Biomedical subjects

Karen Barlow

Publications and source records attributed to Karen Barlow.

9 recordsLinked to original sources

PubMed2006

Chronic restraint stress decreases the expression of glutathione S-transferase pi2 in the mouse hippocampus.

Chronic restraint stress in mice affects hippocampal structure and function. Mice were subjected to daily restraint for 3 weeks, and gene expression in hippocampus was compared to controls using large-scale cDNA microarrays. We found that 444 genes were differentially expressed, and further analysis of 6 genes by real-time reverse transcription PCR confirmed that 3 of them were downregulated by stress. These 3 genes, growth factor receptor-bound protein 2 (Grb2), phosphatidylinositol-4-phosphate 5-kinase, type 1 beta (Pip5k1b), and glutathione S-transferase, pi2 (Gstp2), were also analyzed by in situ hybridization. The downregulation of Gstp2 may induce an increase of oxidative damage in the pyramidal cells of the CA1 and CA3 regions and granular layer of the dentate gyrus, leading to structural and functional damage. Those regions are affected by stress, and our results could help understand further the mechanisms involved in the occurrence of stress-related disorders.

Animals↗

PubMed2006

Genomic anatomy of the Tyrp1 (brown) deletion complex.

Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (l4Rn1, l4Rn2, and l4Rn3) and the fitness mutant brown-associated fitness (baf). We have also characterized misexpression of the basonuclin homologue, Bnc2, associated with the inversion-mediated coat color mutant white-based brown (B(w)). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis.

Animals↗

PubMed2006

A conserved supergene locus controls colour pattern diversity in Heliconius butterflies.

We studied whether similar developmental genetic mechanisms are involved in both convergent and divergent evolution. Mimetic insects are known for their diversity of patterns as well as their remarkable evolutionary convergence, and they have played an important role in controversies over the respective roles of selection and constraints in adaptive evolution. Here we contrast three butterfly species, all classic examples of Müllerian mimicry. We used a genetic linkage map to show that a locus, Yb, which controls the presence of a yellow band in geographic races of Heliconius melpomene, maps precisely to the same location as the locus Cr, which has very similar phenotypic effects in its co-mimic H. erato. Furthermore, the same genomic location acts as a "supergene", determining multiple sympatric morphs in a third species, H. numata. H. numata is a species with a very different phenotypic appearance, whose many forms mimic different unrelated ithomiine butterflies in the genus Melinaea. Other unlinked colour pattern loci map to a homologous linkage group in the co-mimics H. melpomene and H. erato, but they are not involved in mimetic polymorphism in H. numata. Hence, a single region from the multilocus colour pattern architecture of H. melpomene and H. erato appears to have gained control of the entire wing-pattern variability in H. numata, presumably as a result of selection for mimetic "supergene" polymorphism without intermediates. Although we cannot at this stage confirm the homology of the loci segregating in the three species, our results imply that a conserved yet relatively unconstrained mechanism underlying pattern switching can affect mimicry in radically different ways. We also show that adaptive evolution, both convergent and diversifying, can occur by the repeated involvement of the same genomic regions.

Animals↗

PubMed2005

Autosomal recessive cerebellar hypoplasia in the Hutterite population.

Cerebellar hypoplasia is a rare malformation caused by a variety of etiologies. It usually manifests clinically as non-progressive cerebellar ataxia with or without mental retardation. We further characterize a syndrome of autosomal recessive cerebellar hypoplasia in the Hutterite population, referred to as dysequilibrium syndrome (DES). We reviewed 12 patients (eight females, four males; age range 4 to 33 y) with this syndrome. Patients were examined and underwent a standard set of investigations to characterize better the clinical features, natural history, and neuroimaging of this syndrome. DES is an autosomal recessive disorder with distinct clinical features including global developmental delay, late ambulation (after age 6 y), truncal ataxia, and a static clinical course. Neuroimaging is characterized by hypoplasia of the inferior portion of the cerebellar hemispheres and vermis, and mild simplification of cortical gyri.

Adolescent↗

PubMed2005

Sleep disturbances in children with epilepsy compared with their nearest-aged siblings.

The aim of the study was to compare sleep patterns in children with epilepsy with those of their non-epileptic siblings and to determine which epilepsy-specific factors predict greater sleep disturbance. We conducted a case-control study of 55 children with epilepsy (mean age 10y, range 4 to 16y; 27 males, 28 females) and their nearest-aged non-epileptic sibling (mean age 10y, range 4 to 18y; 26 males, 29 females). Epilepsy was idiopathic generalized in eight children (15%), symptomatic generalized in seven (13%), and focal in 40 (73%); the mean duration was 5 years 8 months. Parents or caregivers completed the Sleep Behavior Questionnaire (SBQ) and Child Behavior Checklist (CBCL) for patients and controls, and the Quality of Life in Childhood Epilepsy (QOLCE) for patients. Patients had a higher (more adverse) Total Sleep score (p<0.001) and scored worse than controls on nearly all subscales of the SBQ. In patients, higher Total Sleep scores were correlated with higher scores on the Withdrawn, Somatic complaints, Social problems, and Attention subscales of the CBCL, and significantly lower Total Quality of Life Scores. Refractory epilepsy, mental retardation, and remote symptomatic etiology predicted greater sleep problems in those with epilepsy. We conclude that children with epilepsy in this current study had significantly greater sleep problems than their non-epileptic siblings.

Adolescent↗

PubMed2005

Use of complementary and alternative medical therapies in a pediatric neurology clinic.

BACKGROUND: Complementary and alternative medicine (CAM) is increasingly used in adults and children. Studies on CAM in neurological disorders have focused on the adult population and its use among pediatric neurology patients has not been well characterized. OBJECTIVES: The purpose of this study was: 1) To characterize the prevalence of CAM in pediatric neurology patients; 2) To determine the perceived effectiveness of CAM in these children; 3) To compare the cost of CAM with conventional therapies; and 4) To describe caregiver or patient-related variables associated with the use of CAM. METHODS: This was a cross-sectional survey of patients and families attending the Alberta Children's Hospital neurology clinic between February and May 2004. Patients were considered eligible if they were between two and 18 years of age and had a known history of neurological disorders. Caregivers completed several self-administered questionnaires regarding their socio-demographic profile, their child's neurological illness, and their experience with CAM. Caregivers also rated their child's quality of life using the Pediatric Quality of Life Inventory. RESULTS: One hundred and five of 228 (46%) families completed the survey. The mean age of the neurology patients was 9.8 +/- 4.5 years. Forty-six (44%) out of 105 patients received one or more types of CAM, with the most common types being chiropractic manipulations (15%), dietary therapy (12%), herbal remedies (8%), homeopathy (8%), and prayer/faith healing (8%). Caregivers' sociodemographic variables or pediatric health-related quality of life were not significantly associated with the use of CAM. Fifty-nine percent of CAM users reported benefits, and only one patient experienced side effects. There was no significant difference in the total median cost of CAM compared to conventional therapies (31.70 dollars vs. 50.00 dollars per month). Caregivers' personal experience or success stories from friends and media were common reasons for trying CAM. CONCLUSIONS: The use of CAM was common among pediatric neurology patients. Over half of the families reported benefits with CAM, and side effects were perceived to be few. Physicians should initiate discussion on CAM during clinic visits so that the families and patients can make informed decisions about using CAM. Further studies should address the specific role of CAM in children with neurological disorders, and to determine the potential interactions between CAM and conventional therapies in these patients.

Adolescent↗

PubMed2004

Stroke after varicella vaccination.

Two children presented with acute hemiparesis 5 days and 3 weeks following varicella vaccination. Both showed unilateral infarction of the basal ganglia and internal capsule, a distribution consistent with varicella angiopathy. Both children had small patent foramen ovale (PFO), and one child also had severe iron-deficiency anemia, which may have predisposed the patient to this adverse effect.

Chickenpox Vaccine↗

PubMed2002

Initial sequencing and comparative analysis of the mouse genome.

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

Animals↗

PubMedDate not supplied

The neurological outcome of non-accidental head injury.

PURPOSE: The literature regarding the outcome of non-accidental head injury (NAHI) is scarce and lacks specific detail even though it is generally considered to be poor. The purpose of this study is to review the literature to date and report the neurological outcome of these children in detail. METHODS: A cross-sectional and prospective study of children admitted to hospital with NAHI in Scotland. RESULTS: Twenty-five children were enrolled and 68% of children were neurologically abnormal at an average follow-up of 59 months. A wide range of abnormalities and outcomes was seen. Speech and language difficulties were present in 64% including autistic spectrum disorder. Cranial nerve abnormalities were present in 20%. Visual deficits and epilepsy compounded learning difficulties in 25% of survivors. Consent for follow-up was more likely to be obtained where the perpetrator was known. CONCLUSIONS: The spectrum and degree of severity of neurological abnormalities in survivors of NAHI is extremely variable, with the majority of these children being moderate or severely abnormal. These children require the support of a multi-disciplinary team in the community. Further study regarding the process of follow-up, where complex medicolegal issues exist, are needed in order to facilitate maximum neurological development.

Child, Preschool↗