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L Clarke

Publications and source records attributed to L Clarke.

At least 37 records · Page 2Linked to original sources

The influence of piglet birth weight on physical and behavioural development in early life.

The objective of this study was to determine whether body weight at birth influences the physical and behavioural development of the neonatal pig. Sixteen sows and their litters were randomly allocated into four treatment groups. From the normal distribution curve of their birth weight, piglets were sub-divided into three groups: (1) low (<10th percentile) (2) normal (10-90th percentile) and (3) high (>90th percentile). To assess behavioural development, each litter was exposed to a ball placed in the creep area for a period of 1,800 s, and evaluated once over a 3-day period starting on either 5, 7, 14 or 21 days of postnatal life. Their response to, and interaction with, an object was used to calculate a numerical index of piglet behavioural development. Teat order was calculated following observations during consecutive suckling on days 11, 13 and 15 of life, and dominance hierarchy was assessed on day 12, 14 and 16. Individual body weight was recorded on days 0, 5, 7, 14 and 21 of postnatal life. Statistical differences between groups were analysed using general linear model, analysis of variance. Regression analyses were used to determine relationships between physical and behavioural development with teat order and dominance. There was a significant (p < 0.001) relationship between birth weight, growth performance and behavioural development. Behavioural developmental index (BDI) significantly improved (p < 0.001) with age and was also influenced by the day on which the ball was introduced (p < 0.01). Body weight on day 1 of the test was significantly (p < 0.001) correlated to BDI and age at test. Piglets demonstrating compensatory growth were more dominant and exhibited an improved behavioural developmental score than their slower growing littermates. In conclusion, compromised growth in utero can have a detrimental effect on the physical and behavioural development of the neonate. Animals with an enhanced developmental index in conjunction with a higher dominance value exhibited a improved neonatal growth performance.

Animals↗

Eight-year outcome of very-low-birth-weight infants born in KK hospital.

AIM: To determine the education, neurodevelopmental outcome and educational achievement of babies weighing < 1500 g at 8 years of age. MATERIALS AND METHODS: This prospective study involved 171 of 202 survivors from KK Women's and Children's Hospital (KKWCH). Cognitive function was assessed using the Weschler Intelligence Scale for Children--version III (WISC-III). RESULTS: Of these, 90.1% were in mainstream education and 1.2% were in home or religious schools. Special education programmes were recommended for 11.1% of children [24.4% of 56 extremely-low-birth-weight (ELBW) babies < 1000 g and 9.6% of 115 larger babies weighing 1000 to 1499 g]. Of these, only 7.8% eventually enrolled and 1.2% were not in any programme. In 136 children who had psychological assessments, the mean full-scale, verbal and performance intelligence scores were 87.0 +/- 17.7, 86.6 +/- 17.0 and 90.1 +/- 21.8 in ELBWs and 96.1 +/- 18.3, 93.3 +/- 15.7 and 100.0 +/- 17.5 in larger children, with the former having significantly lower scores than the latter (full scale: P = 0.02, 95% CI -18.23, -4.18; verbal: P = 0.04, 95% CI -13.8, -1.95; performance: P = 0.004, 95% CI -17.67, -3.35). 33.8% of the cohort, 49.0% of ELBWs and 25.3% of larger children had neurodevelopmental impairment (full scale score < 85 or in need of special education). Logistic regression analysis showed that birth weight < 1000 g, female sex, Chinese race, a non-intact family structure and bronchopulmonary dysplasia (BPD) were significant risk factors associated with neurodevelopmental impairment. 72.7% of children scored > or = 50% of total marks for English, Mathematics and second language. 14.1% had Band 4 (< 50% of total marks) in all 3 subjects. Logistic regression analysis showed that the only significant risk factors associated with adverse school performance in any of these three subjects were hypoglycaemia in the newborn period and impaired cognitive function. CONCLUSION: The outcome of ELBWs is a major cause of concern. BPD and hypoglycaemia were the only perinatal factors that still exerted an influence on outcome at 8 years. Better methods of prediction of academic difficulty are critical for this high-risk group of children.

Child↗

Estrogen action and male fertility: roles of the sodium/hydrogen exchanger-3 and fluid reabsorption in reproductive tract function.

Estrogen receptor alpha (ER alpha) is essential for male fertility. Its activity is responsible for maintaining epithelial cytoarchitecture in efferent ductules and the reabsorption of fluid for concentrating sperm in the head of the epididymis. These discoveries and others have helped to establish estrogen's bisexual role in reproductive importance. Reported here is the molecular mechanism to explain estrogen's role in fluid reabsorption in the male reproductive tract. It is shown that estrogen regulates expression of the Na(+)/H(+) exchanger-3 (NHE3) and the rate of (22)Na(+) transport, sensitive to an NHE3 inhibitor. Immunohistochemical staining for NHE3, carbonic anhydrase II (CAII), and aquaporin-I (AQP1) was decreased in ER alpha knockout (alpha ERKO) efferent ductules. Targeted gene-deficient mice were compared with alpha ERKO, and the NHE3 knockout and CAII-deficient mice showed alpha ERKO-like fluid accumulation, but only the NHE3 knockout and alpha ERKO mice were infertile. Northern blot analysis showed decreases in mRNA for NHE3 in alpha ERKO and antiestrogen-treated mice. The changes in AQP1 and CAII in alpha ERKO seemed to be secondary because of the disruption of apical cytoarchitecture. Ductal epithelial ultrastructure was abnormal only in alpha ERKO mice. Thus, in the male, estrogen regulates one of the most important epithelial ion transporters and maintains epithelial morphological differentiation in efferent ductules of the male, independent of its regulation of Na(+) transport. Finally, these data raise the possibility of targeting ER alpha in developing a contraceptive for the male.

Absorption↗

Cost-effectiveness of microsatellite instability screening as a method for detecting hereditary nonpolyposis colorectal cancer.

BACKGROUND: The National Cancer Institute has published consensus guidelines for universal screening for hereditary nonpolyposis colorectal cancer (HNPCC) in patients with newly diagnosed colorectal cancer. OBJECTIVE: To determine the cost-effectiveness of screening compared with standard care in eligible patients with colorectal cancer and their siblings and children. DESIGN: Cost-effectiveness analysis. DATA SOURCES: National colorectal cancer registry data, the Creighton International Hereditary Colorectal Cancer Registry, Medicare claims records, and published literature. TARGET POPULATION: Patients with newly diagnosed colorectal cancer and their siblings and children. TIME HORIZON: Lifetime (varies depending on age at screening). PERSPECTIVE: Societal. INTERVENTIONS: Initial office-based screening to determine eligibility (based on personal and family cancer history), followed by tumor testing for microsatellite instability. Those with microsatellite instability were offered genetic testing for HNPCC. Siblings and children of patients with cancer and the HNPCC mutation were offered genetic testing, and those who were found to carry the mutation received lifelong colorectal cancer screening. MEASUREMENTS: Life-years gained. RESULTS OF BASE-CASE ANALYSIS: When only the patients with cancer were considered, cost-effectiveness of screening was $42 210 per life-year gained. When patients with cancer and their siblings and children were considered together, cost-effectiveness increased to $7556 per life-year gained. RESULTS OF SENSITIVITY ANALYSIS: The model was most sensitive to the estimated survival gain from screening siblings and children, to the prevalence of HNPCC mutations among patients with newly diagnosed cancer, and to the discount rate. In probabilistic analysis, the 90% CI for the cost-effectiveness of screening patients with cancer plus their relatives was $4874 to $21 576 per life-year gained. CONCLUSION: Screening patients with newly diagnosed colorectal cancer for HNPCC is cost-effective, especially if the benefits to their immediate relatives are considered.

Age Distribution↗

Functional redundancies, distinct localizations and interactions among three fission yeast homologs of centromere protein-B.

Several members of protein families that are conserved in higher eukaryotes are known to play a role in centromere function in the fission yeast Schizosaccharomyces pombe, including two homologs of the mammalian centromere protein CENP-B, Abp1p and Cbh1p. Here we characterize a third S. pombe CENP-B homolog, Cbh2p (CENP-B homolog 2). cbh2Delta strains exhibited a modest elevation in minichromosome loss, similar to cbh1Delta or abp1Delta strains. cbh2Delta cbh1Delta strains showed little difference in growth or minichromosome loss rate when compared to single deletion strains. In contrast, cbh2Delta abp1Delta strains displayed dramatic morphological and chromosome segregation defects, as well as enhancement of the slow-growth phenotype of abp1Delta strains, indicating partial functional redundancy between these proteins. Both cbh2Delta abp1Delta and cbh1Delta abp1Delta strains also showed strongly enhanced sensitivity to a microtubule-destabilizing drug, consistent with a mitotic function for these proteins. Cbh2p was localized to the central core and core-associated repeat regions of centromeric heterochromatin, but not at several other centromeric and arm locations tested. Thus, like its mammalian counterpart, Cbh2p appeared to be localized exclusively to a portion of centromeric heterochromatin. In contrast, Abp1p was detected in both centromeric heterochromatin and in chromatin at two of three replication origins tested. Cbh2p and Abp1p homodimerized in the budding yeast two-hybrid assay, but did not interact with each other. These results suggest that indirect cooperation between different CENP-B-like DNA binding proteins with partially overlapping chromatin distributions helps to establish a functional centromere.

Amino Acid Sequence↗

Effect of postnatal age and a beta(3)-adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 abundance in the lamb.

We examined the effect of time after birth and beta(3)-adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 (UCP1) abundance and thermoregulation in the lamb. Forty twin lambs, all born normally at term, were maintained at a cold ambient temperature of between 3 and 8 degrees C. At 0.5, 1.75, 5.25, 11.25 and 23.25 h after birth eight sets of twins were fed 20 ml of formula milk +/- 10 mg kg(-1) of beta(3)-adrenergic agonist, and 45 min after feeding brown adipose tissue (BAT) was sampled. Colonic temperature was measured and BAT analysed for UCP1 abundance, GDP-binding to mitochondrial protein (i.e. thermogenic activity) and catecholamine content. Colonic temperature declined between 1.25 and 6 h from 40.2 degrees C to 39.2 degrees C and then increased to 39.8 degrees C at 12 h, but increased after feeding at all ages. UCP1 abundance increased from 1.25 h after birth, to peak at 2 h after birth in controls, compared with 6 h after birth in beta(3)-adrenergic agonist-treated lambs. The level of GDP-binding to mitochondrial protein did not change significantly with age but was increased by beta(3)-adrenergic agonist treatment. The noradrenaline (norepinephrine) content of BAT increased between 1.25 and 12 h after birth, irrespective of beta(3)-adrenergic agonist administration. The total weight of perirenal BAT plus its lipid, protein and mitochondrial protein content declined over the first 6 h of life. UCP1 development continues over the first 24 h of neonatal life, and can be manipulated by beta(3)-adrenergic agonist administration. This may represent one method of improving thermoregulation in newborn lambs. Experimental Physiology (2001) 86.1, 65-70.

Adipose Tissue, Brown↗

Implementing a community-based social marketing project to improve agricultural worker health.

The Together for Agricultural Safety project is a community-based social marketing project working to reduce the adverse health effects of pesticide exposure among fernery and nursery workers in Florida. In 3 years, the collaboration between university and community researchers has embodied many of the principles of community-based research while completing multiple stages of formative data collection required for a social marketing project. This hybrid approach to developing a health intervention for a minority community has been successful in its early stages because the community partners are organized, empowered, and motivated to execute research activities with the assistance of academic partners. However, this work has also been labor intensive and costly. This article describes the lessons learned by project partners and considers the limitations of this approach for agricultural health research.

Adult↗

Gingko biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy.

An increasing variety of alternative health care products (defined as "over-the-counter," nonprescribed herbal medicines) are taken by patients for a plethora of reasons. Unfortunately these self-prescribed remedies are seldom considered by the patient to be medications and as a result it has been noted that 70 per cent of patients do not reveal herbal use to their allopathic practitioners or hospital personnel. The rapid growth of this herbal self-therapy has important implications for the practice of surgery. A case of post-laparoscopic cholecystectomy bleeding in a patient taking Gingko biloba is reported. This preparation has been reported to cause spontaneous bleeding and may interact with anticoagulants and antiplatelet agents. Other herbal medicines have also been associated with potential increased bleeding including garlic, feverfew, ginger, and ginseng. It is vital for surgeons to be apprised of all substances ingested by patients, to be cognizant of their potential adverse effects and drug interactions, and to be familiar with their therapeutic modality, all of which will help to optimize therapeutic approaches and improve patient outcome.

Adult↗

A novel member of the Swi6p family of fission yeast chromo domain-containing proteins associates with the centromere in vivo and affects chromosome segregation.

We previously used a genetic approach to identify a new class of Schizosaccharomyces pombe genes (chromosome loss when overexpressed; clo genes) that, when present in elevated dosage, cause the loss of an otherwise stable cen1 linear minichromosome at high rates. Here we report the identities of two clo genes; one encodes histone H3.3 and the other, designated clo2, encodes a novel protein with significant homology to fission yeast Swi6p, human and Drosophila HP1 heterochromatin proteins, and other chromo domain-containing proteins. Members of this group have been shown to localize to heterochromatic DNA, including centromeres, and to play roles in chromatin formation and organization. The S. pombe Clo2 protein localizes to centromere DNA in vivo, and overexpression of clo2 leads to a dramatic increase in the rate of mitotic loss of an artificial chromosome. Clo2p is not essential for mitotic growth, however, even in cells that also lack Swi6p. Thus, fission yeast appears to utilize multiple, functionally redundant, HP1-related proteins for heterochromatin-associated activities at centromeres and perhaps elsewhere in the genome.

Amino Acid Sequence↗

Influence of thyrotropin-releasing hormone administration at birth on thermoregulation in lambs delivered by cesarean.

OBJECTIVE: We examined the hypothesis that exogenous stimulation with thyrotropin-releasing hormone immediately before umbilical cord clamping can improve thermoregulation in near-term lambs delivered by cesarean. STUDY DESIGN: Twin lambs were injected with either saline solution alone (control, n = 12) or thyrotropin-releasing hormone in saline solution (n = 16) and were immediately placed in a warm (30 degrees C; n = 14) or cool (15 degrees C; n = 14) ambient temperature. In vivo measurements of temperature control (colonic temperature, oxygen consumption, and incidence of shivering) were then performed during the first 6 hours after birth, in conjunction with plasma thyroid hormone measurements. Brown adipose tissue was then sampled for measurement of uncoupling protein 1 abundance. RESULTS: Plasma triiodothyronine concentrations were significantly higher in lambs treated with thyrotropin-releasing hormone than in control lambs between 3 and 6 hours after birth, as were plasma thyroxine concentrations 1 and 5 hours after birth. Delivery temperature had no effect on plasma thyroid hormone concentrations. At 6 hours after birth the abundance of uncoupling protein 1 was higher in lambs treated with thyrotropin-releasing hormone than in control lambs. Lambs treated with thyrotropin-releasing hormone exhibited a lower incidence of shivering than did control lambs between 5 and 6 hours after birth, and an effect of ambient temperature on the incidence of shivering was observed only in the control group. From 3 to 6 hours after birth colonic temperature was significantly higher in cool-delivered lambs treated with thyrotropin-releasing hormone than in the control group. Oxygen consumption was higher in cool-delivered lambs than warm-delivered lambs, but this was not influenced by thyrotropin-releasing hormone. Irrespective of delivery temperature, lambs treated with thyrotropin-releasing hormone possessed more pericardial adipose tissue and hepatic glycogen than did control lambs. CONCLUSION: Thyrotropin-releasing hormone treatment stimulated thyroid hormone secretion in the neonatal lamb and improved thermoregulation during the first 6 hours after birth in near-term lambs delivered by cesarean under cool conditions.

Adipose Tissue, Brown↗