Annotation: self-injurious behaviour in children with learning disabilities: recent advances in assessment and intervention.
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Adolescent↗
Biomedical subjects
C Oliver
Publications and source records attributed to C Oliver.
Down's syndrome and the links with Alzheimer's disease.
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Aging↗
Microwave fixation improves antigenicity of glutaraldehyde-sensitive antigens while preserving ultrastructural detail.
Microwave fixation for electron microscopy has been used primarily for post-embedding immunocytochemistry. The present study examined the ability of microwave fixation to preserve the antigenicity of glutaraldehyde-sensitive antigens for pre-embedding immunocytochemistry. Five monoclonal antibodies (MAbs) directed against cell surface components of rat mast cells were tested. The MAbs failed to show any labeling of conventionally fixed rat bone marrow-derived mast cells even at glutaraldehyde concentrations as low as 0.1%. Strong staining of mast cell plasma membranes was seen when bone marrow was initially fixed with 2% formaldehyde and then refixed in 2% glutaraldehyde/2% formaldehyde after immunostaining. However, the ultrastructural preservation of the cells was poor. Antigenicity and morphological detail were both preserved when bone marrow was fixed in 0.05% glutaraldehyde/2% formaldehyde for 4 sec in a 550-W microwave oven. With this method, mast cells in various stages of maturation as well as cells that did not contain granules were immunoreactive. This method should prove useful with antigens from many different cell types that are sensitive to glutaraldehyde fixation.
Animals↗
[Regulation of corticotropic function in stressful situations].
ACTH secretion is mainly controlled by two hypothalamic neurohormones: corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both peptides are synthesized in the hypothalamic paraventricular nucleus (PVN) (in parvo-cellular neurons for CRH and in magnocellular neurons for most AVP). Under basal conditions, some CRH neurons coexpress AVP (CRH+/AVP+ neurons). This colocalisation represents a form of functional plasticity since the number of CRH+/AVP+ neurons increases after acute or repeated stress exposure. Experiments in sheep and rat (studies on the secretion of both peptides in hypophysial portal blood, effects of anti-CRH and anti-AVP immunisation upon ACTH secretion) indicate that stress-induced ACTH stimulation involves both CRH and AVP. Unlike CRH which participates also in the maintenance of basal ACTH and glucocorticoids secretion, the role of AVP appears to be limited to corticotropic response to stress.
Adrenocorticotropic Hormone↗
Acute stress stimulates secretion of GHRH and somatostatin into hypophysial portal blood of conscious sheep.
The effects of acute stress on growth hormone (GH) secretion and the mechanisms involved in its changes have been investigated in sheep. An acute isolation-restraint stress induced a rapid and significant increase in jugular GH levels in 12 out of 14 rams. GH-releasing hormone (GHRH) and somatostatin secretion during the same stress were studied in 5 animals prepared for hypophysial portal blood collection. A 3.5-fold increase in portal GHRH levels was observed concomitantly with a slight elevation in portal somatostatin. Portal corticotropin-releasing hormone (CRH) and jugular cortisol plasma levels increased during the same stress. Our data suggest that an isolation-restraint stress stimulates GH secretion in the sheep and that GHRH may be responsible for GH response.
Analysis of Variance↗
The anti-ganglioside monoclonal antibody AA4 induces protein tyrosine phosphorylations, but not degranulation, in rat basophilic leukemia cells.
The monoclonal antibody AA4 (mAb AA4) recognizes novel alpha-galactosyl derivatives of GD1b on rat basophilic leukemia (RBL-2H3) cells. The binding of mAb AA4 induced protein tyrosine phosphorylations without histamine release. Several of the same proteins including Fc epsilon RI beta, Fc epsilon RI gamma, p72syk, and phospholipase C-gamma 1 were tyrosine-phosphorylated by mAb AA4 binding and by the activation of the high affinity IgE receptor, Fc epsilon RI. There was also activation of the p53/56lyn and p72syk protein-tyrosine kinases, but compared to direct Fc epsilon RI activation, mAb AA4 did not result in increased tyrosine phosphorylation of pp105-115 or pp125FAK, and the receptor subunits (Fc epsilon RI beta and Fc epsilon RI gamma) were more heavily phosphorylated. Furthermore, the time course of the phosphorylations with mAb AA4 was slower than that induced by Fc epsilon RI aggregation. By immunofluorescence, the tyrosine-phosphorylated proteins after mAb AA4 stimulation were localized in patches at the cell membrane and in areas of cell-cell contact, whereas after Fc epsilon RI activation, there was a reticular cytoplasmic pattern. There were no protein tyrosine phosphorylations either when Fc epsilon RI was saturated with IgE or when F(ab')2 fragments of mAb AA4 were used, although the F(ab')2 fragments still induced morphological changes. There was also coprecipitation of the beta and gamma subunits of Fc epsilon RI with the anti-ganglioside antibody. These data strongly suggest the involvement of Fc epsilon RI in the antiganglioside-induced protein tyrosine phosphorylations. Moreover, phosphorylations of these proteins including the beta and gamma chains of Fc epsilon RI and activation of p53/56lyn and p72syk did not result in histamine release.
Animals↗
Effect of tianeptine on the hypothalamic somatotropic axis in the conscious sheep.
The action of serotonin on growth hormone (GH) secretion is controversial because of interspecies differences and lack of specificity of serotoninergic drugs. Serotonin (5-HT) appears to inhibit GH release in the sheep and in man. We have investigated the site of action of tianeptine, a 5-HT uptake enhancer, in sheep since it is possible to collect hypophysial portal blood for the simultaneous determination of growth hormone-releasing hormone (GHRH) and somatostatin in this species under conscious, unstressed conditions. Tianeptine injection (10 mg/kg i.v.) resulted in a significant, immediate and short-lasting (30 min) increase in peripheral GH (+750%; P < 0.01) and hypophysial portal GHRH (+180%; P < 0.01). No change in the secretion of somatostatin was recorded during the same time. These data suggest that serotoninergic inputs are inhibitory to GH secretion. Tianeptine acts centrally to stimulate GH secretion in the sheep and its effect is mediated through changes in GHRH but not somatostatin release into hypophysial portal blood.
Animals↗
Effect of chronic treatment with the antidepressant tianeptine on the hypothalamo-pituitary-adrenal axis.
The effects of acute and chronic administration of tianeptine, a novel antidepressant agent, on the hypothalamo-pituitary-adrenal axis were studied in the adult male rat. A single injection of tianeptine did not alter the activity of the hypothalamo-pituitary-adrenal axis. In contrast, chronic administration of tianeptine (10 mg/kg twice a day for 15 days) induced a significant decrease in the concentration of corticotropin-releasing factor (CRF) in the hypothalamus and adrenocorticotropin (ACTH) in the anterior lobe of the pituitary. Chronic tianeptine treatment did not modify CRF levels in the cerebral cortex and hippocampus, and did not alter alpha-melanocyte-stimulating hormone and beta-endorphin levels in the neurointermediate lobe of the pituitary. Using the in situ hybridization technique, we observed that chronic administration of tianeptine did not modify CRF mRNA levels in the paraventricular nucleus of the hypothalamus. The effect of chronic tianeptine treatment on the neuroendocrine response to stress was also investigated. Tube restraint stress for 30 min induced a significant depletion of hypothalamic CRF and a substantial increase of plasma ACTH and corticosterone. Tianeptine abolished the stress-induced reduction of hypothalamic CRF concentration and markedly reduced the stress-induced increase in plasma ACTH and corticosterone levels. Taken together, these results suggest that tianeptine acts primarily at the level of the hypothalamus: (1) in unstressed rats, tianeptine reduces hypothalamic CRF and pituitary ACTH contents; (2) in stressed animals, tianeptine attenuates the activation of the hypothalamo-pituitary-adrenal axis.
Animals↗
Absence of PAX6 gene mutations in Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation).
The PAX6 gene is expressed at high levels in the developing eye and cerebellum and is mutated in patients with autosomal dominant aniridia. We have tested the role of PAX6 mutations in three families with Gillespie syndrome, a rare autosomal recessive condition consisting of partial aniridia, cerebellar ataxia, and mental retardation. Single-strand conformational polymorphism analysis of affected individuals revealed no alteration of PAX6 sequences. In two families, the disease trait segregates independently from chromosome 11p markers flanking PAX6. We conclude that Gillespie syndrome is genetically distinct from autosomal dominant aniridia.
Alleles↗
Relationship between hypophyseal portal GHRH and somatostatin and peripheral GH levels in the conscious sheep.
The mechanisms involved in the genesis of pulsatile GH secretion are not well understood. Recently, methods for hypophyseal portal blood collection in conscious sheep became available. Using this method, GHRH and SRIH secretion into hypophyseal portal blood (HPB) and GH release from the pituitary gland were simultaneous assessed and the relationship between GHRH and SRIH changes in HPB and GH in peripheral blood was investigated. In 23 rams (9-11 month old, 35-45 kg bw), 126 hours of HPB were analysed. Fifty-four spontaneous GH peaks were detected. The majority of GH peaks (48.1%) was associated with an increased portal GHRH and a fall in somatostatin concentrations. A simultaneous increase in GHRH and somatostatin levels was observed in 18.5% of GH peaks while 12.9% of peaks occurred with a fall in SRIH and no modification in GHRH concentrations. Finally, 5/54 (9.3%) GH peaks occurred without any modification in portal GHRH and SRIH release. Our data indicate that the GHRH/SRIH interplay is complex. The occurrence of spontaneous GH peaks may be due not only to a coordinate increase in GHRH and reduction in SRIH release similar to male rat, but also to other patterns of GHRH/SRIH secretion.
Animals↗
Effect of streptozotocin-induced diabetes on somatostatin receptors in the anterior pituitary, hypothalamus and cerebral cortex of the male rat.
In order to better understand the mechanisms underlying the reduction in GH secretion in diabetic rats, we have characterized and measured SRIH receptors in the hypothalamus and anterior pituitary gland 5 and 9 days after induction of diabetes in the rat. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats. Chronic insulin replacement therapy partly restored plasma GH and blood glucose levels in these animals. A significant reduction in SRIH receptor concentrations was demonstrated in the hypothalamus and anterior pituitary gland, 5- and 9- days after STZ injection. These changes were not significantly corrected by insulin replacement. Cerebral cortex SRIH receptor concentrations were unaffected by experimental diabetes. We conclude that hypothalamic and pituitary SRIH receptor levels are lowered in diabetic rats. These changes may contribute to aberrant GH secretion in diabetes and they indicate that pituitary sensitivity to exogenous somatostatin should be tested in diabetic patients.
Animals↗
Independent segregation of a hyperactive hypothalamic-hypophyso-adrenal axis and a reduced behavioural reactivity in pigs.
When compared to European Large White, Chinese Meishan pigs have high levels of circulating ACTH and cortisol, and a reduced behavioural reactivity in various challenging situations such as exposure to a novel environment, two characteristic features of depression. We investigated whether this association is genetically built in or whether these psychobiological characteristics are fortuitously associated. Six-week-old piglets from the segregating F2 crosses between the Meishan and Large White breeds were studied in a standardised protocol of novel environment exposure. As expected from the genetic diversity, a wide range of variation was recorded for behavioural reactivity (locomotion, vocalisations). ACTH, cortisol, and glucose were measured in blood samples taken immediately before the test and at the end of the session. Again these measures varied considerably between animals, and the continuous distribution of the scores suggested that they are under control of numerous genes. Furthermore, no correlation could be found between neuroendocrine and behavioural measures. This result demonstrates that the association between high ACTH/corticosteroid levels and a low behavioural reactivity is not genetically controlled.
Adaptation, Psychological↗
[Abdominal neuropathy of motor expression of diabetic origin. Apropos of a case].
Authors report a case of diabetic truncal neuropathy presenting as a painful abdominal swelling. This entity, which frequently is probably under estimated, may mimic abdominal visceral pathology and patients may be subjected unnecessary to extensive diagnosis procedures.
Abdominal Muscles↗
Calmodulin antagonists inhibit human immunodeficiency virus-induced cell fusion but not virus replication.
We have reported that amphipathic helical segments in the cytoplasmic domain of the HIV-1 envelope glycoproteins bind to calmodulin (CaM) with high affinity, and inhibit calmodulin-regulated proteins. To investigate the possible role of calmodulin activity in HIV-1 replication, we investigated the anti-HIV activity of various CaM antagonists--trifluoperazine and naphthalenesulfonamide W13 or W7--in HeLa T4 cells, PBMCs, and various T lymphocytic cell lines. The different CaM antagonists were found to inhibit the proliferation of the different cell types to varying extent. Also, the CaM antagonists were found to exert a greater antiproliferative effect on H9/HIV-1IIIB, as compared to uninfected H9 cells, suggesting a deficit of CaM function in HIV-infected cells. The CaM antagonists inhibited virus-induced cell fusion in HeLa T4 cells infected with a recombinant vaccinia virus expressing HIV-1 envelope proteins at threshold concentrations that do not inhibit cell proliferation. The fusion-inhibitory effects of the CaM antagonists were also observed in cocultures of HIV-infected (H9/HIV-1IIIB) and uninfected H9 cells. Under these conditions, the synthesis and surface expression of the viral glycoproteins were not affected, although the kinetics of processing of HIV envelope precursor was delayed. Virus production from both HIV-infected peripheral blood mononuclear cell (PBMC) and MT-2 cell cultures was inhibited by CaM antagonists at concentrations that were inhibitory to cell proliferation. Surprisingly, threshold concentrations of CaM antagonists that do not inhibit cell proliferation were found to enhance virus production from HIV-infected MT-2 cells, but not PBMCs.(ABSTRACT TRUNCATED AT 250 WORDS)
Calmodulin↗
Localization of the G-protein G(o) in exocrine glands.
The GTP-binding protein G(o) was localized immunohistochemically in the rat parotid gland and in other exocrine glands with specific G(o) antibodies. Immunohistochemical studies revealed that affinity-purified G(o alpha) polyclonal antibody (GO/85) immunoreacted primarily with duct cells of the rat parotid gland; immunoreactivity was also noted in duct cells of the rat submandibular, mouse parotid, and mouse submandibular glands. Light labeling of rat parotid and submandibular gland acinar cells was also noted. G(o alpha) antiserum (9072) differing in specificity for epitopes within G(o alpha) produced similar results. This antiserum also immunoreacted with rat submandibular duct cell secretory granule membranes. In contrast, in rat and mouse pancreas G(o alpha) antibodies immunoreacted primarily with islet cells. Duct cells were negative but there was light labeling of rat pancreatic acinar cells. The apparent duct specificity of G(o alpha) staining was further verified by demonstrating that G(o alpha) antibodies immunoreacted with HSG-PA cells, a human transformed salivary duct cell line. Specificity in immunohistochemical labeling of HSG-PA cells was confirmed by Western blot analysis. The results demonstrate that G(o) appears to be selectively expressed in the duct cells of rat parotid gland and other salivary glands. The selective enrichment of G(o) in duct cells suggests that this G-protein plays an important role in duct cell physiology.
Animals↗
Metallothionein synthesis and degradation in Indian childhood cirrhosis fibroblasts.
Indian childhood cirrhosis (ICC) is a fatal liver disease characterized by the accumulation of copper-sulfur aggregates. We demonstrated that cultured fibroblasts from a patient with ICC contain vesicular aggregates, fibrillar whorls, and crystalloids along with dilated rough endoplasmic reticulum filled with flocculent material. Although the copper content of the fibroblasts was normal, both basal and metal-induced metallothionein (MT) synthesis was reduced in the ICC cells. The lower MT synthesis in ICC cells was seen at copper concentrations of 100, 200, and 400 microM, zinc concentrations of 50 and 100 microM, and a cadmium concentration of 2 microM. The lower MT synthesis in ICC cells was not due to failure of the cells to take up copper because 67Cu uptake kinetics were normal in the mutant cells. MT degradation was also normal in the ICC cells. The size of human MT IIA mRNA was normal in the ICC cells, but its amount was reduced under both basal and metal-induced conditions. The MT IIA gene, which is the predominant MT gene in human beings, showed no sequence alterations in any of its exons, introns, or promoter region in the ICC cells compared with normal cells. These studies demonstrate that this case of ICC represents a genetic disease with some level of expression in cultured fibroblasts; the basic defect may involve insufficient MT mRNA and protein synthesis for the copper load present. However, it remains to be determined whether reduced MT synthesis is a primary or secondary phenomenon.
Base Sequence↗
Role of growth hormone (GH)-releasing hormone and somatostatin in the mediation of clonidine-induced GH release in sheep.
GH secretion is stimulated by the administration of an alpha 2-adrenergic agonist, clonidine, in several species, including man. This action is probably mediated at the level of the hypothalamus, where the drug may act through inhibition of somatostatin (SRIH) and/or stimulation of GH-releasing hormone (GHRH) release. We have investigated the mode and site of action of clonidine in sheep, because it is possible to collect hypophysial portal blood for the simultaneous determination of GHRH and SRIH in this species under conscious unstressed conditions. Clonidine injection (0.3 mg, iv) resulted in a significant, immediate, and short-lasting (30-min) increase in peripheral GH (14.4 +/- 3.1 vs. 4.8 +/- 1.1 ng/ml; P < 0.01) and portal GHRH (2.7 +/- 0.5 vs. 1.0 +/- 0.2 pg/min; P < 0.01) levels. No change in SRIH secretion was recorded during the same period. Next, we tested the effect of clonidine in sheep actively immunized against GHRH or SRIH. The alpha 2-adrenergic agonist did not affect GH secretion in the anti-GHRH group, whereas immunization against SRIH did not modify the GH response. Finally, we observed that clonidine did not influence GH release from cultured ovine pituitary cells. These data suggest that clonidine acts centrally to stimulate hypophysial GH secretion in the sheep and that this effect is mediated through changes in GHRH, but not SRIH, release into hypophysial portal blood.
Animals↗
Use of immunogold with silver enhancement.
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Animals↗