bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in the Human Muscle LIM Protein Gene in Families With Hypertrophic Cardiomyopathy
Authors: Geier Christian , Perrot Andreas , Özcelik Cemil , Binner Priska , Counsell Damian , Hoffmann Katrin , Pilz Bernhard , Martiniak Yvonne , Gehmlich Katja , van der Ven Peter F.M. , Fürst Dieter O. , Vornwald Arnold , von Hodenberg Eberhard , Nürnberg Peter , Scheffold Thomas , Dietz Rainer , Osterziel Karl Josef
Published: March 2003

Background—

Muscle LIM protein (MLP) is an essential nuclear regulator of myogenic differentiation. Additionally, it may act as an integrator of protein assembly of the actin-based cytoskeleton. MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans.

Methods and Results—

We analyzed 1100 unrelated individuals (400 patients with DCM, 200 patients with HCM, and 500 controls) for mutations in the human
CRP3
gene that encodes MLP. We found 3 different missense mutations in 3 unrelated patients with familial HCM but detected no mutation in the DCM group or the controls. All mutations predicted an amino acid exchange at highly conserved residues in the functionally important LIM1 domain, which is responsible for interaction with α-actinin and with certain muscle-specific transcription factors. Protein-binding studies indicate that mutations in the
CRP3
gene lead to a decreased binding activity of MLP to α-actinin. All 3 index patients were characterized by typical asymmetrical septal hypertrophy. Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP.

Conclusion—

Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM.
Drugs That Induce Repolarization Abnormalities Cause Bradycardia in Zebrafish
Authors: Milan David J. , Peterson Travis A. , Ruskin Jeremy N. , Peterson Randall T. , MacRae Calum A.
Published: March 2003

Background—

Drug-induced QT prolongation and torsades de pointes remain significant and often unpredictable clinical problems. Current in vitro preclinical assays are limited by biological simplicity, and in vivo models suffer from expense and low throughput.

Methods and Results—

During a screen for the effects of 100 small molecules on the heart rate of the zebrafish,
Danio rerio
, we found that drugs that cause QT prolongation in humans consistently caused bradycardia and AV block in the zebrafish. Of 23 such drugs tested, 18 were positive in this initial screen. Poor absorption explained 4 of 5 false-negative results, as demonstrated by microinjection. Overall, 22 of 23 compounds that cause repolarization abnormalities were positive in this assay. Antisense “knockdown” of the zebrafish KCNH2 ortholog yielded bradycardia in a dose dependent manner confirming the effects of reduction of repolarizing potassium current in this model. Classical drug-drug interactions between erythromycin and cisapride, as well as cimetidine and terfenadine, were also reproduced.

Conclusion—

This simple high-throughput assay is a promising addition to the repertoire of preclinical tests for drug-induced repolarization abnormalities. The genetic tractability of the zebrafish will allow the exploration of heritable modifiers of such drug effects.
Toward Trash That Thinks: Product Tags for Environmental Management
Authors: Saar Steven , Thomas Valerie
Published: March 2003

In this article, we explore several options for linking information technology to materials and products through the use of bar codes and radio‐frequency identification (RFID) tags, and the implications for product life‐cycle management. We also describe tests with existing and modified tags, both on and inside products, as would be needed for environmental management applications.

Bar codes are cheap and have an existing infrastructure; RFID tags are more expensive and less widespread, but they can be read without a line of sight between the tag and the reader. Bar codes and RFID tags carrying basic product information could link to different databases for a range of applications. Product tags could increase recycling efficiency by automating the sorting of recyclables or by linking to product dismantling instructions during the recycling process. Product tags could provide incentives for good waste management, through Universal Product Code (UPC) bar‐code recycling coupons or through RFID tag automatic recycling credits for curbside collection programs. Measures to encourage the development of these types of applications include moves toward competitive, market‐based waste management systems, the encouragement of experimental systems, and coordination between manufacturers and waste management industries.
2-Methoxyestradiol alters cell motility, migration, and adhesion
Authors: Sattler Martin , Quinnan Laura R. , Pride Yuri B. , Gramlich Jessica L. , Chu Stephanie C. , Even Gaelle C. , Kraeft Stine-Katherin , Chen Lan Bo , Salgia Ravi
Published: March 2003

The effect of 2-methoxyestradiol, 2ME2, an endogenous metabolite of 17β-estradiol (E2), on cell growth and cytoskeletal functions in a BCR-ABL—transformed cell line model was investigated. We determined the interaction of 2ME2 with STI571 (Gleevec, imatinib mesylate) in STI571 drug-sensitive and -resistant cell lines. In cells expressing BCR-ABL, STI571 cooperated with 2ME2 in reducing cell growth, and STI571-resistant cells were sensitive to 2ME2 treatment. 2ME2 also inhibited growth of several cancer cell lines by a mechanism independent of BCR-ABL. BCR-ABL transformation leads to altered motility, increased adhesion, and spontaneous migration in different in vitro model systems. 2ME2 was found to specifically inhibit the spontaneous motility of BCRABL—transformed Ba/F3 cells and to change the morphology and volume of treated cells. Cells attached to fibronectin-coated surfaces showed a reduced number of filipodia and lamellipodia. In addition, 2ME2 significantly reduced BCRABL—mediated adhesion to fibronectin. The spontaneous migration of BCR-ABL—transformed cells through a transwell membrane also was found to be significantly decreased by 2ME2. Cytoskeletal changes were accompanied by alteration of tubulin formation, distinct from paclitaxel treatment. These results demonstrate that 2ME2 treatment of transformed cells strongly reduces cytoskeletal functions and may also be useful for the treatment of cancers with high metastatic potential. Combination of 2ME2 with other anticancer drugs may be beneficial to treatment of drug-resistant cancers. (Blood. 2003;102:289-296)
A zone of frontonasal ectoderm regulates patterning and growth in the face
Authors: Hu Diane , Marcucio Ralph S. , Helms Jill A.
Published: March 2003

A fundamental set of patterning genes may define the global organization of the craniofacial region. One of our goals has been to identify these basic patterning genes and understand how they regulate outgrowth of the frontonasal process, which gives rise to the mid and upper face. We identified a molecular boundary in the frontonasal process ectoderm, defined by the juxtaposed domains of Fibroblast growth factor 8 and Sonic hedgehog,which presaged the initial site of frontonasal process outgrowth. Fate maps confirmed that this boundary region later demarcated the dorsoventral axis of the upper beak. Ectopic transplantation of the ectodermal boundary region activated a cascade of molecular events that reprogrammed the developmental fate of neural crest-derived mesenchyme, which resulted in duplications of upper and lower beak structures. We discuss these data in the context of boundary/morphogen models of patterning, and in view of the recent controversy regarding neural crest pre-patterning versus neural crest plasticity.
Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice
Authors: Xu Xiaoling , Aprelikova Olga , Moens Peter , Deng Chu-Xia , Furth Priscilla A.
Published: March 2003

Breast tumor suppressor gene 1 (BRCA1) plays an essential role in maintaining genomic integrity. Here we show that mouse Brca1 is required for DNA-damage repair and crossing-over during spermatogenesis. MaleBrca1Δ11/Δ11p53+/- mice that carried a homozygous deletion of Brca1 exon 11 and a p53heterozygous mutation had significantly reduced testicular size and no spermatozoa in their seminiferous tubules. During spermatogenesis, homologous chromosomes from the mutant mice synapsed and advanced to the pachytene stage but failed to progress to the diplotene stage. Our analyses revealed that theBrca1 mutation affected cellular localization of several DNA damage-repair proteins. This included prolonged association of γH2AX with sites of DNA damage, reduced sex body formation, diminished Rad51 foci and absence of Mlh1 foci in the pachytene stage. Consequently, chromosomes from mutant mice did not form chiasmata, a point that connects exchanging homologous chromosomes. Brca1-mutant spermatocytes also exhibited decreased RNA expression levels of several genes that are involved in DNA-damage repair, including RuvB-like DNA helicase, XPB, p62 and TFIID. Of note, the premature termination of spermatogenesis at the pachytene stage was accompanied by increased apoptosis by both p53-dependent and p53-independent mechanisms. Thus, our study revealed an essential role of Brca1 in DNA-damage repair and crossing-over of homologous chromosomes during spermatogenesis.
Strabismus requires Flamingo and Prickle function to regulate tissue polarity in theDrosophilaeye
Authors: Rawls Amy S. , Wolff Tanya
Published: March 2003

Tissue polarity in Drosophila is regulated by a number of genes that are thought to function in a complex, many of which interact genetically and/or physically, co-localize, and require other tissue polarity proteins for their localization. We report the enhancement of the strabismustissue polarity phenotype by mutations in two other tissue polarity genes,flamingo and prickle. Flamingo is autonomously required for the establishment of ommatidial polarity. Its localization is dynamic throughout ommatidial development and is dependent on Frizzled and Notch. Flamingo and Strabismus co-localize for several rows posterior to the morphogenetic furrow and subsequently diverge. While neither of these proteins is required for the other's localization, Prickle localization is influenced by Strabismus function. Our data suggest that Strabismus, Flamingo and Prickle function together to regulate the establishment of tissue polarity in theDrosophila eye.
Joint regulation of the MAP1B promoter by HNF3β/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors
Authors: Foucher Isabelle , Montesinos María Luz , Volovitch Michel , Prochiantz Alain , Trembleau Alain
Published: March 2003

The MAP1B (Mtap1b) promoter presents two evolutionary conserved overlapping homeoproteins and Hepatocyte nuclear factor 3β(HNF3β/Foxa2) cognate binding sites (defining putative homeoprotein/Fox sites, HF1 and HF2). Accordingly, the promoter domain containing HF1 and HF2 is recognized by cerebellum nuclear extracts containing Engrailed and Foxa2 and has regulatory functions in primary cultures of embryonic mesmetencephalic nerve cells. Transfection experiments further demonstrate that Engrailed and Foxa2 interact physiologically in a dose-dependent manner: Foxa2 antagonizes the Engrailed-driven regulation of the MAP1B promoter, and vice versa. This led us to investigate if Engrailed and Foxa2 interact directly. Direct interaction was confirmed by pull-down experiments, and the regions participating in this interaction were identified. In Foxa2 the interacting domain is the Forkhead box DNA-binding domain. In Engrailed, two independent interacting domains exist: the homeodomain and a region that includes the Pbx-binding domain. Finally, Foxa2 not only binds Engrailed but also Lim1, Gsc and Hoxa5 homeoproteins and in the four cases Foxa2 binds at least the homeodomain. Based on the involvement of conserved domains in both classes of proteins, it is proposed that the interaction between Forkhead box transcription factors and homeoproteins is a general phenomenon.
Molecular regionalization of the neocortex is disrupted inFgf8hypomorphic mutants
Authors: Garel Sonia , Huffman Kelly J. , Rubenstein John L. R.
Published: March 2003

The neocortex is divided into multiple areas with specific architecture,molecular identity and pattern of connectivity with the dorsal thalamus. Gradients of transcription factor expression in the cortical primordium regulate molecular regionalization and potentially the patterning of thalamic projections. We show that reduction of Fgf8 levels in hypomorphic mouse mutants shifts early gradients of gene expression rostrally, thereby modifying the molecular identity of rostral cortical progenitors. This shift correlates with a reduction in the size of a molecularly defined rostral neocortical domain and a corresponding rostral expansion of more caudal regions. Despite these molecular changes, the topography of projections between the dorsal thalamus and rostral neocortex in mutant neonates appears the same as the topography of wild-type littermates. Overall, our study demonstrates the role of endogenous Fgf8 in regulating early gradients of transcription factors in cortical progenitor cells and in molecular regionalization of the cortical plate
Relative movements between Kinemax Plus tibial inserts and the tibial base-plates
Authors: Ash H E , Scholes S C , Parkin R , Unsworth A
Published: March 2003

Tests were performed on six large Kinemax Plus knee bearings (snap-fit design) to evaluate the amount of movement between 10- and 15-mm-thick tibial inserts and the tibial base plates. The knee bearings were tested up to 1 × 106 cycles on the Durham six-station knee wear simulator which subjected the bearings to similar motion and loading profiles that would be experienced by the natural knee during walking. Although passive internal/external (I/E) rotation was allowed, no active I/E rotation was applied.

The movement of the tibial inserts was measured with dial gauges (accuracy ±0.01 mm) before and after the bearings were tested on the simulator, when unloaded, and throughout the tests while the bearings were being dynamically loaded in the simulator. Movement occurred between the tibial insert and the tibial base plate after initial assembly due to the snap-fit mechanism used to locate the tibial insert within the tibial base plate. However this decreased appreciably when the bearings were loaded in the simulator. The amount of movement did not change with time when the bearings were continuously loaded in the simulator. However, after each test the amount of movement of the tibial inserts, when unloaded, was only 65 per cent (anterior-posterior) and 46 per cent (medial-lateral) of the values before the test. This was thought to be due to creep of the ultra-high molecular weight polyethylene (UHMWPE) inserts. The movement between the tibial insert and tibial base plate in situ is likely to be much less than that observed by a surgeon at the time of assembly due to loading of the knee bearing in the body. However, the amount of movement when the tibial inserts are loaded may still be great enough to produce a second interface where wear of the tibial insert may take place.
Mechanical strength of a femoral reconstruction in paediatric oncology: A finite element study
Authors: Taddei F , Viceconti M , Manfrini M , Toni A
Published: March 2003

In 1997 the proximal femur of a four-year-old child affected by a Ewing sarcoma was reconstructed using a massive bone allograft in conjunction with a vascularized fibula autograft. During the first three years of follow-up the reconstruction underwent important morphological changes. The aim of the present study was to evaluate the risk of fracture of the reconstructed proximal femur, once the physiological loads are restored, associated with a short, slow but unprotected level walk. Subject-specific finite element models of the operated femur, and of the intact contralateral one, were generated from a computed tomography exam, taken for routine clinical monitoring at month 33 of follow-up. The material properties were mapped on to the mesh and a loading condition comprising the hip joint reaction and the abductor muscle force was simulated. The risk of fracture was locally estimated, for the operated and intact femur, using the ratio between the bone tissue strength and the predicted Von Mises equivalent stress, taking into account the different behaviours of the bone tissue in tension or compression. The results showed that although the fibula grew dramatically during follow-up, the reconstructed femur had not recovered the whole mechanical strength of a normal femur. The reconstructed femoral neck seemed to be weaker than the contralateral one and hence at a higher fracture risk. However, no region reached the failure limit, so the model predicted no fracture of the femur if a short, slow but unprotected walk were allowed. The model predictions found an indirect clinical validation when the child was allowed to perform short unprotected walks and did not experience any fracture.
A preliminary hip joint simulator study of the migration of a cemented femoral stem
Authors: Liu C , Green S M , Watkins N D , Gregg P J , McCaskie A W
Published: March 2003

A hip joint simulator that can be used to evaluate the outcome of the cemented total hip replacement has been designed, manufactured and evaluated. The simulator produces motion of a cemented hip construct in the extension/flexion plane, with a socket to rotate internal/externally. At the same time a dynamic loading cycle is applied to the construct. A validation test was performed on a cemented femoral stem within a novel composite femur. The study demonstrates the value of using a hip joint simulator to evaluate the outcome of the cemented hip construct. A complex migration pattern of the cemented hip prosthesis with respect to load cycling was observed, demonstrated in vitro comparable prosthesis migration behaviour, both the stem migration and migration patterns, to that found clinically.
Clinical Breast and Pelvic Examination Requirements for Hormonal Contraception
Authors: Stewart Felicia H. , Harper Cynthia C. , Ellertson Charlotte E. , Grimes David A. , Sawaya George F. , Trussell James
Published: March 2003

Clinical breast and pelvic examinations are commonly accepted practices prior to provision of hormonal contraception. Such examinations, however, may reduce access to highly effective contraceptive methods, and may therefore increase women's overall health risks. These unnecessary requirements also involve ethical considerations and unwittingly reinforce the widely held but incorrect perception that hormonal contraceptive methods are dangerous.

This article reviews and summarizes the relevant medical literature and policy statements from major organizations active in the field of contraception. Consensus developed during the last decade supports a change in practice: hormonal contraception can safely be provided based on careful review of medical history and blood pressure measurement. For most women, no further evaluation is necessary. Pelvic and breast examinations and screening for cervical neoplasia and sexually transmitted infection, while important in their own right, do not provide information necessary for identifying women who should avoid hormonal contraceptives or who need further evaluation before making a decision about their use.
BCG Vaccination and Risk of Atopy
Authors: rause Tyra G. , Hviid Anders , Koch Anders , Friborg Jeppe , Hjuler Thomas , Wohlfahrt Jan , Olsen Ove Rosing , Kristensen Bjarne , Melbye Mads
Published: March 2003

Context

It has been suggested that BCG vaccination may protect against development of allergic diseases, particularly when given just after birth. BCG vaccination was given routinely to all infants in Greenland until 1990, when it was withdrawn from the vaccination program. Whether this resulted in an increased prevalence of atopy in children born after the stop of BCG vaccination is unknown.

Objective

To determine whether BCG vaccination and age at BCG vaccination are associated with development of atopy.

Design, Setting, and Participants

Cross-sectional study among schoolchildren aged 8 to 16 years in 4 towns on the northwest coast of Greenland. Participants had a blood sample drawn and information on BCG vaccination was obtained during 2 periods, November 1998 and November 2001. A total of 1686 children (79% of available children) participated, 1575 of whom had complete information on vaccination status. Atopy was defined as a positive test result in an assay that tests for IgE specific against the most common inhalant allergens in serum.

Main Outcome Measures

Odds ratio (OR) of atopy in BCG-vaccinated compared with unvaccinated children and OR according to age at vaccination.

Results

The risk of atopy was the same in BCG-vaccinated compared with unvaccinated children after adjustment for confounders (OR, 1.03; 95% confidence interval, 0.72-1.48). The risk of atopy in BCG-vaccinated children was not associated with age at vaccination (P = .17).

Conclusions

BCG vaccination administered to infants is not associated with reduced risk of development of atopy.
Hydrogen‐Assisted Thermal Evaporation Synthesis of ZnS Nanoribbons on a Large Scale
Authors: Jiang Y. , Meng X.‐M. , Liu J. , Xie Z.‐Y. , Lee C.‐S. , Lee S.‐T.
Published: March 2003

Semiconductor nanoribbons of ZnS have been synthesized on a large scale via hydrogen‐assisted thermal evaporation. The product is characterized by means of electron microscopy and energy‐dispersive X‐ray spectroscopy, which show that the as‐prepared ZnS nanoribbons are single crystals with uniform morphology. A stable and strong emission band centered at 534.5 nm is also associated with the nanoribbons.
Selective Dewetting for General Purpose Patterning
Authors: Kim Y.S. , Lee H.H.
Published: March 2003

General purpose patterning based on selective dewetting with an elastomeric mold is described. Several well‐defined nanostructures obtained by this method are presented (see Figure for an example). Unlike other patterning techniques, the same mold can be used to generate features ranging in size from the nanometer to the micrometer, simply by changing the duration of dewetting.
Formation of Silver Nanowires Through a Sandwiched Reduction Process
Authors: Xiong Y. , Xie Y. , Wu C. , Yang J. , Li Z. , Xu F.
Published: March 2003

A polymer‐surfactant‐assisted sandwiched reduction route to silver nanowires is described based on the sandwich organometallic compound (η5‐C5H5)2Fe, in which there is obvious steric hindrance when the iron atoms reduce silver cations to elemental silver (see Figure), leading to a preferred direction. The formation of nanowires occurs in a layered solution with the assistance of poly(ethylene glycol).
Fatal Bacillus cereus sepsis following resolving neutropenic enterocolitis during the treatment of acute leukemia
Authors: Ginsburg Amy S. , Salazar Lupe G. , True Lawrence D. , Disis Mary L.
Published: March 2003

Bacillus cereus is increasingly being acknowledged as a serious bacterial pathogen in immunosuppressed hosts. We report a case of fatal B. cereus sepsis in a patient with newly diagnosed acute leukemia following resolving neutropenic enterocolitis. Gastrointestinal complaints are common during induction chemotherapy, yet some antimicrobial coverage suitable for generalized neutropenia is not optimal for the eradication of B. cereus. This case demonstrates that, in the neutropenic patient with gastrointestinal complaints or in the setting of resolving neutropenic enterocolitis, it is important to anticipate possible B. cereus infection and sepsis. Am. J. Hematol. 72:204–208, 2003. © 2003 Wiley‐Liss, Inc.
Alterations in sensitivity to calcium and enzymatic hydrolysis of membranes from sickle cell disease and trait erythrocytes
Authors: Judd Allan M. , Best Katrina B. , Christensen Kathrine , Rodgers George M. , Bell John D.
Published: March 2003

Normally, human erythrocytes display several responses to elevated intracellular calcium levels. These include a shape transition from discocyte to spherocyte, shedding of microvesicles into the extracellular fluid, and enhanced susceptibility to the hydrolytic action of secretory phospholipase A2. These responses to elevated intracellular calcium were all blunted in erythrocytes containing hemoglobin S. The reduction of both the shape transition and the shedding of microvesicles were greater than the impairment of phospholipase susceptibility, and both correlated strongly with the intracellular content of hemoglobin S. In contrast to the response to elevated intracellular calcium, erythrocytes containing hemoglobin S displayed a 2.5‐fold increase in basal susceptibility to phospholipase A2 compared to control erythrocytes in the absence of ionophore. The effect was more prominent among samples from patients heterozygous for hemoglobin S than in samples from homozygous individuals. These results reveal additional abnormalities in the membranes of sickle cell erythrocytes beyond those described previously and demonstrate that red blood cells from both heterozygous and homozygous are affected. Furthermore, they suggest a possible means by which sickle cell disease and trait patients may display enhanced vulnerability to inflammatory stimuli. Am. J. Hematol. 72:162–169, 2003. © 2003 Wiley‐Liss, Inc.
Tumor lysis syndrome (TLS) following fludarabine therapy for chronic lymphocytic leukemia (CLL): Case report and review of the literature
Authors: Hussain Kashif , Mazza Joseph J. , Clouse Lawrence H.
Published: March 2003

Adenosine deaminase inhibitors have proven superior to alkylating agent‐based therapies in inducing clinical and hematologic remissions in treated and previously untreated chronic lymphocytic leukemia (CLL) patients, and they have become increasingly accepted as a standard for therapy. We report the case of a 66‐year‐old patient with a 7‐year history of CLL who had been previously treated with alkylating agents. Upon presentation with abdominal lymphadenopathy, a 5‐day course of the nucleoside analogue, fludarabine, was administered. Two days after completion, the patient developed acute tumor lysis syndrome (TLS) that induced renal failure with hyperkalemia and hyperuricemia. This resulted in critical, life‐threatening complications requiring hospitalization, aggressive hemodialysis and fluid replacement therapy. While only 5 other cases of TLS associated with fludarabine therapy have been reported since 1989, we recommend that adenosine deaminase inhibitor therapy be initiated with the addition of allopurinol, and that hydration with copious amounts of oral fluids during therapy be encouraged in order to help protect against the renal effects of potential TLS induced by these agents. Am. J. Hematol. 72:212–215, 2003. © 2003 Wiley‐Liss, Inc.
HIV‐Related Hodgkin's disease with central nervous system involvement and association with Epstein‐Barr virus
Authors: Massarweh Suleiman , Udden Mark M. , Shahab Imran , Kroll Michael , Sears David A. , Lynch Garrett R. , Teh Bin S. , Lu Hsin H.
Published: March 2003

Central nervous system (CNS) involvement is a rare occurrence in the course of human immunodeficiency virus (HIV)‐related Hodgkin's disease (HD). We report the clinical course of a patient with HIV infection who developed systemic HD, mixed cellularity subtype, later complicated by leptomeningeal involvement. The patient died from his illness, and autopsy was performed. Examining the brain lesion, Epstein‐Barr virus (EBV) presence was demonstrated in Reed‐Sternberg cells by immunohistochemistry using an EBER probe for EBV RNA. This is the second case report in the English literature of HD involving the CNS in an HIV‐positive individual, and the first demonstrating EBV presence. Extranodal presence of Hodgkin's disease in patients with HIV infection is probably related to immunosuppression, and physicians treating this illness should be alert to the potential of unusual sites of involvement. Am. J. Hematol. 72:216–219, 2003. © 2003 Wiley‐Liss, Inc.
Childhood overweight problem in a selected school district in Hawaii
Authors: Chai Dennis , Kaluhiokalani Norman , Little James , Hetzler Ronald , Zhang Shuqiang , Mikami Judy , Ho Kwok
Published: March 2003

Anthropometric measurements were collected from 1,437 public school students in a selected school district in Hawaii every year from 1992 to 1996. Results showed that boys and girls of Hawaiian ancestry (HA) are generally taller in stature and somewhat heavier in weight than their non‐Hawaiian counterparts (Non‐HA). Also, there are no clear differences between the two groups in BMI, sums of skinfolds, waist and hip circumferences, and waist/hip circumference ratios. When compared to data from NHANES III (Centers for Disease Control and Prevention), the median statures of HA boys and girls are very close to the median statures of NHANES III, but the body weights of HA are heavier at most ages. Also, the BMI values of HA are distinctly higher and their medians are closer to the 75th percentile of NHANES III. In addition, the values of the sums of skinfolds and the waist and hip circumferences of HA are also higher at most ages than NHANES III. These multiple anthropometric indicators suggest that there might be more overweight children and adolescents of HA. When compared to the statistics in NHANES III, there are twice as many HA and Non‐HA boys and girls classified as obese. Clearly, a serious childhood problem exists among the children in this selected school district in Hawaii. More research is needed in other school districts in Hawaii. Also, it is suggested in this study that using multiple anthropometric indicators, rather than a single one, may be more accurate and appropriate in determining overweight problems in a youth population. Am. J. Hum. Biol. 15:164–177, 2003. © 2003 Wiley‐Liss, Inc.
Novel missense mutations and a 288‐bp exonic insertion in PAX9 in families with autosomal dominant hypodontia
Authors: Das Parimal , Hai Mehreen , Elcock Claire , Leal Suzanne M. , Brown Donald T. , Brook Alan H. , Patel Pragna I.
Published: March 2003

We describe the molecular analysis of three families with hypodontia involving primarily molar teeth and report two novel mutational mechanisms. Linkage analysis of two large families revealed that the hypodontia was linked to the PAX9 locus. These two families revealed missense mutations consisting of a glutamic acid substitution for lysine and a proline substitution for leucine within the paired domain of PAX9. A pair of identical twins affected with hypodontia in a third family demonstrated a 288‐bp insertion within exon 2 that resulted in a putative frameshift mutation and a premature stop codon. The insertion was associated with the loss of 7‐bp from exon 2. A block of 256‐bp of sequence within the insertion was completely identical to downstream sequence from the second intron of the PAX9 gene. These studies extend the spectrum of mutations in PAX9 associated with hypodontia to include heretofore undescribed categories, including missense mutations. © 2003 Wiley‐Liss, Inc.
Rapid detection of 17p11.2 rearrangements by FISH without cell culture (direct FISH, DFISH): A prospective study of 130 patients with inherited peripheral neuropathies
Authors: Ravisé Nicole , Dubourg Odile , Tardieu Sandrine , Aurias Françoise , Mercadiel Monique , Coullin Philippe , Ruberg Merle , Catala Martin , Lesourd Sylvie , Brice Alexis , LeGuern Eric
Published: March 2003

Charcot‐Marie‐Tooth (CMT) disease and hereditary neuropathy with pressure palsies (HNPP) are two frequent hereditary motor and sensory neuropathies. CMT is characterized by slowly progressive weakness and atrophy, primarily in peroneal and distal leg muscles. The most frequent form, CMT1A, is due, in most cases, to the duplication of a 1.5 Mb region on chromosome 17p11.2 containing the peripheral myelin protein 22 gene (PMP22). The phenotype seems to result from dosage of the PMP22 gene. This hypothesis is reinforced by the existence of HNPP, which is clinically characterized by various recurrent truncular palsies or sensory loss precipitated by minor trauma, which is caused by deletion of the same 1.5 Mb region in 17p11.2. In clinical practice, the detection of the duplication or the deletion in 17p11.2, which permits a positive diagnosis, is still performed by time consuming methods (Southern blot or various combinations of molecular tools). We developed a method for the rapid detection of 17p11.2 rearrangements, using “direct FISH” and PRINS analyses, which does not require cell culture. In a prospective study of 92 patients with CMT and 38 with suspected HNPP, we compared this new technique to classical strategies like Southern blot. The results demonstrate the high sensitivity and specificity of the new FISH technique for the diagnosis of CMT1A and HNPP. Moreover, because of its simplicity and rapidity, this technique provides a useful alternative to the molecular approaches that have been used to diagnose segmental aneusomies, especially in the case of duplications that often go undetected. © 2003 Wiley‐Liss, Inc.
Variation in the coding sequence and flanking splice junctions of the estrogen receptor alpha (ERα) gene does not play an important role in genetic susceptibility to bipolar disorder or bipolar affective puerperal psychosis
Authors: Middle Fiona , Jones Ian , Robertson Emma , Morey Jaime , Lendon Corinne , Craddock Nick
Published: March 2003

Genes involved in estrogen pathways have been proposed as possible candidates influencing susceptibility to bipolar disorder and the affective symptoms suffered by many women during the puerperal period. The estrogen receptor alpha (ERα) gene in particular has been a subject of interest and has recently been intensively screened for variations of potential relevance to psychiatric disorders, resulting in the identification of four mutations in individuals with bipolar disorder or puerperal psychosis. We have examined the frequency of these four ERα variations in a case control study using a group of mixed gender bipolar individuals (N = 231), further classified into subsets of parous bipolar females with (N = 112) and without (N = 50) puerperal psychosis, and a non‐psychiatric comparison group (N = 110). We have also investigated the families in which the variations were initially detected, for evidence of co‐segregation of the variants with mood disorder. We found no evidence in our case control sample to support the involvement of any of the ERα variations in either the aetiology of bipolar disorder or puerperal triggering of bipolar episodes. Nor did we find co‐segregation of ERα variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the ERα gene does not play an important pathogenic role in the majority of cases of Bipolar Disorder or Bipolar Affective Puerperal Psychosis. © 2003 Wiley‐Liss, Inc.
Gender‐specific molecular heterosis and association studies: Dopamine D2 receptor gene and smoking
Authors: Lee Hong‐Seock
Published: March 2003

If the concept of the gender‐specific molecular heterosis is not considered and tested, incorrect conclusions would easily be drawn in association studies. Therein, heterosis and its gender effect in the genetic effect of DRD2 gene for smoking were examined with 187 healthy Korean individuals. The male smokers showed a higher A1 allele frequency (P = 0.016) and prevalence (P = 0.049) than those of the male non‐smokers, and the female smokers showed a lower frequency of heterozygotes (P = 0.018) than the female non‐smokers. However, the association of DRD2 gene with smoking found in each gender disappeared when both males and females were considered as one group because of the opposite genetic effect of DRD2 gene for smoking: (1) while 75% of heterozygotes males were smokers, only 22% of female heterozygotes were; (2) males showed an excess of heterozygotes and the deviation from Hardy‐Weinberg expectations in smokers, while these were true in the female non‐smokers; and (3) in non‐smokers, females were different from the males exhibiting a significantly higher prevalence (P = 0.005) and frequency (P = 0.015) of A1 allele, and significantly different genotype (P = 0.017) distribution, and higher frequency of heterozygotes (P = 0.055). Meanwhile, in smokers, males showed higher frequency of heterozygotes (P = 0.019) compared to females. The results indicate that gender‐specific molecular heterosis at DRD2 gene for smoking is also applicable in healthy individuals as well as schizophrenics. Moreover, this concept has general applicability to other candidate genes and biological phenotypes. © 2003 Wiley‐Liss, Inc.
Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia
Authors: Iwayama‐Shigeno Yoshimi , Yamada Kazuo , Toyota Tomoko , Shimizu Hiromitsu , Hattori Eiji , Yoshitsugu Kiyoshi , Fujisawa Tetsuya , Yoshida Yukako , Kobayashi Toshio , Toru Michio , Kurumaji Akeo , Detera‐Wadleigh Sevilla , Yoshikawa Takeo
Published: March 2003

Dysregulation in dopaminergic neurotransmission might play a role in the pathogenesis of schizophrenia, and therefore genetic components of the dopamine (DA) pathway may confer risk. The NR4A2 (Nurr1) gene is essential for the development and maintenance of mesencephalic DA‐synthesizing neurons. Moreover, Nurr1 forms a heterodimer with the retinoid X receptor and disturbances in the retinoid‐signaling cascade may be involved in susceptibility to schizophrenia. To investigate the potential genetic contribution of NR4A2, we performed a case‐control association study using three common variants in the gene [−2922(C)2‐3, IVS6 + 17∼+18insG, EX8 + 657(CA)9‐10] that were in strong linkage disequilibrium with each other. We did not detect a significant allelic or genotypic association. Haplotypes derived from all three polymorphisms generated similar results. These data do not support the notion that the NR4A2 gene plays a major role in risk for schizophrenia among Japanese individuals. © 2003 Wiley‐Liss, Inc.
Linkage mapping of beta 2 EEG waves via non‐parametric regression
Authors: Ghosh Saurabh , Begleiter Henri , Porjesz Bernice , Chorlian David B. , Edenberg Howard J. , Foroud Tatiana , Goate Alison , Reich Theodore
Published: March 2003

Parametric linkage methods for analyzing quantitative trait loci are sensitive to violations in trait distributional assumptions. Non‐parametric methods are relatively more robust. In this article, we modify the non‐parametric regression procedure proposed by Ghosh and Majumder [2000: Am J Hum Genet 66:1046–1061] to map Beta 2 EEG waves using genome‐wide data generated in the COGA project. Significant linkage findings are obtained on chromosomes 1, 4, 5, and 15 with findings at multiple regions on chromosomes 4 and 15. We analyze the data both with and without incorporating alcoholism as a covariate. We also test for epistatic interactions between regions of the genome exhibiting significant linkage with the EEG phenotypes and find evidence of epistatic interactions between a region each on chromosome 1 and chromosome 4 with one region on chromosome 15. While regressing out the effect of alcoholism does not affect the linkage findings, the epistatic interactions become statistically insignificant. © 2003 Wiley‐Liss, Inc.
Association analysis of the HOPA12bp polymorphism in schizophrenia and manic depressive illness
Authors: Kirov George , Georgieva Ludmila , Nikolov Ivan , Zammit Stan , Jones Gaynor , Poriazova Nadezhda , Tolev Todor , Owen Richard , Jones Sue , Owen Michael J.
Published: March 2003

Variations in exon 42 of the HOPA (human opposite paired) gene have been associated with mental retardation, hypothyroidism and psychiatric disorders. We attempted to replicate the association with schizophrenia using 309 parent‐offspring trios from Bulgaria and 367 unrelated cases and 368 blood donors from the UK. We also tested 125 bipolar trios from Bulgaria, 112 bipolar trios from the UK and a sample of 178 unrelated bipolar cases and 188 blood donors from the UK. The frequency of HOPA12bp in the 556 UK blood donors was 2.6% and it was not significantly different in the UK patients groups, where it ranged from 1.2 to 3.8%. Sixteen mothers transmitted the HOPA12bp allele to schizophrenic offspring, while 12 did not transmit, a non‐significant difference. There was a trend for under‐transmission of the rare allele to bipolar patients (T/NT = 4/10) and they had a lower rate of that allele than schizophrenic patients in the Bulgarian population (1% vs. 4.2%, P = 0.043). However the two diagnostic groups had similar allele frequencies in the UK populations: 2% versus 2.6%, P = 0.6. We conclude that the HOPA polymorphism is unlikely to be a major risk factor in the pathogenesis of these major psychiatric disorders although there could be a small effect in schizophrenia. © 2003 Wiley‐Liss, Inc.
Enhanced production of amyloid precursor protein mRNA by peripheral mononuclear blood cell in Alzheimer's disease
Authors: Jiang Sanduo , Zhang Mingyuan , Ren Daming , Tang Guomei , Lin Sicui , Qian Yiping , Zhang Ye , Jiang Kaida , Li Fei , Wang Dongxiang
Published: March 2003

Previous studies have suggested the involvement of amyloid precursor protein (APP) in Alzheimer's disease (AD), as exons 16 and 17 of the APP gene mutations have been found in some familial AD patients. Furthermore, overexpression and deposition of the beta amyloid peptide, a proteolytic product of APP, have been considered as a pathological hallmark of Alzheimer's disease. Therefore, it is of particular interest to determine the expression of APP gene at the transcription level for better understanding of the roles of APP gene in AD pathogenesis. In this work, we employed the quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) to quantify APP mRNA transcripts in the peripheral mononuclear blood cells (PMBC) of 52 Alzheimer's patients, 28 vascular dementia (VD) patients, and 60 healthy elderly controls. The results showed that the amount (mean ± SEM) of APP transcripts per microgram of total cDNA was 4.05 ± 0.27, 2.73 ± 0.33, and 2.59 ± 0.27 amole in AD, VD, and healthy controls, respectively. There was a significant increase (P < 0.05) in the expression of APP mRNA transcripts in AD compared with that in VD or in healthy controls. Thus, our data indicated that variation of APP gene expression in PMBC might be a pathogenic source of Alzheimer's disease. © 2003 Wiley‐Liss, Inc.
Ranging behavior and foraging ecology of lowland woolly monkeys (Lagothrix lagotricha poeppigii) in Yasuní National Park, Ecuador
Authors: Fiore Anthony Di
Published: March 2003

In a year‐long study, I investigated the ranging behavior of lowland woolly monkeys (Lagothrix lagotricha poeppigii) in a terra firma rainforest in Yasuní National Park, Ecuador, and examined the relationship between ranging, diet, food availability, and food patch use for this population. In Yasuní the total home range sizes for two social groups were 124 and 108 ha, which are much smaller than has been reported previously for Lagothrix elsewhere in its geographic distribution. The mean yearly day range estimates for these same groups were 1,792 m and 1,878 m, which are well within the range of variation previously reported. Ranging behavior was not correlated with the current habitat‐wide abundance of ripe fruit, which comprises 76.3% of the yearly diet for this population, but was associated with one measure of likely insect prey abundance and with the availability of immature fruits, a minimal part of the diet. Specifically, one study group moved significantly greater distances during months of high likely insect prey abundance and when immature fruits were abundant. The second study group also traveled farther when likely insect prey abundance was high and when immature fruits were abundant, although the latter relationship only approached significance. This group also devoted significantly more of its daily activity budget to travel during these times. These results indicate that variation in ripe fruit abundance makes no meaningful contribution to explaining variation in ranging behavior for this population of woolly monkeys. Instead, the results raise the possibility that some aspects of the ranging behavior of frugivorous primates may be related to the availability of alternative food sources, such as animal prey, or to monitoring the phenological status of important fruit trees, rather than simply reflecting the degree of intragroup feeding competition. Am. J. Primatol. 59:47–66, 2003. © 2003 Wiley‐Liss, Inc.
Dynamic plantar pressure distribution during terrestrial locomotion of bonobos (Pan paniscus)
Authors: Vereecke Evie , D'Août Kristiaan , De Clercq Dirk , Van Elsacker Linda , Aerts Peter
Published: March 2003

We collected high‐resolution plantar pressure distributions of seven bonobos during terrestrial bipedal and quadrupedal locomotion (N = 146). Functional foot length, degree of hallux abduction, and total contact time were determined, and plots, showing pressure as a function of time for six different foot regions, were generated. We also studied five adult humans for comparison (N = 13). Both locomotion types of the bonobo show a large variation in plantar pressure distributions, which could be due to the interference of instantaneous behavior with locomotion and differences in walking speed and body dimensions. The heel and the lateral midfoot typically touch down simultaneously at initial ground contact in bipedal and quadrupedal walking of bonobos, in contrast with the typical heel‐strike of human bipedalism. The center of pressure follows a curved course during quadrupedalism, as a consequence of the medial weight transfer during mid‐stance. Bipedal locomotion of bonobos is characterized by a more plantar positioning of the feet and by a shorter contact time than during quadrupedal walking, according to a smaller stride and step length at a higher frequency. We observed a varus position of the foot with an abducted hallux, which likely possesses an important sustaining and stabilizing function during terrestrial locomotion. Am J Phys Anthropol 120:373–383, 2003. © 2003 Wiley‐Liss, Inc.
Titelbild: Molecular Mousetraps: Gas‐Phase Studies of the Covalent Coupling of Noncovalent Complexes Initiated by Reactive Carbenes Formed by Controlled Activation of Diazo Precursors (Angew. Chem. 9/2003)
Authors: Julian Ryan R. , May Jeremy A. , Stoltz Brian M. , Beauchamp J. L.
Published: March 2003

Molekulare Mausefallen sind eine beispiellose Klasse von Wirt‐Gast‐Verbindungen. Der im Titelbild gezeigte [18]Krone‐6‐Ether wird als “Köder” für Zielmoleküle mit einer protonierten primären Aminogruppe verwendet. Aktivierung des nichtkovalenten Komplexes lässt die “Diazofalle” unter Verknüpfung der beiden Moleküle zuschnappen. Mehr dazu finden Sie in der Zuschrift von J. L. Beauchamp und B. M. Stoltz et al. auf S. 1042 ff.
Efficient Degradation of Organic Pollutants by Using Dioxygen Activated by Resin‐Exchanged Iron(II) Bipyridine under Visible Irradiation
Authors: Ma Wanhong , Li Jing , Tao Xia , He Ju , Xu Yiming , Yu Jimmy C. , Zhao Jincai
Published: March 2003

Excellent response to visible light is shown by the [FeII(bpy)3]–amberlite photocatalyst, which can effectively activate molecular oxygen in such a way as to put us one giant step nearer to our goal—the development of the ultimate green technology for decontamination [Eq. (1)].