bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families
Authors: Wang Xu , Xiao Fuying , Yang Qinbo , Liang Bo , Tang Zhaohui , Jiang Linbin , Zhu Qihui , Chang Wei , Jiang Jiuxi , Jiang Chuanming , Ren Xiang , Liu Jing‐Yu , Wang Qing K. , Liu Mugen 
Published: August 2006

AbstractProximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints and fusion of carpal and tarsal bones. We identified and characterized two five‐generation Chinese families with SYM1. The two families share some similarities (e.g., osseous fusion of interphalangeal joints of the 2–4 fingers) with SYM1 families with mutations in the NOG gene or the family with mutation R438L recently reported in the GDF5 gene (encoding a bone morphogenetic protein family member). However, they show some unique features including the absence of cuboid bone, the lack of shortness of the first and fifth metacarpal bones, and manifestation of flat feet. Genome‐wide linkage analysis of the two families mapped the disease gene to marker D20S112 with a combined LOD score of 4.32. Mutational analysis revealed a novel E491K mutation in the GDF5 gene in both families. The mutation occurs at a highly conserved residue in the TGF‐β domain of GDF5 and represents the second GDF5 mutation identified for SYM1 to date. The E491K mutation co‐segregated with the affected individuals in the two families, and did not exist in unaffected family members or 200 normal controls. These results indicate that defects in GDF5 can cause SYM1 in the Chinese population, and expand the spectrum of clinical phenotypes associated with mutant GDF5. © 2006 Wiley‐Liss, Inc.
Sedaghatian spondylometaphyseal dysplasia with pachygyria and absence of the corpus callosum
Authors: English Sharon J. , Gayatri Neti , Arthur Rosemary , Crow Yanick J. 
Published: August 2006

AbstractWe report on a female infant with a metaphyseal dysplasia and a neuronal migration abnormality consistent with a diagnosis of Sedaghatian spondylometaphyseal dysplasia. This child, born to nonconsanguineous Caucasian parents, was hypotonic from birth and experienced recurrent cyanotic episodes within a few hours of delivery. Cerebral imaging revealed absence of the corpus callosum and marked frontotemporal pachygyria. She developed seizures on day 14 of life and died at the age of 17 days. Our case highlights the possibility for neuronal migration abnormalities in Sedaghatian spondylometaphyseal dysplasia and suggests a novel association of the disorder with agenesis of the corpus callosum. © 2006 Wiley‐Liss, Inc.
Anophthalmia‐esophageal atresia syndrome caused by an SOX2 gene deletion in monozygotic twin brothers with markedly discordant phenotypes
Authors: Zenteno Juan Carlos , Perez‐Cano Hector J. , Aguinaga Monica 
Published: August 2006

AbstractThe clinical combination of anophthalmia/microphthalmia and esophageal atresia was first recognized in 1988 as a distinct variable multi‐system malformation syndrome and since then at least 17 cases of the disease have been described, all of them sporadic in occurrence. We report a heterozygous SOX2 gene mutation underlying the syndrome of anophthalmia/microphthalmia‐esophageal atresia and demonstrate that this entity can be associated to considerable clinical variability as shown by the discordant ocular phenotype observed in monozygotic twin brothers carrying an SOX2 deletion. This is the first report describing a strikingly discordant eye phenotype in monozygotic twins with the condition, with one of our patients being the first reported individual carrying an SOX2 lesion associated with unilateral eye defect. We discuss the probable sources for this remarkable phenotypic heterogeneity of the anophthalmia/microphthalmia syndrome in individuals with an identical genetic constitution. © 2006 Wiley‐Liss, Inc.
A father of four consecutive trisomic pregnancies with elevated frequencies of associated aneuploid sperm
Authors: Tomascik‐Cheeseman Lisa M. , Lowe Xiu R. , Eskenazi Brenda , Kidd Sharon , Nath Joginder , Moore Dan , Wyrobek Andrew J. 
Published: August 2006

AbstractA couple with normal somatic karyotypes had four consecutive trisomic pregnancies, each involving a different chromosome, of which two children were liveborn with confirmed paternal‐origin trisomies. The apparently healthy father produced abnormally high frequencies of disomic sperm for each of the four chromosomes involved in the trisomic pregnancies (P< 0.003, by sperm fluorescence in situ hybridization (FISH)). His elevated sperm aneuploidies persisted over a 2‐year period and affected all chromosomes evaluated, suggesting that he had a genome‐wide defect in meiotic disjunction. He also had the highest frequencies of aneuploid sperm reported for any healthy man to date. His frequencies of aneuploid sperm were comparable to the peak frequencies of the transient responses reported in some cancer patients after receiving aneugenic chemotherapies. These findings indicate that apparently healthy men can produce abnormally high frequencies of sperm aneuploidies that suggest that this condition may contribute to recurrent trisomic pregnancies. © 2006 Wiley‐Liss, Inc.
A novel 8.5 MB dup(1)(p34.1p34.3) characterized by FISH in a child presenting with congenital heart defect and dysmorphic features
Authors: Lennon P.A. , Boerkoel C.F. , Plunkett K. , Soukam S. , Cheung S.W. , Patel A. 
Published: August 2006

AbstractChromosome duplications involving 1p are rarely reported but are apparently associated with short survival as well as congenital malformations and impaired development. Several of these have had congenital heart defects, although too few patients have been reported with similar breakpoints to characterize a syndrome. We present a girl with a novel interstitial duplication in the short arm of chromosome 1 [46,XX,dup(1)(p34.1p34.3)]. She presented with congenital heart defects at 1 month and by 1 year of age manifested delayed acquisition of motor milestones and subsequently of language milestones. By breakpoint‐mapping using FISH analysis, we determined that her 1p duplication spans 8.5 megabases. Her 1p duplication is the smallest reported to date to contain 1p34 in patients with congenital heart defect due to abnormalities of heart looping during development. Thus, her 8.5 MB duplication provides a target region to search for a potentially dosage‐sensitive gene(s) causing abnormal heart looping when duplicated. Two patients have been reported with duplication including 1p34 but without congenital heart defect, and their duplications span all but the distal approximately 2 MB segment duplicated in our patient. Thus, within our patient's 8.5 MB target region for a dosage sensitive gene leading to looping abnormalities (and thereby congenital heart defect), the distal 2 MB region might well be the region to begin the search. © 2006 Wiley‐Liss, Inc.
Major feeding difficulties in the first reported case of interstitial 20q11.22‐q12 microdeletion and molecular cytogenetic characterization
Authors: Callier P. , Faivre L. , Marle N. , Thauvin‐Robinet C. , Sanlaville D. , Gosset P. , Prieur M. , Labenne M. , Huet F. , Mugneret F. 
Published: August 2006

AbstractWe report on a 4‐year‐old female presenting with intrauterine growth retardation, facial dysmorphic features, major feeding difficulties with severe diarrhea and vomiting, mental retardation with abnormal behavior and hypertonia. Feeding difficulties were the most invalidating features with absent oral intake requiring persistent enteral feeding. Standard cytogenetic studies were normal, but high‐resolution chromosome analyses revealed a small de novo interstitial deletion of the long arm of chromosome 20, 46,XX,del(20)(q11.21q12). The deletion was confirmed using metaphase comparative genomic hybridization (CGH) and multicolor high resolution banding (mBAND). The deletion breakpoints were characterized using FISH analyses with YACs, PACs, and BACs clones located in the deleted and adjacent regions. A 6.6‐Mb deleted region between markers D20S815 (20q11.22) and D20S435 (20q12) could be delineated. None of the nine previously reported cases with interstitial 20q deletion found in the literature involve the same breakpoints. This report further emphasizes the indication of high‐resolution chromosome analyses in children with syndromic mental retardation. The description of additional cases would be useful in order to better characterize the phenotype of patients with proximal interstitial 20q deletion. © 2006 Wiley‐Liss, Inc.
Vascular localization and proliferation in the growing tip of the deer antler
Authors: Clark Dawn E. , Li Chunyi , Wang Wenying , Martin Shirley K. , Suttie James M. 
Published: August 2006

AbstractThe process of angiogenesis is of interest because of the significant clinical benefits associated with controlling vascular growth. Within the antler, chondrogenesis and antler elongation are occurring at the rate of 1–2 cm per day and thus blood vessels are growing at this same rapid pace. We demonstrate that the process of angiogenesis in the antler is controlled at various tissue locations. The findings clearly differentiate the spatial location of the stem cells that drive chondrogenesis from the proliferation process driving the angiogenesis. Vessels within the lateral dermis contained BrdU‐positive cells, suggesting that these vessels were elongating. Within the precartilage region, proliferating vessels were detected in bundles of complex structure evenly distributed throughout this tissue layer. The support cells within these bundles of vessels were detected by staining with α‐smooth muscle actin, while the endothelial cells were negative. Additionally, the α‐smooth muscle actin staining was found in association with the cartilage cells of the antler. The marked proliferation of the vascular associated cells in the precartilage region identified this area as a major region of vascular growth in the antler. We propose that within the precartilage region, the most likely mechanisms to explain the observed vascular morphology are that of vascular extension of the existing vessels and intussusceptive angiogenesis or sprouting to generate the small bundles of vessels. Anat Rec Part A, 288A:973–981, 2006. © 2006 Wiley‐Liss, Inc.
Vascular patterning of the quail coronary system during development
Authors: Tomanek Robert J. , Hansen Heidi K. , Dedkov Eduard I. 
Published: August 2006

AbstractRecent studies have provided insights into specific events that contribute to vasculogenesis and angiogenesis in the developing coronary vasculature. This study focused on the developmental progression of coronary vascularization beginning with tube formation and ending with the establishment of a coronary arterial tree. We used electron microscopy, histology of serial sections, and immunohistochemistry in order to provide a comprehensive view of coronary vessel formation during the embryonic and fetal periods of the quail heart, a species that has been used in a number of studies addressing myocardial vascularization. Our data reveal features of progenitor cells and blood islands, tubular formation, and the anatomical relationship of a transformed periarterial tubular network and sympathetic ganglia to the emergence and branching of the right and left coronary arteries. We have traced the pattern of coronary artery branching and documented its innervation. Finally, our data include the relationship of fibronectin, laminin, and apoptosis to coronary artery growth. Our findings bring together morphological events that occur over the embryonic and fetal periods and provide a baseline for studies into the mechanisms that regulate the various events that occur during these time periods. Anat Rec Part A, 288A:989–999, 2006. © 2006 Wiley‐Liss, Inc.
General organization of the perinatal and adult accessory olfactory bulb in mice
Authors: Salazar Ignacio , Sanchez‐Quinteiro Pablo , Cifuentes Jose Manuel , De Troconiz Patricia Fernandez 
Published: August 2006

AbstractThe vomeronasal system is currently a topical issue since the dual functional specificity, vomeronasal system‐pheromones, has recently been questioned. Irrespective of the tools used to put such specificity in doubt, the diversity of the anatomy of the system itself in the animal kingdom is probably of more importance than has previously been considered. It has to be pointed out that a true vomeronasal system is integrated by the vomeronasal organ, the accessory olfactory bulb, and the so‐called vomeronasal amygdala. Therefore, it seems reasonable to establish the corresponding differences between a well‐developed vomeronasal system and other areas of the nasal cavity in which putative olfactory receptors, perhaps present in other kinds of mammals, may be able to detect pheromones and to process them. In consequence, a solid pattern for one such system in one particular species needs to be chosen. Here we report on an analysis of the general morphological characteristics of the accessory olfactory bulb in mice, a species commonly used in the study of the vomeronasal system, during growth and in adults. Our results indicate that the critical period for the formation of this structure comprises the stages between the first and the fifth day after birth, when the stratification of the bulb, the peculiarities of each type of cell, and the final building of glomeruli are completed. In addition, our data suggest that the conventional plexiform layers of the main olfactory bulb are not present in the accessory bulb. Anat Rec Part A, 288A:1009–1025, 2006. © 2006 Wiley‐Liss, Inc.
Cardiac outflow tract: A review of some embryogenetic aspects of the conotruncal region of the heart
Authors: Restivo Angelo , Piacentini Gerardo , Placidi Silvia , Saffirio Claudia , Marino Bruno 
Published: August 2006

AbstractA review concerning some embryogenetic aspects of the cardiac outflow tract is presented. Two main topics are discussed: the truncal septation and the secondary heart field. In the context of the septation of the truncus arteriosus, the development of the arterial valves is largely discussed, particularly in reference to the sinuses of Valsalva. Emphasis is also given to the fate of the external myocardial wall of the truncus arteriosus, as this primordial myocardial surface disappears later in the development. Molecular genetics data concerning Sox4 and NF‐Atc transcription factors are correlated in the present review with rare forms of truncus malformations encountered in human pathology. The roles exerted by the secondary heart field and the neural crest on the development and growth of the conotruncal musculature are largely discussed. Reported experimental ablations of both secondary heart field and neural crest, showed conotruncal defects such as persistent truncus arteriosus, tetralogy of Fallot, and double‐outlet right ventricle, which were considered as the result of a short outflow tract causing, ultimately, a lack of conotruncal rotation. In this regard, some morphologic correlations are carried out, in the present review, between these experimental animal models and human malformations, and it is thought that this sort of conotruncal defects cannot be explained always in terms of conotruncal hypoplasia. Finally, influence of Pitx2c, a left‐right laterality signaling gene, on the modulation of the conotruncal rotation, as most recently reported, is emphasized in terms of very likely multifactorial contributions in the embryogenesis of the conotruncal region of the heart. Anat Rec Part A, 288A:936–943, 2006. © 2006 Wiley‐Liss, Inc.
Tryptamine induces cell death with ultrastructural features of autophagy in neurons and glia: Possible relevance for neurodegenerative disorders
Authors: Herrera Federico , Martin Vanesa , Carrera Pilar , García‐Santos Guillermo , Rodriguez‐Blanco Jezabel , Rodriguez Carmen , Antolín Isaac 
Published: August 2006

AbstractTryptamine derivatives are a family of biogenic amines that have been suggested to be modulators of brain function at physiological concentrations. However, pharmacological concentrations of these amines display amphetamine‐like properties, and they seem to play a role in brain disorders. Amphetamines induce autophagy in nerve cells, and this type of cell death has also been involved in neurodegenerative diseases. In the present work, we clearly demonstrate for the very first time that high concentrations of tryptamine (0.1–1 mM) induce autophagy in HT22 and SK‐N‐SH nerve cell lines and in primary cultures of astrocytes, glial cells being less sensitive than neurons. Ultrastructural cell morphology shows all of the typical hallmarks of autophagy. There is no nuclear chromatin condensation, endoplasmic reticulum and mitochondria are swollen, and a great number of double‐membraned autophagosomes and residual bodies can be shown in the cytoplasm. Autophagosomes and residual bodies contain mitochondria, membranes, and vesicles and remain unabridged until the cell membrane is disrupted and the cell dies. The same results have been found when cells were incubated with high concentrations of 5‐methoxytryptamine (0.1–1 mM). Our results establish a possible link between the role of tryptamine derivatives in brain disorders and the presence of autophagic cell death in these kinds of disorders. Anat Rec Part A, 288A:1026–1030, 2006. © 2006 Wiley‐Liss, Inc.
Regional differences in architecture and mineralization of developing mandibular bone
Authors: Mulder Lars , van Groningen Linde B. , Potgieser Yvonne A. , Koolstra Jan Harm , van Eijden Theo M.G.J. 
Published: August 2006

AbstractThe goal of this study was to investigate the mutual relationship between architecture and mineralization during early development of the pig mandible. These factors are considered to define the balance between the requirements for bone growth on the one hand and for load bearing on the other. Architecture and mineralization were examined using micro‐CT, whereas the mineral composition was assessed spectrophotometrically in groups of fetal and newborn pigs. The development of the condyle coincided with a reorganization of bone elements without an increase in bone volume fraction, but with an increase in mineralization and a change in mineral composition. In the corpus, the bone volume fraction and mineralization increased simultaneously with a restructuring of the bone elements and a change in mineral composition. The growth of the condyle was reflected by regional differences in architecture and mineralization. The anterior and inferior regions were characterized by a more dense bone structure and a higher mineralization as compared to posterior and superior regions, respectively. In the corpus, growth was mainly indicated by differences between buccal and lingual plates as well as between anterior, middle, and posterior regions characterized by a more compact structure and higher mineralization in the lingual and middle regions. In conclusion, the architecture and mineralization in the condyle and corpus started to deviate early during development toward their destiny as trabecular and cortical bone, respectively. These results were compatible with those obtained with mineral composition analysis. Regional differences within condyle and corpus reflected known developmental growth directions. Anat Rec Part A, 288A:954–961, 2006. © 2006 Wiley‐Liss, Inc.
Fitting combinations of exponentials to probability distributions
Authors: Dufresne Daniel 
Published: August 2006

AbstractTwo techniques are described for approximating distributions on the positive half‐line by combinations of exponentials. One is based on Jacobi polynomial expansions, and the other on the logbeta distribution. The techniques are applied to some well‐known distributions (degenerate, uniform, Pareto, lognormal and others). In theory, the techniques yield sequences of combination of exponentials that always converge to the true distribution, but their numerical performance depends on the particular distribution being approximated. An error bound is given in the case the logbeta approximations. Copyright © 2006 John Wiley & Sons, Ltd.
A ‘bottom‐up’ approach for endo‐PK/PD analysis
Authors: Neelakantan S. , Widness J.A. , Schmidt R.L. , Veng‐Pedersen P. 
Published: August 2006

AbstractA ‘bottom‐up’ PK/PD analysis approach employing system analysis principles of convolution/deconvolution and special nonparametric estimation procedures is presented to resolve the complex ‘endo‐PK/PD’ of the endogenous form of recombinant drugs using erythropoietin (EPO) as an example. A novel cellular deconvolution algorithm is presented that facilitates the identification of the functional relationship between the variables involved in EPO's complex PK/PD. Five sheep each underwent two phlebotomies spaced 4–6 weeks apart when their hemoglobin levels were reduced from 12 g/dl to 3–4 g/dl. EPO levels and reticulocyte counts were frequently sampled. The data were analysed using end‐constrained cubic splines. The rate of reticulocyte production was determined using the novel deconvolution methodology. The erythroid progenitor cells activation rate by EPO was estimated from the reticulocyte production rate using a lag‐time parameter which determines the delay in the reticulocyte appearance in the blood relative to the activation of erythroid progenitors. Hysteresis minimization combined with cellular deconvolution was employed to determine the population PK/PD transduction function relating the progenitor activation rate to EPO concentrations in a nonparametric manner without assuming a specific structure. The proposed approach provides a rational informative starting point for developing parametric PK/PD models to resolve the complex endo‐PK/PD of recombinant drugs. Copyright © 2006 John Wiley & Sons, Ltd.
The effect of gender on the pharmacokinetics of verapamil and norverapamil in human
Authors: Dadashzadeh S. , Javadian B. , Sadeghian S. 
Published: August 2006

AbstractThe effects of gender on the pharmacokinetics of verapamil and its active metabolite, norverapamil, following single oral dose (80mg, Isoptin) to 12 healthy male (mean age: 25.75±2.42 years, mean body weight: 70.59±9.94kg) and 12 healthy female subjects (mean age: 24.08±2.84 years, mean body weight: 56.67±5.23kg) were investigated in the present study. Plasma concentrations of verapamil and norverapamil were analysed using a modified high‐pressure liquid chromatography method. Pharmacokinetic parameters were calculated by non‐compartmental analysis for each subject. For verapamil the half‐life (t1/2) and mean residence time (MRT) were significantly shorter in women than men (p<0.01 andp<0.05, respectively). For other pharmacokinetic parameters of verapamil there were no significant differences between males and females. For norverapamil,t1/2,MRTand time to reach to the maximum plasma concentration (Tmax) showed statistically significant differences between the two genders. TheAUC0−24andAUC0−∞ratios of norverapamil to verapamil were also calculated. The ratios were significantly higher in women compared with men. These observations indicate that the elimination rate of verapamil is faster in women than men which may be attributed to the higher activity of CYP3A4 or lower activity of P‐glycoprotein in women compared with men. A contribution of both factors in the appearance of gender differences in verapamil pharmacokinetics is also possible. Copyright © 2006 John Wiley & Sons, Ltd.