bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Progress in the Synthesis of Porous Carbon Materials
Authors: Lee J. , Kim J. , Hyeon T.
Published: August 2006

In this review, the progress made in the last ten years concerning the synthesis of porous carbon materials is summarized. Porous carbon materials with various pore sizes and pore structures have been synthesized using several different routes. Microporous activated carbons have been synthesized through the activation process. Ordered microporous carbon materials have been synthesized using zeolites as templates. Mesoporous carbons with a disordered pore structure have been synthesized using various methods, including catalytic activation using metal species, carbonization of polymer/polymer blends, carbonization of organic aerogels, and template synthesis using silica nanoparticles. Ordered mesoporous carbons with various pore structures have been synthesized using mesoporous silica materials such as MCM‐48, HMS, SBA‐15, MCF, and MSU‐X as templates. Ordered mesoporous carbons with graphitic pore walls have been synthesized using soft‐carbon sources that can be converted to highly ordered graphite at high temperature. Hierarchically ordered mesoporous carbon materials have been synthesized using various designed silica templates. Some of these mesoporous carbon materials have successfully been used as adsorbents for bulky pollutants, as electrodes for supercapacitors and fuel cells, and as hosts for enzyme immobilization. Ordered macroporous carbon materials have been synthesized using colloidal crystals as templates. One‐dimensional carbon nanostructured materials have been fabricated using anodic aluminum oxide (AAO) as a template.
Through‐Space Conjugated Polymers Based on Cyclophanes
Authors: Morisaki Yasuhiro , Chujo Yoshiki
Published: August 2006

Conjugated polymers display unique electronic and optical properties, which favor their use in applications as optoelectronic materials and molecular devices. Despite the recent remarkable progress in the chemistry of conjugated polymers, the synthesis of conjugated polymers containing cyclophane units in the main chain is limited to only a few examples. This Minireview presents recent developments in the synthesis, properties, and applications of through‐space conjugated polymers based on cyclophanes.
Readily Synthesized Chiral Sulfides as Reagents for Asymmetric Epoxidation
Authors: Badine D. Michael , Hebach Christina , Aggarwal Varinder K.
Published: August 2006

Chiral oxathianes were designed, synthesized, and successfully used for asymmetric sulfur ylide mediated epoxidation. A considerable emphasis has been placed upon the design of sulfides with suitable architecture in a small number of steps (three or four). The use of (4aR,6S,8aR)‐6‐isopropenyl‐8a‐methyloctahydro‐1,4‐benzoxathiane in asymmetric epoxidation resulted in good diastereo‐ and enantioselectivity in the formation of stilbene oxide, and (2S,6S)‐2‐allyl‐2,3,3,6‐tetramethyl‐1,4‐oxathiane produced even better results. Moderate to good diastereoselectivities with essentially complete enantioselectivities were observed in the formation of alkyl–aryl‐, vinyl–aryl‐, and propargyl–aryl‐substituted epoxides. The selectivities were rationalized and supported by density functional theory calculations.
Über den Briefwechsel zwischen Karl Jaspers und Heinrich Behnke
Authors: Hartmann Uta
Published: August 2006

On the correspondence between Karl Jaspers and Heinrich Behnke. – In summer 1922 the mathematician Heinrich Behnke (1898–1979) attended lectures by the philosopher Karl Jaspers (1883–1969). This marked the beginning of a friendship over more than 40 years. This article will describe the essential topics of the correspondence between Jaspers and Behnke. Two topics will be pointed out: First their relationship which was characterized by their experiences and sorrows – especially during the Nazi regime. Second their discussion on researching and giving lectures. By this Jaspers' book Die Idee der Universität was the focus of interest.
The risk of second primary tumors in patients with nasopharyngeal carcinoma after definitive radiotherapy
Authors: Kong Lin , Lu Jiade Jay , Hu Chaosu , Guo Xiaomao , Wu Yongru , Zhang Youwang
Published: August 2006

BACKGROUND

Second primary tumors (SPTs) have a substantial impact on survival in cancer patients. However, risk factors for SPTs have not been documented well, especially in nasopharyngeal carcinoma (NPC). The objective of this retrospective analysis was to evaluate such risks in patients with NPC after they received definitive radiation treatment.

METHODS

Three hundred twenty‐six consecutive patients with pathologically confirmed, nonmetastatic, undifferentiated NPC who received treatment between January 1, 1994 and December 30, 1995 were analyzed. All patients were restaged in accordance with the 2002 American Joint Committee on Cancer staging classification. There were 18 patients (5.5%) with Stage I NPC, 152 patients (46.6%) with Stage II NPC, 101 patients (31.0%) with Stage III NPC, and 55 patients (16.9%) with Stage IVA or IVB NPC at initial diagnosis. All patients received definitive radiotherapy with either Cobalt‐60 or megavoltage therapy. High‐dose‐rate brachytherapy was given to 23 patients either as part of their primary treatment or as adjuvant treatment for residual lesions.

RESULTS

The median follow‐up for all patients was 5.6 years (range, 1.0–8.0 years). Seventeen patients (5.2%) developed SPTs, for an average annual rate of 1.0%, and the 5‐year cumulative incidence was 5.8%. Six SPTs were located within the radiation field. The cumulative incidence of in‐field SPTs was 0.35% at 3 years and 1.2% at 5 years, and the average annual rate was 0.35%. Eleven patients (64.7%) had tumors of the upper aerodigestive tract (UADT). Among the 14 SPTs that occurred within 5 years after radiotherapy, only 3 tumors (21.4%) occurred within the radiation field. In contrast, all 3 SPTs that occurred >5 years after radiotherapy occurred within the radiation field (P = .029). Multivariate analysis showed that age was the only independent risk factor for developing SPTs after RT for NPC. Advanced age (age ≥50 years) was associated with a 37% increased risk of developing SPTs (relative risk, 1.367; 95% confidence interval, 1.067–1.1753; P = .014). Other factors, including gender, tumor or lymph node classification, chemotherapy, total radiation dose to the nasopharynx, reirradiation, and adjuvant brachytherapy did not influence the risk of SPTs.

CONCLUSIONS

SPTs in patients with NPC occurred preferentially in the UADT and tended to develop within the irradiated field >5 years after patients received radiation. Older patients with NPC (age ≥50 years) may be at increased risk. Further studies with larger samples and longer follow‐up will be needed to confirm these findings. Cancer 2006. © 2006 American Cancer Society.
The incidence and mortality of cutaneous melanoma in southern Germany
Authors: Lasithiotakis Konstantinos G. , Leiter Ulrike , Gorkievicz Roman , Eigentler Thomas , Breuninger Helmut , Metzler Gisela , Strobel Waltraud , Garbe Claus
Published: August 2006

BACKGROUND

Cutaneous melanoma (CM) incidence and mortality have risen dramatically during the past 2 generations, particularly among Caucasian populations. Detailed, long‐term trends of CM in relation to clinical and pathologic characteristics in a Central European population have not been published to date.

METHODS

The current study was based on 1980 patients with invasive CM diagnosed in Southern Germany during the years from 1976 to 2003 documented by the Central Malignant Melanoma Registry. The German standard population was used to calculate age‐standardized rates, and the annual percent change was estimated by using age, anatomic site, histologic type, and tumor thickness.

RESULTS

During the study period, the incidence of CM approximately was tripled for males and females, reaching 10.3 and 13.3 per 100,000 per year, respectively (P < .001). The largest increases occurred for melanoma localized on the upper limbs (annual change, 5.9% for males and 5.0% for females; P < .001) and superficially spreading melanoma (annual change, 7.8% for males and 5.9% for females; P < .001). Thin tumors (Breslow thickness <1 mm) were presented significantly more often during the study period (annual change, 9.8% for males and 6.1% for females; P < .001), predominantly in younger patients. Thick tumors and nodular melanomas were more frequent among older patients (age >70 years), particularly among males. The age‐standardized mortality decreased from 1.5 to 0.8 per 100,000 males and from 2.6 to 0.8 per 100,000 females with a significant downward trend for the female population (P < .001).

CONCLUSIONS

The current results indicated which diverging trends between incidence and mortality may be explained by improved public awareness regarding suspicious pigmented lesions and the earlier detection of these tumors. Continuation of the current preventive strategy and its expansion to include older age groups in the population are warranted. Cancer 2006. © 2006 American Cancer Society.
On the BIEM solution for a half‐space by Neumann series
Authors: Antes M. Y. , Karinski Y. S. , Yankelevsky D. Z.
Published: August 2006

This paper presents an approach which allows the solution of elastic problems concerning a half‐space (half‐plane) with cavities by the boundary integral equation methods using Neumann's series. To evaluate the series terms at singular points, the regular representations of singular integrals for the external problems were proven and the regular recurrent relationships for the series terms, which can be calculated by any known quadrature rule, are obtained. The numerical proposed procedure was tested by comparison with known theoretical solution and the method convergence was studied for various depths of a buried cavity. Copyright © 2006 John Wiley & Sons, Ltd.
Parallel computation of arbitrarily shaped waveguide modes using BI‐RME and Lanczos methods
Authors: Vidal A. M. , Vidal A. , Boria V. E. , García V. M.
Published: August 2006

This paper is devoted to the parallelization of a new method for solving large, structured eigenvalue problems, which appear in the electromagnetic modal analysis of arbitrarily shaped waveguides, typically present in many modern passive devices. This new method, based on the boundary integral‐resonant mode expansion (BI‐RME) technique and in the Lanczos method (for solution of the eigenvalue problem), was recently proposed by the authors, showing important advantages in terms of CPU time and memory over previously used solutions. As it will be fully described in this paper, the parallel version of such a new method allows further important savings in the overall CPU computation time. Comparative benchmarks and scalability issues related to the implemented parallel algorithm are discussed. Copyright © 2006 John Wiley & Sons, Ltd.
On the resolution of transverse stresses in solid‐shells with a multi‐layer formulation
Authors: Fiolka M. , Matzenmiller A.
Published: August 2006

A locking free solid‐shell element, based on a surface orientated shell formulation, is used for a single‐layer approach as well as for a multi‐layer analysis. Locking is removed by a combination of the assumed strain and enhanced assumed strain methods. The suggested incompatible strain field enables the element to pass the patchtest for plates with a minimum of enhancement parameters. It is tested at various benchmark examples for the resolution of the transverse shear and normal stresses in thin‐walled structures. Copyright © 2006 John Wiley & Sons, Ltd.
ZAP‐70 by flow cytometry: A comparison of different antibodies, anticoagulants, and methods of analysis
Authors: Best O. G. , Ibbotson R. E. , Parker A. E. , Davis Z. A. , Orchard J. A. , Oscier D. G.
Published: August 2006

Background:

The clinical course of chronic lymphocytic leukaemia (CLL) is variable. ZAP‐70 expression is believed to provide prognostic information. The flow cytometric detection of ZAP‐70 is difficult because it is an intracellular antigen with weak expression in CLL. Consensus has not been reached as to the best method for measurement.

Methods:

We analyzed 72 CLL patient samples for ZAP‐70 expression and IgVH mutational status. Sensitivity and specificity of ZAP‐70 expression against IgVH mutational status were assessed for two clones (2F3.2 and 1E7.2) and for four methods of analysis: percentage positivity (PP), comparing test to isotype control, ratio of geometric means of test and isotype control, and percentage and ratiometric methods comparing test and T/NK cell populations. The effects of anticoagulant, collection times, and time to analysis were also evaluated.

Results:

Sensitivity and specificity were 85 and 88%, respectively, for Upstate PP; 70 and 88% for Caltag PP; 89 and 91% for Upstate ratio; 89 and 88% for Caltag ratio. Intraobserver variability was smaller when ZAP‐70 expression was assessed using a ratiometric approach rather than the percentage method. By 48 h, we observed an average decrease of 13% in the Caltag ratio in the heparin preserved samples compared to an increase of 3% in those collected in EDTA. Within the first 24‐h period, a greater percent variability was observed in those samples collected into EDTA compared with heparin.

Conclusion:

Our data support a rapid method for ZAP‐70 measurement using commercially available fixation/permeabilization reagents, a conjugated antibody, and a ratiometric method of analysis that minimizes subjective interpretation of the results. This is a method of ZAP‐70 assessment that could be included in a routine diagnostic CLL panel; however, the choice of anticoagulant and time of analysis after collection are critical factors in accurate assessment of ZAP‐70 expression. © 2006 International Society for Analytical Cytology
Kolmogorov–Smirnov statistical test for analysis of ZAP‐70 expression in B‐CLL, compared with quantitative PCR and IgVH mutation status
Authors: Van Bockstaele Femke , Janssens Ann , Piette Anne , Callewaert Filip , Pede Valerie , Offner Fritz , Verhasselt Bruno , Philippé Jan
Published: August 2006

Background:

ZAP‐70 has been proposed as a surrogate marker for immunoglobulin heavy‐chain variable region (IgVH) mutation status, which is known as a prognostic marker in B‐cell chronic lymphocytic leukemia (CLL). The flow cytometric analysis of ZAP‐70 suffers from difficulties in standardization and interpretation. We applied the Kolmogorov–Smirnov (KS) statistical test to make analysis more straightforward.

Methods:

We examined ZAP‐70 expression by flow cytometry in 53 patients with CLL. Analysis was performed as initially described by Crespo et al. (New England J Med 2003; 348:1764‐1775) and alternatively by application of the KS statistical test comparing T cells with B cells. Receiver‐operating‐characteristics (ROC)‐curve analyses were performed to determine the optimal cut‐off values for ZAP‐70 measured by the two approaches. ZAP‐70 protein expression was compared with ZAP‐70 mRNA expression measured by a quantitative PCR (qPCR) and with the IgVH mutation status.

Results:

Both flow cytometric analyses correlated well with the molecular technique and proved to be of equal value in predicting the IgVH mutation status. Applying the KS test is reproducible, simple, straightforward, and overcomes a number of difficulties encountered in the Crespo‐method.

Conclusions:

The KS statistical test is an essential part of the software delivered with modern routine analytical flow cytometers and is well suited for analysis of ZAP‐70 expression in CLL. © 2006 International Society for Analytical Cytology
Discordant results of flow cytometric ZAP‐70 expression status in B‐CLL samples if different gating strategies are applied
Authors: Wilhelm Christian , Neubauer Andreas , Brendel Cornelia
Published: August 2006

Background:

Recent studies have identified ZAP‐70 expression status as an excellent prognostic parameter in chronic lymphocytic leukemia (CLL). ZAP‐70 expression can be determined by direct antibody staining followed by flow cytometric analysis. However, there are currently several different gating strategies for analysis. We compared those strategies for ZAP‐70 expression analysis.

Methods:

One hundred and one patients with B‐CLL were analyzed employing a directly labeled alexa‐fluor‐488‐ZAP‐70‐antibody. In 27 cases, we additionally measured and analyzed ZAP‐70 expression, together with healthy controls as described previously.

Results:

Applying either T‐/NK‐cell isotype or healthy control analysis strategies on patient samples that were processed in parallel revealed discrepant results in 48% (12/25) of all cases. Taken together with the 74 B‐CLL patients, who were analyzed with regard to average reference values, disconcordant results were obtained in 58% of the samples. We demonstrate that high variances in ZAP‐70 T‐/NK‐cell staining within B‐CLL patients, paired with a close proximity of ZAP‐70 B‐cell values to the suggested cut‐off levels, may lead to interpretation difficulties of ZAP‐70 status.

Conclusions:

We conclude that different gating strategies for determining flow cytometric ZAP‐70 expression status produce highly discordant results. Further standardization is required before ZAP‐70 can be used as a reliable prognostic parameter in immunophenotyping of B‐CLL. © 2006 International Society for Analytical Cytology
What is ZAP‐70?
Authors: Béné Marie Christine
Published: August 2006

Zap‐70, a crucial molecule for the selective activation of T cells, through its interaction with the ζ chain of the TCR/CD3 complex, is a tyrosine kinase. This well studied molecule has gained a renewed interest upon the demonstration of its transduction and expression in B cells from patients with chronic lymphocytic leukemia. Here the major characteristics of this cytosolic protein are reviewed, as well as its expression in various cell types and some indications about its detection. © 2006 International Society for Analytical Cytology
Use of a blocking antibody method for the flow cytometric measurement of ZAP‐70 in B‐CLL
Authors: Shenkin Mark , Maiese Russell
Published: August 2006

Background:

In this study we developed a method to measure the amount of ZAP‐70 [zeta accessory protein] in B‐CLL cells without relying on the ZAP‐70 expression of patient B or T cells to normalize fluorescence intensity.

Methods:

B‐CLL cells were fixed with formaldehyde before surface staining with gating antibodies CD19PC5 and CD5FITC. The cells were permeabilized with saponin, and the ZAP‐70 antigen was blocked in one tube with unlabeled antibody to ZAP‐70 [clone 1E7.2]. Zap‐70‐PE was then added to this tube. ZAP‐70‐PE was added to a second tube without unlabeled antibody to ZAP‐70. The mean fluorescence intensity of the ZAP‐70 in the tube without unlabeled antibody divided by the mean fluorescence intensity of the ZAP‐70 in the tube with unlabeled antibody equals the RATIO of total fluorescence to non‐specific ZAP‐70 fluorescence in the B‐CLL cells. In a second method of analysis, a region is created in the histogram showing ZAP‐70 fluorescence intensity in the tube with unlabeled antibody to ZAP‐70. This region is set to 0.9% positive cells. This same region is then used to measure the % positive [%POS] ZAP‐70 cells in the tube without unlabeled antibody to ZAP‐70. The brighter the ZAP‐70 fluorescence above the non‐specific background, the higher the %POS.

Results:

Due to the varying amount of non‐specific staining between patient B‐CLL cells and other cells, the blocking antibody method yielded a more quantitative and reproducible measure of ZAP‐70 in B‐CLL cells than other methods, which use the ratio of B‐CLL fluorescence to normal B or T‐cell fluorescence. Using this improved method, ZAP‐70 was determined to be negative if the RATIO was less than 2:1 and positive if the RATIO was greater than 2:1. ZAP‐70 was determined to be negative if the %POS was less than 5% and positive if the %POS was greater than 5%, a cut‐off value lower than previous values published, due to exclusion of non‐specific staining. Both cut‐offs were based upon patient specimen distribution profiling.

Conclusions:

Use of a blocking antibody resulted in a robust, reproducible clinical B‐CLL assay that is not influenced by the need to measure the amount of ZAP‐70 in other cells. ZAP‐70 results segre gate patients into indolent and aggressive groups suggested by published clinical outcomes. © 2006 International Society for Analytical Cytology
Flow cytometry for ZAP‐70: New colors for chronic lymphocytic leukemia
Authors: Wiestner Adrian
Published: August 2006

ZAP‐70 has become one of the most studied prognostic markers in Chronic Lymphocytic Leukemia (CLL). ZAP‐70 is remarkable in many ways: ZAP‐70 has been identified as the best discriminating gene between prognostically distinct CLL subtypes using large scale gene expression profiling; ZAP‐70 has been shown to enhance signal transduction in CLL B‐cells and therefore could contribute to disease progression; and ZAP‐70 is one of the rare examples of an intracellular target considered for clinical flow cytometry. This issue attests to the enormous effort and the steady progress made in overcoming technical challenges of testing for ZAP‐70 expression and sets the foundation for a successful translation of this important marker into clinical practice. Despite the best effort, one will likely have to accept that not all cases can be clearly assigned to one or the other group, given that ZAP‐70 expression between CLL patients falls along a continuum from absent to high. Nevertheless, ZAP‐70 expression could become a key parameter to guide patients towards risk adapted treatment strategies in prospective clinical trials. © 2006 International Society for Analytical Cytology
ZAP‐70 expression in B‐cell chronic lymphocytic leukemia: Evaluation by external (isotypic) or internal (T/NK cells) controls and correlation with IgVH mutations
Authors: Zucchetto Antonella , Bomben Riccardo , Bo Michele Dal , Nanni Paola , Bulian Pietro , Rossi Francesca Maria , Del Principe Maria Ilaria , Santini Simone , Del Poeta Giovanni , Degan Massimo , Gattei Valter
Published: August 2006

Background:

Expression of T cell specific zeta‐associated protein 70 (ZAP‐70) by B‐cell chronic lymphocytic leukemia (B‐CLL) cells, as investigated by flow cytometry, has both prognostic relevance and predictive power as surrogate for immunoglobulin heavy chain variable region (IgVH) mutations, although a standardization of the cytometric protocol is still lacking.

Methods:

Flow cytometric analyses for ZAP‐70 were performed in peripheral blood samples from 145 B‐CLL (124 with IgVH mutations) by a standard three‐color protocol. Identification of ZAP‐70+ cell population was based on an external negative control, i.e., the isotypic control (ISO method) or an internal positive control, i.e., the population of residual normal T/NK cells (TNK method). A comparison between these two approaches was performed.

Results:

While 86/145 cases were concordant as for ZAP‐70 expression according to the two methods (ISO+TNK+ or ISO−TNK−), 59/145 cases had discordant ZAP‐70 expression, mainly (56/59) showing a ISO+TNK− profile. These latter cases express higher levels of ZAP‐70 in their normal T cell component. Moreover, discordant ISO+TNK− cases had a IgVH gene mutation profile similar to that of concordantly positive cases and different from ZAP‐70 concordantly negative B‐CLL.

Conclusion:

Analysis of ZAP‐70 expression by B‐CLL cells by using the ISO method allows to overcome the variability in the expression of ZAP‐70 by residual T cells and yields a better correlation with IgVH gene mutations. A receiver operating characteristic analysis suggests to employ a higher cut‐off than the commonly used 20%. A parallel evaluation of the prognostic value of ZAP‐70 expression, as determined according to the ISO and TNK methods, is still needed. © 2006 International Society for Analytical Cytology
Comparison of bone marrow and peripheral blood ZAP‐70 status examined by flow cytometric immunophenotyping in patients with chronic lymphocytic leukemia
Authors: Sheridan Rachel , Mounajjed Taofic , Ehrmann Diane E. , Hurtubise Paul E. , Schrager Jeffrey A.
Published: August 2006

Background:

The mutational status of the immunoglobulin heavy chain variable gene in patients with chronic lymphocytic leukemia correlates with prognosis. Patients with mutated IgVH genes fare better than those with unmutated genes. Gene expression profiling studies identified the tyrosine kinase ZAP‐70 to be expressed in unmutated CLL samples. Flow cytometric examination of ZAP‐70 expression in tumor cells has been proposed to be a convenient surrogate marker for IgVH mutational status. However, a few studies have shown a small number of discordant results between ZAP‐70 positivity, IgVH mutational status, and clinical outcome. There have been no reported studies comparing bone marrow samples with peripheral blood for ZAP‐70 expression in CLL patients.

Methods:

We searched our flow cytometry files from October 2004 through April 2006 and identified CLL in 311 bone marrow and peripheral blood specimens from 256 patients. We defined ZAP‐70 positivity as greater than 30% of the CD19+ B‐cells above the isotype control value that coexpress ZAP‐70. Statistical analyses were performed using the Fisher exact test and student t‐test.

Results:

A significantly greater number of bone marrow specimens were positive for ZAP‐70 when compared with the number of peripheral blood specimens. Of all the ZAP‐70 negative specimens, CLL cells from bone marrow had a greater mean percentage of ZAP‐70 positive cells when compared with the CLL cells from peripheral blood. Finally, six patients were identified who were ZAP‐70 positive in the bone marrow but ZAP‐70 negative in the peripheral blood.

Conclusions:

These results may be due to either an increase in the false positive rate in bone marrow specimens or to an intrinsic feature of CLL cells in the compartment that is biologically distinct from peripheral tumor cells. As prognosis and treatment decisions may be based on ZAP‐70 results from either specimen type, it is prudent to further examine this observation. © 2006 International Society for Analytical Cytology
ZAP‐70 expression is low in normal precursor B cells or hematogones
Authors: Davis Bruce H. , Schwartz Michael
Published: August 2006

Background:

Zeta‐associated protein (ZAP‐70) expression has been associated with a less favorable prognosis in chronic lymphocytic leukemia (CLL). The role of ZAP‐70 in immature B‐cells is not well understood. Immature or precursor B lymphocytes (hematogones) often occur in clinical samples and coexpress CD10, CD38, and CD19 lacking surface immunoglobulin expression. The present study was carried out in an attempt to further elucidate the role of ZAP‐70 in the spectrum of B‐cells seen in clinical specimens.

Methods:

ZAP‐70 expression was evaluated on 25 patient samples that expressed greater than 2% of CD10+/CD38bright/CD19+ coexpression during routine evaluation. In our sample set, the hematogone expression ranged from 2 to 18% of total leukocytes and occurred in a variety of conditions, including CLL, NHL, AML, MDS, Hodgkins Disease, and Multiple Myeloma. The method of ZAP‐70 detection was that routinely applied to our clinical testing of CLL samples supplemented with the determination of ZAP‐70 levels in the CD38bright/CD19+ coexpressing cells.

Results:

In all cases ZAP‐70 was not expressed on the CD5 negative, CD38/CD19 coexpressing precusor B cells. In all cases hematogones were found to not express significant levels of ZAP‐70.

Conclusion:

The presence of hematogones in clinical samples should be recognized so as to not adversely influence prognostic studies of ZAP‐70 or CD38 in CLL. © 2006 International Society for Analytical Cytology
Variations in the detection of ZAP‐70 in chronic lymphocytic leukemia: Comparison with IgVH mutation analysis
Authors: Sheikholeslami M. R. , Jilani I. , Keating M. , Uyeji J. , Chen K. , Kantarjian H. , O'Brien S. , Giles F. , Albitar M.
Published: August 2006

Lack of immunoglobulin heavy chain genes (IgVH) mutation in patients with chronic lymphocytic leukemia (CLL) is associated with rapid disease progression and shorter survival. The zeta‐chain (T‐cell receptor) associated protein kinase 70 kDa (ZAP‐70) has been reported to be a surrogate marker for IgVH mutation status, and its expression in leukemic cells correlates with unmutated IgVH. However, ZAP‐70 detection by flow cytometry varies significantly dependant on the antibodies used, the method of performing the assay, and the condition of the cells in the specimen. The clinical value of ZAP‐70 testing when samples are shipped under poorly controlled conditions is not known. Furthermore, testing in a research environment may differ from testing in a routine clinical laboratory. We validated an assay for ZAP‐70 by comparing results with clinical outcome and the mutation status of the IgVH. Using stored samples, we show significant correlation between ZAP‐70 expression and clinical outcome as well as IgVH mutation at a cut‐off point of 15%. While positive samples (>15% positivity) remain positive when kept in the laboratory environment for 48 h after initial testing, results obtained from samples from CLL patients tested after shipping at room temperature for routine testing showed no correlation with IgVH mutation status when 15% cut‐off was used. In these samples, cut‐point of 10% correlated with the IgVH mutation (P = 0.0001). This data suggests that although ZAP‐70 positivity correlates with IgVH mutation status and survival, variations in sample handling and preparation may influence results. We show that IgVH mutation results, unlike ZAP‐70 remain correlated with CD38 expression and β‐2 microglobulin in shipped samples, and ZAP‐70 testing should not be used as the sole criterion for stratifying patients for therapy. © 2006 International Society for Analytical Cytology
A standardized ZAP‐70 assay—Lessons learned in the trenches
Authors: Shults Keith E. , Miller David T. , Davis Bruce H. , Flye Leanne , Hobbs Leigh Ann , Stelzer Gregory T.
Published: August 2006

Background:

The disease of chronic lymphocytic leukemia (CLL) has been shown to exhibit varying clinical outcomes based on reported laboratory parameters. One of these parameters involves the measurement of the protein levels of zeta‐associated protein (ZAP‐70) in CLL cells. A standardized assay has not yet reached consensus in the clinical cytometry community.

Methods:

We developed a system using the 8‐peak Rainbow beads as our fluorescence calibrator along with a fixed cell control. Using a panel of CD19‐PE, CD5‐FITC, and ZAP‐70‐Alexa 647, we stained normal whole blood, and blood and bone marrow from patients with CLL to determine the level of ZAP‐70 expression in T‐cell, B‐cell, and CLL‐cell populations. ZAP‐70 expression was reported in molecules equivalent fluorescence (MEFL) based on the calibration of the flow cytometer with the 8‐peak Rainbow beads.

Results:

Daily assay performance as well as operating MEFL defined ranges for ZAP‐70 detection in CLL were developed. A rank‐order, nonparametric approach to reference ranges was used to assign a cutoff for “negative” as well as ranges for “intermediate” and “positive” staining using T and B cells from a pool of 50 normal subjects, and CLL cells from 395 patients. The assay was validated in a multi‐institutional study and has demonstrated correlation with published techniques. Since its initial development, the assay has been implemented at two additional laboratory sites and has been shown to produce reproducible, correlated data at all sites.

Conclusions:

Strict adherence to standardization can yield an assay that is predictable, reliable, and reproducible as well as capable of multisite implementation. The Rainbow beads provide a common platform for system calibration. The fixed cell culture controls provide a common target to test antibody. The final level of control tests the sensitivity of ZAP‐70 detection in a normal peripheral blood sample stained along with the submitted CLL patients. The acceptance/rejection of test results must meet all three levels of control before patient results are reported. © 2006 International Society for Analytical Cytology
Induction of IgE and allergic‐type responses in fur mite‐infested mice
Authors: Pochanke Veronika , Hatak Sarah , Hengartner Hans , Zinkernagel Rolf M. , McCoy Kathy D.
Published: August 2006

High serum IgE levels are characteristic of allergic diseases and immune responses to nematode parasites. A murine allergy model based on infestation with the fur mites Myocoptes musculinus and Myobia musculi was investigated. Analysis of mite infestation in various knockout mice revealed that IgE production in response to these ectoparasites was dependent on T cells, IL‐4, and CD40L. Secretion of IL‐4 by CD4+ T cells obtained from peripheral LN draining mite‐infested skin sites was increased with progressing mite infestation and correlated with the serum IgE induction. A time course analysis of the mRNA expression of switched IgE, activation‐induced cytidine deaminase (AID), and ϵ germ‐line transcripts (ϵGLT) suggested that switching to IgE in response to fur mites occurred initially in skin‐draining LN. In addition, mite infestation induced mast cell degranulation in the skin as well as mast cell infiltration into skin‐draining LN. Analysis of the immune response generated in mite‐infested mice is a valuable model for the investigation of allergic disorders and provides information for better understanding of mechanisms involved in IgE induction and regulation in a physiological way of allergen‐exposure resembling atopic sensitization in humans.
Binding Constant of VIVO to Transferrin
Authors: Kiss Tamás , Jakusch Tamás , Bouhsina Saâd , Sakurai Hiromu , Enyedy Éva Anna
Published: August 2006

The interactions of bis‐VIVO‐1,2‐dimethyl‐3‐hydroxy‐4(1H)‐pyridinone (DHP) with apotransferrin (apoTF) were followed by means of electron paramagnetic resonance spectroscopy (EPR) at room temperature and at liquid nitrogen temperature. Partial ligand displacement between DHP and apoTF was observed, and the reaction was used to determine the binding constant of VIVO to apoTF. A value of log K = 14.3 ± 0.6 was obtained for the binding of the first VIVO to apoTF. In order to confirm the validity of the binding constant, UV spectroscopy was used to monitor the displacement reaction between VIVO–apoTF and nitrilotriacetic acid (NTA). The difference between the binding constants obtained by the two different methods (ca. one log unit) was explained in terms of the possible ternary complex formation between VIVO–apoTF and the displacing ligand. The binding constants obtained exhibit a reasonably good agreement with the linear free energy relationship (LFER) estimation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Twisted Intercalating Nucleic Acids – Intercalator Influence on Parallel Triplex Stabilities
Authors: Filichev Vyacheslav V. , Gaber Hatem , Olsen Thomas R. , Jørgensen Per T. , Jessen Carsten H. , Pedersen Erik B.
Published: August 2006

Phosphoramidites of several new twisted intercalating nucleic acid (TINA) monomers and the previously discovered (R)‐1‐O‐[4‐(1‐pyrenylethynyl)phenylmethyl]glycerol (1) were synthesized and used in DNA synthesis. Stabilization of Hoogsteen‐type triplexes was observed in cases of insertion of the novel (R)‐1‐O‐[3‐(naphthalen‐1‐ylethynyl)phenylmethyl]glycerol (2) as a bulge into homopyrimidine oligodeoxynucleotides (ONs), whereas phenylethynyl and 4‐(biphenylylethynyl) derivatives of TINAs resulted in destabilization of parallel triplexes relative to the wild‐type triplex. It was concluded that TINA monomers should possess at least two fused phenyl rings attached through the triple bond at the 4‐position of bulged (R)‐1‐O‐(phenylmethyl)glycerol in homopyrimidine ONs in order to stabilize parallel triplexes. Slight destabilization of DNA/DNA Watson–Crick type duplexes (ΔTm = 1.0–4.5 °C) was detected for 2 inserted as a bulge, while RNA/DNA duplexes and duplexes with other TINA analogues were considerably destabilized (ΔTm > 6.0 °C). In cases of double insertion of 1 opposite to base inversions in dsDNA, the thermal stabilities of the triplexes were higher than that of the wild‐type triplex, which is a new solution to overcome the problem of targeting homopurine stretches with single base pair inversions. A DNA three‐way junction was considerably stabilized (ΔTm in a range of 10.0–15.5 °C) upon insertion of TINA monomers in the junction point as a bulge. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Formation of 4H‐Azepine by the Electrophilic Reaction of a 2‐Methoxyazepinium Ion and Analysis of the Sigmatropic Isomerization
Authors: Cordonier Christopher E. J. , Satake Kyosuke , Okamoto Hideki , Kimura Masaru
Published: August 2006

2‐Aryl‐2H‐, 3‐aryl‐3H‐, and 4‐aryl‐4H‐azepine were formed by the novel, electrophilic, πLUMO‐controlled reaction of the 2‐methoxyazepinium ion, generated in situ by the reaction of TiCl4 with 2,7‐dialkoxy‐2H‐azepine and an aryl compound, for which the kinetic parameters of the sigmatropic hydrogen rearrangement of the 4H‐azepine was measured. The substitution and hydrogen shift of the azepinium ion were analyzed with DFT studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Direct, Mild, and Selective Synthesis of Unprotected Dialdo‐Glycosides
Authors: Angelin Marcus , Hermansson Magnus , Dong Hai , Ramström Olof
Published: August 2006

A direct and highly convenient organocatalytic method for the preparation of 1,5‐dialdo‐pyranosides and 1,4‐dialdo‐furanosides is presented. The method relies on the chemoselective properties of TEMPO in combination with trichloroisocyanuric acid under very mild, basic conditions. Unprotected glycosides are prepared in a single step in high yields and are efficiently purified with the use of solid‐phase imine capture. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Stereoselective Glycosylations Using (R)‐ or (S)‐(Ethoxycarbonyl)benzyl Chiral Auxiliaries at C‐2 of Glycopyranosyl Donors
Authors: Kim Jin‐Hwan , Yang Hai , Khot Vishal , Whitfield Dennis , Boons Geert‐Jan
Published: August 2006

The stereoselective introduction of a glycosidic bond presents the greatest challenge to complex oligosaccharide synthesis. Important developments such as automated polymer‐supported oligosaccharide synthesis will not realize their full potential until this problem is addressed. In this paper, a novel approach for stereoselective glycosylations is described whereby a chiral auxiliary at C‐2 of a glycosyl donor controls the anomeric outcome of a glycosylation. It was found that participation of an (S)‐ethoxycarbonylbenzyl auxiliary led to the formation of 1,2‐cis glycosides, probably through a trans‐fused dioxolenium ion intermediate. On the other hand, the use of an auxiliary with (R) configuration gave 1,2‐trans glycosides, and this glycosylation proceeds through a cis‐fused dioxolenium ion intermediate. The auxiliary could conveniently be removed by Birch reduction. Computational studies support the formation of the proposed ethoxy‐carbonium ion intermediate with all pseudo‐equatorial substituents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Photochemical Reactions of 1,3,3‐Trimethylbicyclo[2.2.2]octa‐5,7‐dien‐2‐ones
Authors: Chang Shi‐Yi , Huang Shih‐Lin , Villarante Nelson R. , Liao Chun‐Chen
Published: August 2006

The photochemistry of 1,3,3‐trimethylbicyclo[2.2.2]octa‐5,7‐dien‐2‐ones 1a–f containing multiple chromophoric moieties under various conditions is described. Upon direct irradiation, dienones 1a–f in benzene, acetonitrile, and methanol were found to aromatize through photoelimination of dimethylketene, which was trapped with 3‐phenylprop‐2‐en‐1‐ol (12). Triplet sensitization of dienone 1a in acetone and in acetone/acetophenone mixed solvents afforded aromatic compound 2a, whilst bicyclic systems 1b–c were found to be unreactive on sensitization. In the cases of dienones 1d–f in acetone, aromatic compounds 2d–f and di‐π‐methane (DPM) photoproducts 3d–f and 4f were observed, but in the acetone/acetophenone mixed solvent system only DPM photoproducts were detected. Plausible mechanisms for these photochemical reactions are described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
The Implication of Electrocatalysis in MCR Strategy: Electrocatalytic Multicomponent Transformation of Cyclic 1,3‐Diketones, Aldehydes and Malononitrile into Substituted 5,6,7,8‐Tetrahydro‐4H‐Chromenes
Authors: Elinson Michail N. , Dorofeev Alexander S. , Feducovich Sergey K. , Gorbunov Sergey V. , Nasybullin Ruslan F. , Miloserdov Fedor M. , Nikishin Gennady I.
Published: August 2006

The electrochemically induced catalytic multicomponent transformation of cyclic 1,3‐diketones, aldehydes and malononitrile in alcoholic solvents results in the formation of substituted 5,6,7,8‐tetrahydro‐4H‐chromenes in 85–95 % yields. The reaction is performed in an undivided cell in the presence of sodium bromide as an electrolyte. The application of this efficient electrocatalytic method to the formation of tetrahydro‐4H‐chromenes is beneficial for diversity‐oriented large‐scale processes. The novel concept of an electrocatalytic multicomponent reaction is also ecologically sound. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Anorexia nervosa: an evolutionary puzzle
Authors: Gatward Nicholas
Published: August 2006

Anorexia nervosa (AN) has proven difficult to explain and is especially so from an evolutionary perspective. It is widespread, has probably existed for centuries and includes a genetic component but leads to starvation, infertility and sometimes death. An attempt to explain AN will be made using a synthesis of evolutionary ideas about responses to threat. Dietary restriction is described as a response to perceived threats of exclusion from the group, which would once have been dangerous. This can develop into AN only where the weight loss sets off an ancient adaptive response to the threat of famine. Eating again and weight gain would mean re‐entering the competition for status and belonging and are therefore felt as threatening. This synthesis can explain the unusual mix of features found in AN that are otherwise resistant to explanation. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.
Evolution of self‐concept deficits in patients with eating disorders: the role of family concern about weight and appearance
Authors: Senra Carmen , Sánchez‐Cao Elizabeth , Seoane Gloria , Leung Freedom Y. K.
Published: August 2006

Objective

The aims of this study were to analyse the influence of family concern about appearance on self‐concept deficits in patients under treatment for eating disorders, and to identify predictors of eating attitudes and behaviours in control and clinical groups.

Method

The participants were 123 women with diagnoses of DSM‐IV‐TR eating disorders and 124 female university students. All completed the eating attitudes test (EAT‐40), the body dissatisfaction of the eating disorders inventory (EDI‐BD), the Rosenberg self‐esteem (RSE), the fear of negative evaluation (FNE) and the family concern about appearance scale (FCAS). Patients were administered with these instruments at admission and after 6 and 12 months of treatment.

Results

ANOVAs indicated that family concern about appearance had no influence on the evolution of self‐concept deficits during treatment. Multiple regression analyses showed that the best predictor of eating attitudes in controls was FCAS score, while among patients the best predictor of how the disorder will evolve after 12 months of treatment was EAT‐40 at admission.

Conclusion

Families may transmit eating concerns, but this is not enough for the emergence of an eating disorder. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.
How important are motivation and initial Body Mass Index for outcome in day therapy services for eating disorders?
Authors: Jones Alysun , Bamford Bryony , Ford Haelli , Schreiber‐Kounine Christa
Published: August 2006

This study was designed to investigate the impact of initial Body Mass Index (BMI) and motivation for recovery on a 12‐week day therapy programme for Eating Disorders. Outcome was assessed by changes in eating disorder symptomology, mood and self‐esteem. A battery of assessment questionnaires was given to 34 eating disorder clients on admission to and completion of the programme. This study found that BMI at admission did not affect treatment outcome directly. Only patient self‐rated motivation directly affected treatment outcome with more highly motivated clients making more significant changes to their eating disorder symptomology across the programme. However, motivation, BMI and duration of illness influenced how likely a patient was to complete the 12 weeks and completion of the programme had a direct effect on eating disorder symptomology, mood and self‐esteem. BMI and motivation can therefore be seen to indirectly effect the outcome of treatment via the ability to complete the programme. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.
Cognitive predictors of functional decline in vascular dementia
Authors: Jefferson Angela L. , Cahn‐Weiner Deborah , Boyle Patricia , Paul Robert H. , Moser David J. , Gordon Norman , Cohen Ronald A.
Published: August 2006

Background

This study examined changes in cognitive‐functional relationships in vascular dementia (VaD) over the course of one year.

Methods

Twenty‐four patients with probable VaD were administered the Dementia Rating Scale (DRS). Caregivers completed an informant‐based measure of instrumental (IADL) and basic activities of daily living (BADL). Follow‐up assessment was conducted one‐year post‐baseline.

Results

Logistic regression revealed that changes in the DRS Initiation/Perseveration and DRS Memory subscales were significantly associated with declines in IADLs and BADLs, respectively.

Conclusions

Among patients with VaD, longitudinal changes in IADLs and BADLs are most strongly associated with changes in executive functioning and memory abilities, respectively. Findings suggest that different cognitive functions subserve complex instrumental and rote, habituated basic functional activities, and neuropsychological screening measures are useful in the prediction of such functional changes. Copyright © 2006 John Wiley & Sons, Ltd.
Psychological processes underlying delusional thinking in late‐onset psychosis: a preliminary investigation
Authors: McCulloch Yvonne , Clare Linda , Howard Rob , Peters Emmanuelle
Published: August 2006

Background and aims

It has been suggested that delusions may serve as a defence against negative self‐representations. The present study investigated general psychological well‐being and evidence for defensive emotional processes among people with late‐onset psychosis.

Method

The performance and responses of older people with late‐onset psychosis (n = 13), older people with depression (n = 15), and age‐matched healthy controls (n = 15) were compared in a cross‐sectional design. Participants rated their own levels of depression and self‐esteem, and completed an emotional Stroop task to establish whether there was evidence of implicit depression in the absence of explicit acknowledgement. Participants rated themselves on a number of personal attributes in relation to two life stages to generate discrepancies in ‘actual’, ‘ideal’ and ‘other’ self‐concepts, and completed measures of their perceptions of current and past psychological well‐being.

Results

People with late‐onset psychosis showed no evidence of overt depression or low‐self esteem. All three groups showed an attentional bias to depression‐related and age‐related words, although response times overall were faster for controls. The psychosis group showed no discrepancies between either their past or their current ‘actual’ and ‘other’ self‐concepts, suggesting that they do not have more negative views about how others see them.

Conclusions

Evidence from this study does not support the application of the ‘delusion‐as‐defence’ model to late‐onset psychosis, but methodological constraints must be borne in mind when interpreting the findings. Copyright © 2006 John Wiley & Sons, Ltd.