). Thus, the data are most consistent with a model in which HMG‐I(Y) participates in repression of promoter activity. The effects of IL‐4 may include derepression at this site.
Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia
Authors: De La Morena Maite , Haire Robert N. , Ohta Yuko , Nelson Robert P. , Litman Ronda T. , Day Noorbibi K. , Good Robert A. , Litman Gary W.
Published: March 2007

The transcription pattern of the heavy chain immunoglobulin gene locus was analyzed in a 6‐month‐old female with agammaglobulinemia characterized by the absence of mature B cells in peripheral blood, arrested B cell development in the bone marrow and lack of germinal center development. DNA sequencing provided no evidence of mutations within the coding region of the Bruton's tyrosine kinase gene. Polymerase chain reaction‐generated cDNA libraries from blood and bone marrow were screened initially using JH and CH oligodeoxynucleotide probes and VH family‐specific probes. Only 10% of the transcripts constituted mature VDJCμ recombinations. Ninety percent of the cDNA were sterile immunoglobulin transcripts comprised of: DJCμ (DH−JHCμ), JCμ (JH−Cμ), ECμ (enhancer spliced to Cμ), SCμ and ICμ [corresponding to switch (S) and intron (I) regions spliced to Cμ]. In the mature immunoglobulin transcripts, VH use indicated germline expression with little evidence of somatic mutation. All cDNA were of the Cμ type. Different D segments, D‐D joining events and unknown D‐like elements were noted in the DJCμ and VDJCμ transcripts. This pattern of immunoglobulin rearrangements, along with the phenotypic cell surface antigen characteristics (CD19−), suggest that an earlier arrest in B cell development than is characteristic of Bruton's X‐linked agammaglobulinemia has occurred in this patient.
Specific hyporesponsiveness of alloreactive peripheral T cells induced by CD4 antibodies
Authors: Vincent Claude , Fournel Sylvie , Wijdenes John , Revillard Jean‐Pierre
Published: March 2007

We investigated whether exposure of naive and in vitro pre‐activated T cells to CD4 monoclonal antibodies (mAb) could induce specific hyporesponsiveness to a subsequent challenge in the absence of CD4 mAb. Unfractionated peripheral blood mononuclear cells were cultured with mitomycin‐treated B cell lines as stimulator cells, in the presence or absence of CD4 mAb, then challenged with the same or unrelated stimulator cells. The kinetics of [3H] thymidine incorporation, blast transformation and CD25 expression were determined. Cells activated in primary or secondary culture in the presence of CD4 mAb demonstrated a markedly decreased response to subsequent challenge in the absence of antibody. This effect was reproduced with three different CD4 mAb of the IgG1 and IgG2a subclasses, which recognize two distinct epitopes of the CD4 molecule. Addition of recombinant interleukin‐2 (rIL‐2) during exposure to CD4 mAb failed to prevent the induction of specific hyporesponsiveness. Similarly, exogenous rIL‐2, added together with stimulating cells, failed to restore the specific proliferative response, indicating that the mechanisms were different from those of classical anergy. The hyporesponsiveness was clonally restricted since CD4 mAb‐pretreated cells developed a normal primary response to third‐party stimulator cells. No increase in the percentage of apoptotic cells was observed in hyporesponsive cell populations, but selective clonal deletion cannot be excluded. The data demonstrate a delayed effect of CD4 ligation on T cell responses to a subsequent challenge.
Interleukin‐12 profoundly up‐regulates the synthesis of antigen‐specific complement‐fixing IgG2a, IgG2b and IgG3 antibody subclasses in vivo
Authors: Germann Tieno , Bongartz Martina , Dlugonska Henryka , Hess Henry , Schmitt Edgar , Kolbe Ludger , Kölsch Eckehart , Podlaski Frank J. , Gately Maurice K. , Rüde Erwin
Published: March 2007

The influence of the cytokine interleukin‐12 (IL‐12) on humoral immune responses was studied in vivo. CBA/J mice immunized with protein antigens (keyhole limpet hemocyanin, phospholipase A2) adsorbed to aluminum hydroxide (Alum) develop a Th2‐like immune response characterized by the production of large amounts of IgG1 as well as some IgE but little IgG2a, IgG2b and IgG3 antibodies. IL‐12 is a cytokine that promotes the development and the activation of Th1 cells. Th1 cells are involved in the induction of cellular immunity, which is characterized by low or absent antibody production. On the other hand, some Th1‐like immune responses are associated with a strong antibody production of the IgG2a, IgG2b and IgG3 subclasses. Thus, we investigated whether treatment with IL‐12 would down‐regulate the humoral immune response or stimulate antibody production of the IgG2a, IgG2b and IgG3 subclasses. We observed that: 1) administration of IL‐12 to mice together with protein antigens adsorbed to Alum strongly enhanced the humoral immune response by increasing the synthesis of antigen‐specific antibodies of the IgG2a, IgG2b and IgG3 subclasses 10‐ to 1000‐fold. The synthesis of IgG1 was not or only slightly (2–5‐fold) enhanced, whereas that of the IgE isotype was suppressed. 2) These effects of IL‐12 were observed when high (10 μg, 100 μg) or low doses (0.1 μg) of antigen were used for immunization. 3) Titration of IL‐12 in vitro revealed that IgG2a is strongly up‐regulated over a wide dose range of IL‐12 (10 to 1000 ng/day). 4) The effects of IL‐12 in vivo are at least partially interferon (IFN)‐γ‐dependent because an anti‐IFN‐γ mAb in combination with IL‐12 prevented most of the enhanced IgG2a production. 5) Mice receiving IL‐12 showed a strong up‐regulation of IFN‐γ but no inhibition of IL‐5 synthesis by spleen cells activated ex vivo with antigen. These results suggest that IL‐12 is a potent adjuvant for enhancing humoral immunity to protein antigens adsorbed to Alum, primarily by inducing the synthesis of the complement‐fixing IgG subclasses 2a, 2b and 3.
Assessment of a functional role of auto‐anti‐idiotypes in idiotype dominance
Authors: Ismaili Jamila , Brait Maryse , Leo Oberdan , Urbain Jacques
Published: March 2007

We have used a well‐defined idiotypic system, the cross‐reactive idiotype of A strain (CRIA) (Ab1) idiotype generated in A/J mice injected with arsonate coupled to keyhole limpet hemocyanin (ARS‐KLH), to determine the frequency of precursors for auto‐anti‐idiotypic antibodies (auto‐Ab2) in naive and immunized A/J mice by limiting dilution analysis after polyclonal activation by lipopolysaccharide. In naive animals, the precursor frequencies of auto‐Ab2 B cells were below the limit of sensitivity of the technique in the majority of A/J mice, and could be detected in only 20% of the animals. Upon immunization with ARS‐KLH, a large increase in auto‐Ab2 precursor frequency was observed. This shift in frequency was not found when A/J mice were injected with KLH alone, or when BALB/c mice, which do not express the CRIA idiotype, were injected with ARS‐KLH. To study the functional role of the auto‐Ab2 B cells, we injected neonatal A/J mice with polyclonal rabbit Ab3 antibodies directed against a recurrent idiotype of auto‐Ab2. Thereafter, these mice were injected with ARS‐KLH. Although the anti‐arsonate response level was normal, the CRIA Ab1 expression was reduced tenfold. Thus, the suppression of auto‐Ab2 affects Ab1 dominance. We further show that the presence of maternal Ab1 can strongly modify the immune response of the offspring by inducing higher levels of the idiotype after immunization. Furthermore, IgM anti‐arsonate antibodies were detected before immunization with antigen. From these data, we conclude that the affinity of antigen alone cannot explain the dominance of CRIA. Network selection is important in the shaping of the available repertoire.