bluuebunny/crossref_metadata_2025 huggingface dataset:
Antirheumatic drug use and the risk of acute myocardial infarction
Authors: Suissa Samy , Bernatsky Sasha , Hudson Marie
Published: July 2006

Objective

To assess the risk of acute myocardial infarction (AMI) associated with the use of disease‐modifying antirheumatic drugs (DMARDs) and other medications commonly used in rheumatoid arthritis (RA).

Methods

We conducted a nested case‐control analysis within a cohort of subjects with RA, observed between 1999 and 2003, identified from the PharMetrics claims database. For each first AMI hospitalization identified during followup, 10 controls matched on sex, age, and time of study entry were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of AMI associated with the current use of anti‐RA therapy, as measured from dispensed prescriptions, after adjustment for AMI risk factors.

Results

The cohort included 107,908 subjects (average age 54 years at cohort entry). During followup, 558 AMI cases occurred (3.4 per 1,000 per year). AMI rate was significantly decreased with the current use of any DMARD (adjusted RR 0.80, 95% confidence interval [95% CI] 0.65–0.98). This effect was consistent across all DMARDs, including methotrexate (RR 0.81, 95% CI 0.60–1.08), leflunomide (RR 0.28, 95% CI 0.12–0.65), and other traditional DMARDs (RR 0.67, 95% CI 0.46–0.97), but not biologic agents (RR 1.30, 95% CI 0.92–1.83). AMI rate increased with the use of glucocorticoids (RR 1.32, 95% CI 1.02–1.72) but not with nonselective nonsteroidal antiinflammatory drugs (RR 1.05, 95% CI 0.81–1.36) or cyclooxygenase 2 (COX‐2) inhibitors (RR 1.11, 95% CI 0.87–1.43).

Conclusion

DMARD use is associated with a reduction in AMI risk in patients with RA. No risk increase was found with the COX‐2 inhibitors in this population.
Assessment of coxib utilization by rheumatologists for nonsteroidal antiinflammatory drug gastroprotection prior to the coxib market withdrawals
Authors: Greenberg Jeffrey D. , Bingham Clifton O. , Abramson Steven B. , Reed George , Kishimoto Mitsumasa , Hinkle Kim , Kremer Joel
Published: July 2006

Objective

To examine cyclooxygenase 2 inhibitor (coxib) utilization by rheumatologists for patients receiving nonsteroidal antiinflammatory drugs (NSAIDs) prior to the coxib market withdrawals.

Methods

A prospective study of patients with rheumatoid arthritis enrolled in the Consortium of Rheumatology Researchers of North America registry was performed.

Results

Of 1,833 patients receiving prescription NSAIDs, 1,380 (75.3%) received gastroprotection, defined as either coxib monotherapy and/or gastroprotective agent (GPA) cotherapy, and 1,207 (65.8%) received coxibs. The distribution of gastroprotective strategies included 860 (46.9%) patients who were prescribed coxib monotherapy, 347 (18.9%) prescribed dual coxib plus GPA cotherapy, 173 (9.4%) prescribed a nonselective NSAID (NS‐NSAID) plus GPA cotherapy, and 453 (24.7%) prescribed an NS‐NSAID without GPA cotherapy. For patients with 0, 1, and ≥2 identifiable gastrointestinal (GI) risk factors, coxib prescribing rates as a proportion of NSAID agents were 64.1%, 66.4%, and 68.6%, respectively; among dual aspirin/NSAID users, coxib prescribing rates were 66.2%, 78.3%, and 68.5% of NSAID prescriptions, respectively.

Conclusion

The majority of NSAID users were prescribed a gastroprotective strategy, primarily attributable to coxib utilization. Coxib utilization rates were consistently high across all levels of GI risk, including patients without identifiable risk factors. These data indicate that rheumatologists broadly adopted the coxib class of NSAIDs in a nonselective manner with respect to underlying GI risk and concomitant aspirin use. As novel therapeutic classes are introduced, early evaluation of prescribing patterns using arthritis registries can determine the appropriateness of prescribing patterns and may improve patient outcomes.
In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin‐induced adverse effects
Authors: Guis S. , Figarella‐branger D. , Mattei J. P. , Nicoli F. , Le Fur Y. , Kozak‐Ribbens G. , Pellissier J. F. , Cozzone P. J. , Amabile N. , Bendahan D.
Published: July 2006

Objective

Statins (3‐hydroxymethylglutaryl‐coenzyme A reductase inhibitor) are widely used to treat hypercholesterolemia. They are generally well tolerated, but myotoxic effects have been reported and the corresponding mechanisms are still a matter of debate. The aim of the present study was to determine whether impairment of calcium homeostasis and/or mitochondrial impairment could account for the adverse effects of statins in skeletal muscle.

Methods

Eleven patients with increased creatine kinase levels and myalgias after statin treatment were evaluated using in vitro contracture tests (IVCTs), histology, and 31P magnetic resonance spectroscopy (31P‐MRS).

Results

IVCT results were abnormal in 7 of the 9 patients, indicating an impaired calcium homeostasis. The 31P‐MRS investigation disclosed no anomaly at rest, and the aerobic function assessed during the postexercise recovery period was normal. On the contrary, the pH recovery kinetics was significantly slowed down as indicated by a reduced proton efflux, which could be ultimately linked to a failure of calcium homeostasis. Overall, our observations indicate a normal mitochondrial function and raise the possibility that statins may unmask a latent pathology involving an impairment of calcium homeostasis such as malignant hyperthermia (MH).

Conclusion

In case of susceptibility to MH, statins treatment must be administered with caution, and signs of adverse effects should be checked.
Development and validation of the Edmonton Ankylosing Spondylitis Metrology Index
Authors: Maksymowych Walter P. , Mallon Cathy , Richardson Rhonda , Conner‐Spady Barbara , JaureguI Edwin , Chung Cecilia , Zappala Lisa , Pile Kevin , Russell Anthony S.
Published: July 2006

Objective

Assessment of spinal and hip mobility has been recommended by the Assessments in Ankylosing Spondylitis (AS) Working Group for clinical trials and record keeping, although suggested measures primarily reflect structural damage. Our objective was to validate a simple, 4‐item composite measure of spinal and hip mobility, the Edmonton AS Metrology Index (EDASMI).

Methods

We assessed the EDASMI and the Bath AS Metrology Index (BASMI) using a total of 263 patients from 3 countries: Canada (n = 205), Australia (n = 29), and Colombia (n = 29). Intra‐ and interobserver reliability were assessed in a subset of 44 patients. Construct validity with respect to disease activity (Bath AS Disease Activity Index [BASDAI]), function (Bath AS Functional Index [BASFI]), and structural damage (modified Stoke AS Spinal Score [mSASSS]) was analyzed using correlation and hierarchical regression. Responsiveness was assessed in a subset of 33 patients who received either anti–tumor necrosis factor α therapy (n = 26) or pamidronate (n = 7) over 24 weeks.

Results

In contrast to the EDASMI, BASMI scores covered a limited range, with 70% of patients demonstrating a score ≤3 (range 0–10) and 4 of 5 individual measures demonstrating substantial floor effects. Both measures were highly reliable (intraclass correlation coefficient >0.90) and demonstrated similar construct validity (EDASMI correlated with disease duration [0.52], BASDAI [0.24], BASFI [0.61], Bath Ankylosing Spondylitis Radiology Index [0.79], mSASSS [0.75]; P < 0.001 for all). The change in EDASMI score was significant after 24 weeks of therapy (standardized response mean 0.40; P = 0.03), but change in the BASMI was not significant.

Conclusion

The EDASMI is a simple, rapid, and reliable tool for the assessment of spinal mobility in AS that is responsive to therapeutic intervention.
Evaluating quality of life in hip and knee replacement: Psychometric properties of the World Health Organization Quality of Life short version instrument
Authors: Ackerman Ilana N. , Graves Stephen E. , Bennell Kim L. , Osborne Richard H.
Published: July 2006

Objective

To evaluate the psychometric properties of the World Health Organization Quality of Life short version instrument (WHOQOL‐BREF), and to determine its responsiveness in assessing early outcome after total hip or knee replacement surgery.

Methods

At baseline (entry to an orthopedic waiting list), 279 participants completed the WHOQOL‐BREF instrument, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Assessment of Quality of Life (AQOL) instrument, Kessler Psychological Distress (K10) scale, and the modified Health Assessment Questionnaire (MHAQ). A total of 74 patients completed reassessments 3 months after surgery.

Results

The WHOQOL‐BREF demonstrated acceptable internal consistency for all domains (Cronbach's α = 0.76–0.84) and moderate concurrent validity for the physical and psychological domains (r = 0.67 for physical versus AQOL; r = −0.71 for psychological versus K10). Minimal ceiling or floor effects were identified at baseline or 3 months, except for the social relationships domain. The disease‐specific WOMAC subscales were most responsive to change (relative efficiency [RE] 0.66–1.00). Apart from social relationships, all WHOQOL‐BREF scores improved significantly after surgery. The physical domain was more responsive than the AQOL (RE 0.50 versus 0.42) and was similar to the MHAQ (RE 0.55 for MHAQ). The responsiveness of the psychological domain was similar to that of the K10 scale (RE 0.11 versus 0.08).

Conclusion

The WHOQOL‐BREF has good psychometric properties for use in persons with severe joint disease, and by providing complementary information, it offers clinicians and researchers an additional tool for comprehensively assessing quality of life in this patient group.
Average Attributable Fractions: A Coherent Theory for Apportioning Excess Risk to Individual Risk Factors and Subpopulations
Authors: Eide Geir Egil , Heuch Ivar
Published: July 2006

The attributable fraction in a population and the attributable fraction in exposed are different epidemiologic measures for quantifying the contribution of a risk factor to the risk of disease. While the attributable fraction in a population depends on both the relative risk of disease and the risk of being exposed in the population, the attributable fraction in exposed depends only on the relative risk. Similar relationships apply to the combined attributable fraction in a population and in exposed, respectively, for quantifying the total contribution of a group of risk factors. Eide and Gefeller (1995) showed how the sequential and average attributable fractions could be applied to quantify the contributions of the individual risk factors to a combined attributable fraction in a population. The present paper shows how this methodology can be extended to the combined attributable fraction in exposed. The resulting average attributable fractions in exposed are compared to other proposed methods. The relationship between the average attributable fractions in a population and in exposed is outlined, thus establishing a coherent theory for apportioning attributable fractions in individuals, groups of individuals and populations, to single risk factors or groups of risk factors like modifiable versus nonmodifiable factors. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A nonreplicating adenoviral vector that contains the wild‐type p53 transgene combined with chemotherapy for primary breast cancer
Authors: Cristofanilli Massimo , Krishnamurthy Savitri , Guerra Laura , Broglio Kristine , Arun Banu , Booser Daniel J. , Menander Kerstin , Van Wart Hood Jill , Valero Vicente , Hortobagyi Gabriel N.
Published: July 2006

BACKGROUND.

Primary systemic therapy (PST) is the standard approach to the management of patients with locally advanced breast cancer (LABC). The authors hypothesized that the intratumoral administration of a nonreplicating adenoviral vector (Ad5) that contains the human wild‐type p53, AdCMV‐p53, combined with chemotherapy, could increase the efficacy of PST as measured by pathologic complete response.

METHODS.

In a prospective, open‐label, Phase II trial, 13 patients with LABC were treated with 6 3‐week cycles of PST, which consisted of intratumoral injections of Ad5CMV‐p53 for 2 consecutive days plus docetaxel and doxorubicin followed by surgery. p53 status was determined at baseline and was assessed immediately after the first injection (up to 48 hours). Clinical response was assessed by clinical and radiologic methods.

RESULTS.

The trial was terminated early, because none of the patients achieved a pathologic complete response. The median age was 56 years (range, 39–71 years), and the median tumor size was 8 cm (range, 5–11 cm). Eight patients (73%) had a p53 mutation. Serial biopsies showed an increase in p53 messenger RNA (mRNA) and p21WAF1/Cip1 mRNA. All 12 evaluable patients achieved an objective clinical response. The surgical specimens revealed scattered tumor cells with extensive tumor‐infiltrate leukocytes (predominantly T‐lymphocytes). At a median follow‐up of 37 months (range, 30–41 months), 4 patients (30%) developed systemic recurrence, and 2 patients died. The estimate breast cancer‐specific survival rate at 3 years was 84% (95% confidence interval, 65.7–100%). There was no increase in systemic toxicity.

CONCLUSIONS.

Ad5CMV‐p53 combined with PST is safe, active, and associated with local immunomodulatory effects. The promising clinical activity of this combination deserves further investigation in randomized studies. Cancer 2006. © 2006 American Cancer Society.
Multicenter evaluation of the breast lesion excision system, a percutaneous, vacuum‐assisted, intact‐specimen breast biopsy device
Authors: Sie Angela , Bryan David C. , Gaines Victor , Killebrew Larry K. , Kim Christine H. , Morrison Carrie C. , Poller William R. , Romilly Ada P. , Schilling Kathy , Sung Janet H.
Published: July 2006

BACKGROUND.

Percutaneous, vacuum‐assisted, large‐gauge core needle biopsy (VACNB) provides an alternative to open surgical biopsy as an initial diagnostic tool for breast lesions, yet rates of underestimating malignant diagnoses remain sufficiently high to warrant surgical biopsy in some cases. The current study was performed to determine if the Breast Lesion Excision System (BLES) provides a feasible alternative to VACNB.

METHODS.

A retrospective review was conducted of 742 consecutive mammographic lesions with microcalcifications classified as Breast Imaging Reporting and Data System (BIRADS) IV or V that had stereotactic percutaneous biopsy using BLES. Initial diagnoses obtained from the histopathologic examination of tissues retrieved at biopsy were compared with the histopathologic examination of tissues received from surgical excision or lumpectomy. Underestimation rates for atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were recorded if open surgical biopsy revealed DCIS or invasive cancer, and invasive cancer, respectively.

RESULTS.

Of the 742 breast lesions, 34 displayed ADH upon biopsy with the BLES device. Two patients did not receive open surgical biopsy. Of the 32 patients who had open surgical excision, 3 (9.4%) had DCIS or invasive cancer. There were 119 diagnoses of DCIS upon biopsy with the BLES device. Four patients did not receive open surgical biopsy. Of the 115 patients who had open surgical excision, 6 (5.2%) had invasive cancer.

CONCLUSIONS.

Breast biopsy can be performed accurately using the BLES device. Compared with VACNB, it does not alter the need for surgical excision in women diagnosed with ADH or DCIS at core biopsy. Cancer 2006. © 2006 American Cancer Society.
Deficiencies in myeloid antigen‐presenting cells in women with cervical squamous intraepithelial lesions
Authors: Lee Bang‐Ning , Follen Michele , Rodriquez Graciela , Shen De‐Yu , Malpica Anais , Shearer William T. , Reuben James M.
Published: July 2006

BACKGROUND.

There is little information on the function of dendritic cells in women with human papillomavirus (HPV)‐related cervical squamous intraepithelial lesions (SILs). In the current study the functions of dendritic cells in the development of T‐cell immunity in women with cervical SILs were assessed.

METHODS.

The percentage of myeloid dendritic cells (MDCs) and plasmacytoid dendritic cells (PDCs) in peripheral blood were enumerated of 44 patients with SIL (low‐grade, 19; high‐grade, 25), 19 patients with atypical squamous cells of undetermined significance (ASCUS), and 18 controls. The expression of costimulatory receptors was assessed and the ability of monocyte‐derived dendritic cells (MDDC) to present HPV16‐E6 and HPV16‐E7 antigens to autologous T cells.

RESULTS.

Patients with either low (L)‐grade or high (H)‐grade SIL had significantly lower median plasma levels of interferon‐γ than did the controls (P = .038 and .031, respectively). Compared with the controls, patients with ASCUS or LSILs had significantly lower median percentages of MDCs (P = .002 and P < .001, respectively), and significantly lower median percentages of MDDCs that expressed CD86 (P < .001 and P = .003, respectively) and major histocompatability complex class‐II antigen human leukocyte antigen DR (HLA‐DR) (P = .012 and P < .001, respectively). T cells of patients with ASCUS or LSILs proliferated less than those of the controls in response to HPV16‐E7 (P = .002 and .046, respectively).

CONCLUSIONS.

Low levels of peripheral blood MDCs and of MDDCs expressing CD86 and HLA‐DR suggest that deficiencies in the ability of MDDC to present antigen to autologous T cells may lead to persistent infection with HPV and the development of cervical SILs in HPV‐infected women. Cancer 2006. © 2006 American Cancer Society.
Formation of the avian nucleus magnocellularis from the auditory anlage
Authors: Hendricks Susan J. , Rubel Edwin W. , Nishi Rae
Published: July 2006

In the avian auditory system, the neural network for computing the localization of sound in space begins with bilateral innervation of nucleus laminaris (NL) by nucleus magnocellularis (NM) neurons. We used antibodies against the neural specific markers Hu C/D, neurofilament, and SV2 together with retrograde fluorescent dextran labeling from the contralateral hindbrain to identify NM neurons within the anlage and follow their development. NM neurons could be identified by retrograde labeling as early as embryonic day (E) 6. While the auditory anlage organized itself into NM and NL in a rostral‐to‐caudal fashion between E6 and E8, labeled NM neurons were visible throughout the extent of the anlage at E6. By observing the pattern of neuronal rearrangements together with the pattern of contralaterally projecting NM fibers, we could identify NL in the ventral anlage. Ipsilateral NM fibers contacted the developing NL at E8, well after NM collaterals had projected contralaterally. Furthermore, the formation of ipsilateral connections between NM and NL neurons appeared to coincide with the arrival of VIIIth nerve fibers in NM. By E10, immunoreactivity for SV2 was heavily concentrated in the dorsal and ventral neuropils of NL. Thus, extensive pathfinding and morphological rearrangement of central auditory nuclei occurs well before the arrival of cochlear afferents. Our results suggest that NM neurons may play a central role in formation of tonotopic connections in the auditory system. J. Comp. Neurol. 498:433–442, 2006. © 2006 Wiley‐Liss, Inc.
Medullary dorsal horn neurons providing axons to both the parabrachial nucleus and thalamus
Authors: Li Jinlian , Xiong Kanghui , Pang Youwang , Dong Yulin , Kaneko Takeshi , Mizuno Noboru
Published: July 2006

It has often been suggested that the trigemino‐ and spino‐thalamic pathways are highly implicated in sensory‐discriminative aspects of pain, whereas the trigemino‐ and spino‐parabrachial pathways are strongly implicated in affective/emotional aspects of pain. On the other hand, the superficial laminae of the spinal dorsal horn, where many nociceptive neurons are distributed, have been reported to contain projection neurons innervating both the parabrachial nucleus (PBN) and thalamus by way of axon collaterals (Hylden et al., 1989). For the medullary dorsal horn (caudal subnucleus of spinal trigeminal nucleus: Vc), however, the existence of such neurons has not been reported. Thus, in the present study, we examined whether the Vc might contain projection neurons sending their axons to both the thalamus and PBN. Dual retrograde labeling with fluorescence dyes was attempted. In each rat, tetramethylrhodamine‐dextran amine and Fluoro‐gold were stereotaxically injected into the PBN and thalamic regions, respectively. The proportion of the dually labeled Vc cells in the total population of all labeled Vc cells was about 20%. More than 90% of the dually labeled neurons were distributed in lamina I (marginal zone), less than 10% of them were located in lamina II (substantia gelatinosa), and only a few (about 1%) were found in lamina III (magnocellular zone). The results indicate that some Vc neurons in the superficial laminae mediate nociceptive information directly to the PBN and thalamus by way of axon collaterals and that the vast majority of them project to the ipsilateral PBN and contralateral thalamus.
J. Comp. Neurol. 498:539–551, 2006. © 2006 Wiley‐Liss, Inc.
Cuneate nucleus reorganization following cervical dorsal rhizotomy in the macaque monkey: Its role in the recovery of manual dexterity
Authors: Darian‐Smith Corinna , Ciferri Melanie
Published: July 2006

Immediately following a dorsal rhizotomy that removes input from the thumb, index, and middle fingers, the macaque is unable to execute movements that require controlled apposition of these digits. We have previously shown that within the early weeks and months following one of these lesions, there is 1) a re‐emergence of part or all of the cortical hand map; 2) central axonal sprouting of spared primary afferents into the dorsal horn and cuneate nucleus; and 3) substantial although incomplete recovery of hand function (Darian‐Smith [204] J. Comp. Neurol. 470:134–150; Darian‐Smith and Ciferri [2005] J. Comp. Neurol. 491:27–45). In this study we asked: What neuronal reorganization occurs in the cuneate nucleus during this “recovery” period? And, does it contribute to the recovery of manual dexterity? To address these questions, the representation of the hand was electrophysiologically mapped (by unitary receptive field [RF] recordings) in the pars rotunda of the cuneate nucleus at either 1–2 weeks (short term) or 16–32 weeks (long term) post‐rhizotomy. In short‐term monkeys, the region deprived of input from the thumb, index, and middle finger was found to be unresponsive to cutaneous stimulation. However, at 16–32 weeks later, when dexterity had largely recovered, RFs of cuneate neurons could again be mapped within the cuneate nucleus, primarily in a region bordering the deprived zone. We conclude that the cuneate pre‐ and postsynaptic reorganization that occurs following dorsal rhizotomy plays a key role in the recovery of hand function. J. Comp. Neurol. 498:552–565, 2006. © 2006 Wiley‐Liss, Inc.
Effects of chronic hyperglycaemia on incident stroke in Hong Kong Chinese patients with type 2 diabetes
Authors: Yang Xilin , Kong Alice P. S. , So Wing Yee , Ma Ronald C. W. , Ho Chung Shun , Lam Christopher W. K. , Chow Chun Chung , Cockram Clive S. , Tong Peter C. Y. , Chan Juliana C. N.
Published: July 2006

Background

It remains unclear whether hyperglycaemia as measured by HbA1c is a significant risk factor for stroke in patients with type 2 diabetes mellitus (T2DM).

Methods

A case‐control study nested in a prospective cohort with 1 : 3 controls matched on age, gender, systolic blood pressure and low‐density lipoprotein cholesterol (LDL‐C) was conducted. The case group included 105 patients who developed incident stroke during 2.88 years (SD: 1.59) of follow‐up of 4150 T2DM patients and 299 matched patients without incident stroke, used as the control group. Stratified Cox proportional hazard regression was used to obtain hazard ratio (HR).

Results

Median age was 71 years (IQR: 9.0 for the case and 10.0 for the control). HbA1c was significantly higher in the cases than in the controls (median 8.0% [IQR: 2.0] versus 7.2% [2.1], p < 0.0001). After controlling for smoker status, haematocrit, drug treatments and other covariates, 1% increase in HbA1c was associated with 1.49 (95% CI: 1.18–1.88, p = 0.0008) folds risk of occurrence of incident stroke. Patients with a history of coronary heart disease (CHD) were also at increased risk of stroke (HR: 8.25, 95% CI: 2.22–30.73, p = 0.0016). Smoker status and haematocrit were marginally significant predictors of incident stroke. Every adjusted month using lipid‐lowering drugs was significantly associated with reduced risk of incident stroke (HR: 0.95, 95% CI: 0.90–0.99, p = 0.0199). Similar analysis using ACEI or ARB as a drug group was marginally significant (p = 0.0555).

Conclusion

Chronic hyperglycaemia is a risk factor of stroke in Chinese patients with T2DM. Copyright © 2006 John Wiley & Sons, Ltd.
A pseudosymmetric cell adhesion regulatory domain in the β7 tail of the integrin α4β7 that interacts with focal adhesion kinase and src
Authors: Krissansen Geoffrey W. , Singh Jaison , Kanwar Rupinder K. , Chan Yih‐Chih , Leung Euphemia , Lehnert Klaus B. , Kanwar Jagat R. , Yang Yi
Published: July 2006

The β7 integrins α4β7 and αEβ7 play key roles in forming the gut‐associated lymphoid tissue, and contribute to chronic inflammation. The α4β7 integrin‐mediated adhesion of activated lymphocytes is largely due to a transient increase in avidity from ligand‐induced clustering of α4β7 at the cell‐surface. Here, we report that L and D enantiomers of a cell‐permeable peptide YDRREY encompassing residues 735–740 of the cytoplasmic tail of the β7 subunit inhibit the adhesion of T cells to β7 integrin ligands. The YDRREY peptide abrogated mucosal addressin cell adhesion molecule‐1‐induced clustering of α4β7 on the surface of activated T cells. A mutated form of the YDRREY peptide carrying either single or double conservative mutations at Tyr735Phe and Tyr740Phe was unable to inhibit T cell adhesion, suggesting that both tandem tyrosines are critical for activity. The YDRREY peptide was bound and phosphorylated by focal adhesion kinase and src, which may serve to sequester cytoskeletal proteins to the cytoplasmic domain of α4β7. The quasi‐palindromic sequence YDRREY within the β7 cytoplasmic tail constitutes a cell adhesion regulatory domain that modulates the interaction of β7‐expressing leukocytes with their endothelial and epithelial ligands. Cell‐permeable peptidomimetics based on this motif have utility as anti‐inflammatory reagents for the treatment of chronic inflammatory disease.
Interallelic class switch recombination can reverse allelic exclusion and allow trans‐complementation of an IgH locus switching defect
Authors: Dougier Hei‐Lanne , Reynaud Stéphane , Pinaud Eric , Carrion Claire , Delpy Laurent , Cogné Michel
Published: July 2006

The predominant path of immunoglobulin class switch recombination follows the paradigm of intra‐chromosomal deletion enabling expression of another heavy chain instead of µ and δ. This was, however, challenged by observations of inter‐allelic class switch recombination in rabbit or mouse IgG3‐ or IgA‐producing B cells. Assuming that the conditions of inter‐chromosomal exchange are likely present at any target S regions in stimulated B cells, we explored trans‐association of VH and C genes in a model allowing all C genes to be checked simultaneously. Heterozygous mutant mice are thus studied, which carry one non‐functional IgH allele inactivated by a non‐translatable mutation of VDJ‐CH transcripts, while the functional allele is deficient for class switching due to a truncated 3′regulatory region. A fair level of switching to all Ig classes is restored in heterozygous mice despite the fact that cis‐recombination is either non productive on one allele or deficient on the other. Molecular evidence at the DNA level of trans‐CSR to IgG3 was demonstrated by cloning and sequencing Sµ‐Sγ3 hybrid junctions. These data demonstrate that inter‐allelic recombination may broadly rescue the production of various class‐switched isotypes and allow complementation between mutations located at both ends of the IgH constant gene cluster.
CArG box‐binding factor‐A interacts with multiple motifs in immunoglobulin promoters and has a regulated subcellular distribution
Authors: Aranburu Alaitz , Liberg David , Honoré Bent , Leanderson Tomas
Published: July 2006

CArG box‐binding factor‐A (CBF‐A) is a protein involved in transcriptional control and interacts specifically with the penta‐decameric (pd) element in κ promoters. We show here that CBF‐A will also bind specifically to a second region in the κ promoter that overlaps with an early B cell factor binding site. Furthermore, the same region is present in multiple Ig promoters and we show that CBF‐A can bind to several of these. Mitogenic stimulation of untransformed B lymphocytes promoted nuclear localisation of CBF‐A. Using enhanced GFP (EGFP)‐tagged constructs and transfection into COS7 cells, a nuclear localisation signal was defined in the C terminus of CBF‐A. Deletion of only 13 amino acids from the C terminus of CBF‐A led to the accumulation of the protein in bright speckles at the nuclear/cytoplasmic border. We also identified the heterogeneous ribonucleoprotein H as a specific interaction partner of CBF‐A, but this interaction could be detected in the cytoplasm only. Thus, CBF‐A has the potential to regulate the expression of multiple Ig V genes and has a complex, mitogen‐responsive regulation of its intracellular localisation.
Crystal Structure and Properties of MgCo4Ge6
Authors: Gieck Christine , Schreyer Martin , Fässler Thomas F. , Raif Fabian , Claus Peter
Published: July 2006

MgCo4Ge6 is a novel compound in the ternary system Mg‐Co‐Ge. Single crystals for a structure analysis were obtained from mixtures of the elements at high temperatures in sealed tantalum ampoules. The tetragonal structure [I$\bar {4}$2m; a = 6.1725(9) and c = 8.660(2) Å; YRu4Sn6 structure type] was determined by X‐ray single crystal analysis and refined to R1 = 0.027 for all data. The electronic structure is discussed by means of density of states and band‐structure analyses on the basis of density functional theory. Chemical bond analysis is performed using the electron localization function (ELF). The catalytic properties of the polar intermetallic alloy with respect to the selective hydrogenation of α,β‐unsaturated aldehydes are discussed and compared with those of the recently investigated MgCo6Ge6. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A Ferromagnetically Coupled, Bent, Trinuclear Copper(II) Complex: Synthesis, Structure, Hydrogen‐Bonding Network, Magnetic Properties and DNA Interaction Study
Authors: Sarkar Sumana , Mondal Amrita , Chopra Deepak , Ribas Joan , Rajak Kajal Krishna
Published: July 2006

A bent trinuclear copper(II) complex (1) incorporating μ‐phenoxo, μ‐syn‐syn carboxylato, and μ3‐chloro bridges and an O,N,N‐coordinated reduced Schiff‐base ligand is reported. The complex shows an intramolecular ferromagnetic interaction in the solid state. The EPR spectra also support the magnetic behaviour of the complex. In the compound, each copper centre has a square‐pyramidal geometry. The separation between the adjacent copper ions is about 3.05 Å and that between the terminal copper ions is about 5.0 Å. The complex forms a supramolecular architecture through N–H···Cl hydrogen bonding between the amine group of the reduced Schiff‐base ligand and the counter chloride anions. Absorption and fluorescence spectral studies and viscosity measurements have been performed to determine the type of interaction with calf‐thymus DNA. The nuclease activity of the complex with plasmid DNA is also studied. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis, Structure and Magnetic Properties of a Tetranuclear Copper(II) Complex on the Basis of a 2‐Substituted Glucopyranoside Schiff Base Ligand
Authors: Burkhardt Anja , Buchholz Axel , Görls Helmar , Plass Winfried
Published: July 2006

Condensation of a derivatized 2‐aminoglucose fragment with salicylaldehyde affords the new sugar‐based Schiff base ligand benzyl 4,6‐O‐benzylidene‐2‐deoxy‐2‐salicylideneamino‐α‐D‐glucopyranoside (H2L). The reaction of the dibasic ligand H2L with [Cu(CH3COO)2]·H2O leads to the formation of the tetranuclear copper(II) complex [{Cu(L)}4] (3) by a self‐assembly process. The X‐ray structural analysis of complex 3 which crystallizes together with two molecules of chloroform and one molecule of ethanol in the space group P212121 revealed for all copper atoms a NO3 coordination environment with a square‐planar geometry. The tetranuclear molecule 3 consists of four chiral building blocks {Cu(L)} with the rare 2,3‐coordination of the trans‐configured donor atoms of the sugar backbone. The observed coordination mode of the building blocks exemplifies how chitosan‐derived polysaccharide ligands can act as a chiral support for transition‐metal complexes. The C‐3 alcoholate oxygen atoms of the carbohydrate unit is bridging adjacent {Cu(L)} moieties resulting in an eight‐membered Cu4O4 ring with a boat‐like conformation. Temperature‐dependent magnetic measurements of 3 indicate moderate antiferromagnetic interactions between the four copper(II) ions with a coupling constant of J = –130 cm–1.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Planarization of the Cyclohexane Ring by Its Incorporation Into a Cyclophane Cage: Hexahydrosuperphane
Authors: Dodziuk Helena , Ostrowski Maciej
Published: July 2006

Calculations at the HF/6‐311G(d,p), DFT B3LYP/6‐311G(d,p), and MP2/6‐311G(d,p) levels show that the hypothetical molecule hexahydrosuperphane should have a planar saturated ring imposed by its incorporation into a cyclophane. The calculated NMR chemical shifts are compared with the experimental literature data for a few compounds with similar structure fragments. The calculated vibrational frequencies and the analysis of possible decomposition routes of the title molecule indicate that the molecule should be stable. Thus, it represents a plausible synthetic target. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Regioselectivity in the Multi‐Component Synthesis of Indolizinoquinoline‐5,12‐dione Derivatives
Authors: Defant Andrea , Guella Graziano , Mancini Ines
Published: July 2006

The one‐pot cyclisation to form the indolizinoquinoline‐5,12‐dione ring system has been investigated starting from 6,7‐dichloroquinoline‐5,8‐dione by reaction with pyridine and ethyl acetoacetate. Both the N,N‐syn and the N,N‐anti products have been fully characterised by mass spectrometry and NMR analysis, and the regioselectivity of their formation is discussed in terms of solvent polarity and/or the nature of the metal ion. We demonstrate here that, among a wide series of polar and apolar solvents, tert‐butyl alcohol is the best choice to enhance the yield of the N,N‐syn regioisomer, while the N,N‐anti regioisomer can be obtained with a very high selectivity when the reaction is carried out with scandium triflate. In the presence of metal chelation, semi‐empirical ZINDO calculations offer an appropriate tool to explain the regioselectivity observed when different metal ions are used. The study of the regioselectivity is also supported by the data for the corresponding two‐step reactions with reversed addition of the nucleophilic reagents, and it has been extended to the cases involving 4‐methylpyridine and 6,7‐dichloroisoquinoline‐5,8‐dione as reagents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Experimental study of rill bank collapse
Authors: Stefanovic Jovan R. , Bryan Rorke B.
Published: July 2006

Rill bank collapse is an important component in the adjustment of channel morphology to changes in discharge and sediment flux. Sediment inputs from bank collapse cause abrupt changes in flow resistance, flow patterns and downstream sediment concentrations. Generally, bank retreat involves gradual lateral erosion, caused by flow shear stress, and sudden bank collapse, triggered by complex interactions between channel flow and bank and soil water conditions. Collapse occurs when bank height exceeds the critical height where gravitational forces overcome soil shear strength. An experimental study examined conditions for collapse in eroding rill channels. Experiments with and without a deep water table were carried out on a meandering rill channel in a loamy sand and sandy loam in a laboratory flume under simulated rainfall and controlled runon. Different discharges were used to initiate knickpoint and rill incision. Soil water dynamics were monitored using microstandpipes, tensiometers and time domain reflectometer probes (TDR probes). Bank collapse occurred with newly developed or rising pre‐existing water tables near rill banks, associated with knickpoint migration. Knickpoint scour increased effective bank height, caused positive pore water pressure in the bank toe and reduced negative pore pressures in the unsaturated zone to near zero. Matric tension in unsaturated parts of the bank and a surface seal on the ‘interrill’ zone behind the bank enhanced stability, while increased effective bank height and positive pore water pressure at the bank toe caused instability. With soil water contents >35 per cent (sandy loam) and >23 per cent (loamy sand), critical bank heights were 0·11–0·12 m and 0·06–0·07 m, respectively. Bank toe undercutting at the outside of the rill bends also triggered instability. Bank displacement was quite different on the two soils. On the loamy sand, the failed block slid to the channel bed, revealing only the upper half of the failure plane, while on the sandy loam the failed block toppled forwards, exposing the failure plane for the complete bank height. This study has shown that it is possible to predict location, frequency and magnitude of the rill bank collapse, providing a basis for incorporation into predictive models for hillslope soil loss or rill network development. Copyright © 2006 John Wiley & Sons, Ltd.
Discussion of landslide self‐organized criticality and the initiation of debris flow
Authors: Chien‐Yuan Chen , Fan‐Chieh Yu , Sheng‐Chi Lin , Kei‐Wai Cheung
Published: July 2006

The study contains descriptions of landslides and debris flows in a small upland catchment in Taiwan between 1986 and 2004. This catchment, the Chushui Creek, is situated near the epicentre of the 1999 M7·6 Chi‐Chi earthquake. This is an area with high background erosion rate. The Chi‐Chi earthquake caused a sharp increase in the rate of mass wasting in the epicentral area, and the data presented in this study illustrates the geomorphic change associated with the earthquake. The measurements of the geometry of the trunk stream of the Chushui catchment also show its change due to the impact of a strong typhoon in 1996. Two channel reaches that were affected by separate debris flows during this event were identified. Each reach has three sections: scour, transfer and deposition. Cross profiles of these sections show a systematic change from V‐shaped bedrock channel in the scour areas to flat‐floored channel in the transfer and deposition areas. Debris flows also occurred on other occasions in this channel, and their frequency has increased since the 1999 earthquake. In addition, this study contains precise geographic and statistical descriptions of the landslides triggered by three typhoons and an earthquake that affected the catchment since 1996. The total landslide area is measured for different time intervals, and a marked increase in landslide incidence is found after the 1999 earthquake. Frequency–area plots of the 126 landslides in the catchment indicate a power‐law scaling with an exponent of about ‐1·5 of these quantities, as has been observed in other studies. We propose that a link exists between landslide frequency–area distributions and initialization of debris flow in the catchment. It may be classified as a self‐organized criticality process with a critical frequency–area distribution for the landslide population. In this case, the landslide frequency–area distribution is useful in quantifying the severity of the trigger and the contribution of landslides to debris flow. Copyright © 2006 John Wiley & Sons, Ltd.
Disaggregate evidence on the persistence of consumer price inflation
Authors: Clark Todd E.
Published: July 2006

This paper uses disaggregate inflation data spanning all of consumption to examine: (i) the persistence of disaggregate inflation relative to aggregate inflation; (ii) the distribution of persistence across consumption sectors; and (iii) whether persistence has changed. Assuming mean inflation to be unchanged, disaggregate persistence inflation is consistently below aggregate persistence. Taking into account an early 1990s shift in mean inflation identified by break tests yields much lower estimates of both aggregate and disaggregate persistence for 1984–2002. But with the mean break, average disaggregate persistence is actually as great as aggregate inflation persistence. A factor model provides a natural framework for interpreting the relationship between aggregate and disaggregate persistence. Copyright © 2006 John Wiley & Sons, Ltd.
Estimates of semiparametric equivalence scales
Authors: Stengos Thanasis , Sun Yiguo , Wang Dianqin
Published: July 2006

Within the semiparametric framework introduced by Pendakur (1999) we introduce a new loss function to estimate equivalence scales. This loss function uses all available information from the total expenditures of both the reference and nonreference households and as such it produces more reliable estimates. Using Canadian family expenditure data for 1996 we apply this loss function to obtain equivalence scale estimates for a variety of expenditure share categories such as food, fuel and clothing. Copyright © 2006 John Wiley & Sons, Ltd.
Crossed polydactyly type I caused by a point mutation in the GLI3 gene in a large Chinese pedigree
Authors: Cheng Baowen , Dong Yongli , He Li , Tang Wenru , Yu Haijing , Lu Jing , Xu Lin , Zheng Bingrong , Li Kaiyuan , Xiao Chunjie
Published: July 2006

Polydactyly is one of the most common forms of congenital malformation in humans, and is displayed by 119 disorders. Crossed polydactyly (CP) is defined as the coexistence of preaxial and postaxial polydactyly with a difference in the axes of polydactyly between the hands and feet. In an effort to map the gene responsible for CP, we studied a seven‐generation Chinese family of 56 individuals, 28 of whom were affected. A thorough search with highly informative polymorphic markers showed no recombination among the affected members with the markers on chromosome 7p15‐q11.23, but no linkage with chromosomes 2q31, 7q36, 13q, and 19p. Mutation analysis showed a substitution mutation of 1927C → T in exon 12 of the GLI3 gene, which is predicted to pretruncate the GLI3 protein. This mutation has variable phenotypes of polydactyly, indicating that other genetic factors also contribute to the diversity of polydactyly phenotypes. Our results increase the phenotypic spectrum caused by GLI3 mutations and are important for the analysis and understanding of the etiology of these limb malformations. J. Clin. Lab. Anal. 20:133–138, 2006. © 2006 Wiley‐Liss, Inc.
22q11 microdeletion studies in the heart tissue of an abortus involving a familial form of congenital heart disease
Authors: Patel Z.M. , Gawde H.M. , Khatkhatay M.I.
Published: July 2006

Microdeletion of chromosome 22 is responsible for DiGeorge syndrome, Velo Cardio Facial syndrome, and conotruncal defects. Here, we report on a case of microdeletion 22q11.2 in the heart tissue of a miscarried fetus in a family whose two children had died due to complex congenital heart disease. Fluorescence in situ hybridization (FISH) analysis in the couple revealed that the mother was mosaic for microdeletion of chromosome 22q11.2 in 10% of her peripheral lymphocytes. Prenatal diagnosis was offered to her in her third pregnancy. On routine ultrasonography at 10 weeks, the overall view of the heart was normal. However, before any further tests could be performed, she miscarried at 16 weeks. FISH studies on the heart tissue of the abortus revealed 22q11.2 microdeletion with two different cell lines. This suggests the importance of performing FISH studies when there is a history of congenital heart disease, even though ultrasonography shows a normal view of the heart. J. Clin. Lab. Anal. 20:160–163, 2006. © 2006 Wiley‐Liss, Inc.
A serological follow‐up of toxocariasis patients after chemotherapy based on the detection of IgG, IgA, and IgE antibodies by enzyme‐linked immunosorbent assay
Authors: Elefant Guita Rubinsky , Shimizu Sumie Hoshino , Arroyo Sanchez Maria Carmen , Jacob Cristina Miuki Abe , Ferreira Antonio Walter
Published: July 2006

A serological follow‐up study was carried out on 27 children (1–12 years old) with visceral and/or ocular toxocariasis, after treatment with thiabendazole. A total of 159 serum samples were collected in a period ranging from 22–116 months. Enzyme‐linked immunosorbent assays (IgG, IgA, and IgE ELISA) were standardized, using excretory–secretory antigens obtained from the second‐stage larvae of aToxocara canisculture. The sensitivity found for the IgG, IgA, and IgE ELISA, as determined in visceral toxocariasis patients, was 100%, 47.8%, and 78.3%, respectively. Approximately 84% of the patients presented single or multiple parasitosis, as diagnosed by stool examination, yet such variables did not appear to affect the anti‐Toxocaraimmune response. Titers of specific IgE antibody showed a significant decrease during the first year after treatment, followed by a decrease in the IgA titers in the second year, and in the IgG titers from the fourth year onwards. Sera from all patients presented high avidity IgG antibodies, indicating that they were in the chronic phase of the disease. Moreover, 1 year after treatment, the level of leukocytes, eosinophils, and anti‐A isohemagglutinin in patients decreased significantly. The present data suggest that IgE antibodies plus eosinophil counts are helpful parameters for patient follow‐up after chemotherapy. J. Clin. Lab. Anal. 20:164–172, 2006. © 2006 Wiley‐Liss, Inc.
Bilaterally symmetrical rhopalial nervous system of the box jellyfish Tripedalia cystophora
Authors: Skogh C. , Garm A. , Nilsson D.‐E. , Ekström P.
Published: July 2006

Cubomedusae, or box jellyfish, have the most elaborate visual system of all cnidarians. They have 24 eyes of four morphological types, distributed on four sensory structures called rhopalia. Box jellyfish also display complex, probably visually guided behaviors such as obstacle avoidance and fast directional swimming. Here we describe the strikingly complex and partially bilaterally symmetrical nervous system found in each rhopalium of the box jellyfish, Tripedalia cystophora, and present the rhopalial neuroanatomy in an atlas‐like series of drawings. Discrete populations of neurons and commissures connecting the left and the right side along with two populations of nonneuronal cells were visualized using several different histochemical staining techniques and electron microscopy. The number of rhopalial nerve cells and their overall arrangement indicates that visual processing and integration at least partly happen within the rhopalia. The larger of the two nonneuronal cell populations comprises ∼2,000 likely undifferentiated cells and may support a rapid cell turnover in the rhopalial nervous system. J. Morphol., 2006. © 2006 Wiley‐Liss, Inc.