bluuebunny/crossref_metadata_2025 huggingface dataset:
Transluminal extraction catheter for the treatment of diseased saphenous vein grafts: A multicenter experience
Authors: Meany Thomas B. , Leon Martin B. , Kramer Barry L. , Margolis James R. , Matthews Ray V. , Whitlow Patrick L. , Moses Jeffrey W. , Knopf William D. , Tommaso Carl L. , Sketch, Jr Michael H. , O'Neill William W.
Published: March 2007

To evaluate the efficacy, safety, and long‐term results of atherectomy using the Transluminal Extraction catheter (TEC®), patients with diseased saphenous vein grafts were enrolled in a prospective nonrandomized trial. Patients were followed to hospital discharge for acute complications and underwent routine 6‐mo reevaluation with repeat cardiac catheterization to assess restenosis.

Atherectomy was performed on 650 graft lesions in 538 consecutive patients (male 81%; mean age 66 yr; range 37–81). Mean graft age was 8.3 yr; (range 0.3–20) with 85% of grafts > 3 yr of age. Complex lesion morphology included thrombus (28%), ulceration (13%), and eccentricity (50%). Lesion success was achieved in 606 lesions (93%) with clinical success in 479 patients (89%). Lesion success was achieved in 90% of thrombus containing lesions, 97% of ulcerated lesions, and 97% of grafts > 3 yr. Complications included nonfatal myocardial infarction in 4 (0.7%) of patients, emergency bypass surgery in 2 (0.41%), and in‐hospital death in 17 patients (3.2%). Angiographic follow‐up at 6 mo was obtained from 268 lesions in 227 patients. The overall lesion angiographic restenosis rate was 60%.

TEC® atherectomy can be performed in patients with diseased saphenous vein grafts with high primary success and low complication rates. It is suitable for use in aged grafts, particularly in the presence of thrombus and ulcerations, and may be superior to balloon angioplasty alone in this group of patients.
Treatment of acute stent thrombosis with local urokinase therapy using catheter‐based, drug delivery systems: A case report
Authors: Mitchel Joseph F. , McKay Raymond G.
Published: March 2007

Abrupt thrombotic stent closure remains a difficult problem to treat in the cardiac catheterization laboratory. A 63‐yr‐old white female initially underwent successful placement of a Palmaz‐Schatz biliary stent in the proximal RCA following failed coronary angioplasty. One week later, the patient represented with an acute inferior infarction and thrombotic occlusion of the stent site in spite of adequate anticoagulation. A new, local drug infusion catheter (the Dispatch™ catheter) was placed at the angioplasty site and 150,000 units of urokinase were locally infused, with immediate restoration of normal distal flow and a subsequent marked decrease in angiographic thrombus. A small, residual thrombotic filling defect was further treated with a urokinase‐coated hydrogel balloon (Hydro Plus™). Following local urokinase delivery with the Dispatch catheter and hydrogel balloon, there was complete resolution of angiographic thrombus with TIMI 3 flow and no evidence of distal embolization or no‐reflow. Local urokinase delivery directly to the site of thrombus with catheter‐based drug delivery systems may be a useful technique for rapidly lysing intracoronary clot and re‐establishing coronary flow in the setting of acute stent thrombosis.
Randomized evaluation of six French Voda‐type guiding catheters for left coronary artery balloon angioplasty
Authors: Hoang Vincent , Urban Philip , Chatelain Pascal , Metz Damien , Camenzind Edoardo , Brzostek Tomasz , Rutishauser Wilhelm
Published: March 2007

In order to evaluate 6 French (6F) Voda‐type guiding catheters for left coronary artery balloon angioplasty, we randomized the choice of the guiding catheter in 100 consecutive patients between a Voda (group 1, n = 50) and a Judkins or Amplatz curve (group 2) guiding catheter. Angioplasty success rate (98% for both), need for guiding catheter crossover exchange (2 in group 1 vs. 1 in group 2), fluoroscopy time, and volume of injected contrast were similar in both groups, but the operator's appreciation of good back‐up support was better with the Voda‐type guiding catheter (90% vs. 74%, P < 0.05). No complications attributed to the guiding catheter were noted in either group. Efficiency of the Voda‐type guiding catheter appeared similar for both left anterior descending (n = 35, success rate 100%) and circumflex (n = 18, success rate 94%) coronary artery angioplasty.

Voda‐type guiding catheters are an efficient and safe approach to routine left coronary angioplasty. They appear to be as effective as a choice bewtween a Judkins or an Amplatz configuration and could be of particular use when a double angioplasty of the left anterior descending and circumflex arteries is attempted during the same procedure. © 1995 Wiley‐Liss, Inc.
Safety of coronary ultrasound angioplasty: Effects of sonication on intact canine coronary arteries
Authors: Rosenschein Uri , Rozenszajn Leon A. , Bernheim Joel , Keren Gad , Alter Ariela , Frimerman Aron , Laniado Shlomo , Roth Arie , Miller Hylton I.
Published: March 2007

The purpose of this work was to examine in vivo the safety of sonication in the coronary arteries in a live animal model. In intact dogs (n = 8), balloon dilatation was performed on the proximal left anterior descending artery (LAD) followed by sonication to the left circumflex artery (LCX) in power levels found to be optimal for thrombus ablation. Postdilatation and post‐ultrasound coronary angiography, echocardiography, histopathology, CK‐MB, indices of hemolysis, and coagulation were compared. Sonication did not induce changes in the ECG or blood pressure. Coronary angiography revealed no adverse side effects or change in arterial diameter (2.3 ± 0.7 vs. 2.4 ± 0.3 mm). Echocardiography showed transient opacification of the myocardium. Histopathology revealed a comparable minimal degree of endothelial denudation. After sonication there were no changes in the level of CK‐MB (312 ± 168 vs. 283 ± 207 IU), hemoglobin (11.3 ± 0.9 vs. 12.7 ± 1.1 gr%), haptoglobin (479 ± 136 vs. 451 ± 121 mg/dL), fibrinogen (142 ± 18 vs. 165 ± 28 mg%), partial thromboplastin time (17.3 ± 3.2 vs. 17.6 ± 3.4 sec), prothrombin time (13.3 ± 7.8 vs. 11.5 ± 2.9 sec), and degree of platelet aggregation (55 ± 17 vs. 62 ± 8%). Thus, the data suggest that transluminal coronary sonication exerts no overt adverse effects in vivo. © 1995 Wiley‐Liss, Inc.
Transhepatic central venous access for cardiac catheterization and radiologic intervention
Authors: Johnson Jeffrey L. , Fellows Kenneth E. , Murphy John D.
Published: March 2007

We describe a technique of direct puncture and catheterization of the hepatic veins for cardiac catheterization and radiologic intervention in children who lack conventional access routes. Four patients underwent eight direct hepatic vein punctures to allow cardiac catheterization (3 patients) and 5–12 F sheath insertions for balloon dilatation of hepatic vein stenoses (1 liver transplant patient). Gelfoam was injected in the sheath tract for hemostasis. All procedures were successful, including five hepatic vein dilatations and right heart access for three cardiac catheterizations. There were no complications. When conventional venous access is precluded, direct percutaneous catheterization of hepatic veins is easy, effective, and probably low risk. © 1995 Wiley‐Liss, Inc.
Guidewire transection during rotational coronary atherectomy due to guide catheter dislodgement and wire kinking
Authors: Foster‐Smith Karl , Garratt Kirk N. , Holmes David R.
Published: March 2007

Rotational coronary atherectomy is an effective treatment for calcified ostial lesions. We report a case of guidewire transection during rotational atherectomy of a right coronary artery ostial stenosis. Guide catheter dislodgement appeared to have caused prolapse and kinking of the guidewire. Advancement of the burr over the kinked wire resulted in transection. The wire fragment was retrieved successfully using an inflated fixed‐wire balloon catheter. This report illustrates the importance of excellent coaxial guide catheter alignment with rotational atherectomy and suggests that operators be vigilant to possible damage to the radiolucent rotational atherectomy guidewire. © 1995 Wiley‐Liss, Inc.
Acute coronary artery closure following intracoronary ultrasound examination
Authors: Ge Junbo , Liu Fengqi , Kearney Peter , Görge Günter , Haude Michael , Erbel Raimund
Published: March 2007

Two patients undergoing intracoronary ultrasound examination were complicated by acute coronary artery closure. One of the complications was thought to be caused by intimal dissection and thrombus formation and the other was thought to be caused by intimal dissection and subsequent embolization. The complications were successfully managed conservatively in both cases. © 1995 Wiley‐Liss, Inc.
Retrieval of directional coronary atherectomy guiding catheter with angioplasty balloon catheter
Authors: El Ghamry Sabe Ahmed A. , Ettinger Steven M.
Published: March 2007

Directional coronary atherectomy (DCA) has been shown to be a safe and effective treatment for occlusive coronary artery disease. We report a case of an atherectomy guiding catheter severing in two with successful retrieval of the dislodged segment by an integrated angioplasty balloon catheter system. © 1995 Wiley‐Liss, Inc.
Separation of a flexible nose cone tip during directional atherectomy
Authors: Rashkow Andrew M.
Published: March 2007

An 82‐yr‐old white female underwent directional coronary atherectomy of a high‐grade proximal left anterior artery stenosis. The nose cone tip of a Simpson Atherocath SCAEX™ separated during loading of the device onto a 360‐cm exchange wire. This was recognized prior to insertion through a rotating hemostatic valve and exchanged for another device. Catheterization laboratory policy regarding defective devices is briefly discussed. © 1995 Wiley‐Liss, Inc.
Clinical effects and utility of intracoronary diltiazem
Authors: McLvor Michael E. , Undemir Cenap , Lawson Janet , Reddinger Judith
Published: March 2007

Coronary artery spasm is a known complication of coronary interventions, for which intracoronary nitroglycerin (ICN) is the treatment of choice. Some forms of intense spasm are resistant to ICN. Calcium channel antagonists are also known to be effective for coronary artery spasm, including nitroglycerin‐resistant spasm. Here we describe a protocol for the clinical use of intracoronary diltiazem (ICD). By this protocol, ICD can be safely given without disturbing the clinical status of patients. ICD (2.5 mg) given slowly over 1 minute produced no vasodilitation of normal vessel segments but did produce significant dilatation of stenotic segments above and beyond the effects of nitrates. Mean minimum lumen diameter increased 18%, from 0.89 ± 0.06 mm to 1.06 ± 0.07 mm (mean ± SEM, P < 0.001). ICD produced clinically Insignificant changes in systolic blood pressure, diastolic blood pressure, heart rate, and PR, QRS, and QT intervals. This protocol has been employed to safely use ICD to relieve both nitroglycerin‐resistant epicardial artery spasm and nitroglycerin‐resistant distal microvascular spasm (the no‐reflow phenomenon). © 1995 Wiley‐Liss, Inc.
Congenital clavicular pseudoarthrosis associated with vascular thoracic outlet syndrome: Case presentation and review of the literature
Authors: Hahn Kenneth , Shah Rita , Shalev Yoseph , Schmidt Donald H. , Bajwa Tanvir
Published: March 2007

Thoracic outlet syndrome (TOS) associated with congenital clavicular pseudoarthrosis is rare in adults and often misdiagnosed. In this case report, we describe an adult female who was found to have thromoosis of the subclavian and axillary arteries with embolization documented by invasive angiography. This unusual vascular manifestation of TOS should remind physicians that anatomic derangements may predispose to upper extremity ischemia. © 1995 Wiley‐Liss, Inc.
Right coronary artery pseudo‐transection due to mechanical straightening during coronary angioplasty
Authors: Blankenship James C.
Published: March 2007

Straightening of tortuous coronary arteries during coronary angioplasty may produce transient angiographic defects that have a typical invaginated appearance. We report a case in which coronary straightening produced an unusual defect mimicking severe damage to the artery. Recognition and conservative management were essential to avoid complications. © 1995 Wiley‐Liss, Inc.
Rotational atherectomy in restenotic lesions at the distal saphenous vein graft anastomosis
Authors: Cardenas Joseph R. , Strumpf Robert K. , Heuser Richard R.
Published: March 2007

Restenotic lesions at distal saphenous vein graft (SVG) anastomoses have been notoriously difficult to treat with standard angioplasty techniques. We explored the potential of rotational atherectomy in three patients with nonthrombotic, focal restenoses at the SVG touchdown. The Rotablator safely and successfully recanalized the lesions, allowing further treatment with dilation or stenting or both. Rotational atherectomy may warrant investigation as a treatment for nonthrombotic restenotic SVG lesions. © 1995 Wiley‐Liss, Inc.
Initial experience with an intracoronary flow support device providing localized drug infusion: The scimed dispatch catheter
Authors: Groh William C. , Kurnik Peter B. , Matthai William H. , Untereker William J.
Published: March 2007

Two cases are presented illustrating the use of a new intracoronary infusion catheter providing flow support using a unique spiral coil design. Good clinical outcomes were obtained employing 4‐hr inflations with localized infusion of urokinase at the site of dissection and extensive clot formation, respectively. This low‐profile catheter‐mounted device may provide an alternative to stent placement in cases of acute dissection complicated by thrombus formation. © 1995 Wiley‐Liss, Inc.
Pilot prospective evaluation of counterpulsation with different intra‐aortic balloon volumes on cardiac performance in humans
Authors: Cohen Marc , Patel Janmejay J. , Dohad Suhail , McBride Ruth , Venkatesulu Sunder , Boston Barbara A. , Chandrasekaran Krishnaswamy
Published: March 2007

Smaller intra‐aortic balloons (IAB) may minimise Peripheral vascular complications. To determine the influence of different IAB valumes on cardiac performance, we studied 20 hemodynamically stable patients on IAB counterpulsation. Variables were measured with either a 40cc or 32cc IAB displacement, at an assist ratio of 1:1 or 1:8 Heart rate, Ao and PA pressures, and Fick cardiac output. By echo‐Doppler, the velocity time integral (VTI) across the LV outflow track, a measure of stroke volume was also calculated. The mean age was 60 yr (range 18–77), height (5′2″–5′11″), and body surface area 1.9M2 (1.5‐2.3). Results presented as mean values were:

IAB/Vol
AR
VTI*
Ao (sys)
PA (mean)
HR (bpm)
CO

40cc
1:1
17.4
111
26
93
5.7

32cc
1:1
17.4
109
26
93
5.9

40cc
1:8
13.7
118
29
98
5.2

32cc
1:8
14.1
118
29
97
5.4

* p < 0.005 1:1 vs. 1:8 for both 40 and 32cc IAB.

Conclusion: IAB pumping at 1:1 with either 40cc or 32cc volumedisplacement yields similar degrees of improvement in cardiac performance. A larger cohort is required to determine if smaller balloons may decrease complications without compromising efficacy. © 1995 Wiley‐Liss, Inc.
Extensive intramural hematoma as the cause of failed coronary angioplasty: Diagnosis by intravascular ultrasound and treatment by stent implantation
Authors: Werner Gerald S. , Figulla Hans R. , Grosse Walter , Kreuzer Heinrich
Published: March 2007

Dissections after coronary angioplasty are the major cause of ischemic events following percutaneous transluminal coronary angioplasty (PTCA) and may require additional measures such as intravascular stent deployment to relieve or prevent acute vessel closure. We describe a rare type of dissection after PTCA which caused a severe obstruction of the vessel segment proximal to the dilatation site without a visible dissection flap. Intravascular ultrasound was used to elucidate the morphology of the proximal vessel obstruction, which revealed an intramural hematoma extending into the proximal vessel segment as underlying mechanism. A Palmaz‐Schatz stent was placed at the entry site of this hematoma, which led to the relief of the proximal vessel obstruction. After 3 months of anticoagulation therapy the repeat coronary angiography showed no significant restenosis. This demonstrates the unique insight into the underlying morphology of failed PTCA by intravascular ultrasound, which can help to manage even rare and unusual complications. © 1995 Wiley‐Liss, Inc.
Percutaneous retrieval of a broken umbilical catheter from left atrium in a premature newborn
Authors: Ruiz Carlos E. , Nystrom Gerald A. , Butt Amjad I. , Zhang He Ping
Published: March 2007

A 30‐week gestational age baby boy weighing 1,117 g born with cesarian section had a broken umbilical vein catheter lodged in the left superior pulmonary vein. We successfully retrieved the foreign body by percutaneous approach using a pigtail catheter and a snare wire under portable fluoroscopy. © 1995 Wiley‐Liss, Inc.
Extraction atherectomy for the recanalization of totally occluded aortocoronary saphenous vein grafts
Authors: Sullebarger J. Thompson , Puleo John
Published: March 2007

This report describes the successful treatment of totally occluded aortocoronary saphenous vein grafts with percutaneous transluminal extraction atherectomy (TEC) in three patients with severe angina and high reoperative surgical risk. The method presented here may provide an alternative to overnight urokinase infusion or repeat surgery in high risk patients. © 1995 Wiley‐Liss, Inc.
Strategies for the palliation of severe unprotected left main coronary artery disease: Use of newer technologies
Authors: Foster‐Smith Karl , Garratt Kirk N. , Núñez Boris D. , Hibbard Michael D. , Holmes David R.
Published: March 2007

Angioplasty of unprotected left main coronary artery lesions is associated with high procedural and late mortalities. We describe the successful use of rotational coronary atherectomy with prophylactic supportive measures in the management of a heavily calcified unprotected left main lesion. This report demonstrates that high‐risk lesions, previously regarded as unapproachable, may be safely treated with newer technologies. © 1995 Wiley‐Liss, Inc.
Biokraftstoffe in Deutschland – Produktionskosten und Marktchancen
Authors: Festel G.
Published: March 2007

Durch die steigende Nachfrage nach Erdöl und dessen Verknappung muss intensiv nach Alternativen gesucht werden. Die Entwicklung alternativer Kraftstoffe hat deshalb eine große Bedeutung erlangt. Aufgrund der Vielzahl an unterschiedlichen Biokraftstoffen und Einflussfaktoren bei der Bewertung der Kraftstoffe besteht im Moment kein klares Meinungsbild bezüglich der Möglichkeiten von Biokraftstoffen. Vorgestellt werden eigene Untersuchungen, die durchgeführt wurden, um geeignete Bewertungskriterien für Kraftstoffalternativen zu finden und die Realisierungschancen abzuschätzen.
On a class of pseudo‐logarithmic amplifiers suitable for use with digitally switched resistors
Authors: Maundy Brent , Westwick David , Gift Stephan
Published: March 2007

This paper describes three circuits that implement pseudo‐logarithmic functions, which are simple and easy to implement. The circuits can be realized using operational amplifiers or current feedback amplifiers. Tuning can be achieved using switched resistors, or active resistors, or tunable transconductors, but are best suited for use with digitally switched resistors. Frequency response and stability considerations for two of the circuits are thoroughly discussed and PSPICE results confirming the theoretical results are presented alongside measured results. Copyright © 2007 John Wiley & Sons, Ltd.
Transcriptional profiling of developing mouse epidermis reveals novel patterns of coordinated gene expression
Authors: Bazzi Hisham , Fantauzzo Katherine A. , Richardson Gavin D. , Jahoda Colin A.B. , Christiano Angela M.
Published: March 2007

The mammalian epidermis is the first line of defense against external environmental challenges including dehydration. The epidermis undergoes a highly intricate developmental program in utero, transforming from a simple to a complex stratified epithelium. During this process of stratification and differentiation, epidermal keratinocytes express a defined set of structural proteins, mainly keratins, whose expression is controlled by largely unknown mechanisms. In order to identify novel factors contributing to epidermal morphogenesis, we performed a global transcriptional analysis of the developing mouse epidermis after separating it from the underlying dermis (E12.5–E15.5). Unexpectedly, the recently identified genes encoding secreted peptides dermokine (Dmkn), keratinocyte differentiation‐associated protein (krtdap), and suprabasin (Sbsn) as well as a largely uncharacterized embryonic keratin (Krt77), were among the most highly differentially expressed genes. The three genes encoding the secreted proteins form a cluster in an ∼40‐Kb locus on human chromosome 19 and the syntenic region on mouse chromosome 7 known as the stratified epithelium secreted peptides complex (SSC). Using whole mount in situ hybridization, we show that these genes show a coordinated spatio‐temporal expression pattern during epidermal morphogenesis. The expression of these genes initiates in the nasal epithelium and correlates with the initiation of other epidermal differentiation markers such as K1 and loricrin (Byrne et al. [1994]Development120:2369–2383), as well as the initiation of barrier formation. Our observations reveal a coordinated mode of expression of the SSC genes as well as the correlation of their initiation in the nasal epithelium with the initiation of barrier formation at this site. Developmental Dynamics 236:913–921, 2007. © 2007 Wiley‐Liss, Inc.
Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection
Authors: Lehmann Frédéric , Marchand Marie , Hainaut Philippe , Pouillart Pierre , Sastre Xavier , Ikeda Hideyuki , Boon Thierry , Coulie Pierre G.
Published: March 2007

We have studied the patterns of antigens recognized by autologous cytolytic T lymphocytes (CTL) on two melanoma cell lines derived from metastases that were removed from patient LB33 at several years distance. Cell line LB33‐MEL. A was obtained after surgery in 1988. A large number of CTL clones directed against LB33‐MEL. A was obtained with blood lymphocytes collected from the patient in 1990. In vitro selection of melanoma cells that were resistant to these CTL clones indicated that at least five different antigens were recognized on LB33‐MEL. A by autologous CTL. Four of these antigens were found to be presented by HLA‐A28, B13, B44 and Cw6, respectively. The patient remained disease‐free until 1993 when a metastasis was detected and was used to obtain cell line LB33‐MEL. B. This cell line proved resistant to lysis by all the CTL clones directed against the LB33‐MEL. A cells and showed no expression of HLA class I molecules except for HLA‐A24. Using LB33‐MEL. B cells to stimulate blood lymphocytes collected from the patient in 1994 we derived CTL clones that lysed these cells. All these CTL clones recognized a new antigen presented by HLA‐A24. These results suggest that in patient LB33 the melanoma cells may have lost the expression of several HLA molecules under the selective pressure of an anti‐tumor CTL response.
T cell receptor γδ repertoire is skewed in cerebrospinal fluid of multiple sclerosis patients: molecular and functional analyses of antigen‐reactive γδ clones
Authors: Nick Sabine , Pileri Piero , Tongiani Stefania , Uematsu Yasushi , Kappos Ludwig , De Libero Gennaro
Published: March 2007

To study the relevance of γδ T cells in multiple sclerosis (MS) we analyzed the T cell receptor (TCR) γδ repertoire and the antigen reactivity of γδ clones isolated from cerebrospinal fluid (CSF). In T cell cultures derived from CSF we found an increased percentage of Vδ1+ cells as compared to peripheral blood of the same donors. Phenotypic analysis of cells from MS CSF with Vγ‐ and Vγ‐specific monoclonal antibodies (mAb) showed that the Vγ1 chain is most frequently associated with γ chains belonging to the VγI family. Sequence analysis of TCR genes revealed heterogeneity of junctional regions in both δ and γ genes indicating polyclonal expansion. γδ clones were established and some recognized glioblastoma, astrocytoma or monocytic cell lines. Stimulation with these targets induced serine esterase release and lymphokine expression characteristic of the TH0‐like phenotype. Remarkably, these tumor‐reactive γδ cells were not detected in the peripheral blood using PCR oligotyping, but were found in other CSF lines independently established from the same MS patient. Altogether, these results demonstrate that in the CSF there is a skewed TCR γδ repertoire and suggest that γδ cells reacting against brain‐derived antigens might have been locally expanded.
Induction of interleukin‐2 transcription by the hamster polyomavirus middle T antigen: a role for Fyn in T cell signal transduction
Authors: Brizuela Leonardo , Ulug Emin T. , Jones Margaret A. , Courtneidge Sara A.
Published: March 2007

The transforming protein of mouse polyomavirus, the mouse middle T antigen (MomT), and its counterpart in the hamster polyomavirus, the hamster middle T antigen (HamT), interact with a number of cellular proteins. Among these are members of the Src family of tyrosine kinases, the phosphatidylinositol 3‐kinase, the serine/threonine phosphatase PP2A and the adaptor protein Shc (in the case of MomT). However, both the relative affinity of these antigens for the members of the Src family and the tumor profile induced by their respective viruses are quite distinct. Particularly noteworthy are the preferential binding of Fyn by HamT and the induction of lymphoid malignancies by the hamster polyomavirus. Here we report that, when expressed in fibroblasts, HamT also associated with phospholipase Cγ (PLCγ), which led to an increased intracellular concentration of inositol‐1, 4, 5‐trisphosphate. We also show that expression of HamT in the mouse T cell line EL4 was sufficient to induce transcription from interleukin‐2 (IL‐2), NFAT and NFxB reporter constructs. The immunosuppressant FK506 as well as dominant negative alleles of Ras and Raf inhibited HamT‐induced IL‐2 transcription. This, together with the observation of NFAT responses, suggests that the action of HamT depended at least in part on the integrity of signal transduction pathways elicited by activated PLCγ. Furthermore, dominant negative Fyn but not the equivalent allele of Lck blocked HamT activation of IL‐2 transcription, while both Lck and Fyn dominant negative alleles blocked LT cell receptor‐mediated IL‐2 transcriptional activation. These results support the hypothesis that Fyn is involved in signal transduction events leading to IL‐2 transcriptional activation in T cells. Finally, the activation of IL‐2 transcription by HamT and not by MomT shown here parallels the ability of the hamster polyomavirus to induce lymphoid malignancies.
Reconstitution of a functional interleukin (IL)‐7 receptor demonstrates that the IL‐2 receptor γ chain is required for IL‐7 signal transduction
Authors: Ziegler Steven F. , Morella Karen K. , Anderson Dirk , Kumaki Noriko , Leonard Warren J. , Cosman David , Baumann Heinz
Published: March 2007

The interleukin (IL)‐2 receptor γ chain has recently been shown to be a component of the IL‐7 and IL‐4 receptors. Using a transient transfection assay and the trans‐activation of reporter gene constructs which are under the control of cytokine‐responsive promoter elements, we have studied signal transduction through the IL‐7 receptor (IL‐7R). The reporter gene expression was not stimulated by receptors that contained the cytoplasmic domain of the IL‐7R, either as intact IL‐7R or as part of a chimeric receptor. However, co‐expression of the IL‐7R with the IL‐2 receptor γ chain was able to stimulate gene activation. For maximal stimulation the intact cytoplasmic domains of each chain was required.
Functional gap junctions in thymic epithelial cells are formed by connexin 43
Authors: Alves Luiz Anastacio , de Carvalho Antonio Carlos Campos , Lima Elizabeth Obino Cirne , Souza Claudio Marcos Rocha E , Dardenne Mireille , Spray David Conover , Savino Wilson
Published: March 2007

A multiparametric study was carried out to investigate the presence and possible role of communicating junctions in the thymus, particularly in the thymic epithelium, the major component of the thymic microenvironment. The presence of direct cell‐cell communication mediated by gap junctions was demonstrated in human and murine thymic epithelial cells (TEC) by means of in situ and in vitro immunohistochemical labeling as well as in vitro fluorochrome injection and double whole‐cell patch clamp experiments. Moreover, both immuno‐ and Northern blot studies revealed that the gap junction protein connexin 43 and its mRNA were present in TEC. Importantly, we showed that thymic endocrine activity, as ascertained by thymulin production, could be specifically downmodulated in vitro by a gap junction inhibitor, octanol. We also investigated the existence of gap junctions between TEC and thymocytes. In thymic nurse cells we were able to detect cell‐cell communication, although only a minor percentage of epithelial/thymocyte pairs were coupled in a given moment. In contrast, intercellular communication was not detected between cultured phagocytic cells of the thymic reticulum and the respective rosetting thymocytes. We suggest that gap junctions formed by connexin 43 may represent a novel (and rather cell type‐specific) pathway for intrathymic cellular communication, including TEC/TEC as well as possible TEC/thymocyte interactions.
Epitope mapping and functional properties of anti‐intercellular adhesion molecule‐3 (CD50) monoclonal antibodies
Authors: Bossy David , Buckley Christopher D. , Holness Claire L. , Littler Amanda J. , Murray Nicholas , Collins Ian , Simmons David L.
Published: March 2007

Intercellular adhesion molecule‐3 (ICAM‐3, CD50), a member of the immunoglobulin gene superfamily, is a major ligand for the lymphocyte functionassociated antigen 1 (LFA‐1, CD18/CD11a) in the resting immune system and plays a role as a signaling and costimulatory molecule on T lymphocytes. In this study we have generated a large panel of anti‐ICAM‐3 monoclonal antibodies (mAb) and show that the biological effects of these antibodies are critically dependent on the epitope recognized. By using an adhesion assay employing COS cells expressing LFA‐1 binding to recombinant chimeric ICAM‐3‐Fc proteins (which overcomes the confounding effects of interleukocyte LFA‐1/ICAM binding events), we have been able to examine the effects of these antibodies in blocking IFA‐1/ICAM‐3 adhesion. Our data suggests that only a small minority of ICAM‐3 mAb, recognizing a distinct epitope, are able to mimic the effects of LFA‐1 binding to ICAM‐3. Moreover these antibodies are functionally distinct as defined by their costimulatory activity and ability to elicit interleukin‐2 production and cell proliferation in T lymphocytes.
Fcγ receptor‐mediated phagocytosis requires tyrosine kinase activity and is ligand independent
Authors: Hutchinson M. J. , Harrison Patrick T. , Floto R. Andres , Allen Janet M.
Published: March 2007

Receptors for the invariant chain of immunoglobulins (FcR) define the cellular response to specific antigens. FcγR recognize IgG and so elicit a variety of effector functions including phagocytosis. We are interested in the structural determinants for FcγR‐mediated phagocytosis, specifically FcγRI(p135) and FcγRIIa isoforms. The low‐affinity receptor, FcγRIIa, is found on macrophages and its cytoplasmic domain contains a tyrosine activation motif which has previously been shown to regulate endocytosis. In contrast, FcγRI has no known signaling motifs, though a functional interaction has recently been demonstrated with the γ chain of the high‐affinity receptor for IgE, FcεRI. This accessory molecule has a cytoplasmic tyrosine activation motif implicated in signal transduction. Here we demonstrate that although FcγRI transiently expressed on COS‐7 cells is able to rosette opsonized SRBC, it cannot phagocytose them. If the cytoplasmic domain of either γ chain or FcγRIIa replaces that of FcγRI in a chimeric receptor, efficient phagocytosis occurs. This particle ingestion is sensitive to the tyrosine kinase inhibitor genistein. Chimeric receptors where the extracellular domain of either FcγRI or FcγRIIa is replaced with that of CD2, a T cell antigen, indicate that FcγR‐mediated phagocytosis is ligand independent. We conclude that phagocytosis is dependent upon close particle apposition, tyrosine kinase activity, and that the process is ligand independent.
Antibody ligation of CD7 leads to association with phosphoinositide 3‐kinase and phosphatidylinositol 3,4,5‐trisphosphate formation in T lymphocytes
Authors: Ward Stephen G. , Parry Richard , Lefeuvre Catherine , Sansom David M. , Westwick John , Lazarovits Andrew I.
Published: March 2007

The CD7 40‐kDa glycoprotein is present on a major subset of human T cells and in the presence of phorbol esters mediates an accessory pathway of T cell activation. Hitherto, the intracellular events elicited by CD7 have been ill‐defined. This report demonstrates that cross‐linking of CD7 results in the formation of phosphatidic acid in the absence of phosphatidylinositol‐4,5‐bisphosphate metabolism and also the formation of D‐3 phosphoinositides lipids which have been postulated to act as intracellular regulatory molecules. The magnitude of D‐3 phosphoinositidé formation was similar to that induced by CD3. Both the CD7‐ and CD3‐induced elevation of phosphatidylinositol 3,4,5‐trisphosphate approximately 5–10 fold less than that elicited by ligation of the costimulatory molecule CD28 by its counter receptor CD80. The formation of D‐3 phosphoinositides following ligation of CD7 coincided with the co‐association of CD7 with phosphoinositide 3‐kinase, the enzyme which mediates the formation of D‐3 phosphoinositide lipids. In contrast, ligation of another reported T cell accessory molecule CD5, failed to elicit formation of D‐3 phosphoinositides, implying that phosphoinositide 3‐kinase is not coupled to all T cell molecules with accessory functions. Since D‐3 phosphoinositides have been suggested to play a pivotal role in T cell costimulatory signals induced by CD28, the results presented in this study suggest that CD7 may also influence T cell activation via this pathway.
CD28 activation promotes Th2 subset differentiation by human CD4+ cells
Authors: King Christopher L. , Stupi Robert J. , Craighead Nancy , June Carl H. , Thyphronitis George
Published: March 2007

Ligation of CD28 provides a costimulatory signal to T cells necessary for their activation resulting in increased interleukin (IL)‐2 production in vitro, but its role in IL‐4 and other cytokine production and functional differentiation of T helper (Th) cells remains uncertain. We studied the pattern of cytokine production by highly purified human adult and neonatal CD4+ T cells activated with anti‐CD3, phorbol 12‐myristate 13‐acetate (PMA) and ionomycin, or phytohemagglutinin (PHA) in the presence or absence of anti‐CD28 in repetitive stimulation‐rest cycles. Initial stimulation of CD4+ cells with anti‐CD3 (or the mitogens PHA or PMA+ionomycin) and anti‐CD28 monoclonal antibodies induced IL‐4, IL‐5 and interferon‐γ (IFN‐γ) production and augmented IL‐2 production (6‐ to 11‐fold) compared to cells stimulated with anti‐CD3 or mitogen alone. The anti‐CD28‐induced cytokine production corresponded with augmented IL‐4 and IL‐5 mRNA levels suggesting increased gene expression and/or mRNA stabilization. Most striking, however, was the progressively enhanced IL‐4 and IL‐5 production and diminished IL‐2 and IFN‐γ production with repetitive consecutive cycles of CD28 stimulation. The enhanced Th2‐like response correlated with an increased frequency of IL‐4‐secreting cells; up to 70% of the cells produced IL‐4 on the third round of stimulation compared to only 5% after the first stimulation as determined by ELISPOT. CD28 activation also promoted a Th2 response in naive neonatal CD4+ cells, indicating that Th cells are induced to express a Th2 response rather than preferential expansion of already established Th2‐type cells. This CD28‐mediated response was IL‐4 independent, since enhanced IL‐5 production with repetitive stimulation cycles was not affected in the presence of neutralizing anti‐IL‐4 antibodies. These results indicate that CD28 activation may play an important role in the differentiation of the Th2 subset in humans.
Linked in vivo expression of soluble interleukin‐4 receptor and interleukin‐4 in murine schistosomiasis
Authors: Fernandez‐Botran Rafael , Wynn Thomas A. , Hieny Sara , Caspar Patricia , Chilton Paula M. , Sher Alan
Published: March 2007

Soluble interleukin‐4 receptors (sIL‐4R) are truncated IL‐4R molecules that are secreted into biological fluids. To gain an insight into the mechanisms that control sIL‐4R synthesis in vivo and their role in the regulation of immune responses, the expression and secretion of sIL‐4R in mice infected with Schistosoma mansoni was studied. Splenocytes from infected animals responded to schistosomal antigen preparations with increased production of both IL‐4 and sIL‐4R. The synthesis of sIL‐4R by spleen cells peaked at 8 weeks following infection and coincided with maximum levels of sIL‐4R in serum and sIL‐4R‐specific mRNA in the liver of infected mice. The expression of IL‐4‐specific mRNA in the liver was different from that of IL‐4R, reaching its peak approximately 2 weeks earlier. A relationship between sIL‐4R production and the development and activation of Th2 cells was suggested by the findings that: (a) in vivo administration of anti‐IL‐4 antibodies (11B11) impaired the ability of splenic cells to secrete either IL‐4 or sIL‐4R; and (b) splenic cells from mice vaccinated with irradiated cercariae, which tend to develop much weaker Th2 responses than mice injected with live cercariae, expressed reduced levels of sIL‐4R when challenged with schistosomal antigens. Moreover, a direct role for IL‐4 in regulating the expression of sIL‐4R was suggested by the ability of anti‐IL‐4 antibodies to inhibit sIL‐4R synthesis in vitro. These data provide the first evidence demonstrating that the production of sIL‐4R in vivo is up‐regulated during immune responses, especially during those characterized by the development and activation of Th2 cells and IL‐4 secretion. The association between sIL‐4R and IL‐4 syntheses is consistent with a potential role for sIL‐4R in the regulation of IL‐4 activity in vivo.
Modulation of Fcγ receptor‐mediated early events by the tyrosine phosphatase CD45 in primary human monocytes. Consequences for interleukin‐6 production
Authors: Corvaïa Nathalie , Reischl Ilona G. , Kroemer Elisabeth , Mudde Geert C.
Published: March 2007

Stimulation of primary human monocytes from several donors by cross‐linking of Fcγ receptor type I (FcγRI) and FcγRII gave rise to calcium mobilization and protein tyrosine phosphorylation. These early events were not observed without cross‐linking. CD45, a transmembrane tyrosine phosphatase, when co‐cross‐linked with either FcγRI or FcγRII, could prevent FcγRI and FcγRII‐mediated calcium mobilization and protein tyrosine phosphorylation. When interleukin (IL)‐6 production was measured, we noted a strong IL‐6 production after activation of primary human monocytes by cross‐linking of FcγRI or FcγRII. In contrast to calcium mobilization and tyrosine phosphorylation of proteins, IL‐6 production was not affected by co‐cross‐linking of CD45 with either FcγRI or FcγRII. Interestingly, cross‐linking of the CD45 itself was sufficient to induce IL‐6 production. Our results show that the CD45 molecule is important in modulating early events following stimulation of primary human monocytes by cross‐linking of FcγRI or FcγRII. However, triggering of CD45 alone can also induce IL‐6 production, indicating that CD45 ligation itself can give signals and may have an important role in cytokine induction pathways.
Induction of Bax‐α precedes apoptosis in a human B lymphoma cell line: potential role of the bcl‐2 gene family in surface IgM‐mediated apoptosi
Authors: Bargou Ralf C. , Bommert Kurt , Weinmann Pamela , Daniel Peter T. , Wagener Christian , Mapara Markus Y. , Dörken Bernd
Published: March 2007

The members of the bcl‐2 gene family are major regulators of programmed cell death, but their role in sIg‐triggered apoptosis remains unclear. Using sensitive and resistant variants of the human B cell line BL‐41, we studied the expression of the bcl‐2 gene family during surface IgM‐mediated apoptosis. We found constitutive Bcl‐2 and Bcl‐x expression, which remained unaltered after sIg cross‐linking, in both resistant and sensitive cells. This and other experiments suggest that constitutive expression of Bcl‐2 or Bcl‐x alone is not sufficient to protect from activation‐induced cell death in B cells. We therefore investigated Bax‐α, the death‐promoting splice variant of Bax, and found strong induction of both mRNA and protein upon sIg stimulation in sensitive cells. However, resistant subclones showed only weak expression, which was not inducible by sIg cross‐linking. We provide evidence that up‐regulation of Bax‐α and the resulting imbalance of Bcl‐2/Bax might be a major regulator of sIg‐mediated apoptosis. Additionally, we found strong constitutive expression of Bcl‐xs, the death promoting variant of Bcl‐x, in sensitive cells, whereas resistant cells showed only weak Bcl‐xs expression. Thus, we observed a much stronger expression of the death‐promoting proteins Bax‐α (inducible) and Bcl‐xs (constitutive) in sensitive cells than in resistant cells. We therefore propose a potential role of the novel bcl‐2 gene family members bcl‐x and bax in surface IgM‐triggered apoptosis.
Recombinant chicken interferon: a potent antiviral agent that lacks intrinsic macrophage activating factor activity
Authors: Schultz Ursula , Kaspers Bernd , Rinderle Conny , Sekellick Margaret J. , Marcus Philip I. , Staeheli Peter
Published: March 2007

Crude preparations of chicken interferon (ChIFN) from various sources contain both antiviral and macrophage‐activating factor (MAF) activity. Previous serological data indicated that unlike mammals, birds might express only a single type of IFN in response to viruses and mitogens that exhibits both activities. We have now expressed a complementary DNA for virus‐induced ChIFN in transfected COS cells and in Escherichia coli. Purified recombinant ChIFN is a powerful antiviral agent and has high Mx promoter‐inducing activity. However, as the sole agent, recombinant ChIFN lacks MAF activity: it does not induce the secretion of nitric oxide in primary monocyte‐derived chicken macrophages. A neutralizing antiserum prepared against cloned ChIFN blocks most of the antiviral and Mx promoter‐inducing activity present in preparations of natural ChIFN, but does not inhibit the MAF activity. These results demonstrate that chicken cells can be induced to secrete a novel cytokine which probably represents the avian homolog of mammalian IFN‐γ.
In the absence of major histocompatibility complex class II molecules, invariant chain is translocated to late endocytic compartments by autophagy
Authors: Chervonsky Alexander , Sant Andrea J.
Published: March 2007

It has been suggested that the cytoplasmic amino‐terminal tail of invariant chain (Ii) contains a sorting signal that directs trafficking of the major histocompatibility complex (MHC) class II: Ii oligomeric complex to endocytic compartments. This model is based, in part, on the observation that in the absence of MHC class II molecules, Ii is detectable in lysosomal structures, a phenotype that is dependent on an intact NH2 terminus. However, the route by which Ii gains access to endosomal compartments in the absence of class II molecules remains uncertain. Here we report a mechanism that localizes Ii in lysosomal compartments independently of class II. We show that murine Ii can be detected by immunofluorescence within late endocytic compartments of stably transfected Ltk− mouse fibroblasts. Immunochemical studies indicate that degradation of Ii in these cells is sensitive to the lysosomotropic agent ammonium chloride, yet the majority of Ii that undergoes this apparent lysosomal degradation is sensitive to the enzyme endoglycosidase H. This finding suggests that Ii may reach the lysosomal compartment by a route that bypasses the Golgi complex. Consistent with this possibility, we found that in contrast to Ii which is complexed to class II molecules, transport of free Ii to lysosomes is prevented by 3‐methyladenine, an inhibitor of the autophagic pathway of protein degradation, a process which involves direct transport from the endoplasmic reticulum to lysosomes. These data suggest the route of transport that leads to endosomal localization of Ii in the absence of class II is distinct from that taken when expressed with class II. This forces a re‐evaluation of the concept that the cytosolic tail of Ii contains a dominant Golgi‐to‐endosomal sorting signal.
Nitric oxide up‐regulates the release of inflammatory mediators by mouse macrophages
Authors: Marcinkiewicz Janusz , Grabowska Agnieszka , Chain Benjamin
Published: March 2007

Nitric oxide (NO) plays a key role in mediating macrophage cytotoxicity towards different targets, including tumoral cells and intracellular pathogens. However, its role in macrophage immunoregulation is less well defined. In this study, we have investigated the effect of altering NO levels on the production by mouse macrophages of cytokines, and reactive oxygen intermediates as measured by luminol‐dependent chemiluminescence. Our results demonstrate that NO can enhance the release of both tumor necrosis factor‐α and interleukin‐1α, and chemiluminescence. Thus, in addition to acting as a powerful effector molecule in mediating cytotoxic activities of mouse macrophages, NO can play a role in enhancing the production of a variety of other inflammatory mediators, and thus can contribute both directly and indirectly to the immunopathology of macrophage‐dependent inflammation.
Co‐ligation of mouse complement receptors 1 and 2 with surface IgM rescues splenic B cells and WEHI‐231 cells from anti‐surface IgM‐induced apoptosis
Authors: Kozono Yuko , Duke Richard C. , Schleicher Mary S. , Holers V. Michael
Published: March 2007

Recent studies have shown that complement receptors play important roles in both T‐dependent and T‐independent B lymphocyte responses to low doses of antigen (Ag) in vivo. Complement activation by either the classical or alternative pathway results in the covalent binding of C3 molecules to Ag in forms that ligate complement receptors type 1 (CR1) and 2 (CR2). We hypothesized that C3‐bound Ag might cross‐link CR2 and/or CR1 with surface (s)IgM and alter the signal that would be transduced through sIgM by Ag binding alone. One result of the altered signal could be the rescue of B lymphocytes from apoptosis that would otherwise be induced by the binding of certain types of Ag alone. We find that co‐cross‐linking of mouse CR2 and CR1 with sIgM rescues both resting B cells and WEHI‐231.7 cells from apoptosis induced by sIgM ligation in a fashion similar to that found using soluble mouse CD40 ligand (mCD40L). Anti‐CR2/CR1‐mediated rescue requires co‐cross‐linking of the receptors with sIgM, and has an additive effect on mCD40L‐mediated apoptosis rescue. Based on these results, it is likely that the CR2/CR1‐derived signal is cooperative with T cell‐derived signals such as CD40L and interleukiin‐4.