Search PubMed⌕ Search

Biomedical subjects

J Philippe

Publications and source records attributed to J Philippe.

At least 109 records · Page 6Linked to original sources
PubMed1991

Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.

Diabetes mellitus is characterized by insulin deficiency and high plasma glucagon levels, which can be normalized by insulin replacement. It has previously been reported that glucagon gene expression is negatively regulated by insulin at the transcriptional level. By transfection studies, I have now localized a DNA control element that mediates insulin effects on glucagon gene transcription. This element also confers insulin responsiveness to a heterologous promoter. DNA-binding proteins that specifically interact with this insulin-responsive element are found in both glucagon- and non-glucagon-producing cells; and the pattern of binding, as assessed by the gel retardation assay, is not modified by prior insulin treatment.

Animals↗
PubMed1991

Quality control in antimicrobial disk susceptibility testing: a Belgian multicenter study.

A Belgian multicenter trial was conducted to evaluate problems encountered with quality control results of antimicrobial disk susceptibility testing and to compare the performance of BBL disks and Rosco tablets. Over a period of four weeks 18 laboratories daily tested three reference strains against eight antibiotics. A standardised method was used by all participants. For all results together 10.4% and 7.3% of the measurements with BBL disks and Rosco tablets, respectively, were outside the recommended range. Major problems were observed for some specific strain-antibiotic combinations. Standard deviations were similar for both systems; their precision was comparable. The results suggest that cooperation between manufacturers and some reference laboratories could be improved in order to establish optimal quality control limits.

Anti-Bacterial Agents↗
PubMed1991

Strict distance requirement for transcriptional activation by two regulatory elements of the glucagon gene.

The glucagon gene is specifically expressed in A cells of the pancreatic islets. We have previously identified three functional DNA control elements within the 5'-flanking sequence of the glucagon gene: an upstream promoter element (G1), responsible for the A-cell-specific expression, and two enhancer-like elements (G2 and G3). Mutations within G1 completely abolished the enhancer activities of G2 and G3. We show here that the loss of transcriptional activity is not due to an absence of binding of nuclear proteins to G2 or G3, but rather to an essential role of G1 to enable G2 and G3 to exert their effects at a distance. When juxtaposed to the TATA box, both enhancers are capable of inducing transcription as efficiently as when an intact G1 is present. However, the tandem arrangement of G2 plus G3 does not result in additional transcriptional activity compared with a single element. We conclude that G2 and G3 are capable of directly activating transcription but in a highly distance-dependent fashion and without cooperatively interacting. G1 may thus serve only as a tissue-specific relay, bringing together factors that bind to enhancers and the TATA box.

Animals↗
PubMed1991

[Integration of carcinogenic viruses in the genome of in-vitro cultured human fibroblasts].

Avian sarcoma viruses are known for inducing no transformation of human diploid fibroblasts. Nevertheless, we show that the Rous sarcoma virus can infect and transform some human fibroblastic cell lines, replicate and express viral proteins, integrate into the host genome and prevent expression of MHC class I antigens on cell membranes. Cell transformation happens together with important and significant abnormalities of the cell karyotype and proviral integration is most often close to the c-src oncogene on chromosomes 1 and 20.

Avian Sarcoma Viruses↗
PubMed1991

[Solitary eosinophilic granuloma of the external wall of the orbit].

Eosinophilic granuloma is a solitary form of histiocytosis X with a usually good prognosis. Sometimes spontaneous healing can even occur. The authors report a case of a 30-month-old boy who presented an eosinophilic granuloma of the lateral orbital wall. The correct diagnosis was obtained after computed tomographic scan followed by fine needle aspiration biopsy with histopathologic examination. The tumor increased rapidly, including a medial displacement of the globe and limitation of the eye movement. So chemotherapy (Vinblastine) with corticotherapy was performed. The clinical course was favorable, with no evidence of recurrence or systemic involvement. The originality of this case was the young age of the patient, the course and the efficacy of treatment. The authors emphasize the management of the disease.

Child, Preschool↗
PubMed1991

[Maxillary cyst of dental origin with uncommon ocular complication].

A 23-year-old woman was referred for decreased vision and central scotoma. Fundus examination disclosed unilateral acute oedematous optic neuritis. A nasolabial cyst was diagnosed, probably of dental origin, because numerous apical granuloma were noticed. The abscess did not produce any fistula which explained the absence of clinical and radiological dental sinusitis. Treatment included excision of the nasolabial cyst and systemic antibiotics. The prognosis was excellent with recovery of a normal visual acuity and normal fundus appearance. There was no evidence of any recurrent episode. The nasolabial cyst was the cause likely of the neuritis. Nevertheless, multiple sclerosis must be considered. Only long-term absence of neurological signs could prove that the maxillary lesion was directly responsible for the optic disorder.

Acute Disease↗
PubMed1990

Characterization of muscarinic acetylcholine receptors on the rat pancreatic gastrin-producing cell line B6 RIN.

The mechanisms of cholinergic stimulation of gastrin cells were studied in the rat pancreatic cell line B6 RIN. Carbachol induced an increase in intracellular Ca2+ and stimulated gastrin release in a dose-dependent manner over the range 10(-5)-10(-3) M. These effects were completely abolished by atropine, suggesting the implication of muscarinic cholinergic receptors. The binding properties of these receptors were investigated. [N-Methyl-3H]scopolamine [( 3H]NMS) binding on cell homogenates was time-dependent, saturable and consistent with a single high-affinity binding class (Kd = 39.5 pM, and Bmax = 7.9 fmol/mg DNA). Carbachol competitively inhibited [3H]NMS binding. The potency of inhibition of [3H]NMS binding by subtype selective antagonists was hexahydrodifenidol greater than pirenzepine greater than AF-DX 116. These results suggest the M3 muscarinic receptors may be involved in the carbachol-induced gastrin release from B6 RIN cells.

Animals↗
PubMed1990

Functional characterization of a cAMP-responsive element of the rat insulin I gene.

Analogues of cAMP have been reported to increase insulin mRNA levels in normal rat beta-cells and hamster insulinoma cells (HIT). To define the mechanisms by which cAMP modulates insulin gene expression, we first investigated its effects on the transcriptional rate of the insulin gene in HIT cells. Nuclear run-on assays revealed a 4-fold increase in transcription observed as early as 1 h after stimulation. To characterize the cis-acting sequences of the rat insulin I gene promoter and the trans-acting factors mediating the cAMP effect on insulin gene transcription, we constructed DNA plasmids containing various lengths of the rat insulin I gene 5'-flanking region linked to the bacterial reporter gene, chloramphenicol acetyltransferase (CAT). Studies of the transcriptional activity of 5'-deletionally and pointly mutated plasmids after transfection into HIT cells revealed the presence of a cAMP-responsive element (CRE), TGACGTCC, between -177 and -184 relative to the transcriptional start site, whose sequence closely matches the previously defined CREs, present in cAMP-responsive genes. Gel retardation and Southwestern assays identify a protein of molecular weight approximately 43,000, binding specifically to the insulin CRE. We conclude that the rat insulin I gene is regulated by cAMP through a CRE and that the nuclear protein interacting with it might be similar or identical to the previously purified cAMP-responsive protein, CREB.

Animals↗
PubMed1990

Dexamethasone inhibits insulin biosynthesis by destabilizing insulin messenger ribonucleic acid in hamster insulinoma cells.

Glucocorticoid effects on insulin biosynthesis and secretion have been controversial. To define whether glucocorticoids affect insulin biosynthesis in vitro, the actions of dexamethasone on insulin gene expression were examined using the HIT cell line, a transformed clonal line of hamster beta-cells. Dexamethasone induced a dose-dependent decrease in steady-state insulin messenger RNA (mRNA) levels, which was prevented by adding an excess of RU 486, a competitive inhibitor for the binding to the glucocorticoid receptor. Inhibition was not observed before 6 h of dexamethasone treatment and was maximal at 24 h. To further assess the molecular mechanisms of the dexamethasone-induced decreases in insulin mRNA levels, we investigated whether transcription of the insulin gene was affected. Run-on assays revealed that transcription rates were not changed by glucocorticoids. Inhibition of RNA and protein synthesis by actinomycin D and cycloheximide, respectively, completely abolished the dexamethasone effects, whereas actinomycin D added 9 h after dexamethasone had no effect on insulin mRNA levels. The present results demonstrate that glucocorticoids can acutely inhibit insulin biosynthesis by destabilizing insulin mRNA; this effect requires the transcriptional activation of a gene encoding a protein responsible for the accelerated disappearance of insulin mRNA.

Adenoma, Islet Cell↗
PubMed1989

Glucagon gene transcription is negatively regulated by insulin in a hamster islet cell line.

Complex interrelationships exist between the four pancreatic islet cell types and their respective secretory products, insulin, glucagon, somatostatin, and pancreatic polypeptide. These hormones are known to interact with the different islet cells and modulate their functions. Insulin inhibits glucagon secretion from the A cell both in vivo and in vitro and, in states of insulin deficiency, high glucagon levels are observed that are normalized by insulin replacement. To determine if insulin also regulates glucagon biosynthesis, we studied its effects on glucagon gene expression. Our studies indicate that insulin, in a dose-dependent fashion decreases steady-state glucagon mRNA levels in a clonal hamster islet cell line, In-R1-G9; this decrease is secondary to an inhibition of glucagon gene transcription as assessed by transcriptional run-on assays and does not involve detectable changes in mRNA stability. Inhibition of glucagon gene transcription is accompanied by corresponding decreases in glucagon immunoreactivity in both cell extracts and medium. We conclude that insulin may not only regulate glucagon secretion but also glucagon gene expression.

Animals↗
PubMed1989

Major histocompatibility complex class II (Ia-like) antigens on chicken embryo fibroblasts: effect of transformation by Rous sarcoma virus.

In this study, three monomorphic monoclonal antibodies to chicken MHC class II molecules (B-L) were tested for reactivity in normal and RSV-transformed embryo fibroblasts. The immunocytochemical staining, the cell-bound ELISA assay, and the immunoprecipitation analysis showed that all three antibodies reacted with the B-L (Ia-like) molecules on normal cells of different genotypes. Conversely, the expression of these antigens was not detected in fibroblasts cultured from feather follicles of adult birds. The level of expression of B-L molecules as well as the class II specific RNA increased consistently after transformation of the cells by the SR-RSV and infection with the avian leukosis virus RAV-1. Analysis of genomic DNA by the Southern blot technique, performed after digestion with several restriction endonucleases, showed that the restriction pattern of B-L genes was not altered in cells transformed by Rous sarcoma virus.

Animals↗