Search PubMed⌕ Search

Biomedical subjects

J Philippe

Publications and source records attributed to J Philippe.

At least 145 records · Page 8Linked to original sources
PubMed1986

Novel expression of the angiotensinogen gene in a rat pancreatic islet cell line. Transcriptional regulation by glucocorticoids.

Angiotensinogen gene expression has a broad tissue specificity. Whereas angiotensinogen mRNA is undetectable in normal rat pancreas, we have identified angiotensinogen mRNA in all tumors and cell lines derived from a rat islet cell line, RIN-r. A subclone with the highest angiotensinogen mRNA levels, 1056A, secreted N-glycosylated angiotensinogen. Angiotensinogen mRNA of 1056A cells was approximately 200 nucleotides longer than that of liver, and this was shown to be due to an extension of the 3'-untranslated region. Dexamethasone increased angiotensinogen mRNA levels approximately 9-fold above control, and this increase was linear over 110 h, indicating a half-life of greater than 55 h for angiotensinogen mRNA during dexamethasone induction. This effect of dexamethasone was inhibited by the glucocorticoid antagonist RU 38486. Dexamethasone increased angiotensinogen gene transcription approximately 5-fold in a nuclear run-on assay. These results demonstrate that dexamethasone induction of angiotensinogen mRNA levels in 1056A cells is due, at least in part, to a transcriptional response and that 1056A cells will be useful for the study of angiotensinogen gene regulation and the identification of glucocorticoid regulatory sequences.

Angiotensinogen↗
PubMed1986

Proglucagon processing in a rat islet cell line resembles phenotype of intestine rather than pancreas.

Proglucagon, synthesized in the pancreatic islets and the intestinal L-cells, contains in its precursor structure glucagon, glicentin, and two glucagon-like peptides (GLP-I and GLP-II) separated by an intervening peptide (IP-II). We have cloned a stable rat islet cell line expressing the glucagon gene at high levels, thereby allowing us to study the posttranslational processing of proglucagon in this cell line. In contrast to the processing of proglucagon in the pancreas, in which glucagon is liberated, in the cell line we found the intestinal pattern of peptides consisting of glicentin, at least two forms of GLP-I [GLP-I-(1-37) and GLP-I-(7-37)], GLP-II, IP-II, and an amidated form of IP-II. No individually processed glucagon peptide was detected. GLP-I-(1-37), GLP-I-(7-37), GLP-II, IP-II, and IP-II amide coeluted with their respective synthetic peptide standards on gel filtration and ion exchange chromatography. The existence of a single glucagon gene in the rat genome and indistinguishable glucagon mRNAs in pancreas and intestine indicates that the neoplastic transformation that occurred in these islet cells is associated with a phenotypic switch in the differential posttranslational processing of proglucagon to a pattern that mimics that found in the intestinal cells. These observations further support the hypothesis of a common progenitor for the intestinal (L) and islet (A) cells.

Animals↗
PubMed1986

Glucocorticoid and thyroid hormone regulation of angiotensinogen gene expression in a pancreatic islet cell line.

The renin-angiotensin system is an important regulator of blood pressure and volume homeostasis in mammals. Angiotensinogen, a precursor of the octapeptide angiotensin II and an effector of the renin-angiotensin system, is synthesized in numerous rat tissues. Angiotensinogen is expressed in an islet cell line (RIN 1056A) derived from a rat pancreatic tumor. Angiotensinogen mRNA detected by Northern analysis is abundant in the cell line and is approximately 200 bases longer than the mRNA isolated from rat liver, due to both a longer poly(A) tract and the use of a second polyadenylation site. Dexamethasone is a potent inducer of angiotensinogen mRNA, producing a progressive accumulation from 3 to 96 hr in culture (9-fold above control levels). The dexamethasone effect is competitively inhibited by the glucocorticoid antagonist RU486, and transcription rate assays using isolated nuclei indicate that the effect is primarily at the transcriptional level.

Angiotensinogen↗
PubMed1981

Increased clearance and degradation of [3H]insulin in streptozotocin diabetic rats.

The role of the insulin-receptor compartment in the pharmacokinetics of intravenously injected insulin in rats was studied. Since streptozotocin-diabetes in rats results in increased insulin binding to tissues in vitro, insulin pharmacokinetics in streptozotocin-diabetic rats were compared to controls, using semisynthetic [(3)H]insulin as the tracer. The initial distribution volume for [(3)H]insulin was elevated by 60% in diabetic rats. By contrast, no difference in initial distribution volume for [(14)C]inulin was observed, and the absolute values were lower than those found for [(3)H]insulin. The metabolic clearance rate of [(3)H]insulin was elevated by 44% in diabetic rats. That these differences were the result of increased binding of insulin to a specific receptor compartment in diabetic rats was shown by three additional experiments. The first involved receptor saturation by injection of 10 U native insulin 2 min before the tracer injection, resulting in identical [(3)H]insulin disappearance rates in the two groups of rats. The second consisted of displacing [(3)H]insulin from receptors by injecting 10 U unlabeled insulin 6 min after the tracer injection. Displacement of intact [(3)H]insulin from receptors and subsequent reappearance in the circulation occurred in both control and diabetic animals; however, such displacement was 25% greater in the diabetic rats. Finally, treatment of diabetic rats with insulin for 8 d normalized [(3)H]insulin clearance even though the tracer was injected at a time when the animals were again hyperglycemic and hypoinsulinemic. This suggests that down-regulation of insulin receptors had occurred during insulin therapy. These results confirm that a specific compartment for insulin exists (the insulin-receptor compartment) and that this compartment plays an important role in insulin clearance.

Animals↗
PubMed1981

[Chondromalacia of the hip].

The authors have shown that the initial phase of coxarthrosis consists purely of cartilaginous lesions, not visible in radiographs. They have studied 200 arthrograms of the hip using a precise technique which is described. They have found cartilaginous lesions both in cases of insufficiency of the lateral wall of the acetabulum, and in cases of insufficiency of the medial wall of the acetabulum. Cartilaginous lesions may range between a simple decrease of articular cartilage height and complete ulceration either on the cephalic or acetabular sides. These lesions may be present at a time when the radiograph is still normal, especially in cases of hip dysplasia. It is concluded that the articular cartilage of the hip may chondromalacic in the same way as in the patello-femoral joint, and that arthrosis may be secondary to this chondromalacia. Arthrography makes early diagnosis possible.

Adult↗
PubMed1980

Swine dysentery. Comparison of experimental diseases produced by infection with colonic mucosa or with Treponema hyodysenteriae, French strains, and of "natural" disease.

Oral inoculation of colonic mucosa scrapings and intestinal contents of animals affected with swine dysentery, or of pathogenic strains of Treponemia hyodysenteriae, as well as spontaneous contamination in infected pens caused in average swine dysentery to appear in 359 out of 409 SPF piglets. The morbidity is high irrespective of the method of contamination: after pen contamination, 75 out of 83 piglets were dysenteric; after only one ingestion of contaminated matter, 265 out of 280 animals were ill; and after inoculation of T. hyodysenteriae, 25 out of 35. Mortality in dysentery was always higher than 80%, respectively 48 out of 60 animals, 132 out of 154, and 13 out of 14. Very few animals were self-cured. The average incubation period varied according to the mode of contamination between 9 and 13 days. Animals having contracted an acute form of the disease died 16 to 23 days after contamination, and those with a chronic from 19 days, also after contamination. The increase in the number of Treponema, of Campylobacter and of Balantidium observed after the onset of the disease was approximately equivalent for all three modes of contamination. This disease was characterized by an alternance of dysentery stricto sensu and of mucoid diarrhea, the latter occurring more frequently in cases of self-cure and in chronic forms.

Animals↗