Cerebral Palsy

Mammalian parthenogenetic embryos are not viable and die due to defects in placental development and genomic imprinting. Parthenogenetic embryonic stem cells (pESC) derived from parthenogenetic embryos might advance regenerative medicine by avoiding immuno-rejection. However, previous reports suggest that pESC may fail to differentiate and contribute to some organs in chimeras, including muscle and pancreas, and it remains unclear whether pESC themselves can form all tissue types in the body. We found that derivation of pESC is more efficient than of fESC, in association with reduced MAPK signaling in parthenogenetic embryos and their ICM outgrowth. Furthermore, in vitro culture modifies the expression of imprinted genes in pESC and these cells, being functionally indistinguishable from fertilized embryo-derived ESCs, can contribute to all organs in chimeras. Even more surprisingly, our study shows that live parthenote pups were produced from pESC via tetraploid embryo complementation, which contributes to placenta development. This is the first demonstration that pESCs are capable of full-term development, and can differentiate into all cell types and functional organs in the body.

Kell (ECE-3), a highly polymorphic blood group glycoprotein, displays more than 30 antigens that produce allo-antibodies and, on red blood cells (RBCs), is complexed through a single disulfide bond with the integral membrane protein, XK. XK is a putative membrane transporter whose absence results in a late onset form of neuromuscular abnormalities known as the McLeod syndrome. Although Kell glycoprotein is known to be an endothelin-3-converting enzyme, the full extent of its physiological function is unknown. To study the functions of Kell glycoprotein, we undertook targeted disruption of the murine Kel gene by homologous recombination. RBCs from Kel(-/-) mice lacked Kell glycoprotein, Kell/XK complex, and endothelin-3-converting enzyme activity and had reduced levels of XK. XK mRNA levels in spleen, brain, and testis were unchanged. In Kel(-/-) mice RBC Gardos channel activity was increased and the normal enhancement by endothelin-3 was blunted. Analysis of the microvessels of tumors produced from LL2 cells indicated that the central portion of tumors from wild-type mice were populated with many mature blood vessels, but that vessels in tumors from Kel(-/-) mice were fewer and smaller. The absence of Kell glycoprotein mildly affected some motor activities identified by foot splay on the drop tests. The targeted disruption of Kel in mouse enabled us to identify phenotypes that would not be easily detected in humans lacking Kell glycoprotein. In this regard, the Kell knockout mouse provides a good animal model for the study of normal and/or pathophysiological functions of Kell glycoprotein. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

Gliomas, the most frequent primitive CNS tumors, have been suggested to originate from astrocytes or from neural progenitor/stem cells. However, the precise identity of the cells at the origin of gliomas remains a matter of debate because no pre-neoplastic state has been yet identified. TGFalpha, an EGF family member, is frequently over-expressed in the early stages of glioma progression. We previously demonstrated that prolonged exposure of astrocytes to TGFalpha is sufficient to trigger their reversion to a neural progenitor-like state. To determine whether TGFalpha de-differentiating effects are associated with cancerous transforming effects, we grafted intra-cerebrally de-differentiated astrocytes. We show that these cells had the same cytogenomic profile as astrocytes, survived in vivo and did not give birth to tumors. When astrocytes de-differentiated with TGFalpha were submitted to oncogenic stress using gamma irradiation, they acquired cancerous properties: they were immortalized, showed cytogenomic abnormalities, and formed high-grade glioma-like tumors after brain grafting. In contrast, irradiation did not modify the lifespan of astrocytes cultivated in serum-free medium. Addition of TGFalpha after irradiation did not promote their transformation but decreased their lifespan. These results demonstrate that reversion of mature astrocytes to an embryonic state without genomic manipulation is sufficient to sensitize them to oncogenic stress.

PURPOSE: To evaluate and compare the accuracy of different formulas to estimate fetal weight using 2D and 3D ultrasound. MATERIALS AND METHODS: We performed a prospective study on unselected singleton pregnancies. All scanned fetuses delivered within 7 days in absence of structural and chromosomal abnormalities were included. The fetal weight was calculated using the 3D Schild, Chang, Liang and 2D Hansmann, Merz and Hadlock formulas. Absolute and mean deviations of estimated fetal weight were calculated. RESULTS: Of 249 scanned fetuses 200 that fulfilled the criteria were included. Birth weights ranged between 535 and 5020 g. The highest correlation between estimated fetal and birth weight was achieved by applying Schild’s equation, and the absolute percentage error was 5.6 %. The corresponding values for 2D Hansmann, Merz and four-parametric Hadlock formulas were 7.5 %, 7.9 %, and 9.2 %, respectively, while these were 13.1 % and 30.7 % for Liang’s and Chang’s 3D equations. Using the Schild formula, a deviation from birth weight below 10 % was achieved in 80 % of fetuses, with Hansmann’s in 73.5 % and with Merz in 72.5 %, while this parameter was much lower in the remaining equations. CONCLUSION: The best option with the highest accuracy for sonographic fetal weight estimation was the 3D Schild equation followed by the 2D Hansmann and Merz formulas. Published data of the accuracy could be reproduced with the exception of the “Asian” 3D equations in our European population. The limited improvement in weight agreement using the 3D technique compared to the 2D technique may be outweighed by the time consumption.

Inhibition of return (IOR) represents a well-known mechanism of human perception that biases attentional orienting to novel locations in the environment. Behaviorally, IOR reflects slower reaction time (RT) to stimuli presented in previously cued locations. In this study, we examined within patients with schizophrenia this inhibitory aftereffect using two different cue types-eye gaze and standard peripheral cues. Results indicated that patients showed evidence of IOR, as reflected in a 3.2% slowing in RT to previously peripherally cued locations. However, for eye gaze, patients failed to show evidence of IOR and instead had 1.7% faster RT to targets presented following delay in locations that had been previously cued. This inhibitory failure correlated strongly with reduced neuropsychological performance and global symptoms ratings of attention and bizarre behavior. Reduced inhibitory aftereffect in RT for eye-gaze cues may reflect disease-related abnormalities in social attention.

Skin and teeth not only share several characteristics in their development but also have a similar ontogenetic origin from the ectoderm. Thus, numerous congenital diseases, such as genetic, infectious, inflammatory, and immune disorders affect both skin and teeth. Particularly skin diseases are often identified by the synopsis of systemic symptoms. The understanding and appreciation of dental abnormalities guides dermatologists in the diagnosis and identification of syndromes as well as in finding an optimal therapy.

SUNCT has been reported in association with abnormalities of the brainstem and pituitary region. We present a patient with a history of left optic nerve hypoplasia, mild hypothalamic-pituitary dysfunction, and SUNCT starting in adolescence. SUNCT with an early age of onset may be associated with congenital abnormality of the hypothalamic-pituitary axis.

This study aimed to determine the relationship between pagophagia (compulsive ice eating) and H. pylori infection in patients with iron-deficiency anemia. We identified H. pylori infection using the (13)C-urea breath test in 45 patients with iron-deficiency anemia (group 1) and 55 patients with iron-deficiency anemia and pagophagia (group 2). Subgroups for testing oral intestinal iron absorption were randomly assigned from both groups. These subgroups consisted of (a) 10 patients with iron-deficiency anemia, (b) 10 patients with iron-deficiency anemia and pagophagia, (c) 10 patients with iron-deficiency anemia, pagophagia, and H. pylori infection before the eradication of H. pylori and (d) subgroup c after eradication therapy. There was no difference in the rate of H. pylori infection in the iron-deficiency anemia groups, with or without pagophagia. Furthermore, oral intestinal iron absorption was not influenced by pagophagia and/or H. pylori infection. Pagophagia did not increase the risk of H. pylori infection in patients with iron-deficiency anemia. Pagophagia and H. pylori infection do not synergistically affect the development of intestinal iron absorption abnormalities.

Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis.

OBJECTIVE: Utilizing a population-based registry, the burden of comorbidity was ascertained in a sample of children with cerebral palsy and stratified according to both neurologic subtype and functional capability with respect to gross motor skills. METHODS: The Quebec Cerebral Palsy Registry was utilized to identify children over a 4-year birth interval (1999-2002 inclusive) with cerebral palsy. Information on neurologic subtype classified according to the qualitative nature and topographic distribution of the motor impairment on neurologic examination, Gross Motor Function Classification System (GMFCS) categorization of motor skills, and the presence of certain comorbidities (cortical blindness, auditory limitations, nonverbal communication skills, gavage feeding status, and coexisting afebrile seizures in the prior 12 months) was obtained. RESULTS: The frequency of individual comorbidities, their proportional distribution, and mean number of occurrences basically falls into a significant dichotomous distribution. Across the spectrum of comorbidities considered, these comorbidities are relatively infrequently encountered in those with spastic hemiplegic or spastic diplegic variants or ambulatory GMFCS status (levels I-III), while these entities occur at a frequent level for those with spastic quadriplegic, dyskinetic, or ataxic-hypotonic variants or nonambulatory GMFCS status (levels IV and V). CONCLUSION: The enhanced burdens of comorbidity are unevenly distributed in children with cerebral palsy in a manner that can be associated with either a specific neurologic subtype (spastic quadriplegic, dyskinetic, ataxic-hypotonic) or nonambulatory motor status (Gross Motor Function Classification System levels IV and V). This provides enhanced value to the utilization of these classification approaches.