bluuebunny/crossref_metadata_2025 huggingface dataset:
A Crossover, Randomized, Controlled Trial of Dornase Alfa Before Versus After Physiotherapy in Cystic Fibrosis
Authors: Fitzgerald Dominic A. , Hilton Jodi , Jepson Beverly , Smith Lucia
Published: September 2005

Objective. Although dornase alfa is a widely used, aerosolized, mucolytic agent in patients with cystic fibrosis (CF), its efficacy in relation to the timing of physiotherapy has not been tested. We sought to determine whether dornase alfa is more efficacious when it is administered 30 minutes before versus 30 minutes after physiotherapy/positive expiratory pressure (PEP) therapy in clinically stable children.

Methods. Using a crossover, randomized, double-blind, and placebo-controlled trial, we undertook a 6-week study of the efficacy of dornase alfa in relation to the timing of physiotherapy at home. There were 2 treatment orders. Dornase alfa before + placebo after physiotherapy/PEP for 2 weeks was followed by a 2-week washout and then the reverse order placebo before and dornase alfa after physiotherapy/PEP for the final 2 weeks. The second treatment order reversed the placebo and dornase alfa therapy for the first and last 2-week blocks. The main outcome measures used included the change in predicted percentage of forced expiratory volume in 1 second (FEV1), a composite quality of well-being score (QWB), and a measure of aerobic fitness (maximal oxygen consumption, [VO2max]), determined using shuttle testing.

Results. Fifty-two patients who had CF (27 female) with mild to moderate suppurative lung disease, were a mean ± SD age of 10.7 ± 3.2 years, had Shwachman scores of 86 ± 11.8, had predicted FEV1 of 83% ± 18%, had quality of well-being score of 0.76 ± 0.08, and had VO2max of 42.6 ± 6.3 ml/kg per min were enrolled. Fifty patients completed the study. Intention-to-treat analysis was used. Nonsignificant mean (95% confidence interval) differences in FEV1 (0.02 L [−0.05 to 0.10]), VO2max (−0.75 ml/kg per min [−1.85 to 0.35]), and QWB (0.005 [−0.94 to 0.0028]) for dornase alfa after physiotherapy/PEP were detected. A post hoc analysis showed that patients who were colonized persistently with Pseudomonas aeruginosa had a significantly greater improvement in FEV1 (0.12 L [0.23 to 0.01] vs −0.04 L [0.05 to −0.13]) when dornase alfa was administered after physiotherapy/PEP.

Conclusions. Dornase alfa is equally efficacious when delivered before or after physiotherapy/PEP in patients with CF. Patients who are colonized persistently with P aeruginosa may derive more improvement in FEV1 when dornase alfa is delivered after physiotherapy/PEP.
Emergency Contraception
Authors:   Committee on Adolescence
Published: September 2005

Teen birth rates in the United States have declined during the last decade but remain much higher than rates in other developed countries. Reduction of unintended pregnancy during adolescence and the associated negative consequences of early pregnancy and early childbearing remain public health concerns. Emergency contraception has the potential to significantly reduce teen-pregnancy rates. This policy statement provides pediatricians with a review of emergency contraception, including a definition of emergency contraception, formulations and potential adverse effects, efficacy and mechanisms of action, typical use, and safety issues, including contraindications. This review includes teens' and young adults' reported knowledge and attitudes about hormonal emergency contraception and issues of access and availability. The American Academy of Pediatrics, as well as other professional organizations, supports over-the-counter availability of emergency contraception. In previous publications, the American Academy of Pediatrics has addressed the issues of adolescent pregnancy and other methods of contraception.
A Novel Human Artificial Chromosome Vector Provides Effective Cell Lineage–Specific Transgene Expression in Human Mesenchymal Stem Cells
Authors: Ren Xianying , Katoh Motonobu , Hoshiya Hidetoshi , Kurimasa Akihiro , Inoue Toshiaki , Ayabe Fumiaki , Shibata Kotaro , Toguchida Junya , Oshimura Mitsuo
Published: September 2005

Mesenchymal stem cells (MSCs) hold promise for use in adult stem cell–mediated gene therapy. One of the major aims of stem cell–mediated gene therapy is to develop vectors that will allow appropriate levels of expression of therapeutic genes along differentiation under physiological regulation of the specialized cells. Human artificial chromosomes (HACs) are stably maintained as independent chromosomes in host cells and should be free from potential insertional mutagenesis problems of conventional transgenes. Therefore, HACs have been proposed as alternative implements to cell-mediated gene therapy. Previously, we constructed a novel HAC, termed 21 Δpq HAC, with a loxP site in which circular DNA can be reproducibly inserted by the Cre/loxP system. We here assessed the feasibility of lineage-specific transgene expression by the 21Δpq HAC vector using an in vitro differentiation system with an MSC cell line, hiMSCs, which has potential for osteogenic, chondrogenic, and adipogenic differentiation. An enhanced green fluorescent protein (EGFP) gene driven by a promoter for osteogenic lineage-specific osteopontin (OPN) gene was inserted onto the 21 Δpq HAC and then transferred into hiMSC. The expression cassette was flanked by the chicken HS4 insulators to block promoter interference from adjacent drug-resistant genes. The EGFP gene was specifically expressed in the hiMSC that differentiated into osteocytes in coordination with the transcription of endogenous OPN gene but was not expressed after adipogenic differentiation induction or in noninduction culture. These results suggest that use of the HAC vector is suitable for regulated expression of transgenes in stem cell–mediated gene therapy.
Blood Monocytes Mimic Endothelial Progenitor Cells
Authors: Rohde Eva , Malischnik Christina , Thaler Daniela , Maierhofer Theresa , Linkesch Werner , Lanzer Gerhard , Guelly Christian , Strunk Dirk
Published: September 2005

The generation of endothelial progenitor cells (EPCs) from blood monocytes has been propagated as a novel approach in the diagnosis and treatment of cardiovascular diseases. Low-density lipoprotein (LDL) uptake and lectin binding together with endothelial marker expression are commonly used to define these EPCs. Considerable controversy exists regarding their nature, in particular, because myelomonocytic cells share several properties with endothelial cells (ECs). This study was performed to elucidate whether the commonly used endothelial marker determination is sufficient to distinguish supposed EPCs from monocytes. We measured endothelial, hematopoietic, and progenitor cell marker expression of monocytes before and after angiogenic culture by fluorescence microscopy, flow cytometry, and real-time reverse transcription–polymerase chain reaction. The function of primary monocytes and monocyte-derived supposed EPCs was investigated during vascular network formation and EC colony-forming unit (CFU-EC) development. Monocytes cultured for 4 to 6 days under angiogenic conditions lost CD14/CD45 and displayed a commonly accepted EPC phenotype, including LDL uptake and lectin binding, CD31/CD105/CD144 reactivity, and formation of cord-like structures. Strikingly, primary monocytes already expressed most tested endothelial genes and proteins at even higher levels than their supposed EPC progeny. Neither fresh nor cultured monocytes formed vascular networks, but CFU-EC formation was strictly dependent on monocyte presence. LDL uptake, lectin binding, and CD31/CD105/CD144 expression are inherent features of monocytes, making them phenotypically indistinguishable from putative EPCs. Consequently, monocytes and their progeny can phenotypically mimic EPCs in various experimental models.
Role of Transcription Factors in Motoneuron Differentiation of Adult Human Olfactory Neuroepithelial-Derived Progenitors
Authors: Zhang Xiaodong , Cai Jun , Klueber Kathleen M. , Guo Zhanfang , Lu Chengliang , Winstead Welby I. , Qiu Mengsheng , Roisen Fred J.
Published: September 2005

Neurosphereforming cell (NSFC) lines have been established from cultures of human adult olfactory neuroepithelium. Few of these cells ever express mature neuronal or glial markers in minimal essential medium supplemented with 10% fetal bovine serum or defined medium. However, these neural progenitors have the potential to differentiate along glial or neuronal lineages. To evaluate the potential of NSFCs to form motoneurons, transcription factors Olig2, Ngn2, and HB9 were introduced into NSFCs to determine if their expression is sufficient for motoneuron specification and differentiation, as has been shown in the early development of the avian and murine central nervous systems in vivo. NSFCs transfected with Olig2, Ngn2, and HB9 alone exhibited no phenotypic lineage restriction. In contrast, simultaneous transfection of Ngn2 and HB9 cDNA increased the expression of Isl1/2, a motoneuron marker, when the cells were maintained in medium supplemented with retinoic acid, forskolin, and sonic hedgehog. Furthermore, a population of Olig2-expressing NSFCs also expressed Ngn2. Cotransfection of NSFCs with Olig2 and HB9, but not Olig2 and Ngn2, increased Isl1/2 expression. Coculture of NSFCs trans-fected with Ngn2-HB92 or Olig2 and HB9 with purified chicken skeletal muscle demonstrated frequent contacts that resembled neuromuscular junctions. These studies demonstrate that transcription factors governing the early development of chick and mouse motoneuron formation are able to drive human adult olfactory neuroepithelial progenitors to differentiate into motoneurons in vitro. Our long-term goal is to develop cell populations for future studies of the therapeutic utility of these olfactory-derived NSFCs for autologous cell replacement strategies for central nervous system trauma and neurodegenerative diseases.
Modelling of a 3D excavation in finite element analysis
Authors: Zdravkovic L. , Potts D. M. , St John H. D.
Published: September 2005

This paper investigates a number of issues related to the modelling of a retaining structure used to support an excavation in 3D finite element analyses. In particular, the effects of wall stiffness in different coordinate directions and the rotational fixity in the corner of the excavation are examined. Both square and rectangular excavations are analysed and compared with the equivalent axisymmetric and plane strain analyses, normally used as approximations for modelling purposes. The chosen geometry, construction sequence and soil conditions are based on a proposed deep excavation at Moorgate in London (next to the Moor House development), which will form part of an underground station for the Crossrail project. The objective of the study is to provide a detailed assessment of wall and ground movements and structural forces in the wall in the light of different modelling assumptions. The study has wider application to a variety of projects that include the development of infrastructure, the construction of deep basement car parks and buried structures, and the effect that these have on the surrounding areas.
A field permeability measurement technique using a conventional self-boring pressuremeter
Authors: Ratnam S. , Soga K. , Whittle R. W.
Published: September 2005

A new permeability measurement method using a conventional self-boring pressuremeter (SBP) is described. The SBP self-bores to a predetermined depth. It is then retracted a short way, leaving a well-defined cavity in the ground. Water is pumped into the cavity at a constant rate, and the permeability is derived from the change in injection pressure with injection flow rate. A sequence of tests at a given horizon involves cavities of varying lengths, including a flush bottom or zero length cavity. In homogeneous materials the data from variable cavity lengths can be used to determine the anisotropy ratio. In heterogeneous materials the same data may allow the scale dependence to be evaluated if the anisotropy ratio can be independently obtained. Potential measurement errors are discussed in relation to smearing, temperature effects and leakage along the instrument. Results from Gault clay, London clay and Bothkennar clay are presented, with corroborating laboratory and other field test results where available. The preliminary assessment of scale dependence at these sites corresponds well to the degree of heterogeneity identified for the tested clays through visual observation.
A Precursor‐Based Route to ZnSe Nanowire Bundles
Authors: Xiong S. , Shen J. , Xie Q. , Gao Y. , Tang Q. , Qian Y. T.
Published: September 2005

A large number of one‐dimensional bundles of ZnSe nanowires with diameters ranging from 15–20 nm and lengths of up to tens of micrometers have been prepared via the thermal treatment of a ribbon‐like precursor (ZnSe·3ethylenediamine), which has been synthesized by a mixed solvothermal route, in an argon atmosphere. The as‐obtained precursor has been characterized by powder X‐ray diffraction (XRD), transmission electron microscopy (TEM), IR spectroscopy, thermogravimetric analysis, and elemental analysis. XRD and high‐resolution TEM characterization reveal that the as‐synthesized ZnSe nanowires have the single‐crystal hexagonal wurtzite structure with the [001] growth direction. The surface chemical composition of ZnSe nanowires has been studied by X‐ray photoelectron spectroscopy. The cooperative action of the mixed solvents may be responsible for the formation of the morphology of the resulting products. Room‐temperature photoluminescence measurements indicate the as‐grown ZnSe nanostructures have a strong emission peak centered at 587 nm and two weak emission peaks centered at 435 and 462 nm. The strong emission from the ZnSe nanostructures reveals their potential as building blocks for optoelectronic devices.
Electrochemical Synthesis of Optically Active Polyaniline Films
Authors: Li W. , Wang H.‐L.
Published: September 2005

Polyaniline (PANI) thin films with high optical activity are prepared electrochemically on indium tin oxide (ITO) substrates by polymerizing aniline in the presence of aniline oligomers and optically active camphor sulfonic acid (CSA). These optimized PANI chiral thin films have an anisotropic factor of 0.03 and an estimated molar ellipticity of 8.8 × 105 deg cm2 dmol–1, ∼ 25 % higher than our previously synthesized chiral PANI nanofibers that were prepared using the chemical method. The thin film prepared without aniline oligomers is basically achiral. The electrochemical method does not require an oxidizing agent and allows control of the rate of polymerization reaction by varying the oxidation potential. The electrochemical polymerization also ensures that the initiation occurs solely with the oligomers. Varying the experimental parameters, such as oxidation potential and the choice of oligomers, allows tuning of optical activity, adsorption properties, crystallinity, and morphology of the PANI thin films.
Cover Picture: Crosslinked Nanoparticle Stripes and Hexagonal Networks Obtained via Selective Patterning of Block Copolymer Thin Films (Adv. Mater. 18/2005)
Authors: Shenhar R. , Jeoung E. , Srivastava S. , Norsten T. B. , Rotello V. M.
Published: September 2005

The construction and fixation of ordered nanoparticle arrays allow not only the exploitation of the array's collective physical properties but also the possibility of manipulating discrete aggregates within a larger‐scale assembly scheme. A simple approach utilizing block copolymer thin films as templates and coordination chemistry as a mild crosslinking mechanism is reported by Shenhar, Rotello, and co‐workers on p. 2206. The cover image (by Nicholas Fischer) shows terpyridine‐functionalized gold nanoparticles organized in stripes on top of a microphase‐separated thin film of polystyrene‐block‐poly(methyl methacrylate) and crosslinked thorough the formation of iron–bisterpyridine complexes.
Two‐scale continuum model for simulation of wormholes in carbonate acidization
Authors: Panga Mohan K. R. , Ziauddin Murtaza , Balakotaiah Vemuri
Published: September 2005

A two‐scale continuum model is developed to describe transport and reaction mechanisms in reactive dissolution of a porous medium, and used to study wormhole formation during acid stimulation of carbonate cores. The model accounts for pore level physics by coupling local pore‐scale phenomena to macroscopic variables (Darcy velocity, pressure and reactant cup‐mixing concentration) through structure‐property relationships (permeability‐porosity, average pore size‐porosity, and so on), and the dependence of mass transfer and dispersion coefficients on evolving pore scale variables (average pore size and local Reynolds and Schmidt numbers). The gradients in concentration at the pore level caused by flow, species diffusion and chemical reaction are described using two concentration variables and a local mass‐transfer coefficient. Numerical simulations of the model on a two‐dimensional (2‐D) domain show that the model captures the different types of dissolution patterns observed in the experiments. A qualitative criterion for wormhole formation is developed and it is given by Λ ∼ O(1), where Λ =
. Here, keff is the effective volumetric dissolution rate constant, DeT is the transverse dispersion coefficient, and uo is the injection velocity. The model is used to examine the influence of the level of dispersion, the heterogeneities present in the core, reaction kinetics and mass transfer on wormhole formation. The model predictions are favorably compared to laboratory data. © 2005 American Institute of Chemical Engineers AIChE J, 2005
A general method of computing the derivative of experimental data
Authors: Lubansky A. S. , Yeow Y. Leong , Leong Yee‐Kwong , Wickramasinghe S. Ranil , Han Binbing
Published: September 2005

Many scientific and engineering investigations require the extraction of the first derivative from experimental data. Direct numerical differentiation is usually impractical because this amplifies the noise in the data, leading to unreliable results. This investigation shows that the problem of differentiating experimental data can be converted into one of solving an integral equation of the first kind. Tikhonov regularization is used to solve this integral equation, leading to a smooth first derivative. By using the built‐in regularization parameter in the method noise amplification is kept under control. The performance of this method is demonstrated by applying it to data taken from the literature. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Mosaic trisomy 9 syndrome with unusual phenotype
Authors: Kaminker Catalina P. , Daín Liliana , Lamas María A. , Sánchez José M. , Opitz John M. , Reynolds James F.
Published: September 2005

We report on a newborn infant with mosaic trisomy 9. The patient shared only a few anomalies with the previously reported cases of this chromosome abnormality but had a severe craniofacial malformation not yet reported in this syndrome.
Creatine‐Kinase and pyruvate‐kinase activities in normal children: Implications in duchenne muscular dystrophy carrier detection
Authors: Passos M. R. , Gonzalez C. H. , Zatz M. , Opitz John M. , Reynolds James F.
Published: September 2005

Serum creatine‐kinase (CK) and pyruvate‐kinase (PK) levels were determined in 201 boys and girls less than 15 years old to establish values and to investigate a possible correlation between enzyme activity, sex, and age.

It was observed that the mean CK activity in boys was significantly higher than in females (of all ages), whereas it did not differ statistically between girls and women. A slight but significant correlation between CK activity and age was found only in females. The mean PK activity in children was significantly greater than in adult women and it decreased significantly with age in children of both sexes. Furthermore, a slight correlation between CK and PK was observed only in girls.

Based on these results, we suggest that the results of CK and PK determinations of females at risk for Duchenne muscular dystrophy should be compared with controls of comparable age and sex.
The Okihiro syndrome of duane anomaly, radial ray abnormalities, and deafness
Authors: Hayes Ailish , Costa Teresa , Polomeno Robert C. , Opitz John M. , Reynolds James F.
Published: September 2005

We report on a child with Duane anomaly, deafness, cervical spine, and radial ray abnormalities. A sister of the proposita had hemifacial microsomia, cervical abnormalities, and hypoplasia of the thenar eminence. Four relatives had hypoplasia of the thenar eminence. A fifth had preaxial polydactyly. Duane anomaly was present in two sixth‐degree relatives. This appears to be an autosomal dominant trait. Singly or in combination the abnormalities seen in this family have all been described in association with Duane anomaly. Their occurrence in the same family suggests that they are not independent entities but represent pleiotropic effects of the same gene.
Partial pyruvate decarboxylase deficiency with profound lactic acidosis and hyperammonemia: Responses to dichloroacetate and benzoate
Authors: McCormick Kenneth , Viscardi Rose M. , Robinson Brian , Heininger James , Opitz John M. , Reynolds James F.
Published: September 2005

We describe the successful use of sodium benzoate in a neonate with hyperammonemia associated with congenital lactic acidosis caused by a partial deficiency of the E1 component of pyruvate dehydrogenase (PDH); of note, this biochemical distrubance has not been previously described in PDH deficiency. The pyruvate dehydrogenase complex in skin fibroblasts had 48% of normal activity with a deficiency of the E1 component. The infant presented with rapid onset of a severe metabolic lactic acidosis, hyperventilation, hyperammonemia, and coma. At 30 hours of age continuous peritoneal dialysis was started; however, plasma NH3 concentrations remained in the 300–400 μg/dl range over the next 12 hours. Sodium benzoate, 250 mg/kg, was infused intravenously with a decrease in plasma ammonia of 25 μg/dl/hr. Hippurate was documented in the urine and peritoneal fluid after benzoate therapy. At 10.5 months of age, 50 mg/kg dichloroacetate was administered orally under fasting conditions, which resulted in a 56 and 62% reduction in the serum lactate and pyruvate levels, respectively; after 2 weeks on dichloroacetate his fasting levels were significantly decreased. Fibroblast PDH activity responded similarly to this drug. In our patient sodium benzoate was rapidly effective in producing a decline in plasma ammonia that was associated with clinical improvement. We feel that its use in organic acidemias deserves further evaluation and, furthermore, that any child with suspected PDH deficiency requires a clinical trial of dichloroacetate.
Familial microtia, meatal atresia, and conductive deafness in three siblings
Authors: Schmid M. , Schröder M. , Langenbeck U. , Opitz John M. , Reynolds James F.
Published: September 2005

We report on three sibs with right‐sided microtia, meatal atresia, and conductive deafness. Two of the sibs also had right‐sided palatoplegia. These sibs may have the autosomal‐recessive form of microtia (No. 25180, McKusick [1983]), of which few familial cases are known to date. The malformation is due to a disturbance of the development of the first and second branchial arches. Review of the literature shows that microtia and meatal atresia with or without middle‐ear involvement are developmental field defects which, either isolated or as a part of the facio‐auriculovertebral spectrum, may occur (1) sporadically, (2) as component manifestation of syndromes, (3) as a multifactorial, or (4) as an apparent Mendelian trait.
A mildly retarded woman with 46,XX/47,XX,+18 mosaicism
Authors: Bensen J. T. , Steele M. W. , Opitz John M. , Reynolds James F.
Published: September 2005

We describe a mildly retarded woman with trisomy 18 mosaicism. The phenotype did not suggest trisomy 18, but the mild mental retardation, asymmetric face with bushy eyebrows and thick lips, short stature, and older maternal age raised the suspicion of a chromosomal cause for her condition.
A therapeutic trial of amniotic epithelial cell implantation in patients with lysosomal storage diseases
Authors: Yeager Andrew M. , Singer Harvey S. , Buck James R. , Matalon Reuben , Brennan Susan , O'Toole Susan O'Donnell , Moser Hugo W. , Opitz John M. , Reynolds James F.
Published: September 2005

To determine whether allografts of normal amniotic epithelium might provide a nonimmunogenic cellular source of exogenous lysosomal enzymes, subcutaneous implants of amniotic epithelium were performed in six children with clinically advanced storage diseases. The clinical and the biochemical status of each patient was observed for several weeks after amniotic epithelial cell implantation (AECI). Serial studies of blood samples from each patient in the post‐AECI period did not demonstrate any increase in levels of deficient lysosomal hydrolase. In two patients, quantitative urinary excretion of substrate was also studied and did not show consistent alterations after AECI. No patient had objective improvement in clinical or neurodevelopmental status following AECI. Two patients died with progressive disease at 2 1/2 and 3 1/2 mo after AECI; no residual amniotic epithelium was found at postmortem examination. Four patients are alive with progressive disease at 6–14 mo after AECI. We conclude that allografts of normal human amnion do not provide sufficient replacement hydrolases for clinical or biochemical improvement in lysosomal storage diseases.
Minute chromosomes replacing the Y chromosome carry Y‐specific sequences by restriction fragment analysis and in situ hybridization
Authors: Münke Maximilian , de Martinville Bérengère , Francke Uta , Lieber Ernest , Opitz John M. , Reynolds James F.
Published: September 2005

Two unrelated males, a 43‐year‐old man with azoospermia and a 4‐year‐old boy with stature at the 10th centile, had similar karyotypes: 46,X,min. The minutes, present in all cells analyzed, stained weakly with G‐, C‐, and Q‐banding methods. To elucidate their origin we used molecular techniques: In HaeIII digests of total genomic DNA from both individuals, no Y‐specific reiterated sequences were detected. However, restriction fragment analysis with probe pDP31 demonstrated that the patients' DNA contained the Y‐specific fragment. In situ hybridization with the same probe showed that these sequences were present on the minute chromosomes and have not been translocated elsewhere.
CAMPS: Computer‐automated metacarpophalangeal profile system
Authors: Coupland Stuart G. , McLeod D. Ross , Lowry R. Brian , Wesenberg Richard L. , Opitz John M. , Reynolds James F.
Published: September 2005

The metacarpophalangeal profile (MCP) pattern has been proven useful in describing individuals with genetic and nongenetic syndromes. However, the measurement of the 19 bone lengths is a tedious procedure requiring use of hand vernier calipers, detailed normative data to be looked up in extensive tables, hand calculator, and manual graphing techniques. Presently there are no reports of microcomputer‐automated systems for the accurate measurement, recording, analysis, and graphing of MCP profiles. We describe a computer‐automated metacarpophalangeal profile system (CAMPS) that will assist in the derivation of the MCP profile. This program allows the user to select different program routines that perform the functions necessary for MCP profile construction. The “data acquisition module” (DAM) assists in bone length measurement from contact prints of hand radiographs and stores the 19 measurements on a floppy disk. The “standardization analysis module” (SAM) then compares the 19 measurements to age‐and sex‐matched normal data and converts the raw data to z‐score values. The “Pearson product‐moment correlation module” (PPM) generates a correlation coefficient describing the degree of similarity between the two hands measured and graphically illustrates the resulting scatterplot. The “MCP plotting module” (MCPM) provides a graphic plot of the 19 bones in either transverse rows or phalangeal rays on a dot‐matrix printer or X‐Y plotter.
Partial aniridia, cerebellar ataxia, and mental deficiency (gillespie syndrome) in two brothers
Authors: Wittig Ehrenfried O. , Moreira Carlos A. , Freire‐Maia Newton , Vianna‐Morgante Angela M. , Opitz John M. , Reynolds James F.
Published: September 2005

We report on two brothers (in a sibship of three) with partial aniridia, cerebellar ataxia, and moderate mental retardation, with normal G‐banded chromosomes. Both present cerebellum hypoplasia; the younger also has congenital pulmonic stenosis. A review of the literature is presented. Cause is unknown, although the possibility of an autosomal recessive gene cannot be ruled out.
Digital and palmar dermatoglyphics in Dementia of the Alzheimer type
Authors: Luxenberg Jay S. , Plato Chris C. , Fox Kathleen M. , Friedland Robert P. , Rapoport Stanley I. , Reynolds James F.
Published: September 2005

Digital and palmar dermatoglyphics were examined in 29 men and 27 women with dementia of the Alzheimer type (DAT) and 112 age‐, sex‐, and racial group‐matched controls. Female patients had significantly (p < 0.05) more accessory triradii and complete Sydney creases than controls; no dermatoglyphic differences were detected in the males. Separating the patients by age of onset prior to or after age 65 years did not help differentiate patients from controls by dermatoglyphic profile. This study failed to confirm either the previously reported dermatoglyphic differences between DAT patients and controls or the reported similarity of the dematoglyphic pattern of DAT to that of Down syndrome patients.
Nager acrofacial dysostosis: Evidence for apparent heterogeneity
Authors: Goldstein David J. , Mirkin L. David , Opitz John M. , Reynolds James F.
Published: September 2005

Nager acrofacial dysostosis is characterized by malar, mandibular, and maxillary hypoplasia, macrostomia, abnormal ears, and radial defects. The lower limbs are usually normal. Two patients were reported with many of these manifestations, in addition to severe facial clefts and limb deficiency. These more severely affected patients were thought to have a severe form of Nager acrofacial dysostosis or a new syndrome. We report on a patient with limb findings of intermediate severity. This patient also had hydrocephalus, micropolygyria, and tetralogy of Fallot. This may indicate apparent heterogeneity or a single condition with widely variable expression.
Cerebral abnormalities in the Neu‐Laxova syndrome
Authors: Ostrovskaya Tereza I. , Lazjuk Gennady I. , Opitz John M. , Reynolds James F.
Published: September 2005

Cerebral abnormalities are considered an obligatory manifestation of the Neu‐Laxova syndrome and include lissencephaly, severe microcephaly, aplasia of the corpus callosum, hypoplasia of the cerebellum, and other pathological changes. We present data on 3 cases with central nervous system anomalies, two of which have not been described previously, and summarize the literature on the subject. The problem of distinguishing type III lissencephaly is discussed.
An unusual bandlike web in an infant with lethal multiple pterygium syndrome
Authors: Froster‐Iskenius Ursula G. , Curry Cynthia , Philp Margaret , Hall Judith G. , Opitz John M. , Reynolds James F.
Published: September 2005

We report on a patient with a lethal multiple pterygium syndrome who also had an unusual, bandlike web across one axilla and partial intestinal atresia. Umbilical cord wrapping with subsequent vascular compromise appears to be the most likely pathogenetic mechanism for the additional anomalies.
Peroxisomal disorders: Clinical commentary and future prospects
Authors: Wilson Golder N. , Holmes Ronald D. , Hajra Amiya K. , Opitz John M. , Reynolds James F.
Published: September 2005

Recent progress in the classification, biochemistry, and molecular biology of peroxisomal disorders is reviewed from a clinical perspective. Diseases such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, hyperpipecolic acidemia, chondrodysplasia punctata, and Leber amaurosis share a common phenotype and involve deficiency of multiple peroxisomal enzymes. These disorders are associated with diverse metabolic abnormalities which are useful in pre‐ or postnatal diagnosis and distinguish these disorders from others such as X‐linked adrenoleukodystrophy, adult Refsum disease, hyperoxaluria type I, and acatalasemia. Peroxisome structure is difficult to quantify historically, since recent studies emphasize its developmental variability and tissue heterogeneity. The ability to manipulate this structure by dietary or pharmaceutical means provides a novel approach to therapy. At the molecular level, deficiency of peroxisomal enzymes responsible for fatty acid beta‐oxidation or ether lipid synthesis reflects enhanced protein degradation due to abnormal peroxisomes; messenger RNA for the beta‐oxidation enzymes is transcribed normally in peroxisomal disorders and can be increased by peroxisome proliferators. At least one integral structural protein of the peroxisome is synthesized normally in Zellweger syndrome. Hypotheses for the basic defect include defective regulation, uptake, or coenzyme stimulation of imported proteins, as well as defective biosynthesis. One clue to this defect may be a similar evolutionary history of peroxisomes and mitochondria which would explain their common alteration in Zellweger syndrome.
Atypical Menkes steely hair disease
Authors: Westman Judith A. , Richardson Delphis C. , Rennert Owen M. , Morrow Grant , Opitz John M. , Reynolds James F.
Published: September 2005

Menkes steely hair disease (MSHD) is a rare disorder which typically results in severe mental retardation and death in early childhood. A 21‐month‐old boy with an atypical milder form was presented by Procopis et al. [1981]. A second child with the atypical form is presented here who has survived to age 9 years and is doing well clinically.
Activation of fatty acid oxidation in the Silver–Russell syndrome and the Brachmann–de Lange syndrome
Authors: Willems Patrick J. , Dijkstra Irene , Schierbeek Henk H. , Berger Ruud , Smit G. Peter A. , Opitz John M. , Reynolds James F.
Published: September 2005

We describe a similar metabolic pattern of hyperketosis, ketonaciduria, and C6–C12 dicarboxylic aciduria in a patient with the Silver–Russell syndrome and a patient with the Brachmann–de Lange syndrome. Fasting blood levels of beta‐hydroxybutyrate and acetoacetate were significantly higher than in age‐matched controls, and both patients showed massive urinary excretion of beta‐hydroxybutyrate, acetoacetate and C6–C12 dicarboxylic acids.
The diagnostic management of newborns with congenital contractures: A nosologic study of 75 cases
Authors: Hageman Gerard , Ippel Elly P. F. , Beemer Frits A. , de Pater Joke M. , Lindhout Dick , Willemse Jakobus
Published: September 2005

A prospective clinical study is presented of 75 patients with multiple congenital contractures. With the data from medical history, child neurologic examinations, laboratory tests including chromosome and dermatoglyphic analysis, and neuropathology in 23 cases with perinatal death, a nosological or syndromal diagnosis was made in 61 cases. These cases were classified by localization of causal pathology in the categories “cerebral dysgenesis”, spinal cord defects, neuromuscular disorders and miscellaneous disorders without muscle weakness. Following this concept, the various modes of inheritance of specific disorders presenting with congenital contractures, as well as possibilities for prenatal diagnosis by ultrasonography are discussed. A guideline for the child neurologic evaluation of infants with congenital contractures is proposed. It is concluded that: (1) specification of the causal lesion and proper classification of disorders with congenital contractures is crucial for genetic counseling, (prenatal) diagnosis and management; (2) the analysis of dermatoglyphics in differential diagnosis of congenital contractures should be restudied; and (3) more study and experience is required in the observation of abnormal or decreased fetal movements by ultrasonography.
Ring chromosome 11 and café‐au‐lait spots
Authors: Fagan K. , Suthers G. K. , Hardacre G.
Published: September 2005

We report on the segregation of a cytogenetically non‐deleted ring chromosome 11 and café‐au‐lait spots in a family. This appears to be the largest inherited ring autosome yet reported.
Holoprosencephaly: Association with interstitial deletion of 2p and review of the cytogenetic literature
Authors: Münke Maximilian , Emanuel Beverly S. , Zackai Elaine H.
Published: September 2005

Chromosome analysis with high‐resolution banding showed a small de novo interstitial deletion of chromosome 2(p21 → p22.2) in an infant with holoprosencephaly. This is the first such observation. There is a well‐known association with abnormalities of chromosome 13 (most commonly trisomy 13, but also dup(13q) and del(13q) and chromosome 18 (most often del(18p), but also trisomy 18). Review of the literature also showed duplications of 3p and deletions of 7q to be causes of the holoprosencephaly defect.
MCA/MR syndrome in a female infant with tetraploidy mosaicism: Review of the human polyploid phenotype
Authors: Wilson Golder N. , Vekemans Michel J. J. , Kaplan Paige
Published: September 2005

We report on a 3‐month‐old girl with unusual facial appearance, short neck with low posterior hairline, wide chest, valvular pulmonic stenosis, abnormal fingernails, and diploid‐tetraploid mosaicism (46,XX/92,XXXX in 7.2% of peripheral leucocytes and in 29% of skin fibroblasts). Comparison with 11 previously reported cases with mosaic or complete tetraploidy does not establish an easily recognizable syndrome. However, a malformation pattern is apparent when tetraploidy patients are compared with 14 cases of triploid mosaicism and 44 previously reported cases of nonmosaic triploidy. A history of sex hormone exposure was present in 5 of 11 pregnancies resulting in tetraploidy; this exposure may correlate with the occurrence of tetraploidy in polycystic ovary syndrome and in tumors of the female reproductive tract. The mechanism of dysmorphogenesis involved in polyploidy is considered, including hypotheses of altered nuclear/cytoplasmic ratio, of trophoblastic alteration, of delayed cell division, or of altered autosome/active X chromosome ratio.
First demonstration of recombination between the gene for Norrie disease and probe L1.28
Authors: Katayama Susumu , Wohlferd Monica , Golbus Mitchell S.
Published: September 2005

Norrie disease is an X‐linked trait thought ot be tightly linked to the anonymous probe L1.28. Here we repost the first recombinational event amony 24 informative meioses. This indicates there is a 4% (95% C.L. 0.1%–21%) error rate introduced by meiotic crossovers in carrier or prenatal diagnosis based on linkage between Norrie disease and L1.28.
Acrodysostosis: Report of a 13‐year‐old boy with review of literature and metacarphphalangeal pattern profile analysis
Authors: Butler Merlin G. , Rames Laura J. , Wadlington William B.
Published: September 2005

We repost on a 13‐yr‐old boy with acrodysostosis, a review of 30 cases in the literature, and metacarpophalangeal pattern profile (MCPP) analysis. The prominent manifestations (present in >75% od cases) of this condition include nasal and maxillary hypoplasia, peripheral dysostosis, first ray hyperplasia of the foot, acromesomelic brachymelia, decreased interpedicular distance, advanced skeletal maturation and mental retardation. Results fo chromosome studies have been normal. An autosomal dominant inherance pattern was reported in two families. Maternal and paternal ages were 2 and 3 yr, respectively, above the average age of the general parent population, which suggests that advanced parental age may be a factor in the cause of this condition. A characteristically abnormal MCPP was found in our patient and in 16 additional cases studied from the literature. A mean NCPP was developed for the syndrome. MCPP analysis may ge useful as a diagnositic tool in patients suspected to have acrodysostosis.
Evidence for autosomal recessive inheritance of progeria (Hutchinson Gilford)
Authors: Maciel Andréa Trevas , Opitz John M. , Reynolds James F.
Published: September 2005

We have studied a boy with progeria (Hutchinson Gilford) born to third cousins. Four other individuals with progeria were born in another consanguineous sibship in the same family. Thus, this disorder can be inherited as an autosomal recessive trait.
Two mosaic cases with nonfluorescent Y chromosome analysed with Y‐specific DNA probes
Authors: Kałużewski Bogdan , Jakubowski Lucjusz , Dȩbiec‐Rychter Maria , Grzeschik Karl‐Heinz , Limon Janusz , Gibas Zenon , Opitz John M. , Reynolds James F.
Published: September 2005

Two cases of a nonfluorescent Y (Ynf) chromosome were diagnosed: one in a male, the other in a female. Both bad similar complex mosaic chromosome constitutions with a 45,X cell line.

DNA studies were applied in both cases for verification of the cytogenetic diagnosis. The results on the two patients were compared with data obtained from seven healthy men (46,XY), three healthy women (46,XX), two females with 46,XY karyotype, and from cell lines with 49,XXXXY and 48, XXXX chromosome constitution.

The highly repetitive Y ‐specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients.

The highly repetitive Y ‐specific DNA sequences located in the heterochromatic region of the long arm were absent in these patients. Differences in the composition of the euchromatic part of the Y chromosome were demonstrable in both patients.

The suggestion that the Ynf chromosome originates from a dicentric Y chromosome cannot be accepted as a complete explanation of the phenomenon, as it probably involves more complex molecular alterations of the abnormal Y chromosome.

The presence of Ynf is associated with the presence of a 45,X cell line more often than in cases of simple Y chromosome deletions with the breakpoint localized in or below the Y euchromatin/heterochromatin junction.
Fragile site in chromosome 12 in a patient with two miscarriages
Authors: Stetten Gail , Sroka Bernadette , Norbury‐Glaser Mary , Corson Virginia L. , Opitz John M. , Reynolds James F.
Published: September 2005

A heritable fragile site at 12q 13 is described in lymphocytes from a woman with a history of multiple miscarriage. The fragile site was not typically folate‐sensitive, being expressed in standard medium. The presence of this fragile site may have led to meiotic chromosome breakage and consequent infertility.
Interstitial and terminal deletions of the long arm of chromosome 4: Further delineation of phenotypes
Authors: Lin Angela E. , Garver Kenneth L. , Diggans Gerard , Clemens Michele , Wenger Sharon L. , Steele Mark W. , Jones Marilyn C. , Israel Jeannette , Opitz John M. , Reynolds James F.
Published: September 2005

We reviewed 45 patients with a deletion of the long arm of chromosome 4. Forty‐one were previous reports (25 terminal deletions and 16 interstitial deletions) and 4 are new cases with terminal deletions. Of the 29 patients with terminal deletions, 18 with deletion at 4q31 and 4 at 4q32 → qter had an identifiable phenotype consisting of abnormal skull shape, hypertelorism, cleft palate, apparently low‐set abnormal pinnae, short nose with abnormal bridge, virtually pathognomonic pointed fifth finger and nail, congenital heart and genitourinary defects, moderate‐severe mental retardation, poor postnatal growth, and hypotonia. Six patients with a deletion at 4q33 and one patient with deletion 4q34 were less severely affected. In general, patients with various interstitial deletions proximal to 4q31 had a phenotype that was less specific, although mental retardation and minor craniofacial anomalies were also present. There were 3 patients with piebaldism and one with Rieger syndrome. We conclude that terminal deletion of chromosome 4q (4q31 → qter) appears to produce a distinctive malformation (MCA/MR) syndrome in which the phenotype correlates with the amount of chromosome material missing and which differs from the more variable phenotype associated with interstitial deletions of 4q.
A patient with an interstitial deletion of the proximal portion of the long arm of chromosome 4
Authors: Beall Marie H. , Falk Rena E. , Ying Kuang‐Lin , Opitz John M. , Reynolds James F.
Published: September 2005

A patient with a proximal deletion of the long arm of chromosome 4 is presented. This patient and 6 others previously described appear to have similar findings of moderate to severe developmental delay, small size, small hands and feet, and similar facial appearance. These patients appear to be quite different from those with more distal 4q deletions.
Familial simple hypohidrosis with abnormal palmar dermal ridges
Authors: Frydman Moshe , Cohen Herman A. , Kauschansky Arieh , Matoth Yehuda , Opitz John M. , Reynolds James F.
Published: September 2005

A brother and sister born to nonconsanguineous, Iranian Jewish parents were found to have simple hypohidrosis. Pilocarpine produced only little sweating, and external heat and physical effort were associated with elevation of body temperature. Abnormal palmar dermal ridges were considered to be associated with paucity of sweat pores and glands. Biopsy supported this view since only one normal sweat gland and duct was found in a 5 mm punch.
Obesity in achondroplasia
Authors: Hecht Jacqueline T. , Hood Opal Jean , Schwartz Robert J. , Hennessey Jill C. , Bernhardt Barbara A. , Horton William A. , Opitz John M. , Reynolds James F.
Published: September 2005

Obesity is a significant and potentially serious health problem in achondroplasia. Body mass indices, weight‐to‐square of the height ratio (W/H2), and triceps skinfold measurements show that obesity is common. It begins in early childhood and is prevalent at all ages. We recommend that weight be monitored closely in all persons with achondroplasia and that dietary intervention be instituted whenever the body mass indices, W/H2, and triceps skinfold measurements exceed the 95th centile for the general population.
Complex glycerol kinase deficiency: Molecular‐genetic, cytogenetic, and clinical studies of five Japanese patients
Authors: Matsumoto Tadashi , Kondoh Tatsuro , Yoshimoto Masaaki , Fujieda Kenji , Matsuura Nobuo , Matsuda Ichiro , Miike Teruhisa , Yano Koichi , Okuno Akimasa , Aoki Yoshiharu , Murano Ichiro , Toyota Shigeki , Ohnishi Shouju , Niikawa Norio , Opitz John M. , Reynolds James F.
Published: September 2005

Five male Japanese patients with complex glycerol kinase deficiency (CGKD) and their relatives were studied clinically, cytogenetically, and molecular‐genetically. All patients had muscular dystrophy or muscle weakness, mental retardation, congenital adrenal hypoplasia, and glycerol kinase deficiency. High‐resolution GTG‐banded chromosomes showed a microdeletion in the Xp21 region in all four patients examined and in all five mothers. Southern hybridizations, after digestions by restriction endonucleases, with various cloned DNAs (D2, 99‐6, B24, C7, L1‐4, cDMD13‐14, J66‐HI, P20, J‐Bir, ERT87‐30, ERT87‐15, ERT87‐8, ERT87‐1, XJ‐1.1, 754, cx5.7, and OTC‐1) that are located around Xp21 also showed a deletion in the genome of all patients and mothers. Although the deletion differed in size among patients, a segment commonly absent was located between the genomic sequences corresponding to L1‐4 and cDMD 13‐14. This finding indicated that the gene coding for glycerol kinase (GK) is located within this segment. A comparison of the clinical manifestations of the present five patients and reported CGKD or Duchenne muscular dystrophy (DMD) patients with DNA deletion suggests the existence of a certain gene responsible for gonadotropin deficiency (GTD). The result of the present study and results of previous studies suggest that genes for ornithine transcarbamylase (OTC), DMD, and GK and putative genes responsible for congenital adrenal hypoplasia (AHC) and GTD are arranged from telomere to centromere as pter—GTD—AHC—GK—DMD—OTC—cen.