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Biomedical subjects

S Leonard

Publications and source records attributed to S Leonard.

At least 19 recordsLinked to original sources
PubMed2006

Brain pH has a significant impact on human postmortem hippocampal gene expression profiles.

Studies of neurobiological disorders in the brain, including schizophrenia, rely on the use of postmortem brain tissues, in which an understanding of the effects of various pre- and postmortem variables on gene expression is critical. In several different brain regions, pH has been shown to have a large effect on postmortem brain gene expression patterns. One region that has not yet been evaluated in such studies is the hippocampus, a region often implicated in schizophrenia research. In the present study, we show that postmortem brain pH is similar across different brain regions. Brain pH accounted for greater variation in hippocampal gene expression profiles than any other parameter evaluated, including gender and schizophrenia. The predictive value of brain pH in an independent sample set was also greater than the disease, demonstrating that pH represents one of the most important control parameters in human postmortem gene expression studies in schizophrenia.

Adult↗
PubMed2006

Mechanisms regulating immune cell contributions to spiral artery modification -- facts and hypotheses -- a review.

Early during murine, human and porcine pregnancy, endometrium associated with developing placentae is enriched for uterine Natural Killer (uNK) cells. A shared role for uNK cells in each of these species is production of angiogenic growth factors. Many uNK cells are located in close proximity to or structurally integrated within the walls of endometrial vessels. In mice, uNK cells have been found essential for the initiation of pregnancy-associated spiral arterial modification through their production of interferon-gamma. Unique aspects of uNK cell interactions with decidual endothelium are being defined using cell and tissue transfer into pregnant, alymphoid mice, adhesion of viable lymphocytes to frozen uterine tissue sections under shear forces, laser capture microdissection of uNK cells for quantitative RNA analyses and intravital microscopy. These studies indicate that uterine lymphocytes have a fundamental and major importance in promotion of angiogenesis within implantation sites that is regulated by the reproductive hormone cycle. Further, this work suggests that the pro-inflammatory endometrial cytokine response seen when peri-implantation conceptuses arrest has, as its target for destruction, newly developed endometrial vasculature rather than fetal trophoblast.

Animals↗
PubMed2006

Characterization of allelic variants at chromosome 15q14 in schizophrenia.

Evidence of genetic linkage for schizophrenia at chromosome 15q14 has been reported in nine independent studies, but the molecular variants responsible for transmission of genetic risk are unknown. National Institute of Mental Health Schizophrenia Genetics Initiative families were genotyped for single nucleotide polymorphisms (SNPs) and dinucleotide repeat markers in the 15q14 linkage region and analyzed based on the presence of particular alleles of the dinucleotide repeat marker D15S165 in the 15q14 region. Two alleles showed both familial transmission disequilibrium and population-wide association with schizophrenia. The two groups identified by these two D15S165 alleles differ in age of onset, number of hospitalizations and intensity of nicotine abuse, as well as in predominant ethnicity. Variations in the frequency of SNPs in CHRNA7, the alpha-7-nicotinic acetylcholine receptor subunit gene at 15q14, were found in each group. Further sequencing in these two groups may yield more definitive identification of the molecular pathology.

Adult↗
PubMed2005

Differential modulation of gene expression in the NMDA postsynaptic density of schizophrenic and control smokers.

Nicotine is known to induce the release of multiple neurotransmitters, including glutamate and dopamine, through activation of nicotinic receptors. Gene expression in the N-methyl-d-aspartate postsynaptic density (NMDA-PSD), as well as other functional groups, was compared in postmortem hippocampus of schizophrenic and nonmentally ill smokers and nonsmokers utilizing a microarray and quantitative RT-PCR approach. The expression of 277 genes was significantly changed between all smokers and nonsmokers. Specific gene groups, most notably genes expressed in the NMDA-PSD, were prevalent among these transcripts. Analysis of the interaction between smoking and schizophrenia identified several genes in the NMDA-PSD that were differentially affected by smoking in patients. The present findings suggest that smoking may differentially modulate glutamatergic function in schizophrenic patients and control subjects. The biological mechanisms underlying chronic tobacco use are likely to differ substantially between these two groups.

Aged↗
PubMed2005

Ovum pick up and in vitro embryo production in cows superstimulated with an individually adapted superstimulation protocol.

The aim of this experiment was to apply an ovarian superstimulation protocol prior to ovum pick up (OPU), tailored to the individual donor response, to evaluate its advantages and disadvantages in terms of follicle numbers and diameters, the numbers of retrieved oocytes and day 7 cultured blastocysts. Ten adult non-lactating dairy cows were superstimulated with pFSH and subjected to ovum pick up-in vitro fertilisation (OPU-IVF) 6 times at 2-week intervals. On day 0 of each 2-week period, all follicles >8mm were ablated and an ear implant (Crestar, Intervet, Belgium) was inserted. On day 2, 48 h after follicle ablation the animals were administered six equal doses of pFSH, divided into morning and evening doses for 3 days. On day 7, 48 h following the last pFSH injection, follicle diameters were measured by ultrasound and all follicles were subjected to OPU. All cumulus-oocyte complexes (COC), regardless of their quality, were subjected to in vitro maturation-in vitro fertilisation-in vitro culture (IVM-IVF-IVC). The total dose of pFSH prior to the first OPU session was 300 microg per animal. During the following OPU sessions, the total pFSH dose was either kept unchanged, increased or reduced (+/-50 microg), according to the percentage of follicles of more than 11 mm in diameter, present in the previous session of that particular donor. The mean number of punctured follicles per session was 11.9 +/- 7.7 (mean +/- S.D.), with 16% of follicles exceeding 11 mm. These follicles yielded a mean of 5.6 +/- 4.1 cumulus oocyte complexes (COC), 32% of which had >/=3 layers of cumulus cells (quality 1 and 2). The recovery rate was 47%. Finally, all COC were subjected to IVM-IVF-IVC, which resulted in a mean of 2.0 +/- 2.3 blastocysts on day 7 postinsemination. The subtle changes in pFSH dose influenced the sizes but not the numbers of follicles, the latter parameter was influenced by the individual donor and the OPU session.

Animals↗
PubMed2005

Parturition following transfer of embryos produced in two media under two oxygen concentrations.

In vitro-produced blastocysts were transferred singly to 99 Angus crossbred recipients. Culture treatments were a 2 x 2 factorial of medium (KSOM or SOF) and oxygen concentration (5 or 20%). At parturition, birth weight and frame measurement before colostrum intake were recorded. Fetal membranes were collected; distribution and diameter of cotyledons was recorded. Cotyledon surface area was calculated. Culture with 5% O2 tended to yield smaller birth weights than culture with 20% O2 (39.7+/-1.3 kg versus 43.1+/-1.4 kg; P < 0.1); this effect was pronounced in KSOM, suggesting a medium by oxygen interaction (P < 0.1). When expressed on a body weight basis, calves born following culture with 20% O2 had consistently smaller skeletal measurements than those from culture with 5% O2. Culture with 20% O2 significantly increased individual cotyledon areas both overall and in the fetal horn and cotyledon surface area in the fetal horn. Overall, individual cotyledons were 32% larger when culture involved 20% O2 versus 5% O2; in the fetal horn the increase was 49%. Cotyledon surface area was greater for 20% compared to 5% O2 culture, though a medium by oxygen interaction was also significant (P < 0.05). Cotyledon surface area in the nonfetal horn was greater for KSOM fetal membranes than those from culture in SOF. There was a significant medium by oxygen interaction for total cotyledon number. These data demonstrate culture system-specific effects on calf and fetal membrane traits.

Animals↗
PubMed2005

Thirty-day mortality from colorectal cancer surgery within a deprived population.

OBJECTIVE: A recently published model for predicting 30-day mortality has been devised using data from 73 hospitals in the UK. Deprivation category was not one of the data sets used in predicting mortality and was not included in formulating this model. We wished to assess if the model was applicable to a population with high deprivation category scores. METHODS: Data on all colorectal cancer operations included in the model (age, ASA, cancer resected, Dukes stage and urgency) had been collected prospectively since January 1999. This data was applied to the model. RESULTS: Two hundred and thirty patients were included in analysis. Overall predicted mortality was 8.2% and actual mortality 7.8%. Within different categories of deprivation, predicted and actual mortality are similar and not significantly different. 137 patients lived in areas of deprivation category 3-5. Predicted and actual mortality were 8.4% and 8.0%, respectively. In areas of deprivation category 6-7, 91 patients had a predicted and actual mortality of 8.0% and 7.7%. CONCLUSION: Although deprivation data was not included in the production of the mathematical model to predict postoperative death, the model appears to predict well in the deprived population. It is likely that poorer socio-economic status is accounted for by increased ASA and cancer stage.

Adult↗
PubMed2005

Effects of the osteopontin gene variants on milk production traits in dairy cattle.

Osteopontin (OPN) is a highly phosphorylated glycoprotein whose gene has been cloned and sequenced in different species. Several whole genome scans have identified quantitative trait loci (QTL) affecting milk production traits on bovine chromosome 6 close to the osteopontin gene (OPN) location. The presence of OPN in milk and its elevated expression in mammary gland epithelial cells together with previous QTL studies have prompted us to investigate the effects of OPN variants on milk production traits in the Holstein dairy cattle population. A single nucleotide polymorphism in intron 4 (C/T) was detected and primers were designed to amplify genomic DNA from 1362 bulls obtained from Cooperative Dairy DNA Repository and from 214 cows from the University of Wisconsin herd. For the Repository population, the C allele was associated with an increase in milk protein percentage and milk fat percentage. Correlation between milk protein percentage and milk fat percentage was about 0.57. For the University of Wisconsin herd, the estimates of the effects of allele C were in the same direction as for the Repository population, although these estimates did not reach statistical significance. Our results are consistent with other studies that showed a significant association of the microsatellite markers in the region of OPN with milk protein percentage and other correlated traits.

Alleles↗
PubMed2004

Induction of murine spiral artery modification by recombinant human interferon-gamma.

Functions of uterine natural killer (uNK) cells during mouse pregnancy are maintenance of decidua basalis and promotion of uterine spiral artery modification, a process that results in thin-walled, dilated, elongated arteries with lowered resistance. Murine models indicate spiral artery modifications are triggered by release of the cytokine interferon (IFN)-gamma from uNK cells. The purpose of this study was to determine if human IFN-gamma could induce structural changes in the unmodified spiral arteries found in pregnant, alymphoid (uNK-, NK-, T-, B-) mice. Spiral arteries in pregnant Rag2 null/common cytokine chain (c) gamma null mice were modified, in a dose response manner, by daily injections of rhIFN-gamma. Administration of low dose LPS did not induce morphologically recognized structural changes. These findings are key in building humanized murine models of pregnancy since they suggest Rag2 null/gammac null mice provide a bioassay system that would detect the functioning of human uNK cells under in vivo conditions.

Animals↗
PubMed2004

Comparison of inhibitory effects of oxygen radicals and calf serum protein on surfactant activity.

The effects of the reactive oxygen species (ROS) superoxide anion (O2*-) and hydroxyl radical (*OH) on the surface tension lowering properties of bovine lipid extract surfactant (BLES) were compared to the effects of calf serum protein (CSP) in a captive bubble surfactometer (CBS). O2*- was generated from xanthine/xanthine oxidase (X/XO), and *OH was generated by the Fenton reaction. ROS were demonstrated by electron spin resonance (ESR) using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap. Lipid peroxidation was measured using the thiobarbituric acid method. *OH had broad inhibitory effects on surface tension parameters, including adsorption, minimum surface tension, percentage film area change and film compressibility. O2*- showed inhibitory effects on adsorption, film area change and film compressibility but had no significant effect on minimum surface tension. Both O2*- and *OH treatment were associated with a large 'squeezeout' plateau around 20-25 mN/m in the surface tension-area relation, indicating poor film organization during the compression phase. At the concentrations used, ROS were associated with lipid peroxidation of BLES, which also demonstrated radical scavenging properties. Calf serum protein produced inhibitory effects on adsorption, minimum surface tension and percentage film area change that were quantitatively similar to those produced by *OH. The effects on film compression were significantly greater and qualitatively different from those seen with either O2*- or *OH. We conclude that the inhibition of BLES surface activity by ROS and inhibitory proteins can be distinguished in the captive bubble surfactometer and, particularly, by changes in the film compressibility modulus.

Adsorption↗
PubMed2004

The development and evaluation of a telepsychiatry service for prisoners.

The introduction of increasingly sophisticated telecommunication systems seems to offer opportunities to respond to some of the key problems around structural and spatial inequalities in access to health care. There is evidence which suggests that serious mental health problems are common among prisoners and psychiatric comorbidity is the norm. Many prisoners have complex mental health needs, but more often than not these remain unaddressed. Telepsychiatry is one strategy to improve the accessibility and quality of mental health care in the prison setting. This paper firstly reviews the current prison health care system and then describes a research study which is focused on the development and evaluation of a telepsychiatry service for prisoners. This study has investigated what is lost or gained in a psychiatric assessment when it is conducted via telepsychiatry. The researcher compared the inter-rater reliability between two raters interviewing 80 participants in an observer/interviewer split configuration in telepsychiatry and same room settings. The measure used was the Comprehensive Psychopathology Rating Scale. Prisoners and prison staff also took part in semi-structured interviews which focused on their satisfaction and acceptability of the telepsychiatry service. A cost comparison of the telepsychiatry service with the existing visiting service was conducted. This paper outlines the study design and focuses on the potential impact that telepsychiatry may have upon the practice setting.

Attitude of Health Personnel↗
PubMed2003

Mechanism of simmondsin decomposition during sodium hydroxide treatment.

Jojoba seed meal shows appetite-suppressing activity due to the presence of simmondsin. This pharmacological activity disappears with treatment of the meal with sodium hydroxide. To elucidate this mechanism of inactivation, the reaction of simmondsin in 1 N NaOH at 20 degrees C was monitored as a function of time. The end products of the reaction as well as intermediates were isolated and identified. The half-life of simmondsin was approximately 60 min with d-glucose and 2-hydroxy-3-methoxyphenylacetonitrile as reaction end products. The reaction mechanism could be elucidated by the isolation of isosimmondsin and a simmondsin lactone derivative. Those compounds were isolated and purified by a combination of column chromatography and HPLC and identified mainly by HRMS and NMR spectroscopy.

Acetonitriles↗
PubMed2003

Describing the phenotype in Rett syndrome using a population database.

BACKGROUND: Mutations in the MECP2 gene have been recently identified as the cause of Rett syndrome, prompting research into genotype-phenotype relations. However, despite these genetic advances there has been little descriptive epidemiology of the full range of phenotypes. AIMS: To describe the variation in phenotype in Rett syndrome using four different scales, by means of a population database. METHODS: Using multiple sources of ascertainment including the Australian Paediatric Surveillance Unit, the development of an Australian cohort of Rett syndrome cases born since 1976 has provided the first genetically characterised population based study of Rett syndrome. Follow up questionnaires were administered in 2000 to families and used to provide responses for items in four different severity scales. RESULTS: A total of 199 verified cases of Rett syndrome were reported between January 1993 and July 2000; 152 families provided information for the follow up study. The mean score using the Kerr scale was 22.9 (SD 4.8) and ranged from 20.5 in those under 7 years to 24.2 in those over 17 years. The mean Percy score was 24.9 (SD 6.6) and also increased with age group from 23.0 to 26.9. The mean Pineda score was 16.3 (SD 4.5) and did not differ by age group. The mean WeeFIM was 29.0 (SD 11.9), indicating extreme dependence, and ranged from 18 to 75. CONCLUSION: We have expanded on the descriptive epidemiology of Rett syndrome and shown different patterns according to the severity scale selected. Although all affected children are severely functionally dependent, it is still possible to identify some variation in ability, even in children with identified MECP2 mutations.

Adolescent↗
PubMed2002

Fun stories about Brucella: the "furtive nasty bug".

Although Brucella is responsible for one of the major worldwide zoonosis, our understanding of its pathogenesis remains in its infancy. In this paper, we summarize some of the research in progress in our laboratory that we think could contribute to a better understanding of the Brucella molecular virulence mechanisms and their regulation.

Animals↗
PubMed2002

Functional status of school-aged children with Down syndrome.

OBJECTIVE: To field test, in questionnaire format, the Functional Independence Measure for Children (WeeFIM, a schedule usually administered by interview) on parents of a cohort of school-aged children with Down syndrome. METHODS: The parents of 211 Western Australian children with Down syndrome participated in the present study, representing 79.9% of all children with Down syndrome in the State. Subjects were identified using two sources: (i) the Birth Defects Registry; and (ii) the Disability Services Commission. RESULTS: The total WeeFIM score was 106.2 +/- 17.0 (mean +/- SD) out of a possible 126. Girls scored higher than boys (108.6 vs 103.6; P = 0.05). Scores increased across all age groups (P < 0.0001), even relative to normative data. Performance was strongest in the transfer and locomotion domains and weakest in social cognition. CONCLUSION: We found that severe functional limitations are rare in school-aged children with Down syndrome. Some support and supervision are required for complex self-care, communication and social skill tasks. This study demonstrates the feasibility of using the WeeFIM for collecting population survey data in children with developmental disability. This may be useful for the longitudinal tracking of such populations, as well as the monitoring of response to interventions.

Activities of Daily Living↗