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Biomedical subjects

C Oliver

Publications and source records attributed to C Oliver.

At least 37 records · Page 2Linked to original sources
PubMed2002

Molecular cloning and tissue distribution of the ovine somatostatin receptor subtype 5: osst5.

The sheep is a valuable model to study growth hormone (GH) neuroregulation since its GH secretion pattern is close to that in humans and an integrated physiological approach is possible in this species. Somatostatin receptor subtype 5 (sst5) appears to be important in GH regulation but the ovine sst5 gene (osst5) has not yet been cloned. We report here the cloning of sst5 in that species. We screened a cDNA sheep library and isolated a 1.24 kb cDNA, which includes the whole coding region of osst5. The predicted protein consists of 367 amino acids exhibiting a putative seven transmembrane domain topology typical of G protein-coupled receptors. Nucleotide sequence comparisons with that of other species sst5 showed that osst5 displays 83.8, 81 and 79.7% homology with human, rat, and mice sst5, respectively. Southern blot analysis of ovine cortex DNA demonstrated that osst5 is encoded by a single gene. Osst5 transiently expressed in Chinese Hamster ovary (CHO) cells exhibit a high affinity for somatostatin-14. Reverse transcriptase-polymerase chain reaction (RT-PCR) studies demonstrated that osst5 mRNAs are present in pituitary, cortex, hypothalamus, hippocampus, colon and adrenal gland. The cloning of osst5 should provide a useful tool to study the mechanisms through which somatostatin inhibits hormone secretion in the sheep.

Adrenal Glands↗
PubMed2002

The relationship between levels of mood, interest and pleasure and 'challenging behaviour' in adults with severe and profound intellectual disability.

BACKGROUND: Research on affective disorders in adults with intellectual disability (ID) suggests that depression may not present a 'classic picture' in individuals with severe and profound ID, but may include challenging behaviours, which are referred to as 'atypical symptoms', such as self-injury, aggression and irritability. The aim of the present study was to explore whether there is an association between constructs relating closely to the core symptoms of depression and challenging behaviours in adults with severe and profound ID. METHOD: Mood and levels of interest and pleasure were measured in 53 adults with severe or pro-found ID using the Mood, Interest and Pleasure Questionnaire (MIPQ). RESULTS: Two groups of adults were identified based on MIPQ scores: (1) a 'low mood' group (lowest score = 12); and (2) a comparison group (highest scoring = 12). The groups were clearly differentiated on the MIPQ (P < 0.0001), but were comparable on age, gender and medication use. The Challenging Behaviour Interview showed no difference between the two groups in self-injury, aggression or disrupting the environment. A secondary analysis revealed that participants who showed challenging behaviour scored significantly lower on the MIPQ than those who did not show challenging behaviour. CONCLUSIONS: Possible reasons for these results and considerations for future studies are discussed.

Adult↗
PubMed2001

The ovine somatostatin receptor subtype 1 (osst1): partial cloning and tissue distribution.

The sheep is a valuable model to study GH neuroregulation since its GH secretion pattern is close to that in human. Somatostatin receptor subtype 1 (sst1) appears to be important in central regulation of GH but ovine sst1 (osst1) has not yet been cloned. We report here the cloning of the major part of sst1 in that species. Using human primers from transmembrane domain 2 and 7, we amplified from sheep tissue by RT-PCR a 700 bp fragment. By screening a cDNA sheep library with this fragment, we isolated a 1.4 kb cDNA which contained the major part of the coding cDNA of osst1. The partial predicted protein consists of 347 amino acids exhibiting a putative seven transmembrane domain topology typical of G protein-coupled receptors. Nucleotide sequence comparisons with that of other species showed that osst1 displays 88% homology with human sst1, 84% with rat sst1 and 87% with mouse sst1. Southern blot analysis of ovine cortex DNA demonstrated that osst1 is encoded by a single gene. Northern blot studies evidenced a 3.9 kb transcript highly expressed in the cortex and the hippocampus. This transcript was also present in hypothalamus, striatum, cerebellum, olfactory bulb, spinal cord, brain stem, the lung, kidney, liver, adrenal glands and at a low level in the pituitary gland. No signal was noticeable in the pineal gland. The sequence homology, the tissue distribution, the length of the transcript link this cDNA to the somatostatin receptor family and particularly to sst1.

Amino Acid Sequence↗
PubMed2001

Self-injurious behaviour in young children with Lesch-Nyhan syndrome.

The early development of self-injurious behaviour in three young boys (aged 17, 25, and 30 months at start of study) with Lesch-Nyhan syndrome was examined by means of parental interviews and by direct observations completed at 3 to 4 monthly intervals over an 18-month period. Results suggest that the self-injury began in a different way from that of other young children with autism and/or developmental disabilities in that, from the start, self-injurious responses were sudden and violent, rather than emerging gradually over time. Drastic measures, such as removal of the teeth or provision of tooth guards, were often taken to prevent further tissue damage. Direct observations showed that the boys' self-injury occurred at lower rates, but their carers were highly concerned about the behaviour. Sequential analysis of the observational data indicated that on some occasions the children were more likely to self-injure during periods of low social interaction, suggesting that their self-injury may have been influenced by environmental factors. The theoretical and practical implications of these findings are discussed.

Child, Preschool↗
PubMed2001

A preliminary open label dose comparison using an antioxidant regimen to determine the effect on viral load and oxidative stress in men with HIV/AIDS.

OBJECTIVE: To investigate the effect of antioxidant supplementation on viral load and the antioxidant/reactive oxygen species system in people with HIV. DESIGN: Single centre, prospective, dose comparison study. SETTING: Outpatient clinic specializing in HIV care. SUBJECTS: Sixty-six participants were sequentially recruited by advertisement, and 48 subjects completed the study. INTERVENTIONS: A recommended dose antioxidant regimen (5,450 IU vitamin A as beta-carotene, 250 mg vitamin C, 100 IU vitamin E, 100 microg selenium, 50 mg coenzyme Q10) or a high-dose antioxidant regimen (21,800 IU vitamin A as beta-carotene, 1,000 mg vitamin C, 400 IU vitamin E, 200 microg selenium, 200 mg coenzyme Q10) for a 12 week period. RESULTS: Using repeated measures analysis of variance, the changes over treatment time were significant for selenium, glutathione, glutathione peroxidase and lipid peroxides (P < 0.03). Changes in allantoin, uric acid and viral load were not significant (P > 0.05). The main effects for group and the interaction effects were not significant for any of the parameters measured (P > or = 0.05). CONCLUSION: Antioxidant supplementation significantly improved some measures of oxidative defence. There was no benefit in using a high-dose supplement in this study.

Adult↗
PubMed2001

Causal explanations, concern and optimism regarding self-injurious behaviour displayed by individuals with Cornelia de Lange syndrome: the parents' perspective.

Research into behaviours associated with specific syndromes, such as Cornelia de Lange syndrome (CdLS), has neglected to explore the parents' perspective, particularly the potential impact of the notion of behavioural phenotypes on parents' causal explanations. Given the research focus on self-injurious behaviour (SIB) in CdLS, the present study examined parental concern across four topographies of challenging behaviour, causal explanations for these behaviours and optimism for change. As part of a larger study, a questionnaire survey of 86 parents of children and adults with CdLS was conducted. Quantitative data on parental concern and optimism with regard to behaviour problems were collected. Causal explanations for behaviour problems were examined by subjecting open-ended responses to a content analysis. Parents were as concerned about physical aggression and disruptive behaviours as they were about SIB. The majority of parents had deconstructed how CdLS might be associated with SIB in terms of other factors associated with CdLS, such as degree of intellectual disability. Parents did not believe that CdLS influenced SIB more than other challenging behaviours and their beliefs did not effect optimism regarding future change in the behaviour. Despite the focus of research on SIB in CdLS, parents of children and adults with CdLS are also concerned about other challenging behaviours. There was no evidence that a deterministic perspective had been adopted by parents and causal explanations were unrelated to optimism for future change.

Adolescent↗
PubMed2001

Human decidual stromal cells express CD34 and STRO-1 and are related to bone marrow stromal precursors.

Decidual stromal cells (DSC) are the main cellular component of the human decidua, but thus far their ascription to a given cell lineage is uncertain. In previous studies, these cells have been isolated and maintained in culture, and their antigen phenotype has been analysed to determine their affiliation. However, the presence in the culture medium of high proportions of fetal calf serum (FCS) may inhibit the expression of some surface antigens. In the present study, we show by flow cytometry that CD34 is rapidly down-regulated in human DSC cultured in RPMI 1640 with 20% FCS. For this reason, we used fibroblast medium, which contains only a small proportion (2%) of FCS, to isolate and culture these cells. Under these conditions DSC exhibited a stable antigen phenotype highly similar to that of these cells in vivo. Flow cytometry results confirmed that DSC cultured in fibroblast medium expressed CD34 protein, and reverse transcription-polymerase chain reaction findings showed that they have CD34 mRNA. Decidual stromal cells were also positive for STRO-1, an antigen that identifies stromal precursors of the bone marrow which also expresses CD34. The expression of CD10, CD13, alkaline phosphatase and alpha-smooth muscle actin by DSC, and the absence of expression of CD14 and CD45, further confirmed their relationship with the stromal precursors.

ADP-ribosyl Cyclase↗
PubMed2001

Identification and isolation of rat bone marrow-derived mast cells using the mast cell-specific monoclonal antibody AA4.

Previous studies of mast cell maturation, structure, and function have been hampered by the lack of mast cell-specific markers. In this study, using a well-characterized mast cell-specific monoclonal antibody, MAb AA4, mast cells from rat bone marrow in various stages of maturation were isolated and characterized. The very immature mast cells, which have not been previously described, contained few granules and would not be recognized as mast cells by standard cytological methods. Pure populations of mast cells were isolated from the bone marrow using MAb AA4-conjugated magnetic beads. The same stages of maturation were observed in the isolated mast cells as were seen in the unfractionated bone marrow. All of these cells were immunopositive for the alpha-subunit of Fc epsilon RI, IgE, and c-kit, confirming their identity as mast cells. By direct counting of immunolabled cells and by flow cytometry, approximately 2.4% of the cells in the bone marrow are mast cells. Staining with toluidine blue and berberine sulfate, as well as RT-PCR of the cells, indicates that these cells are connective tissue-type mast cells. The use of immunological methods for identification of mast cell precursors should facilitate the study of these cells. (J Histochem Cytochem 49:219-228, 2001)

Animals↗
PubMed2001

Early development of self-injurious behavior: an empirical study.

The early development of SIB in young children with developmental disabilities was examined by tracking over an 18-month period 16 school-age children who had recently started to show early SIB. Naturalistic observations were conducted in each child's classroom every 3 months, and the association between early SIB and environmental events was examined. Results showed that for the 4 children whose early SIB had escalated over this period, there was a significant association between early SIB and low levels of social contact across observation points, supporting models of the development of SIB. This association might be considered as a risk marker for the exacerbation of SIB. Implications of this finding for targeting early interventions for SIB are discussed.

Adolescent↗
PubMed2001

Effects of social proximity on multiple aggressive behaviors.

We systematically manipulated social proximity to examine its influence on multiple topographies of aggression. Aggression occurred at high levels during close-proximity sessions and at low levels during distant-proximity sessions even though social contact was presented continuously during both conditions. Topographies of aggression emerged sequentially across the close-proximity sessions, and all topographies were reduced to zero following extended sessions of this condition.

Adolescent↗
PubMed2000

Effects of experimental hypothyroidism on the development of the hypothalamo-pituitary-adrenal axis in the rat.

Hypothyroid pups were obtained by adding methimazole in the mother's drinking water from day 15 of gestation and sacrificed at 4, 8 or 15 days. Circulating corticosterone decreased at all ages, while CBG concentrations diminished at day 4, increased at day 8 and did not change at day 15 in hypothyroid rats. As opposed to controls, plasma ACTH concentrations decreased steadily with age while there was an accumulation of ACTH in the anterior pituitary of hypothyroid 15-day-old rats. Anterior pituitary POMC contents were unaffected by the treatment. In the hypothalamic PVN, CRF mRNA levels in the total population of CRF-synthesizing cells and in the CRF+/AVP+ subpopulation were below those of controls whatever the age considered while AVP mRNA in the CRF+/AVP+ subpopulation did not change at day 4 and decreased at day 8 and 15 in hypothyroid animals. Both the number of cell bodies expressing detectable levels of CRF mRNA and the percentage of CRF and AVP colocalization decreased at day 4 and were unchanged thereafter. CRF and AVP immunoreactivity in the zona externa of the median eminence increased with age but was not affected by methimazole treatment. The concentration of AVP mRNA in the magnocellular cell bodies of the PVN and the SON as well as AVP immunoreactivity in the zona interna of the median eminence were not changed by the treatment at days 4 and 8. In hypothyroid 15-day-old rats, SON AVP mRNA increased, AVP immunoreactivity decreased while plasma osmolality was enhanced. In conclusion, our data demonstrate that experimental hypothyroidism impairs specifically the maturation of hypothalamic parvocellular CRF and AVP gene expression during the stress hyporesponsive period. These observations suggest that the physiological peak in plasma thyroxine concentrations that occur between day 8-12 may participate in the maturation of hypothalamic CRF- and AVP-synthesizing cells.

Administration, Oral↗
PubMed2000

Mutations of the serine phosphorylated in the protein phosphatase-1-binding motif in the skeletal muscle glycogen-targeting subunit.

Cellular functions of protein phosphatase-1 (PP1) are determined by regulatory subunits that contain the consensus PP1-binding motif, RVXF. This motif was first identified as the site of phosphorylation by cAMP-dependent protein kinase (PKA) in a skeletal muscle glycogen-targeting subunit (G(M)). We reported previously that a recombinant fusion protein of glutathione S-transferase (GST) and the N-terminal domain of G(M) [GST-G(M)-(1-240)] bound PP1 in a pull down assay, and phosphorylation by PKA prevented PP1 binding. Here we report that substitution of either Ala or Val for Ser-67 in the RVS(67)F motif in GST-G(M)-(1-240) essentially eliminated PP1 binding. This was unexpected because other glycogen-targeting subunits have a Val residue at the position corresponding to Ser-67. In contrast, a mutation of Ser-67 to Thr (S67T) in GST-G(M)(1-240) gave a protein that bound PP1 the same as wild type and was unaffected by PKA phosphorylation. Full length G(M) tagged with the epitope sequence DYKDDDDK (FLAG) expressed in COS7 cells bound PP1 that was recovered by co-immunoprecipitation, but this association was prevented by treatment of the cells with forskolin. By comparison, PP1 binding with FLAG-G(M)(S67T) was not disrupted by forskolin treatment. Neither FLAG-G(M)(S67A) nor FLAG-G(M)(S67V) formed stable complexes with PP1 in COS7 cells. These results emphasise the unique contribution of Ser-67 in PP1 binding to G(M). The constitutive PP1-binding activity shown by G(M)(S67T) opens the way for studying the role of G(M) multisite phosphorylation in hormonal control of glycogen metabolism.

Amino Acid Motifs↗
PubMed2000

Thyroxine modulates corticotropin-releasing factor but not arginine vasopressin gene expression in the hypothalamic paraventricular nucleus of the developing Rat.

Neonatal rats were daily injected with 100 microg/kg T4 and killed at 4, 8 or 15 days. Circulating corticosterone and corticosteroid binding globulin concentrations increased in 8- and 15-day-old rats after T4 treatment. Plasma adrenocorticotropic hormone (ACTH) concentrations, pituitary ACTH content and pro-opiomelanocortin mRNA expression were unaffected in T4-treated rats. T4 treatment induced an increase in corticotropin-releasing factor (CRF) mRNA expression in the whole population of CRF synthesizing cells of the paraventricular nucleus (PVN) that became significant at day 8 and disappeared at day 15. Double labelling in situ hybridization revealed that CRF gene expression in the CRF+/arginine vasopressin (AVP)+ subpopulation was increased at days 4 and 8 and decreased at day 15. CRF immunoreactivity in the zona externa of the median eminence increased with age but was not affected by the experimental hyperthyroidism. The degree of CRF and AVP colocalization, the concentration of AVP mRNA in the parvo and magnocellular cell bodies of the PVN and the density of immunoreactive AVP in the zona interna or zona externa of the median eminence did not change after T4 treatment. Our data demonstrate that experimental hyperthyroidism accelerates the maturation of hypothalamic CRF gene expression, including in particular in the CRF+/AVP+ subpopulation, during the stress hyporesponsive period. These observations suggest that the physiological peak of plasma thyroxine that occurs between days 8-12 may participate in the maturation of hypothalamic CRF cells.

Adrenocorticotropic Hormone↗
PubMed2000

The effects of ionotropic agonists of excitatory amino acids on the release of arginine vasopressin in rat hypothalamic slices.

The effects of ionotropic excitatory amino acids agonists on the release of vasopressin from rat hypothalamic slices were studied. Incubation with increasing doses of NMDA, kainate or AMPA decreased the release of vasopressin in a dose-dependent manner. The values of the IC50 were 1.0, 9.6, or 3.7 x 10-8 M, respectively. The inhibitory effect of the various excitatory amino acids tested was blocked by coincubation with their respective antagonists. Vasopressin secretion was stimulated to 140.3 +/- 7.6% of controls when the slices were obtained from chronically (7 days) salt-loaded rats. Addition of 1 x 10-7 M NMDA or 1 x 10-6 M kainate to the incubation medium antagonized the salt loading-induced increase in vasopressin release. Incubation with 1 x 10-4 M tetrodotoxin did not change basal vasopressin release, but it blocked the decrease in vasopressin secretion induced by 1 x 10-7 M NMDA or 1 x 10-6 M kainate or 1 x 10-6 M AMPA. Incubation with 1 x 10-5 M phaclophen (a GABAB antagonist) and 1 x 10-5 M bicuculline (a GABAA antagonist) was without effect on basal vasopressin secretion while it reversed the inhibition of vasopressin release induced by 1 x 10-7 M NMDA. Incubation with 1 x 10-6 M GABA alone decreased vasopressin secretion to 64.6 +/- 6.9% of control values. The inhibitory effect of GABA did not change when 1 x 10-7 M NMDA was added to the incubation medium. These findings demonstrate that ionotropic excitatory amino acids agonists inhibit vasopressin secretion from hypothalamic slices. They strongly suggest that this inhibitory effect is mediated through local GABAergic interneurones.

Animals↗
PubMed2000

Cognitive deterioration in adults with Down syndrome: effects on the individual, caregivers, and service use.

Individuals with Down syndrome (N = 49) who had participated in serial neuropsychological assessments were assigned to one of three groups comparable in level of premorbid mental retardation: those showing cognitive deterioration, those comparable in age but not showing cognitive deterioration, and those not showing cognitive deterioration but younger. Those experiencing cognitive deterioration were less likely to receive day services, had more impoverished life experiences, and required more support compared to groups without cognitive deterioration. When age was controlled for, cognitive deterioration was significantly positively associated with caregiver difficulties and service use and negatively associated with life experiences for the individual. Results suggest a potential role for caregiver difficulties in influencing life experiences of adults with Down syndrome showing cognitive decline.

Adult↗
PubMed2000

Pro-opiomelanocortin in human pregnancy: evolution of maternal plasma levels, concentrations in cord blood, amniotic fluid and at the feto-maternal interface.

OBJECTIVE: The human placenta normally expresses the pro-opiomelanocortin (POMC) gene. The pattern and secretory kinetics of POMC and/or POMC-derived peptides by the placenta during gestation is still debated. We recently demonstrated that full length POMC was a normal product of the human placenta. The aim of our study was to establish its normal secretory kinetics and to explore its physiological relevance. DESIGN: In a prospective, longitudinal study, thirty normal pregnant women had monthly measurements of plasma POMC. In a cross-sectional study of 128 healthy pregnant women, plasma POMC and human chorionic gonadotrophin (hCG) were concomitantly measured to assess their correlation. Finally, POMC levels were assessed in venous and arterial cord blood samples, in amniotic fluid and in retroplacental blood. METHODS: Plasma POMC was measured by a specific IRMA in unextracted blood or biological fluid. RESULTS: Plasma POMC became detectable by the 8th week of pregnancy and reached its maximum at around the 20th week, remaining stable thereafter. The relationship between POMC and gestation time (weeks) best fitted with a third degree polynomia curve. A significant negative correlation (P=0.01) was observed between plasma levels of POMC and hCG after adjustment for gestation time to take into account the dependence of both hormones on this parameter. POMC was not secreted into the fetal circulation at term, but was present in very high levels in amniotic fluid. The highest levels of POMC were present in the retroplacental blood where the values were 35 times higher than in maternal blood; by comparison, corticotrophin releasing hormone and ACTH values in this compartment were twice or equal to those in the maternal blood. CONCLUSION: Placental POMC secretion increases during the first half of pregnancy and reaches a plateau from the 20th week to delivery. The inverse correlation between POMC and hCG plasma levels, and very high POMC levels at the feto-maternal interface suggest a physiological role for this precursor during pregnancy.

Adrenocorticotropic Hormone↗