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Biomedical subjects

Sandra C Kirkwood

Publications and source records attributed to Sandra C Kirkwood.

4 recordsLinked to original sources
PubMed2004

Phencyclidine-induced changes in rat cortical gene expression identified by microarray analysis: implications for schizophrenia.

Acute phencyclidine induces schizophrenia-like symptoms in healthy humans and psychotic episodes in schizophrenics. Although phencyclidine is known as a N-methyl d-aspartate receptor antagonist (NMDA-R), the molecular events underlying the behavioral symptoms remain largely unknown. Statistical analysis of oligonucleotide microarray data was used to identify phencyclidine-induced alterations in rat cortical gene expression. Acute phencyclidine produced a statistically significant change in 477 genes in rat prefrontal cortex (PFC), a brain area associated with cognitive dysfunction in schizophrenics. Real-time quantitative PCR (RTQ-PCR) confirmed a subset of these changes ranging from -59% to 255% (smallest confirmation: -19%). Subsequent time-course and dose-response studies using RTQ-PCR confirmed and extended the original microarray results. At the molecular level, genes altered by phencyclidine are related to diverse biological processes including stress, inflammatory response, growth and development, neural plasticity and signal transduction. Further analysis, aimed at assessing the relevance of our results to schizophrenia, revealed dysregulation of genes related to: (i) thalamocortical projections, (ii) neurotransmission and neuromodulation, (iii) thyroid hormone activity, (iv) oligodendrocyte linage, (v) brain lipid metabolism, (vi) sleep architecture and (viii) the velocardiofacial syndrome.

Animals↗
PubMed2003

Visual function in Huntington's disease patients and presymptomatic gene carriers.

Disturbances of visual cognition, visuomotor performance, and visual memory have been described frequently in Huntington's disease (HD). Early stage visual abnormalities could contribute to these deficits. We evaluated visual processing in 20 control subjects who were non-gene carriers at risk for HD, nine presymptomatic gene-positive subjects, and eight subjects with a recent diagnosis of Huntington's disease. Visual perceptual tests of contrast sensitivity and motion discrimination were used to probe early stage visual processing. Extraocular movements were evaluated in a neurologic examination, and the Digit Symbol test was used to test visual motor performance. Contrast sensitivity did not differ among the three groups. Motion discrimination was impaired in HD subjects but not in the presymptomatic gene carriers when compared to gene noncarriers. Among gene carriers, impaired motion discrimination performance was associated with poorer Digit Symbol performance and extraocular abnormalities. These findings suggest that the early stages of HD are associated with disturbances of motion perception as well as disruptions of visual motor and ocular motor performance.

Adult↗
PubMed2002

Pharmacogenomic biomarkers.

Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

Drug Design↗