Montreal Children's Hospital

About: Montreal Children's Hospital is a healthcare organization based out in Montreal, Quebec, Canada. It is known for research contribution in the topics: Population & Poison control. The organization has 3842 authors who have published 4816 publications receiving 200198 citations.

Effect of Nitroglycerin and Dipyridamole on Regional Coronary Resistance

Abstract: We studied the changes caused by intravenous injection of nitroglycerin (0.3 to 0.6 mg) and dipyridamole (5 to 10 mg) on the resistance of large and small coronary arteries of dogs. The direction of change in resistance of large conductive vessels (Rc) was estimated by dividing the pressure drop from aorta to a superficial branch by the flow in that vessel. The total resistance (Rt) in the same vessel was estimated by relating aortic pressure to the same flow. The effects of both drugs on aortic pressure were comparable 3 to 7 minutes after injection. Nitroglycerin during this period caused a reduction in Rc, whereas dipyridamole caused a significant reduction in Rt for 12 minutes but no consistent changes in Rc. In the same preparation, small intracoronary doses of the drugs, which hardly affected the aortic pressure, caused comparable changes in resistance. This was also evident in a preparation in which the flow in the coronary vessel was held constant. These two drugs therefore differ in their site of action on the coronary vascular bed, a difference which may explain their contrasting therapeutic effects in chronic coronary disease in man.

Aphasia and handedness in relation to hemispheric side, age at injury and severity of cerebral lesion during childhood

Abstract: The effects of the variables of hemispheric side of lesion, age at injury and severity of cerebral damage on language performance and hand dominance were investigated in groups of hemiparetic children. Severity of cerebral damage was defined by the degree of structural abnormality shown on computed tomography (CT) scans. Tests of auditory verbal comprehension and object naming were used as indicators of productive and receptive language skills. The responses to a series of questions on a handedness inventory provided a rated measure of hand dominance. The results indicated that language deficits characterize the performance of all patient groups with left cerebral injuries. Impairments are more profound, however, in the case of left hemisphere injuries acquired after the age of 5 years. In addition, prenatal and early postnatal left cerebral lesions consistently result in strong sinistrality. It is concluded that the crucial variable underlying the demonstration of language deficits and left hand dominance is not severity of lesion but age at injury and hemispheric side of lesion.

Human microphthalmia associated with mutations in the retinal homeobox gene CHX10.

Abstract: Isolated human microphthalmia/anophthalmia, a cause of congenital blindness, is a clinically and genetically heterogeneous developmental disorder characterized by a small eye and other ocular abnormalities. Three microphthalmia/anophthalmia loci have been identified, and two others have been inferred by the co-segregation of translocations with the phenotype. We previously found that mice with ocular retardation (the or-J allele), a microphthalmia phenotype, have a null mutation in the retinal homeobox gene Chx10 (refs 7,8). We report here the mapping of a human microphthalmia locus on chromosome 14q24.3, the cloning of CHX10 at this locus and the identification of recessive CHX10 mutations in two families with non-syndromic microphthalmia (MIM 251600), cataracts and severe abnormalities of the iris. In affected individuals, a highly conserved arginine residue in the DNA-recognition helix of the homeodomain is replaced by glutamine or proline (R200Q and R200P, respectively). Identification of the CHX10 consensus DNA-binding sequence (TAATTAGC) allowed us to demonstrate that both mutations severely disrupt CHX10 function. Human CHX10 is expressed in progenitor cells of the developing neuroretina and in the inner nuclear layer of the mature retina. The strong conservation in vertebrates of the CHX10 sequence, pattern of expression and loss-of-function phenotypes demonstrates the evolutionary importance of the genetic network through which this gene regulates eye development.

Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.

Abstract: Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n=142; 122 males and 20 females) or SCZ (n=143; 95 males and 48 females). We identified >200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1).