bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pathomorphology of Daunorubicin-injured and ICRF-159 (Razoxane)-protected Murine Myocardium: Progress Report
Authors: Fischer Vernon W. , Larose Lori S. , Wang Geng M.
Published: November 2007

This study was designed to establish the feasibility of the mouse as a model for the investigations of (1) the cardiac myopathy associated with daunorubicin (DNR) administration and (2) the mitigation of this disorder by pretreatment with razoxane (RZ). BDF1 mice were divided into three groups: 12 mice were injected at 6-weekly intervals with DNR; a second group of 12 mice received the same regimen but, in addition, were pretreated each time with RZ; a third group was injected with the carrier only. Ten/twelve mice injected with DNR died within the length of the experiment (6 weeks), while 9/12 of the pretreated animals survived that time span. Four of the DNR-exposed group were sacrificed prior to death to permit ultrastructural examination. All 9 surviving RZ-pretreated mice were processed for electron microscopy. Myocardial tissue was also examined light microscopically and histochemically. The ultrastructure of the DNR-treated myocardium showed a number of focally distributed abnormalities, including changes in nuclear topography, early alterations demarcated by lysosomal aggregations, and dilatations of the sarcoplasmic reticulum, and more severe lesions consisting of large, coalesced vacuolar spaces within the cardiomyocytic cytoplasm and extensive distortion of the myofibrillar architecture. The heart protected by RZ, in general, only showed either minimal or mild changes. In a few animals, the protection did not appear to be as effective as in the majority of the pretreated mice. However, extensive structural alterations were never seen in the RZ-protected myocardium. These results confirm our previous preliminary findings that a DNR-associated cardiomyopathy is inducible in mice and that pretreatment with RZ may mitigate the structural alterations in this disorder.
The Effect of RNA Inactivator(s) Synthesized from Cu2+ and Hydroquinone on Monoribonucleotides
Authors: Masoud Asaad N. , Al-Moslih Moslih I. , Dubes George R.
Published: November 2007

Preparations containing RNA inactivator(s) synthesized from Cu2+ and hydroquinone were tested for their effect on monoribonucleotides. The preparations caused the disappearance of large fractions of all of the monoribonucleotides tested, which were the 3′-ribonucleotides and the 5-ribonucleotides of adenine, cytosine, guanine, and uracil, and an impurity identified as the 2′-ribonucleotide of uracil. Control preparations with Cu2+ but without hydroquinone had no effect on the ribonucleotides. Control preparations with hydroquinone but without deliberately added Cu2+ caused the disappearance of relatively small fractions of the ribonucleotides tested. The activity of these control preparations is probably attributable, at least in part, to trace copper impurity or contamination. The addition of L-histidine protected the ribonucleotides against the effect of the RNA inactivator preparations from Cu2+ and hydroquinone, just as the L-histidine protects naked viral RNA against the RNA inactivator(s). The hypothesis that the ribonucleotide moieties of the viral RNA are the targets of the RNA inactivator(s) is discussed.
The Effect of RNA Inactivator(s) Synthesized from Cu2+ and Hydroquinone on Adenine, Cytosine, Guanine, and Uracil
Authors: Masoud Asaad N. , Al-Moslih Moslih I. , Dubes George R.
Published: November 2007

The RNA inactivator(s) synthesized from Cu2+ and hydroquinone reacts with ail four free bases: adenine, cytosine, guanine, and uracil. After 1 day at 23°C, losses of these bases averaged 66%, 39%, 97%, and 25%, respectively. In the controls with neither Cu2+ nor hydroquinone and with either one without the other, there was no significant loss of any of the bases, except for the possibly significant loss (14%) of adenine after incubation with Cu2+ without hydroquinone. L-Histidine, a chelator of Cu2+, protected all four bases against the inactivation. The hypothesis that the chemical target(s) for the inactivator(s) in monoribonucleotides and in the naked viral RNA genome is the base moiety(ies) is discussed.
Target Organ Specificity: Diethylnitrosamine-and Dibenzylnitrosamine-induced Single-strand Breaks Plus Alkali-labile Bonds
Authors: Brash Douglas E. , Su Cheng M. , Nabi Hani A. , Reuter Kathleen S. , Ortman Judith , Sheikh Yunis , Hart Ronald W.
Published: November 2007

Quantitative dose response measurements of diethylnitrosamine-and dibenzylnitrosamine-induced DNA single-strand breaks plus alkali-labile bonds (SSB + ALB) (single-strand breaks, apurinic/apyrimidinic sites, and phosphotriesters) were performed on samples of 100,000 nuclei from Sprague-Dawley rats. Twenty-four hours after diethylnitrosamine injection, there were no SSB + ALB in brain (nontarget), SSB + ALB in kidney (target), and SSB + ALB in liver (target only after partial hepatectomy, tumor promoters, or chronic administration). Seven days after diethylnitrosamine injection, liver SSB + ALB had declined. The noncarcinogenic diethylnitrosamine analog, dibenzylnitrosamine, induced no SSB + ALB at 6 hours or 7 days postinjection. Induction of DNA damage, therefore, correlates well with target organ specificity of tumorigenesis when specificity is broadened to include those organs that exhibit tumors only when DNA damage is followed by additional treatments.
Effect of frequency altered feedback and audience size on stuttering
Authors: ARMSON JOY , FOOTE SHEILA , WITT COLLEEN , KALINOWSKI JOSEPH , STUART ANDREW
Published: November 2007

Abstracts

The effect of frequency altered feedback (FAF) and audience size on stuttering frequency was examined. Nine adults who stutter orally read to audiences of two, four and 15 people under conditions of FAF (one‐half octave shift down) and non‐altered auditory feedback (NAF). There was no statistically significant effect of audience size on stuttering frequency (p>0.05). A statistically significant reduction in stuttering frequency was found under FAF relative to NAF (p<0.5). Collapsed across audience conditions, stuttering frequency was reduced by 74%. These findings suggest that FAF may be useful as a treatment tool.

L'on a examiné l'effet sur la fréquence de bégaiement, du feedback avec changement de fréquence fondamentale (FAF dans le texte en anglais), et due nombre des auditeurs. Neuf adultes bègues ont lu à voix haute à des groupes de respectivement deux, quatre et 15 auditeurs, soit avec un feedback FAF baissé d'un demi octave, soit avec un feedback auditif non modifié (NAF). Il n'y a eu aucun effet significatif du nombre des auditeurs sur la fréquence de bégaiement (p<0,05). L'on a remaré une réduction statistiquement significative de cette fréquence pendant le FAF, par rapport au NAF (p<0,5). Etalée à travers les diverses conditions de nombre d'auditeurs la fréquence de bégaiement était réduite de 74%. Ces données suggèrent que le FAF peut ětre utile en tant 'instrument de traitement.

Der Einfluβ auf das Stottern von frequenzveränderter Rückkopplung (frequency altered feedback: FAF) und Gröβe der Zuhörergruppe wurde untersucht. Neun erwachsene Stotterer fasen vor Gruppen von 2, 4 und 15 Zuhören under FAF‐Bedingungen (Frequenzsenkung von 6,5 Oktave) und nichveränderten Bedingungen (NAF) vor. Der Effekt der Zuhörergruppe war nicht signifikant (p>0,05). Unter FAF‐Bedingungen wurde eine signifikant Reduktion des Stotterns (p>0,05) gefunden. Die verschiedenen Zuhörerbedingungen zusammengenommen reduzierte sich das Stottern um 74%. Dieses Ergebnis weist auf das Potential der FAF als Behandlungsmethode hin.
Governance of supplier-customer relations: An empirical review
Authors: Sande Jon Bingen
Published: November 2007

The forest industry is riddled with exchange relationships. The parties to exchanges may have diverging goals and interests, but still depend upon each other due to non-redeployable specific assets. Formal and relational contracts may be used to deal with the resulting cooperation problems. This paper proposes a framework based on transaction cost economics and relational exchange theory, and examines to what extent empirical research has found formal and relational contracts to deal with three different governance problems. To that end, I review the results from 32 studies in a range of settings. These studies generally support the view that exchanges characterized by high degrees of specific assets should be supported by formal and relational contracts.
The Visceral City and the Theatre of Fear
Authors: Sundaram Ravi
Published: November 2007

Over the last decade in India, intensive urbanisation, with the aid of the mass media, has unleashed a new culture of fear. Widespread access to TV, text messaging and the Internet have heightened and played upon individuals' anxieties. Ravi Sundaram describes how in Delhi, in particular, the media provided the catalyst for ‘mass hysteria’ and ‘psychosis’ during the summer of 2002. Copyright © 2007 John Wiley & Sons, Ltd.
Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment
Authors: Teng Y. K. Onno , Levarht E. W. Nivine , Hashemi Mojtaba , Bajema Ingeborg M. , Toes René E. M. , Huizinga Tom W. J. , van Laar Jacob M.
Published: November 2007

Objective

Anti‐CD20–mediated B cell depletion with rituximab is a new and effective therapy for rheumatoid arthritis (RA). Although B cells in peripheral blood (PB) are consistently depleted in all patients, the clinical effects are more heterogeneous, possibly related to differences in the depleting effects of lymphoid or solid tissues. The aim of this study was to investigate B cell depletion in different compartments (PB, bone marrow, and synovium) and determine predictive variables for responsiveness to rituximab therapy.

Methods

Before and 12 weeks after rituximab treatment, samples of PB, bone marrow, and synovium were collected from 25 patients with RA refractory to disease‐modifying antirheumatic drugs and tumor necrosis factor–blocking agents. CD19+ and CD20+ B cells in PB and bone marrow were measured by flow cytometric analysis, whereas CD79a+ and cytoplasmic CD20+ B cells in the synovium were stained by immunohistochemistry. The effects of rituximab on serum Ig and autoantibodies were measured by enzyme‐linked immunosorbent assay.

Results

Rituximab effectively depleted the CD20+ subset of B cells in the PB, bone marrow, and synovium of RA patients. Rituximab significantly reduced autoantibody production (anti–citrullinated protein antibodies [ACPAs] and rheumatoid factor [RF]), in part due to a nonspecific decrease in total Ig production. Importantly, positivity for circulating ACPA IgM, in combination with a high infiltration of CD79a+ B cells in the synovium, but not of CD138+ plasma cells, was a predictor of clinical outcome after rituximab treatment. ACPA IgM titers were independently associated with synovial infiltration of CD20−,CD79a+ B cells, but not with CD138+ plasma cells.

Conclusion

These data provide novel insights into the mechanisms of CD20‐mediated B cell depletion in the lymphoid and solid tissues of RA patients and suggest a pivotal role for ACPA IgM–producing plasmablasts in RA.
Retracted:The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: A randomized, multicenter, double‐blind, placebo‐controlled study with primary end points at two months after the end of a three‐month treatment period
Authors: Pavelka Karel , Trč Tomáš , Karpaš Karel , Vı´tek Petr , Sedláčková Marie , Vlasáková Věra , Böhmová Jana , Rovenský Jozef
Published: November 2007

Objective

To determine whether the efficacy of diacerein persists at 2 months after the end of a 3‐month treatment period, compared with placebo, in patients with painful knee osteoarthritis (OA).

Methods

After a 1‐week nonsteroidal antiinflammatory drug washout period, patients received either diacerein or placebo for 3 months, followed by an off‐treatment period of 3 months to determine the carryover effects of the drug. Although patients were followed up through month 6, the primary efficacy end point was the percent change from baseline in pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] A) at month 5 (i.e., 2 months after the end of treatment) compared with placebo. The co–primary efficacy end point was the percent change from baseline in the total WOMAC score, also at month 5 versus placebo.

Results

Two hundred three patients were screened, and 168 patients with painful knee OA were randomized. One hundred sixty‐five patients were analyzed in an intent‐to‐treat analysis. At month 5, diacerein showed statistically significant superiority versus placebo as assessed with both the WOMAC A (P< 0.0001) and the total WOMAC (P< 0.0001), demonstrating the carryover effect of the drug. This superiority was already evident from month 2 for pain (P= 0.001) and month 1 for total WOMAC (P= 0.0021). Diacerein was safe and well tolerated. No serious or previously undocumented adverse events were observed during the study.

Conclusion

This is the first published study of a symptomatic slow‐acting OA drug in which the time of assessment of the primary outcome end points was 2 months after the end of a 3‐month treatment period. The results show that diacerein is safe and effective for the treatment of knee OA and has a long carryover effect.
Identification of novel susceptibility genes in childhood‐onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform
Authors: Jacob Chaim O. , Reiff Andreas , Armstrong Don L. , Myones Barry L. , Silverman Earl , Klein‐Gitelman Marisa , McCurdy Deborah , Wagner‐Weiner Linda , Nocton James J. , Solomon Aaron , Zidovetzki Raphael
Published: November 2007

Objective

Childhood‐onset systemic lupus erythematosus (SLE) presents a unique subgroup of patients for genetic study. The present study was undertaken to identify susceptibility genes contributing to SLE, using a novel candidate gene pathway microarray platform to investigate gene expression in patients with childhood‐onset SLE and both of their parents.

Methods

Utilizing bioinformatic tools, a platform of 9,412 single‐nucleotide polymorphisms (SNPs) from 1,204 genes was designed and validated. Molecular inversion probes and high‐throughput SNP technologies were used for assay development. Seven hundred fifty three subjects, corresponding to 251 full trios of childhood‐onset SLE families, were genotyped and analyzed using transmission disequilibrium testing (TDT) and multitest corrections.

Results

Family‐based TDT showed a significant association of SLE with a N673S polymorphism in the P‐selectin gene (SELP) (P= 5.74 × 10−6) and a C203S polymorphism in the interleukin‐1 receptor–associated kinase 1 gene (IRAK1) (P= 9.58 × 10−6). These 2 SNPs had a false discovery rate for multitest correction of <0.05, and therefore a >95% probability of being considered as proven. Furthermore, 7 additional SNPs showed q values of <0.5, suggesting association with SLE and providing a direction for followup studies. These additional genes notably included TNFRSF6 (Fas) and IRF5, supporting previous findings of their association with SLE pathogenesis.

Conclusion

SELP and IRAK1 were identified as novel SLE‐associated genes with a high degree of significance, suggesting new directions in understanding the pathogenesis of SLE. The overall design and results of this study demonstrate that the candidate gene pathway microarray platform used provides a novel and powerful approach that is generally applicable in identifying genetic foundations of complex diseases.
Hypoxia‐induced increase in the production of extracellular matrix proteins in systemic sclerosis
Authors: Distler Jörg H. W. , Jüngel Astrid , Pileckyte Margarita , Zwerina Jochen , Michel Beat A. , Gay Renate E. , Kowal‐Bielecka Otylia , Matucci‐Cerinic Marco , Schett Georg , Marti Hugo H. , Gay Steffen , Distler Oliver
Published: November 2007

Objective

Insufficient angiogenesis with tissue ischemia and accumulation of extracellular matrix are hallmarks of systemic sclerosis (SSc). Based on the severely decreased oxygen levels in the skin of patients with SSc, we aimed to investigate the role of hypoxia in the pathogenesis of SSc.

Methods

Subtractive hybridization was used to compare gene expression in dermal fibroblasts under hypoxic and normoxic conditions. Dermal fibroblasts were further characterized by exposure to different concentrations of oxygen and for different time periods as well as by interference with hypoxia‐inducible factor 1α (HIF‐1α). The systemic normobaric hypoxia model in mice was used for in vivo analyses.

Results

Several extracellular matrix proteins and genes involved in extracellular matrix turnover, such as thrombospondin 1, proα2(I) collagen, fibronectin 1, insulin‐like growth factor binding protein 3, and transforming growth factor β–induced protein, were induced by hypoxia in SSc and healthy dermal fibroblasts. The induction of these genes was time‐ and dose‐dependent. Experiments with HIF‐1α–knockout mouse embryonic fibroblasts, deferoxamine/cobalt ions as chemical stabilizers of HIF‐1α, and HIF‐1α small interfering RNA consistently showed that extracellular matrix genes are induced in dermal fibroblasts by HIF‐1α–dependent, as well as HIF‐1α–independent, mechanisms. Using the systemic normobaric hypoxia mouse model, we demonstrated that dermal hypoxia leads to the induction of the identified extracellular matrix genes in vivo after both short exposure and prolonged exposure to hypoxia.

Conclusion

These data show that hypoxia contributes directly to the progression of fibrosis in patients with SSc by increasing the release of major extracellular matrix proteins. Targeting of hypoxia pathways might therefore be of therapeutic value in patients with SSc.
Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts
Authors: Seki Masako , Sakata Ken‐Mei , Oomizu Souichi , Arikawa Tomohiro , Sakata Atsuko , Ueno Masaki , Nobumoto Atsuya , Niki Toshiro , Saita Naoki , Ito Kanako , Dai Shu‐Yan , Katoh Shigeki , Nishi Nozomu , Tsukano Michishi , Ishikawa Kouichiro , Yamauchi Akira , Kuchroo Vijay , Hirashima Mitsuomi
Published: November 2007

Objective

To compare the expression of galectin 9 (Gal‐9) in synovial tissue (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and to evaluate the effects of Gal‐9 on fibroblast‐like synoviocytes (FLS) in these patients.

Methods

The expression of Gal‐9 in ST and FLS was compared using immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub‐G1 method in vitro. The in vivo suppressive effects of Gal‐9 on collagen‐induced arthritis (CIA) in a mouse model were also elucidated.

Results

The percentage of Gal‐9–positive cells in ST samples and the amount of Gal‐9 in synovial fluid samples were significantly higher in patients with RA than in patients with OA, suggesting the involvement of Gal‐9 in the development of RA. Compared with the 2 wild‐type Gal‐9 forms, stable Gal‐9, a mutant protein resistant to proteolysis, significantly induced apoptosis of FLS from RA patients. In contrast, other galectins, such as Gal‐1, Gal‐3, and Gal‐8, did not induce apoptosis or suppress the proliferation of human RA FLS. Stable Gal‐9 preferentially induced apoptosis and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA, apoptotic cells were detected in the joints of stable Gal‐9–treated mice, but not phosphate buffered saline–treated mice, and suppressed CIA characterized by pannus formation with inflammatory cell infiltration and bone/cartilage destruction.

Conclusion

Gal‐9–induced apoptosis of hyperproliferative RA FLS may play a critical role in the suppression of RA.
Influence of −308 A/G polymorphism in the tumor necrosis factor α gene on etanercept treatment in rheumatoid arthritis
Authors: Guis Sandrine , Balandraud Nathalie , Bouvenot Julien , Auger Isabelle , Toussirot Eric , Wendling Daniel , Mattei Jean‐Pierre , Nogueira Leonor , Mugnier Benedicte , Legeron Pierre , Landt Olfert , Serre Guy , Roudier Jean , Roudier Chantal
Published: November 2007

Objective

To determine whether the −308 A/G tumor necrosis factor α (TNFα) gene polymorphism can predict the outcome of etanercept therapy in 86 patients with rheumatoid arthritis (RA), as already observed in patients treated with infliximab.

Methods

Eighty‐six RA patients treated with etanercept were genotyped for −308 A/G TNFα gene polymorphism by polymerase chain reaction and melting curve analysis, using specific gene primers and probes. Patients were subdivided into group A (G/A genotype) and group G (G/G genotype). We compared clinical responses to etanercept between groups A and G after 6 months, using the Disease Activity Score in 28 joints (DAS28). After 12‐month treatment, 48 of 86 patients were evaluated again.

Results

Of 86 patients, 18 (21%) belonged in group A and 68 (79%) belonged in group G. After 6‐month treatment, 55.6% of patients in group A and 82.4% of patients in group G had DAS28 improvement >1.2 (P = 0.027 by chi‐square). The mean ± SD DAS28 improvement was 1.69 ± 1.31 in group A and 2.23 ± 1.19 in group G (P = 0.098 by t‐test). After 1‐year treatment 48 patients were tested again: 10 (21%) belonged in group A and 38 (79%) belonged in group G. Forty percent of patients in group A and 87% in group G had DAS28 improvement >1.2 (P = 0.005 by chi‐square). The mean ± SD DAS28 improvement was 1.334 ± 1.37 in group A and 2.29 ± 1.47 in group G (Mann‐Whitney U test = 115, P = 0.0057).

Conclusion

RA patients with a −308 G/G TNFα genotype respond to etanercept better than patients with a −308 A/G genotype.
Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis
Authors: van der Heijde D. , Klareskog L. , Landewé R. , Bruyn G. A. W. , Cantagrel A. , Durez P. , Herrero‐Beaumont G. , Molad Y. , Codreanu C. , Valentini G. , Zahora R. , Pedersen R. , MacPeek D. , Wajdula J. , Fatenejad S.
Published: November 2007

Objective

The Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) is a 3‐year, double‐blind, multicenter study evaluating the efficacy and safety of etanercept, methotrexate, and the combination of etanercept plus methotrexate in patients with active rheumatoid arthritis (RA). The results after 1 and 2 years of the study have been previously reported. Here we provide the 3‐year clinical and radiographic outcomes and safety of etanercept, methotrexate, and the combination in patients with RA.

Methods

In this randomized, double‐blind, multicenter TEMPO study, 682 patients received etanercept 25 mg twice weekly, methotrexate ≤20 mg weekly, or the combination. Key efficacy assessments included the Disease Activity Score (DAS) and the DAS in 28 joints.

Results

Combination therapy resulted in significantly greater improvement in the DAS and in more patients with disease in remission than either monotherapy. This finding was confirmed by longitudinal analysis; patients receiving combination therapy were more than twice as likely to have disease in remission than those receiving either monotherapy. Independent predictors of remission included male sex, lower disease activity, lower level of joint destruction, and/or better physical function. Combination and etanercept therapy both resulted in significantly less radiographic progression than did methotrexate (P < 0.05). Etanercept and combination treatment were well tolerated, with no new safety findings.

Conclusion

Etanercept plus methotrexate showed sustained efficacy through 3 years and remained more effective than either monotherapy, even after adjustment for patient withdrawal. Combination therapy for 3 years led to disease remission and inhibition of radiographic progression, 2 key goals for treatment of patients with RA.
Impact of folic acid food fortification on the birth prevalence of lipomyelomeningocele in Canada
Authors: De Wals Philippe , Van Allen Margot I. , Lowry R. Brian , Evans Jane A. , Van den Hof Michiel C. , Crowley Marian , Tairou Fassiatou , Uh Soo‐Hong , Sibbald Barbara , Zimmer Pamela , Fernandez Bridget , Lee Nora S. , Niyonsenga Théophile
Published: November 2007

BACKGROUND: Recent studies reported no reduction in the frequency of lipomeningomyelocele (LMMC) in Hawaii and Nova Scotia after the implementation of a folic acid food fortification policy in 1998, while a marked reduction in the prevalence of other NTDs was observed. This study was performed to assess the prevalence of LMMC in Canada in relation to the timing of food fortification. METHODS: The study population included livebirths, stillbirths, and terminations of pregnancies because of fetal anomaly to women residing in seven Canadian provinces, from 1993 to 2002. In each province, the ascertainment of NTD cases relied on multiple sources, and in addition all medical charts were reviewed. The study period was divided into pre‐, partial, and full fortification periods, based on results of red cell folate tests published in the literature. RESULTS: A total of 86 LMMC cases were recorded among approximately 1.9 million live births. The average birth prevalence rate was 0.05/1,000, ranging from a minimum of 0.01/1,000 in 2002 to a maximum of 0.08/1,000 in 1999. There was statistical heterogeneity between years (p = .01), but no pattern compatible with a decrease following fortification. Comparing the full fortification period with the prefortification period, there was a slight but not statistically significant decrease in LMMC birth prevalence. CONCLUSIONS: LMMC seems to be pathogenically distinct from myelomeningocele and more studies are needed to understand the embryologic mechanisms leading to this condition, and the environmental and genetic factors involved in its etiology. Birth Defects Research (Part A), 2008. © 2007 Wiley‐Liss, Inc.
Visualization and interpretation of birth defects data using linked micromap plots
Authors: Gebreab Samson Y. , Gillies Robert R. , Munger Ronald G. , Symanzik Jürgen
Published: November 2007

BACKGROUND: Many states have implemented birth defects surveillance systems to monitor and disseminate information regarding birth defects. However, many of these states rely on tabular methods to disseminate statistical birth defects summaries. An innovative presentation technique for birth defect data that portrays the information in a joint geographical and statistical context is the linked micromap (LM) plot. METHODS: LM plots were generated for oral cleft data at two geographical resolutions—USA states and counties of Utah. The LM plots also included demographic and behavioral risk data. RESULTS: A LM plot for the USA reveals spatial patterns indicating higher oral cleft occurrence in the southwest and the midwest and lower occurrence in the east. The LM plot also indicates relationships between oral cleft occurrence and maternal smoking rates and the proportion of American Indians and Alaskan Natives. In particular, the five states with the highest oral cleft occurrence had a higher proportion of American Indians and Alaskan Natives. Among the 15 states with the highest oral cleft occurrence, nine had a smoking rate of 16% or higher while among the 15 states with the lowest oral cleft occurrence only one state had a smoking rate greater than 16%. The LM plot for the state of Utah shows no clear geographic pattern, due perhaps to a relatively small number of cases in a limited geographic area. CONCLUSIONS: LM plots are effective in representing complex and large volume birth defects data. Integration to birth defects surveillance systems will improve both presentation and interpretation. Birth Defects Research (Part A), 2008. © 2007 Wiley‐Liss, Inc.
Asymmetric Synthesis and Receptor Pharmacology of the Group II mGlu Receptor Ligand (1S,2R,3R,5R,6S)‐2‐Amino‐3‐hydroxy‐bicyclo[3.1.0]hexane‐2,6‐dicarboxylic Acid—HYDIA
Authors: Woltering Thomas J. , Adam Geo , Huguenin Philipp , Wichmann Jürgen , Kolczewski Sabine , Gatti Silvia , Bourson Anne , Kew James N. C. , Richards Grayson , Kemp John A. , Mutel Vincent , Knoflach Frédéric
Published: November 2007

The asymmetric synthesis and receptor pharmacology of (1S,2R,3R,5R,6S)‐2‐amino‐3‐Hydroxy‐bicyclo[3.1.0]hexane‐2,6‐dicarboxylic Acid (+)‐9(HYDIA) and a few of its O‐alkylated derivatives are described. The key step of the synthesis utilizes Sharpless’ asymmetric dihydroxylation (AD‐β) for the kinetic resolution of a bicyclic racemic precursor olefin. In contrast to the bicyclic glutamate analogue LY354740, which is a potent and selective agonist for the group II metabotropic glutamate receptors (mGluRs), these new conformationally restricted and also hydroxylated or alkoxylated glutamate analogues are potent and selective antagonists for the group II mGluRs.
Absolute lymphocyte count is a novel prognostic indicator in ALL and AML
Authors: De Angulo Guillermo , Yuen Carrie , Palla Shana L. , Anderson Peter M. , Zweidler‐McKay Patrick A.
Published: November 2007

BACKGROUND.

Leukemia is the leading cause of disease‐related death in children, despite significant improvement in survival and modern risk stratification. The prognostic significance of absolute lymphocyte counts (ALC) was evaluated in young patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL).

METHODS.

In all, 171 consecutive de novo cases of AML and ALL, age ≤21 years, were analyzed. Age, initial white blood cell count, cytogenetics, and bone marrow response were compared with lymphocyte, neutrophil, and platelet counts at weekly intervals during induction chemotherapy.

RESULTS.

ALC is a significant independent predictor of relapse and survival. For example, in patients with AML an ALC on Day 28 of induction (ALC‐28) <350 cells/μL predicts very poor survival, with a 5‐year relapse‐free survival (RFS) of only 10% (hazard ratio [HR] 3.7,P= .003). In contrast, an ALC‐15 >350 cells/μL carries an excellent prognosis, with a 5‐year overall survival (OS) of 85% (HR 0.2,P= .012). Similarly in ALL, an ALC‐15 <350 cells/μL predicts poor survival, with a 6‐year RFS of 43% (HR 4.5,P= .002), whereas an ALC‐15 >350 cells/μL predicts excellent outcome, with a 6‐year OS of 87% (HR 0.2,P= .018). Importantly, ALC remains a strong predictor in multivariate analysis with known prognostic factors.

CONCLUSIONS.

ALC is a simple, statistically powerful measurement for patients with de novo AML and ALL. The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies. These findings suggest a need for further exploration of postchemotherapy immune status and immune‐modulating cancer therapies. Cancer 2008. © 2007 American Cancer Society.
Static self‐gravitating elastic bodies in Einstein gravity
Authors: Andersson Lars , Beig Robert , Schmidt Bernd G.
Published: November 2007

We prove that given a stress‐free elastic body there exists, for sufficiently small values of the gravitational constant, a unique static solution of the Einstein equations coupled to the equations of relativistic elasticity. The solution constructed is a small deformation of the relaxed configuration. This result yields the first proof of existence of static solutions of the Einstein equations without symmetries. © 2007 Wiley Periodicals, Inc.
Supersonic flow onto a solid wedge
Authors: Elling Volker , Liu Tai‐Ping
Published: November 2007

We consider the problem of two‐dimensional supersonic flow onto a solid wedge, or equivalently in a concave corner formed by two solid walls. For mild corners, there are two possible steady state solutions, one with a strong and one with a weak shock emanating from the corner. The weak shock is observed in supersonic flights. A longstanding natural conjecture is that the strong shock is unstable in some sense.

We resolve this issue by showing that a sharp wedge will eventually produce weak shocks at the tip when accelerated to a supersonic speed. More precisely, we prove that for upstream state as initial data in the entire domain, the time‐dependent solution is self‐similar, with a weak shock at the tip of the wedge. We construct analytic solutions for self‐similar potential flow, both isothermal and isentropic with arbitrary γ ≥ 1.

In the process of constructing the self‐similar solution, we develop a large number of theoretical tools for these elliptic regions. These tools allow us to establish large‐data results rather than a small perturbation. We show that the wave pattern persists as long as the weak shock is supersonic‐supersonic; when this is no longer true, numerics show a physical change of behavior. In addition, we obtain rather detailed information about the elliptic region, including analyticity as well as bounds for velocity components and shock tangents. © 2007 Wiley Periodicals, Inc.
Autoreactive B cells get activated in extrafollicular sites
Authors: Weisel Florian , Wellmann Ute , Winkler Thomas H.
Published: November 2007

Autoreactive B cells are prevented from producing autoantibodies that may cause pathogenicity in autoimmune diseases by the induction of tolerance. When autoreactive B cells escape regulation in autoimmune‐prone individuals, large amounts of autoantibodies are produced with somatic mutations in their variable regions. In this issue of the European Journal of Immunology, a new and very useful model is presented that induces activation and hypermutation of autoreactive B cells upon injection of chromatin‐containing immune complexes. The differentiation and hypermutation of autoreactive B cells takes place at extrafollicular sites.

See accompanying article: http://dx.doi.org/10.1002/eji200737752
Monitoring of Photocatalytic Degradation of Selected Neonicotinoid Insecticides by Cathodic Voltammetry with a Bismuth Film Electrode
Authors: Guzsvány Valéria , Kádár Mihály , Papp Zsigmond , Bjelica Luka , Gaál Ferenc , Tóth Klára
Published: November 2007

An electroanalytical method has been developed for the determination of two water soluble pyridine based neonicotinoid insecticides (imidacloprid and acetamiprid) by differential pulse voltammetry with a bismuth film electrode in aqueous Britton–Robinson buffer solution as supporting electrolyte. The bismuth film electrode preparation was optimized for cathodic voltammetric application. The reduction peaks of the neonicotionids appeared at potentials more negative than −0.5 V (BiFE vs. Ag/AgCl/3.0 M KCl) and the signal characteristics depended on the pH of the supporting electrolyte. The best analysis conditions were found to be pH 8.0 for imidacloprid and pH 3.0 for acetamiprid at the following measurement parameters: pulse amplitude 50 mV, pulse width 50 ms and scan rate 25 mV. Calibration curves were linear in the concentration range of 2.43–51.1 μg/cm3 for imidacloprid and 2.95–47.3 μg/cm3 for acetamiprid, while the detection limits were 0.73 μg/cm3 and 0.88 μg/cm3 for imidacloprid and acetamiprid, respectively. The electroanalytical method has allowed monitoring the heterogeneous photocatalytic (O2/TiO2/UV) degradation of the two insecticides via their disappearance. The dynamics and the reaction rate determined on the basis of the electrochemical data were validated with HPLC/DAD and FTIR measurements.
Recent innovations in protein separation on microchips by electrophoretic methods
Authors: Peng Youyuan , Pallandre Antoine , Tran N. Thuy , Taverna Myriam
Published: November 2007

Microchips for analytical purposes have attracted great attention over the last 20 years. In the present review, we focus on the most recent development of microchips for electrophoretic separation of proteins. This review starts with a short recalling about the microchips covering the basic microchip layout for CE and the commercial chips and microchip platforms. A short paragraph is dedicated to the surface treatment of microchips, which is of paramount importance in protein analysis. One section is dedicated to on‐line sample pretreatment in microchips and summarizes different strategies to pre‐concentrate or to purify proteins from complex matrixes. Most of the common modes used for CE of proteins have already been adapted to the chip format, while multidimensional approaches are still in progress. The different routes to achieve detection in microchip are also presented with a special attention to derivatization or labeling of proteins. Finally, several recent applications are mentioned. They highlight the great potential of electrophoretic separations of proteins in numerous fields such as biological, pharmaceutical or agricultural and food analysis. A bibliography with 151 references is provided covering papers published from 2000 to the early 2007.
Developing evaluation capacity through process use
Authors: King Jean A.
Published: November 2007

Over time, intentional process use can have the practical effect of building the evaluation capacity of an organization. This chapter outlines possible steps that take purposeful advantage of the evaluation process.
The adoption of hospital information systems
Authors: McCullough Jeffrey S.
Published: November 2007

This paper empirically examines the diffusion of hospital information systems (ISs), specifically, pharmacy, laboratory, and radiology systems. Given the policy significance of health IS and the widespread perception that it's diffusion is slow, a better understanding of the mechanisms driving IS adoption is needed. A novel data set incorporating both IS adoption and hospital characteristics was constructed. These data follow the behavior of 1965 hospitals for the years 1990–2000. Hypotheses pertaining to hospital characteristics, hospital competition, and strategic behavior are tested utilizing proportional hazard models. I find that IS adoption is related to multi‐hospital system membership, payer mix, and hospital scale. The role of scale, however, significantly diminishes throughout the time period, likely reflecting improved personal computer performance and improved IT scalability. Conversely, I find little that strategic behavior or hospital competition affects IS adoption. Likewise, hospital ownership does not affect the adoption of these systems. Overall, these results suggest that hospital IS diffusion has not been normatively slow. Copyright © 2007 John Wiley & Sons, Ltd.
Landscape structure and use, climate, and water movement in the Mekong River basin
Authors: Costa‐Cabral Mariza C. , Richey Jeffrey E. , Goteti Gopi , Lettenmaier Dennis P. , Feldkötter Christoph , Snidvongs Anond
Published: November 2007

In this article the relative roles of precipitation and soil moisture in influencing runoff variability in the Mekong River basin are addressed. The factors controlling runoff generation are analysed in a calibrated macro‐scale hydrologic model, and it is demonstrated that, in addition to rainfall, simulated soil moisture plays a decisive role in establishing the timing and amount of generated runoff. Soil moisture is a variable with a long memory for antecedent hydrologic fluxes that is influenced by soil hydrologic parameters, topography, and land cover type. The influence of land cover on soil moisture implies significant hydrologic consequences for large‐scale deforestation and expansion of agricultural land. Copyright © 2007 John Wiley & Sons, Ltd.
SPR identification of mild elution conditions for affinity purification of E6 oncoprotein, using a multivariate experimental design
Authors: Sibler Annie‐Paule , Baltzinger Mireille , Choulier Laurence , Desplancq Dominique , Altschuh Danièle
Published: November 2007

The purification of “difficult” proteins for structural and functional studies remains a challenge. A widely used approach is their production as fusions with an affinity tag, so that a generic tag‐based purification protocol can be applied. Alternatively, immuno‐affinity using a protein‐specific antibody allows purification of unmodified proteins in a single step, if mild elution conditions can be identified for dissociating the complex without disrupting the folding of the protein. Here, we describe a quantitative structure activity relationship (QSAR) strategy to predict optimized elution conditions from a mathematical model that relates target/antibody dissociation to environmental changes. We illustrate the strategy with the E6 protein of the human papilloma virus (HPV) 16, a highly unstable protein central to HPV‐induced carcinogenesis. Surface plasmon resonance (SPR) was used to measure the kinetics of dissociation of an E6 peptide from an E6‐specific antibody in a set of multivariate conditions, where three environmental factors (pH, NaCl concentration, and temperature) were varied. The QSAR model indicated that dissociation is favored at pH < 5, which is detrimental to E6 folding, and also at pH ≥ 10 if the temperature is high. We verified that the conclusions of the QSAR study with the peptide were valid for the scFv1F4/E6 protein complex, and that the recovered protein was capable of mediating p53 degradation. Finally, we demonstrated that the optimized elution conditions (pH 10, 35°C) were adequate for purifying the recombinant E6 protein from crude cell extracts. Copyright © 2007 John Wiley & Sons, Ltd.
Diffusion imaging concepts for clinicians
Authors: Neil Jeffrey J.
Published: November 2007

This review covers the fundamentals of diffusion tensor imaging. It is written with the clinician in mind and assumes the reader has a passing familiarity with magnetic resonance imaging (MRI). Topics covered include comparison of diffusion MRI with conventional MRI, water apparent diffusion coefficient (ADC), diffusion anisotropy, tract tracing, and changes of water apparent diffusion in response to injury. The discussion centers primarily on applications to the central nervous system, but examples from other tissues are included. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Renal T2‐weighted turbo‐spin‐echo imaging with BLADE at 3.0 Tesla: Initial experience
Authors: Michaely Henrik J. , Kramer Harald , Weckbach Sabine , Dietrich Olaf , Reiser Maximilian F. , Schoenberg Stefan O.
Published: November 2007

Purpose

The purpose of this study is to evaluate the feasibility and image quality of multishot T2‐weighted (T2w) renal morphologic imaging based on the acquisition of rotating rectangular strips of k‐space data after successive radiofrequency excitations (BLADE technique).

Materials and Methods

A total of 7 healthy volunteers and 27 patients with suspected renal and renovascular diseases were included in this prospective intraindividual study. All exams were performed at 3.0T in a random order with a standard T2w turbo‐spin‐echo (TSE) sequence and with a T2w‐BLADE sequence with equal spatial resolution. Phantom measurements were performed to measure the objective signal‐to‐noise ratio (SNR). Two radiologists rated the image sharpness, the flow signal suppression, the presence of artifacts, and the overall image quality of both techniques and determined their preferred sequence.

Results

The SNR did not show significant differences. The overall image quality was rated significantly higher for the T2w‐BLADE (P < 0.05). Equally, the presence of disturbing artifacts and the sharpness was ranked significantly better for T2w‐BLADE than for the T2w‐TSE (P < 0.05). The T2w‐BLADE was the preferred sequence in 59% of all cases, the T2w‐TSE in 9%.T2w‐BLADE sequences seem to be superior for the depiction of the kidneys at 3.0T, particularly due to the decreased number of artifacts and sharper delineation of the organs. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
VGluT2 expression in painful Achilles and patellar tendinosis: Evidence of local glutamate release by tenocytes
Authors: Scott Alexander , Alfredson Håkan , Forsgren Sture
Published: November 2007

The pathogenesis of chronic tendinopathy is unclear. We have previously measured high intratendinous levels of glutamate in patients with tendinosis, suggesting potential roles of glutamate in the modulation of pain, vascular function, and degenerative changes including apoptosis of tenocytes. However, the origin of free glutamate found in tendon tissue is completely unknown. Surgical biopsies of pain‐free normal tendons and tendinosis tendons (Achilles and patellar) were examined immunohistochemically using antibodies against vesicular glutamate transporters (VGluT1 and VGluT2), as indirect markers of glutamate release. In situ hybridization for VGluT2 mRNA was also conducted. Specific immunoreactions for VGluT2, but not VGluT1, could be consistently detected in tenocytes. However, there were interindividual variations in the levels of immunoreactivity. The level of immunoreaction for VGluT2 was higher in tendinosis tendons compared to normal tendons (p < 0.05). In situ hybridization of VGluT2 demonstrated that mRNA was localized in a similar pattern as the protein, with marked expression by certain tenocytes, particularly those showing abnormal appearances. Reactivity for VGluT1 and ‐2 was absent from nerves and vessel structures in both normal and painful tendons. The current data demonstrate that tenocytes may be involved in the regulation of extracellular glutamate levels in tendons. Specifically, the observations suggest that free glutamate may be locally produced and released by tenocytes, rather than by peripheral neurons. Excessive free glutamate is expected to impact a variety of autocrine and paracrine functions important in the development of tendinosis, including tenocyte proliferation and apoptosis, extracellular matrix metabolism, nociception, and blood flow. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:685–692, 2008
Management of carcinoma of the gallbladder: A single‐institution experience in 16 years
Authors: Chan Siu Yin , Poon Ronnie T.P. , Lo Chung Mau , Ng Kelvin K. , Fan Sheung Tat
Published: November 2007

Background

Radical surgery is the only curative treatment for carcinoma of gallbladder. This study aimed to evaluate the outcome of patients with carcinoma of gallbladder managed in a single institution over 16 years.

Methods

From April 1988 to November 2003, 86 patients (29 males, 57 females) were diagnosed to have carcinoma of gallbladder. Tumor staging, treatment modalities and clinical outcome of these patients were evaluated. Thirty‐two patients (37%) had early stage (TNM stage I or II) disease whereas 54 patients (63%) had advanced stage (TNM stage III or IV) disease. Curative treatment by surgical resection was performed in 23 patients (27%).

Results

Overall survival was significantly better in patients with curative treatment (1‐year: 85%; 2‐year: 63%; 3‐year: 55%) than those with palliative treatment (1‐year: 11%; 2‐year: 3%; 3‐year: 0%; P < 0.01). Using Cox regression model, curative treatment was the only independent prognostic factor affecting overall survival of patients with carcinoma of gallbladder. A significantly better survival was associated with curative treatment compared with palliative treatment in patients with incidental gallbladder cancer. The median survival was 33.9 months for the curative treatment group versus 3 months for the palliative treatment group (P = 0.0001).

Conclusion

Favorable survival outcome can be achieved in patients with carcinoma of gallbladder after curative resection. J. Surg. Oncol. 2008;97:156–164. © 2007 Wiley‐Liss, Inc.