bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinctive metaphyseal chondrodysplasia with severe distal radius and ulna involvement (upper extremity mesomelia) and normal height
Authors: Camera Andrea , Camera Gianni 
Published: September 2003

AbstractMetaphyseal chondrodysplasias (MCD) are skeletal disorders characterized by metaphyseal irregularities and, usually, by short stature. In MCD, wide heterogeneity exists with regard to clinical and radiological changes. We report on a patient with clinical and radiological findings of MCD who had coxa valga and normal height with metaphyseal involvement of the long bones. The short radii and ulnae showed a very severe change in their distal metaphyses, leading to mesomelic shortening confined to the upper limbs. Hematological, ophthalmological, and hearing examinations were normal. This type of MCD appears to represent a yet undescribed syndrome. © 2003 Wiley‐Liss, Inc.
A familial contiguous gene deletion syndrome at Xp22.3 characterized by severe learning disabilities and ADHD
Authors: Boycott Kym M. , Parslow Malcolm I. , Ross Judith L. , Miller Ivan P. , Bech‐Hansen N. Torben , MacLeod Patrick M. 
Published: September 2003

AbstractWe describe a mother and two sons with a 6‐Mb terminal deletion of the short arm of the X chromosome. The breakpoint was localized to a region between DXS6837 and sAJ243947 in Xp22.33. The two boys were shown to be deleted for the SHOX and ARSE genes on their X chromosome. Both sons were short in stature and showed mild to moderate skeletal abnormalities. The most significant findings in the younger son were severe learning disabilities and attention deficit hyperactivity disorder (ADHD). The older son tested in the mild mental retardation range and was also affected by ADHD. The VCX‐A gene, implicated recently in X‐linked nonspecific mental retardation, was found to be present in both boys. The mother's stature was greater than one standard deviation below her target height and she had only subtle radiographic evidence of Madelung deformity. Our findings indicate that loss of the Xp22.3 region is not always associated with the classic presentations of Léri‐Weill syndrome, or chondrodysplasia punctata, and that one or more genes involved in learning and attention may reside in Xp22.3. © 2003 Wiley‐Liss, Inc.
Prenatal diagnosis of boomerang dysplasia
Authors: Wessels Marja W. , Den Hollander Nicolette S. , De Krijger Ronald R. , Bonifé Luisa , Superti‐Furga Andrea , Nikkels Peter G. , Willems Patrick J. 
Published: September 2003

AbstractBoomerang dysplasia, atelosteogenesis type 1 and Piepkorn dysplasia are bone dysplasias with an overlapping clinical spectrum characterized by deficient formation and ossification of specific elements of the skeleton. Typical symptoms include micromelia with diminished ossification, and a characteristic bowed and boomerang‐like aspect of the long tubular bones. We report here a new case of boomerang dysplasia, which was detected prenatally in the 16th week of gestation by ultrasound. © 2003 Wiley‐Liss, Inc.
Subtle trisomy 12q24.3 and subtle monosomy 22q13.3: Three new cases and review
Authors: Rodríguez Laura , Guardia Nieves Martínez , Herens Christian , Jamar Mauricette , Verloes Alain , López Fermina , Mun̄oz José Santos , Martínez‐Frías María Luisa 
Published: September 2003

AbstractThe high resolution G‐bands (850 bands) karyotype have made it possible to identify small chromosome anomalies (5 megabases) which are now microscopically visible. New techniques have been improved, such as the Fluorescent in situ hybridization (FISH) with subtelomeric probes, which can be employed to detect cryptic chromosome alterations not visible microscopically. We present three cases which had been remitted for a high resolution karyotype. The high resolution G‐band karyotype and the FISH techniques led us to conclude that the three cases were carriers of a similar subtle chromosomal alteration. Case I is a new born female with developmental and psychomotor delay, hypotonia, and long limbs with arachnodactily. A high resolution G‐band karyotype showed an abnormal chromosome 22. FISH techniques confirmed a der(22)t(12;22)(q24.31;q13.3). Case II is a 12‐year‐old girl, with growth retardation, long shaped face with thick eyebrows, smooth philtrum, and thin upper lip with severe mental retardation (still no language), with a phenotype very similar to that of his sister: long shaped face, thick eyebrows, smooth philtrum, and thin upper lip. A high resolution G‐band karyotype also showed in Case II and III an abnormal chromosome 22, studied by FISH techniques which confirmed a der(22)t(12;22)(q24.3;q13.3) in both cases. © 2003 Wiley‐Liss, Inc.
Second reported patient with del(1)(p32.1p32.3) and similar clinical features suggesting a recognizable chromosomal syndrome
Authors: Zinner Samuel H. , Batanian Jacqueline R. 
Published: September 2003

AbstractInterstitial deletion of the short arm of chromosome 1 is rare. Eleven different breakpoints have been described in 12 children. We report a patient with del(1)(p32.1p32.3). Only one of the previously reported patients had an apparent identical deletion to that of the present case. The phenotypes of the two patients are strikingly similar. Distinctive features include excessive weight gain during the first 30 months, macrocephaly, frontal bossing, rounded face, mild synophyrs, slightly upslanting eyes, short palpebral fissures, broad nasal bridge, low set ears, prominent philtrum, long eyelashes, and delayed psychomotor development. © 2003 Wiley‐Liss, Inc.
Gershoni–Baruch syndrome: Report of a new family confirming autosomal recessive inheritance
Authors: Franceschini P. , Guala A. , Licata D. , Botta G. , Flora F. , Angeli G. , Di Cara G. , Franceschini D. 
Published: September 2003

AbstractGershoni–Baruch syndrome is a multiple congenital malformation complex characterized by omphalocele, diaphragmatic hernia, cardiovascular abnormalities, and radial ray defects. Autosomal recessive inheritance is suggested. We describe two additional cases from a single family (sister and brother) delivered through termination at 23 and 9 weeks of gestation, respectively. The first fetus showed a spectrum of schisis defects without any limb involvement while the second bore mainly malformations of hands and feet. The occurrence of two different syndromes in the same family is highly improbable, but, considering both malformation complexes as possible manifestations of the same disease, a diagnosis of Gershoni–Baruch syndrome appears the most reasonable. These new familial cases bring further support to the hypothesis of an autosomal recessive inheritance of this syndrome. © 2003 Wiley‐Liss, Inc.
Deletion of the SLUG (SNAI2) gene results in human piebaldism
Authors: Sánchez‐Martín Manuel , Pérez‐Losada Jesús , Rodríguez‐García Arancha , González‐Sánchez Belén , Korf Bruce R. , Kuster W. , Moss Celia , Spritz Richard A. , Sánchez‐García I. 
Published: September 2003

AbstractSlug is a zinc‐finger neural crest transcription factor, encoded by the SLUG gene, which is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. In mouse, heterozygous and homozygous slug mutations result in anemia, infertility, white forehead blaze, and depigmentation of the ventral body, tail, and feet. This phenotype is very similar to the heterozygous W (KIT)‐mutant mouse phenotype and to human piebaldism, which is characterized by a congenital depigmented patches and poliosis (white forelock). To investigate the possibility that some cases of human piebaldism might result from abnormalities of the human SLUG (SNAI2) gene, we carried out Southern blot analysis of the SLUG gene in 17 unrelated patients with piebaldism, who lack apparent KIT mutations. Three of these patients had evident heterozygous deletions of the SLUG gene encompassing the entire coding region. Real‐time PCR confirmed the deletion in all cases. Fluoresence in situ hybridization (FISH) of genomic SLUG probes to metaphase chromosomes independently confirmed the deletion in one of the cases. These findings indicate that some cases of human piebaldism result from mutation of the SLUG gene on chromosome 8, and provide further strong evidence for the role of SLUG in the development of human melanocytes. © 2003 Wiley‐Liss, Inc.
Schwann cell chemokine receptors mediate HIV‐1 gp120 toxicity to sensory neurons
Authors: Keswani Sanjay C. , Polley Michelle , Pardo Carlos A. , Griffin John W. , McArthur Justin C. , Hoke Ahmet 
Published: September 2003

AbstractHuman immunodeficiency virus (HIV)–associated sensory neuropathy (HIV‐SN) is the most common neurological complication of HIV infection. Currently, the pathogenesis of HIV‐SN is unknown. Because there is no convincing evidence of neuronal infection, HIV neurotoxicity is likely to be effected either by secreted viral proteins such as the envelope glycoprotein gp120 or by neurotoxic cytokines released from infected/activated glial cells. We describe a model of gp120 toxicity to primary sensory neurons, in which gp120 induces neuritic degeneration and neuronal apoptosis. We show that Schwann cells, the cells that ensheath peripheral nerve axons, and which traditionally have been viewed as having a passive, supporting role, mediate this neurotoxicity. Ligation of the chemokine receptor CXCR4 on Schwann cells by gp120 resulted in the release of RANTES, which induced dorsal root ganglion neurons to produce tumor necrosis factor–α and subsequent TNFR1‐mediated neurotoxicity in an autocrine fashion. This newly described Schwann cell–neuron interaction may be pathogenically relevant not only in HIV‐SN but also in other peripheral neuropathies. Ann Neurol 2003;54:287–296
Intraoperative infrared functional imaging of human brain
Authors: Gorbach Alexander M. , Heiss John , Kufta Conrad , Sato Susumo , Fedio Paul , Kammerer William A. , Solomon Jeffrey , Oldfield Edward H. 
Published: September 2003

AbstractWe hypothesized that it would be possible to detect the distribution of cortical activation by using a sensitive, rapid, high‐resolution infrared imaging technique to monitor changes in local cerebral blood flow induced by changes in focal cortical metabolism. In a prospective study, we recorded in 21 patients the emission of infrared radiation from the exposed human cerebral cortex at baseline, during language and motor tasks, and during stimulation of the contralateral median nerve using an infrared camera (sensitivity 0.02°C). The language and sensorimotor cortex was identified by standard mapping methods (cortical stimulation, median nerve somatosensory‐evoked potential, functional magnetic resonance imaging), which were compared with infrared functional localization. The temperature gradients measured during surgery are dominated by changes in local cerebral blood flow associated with evoked functional activation. The distribution of the evoked temperature changes overlaps with, but extends beyond, functional regions identified by standard mapping techniques. The distribution observed via infrared mapping is consistent with distributed and complex functional representation of the cerebral cortex, rather than the traditional concept of discrete functional loci demonstrated by brief cortical stimulation during surgery and by noninvasive functional imaging techniques. By providing information on the spatial and temporal patterns of sensory‐motor and language representation, infrared imaging may prove to be a useful approach to study brain function. Ann Neurol 2003
Speech production after stroke: The role of the right pars opercularis
Authors: Blank S. Catrin , Bird Helen , Turkheimer Federico , Wise Richard J. S. 
Published: September 2003

AbstractRecovery of speech after infarction of the left pars opercularis (POp) may be due to recruitment of homotopic cortex in the right hemisphere. Using positron emission tomography, we investigated activity within left and right POp during everyday propositional speech. We studied seven aphasic patients with left anterior perisylvian infarction which included the POp. We compared their data with two control groups: 12 normal subjects and 7 anterior aphasic patients whose infarcts spared the left POp. During propositional speech, normal subjects activated the left POp, left posterior perisylvian cortex, and a distributed, predominantly left‐lateralized, extrasylvian neural network. Importantly, activity in the right POp was reduced relative to a baseline nonspeech condition. In patients with infarction of the left POp, activity in the right POp was reversed: speech activated the right POp above baseline. Patient controls activated the left POp but did not show the normal relative reduction in activity in the right POp. In both patient groups, posterior perisylvian and extrasylvian activations remained unchanged from normal. This result demonstrates that infarction of the left POp is associated with a chronic change in function of the contralateral homotopic cortex during speech. Ann Neurol 2003;54:000–000
Aphasia in hyperacute stroke: Language follows brain penumbra dynamics
Authors: Croquelois Alexandre , Wintermark Max , Reichhart Marc , Meuli Reto , Bogousslavsky Julien 
Published: September 2003

AbstractDuring the first few hours after onset, stroke symptoms may evolve rapidly. We studied the correlation between brain perfusion and aphasia changes during the hyperacute phase of stroke using a new technique of perfusion computed tomography (P‐CT). Using an aphasia score developed for each language modality, language was evaluated within 6 hours after onset, then sequentially during the first week. Maps of the penumbra and infarct obtained from P‐CT images and definite infarct size evaluated using T2 and diffusion‐weighted MRI (DWI) on day 3 were rated by a neuroradiologist, blinded to the clinical deficit. Within 6 hours, deficits in all language modalities were present in 13 out of 24 consecutive patients, corresponding to large anterior‐posterior perfusion deficits of the left middle cerebral artery (MCA) territory. The aphasia score correlated with a corresponding perfusion deficit in specific areas of the MCA territory, and showed significantly less improvement when the penumbra evolved toward infarction than when at least part of the penumbra was rescued. Our findings suggest a particularly good correlation between the evolution of aphasic symptoms and penumbra dynamics. Further studies on the relevance of penumbra dynamics in function‐specific brain areas to decision taking in hyperacute stroke management are required.
Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia
Authors: Ginsberg Myron D. , Becker David A. , Busto Raul , Belayev Andrey , Zhang Yongbo , Khoutorova Larissa , Ley James J. , Zhao Weizhao , Belayev Ludmila 
Published: September 2003

AbstractAzulenyl nitrones are novel chain‐breaking antioxidants with low oxidation potentials and high lipophilicity—properties favoring their efficacy as neuroprotectants. We tested the second‐generation azulenyl nitrone, stilbazunenlyl nitrone (STAZN), in focal ischemic stroke. Physiologically monitored rats received 2 hours of middle cerebral artery occlusion by intraluminal suture, resulting in substantial cortical and striatal infarcation. Neurobehavior was quantified on a standard battery, and brains were perfusion‐fixed for quantitative histopathology at 3 days. In 3 independent series, rats were treated at either 2h + 4h, or 2h + 4h + 24h + 48h, after onset of ischemia; vehicle‐treated rats received dimethylsulfoxide or saline. All animals (n = 52) developed high‐grade neurological deficits (score 11 of 12) during ischemia, which improved, in STAZN‐treated rats, within 1–1.5 h of the initial dose and fell to a median score of 3 at 72 h, compared to 8 in vehicle rats. STAZN treatment reduced mean cortical infarct volume by 64–97%, and total infarct volume by 42–72%. In over one‐half of STAZN‐treated animals, cortical infarction was virtually abolished. Regression analysis predicted that STAZN would confer ∼50% cortical neuroprotection even in the most severely affected cases. The potency of STAZN was orders‐of‐magnitude greater than other nitrones such as NXY‐059. These results suggest that STAZN has great promise for ischemic stroke. Ann Neurol 2003
Cerebral hemorrhage produced by ruptured dissecting aneurysm in miliary aneurysm
Authors: Rosenblum William I. 
Published: September 2003

AbstractThis report describes, for what may be only the second time, a ruptured miliary aneurysm within a cerebral hemorrhage. The report is unique in that the aneurysm has arisen at the site of a dissection within the wall of an arteriole at a site of fibrinoid necrosis. The case not only is a unique illustration of this pathogenetic pathway to miliary aneurysm formation, but also reemphasizes the relationship between fibrinoid and miliary aneurysm formation.
Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment
Authors: Nestor Peter J. , Fryer Tim D. , Smielewski Peter , Hodges John R. 
Published: September 2003

AbstractThe neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction.
Matrix metalloproteinase–9 and spontaneous hemorrhage in an animal model of cerebral amyloid angiopathy
Authors: Lee Jin‐Moo , Yin Ke‐Jie , Hsin Idar , Chen Shawei , Fryer John D. , Holtzman David M. , Hsu Chung Y. , Xu Jian 
Published: September 2003

AbstractWe examined the potential role of the extra‐cellular matrix‐degrading enzyme, matrix metalloproteinase‐9 (MMP‐9), in the pathogenesis of cerebral amyloid angiopathy (CAA)‐induced spontaneous hemorrhage. The amyloid‐beta peptide (Aβ) induced the synthesis, release and activation of MMP‐9 in murine cerebral endothelial cells, resulting in increased extracellular matrix degradation. Furthermore, extensive MMP‐9 immunoreactivity was observed in CAA‐vessels with evidence of microhemorrhage in aged APPsw transgenic mice, but not detected in aged wild type or young APPsw mice. These results suggest that increased vascular MMP‐9 expression, stimulated by Aβ, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage in patients with CAA. Ann Neurol 2003;54:000–000
Transfer of the von Hippel‐Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease
Authors: Yamada Hitoshi , Dezawa Mari , Shimazu Seiichiro , Baba Masaya , Sawada Hajime , Kuroiwa Yoshiyuki , Yamamoto Isao , Kanno Hiroshi 
Published: September 2003

AbstractNeuronal progenitor cells (NPCs) may provide dopaminergic neurons for the treatment of Parkinson's disease (PD). However, transplantation of NPCs into the striatum by current methods has had limited success. It is possible to reverse the symptoms of PD in model rats but difficult to reverse them in humans because the number of dopaminergic neurons generated from NPCs is low. We transduced the von Hippel–Lindau (VHL) gene into NPCs isolated from embryonic rat brain. The NPCs with the transduced VHL gene efficiently differentiated into tyrosine hydroxylase–positive neurons in vitro. NPCs with the transduced VHL gene, which were labeled in advance with bromodeoxyuridine, were transplanted into the striatum of a rat model of PD. Numerous bromodeoxyuridine–tyrosine hydroxylase double‐labeled cells were seen close to the transplant site, showing that the transplanted cells efficiently generated new dopaminergic neurons within the host striatum. Moreover, all of the animals with NPCs with VHL showed a remarkable decrease in apomorphine‐induced rotations. These findings show that NPCs with the VHL gene can efficiently generate dopaminergic neurons and that a sufficient number of dopaminergic neurons can develop from them to reverse the symptoms of PD in humans. VHL gene transduction provides a new therapeutic approach for treatment of PD. Ann Neurol 2003; 54:352–359
Novel mutations in the Na+, K+‐ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions
Authors: Vanmolkot Kaate R. J. , Kors Esther E. , Hottenga Jouke‐Jan , Terwindt Gisela M. , Haan Joost , Hoefnagels Wil A. J. , Black David F. , Sandkuijl Lodewijk A. , Frants Rune R. , Ferrari Michel D. , Van Den Maagdenberg Arn M. J. M. 
Published: September 2003

AbstractFamilial hemiplegic migraine (FHM) is a rare, severe, autosomal dominant subtype of migraine with aura. Up to 75% of FHM families have a mutation in the P/Q‐type calcium channel Cav2.1 subunit CACNA1A gene on chromosome 19p13. Some CACNA1A mutations also may cause epilepsy. Here, we describe novel missense mutations in the ATP1A2 Na+,K+‐ATPase pump gene on chromosome 1q23 in two families with FHM. The M731T mutation was found in a family with pure FHM. The R689Q mutation was identified in a family in which FHM and benign familial infantile convulsions partially cosegregate. In this family, all available affected family members with FHM, benign familial infantile convulsions, or both, carry the ATP1A2 mutation. Like FHM linked to 19p13, FHM linked to 1q23 also involves dysfunction of ion transportation and epilepsy is part of its phenotypic spectrum.
The role of pathogenic DJ‐1 mutations in Parkinson's disease
Authors: Abou‐Sleiman Patrick M. , Healy Daniel G. , Quinn Niall , Lees Andrew J. , Wood Nicholas W. 
Published: September 2003

AbstractMutations in DJ‐1 (PARK7) have been reported in two consanguineous families with young‐onset Parkinson's disease (YOPD). This study aims to confirm the presence of pathogenic DJ‐1 mutations and determine their contribution in young‐onset and more typical later onset Parkinson's disease (PD). The entire open reading frame of the DJ‐1 gene was screened by direct sequencing in 185 unrelated YOPD patients and a separate cohort of 190 pathologically proven cases of PD. Ethnically matched controls were screened for all mutations identified. We report a low frequency of pathogenic DJ‐1 mutations in our cohort of patients. One homozygous missense mutation and one heterozygous mutation were found in two YOPD samples. In addition, several variants were found in the coding sequence of the gene, which are likely to represent polymorphisms. In one case, the polymorphism was population specific. The reported 14Kbp deletion was not found in any of our samples or controls. We confirm the presence of pathogenic DJ‐1 mutations in YOPD and estimate their frequency at approximately 1%. No mutations were found in our cohort of later onset sporadic pathologically confirmed cases, suggesting that DJ‐1 mutations may only rarely contribute to the cause of this more typical sporadic form of the disease.