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Biomedical subjects

P Larkin

Publications and source records attributed to P Larkin.

15 recordsLinked to original sources
PubMed2003

Differential gene expression analysis in fish exposed to endocrine disrupting compounds.

This review discusses various methodologies that can be used to understand, at the gene level, the consequences to fish upon exposure to endocrine disrupting compounds (EDCs). Several approaches for measuring expression of gene transcripts are discussed, including directed approaches, such as Northern blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) as well as open-ended approaches, such as differential display RT-PCR, subtractive hybridizations, and gene arrays. Each of these systems has advantages and disadvantages, strengths and weaknesses. Conducting experiments with each of these methods provides important information about the molecular mechanisms that result from exposure to EDCs, information which can be used in risk assessment of polluted sites found in the environment.

Animals↗
PubMed2003

Analysis of gene expression profiles in largemouth bass exposed to 17-beta-estradiol and to anthropogenic contaminants that behave as estrogens.

Novel molecular based methods are being developed to study changes in gene expression in wildlife exposed to anthropogenic chemicals. Gene arrays, in particular, are useful tools that can be used to simultaneously monitor hundreds to thousands of genes within a single experiment, giving an investigator the ability to determine how exposure affects multiple metabolic pathways. These methods are thought to be both sensitive and able to reveal biochemical mechanisms of action. A largemouth bass (LMB) array containing 132 genes has been designed to study the impact of gene expression in male fish exposed to 17-beta estradiol or to the compounds 4-nonylphenol (4-NP) or 1,1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p,p'-DDE). The results of these experiments demonstrate distinct gene expression patterns in LMB exposed to these compounds.

Animals↗
PubMed2002

Gene expression analysis of largemouth bass exposed to estradiol, nonylphenol, and p,p'-DDE.

The purpose of this study was to determine the specific expression profile of 132 genes, some of which are estrogen responsive, in largemouth bass (LMB) following exposure to estradiol (E(2)), or to two hormonally active agents, 4-nonylphenol (4-NP) and 1,1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p,p'-DDE), using gene array technology. The results of these experiments show that LMB exposed to E(2) and 4-NP had similar, but not identical genetic signatures for the genes examined, some of which are known to be estrogen-responsive genes. The differences suggest that 4-NP may have additional modes of action that are independent of the estrogen receptor (ER). We have also shown that exposure of male LMB to p,p'-DDE results in an increase in some estrogen-responsive genes. But in female LMB, the observed changes were a down-regulation of the normally up-regulated estrogen responsive genes. Other genes were also down-regulated. These results suggest that p,p'-DDE may affect regulation of genes differently in male and female LMB. This study further suggests that gene arrays have the potential to map out the gene activation pathways of hormonally active compounds.

Animals↗
PubMed2001

A null mutation in guanylate cyclase-1 alters the temporal dynamics and light entrainment properties of the iodopsin rhythm in cone photoreceptor cells.

Guanylate cyclase-1 (GC1) plays a critical role in visual phototransduction and its absence severely compromises the ability of the photoreceptor cells to transduce light for vision. In this study we sought to determine if the absence of GC1 has any effect on light entrainment of the circadian oscillators located in these cells. We compared the rhythmic changes in transcript levels of iodopsin, a photoreceptor-specific gene whose expression is regulated by circadian oscillators, in retinas of normal chickens and GUCY1*B (*B) chickens that carry a null mutation in GC1. Our results show that iodopsin rhythms are present in *B retinas and that they can be entrained to light; however, the rise and fall of iodopsin transcript levels in *B retina under cyclic light conditions is significantly more rapid than that observed in normal retina, and under constant dark conditions, the phase of the iodopsin rhythm in *B retina is advanced by 6 h relative to that observed in normal retina. In addition, the rate of entrainment of the iodopsin rhythm in *B retina to a reversal of the light cycle is significantly slower than normal. The results of our study show that a functioning visual phototransduction cascade is not essential for light entrainment of the oscillators that drive the iodopsin rhythm in photoreceptor cells. We propose that the abnormal synthesis of cGMP in *B photoreceptors underlies the irregular iodopsin rhythms observed in post-hatch *B retina.

Animals↗
PubMed1999

Characterization of the chicken GCAP gene array and analyses of GCAP1, GCAP2, and GC1 gene expression in normal and rd chicken pineal.

PURPOSE: This study had three objectives: (1) to characterize the structures of the chicken GCAP1 and GCAP2 genes; (2) to determine if GCAP1, GCAP2, and GC1 genes are expressed in chicken pineal gland; (3) if GC1 is expressed in chicken pineal, to determine if the GC1 null mutation carried by the retinal degeneration (rd) chicken is associated with degenerative changes within the pineal glands of these animals. METHODS: GCAP1 and GCAP2 gene structures were determined by analyses of chicken cosmid and cDNA clones. The putative transcription start points for these genes were determined using 5'-RACE. GCAP1, GCAP2 and GC1 transcripts were analyzed using Northern blot and RT-PCR. Routine light microscopy was used to examine pineal morphology. RESULTS: Chicken GCAP1 and GCAP2 genes are arranged in a tail-to-tail array. Each protein is encoded by 4 exons that are interrupted by 3 introns of variable length, the positions of which are identical within each gene. The putative transcription start points for GCAP1 and GCAP2 are 314 and 243 bases upstream of the translation start codons of these genes, respectively. As in retina, GCAP1, GCAP2 and GC1 genes are expressed in the chicken pineal. Although the GC1 null mutation is present in both the retina and pineal of the rd chicken, only the retina appears to undergo degeneration. CONCLUSIONS: The identical arrangement of chicken, human, and mouse GCAP1/2 genes suggests that these genes originated from an ancient gene duplication/inversion event that occurred during evolution prior to vertebrate diversification. The expression of GC1, GCAP1, and GCAP2 in chicken pineal is consistent with the hypothesis that chicken pineal contains a functional phototransduction cascade. The absence of cellular degeneration in the rd pineal gland suggests that GC1 is not critical for pineal cell survival.

Amino Acid Sequence↗
PubMed1999

Circadian regulation of iodopsin and clock is altered in the retinal degeneration chicken retina.

We are interested in determining if the visual phototransduction cascade plays a role in light entrainment of photoreceptor circadian oscillators. In this study, we compared mRNA levels of iodopsin and the chicken homolog of Clock (cClock) in the retinas of normal and rd (retinal degeneration) chickens that lack functional rod and cone phototransduction cascades. Iodopsin is a circadian-regulated, photoreceptor-specific gene expressed in chicken retina, and Clock is a transcription factor that has been shown to play a role in the circadian clock mechanism in mouse and Drosophila. The results of our analyses show that cClock and iodopsin transcript levels undergo daily oscillations in retinas of normal animals housed under 12 h light:12 h dark (12L:12D) conditions, and that these oscillations are maintained in the absence of light. Levels of these transcripts in the retinas of rd/rd chickens housed under cyclic light conditions did not change significantly over the course of a 12L:12D cycle; however, there was evidence that the photoreceptor oscillators were entrained in these animals. Comparisons of our normal and rd/rd data suggest that there are at least two light entrainment pathways that impinge on the oscillators found in photoreceptor cells, one of which is effectively disabled by the GC1 null mutation carried by the rd chicken.

Amino Acid Sequence↗
PubMed1992

Asthma prevalence and management in Australian adolescents: results from three community surveys.

Three population surveys of asthma, conducted as part of a community-based asthma education program in southwestern Sydney, Australia, illustrate the relationship between health behaviors and asthma morbidity. The first survey was carried out in five secondary schools (n = 2514, 52% participation rate); the second survey, in eight schools (n = 4550, 82% participation rate); and, the third survey was conducted among patients who attended 38 general practices in the region (n = 633 adolescents, 72% participation rate). The prevalence of diagnosed asthma in Australian adolescents across all three studies was 16.5% (95% CI, 15.7%-17.3%). Asthma prevalence declined in males, but increased in females from ages 12-15 years. It was noted that smoking prevalence was similar in asthmatic adolescents, compared with nonasthmatics, and that the adoption of smoking occurred at similar ages. Further, behavioral self-management of asthma was infrequent in this group, with low levels of preventive practice and preventive medication use. We present a conceptual model of the barriers to optimal asthma management among asthmatic adolescents. The results of these surveys have led to community-wide efforts to improve asthma management and decrease smoking prevalence among these adolescents.

Adolescent↗
PubMed1992

Asthma under-recognition and under-treatment in an Australian community.

In a study in south-western Sydney, we examined asthma symptoms in a random sample of 4239 schoolchildren aged five-12 years. The prevalence of current wheeze and cough was 17.1% (95% CI 16.0-18.2%). Interviews were conducted with the parents of all 214 symptomatic children from two of the six schools. Only 60% of these children had ever been labelled as asthma, and only 20% were using appropriate asthma treatment. Fewer than 6% had ever had their airway function assessed. There was a socio-economic difference, with better levels of asthma recognition and management in children attending the school in the more affluent region. The findings suggest that asthma recognition, assessment and management in the Australian community, as in New Zealand and the UK, may need to be improved.

Asthma↗
PubMed1986

Effect of resisted knee flexion on knee extension torque.

We tested the principle of "reversal of antagonists" by measuring the effect of resisted knee flexion on subsequent peak knee extension torque at velocities of 60 degrees/sec and 120 degrees/sec using an isokinetic dynamometer. We determined peak knee extension torques from torque curves produced during knee extension that was performed reciprocally with either passive or maximum voluntary resisted knee flexion. We used a crossover design so that all 18 healthy adult subjects performed knee extension reciprocally with both passive and resisted knee flexion. Paired means t tests revealed no statistically significant difference between the peak knee extension torques produced under the two knee flexion conditions either at 60 degrees/sec or 120 degrees/sec. We, therefore, concluded that resisted knee flexion does not augment peak knee extension torque under our conditions of testing. The concept of reversal of antagonists was not supported. Antagonistic muscle functioning, therefore, may be irrelevant to agonist isokinetic testing and training in neurologically healthy persons.

Adult↗
PubMed1977

The obstetric performance of the grand multipara.

The computerized records of all women delivered between July, 1974, and June, 1975, at the Mater Mothers' Hospital were analysed, and the obstetric complications associated with grand multiparity were examined. Hypertension, preeclampsia, unstable lie, malpresentation and retained placenta are found to be more common in women of high parity. The low morbidity associated with these conditions in the data may have been related to the close supervision and active management carried out. Anaemia remained more frequent in the grand multiparous women despite modern antenatal care. Hypertension in the grand multiparous women could not be explained by age in the data presented. The cause for hypertension in this group of women remains obscure. Newborn babies of grand multiparas developed neonatal jaundice more frequently. The association between jaundice and oxytocic usage in the data only partially accounted for this observation.

Adult↗