Analysis of a sequenced cDNA library from multiple sclerosis lesions

To identify genes that are expressed in MS pathogenesis, we have analyzed a normalized cDNA library made from mRNA obtained from CNS lesions of a patient with primary progressive MS. Complementary DNA clones obtained from this library were subjected to automated DNA sequencing to generate expressed sequence tags. Analysis of this MS cDNA library revealed the presence of 54 cDNAs that were associated with immune activation and indicated the presence of an ongoing inflammatory response with evidence of both cell-mediated and humoral immune responses. The surprising finding was that 16 of the cDNAs encoded autoantigens associated with seven other autoimmune disorders, while only three of these 16 autoantigen cDNAs were present in a similarly constructed adult brain library. Such aberrant autoantigen expression could provide a source of secondary autoimmune stimulation that could contribute to the ongoing inflammatory response in MS. In addition, two cDNAs were found that mapped to a known MS susceptibility locus (5p14–p12): one encoded an excitatory amino acid transporter and the other a human homologue of the Drosophila disabled gene. This approach to the molecular biology of MS pathogenesis may help to illuminate previously unappreciated aspects of this disease.     

Inter-rater reliability of manual segmentation of the superior, inferior and middle frontal gyri

Precise rules for locating the anatomical boundaries of the dorsolateral prefrontal cortex (DLPFC) or its subdivisions, i.e., superior, inferior and middle frontal gyri (SFG, IFG and MFG) on magnetic resonance images (MRI), have not been defined. The present study describes the inter-rater reliability of manual segmentation of the SFG, IFG and MFG using guidelines based on sulcal-gyral anatomical boundaries as well as the cytoarchitectonic features of the sub-regions of the prefrontal cortex (PFC). Variations in the application of these guidelines in different subjects to account for normal sulcal variability were developed using the atlas of Ono et al. (Ono, M., Kubik, S., Abernathey, C.D., 1990. Atlas of the Cerebral Sulci. Georg Thieme Verlag, New York). Based on previous cytoarchitectonic studies, the coronal plane of the anterior termination of olfactory sulcus (ATOS) was used as a landmark for delimiting the boundary between the frontal pole (FP) and the frontal gyri. The left hemisphere gray-matter volumes of the SFG, IFG and MFG were determined using a set of 10 MRIs (5 normal and 5 schizophrenia subjects) by two trained raters independently. The intra-class correlation coefficients (ICC) for the SFG, IFG and MFG volumes by the two raters were 0.97, 0.94 and 0.93, respectively. Thus, we describe a reliable method of parcellating the SFG, IFG and MFG, which constitute the DLPFC, a brain region involved in a variety of neuropsychiatric conditions.     

Water content and water structure in CT and MR signal changes: possible influence in detection of early stroke

Recent work by the authors and others has shown that MR imaging is more sensitive than CT in the detection of acute stroke. To separate the effects of water content and water structure on MR signal intensity, we undertook two sets of experiments that used simple model systems: gelatin gels with increasing water content and hardened hens' eggs. CT and MR were performed on both systems. On CT there was a direct linear relationship between CT attenuation (Hounsfield units) and the specific gravity of the gelatin gels, and an inverse relationship with water content. There was only a minimal change in the specific gravity of egg samples with hardening and, as expected on CT, no change in linear attenuation accompanying hardening. On MR there was a linear relationship between water content in gelatin gels and spin-lattice (T1) relaxation time (r = .92, p less than .01) and spin-spin (T2) relaxation time (r = .91, p less than .05). However, these changes were insufficient to explain the changes of signal intensity that occur in the brain with infarction. The simple cellular system with hens' eggs demonstrated that shortening of T1 and T2 accompanied egg hardening with minimal change in water content; the shift of water from bulk water to a bound or structured form was probably the basis of this phenomenon. We found that water structure and not merely water content is a significant mechanism underlying relaxation time changes and signal intensity changes in acute stroke.     

High-intensity basal ganglia lesions on T1-weighted MR images in neurofibromatosis

Basal ganglia lesions, characterized on MR by increased signal intensity on T1-weighted images, were observed in seven patients with documented neurofibromatosis. These lesions most often involved the globus pallidus and internal capsules in a bilateral and symmetric fashion, and extended across the anterior commissure resulting in a "dumbbell" configuration. Smaller and less prominent foci of increased signal also were present on corresponding T2-weighted images. These lesions did not exhibit mass effect, edema, or enhancement with gadolinium-DTPA. They were not visible on CT (performed in two patients) and demonstrated no progression during a 2-year interval in three patients. Their signal characteristics and morphology suggest that they represent heterotopias containing Schwann cells and/or melanin deposits. Migrational abnormalities of these neural crest derivatives are known to occur in neurofibromatosis, and the presence of such heterotopias has been documented pathologically in patients with this disorder. While recent reports discuss foci of increased signal intensity on T2-weighted MR images in patients with neurofibromatosis, signal abnormalities on T1-weighted images have not yet been described. When lesions characterized by similar signal as well as morphologic characteristics are encountered on MR, the diagnosis of neurofibromatosis should be considered.     

Divided nevus of the eyelids: three case studies

Divided nevus or kissing nevus is a rare form of congenital nevus that usually occurs on adjacent parts of the upper and lower eyelids of one eye. Most often, the formation is present from birth, but it may also appear later. Three new cases during the period 1996 to 2004 are reported. Two of them were treated in our unit for oncological, functional and aesthetic purposes, and one preferred not to be operated on. All our patients had divided nevus of the left eyelid. In the first case, the reconstruction was achieved with two tarso-conjunctival flaps covered with skin grafts. In the second case, we used a technique based on autologous cultivated conjunctival epithelium. The third patient preferred not to be operated on and is still under clinical follow-up. Because of the severe disfigurement, risk of later malignant change in the lesion, and the possibility of deprivation amblyopia, early surgical treatment is very important.     

Prevalence of physical, psychological, and sexual abuse among a nationwide sample of Arab high school students: association with family characteristics, anxiety, depression, self-esteem, and quality of life

Objectives  

The objectives were first, to assess the lifetime and 12-month prevalence of physical, psychological, and sexual abuse among a stratified random sample of Kuwaiti high school students and second, to explore the association of child abuse with parental characteristics, subjective quality of life (QOL), self-esteem, anxiety, and depression.     

Challenge of reducing perinatal mortality in rural Congo: findings of a prospective, population-based study

Each year, an estimated six million perinatal deaths occur worldwide, and 98% of these deaths occur in low- and middle-income countries. These estimates are based on surveys in both urban and rural areas, and they may underrepresent the problem in rural areas. This study was conducted to quantify perinatal mortality, to identify the associated risk factors, and to determine the most common causes of early neonatal death in a rural area of the Democratic Republic of the Congo (DRC). Data were collected on 1,892 births. Risk factors associated with perinatal deaths were identified using multivariate analysis with logistic regression models. Causes of early neonatal deaths were determined by physician-review of information describing death. The perinatal mortality rate was 61 per 1,000 births; the stillbirth rate was 30 per 1,000 births; and the early neonatal death rate was 32 per 1,000 livebirths. Clinically-relevant factors independently associated with perinatal death included: low birthweight [odds ratio (OR)=13.51, 95% confidence interval (CI) 7.82-23.35], breech presentation (OR)=12.41; 95% CI 4.62-33.33), lack of prenatal care (OR=2.70, 95% CI 1.81-4.02), and parity greater than 4 (OR=1.93 95% CI 1.11-3.37). Over one-half of early neonatal deaths (n=37) occurred during the first two postnatal days, and the most common causes were low birthweight/prematurity (47%), asphyxia (34%), and infection (8%). The high perinatal mortality rate in rural communities in the DRC, approximately one-half of which is attributable to early neonatal death, may be modifiable. Specifically, deaths due to breech presentation, the second most common risk factor, may be reduced by making available emergency obstetric care. Most neonatal deaths occur soon after birth, and nearly three-quarters are caused by low birthweight/prematurity or asphyxia. Neonatal mortality might be reduced by targeting interventions to improve neonatal resuscitation and care of larger preterm infants.     

In Vivo Survival of ?Viral Antigen–specific T Cells that Induce Experimental Autoimmune Encephalomyelitis

A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide–specific T cells that cross-reacted with MBP(87–99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Barr virus (EBV). These low dose viral peptide– specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide–specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen–specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide–specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide–specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.