bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in Testicular Temperature and Vascularization Induced by Hypobaric Hypoxia in Rats
Authors: Farías Jorge G. , Bustos‐Obregón Eduardo , Reyes Juan G.
Published: November 2005

ABSTRACT: The exposure of male rats to continuous chronic hypobaric hypoxia (HH) and intermittent chronic hypobaric hypoxia induced evident changes in testicular morphology and spermatogenic cell metabolism. The mechanisms that underlie these changes under HH are not known. In this work, we have tested the hypothesis that in rats subjected to HH, the testis undergoes changes in vascularization leading to changes in temperature homeostasis. Male Wistar rats (247 ± 16 g) were maintained in normobaric or hypobaric (428 torr, equivalent to 4600 m a.s.l) conditions. At days 0, 5, 15, and 30 postexposure, 12 rats were anesthetized with ketamine, and the intratesticular temperature was determined. These rats were subsequently sacrificed and the testicles were fixed in formaldehyde and processed for routine histological analysis. Our results showed that the height of the seminiferous epithelium decreased significantly at day 5 posthypoxia and thereafter, indicating a decreased spermatogenesis. Intratesticular temperature increased (1.5°C) and remained high after 5 days of hypoxia exposure. Correlated with these changes, histometrical analysis of the number of blood vessels in the testicular interstitium was significantly increased by day 5 and afterwards. Morphological classification of interstitial blood vessels indicates a transition from capillaries to larger vessels as the hypoxia exposure progresses.
Trisialoganglioside GT1b Prevents Increase in Sperm Membrane Molecular Ordering Induced by In Vitro Lipid Peroxidation
Authors: Gavella Mirjana , Kveder Marina , Lipovac Vaskresenija , Rakos Romina , Pifat Greta
Published: November 2005

ABSTRACT: The effect of various types of gangliosides, the sialic acid‐containing glycosphingolipids, on human sperm membrane during lipid peroxidation induced by Fe2+/ascorbate ions was investigated. The monosialoganglioside (GM1), disialogangliosides (GD1a and GD1b), and trisialoganglioside (GT1b) were examined at a concentration of 100 μM, which was above their respective critical micellar concentrations. Lipid peroxidation was determined by quantification of malondialdehyde (MDA) concentration. The molecular orientational order in the membrane was assessed by fluorescence spectroscopy and electron paramagnetic resonance spectroscopy. Both approaches revealed a significant increase in membrane rigidity following oxidation, which correlated with an increase in the MDA level. The preincubation of spermatozoa with GM1 and GD1a did not have any effect on induced lipid peroxidation. In the presence of GD1b and GT1b, a reduced formation of MDA and a decrease in membrane rigidity was detected. The inhibitory effect of GT1b micelles toward membrane oxidation damage was found to be greater than that of GD1b. In conclusion, a direct relationship between the reduced content of the accumulated MDA and the longer preservation of the native‐like membrane molecular ordering during sperm oxidation in the presence of GT1b suggests its protective effect. This phenomenon could be due to the specific GT1b conformation and its negative surface potential.
Severe Hypospermatogenesis in Cases of Nonobstructive Azoospermia: Should We Use Fresh or Frozen Testicular Spermatozoa?
Authors: Hauser Ron , Yogev Leah , Amit Ami , Yavetz Haim , Botchan Amnon , Azem Fuad , Lessing Joseph B. , Ben‐Yosef Dalit
Published: November 2005

ABSTRACT: The aim of this comparative clinical study was to examine whether the fertilizing potential of frozen‐thawed testicular sperm in the most severe cases of hypospermatogenesis is reduced compared with fresh testicular sperm. The results could determine the necessity of using fresh testicular sperm cells, which mandates involving the spouse by performing simultaneous in vitro fertilization intracytoplasmic sperm injection (IVF‐ICSI) treatment in this subgroup of nonobstructive azoospermia (NOA) patients. We studied 13 couples in which the husband was diagnosed as having NOA and few motile testicular sperm cells or only immotile testicular sperm cells were isolated by testicular sperm extraction (TESE). Each couple underwent both an ICSI cycle, in which fresh testicular sperm that were retrieved shortly beforehand were injected, and a consecutive cycle, which used frozen‐thawed sperm that were retrieved in the original TESE procedure but were cryopreserved and stored until use. We found that motility was lost during the freezing and thawing process in some cases, which resulted in significantly more cycles with only immotile sperm cells for injection in the frozen‐thawed sperm group (38.5%) than in the fresh sperm group (7.7%; P < .05). Availability of only immotile sperm cells significantly reduced fertilization rates in both fresh and frozen‐thawed groups, but the respective overall fertilization rate (44.9% vs 41.1%) and quality of embryos and pregnancy rate (18.2% vs 15.4%) were not significantly different between groups. Implantation rates were more favorable in the fresh sperm group (10.5% vs 5.9%), but not significantly so. We conclude that, although cryopreservation does impair motility, which results in significantly more cycles with only immotile sperm cells for ICSI in the most severe forms of hypospermatogenesis, fertilization and pregnancy rates are not significantly compromised.
A Cyclic Adenosine 3′,5′‐Monophosphate Stimulates Phospholipase Cγ1‐Calcium Signaling via the Activation of Tyrosine Kinase in Boar Spermatozoa
Authors: Harayama Hiroshi , Murase Tetsuma , Miyake Masashi
Published: November 2005

ABSTRACT: The aim of this study was to reveal a downstream part of the intracellular signaling that is mediated by cyclic adenosine monophosphate (cAMP)‐dependent tyrosine kinases, including spleen tyrosine (Y) kinase (SYK), in boar spermatozoa. Ejaculated spermatozoa were incubated with cBiMPS (a cell‐permeable cAMP analog; 0.1 mM) at 38.5°C for 180 minutes and then used for Western blot and indirect immunofluorescence. Incubation of spermatozoa with cBiMPS induced tyrosine phosphorylation at the linker region of SYK (which was essential to binding to phospholipase C [PLC]γ1) in the connecting and principal pieces, but the tyrosine phosphorylation was abolished by the addition of H‐89 (a protein kinase A [PKA] inhibitor; 0.01‐0.1 mM). Moreover, the cAMP‐dependent tyrosine phosphorylation was also induced at the key regulatory residue of PLCγ1 in the same segments of spermatozoa, but it was inhibited by the addition of herbimycin A (a tyrosine kinase inhibitor; 5 μM). These results suggest that the sperm cAMP‐dependent tyrosine kinases, including SYK, are linked to the activation of PLCγ1. Indirect immunofluorescence clearly detected both inositol 1,4,5‐trisphosphate (IP3) receptor and calreticulin in the connecting piece, indicating the presence of internal calcium store. Cell imaging with fluo‐3/AM (a cell‐permeable Ca2+ indicator) showed that incubation of spermatozoa with cBiMPS increased intracellular free calcium in the middle piece, but that it was reduced by the addition of U‐73122 (a PLC inhibitor; 0.02 mM). Based on our findings, we conclude that the connecting piece of boar spermatozoa possesses the PLCγ1‐IP3 receptor‐calcium signaling that is triggered by cAMP and mediated by PKA and herbimycin A‐sensitive tyrosine kinases, including SYK.
Organic Materials and Thin‐Film Structures for Cross‐Point Memory Cells Based on Trapping in Metallic Nanoparticles
Authors: Bozano L. D. , Kean B. W. , Beinhoff M. , Carter K. R. , Rice P. M. , Scott J. C.
Published: November 2005

Non‐volatile solid‐state memory cells based on composites of metal nanoparticles and polymers are embedded in organic semiconducting host materials. This paper presents data from a wide range of materials and device structures and shows that the switching phenomenon is commonly observed.
Open‐Pore Organic Material for Retaining Radioactive I2 and CH3I
Authors: Hertzsch T. , Gervais C. , Hulliger J. , Jaeckel B. , Guentay S. , Bruchertseifer H. , Neels A.
Published: November 2005

Application of ultrasound and ball milling produces micrometer‐sized crystallites of tris‐(o‐phenylenedioxy)‐cyclotriphosphazene (TPP) that show zeolite‐like reversible sorption of I2 and CH3I (methyl iodide). The thermal stability of open‐pore TPP is improved by partial loading with pyrazine. The sorption properties of open‐pore TPP are investigated by the 131I radioactive tracer method. Comparison with activated charcoal (ACC) shows that TPP has a higher sorption efficiency for I2 dissolved in water than ACC. In the case of a humid gaseous source of CH3I also, TPP exhibits better sorption properties than ACC. Partial loading of open‐pore TPP by pyrazine increases its thermal stability by 50 °C and the binding properties for retaining CH3I are also improved. Force‐field calculations show a difference of ΔE ≈ 20 kJ mol–1, making the open‐pore system less stable than the apohost.
Biomimetic Formation of Hydroxyapatite Nanorods by a Single‐Crystal‐to‐Single‐Crystal Transformation
Authors: Zhan J. , Tseng Y.‐H. , Chan J. C. C. , Mou C.‐Y.
Published: November 2005

Uniform nanorods of hydroxyapatite (HAP) with an unusual orthorhombic shape have been synthesized from homogeneous solutions of Ca2+and HPO42–in the presence of gelatin and urea. The lengths of the nanorods are in the range of hundreds of micrometers, and the widths are about 100 nm. The HAP phase is generated by the transformation from its precursor phase of octacalcium phosphate (OCP), which has been monitored by X‐ray diffraction, NMR spectroscopy, scanning electron microscopy, and transmission electron microscopy. The rise in pH due to the decomposition of urea drives the OCP transformation to HAP. In the presence of gelatin, nanorods of OCP phase formed first and then transformed into the HAP phase, preserving the single‐crystal morphology. On the other hand, blade‐like OCP crystals form from the solution in the absence of gelatin. On increasing the pH of the solution, the large, blade‐like OCP crystals tend to crash into irregular, hexagonal HAP crystallites. A single‐crystal‐to‐single‐crystal topochemical transformation may be attributed to the evolution of HAP nanorods from the precursor OCP phase. This gives a strong indication as to the OCP to HAP transformation mechanism in the mineralization of biological apatite in tooth enamel and bone.
Fabrication of Microcantilever Sensors Actuated by Piezoelectric Pb(Zr0.52Ti0.48)O3 Thick Films and Determination of Their Electromechanical Characteristics
Authors: Park J. H. , Kwon T. Y. , Yoon D. S. , Kim H. , Kim T. S.
Published: November 2005

The integration and the device realization of Pb(Zr, Ti)O3 (PZT) thick films on Si substrates are known to be extremely difficult because the processing temperature of the PZT thick film is close to the melting point of Si. However, PZT thick‐film devices on Si warrant attention as they are appropriate for biological transducers; they generate large actuating forces and have a relatively high sensitivity for mass detection, especially in liquids. In this study, Pb(Zr0.52Ti0.48)O3 thick‐film cantilever devices are successfully fabricated on a Pt/TiO2/SiNx/Si substrate using a screen‐printing method and microelectromechanical systems (MEMS) process. Elastic and electromechanical properties such as the Young's modulus and transverse piezoelectric coefficient are determined from microstructural and electrical analyses for further mechanical study. The calculated Young's modulus of the thick film, 53.9 ± 3.85 GPa, corresponds to the resonant frequency obtained from the measured harmonic oscillation response. The transverse piezoelectric constant, d31, of –20.7 to –18.8 pC N–1 is comparable to that of a dense thin film. These values promise the possibility of determining the resonance properties of a thick‐film cantilever by designing its structure and then simulating the harmonic oscillation response. Using the PZT thick‐film cantilever, a strong harmonic oscillation with a quality (Q) factor of about 23 is demonstrated in water. The observation of strong harmonic oscillation in liquid implies the feasibility of precise real‐time recognition of biomolecules using PZT thick‐film cantilevers.
Fabrication and Characterization of Two‐Photon Polymerized Features in Colloidal Crystals
Authors: Pruzinsky S. A. , Braun P. V.
Published: November 2005

The fabrication and characterization of two‐photon polymerized features written within and outside of colloidal crystals is presented. Two‐photon polymerization (TPP) response diagrams are introduced and developed to map the polymerization and damage thresholds for features written via modulated beam rastering. The use of tris[4‐(7‐benzothiazol‐2‐yl‐9,9‐diethylfluoren‐2‐yl)phenyl]amine (AF‐350) as an initiator for TPP is demonstrated for the first time and TPP response diagrams illustrate the polymerization window. These diagrams also demonstrate that the polymerization behavior within and outside of colloidal crystals is similar and electron microscopy reveals nearly identical resolution. Fluorescence confocal microscopy further enables visualization of non‐self‐supporting, three‐dimensional TPP features within self‐assembled photonic crystals. Finally, microspot spectroscopy is collected from a two‐photon feature written within a colloidal crystal and this is compared with simulation.
Cover Picture: Acceleration of Calcite Kinetics by Abalone Nacre Proteins (Adv. Mater. 22/2005)
Authors: Fu G. , Qiu S. R. , Orme C. A. , Morse D. E. , De Yoreo J. J.
Published: November 2005

Abalone utilizes a system of macromolecular matrices and soluble proteins to produce beautiful and mechanically robust shells. The cover shows work by Qiu and co‐workers reported on p. 2678, in which AP8 proteins isolated from the shell of red abalone are shown to alter the growth of calcite both by accelerating the rate and modifying the shape from the simple rhombohedra seen in the upper left of the scheme to the more complex form seem in the lower right. The changes are made manifest at an atomic scale through alterations in the growth speed and shape of the atomic steps that form the growth hillocks (background).
Effect of steaming treatment in the structure and reactivity of FCC catalysts
Authors: Tonetto G. M. , Ferreira M. L. , Atias J. A. , de Lasa H. I.
Published: November 2005

The shape selectivity properties of USY zeolite crystallites is discussed, and is based on catalyst characterization, molecular simulation, catalytic experiments of model compounds and kinetic modeling. Typical FCC catalysts are prepared with different HY crystallite sizes (0.4 and 0.9 μm), and are structurally and chemically characterized with nitrogen and argon adsorption/desorption isotherms, temperature‐programmed desorption of ammonia and infrared spectroscopy. Catalyst characterization is carried out before and after the hydrothermal treatment (steaming) of the catalyst. Pore‐size distribution analysis demonstrates that the effect of the steaming treatment in the Y zeolite results in window enlargement. The influences of structural changes of steam treatment on reactivity is evaluated with the catalytic conversion of 1,2,4‐trimethylbenzene in a novel fluidized CREC riser simulator. It is proven that steaming enlarges zeolite windows and influence the 1,2,4‐TMB product distribution. A slight modification of the window diameter is proven to significantly affect the adsorbent‐adsorbate interactions. Focus is particularly given to the catalyst selectivity toward the tetramethylbenzene isomers, and the “transition‐state shape selectivity” is proven to be controlling the product distribution and is consistent with molecular mechanics calculations. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Size distributions and stability of toluene diluted heavy oil emulsions
Authors: Angle Chandra W. , Hamza Hassan A. , Dabros Tadeusz
Published: November 2005

The sizes and stability of oil droplets created from various concentrations of heavy oil‐in‐toluene at a fixed oil:water ratio were investigated during turbulent flow in model process water. The Reynolds number (Re) ranged from 17,000 to 34,500 and was obtained by stirred tank mixing with a Rushton turbine. The droplet sizes were monitored using laser light scattering. Results showed that at high Re and low oil concentrations (that is, low drop‐surface coverage), breakage of the droplets was the dominant process, but as Re was reduced, coalescence was dominant. Droplets were less prone to breakage as the oil concentrations in toluene increased, and droplet sizes approached a steady state quickly during mixing. Their size distributions broadened and stability increased as heavy oil in toluene increased. Stability was attributed to a surface coverage by asphaltenes and the consequent interfacial elasticity that provided resilience to breakage. Equilibrium interfacial tension σE was determined by fitting a diffusion‐limited kinetic mathematical model to the data. The Gibbs adsorption model gave a monolayer surface coverage of 3 nm2/mol asphaltenes, consistent with other published results. High zeta potential of the droplets also hindered coalescence. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Hybrid generalized modular/collocation framework for distillation column synthesis
Authors: Proios Petros , Pistikopoulos Efstratios N.
Published: November 2005

Systematic and detailed methods are proposed for the synthesis of simple, heat integrated, and complex distillation column sequences for the separation of non‐azeotropic mixtures based on formal superstructure optimization techniques. The Generalized Modular Framework (GMF) developed in previous works for the conceptual synthesis of the aforementioned sequencing problems is enhanced through the incorporation of principles of Collocation techniques for distillation order reduction. The proposed GMF/Collocation methods overcome structural complexities through systematically composed structural models and provide accurate and detailed guidelines for the optimal design and operation of the represented distillation sequences. The synthesis methods are applied for a number of sequencing case studies, generating substantial economic savings by finding systematically, accurately, and in a unified way the most cost efficient distillation column sequence. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Multiobjective molecular design for integrated process‐solvent systems synthesis
Authors: Papadopoulos Athanasios I. , Linke Patrick
Published: November 2005

The limitations are addressed that emerge from the computer aided molecular design (CAMD) applications in the optimal synthesis of solvents through a novel approach of designing solvents built upon multiple objective optimization technology. This technology has certain advantages over single objective optimization approaches that have been used for the design of optimal solvent molecules in the past. The different synthesis drives, described by the various objective functions, are treated independently without being submitted to unnecessary fixed assumptions that bias the designs. As a result, all the underlying trends and trade‐offs among the properties of the candidate optimal molecules, as well as the structure – property relations are allowed to be revealed. The ability of the presented synthesis framework to embed highly inclusive solutions is elaborated, and the trends are revealed that dominate the relations between the utilized objective functions. It is also shown that solvent molecules, designed in the event that process performance feedback is accounted for, are existent in the Pareto optimal front. The proposed methodology is illustrated with two comprehensive examples in the design of solvents for liquid‐liquid extraction and gas‐absorption processes. © 2005 American Institute of Chemical Engineers AIChE J, 2006
A numerical study of combustion stability in emergency oxygen generators
Authors: Diakov Victor , Shafirovich Evgeny , Varma Arvind
Published: November 2005

Combustion in sodium chlorate based emergency oxygen generators is accompanied by significant oscillations of the product oxygen flow rate, which decrease the efficiency of these devices. Reactant melting and convective heat transfer from the generated gas are key steps in the process. In this work, the effect of reactant melting on filtration combustion front propagation stability in gas generating mixtures is investigated numerically. The formation of melting regions is demonstrated in cases with significant convective gas‐to‐core heat transfer. Numerical simulations exhibit the oscillatory behavior of oxygen generation. By decreasing the effective heat of reaction, reactant melting is detrimental to combustion front stability. The simulations show growth of pulsations with increasing reaction activation energy and decreasing convective heat transfer. A strong stabilization of front propagation is observed when combustion temperature reaches the melting point of reaction product. These results identify the important factors responsible for pulsating behavior of chemical oxygen generators. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Ebstein anomaly and duplication of the distal arm of chromosome 15: Report of two patients
Authors: Miller Michelle S. , Rao P. Nagesh , Dudovitz Rebecca N. , Falk Rena E.
Published: November 2005

Ebstein anomaly of the tricuspid valve is an uncommon congenital heart defect. We report two unrelated patients with Ebstein anomaly and duplication of the distal long arm of chromosome 15 (15q22 → qter and 15q24 → qter). Duplication of 15q is a well‐described phenotype that includes congenital heart defects, and these are the first cases with Ebstein anomaly. Duplication of 15q likely affects the early morphogenesis of cardiac structures, including the normal formation of the tricuspid valve. © 2005 Wiley‐Liss, Inc.
Molecular cytogenetic characterization of a familial der(1)del(1)(p36.33)dup(1)(p36.33p36.22) with variable phenotype
Authors: Tonk Vijay S. , Wilson Golder N. , Yatsenko Svetlana A. , Stankiewicz Pawel , Lupski James R. , Schutt Robert C. , Northup J.K. , Velagaleti Gopalrao V.N.
Published: November 2005

Chromosome deletions involving 1p36 are the most common known terminal rearrangements occurring at a frequency of ∼1 in 5,000 live births. In contrast, duplications of the same region have been reported rarely. We describe a familial rearrangement der(1)del(1)(p36.33)dup(1)(p36.33p36.22) identified in a mother, daughter, and son. These individuals help define a syndrome with variable mental disability, attention deficit‐hyperactivity disorder, and a distinctive facial appearance with wide palpebral fissures, broad nasal root, macrostomia, ear malformations, and prominent incisors. Based on our results we suggest that the complex rearrangement seen in our family could be the result of the breakage‐fusion‐bridge (BFB) cycles model of formation. © 2005 Wiley‐Liss, Inc.
Myhre syndrome in a female with previously undescribed symptoms: Further delineation of the phenotype
Authors: van Steensel M.A.M. , Vreeburg M. , Steijlen P.M. , de Die‐Smulders C.
Published: November 2005

Myhre syndrome is a rare connective tissue disease characterized by nonprogressive stiffness of the large joints, short stature with a peculiar build, and a distinctive facial phenotype. Developmental delay is common. Three female patients have so far been described. Here, we report on a 16‐year‐old female with Myhre syndrome. She has vertebral defects, hypertrophic scar formation, and a stiff skin in addition to the features that have previously been reported in association with Myhre syndrome. © 2005 Wiley‐Liss, Inc.
Perlman syndrome: Clinical report and nine‐year follow‐up
Authors: Piccione Maria , Cecconi Massimiliano , Giuffrè Mario , Curto Margherita Lo , Malacarne Michela , Piro Ettore , Riccio Andrea , Corsello Giovanni
Published: November 2005

We present the clinical and follow‐up data of a female infant with Perlman syndrome from birth to the age of 9 years. Main features of Perlman syndrome include polyhydramnios, fetal overgrowth, neonatal macrosomia, macrocephaly, dysmorphic facial features, visceromegaly, nephroblastomatosis, and a predisposition for Wilm's tumor. In our patient, the nephromegaly with nephroblastomatosis was not present at birth or during the neonatal period; it became evident in the first months of postnatal life. A Wilm's tumor was diagnosed when she was about 1 year old. Long term follow‐up documents the natural history of Perlman syndrome and allows us to establish the long‐term prognosis of the affected individuals. © 2005 Wiley‐Liss, Inc.
A paternally derived inverted duplication of distal 14q with a terminal 14q deletion
Authors: Chen Chih‐Ping , Chern Schu‐Rern , Lin Shuan‐Pei , Lin Chyi‐Chyang , Li Yueh‐Chun , Wang Tzu‐Hao , Lee Chen‐Chi , Pan Chen‐Wen , Hsieh Lie‐Jiau , Wang Wayseen
Published: November 2005

A girl presented with a phenotype including neonatal hypotonia, psychomotor retardation, mental retardation, short stature, and facial dysmorphism. She demonstrated common features of both 14q31‐qter duplication and terminal 14q deletion. She had undergone surgery for patent ductus arteriosus and pyloric stenosis in infancy. Her karyotype was 46,XX,der(14) dup(14)(q32.3 q31.3)del(14)(q32.3). Molecular cytogenetic analysis showed a paternally derived 14q31.3‐q32.3 duplication and a terminal 14q deletion and led to the correlations between a particular genotype and phenotype. This is the first description of a deletion and inverted duplication of 14q, and adds 14q to the growing list of the inverted duplication associated with a terminal deletion. © 2005 Wiley‐Liss, Inc.
Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: Unusual manifestations of Menkes disease
Authors: Grange Dorothy K. , Kaler Stephen G. , Albers Gary M. , Petterchak James A. , Thorpe Connie M. , deMello Daphne E.
Published: November 2005

Menkes disease is an X‐linked recessive disorder of copper transport characterized by neurological deterioration, connective tissue, and vascular defects, abnormal hair, and death in early childhood. We report on a patient with Menkes disease in whom severe diffuse emphysema caused respiratory failure and death at 14 months of age. He had severe growth and developmental delays and other typical clinical manifestations of Menkes disease. He developed respiratory problems requiring continuous supplemental oxygen and a progressively enlarging soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in multiple lobes of the lung consistent with bullous emphysema. The neck mass was determined to be an internal jugular venous aneurysm. At autopsy, extensive emphysematous change was evident. Post‐mortem barium injections of the pulmonary arterial system revealed marked dilatation and tortuosity of the preacinar pulmonary arteries and reduced numbers of intra‐acinar arteries. Severe emphysema, presumably caused by abnormal elastin due to deficiency of the copper‐dependent enzyme lysyl oxidase, may represent an underestimated clinical complication of Menkes disease and should be considered in the differential diagnosis of chronic respiratory disease in these patients. © 2005 Wiley‐Liss, Inc.
Costello syndrome and hyperinsulinemic hypoglycemia
Authors: Alexander Saji , Ramadan Dina , Alkhayyat Haya , Al‐Sharkawi Ibrahim , Backer K.C. Aboo , El‐Sabban Fatma , Hussain Khalid
Published: November 2005

Costello syndrome is characterized by mental retardation, loose skin, coarse facies, skeletal abnormalities, cardiovascular abnormalities (congenital heart defects, cardiomyopathy, rhythm disturbances), and predisposition to neoplasia. Endocrine abnormalities including growth hormone deficiency, adrenal insufficiency, glucose intolerance, parathyroid adenoma with hyperprolactinemia and hypoglycemia have been described. Hypoglycemia has been documented due to growth hormone and cortisol deficiency. We report on two patients with Costello syndrome and persistent hyperinsulinemic hypoglycemia and review the endocrine manifestations of Costello syndrome. Both patients required diazoxide therapy to stop the unregulated insulin secretion and maintain normoglycemia. The mechanism of persistent hyperinsulinism in patients with Costello syndrome is unclear. © 2005 Wiley‐Liss, Inc.
A patient with monosomy 1p36, atypical features and phenotypic similarities with Cantu syndrome
Authors: Tan Tiong Yang , Bankier Agnes , Slater Howard R. , Northrop Emma L. , Zacharin Margaret , Savarirayan Ravi
Published: November 2005

We report on a 16‐year‐old boy with a distal 1p36 deletion with some clinical features consistent with Cantu syndrome (OMIM#239850). He also has hypercholesterolemia, type II diabetes, recurrent bony fractures, and non‐alcoholic steatohepatitis, not previously described in either condition. The 1p36 deletion was detected in a screen of all chromosome subtelomeres using multiplex ligation‐dependent probe amplification and was verified using FISH with a region‐specific BAC clone. We suggest that patients suspected of having Cantu syndrome, especially those with unusual or more severe manifestations be analyzed for distal 1p36 deletions. © 2005 Wiley‐Liss, Inc.
Submicroscopic deletions and duplications in individuals with intellectual disability detected by array‐CGH
Authors: Tyson C. , Harvard C. , Locker R. , Friedman J.M. , Langlois S. , Lewis M.E.S. , Van Allen M. , Somerville M. , Arbour L. , Clarke L. , McGilivray B. , Yong S.L. , Siegel‐Bartel J. , Rajcan‐Separovic E.
Published: November 2005

Intellectual disability (ID) affects about 3% of the population (IQ < 70), and in about 40% of moderate (IQ 35–49) to severe ID (IQ < 34), and 70% of cases of mild ID (IQ 50–70), the etiology of the disease remains unknown. It has long been suspected that chromosomal gains and losses undetectable by routine cytogenetic analysis (i.e., less than 5–10 Mb in size) are implicated in ID of unknown etiology. Array CGH has recently been used to perform a genome‐wide screen for submicroscopic gains and losses in individuals with a normal karyotype but with features suggestive of a chromosome abnormality. In two recent studies, the technique has demonstrated a ∼15% detection rate for de novo copy number changes of individual clones or groups of clones. Here, we describe a study of 22 individuals with mild to moderate ID and nonsyndromic pattern of dysmorphic features suspicious of an underlying chromosome abnormality, using the 3 Mb and 1 Mb commercial arrays (Spectral Genomics). Deletions and duplications of 16 clones, previously described to show copy number variability in normal individuals [Iafrate et al., 2004; Lapierre et al., 2004; Schoumans et al., 2004; Vermeesch et al., 2005] were seen in 21/22 subjects and were considered polymorphisms. In addition, three subjects showed submicroscopic deletions and duplications not previously reported as normal variants. Two of these submicroscopic changes were of de novo origin (microdeletions at 7q36.3 and a microduplication at 11q12.3‐13.1) and one was of unknown origin as parental testing of origin could not be performed (microduplication of Xp22.3). The clinical description of the three subjects with submicroscopic chromosomal changes at 7q36.3, 11q12.3‐13.1, Xp22.3 is provided. © 2005 Wiley‐Liss, Inc.
Cardiovascular malformations in Fryns syndrome: Is there a pathogenic role for neural crest cells?
Authors: Lin Angela E. , Pober Barbara R. , Mullen Mary P. , Slavotinek Anne M.
Published: November 2005

We performed a comprehensive literature and case report review to characterize the cardiovascular malformations (CVMs) associated with Fryns syndrome (OMIM #229850), a multiple congenital anomaly/mental retardation syndrome consisting of diaphragmatic defects, significant pulmonary hypoplasia, distinctive facial appearance, distal digital hypoplasia, and numerous other external and internal anomalies. A total of 112 patients meeting diagnostic guidelines for Fryns syndrome were identified, of whom 82 met narrowly defined criteria (Group I) and 30 met broader diagnostic criteria (Group II). Twelve patients reported as having Fryns syndrome with atypical features (Group III) were also analyzed. A CVM was reported in 51% (42 of 82) of Group I patients, most commonly an atrial or ventricular septal defect (VSD) (23 of 42, 55%). Conotruncal and aortic arch CVMs were common (11 of 42, 26%), but not significantly so compared to the general population of infants to age 1 year [Ferencz et al., 1997]. Recognizing that minor septal defects associated with congenital diaphragmatic hernia (CDH) may occur in response to altered hemodynamics (instead of being a bonafide CVM), we excluded four patients reported as having hemodynamically insignificant VSDs. Following these exclusions, conotruncal CVMs were found more commonly than in the general population (11 of 38, 29%, P ≤ 0.025). In Group II, 9 of 30 (30%) had a CVM with no predominant type among the small number of cases reviewed. Among the atypical Fryns syndrome patients in Group III, half (6 of 12, 50%) had a CVM; most (4 of 6, 67%) were conotruncal, in particular, type B interrupted aortic arch (3 of 4). Patients with Fryns syndrome have a high rate of CVMs, warranting thorough cardiac evaluation including echocardiogram (fetal and/or postnatal) in all patients, similar to the evaluation for other patients with diaphragmatic hernia. The possible association between conotruncal CVMs and Fryns syndrome may provide additional support for an etiologic role of genes related to neural crest cell development in the pathogenesis of Fryns syndrome and hence, congenital diaphragmatic hernia. © 2005 Wiley‐Liss, Inc.
A preliminary comparison of the hopes of researchers, clinicians, and families for the future ethical use of genetic findings on schizophrenia
Authors: DeLisi Lynn E. , Bertisch Hilary
Published: November 2005

A written questionnaire about genetic testing was distributed to all registrants at The 2004 World Congress of Psychiatric Genetics, mailed to clinical psychiatrists obtained from a directory of clinicians practicing in New York City, and mailed to members of families who have multiple affected family members with schizophrenia. A total of 274 individuals responded (162 researchers, 64 clinicians, and 48 family members). This survey shows that the majority of family members who completed the questionnaire (83.3%) would want to be tested if a genetic test were to become available. Over half of the family members (56.2%) would want prenatal testing. Similarly, over half of the clinicians (56.3%) would recommend it, despite only 25% of the researchers reporting that it would be a future useful tool. All of the clinicians surveyed thought adoption agencies should inform families about a family history of schizophrenia, while only half of the researchers thought this should be done (51.9%). These differences in opinions between consumers, their clinicians, and researchers could be based on a lack of understanding of the amount of risk conferred to family members by reported gene variants. Providing public discussions for placing these risks in perspective should be the responsibility of researchers. Open public discussion of the ethical and social uses of the information gained from psychiatric genetic research and its limitations is encouraged. © 2005 Wiley‐Liss, Inc.
Genetic basis of thoracic aortic aneurysms and aortic dissections
Authors: Pannu Hariyadarshi , Tran‐Fadulu Van , Milewicz Dianna M.
Published: November 2005

Ascending thoracic aortic aneurysms leading to type A dissections (TAAD) can occur in association with a genetic syndrome, such as Marfan syndrome (MFS), or as an autosomal dominant disorder in the absence of syndromic features, termed familial TAAD. Familial TAAD demonstrates genetic heterogeneity, and linkage studies have identified three TAAD loci at 5q13‐14 (TAAD1), 11q23 (FAA1), and 3p24‐25 (TAAD2). The underlying genetic heterogeneity of TAAD is reflected in the phenotypic variation associated with familial TAAD with respect to age of onset, progression, penetrance, and association with additional cardiac and vascular features. Recently, mutations in the TGFBR2 gene have been identified as the cause of disease linked to the TAAD2 locus, supporting the hypothesis that dysregulation of TGFβ signaling is a mechanism leading to aneurysms and dissections. The recent identification of the TGFβ pathway as a key target in the molecular pathogenesis of TAAD has opened new avenues for future genetic and therapeutic research. © 2005 Wiley‐Liss, Inc.
Molecular genetics in classic Ehlers–Danlos syndrome
Authors: Malfait Fransiska , de Paepe Anne
Published: November 2005

Classic Ehlers–Danlos syndrome is a heritable disorder of connective tissue that is characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. Mutations in the COL5A1 and the COL5A2 gene, encoding the α1 and the α2‐chain of type V collagen respectively, are identified in approximately 50% of patients with a clinical diagnosis of classic EDS. In approximately one third of patients, the disease is caused by a mutation leading to a non‐functional COL5A1 allele, and resulting in haplo‐insufficiency of type V collagen. In a smaller proportion of patients, a structural mutation in COL5A1 or COL5A2, resulting in the production of a functionally defective type V collagen protein, is responsible for the phenotype. Inter‐ and intrafamilial phenotypic variability is observed, but no genotype–phenotype correlations can be made so far. The relatively low mutation detection rate in the COL5A1/A2 genes suggests genetic heterogeneity. Indeed rarely mutations in type I collagen have been identified in patients with classic EDS. Mutations in the gene for tenascin‐X have been implicated in an autosomal recessive condition phenotypically overlapping with classic EDS. Several other candidate genes, such as decorin, have emerged from the study of transgenic mouse models with clinical and ultrastructural features reminiscent of classic EDS. However, to date, no human examples have been reported for these mouse models. © 2005 Wiley‐Liss, Inc.
Tenascin‐X, collagen, elastin, and the Ehlers–Danlos syndrome
Authors: Bristow James , Carey William , Egging David , Schalkwijk Joost
Published: November 2005

Tenascin‐X is an extracellular matrix protein initially identified because the gene encoding it overlaps with the human CYP21B gene. Because studies of gene and protein function of other tenascins had been poorly predictive of essential functions in vivo, we used a genetic approach that critically relied on an understanding of the genomic locus to uncover an association between inactivating tenascin‐X mutations and novel recessive and dominant forms of Ehlers–Danlos syndrome (EDS). Tenascin‐X provides the first example of a gene outside of the fibrillar collagens and their processing enzymes that causes EDS. Tenascin‐X null mice recapitulate the skin findings of the human disease, confirming a causative role for this gene in EDS. Further evaluation of these mice showed that tenascin‐X is an important regulator of collagen deposition in vivo, suggesting a novel mechanism of disease in this form of EDS. Further studies suggest that tenascin‐X may do this through both direct and indirect interactions with the collagen fibril. Recent studies show that TNX effects on matrix extend beyond the collagen to the elastogenic pathway and matrix remodeling enzymes. Tenascin‐X serves as a compelling example of how human “experiments of nature” can guide us to an understanding of genes whose function may not be evident from their sequence or in vitro studies of their encoded proteins. © 2005 Wiley‐Liss, Inc.
Osteogenesis imperfecta, current and future medical treatment
Authors: Rauch Frank , Glorieux Francis H.
Published: November 2005

Physiotherapy, rehabilitation, and orthopedic surgery are the mainstay of treatment in moderate to severe forms of osteogenesis imperfecta (OI). Nevertheless, medical treatment with bisphosphonates can bring significant additional improvements. Benefits include decreased pain, lower fracture incidence, and better mobility. Among the various bisphosphonates, intravenous pamidronate has been studied in most detail. It is unclear whether oral bisphosphonates are as effective as intravenous pamidronate. As the effect of bisphosphonates on the skeleton is largest during growth, it appears logical to start medical therapy of OI patients as early as possible. However, the optimal treatment regimen and the long‐term consequences of pamidronate treatment in children are currently unknown. Given these uncertainties, treatment with bisphosphonates during growth should be reserved for patients who have significant clinical problems, such as vertebral compression fractures or long bone deformities. Medical therapies other than bisphosphonates, such as growth hormone and parathyroid hormone, play a minor role at present. Gene‐based therapy currently remains in the early stages of preclinical research. © 2005 Wiley‐Liss, Inc.
Phase II jaw movements and masseter muscle activity during chewing in Papio anubis
Authors: Wall Christine E. , Vinyard Christopher J. , Johnson Kirk R. , Williams Susan H. , Hylander William L.
Published: November 2005

It was proposed that the power stroke in primates has two distinct periods of occlusal contact, each with a characteristic motion of the mandibular molars relative to the maxillary molars. The two movements are called phase I and phase II, and they occur sequentially in that order (Kay and Hiiemae [1974] Am J. Phys. Anthropol. 40:227–256, Kay and Hiiemae [1974] Prosimian Biology, Pittsburgh: University of Pittsburgh Press, p. 501–530). Phase I movement is said to be associated with shearing along a series of crests, producing planar phase I facets and crushing on surfaces on the basins of the molars. Phase I terminates in centric occlusion. Phase II movement is said to be associated with grinding along the same surfaces that were used for crushing at the termination of phase I. Hylander et al. ([1987] Am J. Phys. Anthropol. 72:287–312; see also Hiiemae [1984] Food Acquisition and Processing, London: Academic Press, p. 257–281; Hylander and Crompton [1980] Am J. Phys. Anthropol. 52:239–251, [1986] Arch. Oral. Biol. 31:841–848) analyzed data on macaques and suggested that phase II movement may not be nearly as significant for food breakdown as phase I movement simply because, based on the magnitude of mandibular bone strain patterns, adductor muscle and occlusal forces are likely negligible during movement out of centric occlusion. Our goal is to better understand the functional significance of phase II movement within the broader context of masticatory kinematics during the power stroke. We analyze vertical and transverse mandibular motion and relative activity of the masseter and temporalis muscles during phase I and II movements in Papio anubis. We test whether significant muscle activity and, by inference, occlusal force occurs during phase II movement. We find that during phase II movement, there is negligible force developed in the superficial and deep masseter and the anterior and posterior temporalis muscles. Furthermore, mandibular movements are small during phase II compared to phase I. These results suggest that grinding during phase II movement is of minimal importance for food breakdown, and that most food breakdown on phase II facets occurs primarily at the end of phase I movement (i.e., crushing during phase I movement). We note, however, that depending on the orientation of phase I facets, significant grinding also occurs along phase I facets during phase I. Am J Phys Anthropol, 2006. © 2005 Wiley‐Liss, Inc.
In vivo butyrylcholinesterase activity is not increased in Alzheimer's disease synapses
Authors: Kuhl David E. , Koeppe Robert A. , Snyder Scott E. , Minoshima Satoshi , Frey Kirk A. , Kilbourn Michael R.
Published: November 2005

Objective

We tested the premise that cholinesterase inhibitor therapy should target butyrylcholinesterase (BuChE) in Alzheimer's disease (AD), not acetylcholinesterase (AChE) alone, because both enzymes hydrolyze acetylcholine, and BuChE is increased in AD cerebral cortex.

Methods

To examine this issue in vivo, we quantified human cerebral cortical BuChE activity using tracer kinetic estimates (k3) of 1‐[11C]methyl‐4‐piperidinyl n‐butyrate ([11C]BMP) hydrolysis determined by positron emission tomography. Validation of the putative positron emission tomography method included regional distribution, positive correlation with age, and attenuation by the nonselective cholinesterase inhibitor physostigmine, but no attenuation by the AChE‐selective inhibitor donepezil. Positron emission tomography scans in AD patients (n = 15) and control subjects (n = 12) measured both BuChE (using [11C]BMP) and AChE activity (using N‐[11C] methylpiperidin‐4‐yl propionate, an established method).

Results

As expected, AChE activity in AD cerebral cortex was decreased to 75 ± 13% of normal (p = 0.00001). Contrary to prediction, accompanying BuChE activity also was decreased to 82 ± 14% of normal (p = 0.001).

Interpretation

Failure to observe increased [11C]BMP hydrolysis in vivo makes it less likely that incremental BuChE contributes importantly to acetylcholine hydrolysis in AD. The findings do not support the premise that inhibitor therapy should target BuChE so as to prevent increased levels of BuChE from hydrolyzing acetylcholine in AD cerebral cortex. Ann Neurol 2006
Ubiquilin 1 polymorphisms are not associated with late‐onset Alzheimer's disease
Authors: Smemo Scott , Nowotny Petra , Hinrichs Anthony L. , Kauwe John S. K. , Cherny Sara , Erickson Katherine , Myers Amanda J. , Kaleem Mona , Marlowe Lauren , Gibson Alison M. , Hollingworth Paul , O'Donovan Michael C. , Morris Chris M. , Holmans Peter , Lovestone Simon , Morris John C. , Thal Leon , Li Yonghong , Grupe Andrew , Hardy John , Owen Michael J. , Williams Julie , Goate Alison
Published: November 2005

Several studies have reported evidence for linkage of late‐onset Alzheimer's disease (LOAD) to chromosome 9. Recently, an intronic polymorphism affecting alternative splicing of exon 8 of ubiquilin 1 (UBQLN1) was reported to be associated with LOAD. We attempted to replicate this observation by genotyping this polymorphism, rs12344615 (also known as UBQ‐8i), in a large sample of 1,544 LOAD cases and 1,642 nondemented controls. We did not find any evidence that this single nucleotide polymorphism, or any of six others tested in UBQLN1, increases risk for LOAD. Ann Neurol 2005
Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”
Authors: Polman Chris H. , Reingold Stephen C. , Edan Gilles , Filippi Massimo , Hartung Hans‐Peter , Kappos Ludwig , Lublin Fred D. , Metz Luanne M. , McFarland Henry F. , O'Connor Paul W. , Sandberg‐Wollheim Magnhild , Thompson Alan J. , Weinshenker Brian G. , Wolinsky Jerry S.
Published: November 2005

New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The “McDonald Criteria” have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity. Ann Neurol 2005