bluuebunny/crossref_metadata_2025 huggingface dataset:
Histo‐Blood Group Antigens as Allo‐ and Autoantigens
Authors: NYDEGGER URS E. , TEVAEARAI HENDRIK , BERDAT PASCAL , RIEBEN ROBERT , CARREL THIERRY , MOHACSI PAUL , FLEGEL WILLY A.
Published: July 2005

Abstract: The science of blood groups has made giant steps forward during the last decade. Blood‐group typing of red blood cells (RBCs) is performed on more than 15 million samples per year in Europe, today much less often for forensic reasons than for clinical purposes such as transfusion and organ transplantation. Specific monoclonal antibodies are used with interpretation on the basis of RBC agglutination patterns, and mass genotyping may well be on its way to becoming a routine procedure. The discovery that most blood group systems, whose antigens are by definition found on RBCs, are also expressed in multiple other tissues has sparked the interest of transplantation medicine in immunohematology beyond the HLA system. The one and only “histo‐blood group” (HBG) system that is routinely considered in transplantation medicine is ABO, because ABO antigen‐incompatible donor/recipient constellations are preferably avoided. However, other HBG systems may also play a role, thus far underestimated. This paper is an up‐to‐date analysis of the importance of HBG systems in the alloimmunity of transplantation and autoimmune events, such as hemolytic anemia.
Central Memory and Effector Memory Subsets of Human CD4+ and CD8+ T Cells Display Differential Sensitivity to TNF‐α‐Induced Apoptosis
Authors: GUPTA SUDHIR , BI RUIFEN , GOLLAPUDI SASTRY
Published: July 2005

Abstract: Upon activation by antigen, naive T cell subsets undergo proliferation and differentiation into effector cells, followed by the generation of a pool of memory T cells. Based upon migration pattern and functions, they are classified into central memory (predominantly homing to the lymph nodes) and effector memory (predominantly homing to extralymphoid sites) subsets. These subsets are defined phenotypically by a set of cell surface molecules. In this investigation, we demonstrate that naive and central memory CD4+ and CD8+ T cells in humans undergo tumor necrosis factor‐α (TNF‐α)‐induced apoptosis, whereas effector memory CD4+ and CD8+ T cells are relatively resistant to TNF‐α‐induced apoptosis. We also provide evidence for the molecular mechanisms underlying the differential sensitivity of naive and different sets of memory T cells to TNF‐α‐induced apoptosis.
Long‐Lived Plasma Cells and Their Contribution to Autoimmunity
Authors: HOYER BIMBA F. , MANZ RUDOLF A. , RADBRUCH ANDREAS , HIEPE FALK
Published: July 2005

Abstract: The current view holds that chronic autoimmune diseases are driven by the continuous activation of autoreactive B and T lymphocytes. However, despite the use of potent immunosuppressants, the production of autoantibodies may persist and contribute to the autoimmune pathology. We recently demonstrated in autoimmune mice that both short‐lived plasmablasts and long‐lived plasma cells are involved in autoantibody production. While anti‐proliferative immunosuppressive therapy and monoclonal anti‐CD20 antibody deplete short‐lived plasmablasts, long‐lived plasma cells survive and continue to produce (auto)antibodies. Thus, strategies for targeting long‐lived plasma cells may provide potent new treatment modalities.
Anti‐Endothelial Cell Antibodies Determination by Cyto‐ELISA: A Comparative Study between Three Cell Types Used as Substrates
Authors: SAKLY NABIL , MIRSHAHI PEJMAN , SORIA JEANNETTE , GHEDIRA IBTISSEM , MIRSHAHI MASSOUD
Published: July 2005

Abstract:Cyto‐ELISA has been widely used to investigate anti‐endothelial cell antibodies (AECAs); however, because various types of endothelial cells have been used, the results among studies differ. The aim of our study was to analyze and compare the results when determining AECAs in patients with connective tissue disease (CTD). We did so using a cyto‐ELISA with different cells as antigenic substrates: two different endothelial cells, one microvascular (HMEC‐1) and one from human bone marrow (HBMEC), and one epithelial cell line from breast adenocarcinoma as negative controls (MDA‐MB‐231). In this trial, we performed a retrospective study in 60 patients with CTD [46 with systemic lupus erythematosus, 8 with Sjögren's syndrome, and 6 with systemic sclerosis] and 32 healthy volunteers. Using cyto‐ELISA, the antibody against a cell was considered positive when the optical density (OD) obtained was higher than the mean OD obtained in the control group + 2 standard deviations (upper normal range). Patients were classified into three groups according to the OD obtained with the different cell lines: group 1: patients without any antibody; group 2: patients with specific AECAs; and group 3: patients with nonspecific AECAs. According to this classification, we found that 43.3% of patients with CTD have specific AECAs, and 28.3% have nonspecific antibodies. Our study delineates the heterogeneity of AECAs in patients with CTD. The use of HBMEC in cyto‐ELISA may increase the sensitivity of the test, and the use of nonendothelial cells as negative controls may improve its specificity.
Prevalence of IgG Anti‐α‐Fodrin Antibodies in Sjögren's Syndrome
Authors: RUIZ‐TÍSCAR J.L , LÓPEZ‐LONGO F J , SÁNCHEZ‐RAMÓN S , SANTAMARÍA B , URREA R , CARREÑO L , ESTECHA A , VIGIL D , FERNÁNDEZ‐CRUZ E , RODRÍGUEZ‐MAHOU M
Published: July 2005

Abstract: The objective of this study was to determine the prevalence of antibodies against alpha‐fodrin (α‐fodrin) of the immunoglobulin G (IgG) isotype in Sjögren's syndrome (SS), as defined by European Community Study Group (ESG) and ESG‐modified criteria. We arrived at the prevalence and mean concentrations of IgG anti‐α‐fodrin antibodies using enzyme‐linked immunosorbent assay (ELISA) in 507 patients with SS, primary SS (pSS), and secondary SS (sSS), classified according to either the ESG or the ESG‐modified criteria. IgG anti‐α‐fodrin antibodies were detected in 6/507 (1.2%) and 4/228 (1.7%) of the SS group, according to the ESG or ESG‐modified criteria, respectively. Similar prevalence was found for patients with pSS or sSS. Anti‐Ro/SSA antibodies were present in 151/409 (36.9%) vs. 149/213 (70.0%) of the SS group, 85/195 (43.6%) vs. 83/101 (82.2%) of the pSS group, and 66/214 (30.8%) vs. 66/112 (58.9%) of the sSS group. Anti‐La/SSB antibodies were detected in 77/403 (19.1%) vs. 73/212 (34.4%) of the SS group, 47/194 (24.2%) vs. 45/101 (44.5%) of the pSS group, and 30/209 (14.3%) vs. 28/111 (25.2%) of the sSS group. No clinical associations were found. Only two IgG anti‐α‐fodrin‐positive sera were anti‐Ro/SSA‐negative. We conclude that IgG antibodies against α‐fodrin are present in a small percentage of people with SS, pSS, and sSS. The lower prevalence in patients classified according to the ESG criteria reflects the lower specificity of these criteria. IgG anti‐α‐fodrin antibodies can be detected in some SS patients whose sera do not contain anti/Ro/SSA antibodies.
Effective Use of Autoantibody Tests in the Diagnosis of Systemic Autoimmune Disease
Authors: LYONS ROBERT , NARAIN SONALI , NICHOLS CODY , SATOH MINORU , REEVES WESTLEY H.
Published: July 2005

Abstract: Screening for disease‐specific autoantibodies may be useful in asymptomatic ANA‐positive individuals as a means of evaluating the risk of developing a systemic autoimmune disease such as systemic lupus erythematosus (SLE), polymyositis/dermatomyositis /PM/DM), scleroderma (SSc), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or primary biliary cirrhosis (PBC) in the future. In patients with known or suspected systemic autoimmune disease, a panel of disease‐specific markers may help to establish a diagnosis and to assess the prognosis. The great strides in autoantibody testing over the last 20 years make it feasible to use specific autoantibody markers to improve diagnostic accuracy in systemic autoimmune disease. New technology enabling screening for multiple autoantibodies may further enhance the clinical usefulness of autoantibody testing, making it possible to diagnose autoimmune disease in its earliest stages and to intervene before serious end organ damage occurs.
A Deiminated Viral Peptide to Detect Antibodies in Rheumatoid Arthritis
Authors: MERLINI GIUSEPPINA , ANZILOTTI CONSUELO , CHIMENTI DANIELE , TOMMASI CRISTINA , BOMBARDIERI STEFANO , MIGLIORINI PAOLA
Published: July 2005

Abstract: The data presented suggest that a deiminated viral peptide is specifically recognized by antibodies contained in rheumatoid arthritis (RA) sera. Antipeptide antibodies are not associated with the presence or severity of specific manifestations of RA, but are more frequent in subjects with erosive arthritis. Taking into account the association with rheumatoid factor and with erosive arthritis, we can conclude that antipeptide antibodies are markers of severe forms of RA. Our data also show familial aggregation of anticitrullinated peptide antibodies.
Association of Anti‐Cyclic Citrullinated Peptide Antibodies, Anti‐Citrullin Antibodies, and IgM and IgA Rheumatoid Factors with Serological Parameters of Disease Activity in Rheumatoid Arthritis
Authors: GREINER ALEXANDER , PLISCHKE HERBERT , KELLNER HERBERT , GRUBER RUDOLF
Published: July 2005

Abstract: We evaluated the association of anti‐cyclic citrullinated peptide (CCP) antibody titers with serological markers of disease activity. We also compared three different anti‐CCP antibody ELISAs with an anti‐citrullin ELISA and the IgM and the IgA rheumatoid factor (RF) in their performance of discriminating between rheumatoid arthritis (RA) and other rheumatic diseases. Sera from 333 consecutive patients of the Rheumaeinheit der Medizinischen Poliklinik Munchen, an outpatient clinic for rheumatic diseases, were collected and tested. Anti‐CCP antibodies were assayed with three different commercially available ELISAs. Antifilaggrin antibodies were tested with a commercially available ELISA using in vitro deiminated recombinant rat filaggrin. IgA‐RF was analyzed with an ELISA, whereas IgM‐RF was measured by latex‐enhanced turbidimetry. Rheumatoid arthritis (RA) was diagnosed in 87 patients according to the revised classification criteria of the American College of Rheumatology (ACR), probable RA was diagnosed in 23 patients in an early phase not (yet) fulfilling the ACR criteria, and 223 patients had other rheumatic diseases. Differences in sensitivity and specificity were calculated using McNemar's test. A measure of agreement (kappa statistic) was used to examine whether the tests tended to identify the same patients as positive or negative. Correlations between CCP titers and other tests were analyzed by Spearman nonparametric rank correlation. No significant differences in sensitivity and specificity were found between the tested CCP assays (80.0‐80.9% and 97.3‐98.1%, respectively). All three CCP tests were slightly but not significantly more sensitive and specific than the anti‐citrullin assay (77% and 92%, respectively), comparably sensitive but significantly more specific compared with the IgM‐RF (86% and 82%, respectively), and significantly more sensitive but comparably specific compared with the IgA‐RF (63% and 94.4%, respectively) in detecting the patients with RA. There was no significant correlation between anti‐CCP, anti‐citrullin, or IgM‐RF or IgA‐RF antibody titers and C‐reactive protein, erythrocyte sedimentation rate, or white blood cell count. A weak but significant linear correlation was found between anti‐CCP titers and IgM‐RF titers (r= 0.2, P= 0.03). We could not find a significant difference between the three tested anti‐CCP assays and the anti‐citrullin test in terms of sensitivity and specificity. Compared with the IgM‐RF, all the anti‐CCP assays were superior in specificity and comparable in sensitivity. Compared with the IgA‐RF, they were more sensitive and comparably specific in the discrimination of patients with RA from other rheumatic diseases. No correlation of any tested autoantibody titer with serological parameters of inflammation was found.
Detection of TT Virus in Patients with Idiopathic Inflammatory Myopathies
Authors: GERGELY PETER , BLAZSEK ANTAL , DANKÓ KATALIN , PONYI ANDREA , POÓR GYULA
Published: July 2005

Abstract: The TT virus, a recently identified single‐stranded DNA virus with unknown pathogenicity, has been shown to commonly infect humans. Viruses have been considered to contribute to disease pathogenesis in autoimmune disorders including idiopathic inflammatory myopathies (IIMs) and rheumatoid arthritis (RA). We assessed the prevalence of TTV infection in IIM compared with that in patients with RA and healthy blood donors. Detection of TTV was conducted by nested PCR and real‐time PCR in the sera of 94 patients with IIM, 95 RA patients. and 95 age‐ and sex‐matched healthy blood donors. Identity of the PCR products was confirmed by sequencing. TTV DNA was detected in 61 of 94 (64.9%) patients with IIM, in 64 of 95 (67.4%) patients with RA, and in 62 of 95 (65.3%; P > 0.05) healthy individuals. Age, sex, activity, or duration of disease had no influence on TTV positivity in either group. However, patients with severe IIM (n= 36) had a significantly higher rate of TTV infection (31/36, 86.1%) than patients with mild disease (30/58, 51.7%, P < 0.05, χ2= 10.0). Disease was considered severe in IIM when immunosuppressive treatment was necessary because of continuous high activity and/or serious inner‐organ involvement despite corticosteroid treatment. In conclusion, although we found the detection rate of TTV similar in patients with idiopathic inflammatory myopathies and rheumatoid arthritis and comparable to that in healthy controls, our data suggest that infection with TT virus may result in a more severe disease in patients with idiopathic inflammatory myopathies.
Evaluation of the BioPlex™ 2200 ANA Screen: Analysis of 510 Healthy Subjects: Incidence of Natural/Predictive Autoantibodies
Authors: SHOVMAN O , GILBURD B , BARZILAI O , SHINAR E , LARIDA B , ZANDMAN‐GODDARD G , BINDER S R , SHOENFELD Y
Published: July 2005

Abstract: The BioPlex™ 2200 ANA Screen is a fully automated system that determines levels for 13 different autoimmune antibodies of established clinical significance. The objective of this study was to determine the specificity of the BioPlex™ 2200 ANA Screen assay and to analyze the antibody profile samples collected from healthy subjects against comparative ELISA and IIF screening methods. A total of 510 specimens were randomly selected from a cohort of apparently healthy blood bank donors. Samples were distributed to five age brackets. All samples were tested using Bio‐Rad's ANA Screen kit. Specificity was compared to IIF and ELISA results. Most of the samples were found negative in all ANA screening systems (84.5% by IIF, 92.5% by BioPlex™ 2200 ANA Screen kit, and 94.5% by ELISA). The frequency of positive results was highest (15.5%) using IIF, in comparison to almost similar results (5.5% vs. 7.5%) achieved by ANA ELISA and BioPlex™ 2200 ANA Screen kits. The positive rate of autoantibodies was significantly reduced when analyzed by different combinations of ANA screen assays (from 2.35% using IIF + BioPlex ANA Screen tests to 0.98% by using all three tests). Using the BioPlex™ 2200 ANA Screen system, we were able to identify samples with high levels of individual antibodies: anti‐dsDNA at 20‐63/IU/mL, antichromatin at 4–8 AI, anti‐SmRNP at 2–6 AI, and anti‐RNPA at 2‐4.5 AI. Importantly, from 7 IIF and ELISA positive sera, 5 of these were also BioPlex 2200 positive, suggesting that the BioPlex is seeing the samples that are of the greatest interest, using the established techniques. The specificity of the BioPlex 2200 ANA Screen analysis of 13 different analytes (dsDNA, centromere B, chromatin, Jo1, ribosomal P, RNP 68, RNP A, Scl‐70, Sm, SmPNP, SS‐A52, SS‐A60, SS‐B) is comparable (P < 0.252) to the ELISA ANA screening test. Like the ELISA, the BioPlex 2200 has a lower (P < 0.001) positive rate than IIF for the autoantibody screening.
Switching to Anastrozole Versus Continued Tamoxifen Treatment of Early Breast Cancer: Preliminary Results of the Italian Tamoxifen Anastrozole Trial
Authors: Boccardo Francesco , Rubagotti Alessandra , Puntoni Matteo , Guglielmini Pamela , Amoroso Domenico , Fini Angela , Paladini Giuseppe , Mesiti Mario , Romeo Domenico , Rinaldini Michela , Scali Simona , Porpiglia Mauro , Benedetto Chiara , Restuccia Nunzio , Buzzi Franco , Franchi Roberto , Massidda Bruno , Distante Vito , Amadori Dino , Sismondi Piero
Published: July 2005

Purpose

Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor–positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required.

Patients and Methods

We conducted a prospective randomized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole. After 2 to 3 years of tamoxifen treatment, patients were randomly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d, for a total duration of treatment of 5 years. Disease-free survival was the primary end point. Event-free survival, overall survival, and safety were secondary end points.

Results

Four hundred forty-eight patients were enrolled. All women had node-positive, estrogen receptor–positive tumors. At a median follow-up time of 36 months, 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group (P = .0002). Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group (hazard ratio [HR] = 0.35; 95% CI, 0.18 to 0.68; P = .001 and HR = 0.15; 95% CI, 0.03 to 0.65; P = .003, respectively). Overall, more adverse events were recorded in the anastrozole group compared with the tamoxifen group (203 v 150, respectively; P = .04). However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04).

Conclusion

Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer.
Functional Magnetic Resonance Imaging in Anesthetized Patients: A Relevant Step toward Real-time Intraoperative Functional Neuroimaging
Authors: Gasser Thomas , Sandalcioglu Erol , Schoch Beate , Gizewski Elke , Forsting Michael , Stolke Dietmar , Wiedemayer Helmut
Published: July 2005

OBJECTIVE:

The introduction of intraoperative 1.5-T magnetic resonance imaging may provide up-to-date functional information in the surgical environment. However, feasible passive paradigms that allow the examination of anesthetized patients will be a precondition for intraoperative functional magnetic resonance imaging (fMRI). The aim of this study is to evaluate the feasibility of a recently developed passive fMRI paradigm for functional neuroimaging in anesthetized patients.

METHODS:

We investigated four anesthetized patients with intracranial pathological conditions not related to the sensorimotor cortex. All patients had been anesthetized with standard total intravenous anesthesia for more than 24 hours before the fMRI scan. Anesthesia and monitoring were sustained during the scanning procedure. A simultaneous electrical stimulation of the median and tibial nerves was applied to elicit a cortical activation using a custom-designed magnetoelectrically shielded conductor. Statistical evaluation using Statistical Parametric Mapping software (Wellcome Department of Imaging Neuroscience, University College, London, England) and the Talairach Daemon Client (Version 1.1; Research Imaging Center, University of Texas Health Science Center, San Antonio, TX) followed.

RESULTS:

Three of four patients showed a good activation of the sensorimotor cortex under anesthesia. In one patient, no significant activation was observed, presumably as a result of increased body impedance because of severe edema. Standard dosages of the narcotics did not influence the cortical response; however, stimulation intensity had to be increased compared with awake patients. We did not detect relevant interferences with magnetic resonance imaging arising from the technical setup.

CONCLUSION:

The method presented proved to be a feasible paradigm for fMRI evaluation of the sensorimotor cortex in anesthetized patients and thus forms a relevant step toward real intraoperative functional neuroimaging.
Craniotomy for Fenestration of Multiloculated Hydrocephalus in Pediatric Patients
Authors: Sandberg David I. , McComb J. Gordon , Krieger Mark D.
Published: July 2005

OBJECTIVE:

To assess the treatment of progressive multiloculated hydrocephalus by craniotomy for microsurgical fenestration of cerebrospinal fluid (CSF) compartments to minimize the number of ventricular catheters.

METHODS:

We studied 33 pediatric patients who underwent craniotomies for fenestration of progressive multiloculated hydrocephalus between 1989 and 2003. In 20 of 33 patients, hydrocephalus was attributed to intraventricular hemorrhage associated with prematurity. Twenty-three of 33 patients had previous central nervous system infections. Craniotomy was typically performed via a posterior parietal approach. Communication between bilateral supratentorial loculated compartments and posterior fossa compartments was achieved. Surgical and neurological outcomes were assessed.

RESULTS:

Fenestration of loculated CSF spaces was performed successfully in all patients. No new neurological deficits were noted after surgery, and no patients required intraoperative blood transfusions. CSF infections within 3 months after surgery occurred in 4 of 33 patients. Over a median follow-up period of 3.7 years (range, 1.5 mo to 8.7 yr), 19 of 33 patients required additional fenestration procedures. The number of repeat fenestration procedures ranged from one to six, and a total of 47 additional fenestrations were performed in these 19 patients. The majority of patients (n = 25) ultimately required shunt systems with only one ventricular catheter. The neurological status of these patients was extremely poor both before and after surgery. Twenty-nine of 33 patients were severely delayed, and four were mildly delayed.

CONCLUSION:

Fenestration of multiloculated CSF compartments can enable most patients to function with a single ventricular catheter shunt system. Neurological status remains poor in this patient population.
Intraoperative and Postoperative Gamma Detection of Somatostatin Receptors in Bone-invasive en Plaque Meningiomas
Authors: Gay Emmanuel , Vuillez Jean Philippe , Palombi Olivier , Brard Pierre Yves , Bessou Pierre , Passagia Jean Guy
Published: July 2005

OBJECTIVE:

Scintigraphy with a radiolabeled somatostatin analog (111In-diethylenetriaminepenta-acetic acid octreotide) detects the somatostatin receptors that are found in vitro in all meningiomas. Previous studies have proved the benefit of radioimmunoguided surgery, with a hand-held gamma probe, for the assessment and removal of neuroendocrine tumors. We conducted a study to determine whether intraoperative radiodetection of somatostatin receptors is feasible and could increase the probability of complete meningioma resection, especially for bone-invasive en plaque meningiomas, which are difficult to control surgically.

METHODS

Eighteen patients with en plaque sphenoid wing and cranial convexity meningiomas were studied by preoperative and postoperative somatostatin receptor scintigraphy. In 10 of them, intraoperative radiodetection with a hand-held gamma probe was performed 24 hours after the intravenous administration of 111In-diethylenetriaminepenta-acetic acid octreotide. This procedure was combined with a computer-aided navigation system.

RESULTS:

All preoperative scintigrams were positive. Intraoperative gamma probe detection was achieved for the invaded bone, dura, and periorbit of sphenoid wing meningiomas. The average tumor/nontumor count ratio was 2:1, with a maximum of 12:1, thus allowing precise detection capable of defining the tumor margins. In three cases of sphenoid wing meningiomas, postoperative scintigrams were helpful for the determination of recurrences that magnetic resonance imaging failed to detect.

CONCLUSION:

These preliminary data show that intraoperative radiodetection of somatostatin receptors with a hand-held gamma probe is feasible and may be helpful to guide the surgical removal of bone-invasive en plaque meningiomas. Preoperative and postoperative scintigraphy may be useful for the management and follow-up of patients with these tumors.
In Situ Bypass in the Management of Complex Intracranial Aneurysms: Technique Application in 13 Patients
Authors: Quiñones-Hinojosa Alfredo , Lawton Michael T.
Published: July 2005

OBJECTIVE:

Cerebral revascularization is an important part of the treatment of complex intracranial aneurysms that require deliberate occlusion of a parent artery. In situ bypass brings together intracranial donor and recipient arteries that lie parallel and in close proximity to one another rather than using an extracranial donor artery. An experience with in situ bypasses was retrospectively reviewed.

METHODS:

Thirteen aneurysms were treated with in situ bypasses between 1997 and 2004. During this time, 1071 aneurysms were treated microsurgically and 46 bypasses were performed as part of the aneurysm treatment.

RESULTS:

Treated aneurysms were located at the middle cerebral artery (MCA) in five patients, posteroinferior cerebellar artery (PICA) in three patients, vertebral artery in three patients, and anterior communicating artery in two patients. Seven aneurysms were fusiform or dolichoectatic, and six aneurysms were saccular. Microsurgical revascularization techniques included side-to-side anastomosis of intracranial arteries in eight patients and aneurysm excision with end-to-end reanastomosis of the parent artery in five patients. In situ bypasses included A3–A3 anterior cerebral artery bypass in two patients, anterior temporal artery-MCA bypass in one patient, MCA–MCA bypass in one patient, and PICA–PICA bypass in four patients. Aneurysm excision with arterial reanastomosis included three MCA aneurysms and two PICA aneurysms. On angiography, all aneurysms were completely obliterated and 12 bypasses were patent.

CONCLUSION:

In situ bypass is a safe and effective alternative to extracranial-intracranial bypasses and high-flow bypasses using saphenous vein or radial artery grafts. Although in situ bypasses are more demanding technically, they do not require harvesting a donor artery, can be accomplished with one anastomosis, and are less vulnerable to injury or occlusion.
A Novel Minimally Occlusive Microvascular Anastomosis Technique Using a Temporary Intraluminal Shunt: A Prospective Technique to Minimize Brain Ischemia Time during Superficial Temporal Artery-to-Middle Cerebral Artery Bypass
Authors: Krishnan Kartik G. , Tsirekidze Papuna , Pinzer Thomas , Schackert Gabriele
Published: July 2005

OBJECTIVE:

To describe a new technique of suturing microvessels with persistent perfusion via a temporary intraluminal microshunt.

METHODS:

Experiments were conducted in Wistar rats. Abdominal aorta grafts were explanted from donor rats. A soft silicon microcatheter was introduced into the lumen of this graft. The abdominal aorta of a recipient rat was prepared for end-to-side microvascular anastomosis. Acland clamps (S&T AG, Neuhausen, Switzerland) were applied, and a linear arteriotomy was made. One end of the graft-clad microcatheter was introduced into the lumen and occluded with a fenestrated Acland clamp. At a more distal part, a similar arteriotomy was performed, and the other end of the microcatheter was introduced into the lumen and clamped with a fenestrated Acland clip. This created a temporary shunt through the graft-clad microcatheter. Then, the graft was anastomosed to the arteriotomies at both ends, over the microcatheter, in an end-to-side manner. The microcatheter was explanted from the vessel lumen through an arteriotomy in the middle of the graft. The graft was clipped short to close this arteriotomy. The mean total occlusion time before perfusion was reestablished amounted to 3.7 minutes. This experiment was repeated in 12 animals (6 with and 6 without heparin) without technical complications. As controls, conventional anastomoses were made in 2 animals.

RESULTS:

Suturing microvessels mandates their occlusion during the period of anastomosis. Although ischemia is well tolerated by other tissue types, the brain is quite sensitive to even short windows of ischemia. Nonocclusive anastomotic techniques have been developed recently. These are confined to vessels with luminal diameters greater than 3 mm. We have evolved a novel technique that can be used with microvessels, as pertinent to superficial temporal artery-to-middle cerebral artery bypass.

CONCLUSION:

We have described a new technique for performing microvascular anastomoses over a temporary intraluminal microcatheter shunt.
Revascularization of the Anterior Cerebral Artery with an A3–A3 Anastomosis and a Superficial Temporal Artery Bypass Using an A3-Radial Artery Graft to Trap a Giant Anterior Communicating Artery Aneurysm: Technical Case Report
Authors: Inoue Tomohiro , Tsutsumi Kazuo , Ohno Hiroyasu , Shinozaki Munehisa
Published: July 2005

OBJECTIVE AND IMPORTANCE:

How to manage the distal anterior cerebral artery (ACA) circulation in the treatment of a giant anterior communicating artery aneurysm or a giant azygous A2 aneurysm is still controversial.

CLINICAL PRESENTATION:

We are reporting the case of a 70-year-old man who presented with an evolving giant thrombosed anterior communicating artery aneurysm.

INTERVENTION:

He was successfully treated by trapping the aneurysm in conjunction with an A3–A3 side-to-side anastomosis and a superficial temporal artery bypass using an A3-radial artery graft. The postoperative angiography showed an excellent filling of all the bilateral distal ACA area through the bypass.

CONCLUSION:

In cases in which direct clipping to preserve distal ACA flow is quite difficult, the bilateral ACA revascularization described here should be considered as another possibility.
Treatment of a Middle Cerebral Artery Bifurcation Aneurysm Using a Double Neuroform Stent “Y” Configuration and Coil Embolization: Technical Case Report
Authors: Sani Sepehr , Lopes Demetrius Klee
Published: July 2005

OBJECTIVE AND IMPORTANCE:

Wide-necked cerebral aneurysms have been particularly difficult to treat using coil embolization. The introduction of the first intracranial flexible stent (Neuroform stent; Boston Scientific/Target, Fremont, CA) has provided a great advantage to this dilemma by forming a bridge across the aneurysm neck and allowing the packing of coils. Despite this advancement, some parent vessel bifurcation aneurysms can still remain elusive to single stent and coiling technique.

CLINICAL PRESENTATION:

A 55-year-old woman presented for a routine follow-up angiogram. Her past history was significant for a subarachnoid hemorrhage and clipping of an anterior communicating aneurysm with full recovery. An incidental new right middle cerebral artery aneurysm was found on the angiogram. We report here a case of an unruptured asymptomatic wide-neck middle cerebral artery bifurcation aneurysm that was treated with a novel endovascular repair.

INTERVENTION:

The aneurysm was successfully treated using a double stent “Y” configuration and coil embolization technique using the Neuroform stent. Technical aspects are discussed. Perioperative management issues and potential pitfalls are also considered.

CONCLUSION:

Double stenting in “Y” configuration and coiling is feasible. This technique should increase the ability to endovascularly treat wide-necked aneurysms.
DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling
Authors: Fan Guoping , Martinowich Keri , Chin Mark H. , He Fei , Fouse Shaun D. , Hutnick Leah , Hattori Daisuke , Ge Weihong , Shen Yin , Wu Hao , ten Hoeve Johanna , Shuai Ke , Sun Yi E.
Published: July 2005

DNA methylation is a major epigenetic factor that has been postulated to regulate cell lineage differentiation. We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation. The developmentally regulated demethylation of astrocyte marker genes as well as genes encoding the crucial components of the gliogenic JAK-STAT pathway is accelerated in Dnmt1–/– NPCs. Through a chromatin remodeling process, demethylation of genes in the JAK-STAT pathway leads to an enhanced activation of STATs, which in turn triggers astrocyte differentiation. Our study suggests that during the neurogenic period, DNA methylation inhibits not only astroglial marker genes but also genes that are essential for JAK-STAT signaling. Thus, demethylation of these two groups of genes and subsequent elevation of STAT activity are key mechanisms that control the timing and magnitude of astroglial differentiation.
Dynamic interaction of NtMAP65-1a with microtubules in vivo
Authors: Chang Hsin-Yu , Smertenko Andrei P. , Igarashi Hisako , Dixon David P. , Hussey Patrick J.
Published: July 2005

Plant microtubules are intrinsically more dynamic than those from animals. We know little about the dynamics of the interaction of plant microtubule-associated proteins (MAPs) with microtubules. Here, we have used tobacco and Arabidopsis MAPs with relative molecular mass 65 kDa (NtMAP65-1a and AtMAP65-1), to study their interaction with microtubules in vivo. Using fluorescence recovery after photobleaching we report that the turnover of both NtMAP65-1a and AtMAP65-1 bound to microtubules is four- to fivefold faster than microtubule treadmilling (13 seconds compared with 56 seconds, respectively) and that the replacement of NtMAP65-1a on microtubules is by random association rather than by translocation along microtubules. MAP65 will only bind polymerised microtubules and not its component tubulin dimers. The turnover of NtMAP65-1a and AtMAP65-1 on microtubules is similar in the interphase cortical array, the preprophase band and the phragmoplast, strongly suggesting that their role in these arrays is the same. NtMAP65-1a and AtMAP65-1 are not observed to bind microtubules in the metaphase spindle and their rate of recovery is consistent with their cytoplasmic localisation. In addition, the dramatic reappearance of NtMAP65-1a on microtubules at the spindle midzone in anaphase B suggests that NtMAP65-1a is controlled post-translationally. We conclude that the dynamic properties of these MAPs in vivo taken together with the fact that they have been shown not to effect microtubule polymerisation in vitro, makes them ideally suited to a role in crossbridging microtubules that need to retain spatial organisation in rapidly reorganising microtubule arrays.
The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF–β-catenin-mediated transcription
Authors: Weiske Jörg , Huber Otmar
Published: July 2005

Pontin and Reptin previously were identified as nuclear β-catenin interaction partners that antagonistically modulate β-catenin transcriptional activity. In this study, Hint1/PKCI, a member of the evolutionary conserved family of histidine triad proteins, was characterised as a new interaction partner of Pontin and Reptin. Pull-down assays and co-immunoprecipitation experiments show that Hint1/PKCI directly binds to Pontin and Reptin. The Hint1/PKCI-binding site was mapped to amino acids 214-295 and 218-289 in Pontin and Reptin, respectively. Conversely, Pontin and Reptin bind to the N-terminus of Hint1/PKCI. Moreover, by its interaction with Pontin and Reptin, Hint1/PKCI is associated with the LEF-1/TCF–β-catenin transcription complex. In this context, Hint1/PKCI acts as a negative regulator of TCF–β-catenin transcriptional activity in Wnt-transfected cells and in SW480 colon carcinoma cells as shown in reporter gene assays. Consistent with these observations, Hint1/PKCI represses expression of the endogenous target genes cyclin D1 and axin2 whereas knockdown of Hint1/PKCI by RNA interference increases their expression. Disruption of the Pontin/Reptin complex appears to mediate this modulatory effect of Hint1/PKCI on TCF–β-catenin-mediated transcription. These data now provide a molecular mechanism to explain the tumor suppressor function of Hint1/PKCI recently suggested from the analysis of Hint1/PKCI knockout mice.
Cold-induced coalescence of T-cell plasma membrane microdomains activates signalling pathways
Authors: Magee Anthony I. , Adler Jeremy , Parmryd Ingela
Published: July 2005

The plasma membranes of eukaryotic cells are hypothesised to contain microdomains with distinct lipid and protein composition known as lipid rafts. In T cells, cross-linking of lipid raft components triggers signalling cascades. We show that the T-cell antigen receptor (TCR) and a protein tyrosine kinase, Lck, have a patchy plasma membrane distribution in Jurkat T cells at reduced temperatures, although they have a continuous distribution at physiological temperature (37°C). GM1 displays a patchy distribution at reduced temperature after Triton X-100 extraction. The archetypal non-lipid raft marker, the transferrin receptor, displays a more continuous plasma membrane distribution uncorrelated with that of Lck at 0°C. Cold-induced aggregation of the lipid raft-partitioning proteins is accompanied by increased tyrosine phosphorylation and ERK activation, peaking at 10-20°C. Tyrosine phosphorylation is further greatly increased by ligating the TCR with anti-CD3 at 10-20°C. The tyrosine phosphorylation mainly occurred at the plasma membrane, was dependent on Lck and on the surface expression of the TCR. The activation of tyrosine phosphorylation and ERK by TCR ligation at reduced temperature also occurred in human primary T cells. These results support the concept that lipid rafts can form in membranes of live cells and that their coalescence stimulates signalling.
Nuclear inositol 1,4,5-trisphosphate receptors regulate local Ca2+ transients and modulate cAMP response element binding protein phosphorylation
Authors: Cárdenas Cesar , Liberona José Luis , Molgó Jordi , Colasante Cesare , Mignery Gregory A. , Jaimovich Enrique
Published: July 2005

Several lines of evidence indicate that increases in nuclear Ca2+ have specific biological effects that differ from those of cytosolic Ca2+, suggesting that they occur independently. The mechanisms involved in controlling nuclear Ca2+ signaling are both controversial and still poorly understood. Using hypotonic shock combined with mechanical disruption, we obtained and characterized a fraction of purified nuclei from cultured rat skeletal myotubes. Both immunoblot studies and radiolabeled inositol 1,4,5-trisphosphate [IP3] binding revealed an important concentration of IP3 receptors in the nuclear fraction. Immunofluorescence and immunoelectron microscopy studies localized type-1 and type-3 IP3 receptors in the nucleus with type-1 receptors preferentially localized in the inner nuclear membrane. Type-2 IP3 receptor was confined to the sarcoplasmic reticulum. Isolated nuclei responded to IP3 with rapid and transient Ca2+ concentration elevations, which were inhibited by known blockers of IP3 signals. Similar results were obtained with isolated nuclei from the 1B5 cell line, which does not express ryanodine receptors but releases nuclear Ca2+ in an IP3-dependent manner. Nuclear Ca2+ increases triggered by IP3 evoked phosphorylation of cAMP response element binding protein with kinetics compatible with sequential activation. These results support the idea that Ca2+ signals, mediated by nuclear IP3 receptors in muscle cells, are part of a distinct Ca2+ release component that originates in the nucleus and probably participates in gene regulation mediated by cAMP response element binding protein.
Pharmaceutical Care in Community Pharmacies: Practice and Research in Canada
Authors: Jones Erika JM , MacKinnon Neil J , Tsuyuki Ross T
Published: July 2005

OBJECTIVE:

To discuss the provision of pharmaceutical care in community pharmacies in Canada including the following topics: organization and delivery of health services, health service policy, methods of payment, types of pharmacy services provided, types of cognitive pharmacy services, research in community pharmacy, and future plans for community pharmacy services.

DATA SYNTHESIS:

The implementation of pharmaceutical care in Canadian community pharmacies continues to become more widespread. However, barriers to the provision of pharmaceutical care still exist, including the current shortage of pharmacists and lack of reimbursement systems for cognitive services. Evidence of the value of pharmaceutical care in Canadian community pharmacies has been supported by several pharmacy practice research projects. The pharmacist's role in patient care is expected to continue to expand.

CONCLUSIONS:

Although Canadian pharmacists' capabilities are not yet universally recognized and applied to their full potential, there is reason to be optimistic about the future of pharmaceutical care in the community setting in Canada.
Life-Threatening Interaction Between Complementary Medicines: Cyanide Toxicity Following Ingestion of Amygdalin and Vitamin C
Authors: Bromley Jonathan , Hughes Brett GM , Leong David CS , Buckley Nicholas A
Published: July 2005

OBJECTIVE:

To describe a case of severe accidental cyanide poisoning following a single ingestion of amygdalin with therapeutic intent.

CASE SUMMARY:

A 68-year-old patient with cancer presented to the emergency department shortly after her first dose (3 g) of amygdalin with a reduced Glasgow Coma Score, seizures, and severe lactic acidosis requiring intubation and ventilation. The patient also ingested 4800 mg of vitamin C per day. She responded rapidly to hydroxocobalamin treatment. The adverse drug reaction was rated probable on the Naranjo probability scale.

DISCUSSION:

Amygdalin and laetrile (a synthetic form of amygdalin) are commonly used as complementary or alternative medicine (CAM) for the treatment of cancer. Vitamin C is known to increase the in vitro conversion of amygdalin to cyanide and reduce body stores of cysteine, which is used to detoxify cyanide. Amygdalin has been used for decades by patients with cancer who are seeking alternative therapies, and severe reactions have not been reported with this dose. An interaction with vitamin C is a plausible explanation for this life-threatening response.

CONCLUSIONS:

This case highlights the fact that CAMs can produce life-threatening toxicity. This case also adds a further note of caution, namely, the potential for serious interactions between CAMs, particularly where there is no tradition of concomitant use.
Determination of Organic Compounds by IR/ATR Spectroscopy with Polymer-Coated Internal Reflection Elements
Authors: Heinrich Petra , Wyzgol Raimund , Schrader Bernhard , Hatzilazaru Arhontula , Lübbers D. W.
Published: July 2005

The possibility of quantitative determination of organic compounds in aqueous solution or in the gaseous phase by FT-IR/ATR spectroscopy by the aid of polymer-covered internal reflection elements has been studied. In general this method has three effects: (1) exclusion of water from the measurement, (2) lowering of the limit of detection because of the continuous and reversible enrichment of organic compounds, and (3) reduction of the half-width of the absorption bands for gases by insertion of the molecules in a polymer film. The enrichment of some halogenated hydrocarbons in three different polymer materials was used to determine the concentrations of these substances in water by IR spectroscopy with very good limits of detection (sometimes less than 1 mg/dm3). In all cases a linear relationship between concentration of the sample and apparent extinction of the absorption band of interest is recorded. The time constants for 90% saturation of the polymer are several seconds for measurements of gases and some minutes for aqueous solutions, depending on the polymer material and the character of the substance.
Time-Resolved Laser-Induced Breakdown Spectroscopy of Iron Ore
Authors: Grant Kenneth J. , Paul George L. , O'Neill James A.
Published: July 2005

Laser-induced plasmas are highly transient phenomena, lasting for several microseconds. The lines of a plasma spectrum do not appear simultaneously, and, furthermore, they exist for a range of lifetimes. Time-resolved laser-induced breakdown spectroscopy (TRELIBS) has been shown to be effective in increasing the line-to-background ratios of spectra. The results of time-resolved spectroscopy of the excimer laser-induced plasmas of iron ore are presented. The period of the plasma lifetime which is optimum for spectrochemical analysis of ore was determined.
X-Ray Photoelectron Spectroscopic Studies of Carbon Fibers. Part XIV: Electrochemical Treatment of Pitch-Based Fibers and the Surface and Bulk Structure Changes Monitored by XPS, XRD, and SEM
Authors: Xie Yaoming , Sherwood Peter M. A.
Published: July 2005

Core and valence band X-ray Photoelectron Spectroscopy, as well as X-ray Diffraction and Scanning Electron Microscopy, has been used to monitor the surface chemistry and bulk structure changes when DuPont E-120 high-modulus pitch-based carbon fibers are anodically oxidized in 1 M HNO3 solution at different anodic potentials. Electrochemical treatments changed both the surface and bulk chemistry of the fiber, while plasma treatment only affected the surface structure. Electrochemically treated fibers showed significant surface functional group decomposition after exposure to the x-ray radiation during the x-ray photoelectron spectroscopy experiment, but the decomposition occurred only on the top surface layer.
Automated Micro-Raman Mapping and Imaging Applied to Silicon Devices and Zirconia Ceramic Stress and Grain Boundary Morphology
Authors: Bowden Michael , Dickson George D. , Gardiner Derek J. , Wood David J.
Published: July 2005

An automated, point-by-point, Raman mapping and imaging system is described that combines a 0.5- μm stepper-motor-driven stage, a Raman microscope, and a filter spectrograph with an intensified diode array detector. High-resolution Raman images of a silicon device structure and a map showing the presence of the monoclinic phase of zirconia (ZrO2) at grain boundaries and in stressed regions of a sintered tetragonally stabilized ceramic are reported. The importance of image processing is demonstrated and emphasised.
Noise Characterization of a “Surfatron” MIP and the Implications for Fourier-Transform-Based Detection in GC-MIP-AES
Authors: Sing Robert L. A. , Hubert Joseph
Published: July 2005

The noise amplitude spectra of a “Surfatron” microwave-induced plasma have been characterized. These are found to be similar to the noise amplitude spectra of conventional microwave plasmas sustained in TM010 cavities. Interference noises due to power line pickup and low-frequency 1/f noise extending to approximately 1 Hz are the major features observed on a largely white noise amplitude spectrum. The features observed in the noise amplitude spectra correlate well with the noise features in optical spectra of the source acquired by Fourier transform spectroscopy.