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Biomedical subjects

C Oliver

Publications and source records attributed to C Oliver.

At least 55 records · Page 3Linked to original sources
PubMed2000

Increased expression of the mRNA encoding the somatostatin receptor subtype five in human colorectal adenocarcinoma.

Numerous studies have suggested that the antiproliferative potency of somatostatin (SS) analogues may be an efficient tool to improve the prognosis of colorectal cancer. In order to facilitate current efforts to design potent antitumour SS analogues, we studied the distribution of human SS receptors (hsst1-5) mRNAs in a large set of tumoural and normal colonic tissues. Localisation of hsst1-5 mRNAs in normal and tumoural tissues was performed by in situ hybridisation using radioactive antisense or sense riboprobes. Semi-quantitative analysis of hsst5 mRNA was performed using a computerised image analysis system. Hsst binding sites were characterised by studying the relative potency of SS14, SS28 or SS analogues in displacing [(125)I]Tyr degrees -d-Trp(8)-SS14 bound to HT29-D4 cells. Hsst5 mRNA was by far the most expressed subtype in both normal and transformed epithelial cells as well as in the HT29-D4 cell line. An increased expression of hsst5 mRNA was found in tumours. Hsst1 mRNA was expressed preferentially as clusters in immune cells in lamina propria and in stroma close to the tumour. A low expression of hsst4, hsst3 and hsst2 was seen in normal and tumoural tissue. In HT29-D4, binding experiments with SS14 demonstrated the existence of one SS binding class (K(d)=524 nM, B(max)=1fmol/10(6 )cells). In competition binding studies, SS28 and BIM23268 (an analogue that shows preferential specificity towards hsst5) effectively inhibited binding of [(125)I]Tyr degrees -d-Trp(8)-SS14 (IC(50)=15 and 157 nM respectively), while BIM23197 (an analogue that shows preferential affinity for hsst2) was ineffective. Our results show a high expression of hsst5 mRNA in human tumoural colonic tissue, while hsst5 protein is the predominant hsst protein subtype in a tumoural colonic cell line.

Adenocarcinoma↗
PubMed2000

IGF-I/IGFBPs system response to endotoxin challenge in sheep.

Endotoxin (LPS), a membrane component of gram-negative bacteria produces multiple endocrine and metabolic effects that mimic those seen in acute sepsis. It induces species-dependent alterations of the growth hormone (GH) axis that may participate in the shift of the metabolism towards catabolic events. Humans and sheep show increased GH secretion in response to LPS, as opposed to rats, which have been the most studied. The purpose of our work was to evaluate the effects in intact rams of an acute intravenous administration of a high dose of LPS on the insulin-like growth factor (IGF)-I/IGF-binding proteins (IGFBPs) system and to analyse the temporal relationship of GH axis changes with those of several hormonal and metabolic parameters such as somatostatin, cortisol, insulin, and glucose. LPS induced a late moderate decrease of total IGF-I plasma levels following a 5-h steady-state period (-26.6+/-4. 2%, P<0.05, 9 h after LPS), despite a biphasic and sustained increase of GH secretion in the same animals (2.48+/-0.39 ng/ml 2 h after LPS and 2.7+/-0.37 ng/ml 5 h after LPS vs 0.77+/-0.10 before LPS; Briard et al. 1998a). Western ligand blot analysis in IGFBPs showed an early short-lasting increase in IGFBP-1 (188.8+/-39% P<0. 05, 3 h after LPS). No significant change was seen for either IGFBP-2, -3 or -4. We observed a marked and sustained increase in cortisol (128.18+/-7.21 ng/ml 3 h after LPS, vs 21.17+/-4.22 before LPS). Insulin also increased (27.69+/-3.90 microU/ml 3 h after LPS, vs 13.48+/-1.69 before LPS) and its burst coincided with that of IGFBP-1. Moderately decreased IGF-I and increased IGFBP-1 plasma levels contrasted with the sustained increase in GH secretion that we recently described, thereby suggesting that endotoxin causes a state of resistance to GH. This may be exacerbated by reduced IGF-I bioavailability and/or action, and which may participate in the pathophysiology of the catabolic state seen in sepsis. The temporal analysis of hormone responses suggests that endotoxin-induced alterations of the IGF-I/IGFBPs system may involve the prolonged and substantial somatostatin rise that we recently demonstrated, together with an increase in glucocorticoid and cytokine as more generally assumed.

Animals↗
PubMed1999

Alpha1-adrenergic regulation of peptidylglycine alpha-amidating monooxygenase gene expression in cultured rat cardiac myocytes: transcriptional studies and messenger ribonucleic acid stability.

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a bifunctional protein containing two enzymes that act sequentially to catalyse the alpha-amidation of neuroendocrine peptides. Previous studies have demonstrated that alpha-adrenergic stimulation results in an increase in intracellular volume and protein content of cultured neonatal rat myocardial cells. The present study examined the regulated expression of PAM during alpha-adrenergic stimulation. Alpha1-adrenergic stimulation activates the expression and release of PAM from myocytes. Following phenylephrine treatment, myocardial cells displayed a several fold increase in PAM activity, and a 2-4-fold increase in the steady state levels of PAM mRNA. This effect of alpha-adrenergic stimulation was dependent on the concentration and duration of exposure to the agonist, and displayed alpha1-adrenergic receptor specificity. The transcription rate experiments indicated that these alpha-adrenergic effects were not due to increased PAM gene activity, suggesting that a post-transcriptional mechanism was involved. The most common mechanism of post-transcriptional regulation affects cytoplasmic mRNA stability. Cardiomyocytes cultures from atria and ventricles in the presence of 5,6 dichloro-1-beta ribofuranosyl benzamidazole (DRB) showed that phenylephrine treatment increased the half-life of PAM mRNA from 13 +/- 1 to 21 +/- 1 h in atrial cells and from 8 +/- 1 to 12 +/- 1 h in ventricle cells. Analysis of nuclear RNA with probes specific for PAM intron sequences shows that increased PAM expression after phenylephrine treatment was not due to intranuclear stabilisation of the primary transcript. Protein kinase C inhibitors H7 and GF109203x, completely blocked the phenylephrine stimulated PAM expression. These results suggest that alpha-adrenergic agonist induces PAM mRNA levels by increasing its stability in the cytoplasm. They indicate that PAM gene expression augments through a H7 and GF109203x sensitive pathway, involving the activation of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Kappa1-opioid binding sites are the dominant opioid binding sites in surgical specimens of human pheochromocytomas and in a human pheochromocytoma (KAT45) cell line.

The adrenal medulla produces opioids which exert paracrine effects on adrenal cortical and chromaffin cells and on adrenal splanchnic nerves, via specific binding sites. The opioid binding sites in the adrenals are detectable mainly in the medullary part of it and differ in type between species. Thus, the bovine adrenal medulla contains mostly kappa-opioid binding sites and fewer delta- and mu-opioid binding sites while primate adrenals contain mainly delta sites and few kappa-opioid binding sites. Most chromaffin cell tumors, the pheochromocytomas, produce opioids which suppress catecholamine production by the tumor. The aim of the present work was to identify the types of opioid binding sites in human pheochromocytomas. For this purpose, we characterized the opioid binding sites on crude membrane fractions prepared from 14 surgically excised pheohromocytomas and on whole KAT45 cells, a recently characterized human pheochromocytoma cell line. Our data showed that human pheohromocytomas are heterogeneous, as expected, with regard to the production of catecholamines and the distribution and profile of their opioid binding sites. Indeed, only one out of the 14 pheochromocytomas expressed exclusively delta and mu opioid sites, while in the remaining 13 tumors kappa-type binding sites were dominant. The KAT45 cell line possessed a significant number of kappa1 binding sites, fewer kappa2-opioid binding sites and kappa3-opioid binding sites, and minimal binding capacity for delta- and mu-opioid receptor agonists sites. More specifically, the kappa1 sites/cell were approximately 18,000, the kappa2 4500/cell and the kappa3 sites 2000/cell. Our findings for the surgical specimens and the cell line combined with previously published pharmacological data obtained from KAT45 cells suggest that kappa sites appear to be the most prevalent opioid binding sites in pheochromocytomas. Finally, in normal bovine adrenals the profile of opioid binding sites differs in adrenaline and noradrenaline producing chromaffin cells. To test the hypothesis that the type of catecholamine produced by a pheochromocytoma depends on its cell of origin, we compared our binding data with the catecholamine content of each pheochromocytoma examined. We found no correlation between the type of the predominant catecholamine produced and the opioid binding profile of each tumor suggesting that this hypothesis may not be valid.

Analgesics, Opioid↗
PubMed1999

Cockroach allergens and asthma in Brazil: identification of tropomyosin as a major allergen with potential cross-reactivity with mite and shrimp allergens.

BACKGROUND: Cockroaches produce several proteins that induce IgE antibody responses. Although cockroaches are abundant in warm and humid areas, sensitization to cockroach allergens has not been investigated in Brazil. OBJECTIVE: The aims of this study were to investigate the frequency of cockroach allergy among patients with asthma, rhinitis, or both in Brazil and to identify American cockroach allergens. METHODS: Skin tests using cockroach extracts were performed on children and young adults with asthma, rhinitis, or both. A Periplaneta americana complementary (c)DNA library was screened by using IgE antibodies from Brazilian patients allergic to cockroaches. Reactivity of an mAb directed to Dermatophagoides pteronyssinus tropomyosin against cockroach tissue was examined by immunofluorescence. RESULTS: Cockroach allergy was present in 55% and 79% of the patients, as determined by using skin prick tests alone or combined prick and intradermal tests, respectively. Five cDNA clones reacted with IgE antibody and contained the same sequence. A representative clone (1300 bp), pa 12, coded for a protein that reacted with 50% of the sera from patients allergic to cockroaches on plaque immunoassay and showed a high degree of homology to tropomyosins, particularly those from invertebrates. P americana tropomyosin showed 80%, 81%, and 82% sequence identity to tropomyosins from D pteronyssinus, D farinae, and shrimp, respectively, which have been previously defined as important allergens. An mAb directed against D pteronyssinus tropomyosin, which also recognizes shrimp tropomyosin, showed binding to cockroach striated muscle. CONCLUSION: Our results support the recommendation that cockroach extracts should be routinely used for the evaluation of patients with asthma, rhinitis, or both in Brazil. The identification of P americana tropomyosin as an important allergen will make it possible to investigate cross-reactivity among cockroaches, mites, and food derived from invertebrates.

Adolescent↗
PubMed1999

Antigen phenotype of cultured decidual stromal cells of human term decidua.

We previously reported that decidual stromal cells (DSC) from early human decidua express antigens associated with hematopoietic cells and develop different immune functions. Here we study the antigenic phenotype of DSC from term decidua and compare it with the phenotype reported for DSC from early decidua. Decidual stromal cells were isolated from human term deciduas and maintained in culture until highly purified DSC cultures were obtained. Most term DSC, like most early DSC, expressed CD10. Term DSC expressed antigens specific for follicular dendritic cells (FDC), such as DRC-1 (CD21L) and HJ2, together with CD21, CD23 and CD80, which are detected on FDC as well. Also like early DSC, term DSC were negative for CD3, CD14, CD15 and CD45. Although early DSC were reported to be HLA-DR-positive and CD86-positive, these antigens were not expressed by term DSC. These discrepant results suggest that two types of cells, or cells at different stages of differentiation (decidualization) were selected during culture of decidual cells from different periods of gestation. This possibility was further supported by the finding that term DSC expressed desmin and prolactin, two markers of decidualization, whereas these molecules have not previously been detected in early DSC.

Antigens, CD↗
PubMed1999

High precursor level in maternal blood results from the alternate mode of proopiomelanocortin processing in human placenta.

OBJECTIVE: ACTH-producing non-pituitary tumours are often associated with altered precursor processing, particularly in the most aggressive ones. Since placental tissue is characterized by its ability to express the proopiomelanocortin (POMC) gene and rapid cellular proliferation, we examined whether intact POMC could be released physiologically during human gestation. SUBJECTS: One hundred and fifty six normal pregnant women, 12 with multiple pregnancies, and 23 non-pregnant controls. Twenty-eight women were studied in the immediate postpartum period. MEASUREMENTS: We measured plasma POMC levels with a specific immunoradiometric assay (IRMA) using a combination of antibodies directed against ACTH and beta endorphin. Results obtained with this first IRMA were confirmed in 22 subjects with a second assay using the same beta endorphin antibody and a more distal antibody directed against the N-terminal fragment of POMC. Reverse transcription-PCR detected full length, pituitary-like, POMC mRNA in human placenta. RESULTS: Plasma POMC was undetectable (< 60 U/ml) in 23 normal subjects. In normal monofetal pregnancies, POMC became detectable in most women by the third month and then increased steadily until midgestation: 168 +/- 108 (U/ml; mean +/- SD) between 12 and 15 weeks, 190 +/- 103 between 16 and 19 weeks, 324 +/- 180 between 20 and 23 weeks, 276 +/- 171 between 24 and 27 weeks, 292 +/- 177 between 28 and 31 weeks, 290 +/- 235 between 32 and 35 weeks and 308 +/- 210 between 36 weeks and parturition. Plasma POMC was significantly higher in multiple pregnancies with very high levels in three triplet-bearing mothers: 671, 941, and 1731 U/ml at 31, 33 and 32 weeks, respectively. POMC levels felt quickly in post partum, becoming undetectable in five of 13 women on day 1, seven of eight on day 2 and five of six on day 3. Plasma POMC displayed no diurnal variation, was not suppressed by glucocorticoid administration and did not correlate with plasma ACTH or cortisol. In contrast, plasma POMC positively correlated with plasma CRH. CONCLUSIONS: Pregnancy is the only condition in which POMC is produced and released physiologically, similar in some respects to the ectopic ACTH syndrome. POMC is derived solely from the placenta, with no interference from maternal pituitary secretion, and is thus a new and specific placental marker.

Adrenocorticotropic Hormone↗
PubMed1999

Identification of early self-injurious behaviour in young children with intellectual disability.

Very little is known about the early stages of self-injurious behaviour (SIB) in young children with developmental disabilities, even though there has been a great deal of research into the prevalence, assessment and treatment of well-established SIB in older individuals. In the present initial study, teachers in special schools for children under II years of age with severe intellectual disability and/or autism were asked to identify children who were beginning to show early self-injury (the index group). These children were then matched to classroom controls (of the same ability level and mobility), and teachers were interviewed about the children's behaviours and skills. The index children showed significantly more potential SIB than the control group children, but there was overlap between the groups in terms of percentage duration of potential SIB, suggesting that teachers do not find it easy to identify children with 'early' SIB. The index children's skills and problem behaviours, their sensory impairments and degree of autism did not differ significantly from those of the control group. When all the children showing any potential SIB were pooled together, it transpired that developmental age and degree of mobility were significantly correlated with percentage duration of SIB, suggesting that these characteristics may be important risk markers. The index children were also observed at 3-month intervals at school over the following 18 months and self-injury clearly escalated for some of the index children, while it did not do so for others. Using regression analysis, increases in SIB were shown to be associated only with the degree of concern expressed about the child's behaviour at time I by the teacher, no other variables predicting increases in SIB.

Age Factors↗
PubMed1999

Human decidual stromal cells express alpha-smooth muscle actin and show ultrastructural similarities with myofibroblasts.

Previous reports in human and mouse material demonstrated that decidual stromal cells expressed antigens associated with haematopoietic cells, exerted immune functions, and originated from bone marrow. These findings suggested that these cells belonged to the haematopoietic lineage. We purified and expanded in culture precursors of human decidual stromal cells, and found in electron microscopic images that the ultrastructure of these cells was similar to that of myofibroblasts, which are of mesenchymal origin. The relationship between these two types of cell was confirmed by the detection (by flow cytometry) in the decidual precursors of alpha-smooth muscle actin, a contractile microfilament expressed solely by smooth muscle cells, myofibroblasts and related cells. This filament was also detected in decidual stromal cells decidualized in vitro by the effect of progesterone. We also found vimentin in decidual precursors and decidualized cells. This intermediate filament has been previously reported to be expressed by all decidual stromal cells and also by myofibroblasts. Desmin, another intermediate filament expressed by myofibroblasts, was not detected in the decidual precursors; however, this filament was observed in decidualized cells. The expression of alpha-smooth muscle actin by decidual stromal cells was also found by immunostaining in cryostat sections of early decidua. Our results suggest that decidual stromal cells are related to myofibroblasts.

Actins↗